Enhancing Trial Delivery in Parkinson\u27s Disease: Qualitative Insights from PD STAT

\ua9 2022 - The authors. Published by IOS Press. Background: Recruitment and retention of participants in clinical trials for Parkinson\u27s disease (PD) is challenging. A qualitative study embedded in the PD STAT multi-centre randomised controlled trial of simvastatin for neuroprotection in PD explored the motivators, barriers and challenges of participants, care partners and research staff. Objective: To outline a set of considerations informing a patient-centred approach to trial recruitment, retention, and delivery. Method: We performed semi-structured interviews and focus groups with a subset of trial participants and their care partners. Quantitative and qualitative data were obtained through surveys circulated among the 235 participants across 23 UK sites at the beginning, middle and end of the 2-year trial. We also interviewed and surveyed research staff at trial closure. Results: Twenty-seven people with PD, 6 care partners and 9 researchers participated in interviews and focus groups. A total of 463 trial participant survey datasets were obtained across three timepoints, and 53 staff survey datasets at trial closure. Trial participants discussed the physical and psychological challenges they faced, especially in the context of OFF state assessments, relationships, and communication with research staff. Care partners shared their insights into OFF state challenges, and the value of being heard by research teams. Research staff echoed many concerns with suggestions on flexible, person-centred approaches to maximising convenience, comfort, and privacy. Conclusion: These considerations, in favour of person-centred research protocols informed by the variable needs of participants, care partners and staff, could be developed into a set of recommendations for future trials

Can group-based strategies increase community resilience? Longitudinal predictors of sustained participation in Covid-19 mutual aid and community support groups

Mutual aid groups have been a critical part of the coronavirus disease-2019 (Covid-19) response and continue to address the needs of people in their communities. To understand how mutual aid and similar community support groups can be sustained over time, we test the idea that using group-based strategies initiates psychological trajectories that shape future participation. We conducted a preregistered longitudinal survey among Covid-19 mutual aid and community support volunteers in the United Kingdom (nWave 1 = 600, May 2021; nWave 2 = 299, July–August 2021) who were registered panelists of an independent research organization. Assessments included measures of group-based strategies, collective participation predictors, participation experience, and sustained participation. Volunteers engaged in a wide range of support activities including shopping, emotional support provision, and deliveries. Two group-based strategies—group alliances and group horizontality—longitudinally predicted sustained participation. In addition, sense of community responsibility and burnout were longitudinal predictors of sustained participation. Importantly, predictors of sustained participation diverged for volunteers with different levels of volunteering experience. Our findings highlight group-based strategies as a potential resource for organizers seeking to sustain participation. Use can be tailored depending on the profiles of individual Covid-19 mutual aid volunteers. These findings have significance beyond Covid-19 as they are relevant to sustaining community resilience more generally

Microscopic dynamics in liquid metals: the experimental point of view

The experimental results relevant for the understanding of the microscopic dynamics in liquid metals are reviewed, with special regards to the ones achieved in the last two decades. Inelastic Neutron Scattering played a major role since the development of neutron facilities in the sixties. The last ten years, however, saw the development of third generation radiation sources, which opened the possibility of performing Inelastic Scattering with X rays, thus disclosing previously unaccessible energy-momentum regions. The purely coherent response of X rays, moreover, combined with the mixed coherent/incoherent response typical of neutron scattering, provides enormous potentialities to disentangle aspects related to the collectivity of motion from the single particle dynamics. If the last twenty years saw major experimental developments, on the theoretical side fresh ideas came up to the side of the most traditional and established theories. Beside the raw experimental results, therefore, we review models and theoretical approaches for the description of microscopic dynamics over different length-scales, from the hydrodynamic region down to the single particle regime, walking the perilous and sometimes uncharted path of the generalized hydrodynamics extension. Approaches peculiar of conductive systems, based on the ionic plasma theory, are also considered, as well as kinetic and mode coupling theory applied to hard sphere systems, which turn out to mimic with remarkable detail the atomic dynamics of liquid metals. Finally, cutting edges issues and open problems, such as the ultimate origin of the anomalous acoustic dispersion or the relevance of transport properties of a conductive systems in ruling the ionic dynamic structure factor are discussed.Comment: 53 pages, 41 figures, to appear in "The Review of Modern Physics". Tentatively scheduled for July issu

