Investigating trial design variability in trials of disease-modifying therapies in Parkinson's disease: a scoping review protocol.

INTRODUCTION: Parkinson's disease (PD) is a debilitating neurological disorder for which the identification of disease-modifying interventions represents a major unmet need. Diverse trial designs have attempted to mitigate challenges of population heterogeneity, efficacious symptomatic therapy and lack of outcome measures that are objective and sensitive to change in a disease modification setting. It is not clear whether consensus is emerging regarding trial design choices. Here, we report the protocol of a scoping review that will provide a contemporary update on trial design variability for disease-modifying interventions in PD. METHODS AND ANALYSIS: The Population, Intervention, Comparator, Outcome and Study design (PICOS) framework will be used to structure the review, inform study selection and analysis. The databases MEDLINE, Web of Science, Cochrane and the trial registry ClinicalTrials.gov will be systematically searched to identify published studies and registry entries in English. Two independent reviewers will screen study titles, abstracts and full text for eligibility, with disagreements being resolved through discussion or by a third reviewer where necessary. Data on general study information, eligibility criteria, outcome measures, trial design, retention and statistically significant findings will be extracted into a standardised form. Extracted data will be presented in a descriptive analysis. We will report our findings using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Scoping Review extension. ETHICS AND DISSEMINATION: This work will provide an overview of variation and emerging trends in trial design choices for disease-modifying trials of PD. Due to the nature of this study, there are no ethical or safety considerations. We plan to publish our findings in a peer-reviewed journal.

Rapid progression of probable Creutzfeldt-Jakob disease with concomitant COVID-19 infection.

A previously healthy man in his 80s was admitted to a district general hospital with rapidly progressing dementia, gait abnormalities and myoclonus alongside COVID-19 infection. Investigations showed mild elevation of C-reactive protein and neutrophils, unremarkable CT head and mildly raised protein in cerebrospinal spinal fluid (CSF). Brain MRI revealed bilateral cortical and striatal diffusion restriction and electroencephalogram (EEG) findings showed diffuse activity slowing with high amplitude sharp/slow-wave complexes. He was diagnosed with probable sporadic Creutzfeldt-Jakob disease (CJD) and management prioritised comfort and care. He passed away two weeks following admission and a mere 8 weeks after the first onset of symptoms.We present the first documented case of probable CJD with concomitant COVID-19 infection in the UK. We identified six other cases worldwide identified in our literature review. These cases suggest a role of COVID-19 in the rapid progression of CJD and add to the growing evidence of its neuroinflammatory role in other forms of neurodegenerative diseases.

Body mass index trajectories and mortality in community-dwelling older adults: population-based cohort study.

OBJECTIVE: Both low and high body mass index (BMI) have been associated with greater mortality in older adults. This study aimed to evaluate the trajectory of BMI in the final years of life. METHODS: A population-based cohort study was conducted including community-dwelling adults in the English Longitudinal Study of Ageing between 1998 and 2012. BMI was evaluated in relation to age and years before death. Number of long-term conditions, cigarette smoking and socioeconomic position were evaluated as effect modifiers. RESULTS: Data were analysed for 16 924 participants with 31 857 BMI records; mean age at study starts, 61.6 (SD 10.9) years; mean BMI, 27.5 (4.7) Kg/m2. There were 3686 participants (4794 BMI records) who died and 13 238 participants (27 063 BMI records) who were alive at last follow-up. Mean BMI increased with age to 60-69 years but then declined, but the age-related decline was more rapid in decedents. From 4 to 7 years before death or end of study, adjusted mean BMI was 0.87 (95% CI 0.50 to 1.24) Kg/m2 lower for male decedents than survivors and 1.02 (0.56 to 1.47) lower in women; and from 3 to 0 years before death, BMI was 1.39 (0.98 to 1.80) Kg/m2 lower in male decedents and 2.12 (1.60 to 2.64) lower in female decedents. Multiple long-term conditions and lower socioeconomic position were associated with higher peak BMI and greater BMI decline; current smoking was associated with lower BMI and greater BMI decline. CONCLUSIONS: In community-dwelling older adults, mean BMI enters an accelerating decline from up to 8 years before death. Multiple long-term conditions, smoking and lower socioeconomic position are associated with BMI decline.

Pilot study: undergraduate sports & exercise medicine conferences: what role do they play?

OBJECTIVES: Sports & exercise medicine (SEM) is a specialty encompassing the management of medical problems and injuries related to physical activity through means such as exercise advice and prescription. The field of SEM has been recognised in the UK since 2005 yet there is inadequate exposure of SEM in medical curricula. Conferences may be a way to increase exposure where students meet SEM professionals, gaining greater understanding of SEM career pathways. We therefore carried out a pilot study to assess this. METHODS: The King's College London Sports & Exercise Medicine Society organised a student-led conference consisting of six lectures. Seventy-five delegates were given questionnaires on their views on SEM before and after the conference, assessed using the 5-point Likert scale. Results were analysed using a Wilcoxon-Signed Rank statistical test. RESULTS: Questionnaire feedback showed 67.4% of delegates (n=46) had received SEM related teaching in their current degree. Results of our statistical analysis showed an increase in SEM career interest (p=0.0359), an increase in understanding of what a career in SEM involves (p=0.0009) and an increase in delegate's understanding of what is required to pursue a career in SEM (p=0.0004) after our conference. CONCLUSION: The study showed issues regarding poor exposure to SEM in medical curricula and highlighted the value of student conferences. Students felt they learnt more about the roles within the SEM specialty, aiding future career progression. Thus, we suggest that student-led conferences are a good platform to bridge this gap while medical schools introduce more SEM into their curricula.