Evaluation of Simvastatin as a Disease-Modifying Treatment for Patients With Parkinson Disease: A Randomized Clinical Trial

\ua9 2022 American Medical Association. All rights reserved.Importance: Current treatments manage symptoms of Parkinson disease (PD), but no known treatment slows disease progression. Preclinical and epidemiological studies support the potential use of statins as disease-modifying therapy. Objective: To determine whether simvastatin has potential as a disease-modifying treatment for patients with moderate PD. Design, Setting, and Participants: This randomized clinical trial, a double-blind, parallel-group, placebo-controlled futility trial, was conducted between March 2016 and May 2020 within 23 National Health Service Trusts in England. Participants aged 40 to 90 years with a diagnosis of idiopathic PD, with a modified Hoehn and Yahr stage of 3.0 or less while taking medication, and taking dopaminergic medication with wearing-off phenomenon were included. Data were analyzed from May 2020 to September 2020, with additional analysis in February 2021. Interventions: Participants were allocated 1:1 to simvastatin or matched placebo via a computer-generated random sequence, stratified by site and Hoehn and Yahr stage. In the simvastatin arm, participants entered a 1-month phase of simvastatin, 40 mg daily, followed by 23 months of simvastatin, 80 mg daily, before a 2-month washout period. Main Outcomes and Measures: The prespecified primary outcome was 24-month change in Movement Disorder Society Unified Parkinson Disease Rating Scale (MDS-UPDRS) part III score measured while not taking medication (high scores indicate worse outcome). The primary futility analysis included participants who commenced the 80-mg phase and had valid primary outcome data. The safety analysis included all participants who commenced trial treatment and is reported by dose at time of event. Results: Of 332 patients assessed for eligibility, 32 declined and 65 were ineligible. Of 235 recruited participants, 97 (41%) were female, 233 (99%) were White, and the mean (SD) age was 65.4 (9.4) years. A total of 216 patients progressed to the 80-mg dose. Primary outcome analysis (n = 178) indicated the simvastatin group had an additional deterioration in MDS-UPDRS III score while not taking medication at 24 months compared with the placebo group (1.52 points; 2-sided 80% CI, -0.77 to 3.80; 1-sided futility test P =.006). A total of 37 serious adverse events (AEs), including 3 deaths, and 171 AEs were reported for participants receiving 0-mg simvastatin; 37 serious AEs and 150 AEs were reported for participants taking 40 mg or 80 mg of simvastatin. Four participants withdrew from the trial because of an AE. Conclusions and Relevance: In this randomized clinical trial, simvastatin was futile as a disease-modifying therapy in patients with PD of moderate severity, providing no evidence to support proceeding to a phase 3 trial. Trial Registration: ISRCTN Identifier: 16108482

PAin SoluTions In the Emergency Setting (PASTIES)--patient controlled analgesia versus routine care in emergency department patients with non-traumatic abdominal pain: randomised trial

© Smith et al 2015. OBJECTIVE: To determine whether patient controlled analgesia (PCA) is better than routine care in providing effective analgesia for patients presenting to emergency departments with moderate to severe non-traumatic abdominal pain.DESIGN: Pragmatic, multicentre, parallel group, randomised controlled trialSETTING: Five English hospitals.PARTICIPANTS: 200 adults (66% (n=130) female), aged 18 to 75 years, who presented to the emergency department requiring intravenous opioid analgesia for the treatment of moderate to severe non-traumatic abdominal pain and were expected to be admitted to hospital for at least 12 hours.INTERVENTIONS: Patient controlled analgesia or nurse titrated analgesia (treatment as usual).MAIN OUTCOME MEASURES: The primary outcome was total pain experienced over the 12 hour study period, derived by standardised area under the curve (scaled from 0 to 100) of each participant's hourly pain scores, captured using a visual analogue scale. Pre-specified secondary outcomes included total morphine use, percentage of study period in moderate or severe pain, percentage of study period asleep, length of hospital stay, and satisfaction with pain management.RESULTS: 196 participants were included in the primary analyses (99 allocated to PCA and 97 to treatment as usual). Mean total pain experienced was 35.3 (SD 25.8) in the PCA group compared with 47.3 (24.7) in the treatment as usual group. The adjusted between group difference was 6.3 (95% confidence interval 0.7 to 11.9). Participants in the PCA group received significantly more morphine (mean 36.1 (SD 22.4) v 23.6 (13.1) mg; mean difference 12.3 (95% confidence interval 7.2 to 17.4) mg), spent less of the study period in moderate or severe pain (32.6% v 46.9%; mean difference 14.5% (5.6% to 23.5%)), and were more likely to be perfectly or very satisfied with the management of their pain (83% (73/88) v 66% (57/87); adjusted odds ratio 2.56 (1.25 to 5.23)) in comparison with participants in the treatment as usual group.CONCLUSIONS: Significant reductions in pain can be achieved by PCA compared with treatment as usual in patients presenting to the emergency department with non-traumatic abdominal pain. Trial registration European Clinical Trials Database EudraCT2011-000194-31; Current Controlled Trials ISRCTN25343280

Enhancing Trial Delivery in Parkinson’s Disease: Qualitative Insights from PD STAT

Background: Recruitment and retention of participants in clinical trials for Parkinson’s disease (PD) is challenging. A qualitative study embedded in the PD STAT multi-centre randomised controlled trial of simvastatin for neuroprotection in PD explored the motivators, barriers and challenges of participants, care partners and research staff. Objective: To outline a set of considerations informing a patient-centred approach to trial recruitment, retention, and delivery. Method: We performed semi-structured interviews and focus groups with a subset of trial participants and their care partners. Quantitative and qualitative data were obtained through surveys circulated among the 235 participants across 23 UK sites at the beginning, middle and end of the 2-year trial. We also interviewed and surveyed research staff at trial closure. Results: Twenty-seven people with PD, 6 care partners and 9 researchers participated in interviews and focus groups. A total of 463 trial participant survey datasets were obtained across three timepoints, and 53 staff survey datasets at trial closure. Trial participants discussed the physical and psychological challenges they faced, especially in the context of OFF state assessments, relationships, and communication with research staff. Care partners shared their insights into OFF state challenges, and the value of being heard by research teams. Research staff echoed many concerns with suggestions on flexible, person-centred approaches to maximising convenience, comfort, and privacy. Conclusion: These considerations, in favour of person-centred research protocols informed by the variable needs of participants, care partners and staff, could be developed into a set of recommendations for future trials.</jats:p

Evaluation of Simvastatin as a Disease-Modifying Treatment for Patients With Parkinson Disease: A Randomized Clinical Trial.

Importance: Current treatments manage symptoms of Parkinson disease (PD), but no known treatment slows disease progression. Preclinical and epidemiological studies support the potential use of statins as disease-modifying therapy. Objective: To determine whether simvastatin has potential as a disease-modifying treatment for patients with moderate PD. Design, Setting, and Participants: This randomized clinical trial, a double-blind, parallel-group, placebo-controlled futility trial, was conducted between March 2016 and May 2020 within 23 National Health Service Trusts in England. Participants aged 40 to 90 years with a diagnosis of idiopathic PD, with a modified Hoehn and Yahr stage of 3.0 or less while taking medication, and taking dopaminergic medication with wearing-off phenomenon were included. Data were analyzed from May 2020 to September 2020, with additional analysis in February 2021. Interventions: Participants were allocated 1:1 to simvastatin or matched placebo via a computer-generated random sequence, stratified by site and Hoehn and Yahr stage. In the simvastatin arm, participants entered a 1-month phase of simvastatin, 40 mg daily, followed by 23 months of simvastatin, 80 mg daily, before a 2-month washout period. Main Outcomes and Measures: The prespecified primary outcome was 24-month change in Movement Disorder Society Unified Parkinson Disease Rating Scale (MDS-UPDRS) part III score measured while not taking medication (high scores indicate worse outcome). The primary futility analysis included participants who commenced the 80-mg phase and had valid primary outcome data. The safety analysis included all participants who commenced trial treatment and is reported by dose at time of event. Results: Of 332 patients assessed for eligibility, 32 declined and 65 were ineligible. Of 235 recruited participants, 97 (41%) were female, 233 (99%) were White, and the mean (SD) age was 65.4 (9.4) years. A total of 216 patients progressed to the 80-mg dose. Primary outcome analysis (n = 178) indicated the simvastatin group had an additional deterioration in MDS-UPDRS III score while not taking medication at 24 months compared with the placebo group (1.52 points; 2-sided 80% CI, -0.77 to 3.80; 1-sided futility test P = .006). A total of 37 serious adverse events (AEs), including 3 deaths, and 171 AEs were reported for participants receiving 0-mg simvastatin; 37 serious AEs and 150 AEs were reported for participants taking 40 mg or 80 mg of simvastatin. Four participants withdrew from the trial because of an AE. Conclusions and Relevance: In this randomized clinical trial, simvastatin was futile as a disease-modifying therapy in patients with PD of moderate severity, providing no evidence to support proceeding to a phase 3 trial. Trial Registration: ISRCTN Identifier: 16108482

Post-activation Potentiation: Effect of Recovery Duration and Gender on Countermovement Jump, Agility, and Linear Speed in Team-Sport Athletes

Background: Studies assessing post-activation potentiation (PAP) responses comparing male and female athletes are conflicting. Objectives: This study investigated whether differences exist in the duration for optimal post-preload stimulus measures on performance in male and female team sport athletes. Methods: Twenty-four participants (12 males and 12 females) participated in the study. Two familiarization sessions were conducted with each participant. Then, three experimental conditions were implemented, incorporating a standardized warm-up, followed by back squats (conditioning exercises) and varying passive recovery times of 4 min (PAP4), 8 min (PAP8), or 12 min (PAP12). Following the recovery, players performed three physical performance measures related to team sports: A countermovement jump, a modified agility t-test, and a 20-m linear sprint. The significance level was set at P < 0.05. Results: All performance measures were significantly greater in PAP12 than in PAP4 and PAP8 conditions in both males (1.50 to 2.95%) and females (1.09 to 5.79%) (P < 0.05). The PAP12 condition also had significantly lower values for HR (3.18 to 5.15 beats.min-1; P < 0.0005) and ratings of perceived exertion (RPE) (0.63 to 1.02; P < 0.05) than PAP8 and PAP4. Males performed better on all the performance tests (19.33 to 26.34%) compared to their female counterparts (P < 0.0005). Conclusions: A pre-load stimulus consisting of one set of 5 repetitions of back squat at 85% one-repetition maximum can elicit a PAP response. A 12-min passive rest after the pre-load stimulus was most beneficial in improving physical performance measures in both male and female team-sport athletes

The cost-effectiveness of patient-controlled analgesia vs. standard care in patients presenting to the emergency department in pain, who are subsequently admitted to hospital.

The clinical effectiveness of patient-controlled analgesia has been demonstrated in a variety of settings. However, patient-controlled analgesia is rarely utilised in the emergency department. The aim of this study was to compare the cost-effectiveness of patient-controlled analgesia vs. standard care in participants admitted to hospital from the emergency department with pain due to traumatic injury or non-traumatic abdominal pain. Pain scores were measured hourly for 12 h using a visual analogue scale. Cost-effectiveness was measured as the additional cost per hour in moderate to severe pain avoided by using patient-controlled analgesia rather than standard care (the incremental cost-effectiveness ratio). Sampling variation was estimated using bootstrap methods and the effects of parameter uncertainty explored in a sensitivity analysis. The cost per hour in moderate or severe pain averted was estimated as £24.77 (€29.05, US$30.80) (bootstrap estimated 95$18.86) (bootstrap estimate 95%CI £9.03 to £46.00) for participants with non-traumatic abdominal pain. Overall costs were higher with patient-controlled analgesia than standard care in both groups: pain from traumatic injuries incurred an additional £18.58 (€21.79 US$23.10) (95$25.09) (95%CI £19.45 to £20.84) per 12 h

Evaluation of Simvastatin as a Disease-Modifying Treatment for Patients With Parkinson Disease: A Randomized Clinical Trial

This is the final version. Available on open access from the American Medical Association via the DOI in this recordData Sharing Statement Stevens. Evaluation of Simvastatin as a Neuroprotective Treatment for Patients With Parkinson Disease. JAMA Neurol. Published October 31, 2022. doi:10.1001/jamaneurol.2022.3718 Data Data available: Yes Data types: Deidentified participant data How to access data: By request to the data custodian/sponsor representative ([email protected] ). When available: With publication Supporting Documents Document types: None Additional Information Who can access the data: Researchers undertaking ethically approved purposes and on execution of a valid data sharing agreement. Types of analyses: Specified ethically approved purpose. Mechanisms of data availability: With a signed valid data sharing agreement.mportance Current treatments manage symptoms of Parkinson disease (PD), but no known treatment slows disease progression. Preclinical and epidemiological studies support the potential use of statins as disease-modifying therapy. Objective To determine whether simvastatin has potential as a disease-modifying treatment for patients with moderate PD. Design, Setting, and Participants This randomized clinical trial, a double-blind, parallel-group, placebo-controlled futility trial, was conducted between March 2016 and May 2020 within 23 National Health Service Trusts in England. Participants aged 40 to 90 years with a diagnosis of idiopathic PD, with a modified Hoehn and Yahr stage of 3.0 or less while taking medication, and taking dopaminergic medication with wearing-off phenomenon were included. Data were analyzed from May 2020 to September 2020, with additional analysis in February 2021. Interventions Participants were allocated 1:1 to simvastatin or matched placebo via a computer-generated random sequence, stratified by site and Hoehn and Yahr stage. In the simvastatin arm, participants entered a 1-month phase of simvastatin, 40 mg daily, followed by 23 months of simvastatin, 80 mg daily, before a 2-month washout period. Main Outcomes and Measures The prespecified primary outcome was 24-month change in Movement Disorder Society Unified Parkinson Disease Rating Scale (MDS-UPDRS) part III score measured while not taking medication (high scores indicate worse outcome). The primary futility analysis included participants who commenced the 80-mg phase and had valid primary outcome data. The safety analysis included all participants who commenced trial treatment and is reported by dose at time of event. Results Of 332 patients assessed for eligibility, 32 declined and 65 were ineligible. Of 235 recruited participants, 97 (41%) were female, 233 (99%) were White, and the mean (SD) age was 65.4 (9.4) years. A total of 216 patients progressed to the 80-mg dose. Primary outcome analysis (n = 178) indicated the simvastatin group had an additional deterioration in MDS-UPDRS III score while not taking medication at 24 months compared with the placebo group (1.52 points; 2-sided 80% CI, −0.77 to 3.80; 1-sided futility test P = .006). A total of 37 serious adverse events (AEs), including 3 deaths, and 171 AEs were reported for participants receiving 0-mg simvastatin; 37 serious AEs and 150 AEs were reported for participants taking 40 mg or 80 mg of simvastatin. Four participants withdrew from the trial because of an AE. Conclusions and Relevance In this randomized clinical trial, simvastatin was futile as a disease-modifying therapy in patients with PD of moderate severity, providing no evidence to support proceeding to a phase 3 trial. Trial Registration ISRCTN Identifier: 16108482JP Moulton Charitable FoundationCure Parkinson’s Trus