Improving the management of Parkinson's disease: the experience of hospitalisation and a novel mri-based diagnostic tool

Parkinson's disease (PD) motor and non-motor symptoms progress relentlessly leading to frequent hospitalisations and an increase in the economic and societal burden of the disease. A major challenge in assessing treatments which can potentially reduce neurodegeneration, is the lack of tools that can be used to identify individuals with early PD with high sensitivity and specificity. There were several facets to this thesis, which were aimed at addressing these issues. Firstly a retrospective analysis of PD hospital admissions was conducted to provide background data on hospitalisation and clinical coding accuracy. A systematic review of literature for interventions to reduce hospital admissions was performed. Effect of treatments for PD motor symptoms on hospitalisation was also evaluated. Lastly, screening of potential lanthanide and 19 Fluorine based MRI probes for future use as diagnostic tools in PD was conducted. Results of these studies highlight significant underreporting of PD hospitalisation which has a negative effect on PD resource allocation. A lack of robust evidence for measures which reduce PD admissions was demonstrated. Although the initial attempts to develop a novel MRI sensitive tool for use in PD were negative, the study refined a protocol that has potential for use in screening future probes

Long-term Effectiveness of Adjuvant Treatment With Catechol-O-Methyltransferase or Monoamine Oxidase B Inhibitors Compared With Dopamine Agonists Among Patients With Parkinson Disease Uncontrolled by Levodopa Therapy : The PD MED Randomized Clinical Trial

Funding/Support: The PD MED clinical trial was supported by funding from the Health Technology Assessment Programme of the UK National Institute for Health Research (project number 98/03/02), the UK Department of Health through March 2012 (University of Birmingham Clinical Trials Unit, supporting the salaries of Mss Ives and Patel), the UK Medical Research Council (Mr R. Gray), and Parkinson’s UK (Dr McIntosh). We thank all of the patients who agreed to enter the study, the many investigators who also contributed to the clinical trial, and NHS Digital, which provided data on mortality and data from the Hospital Episodes Statistics database. The investigators received no payment or other compensation for taking part in the PD MED clinical trial.Peer reviewedPublisher PD

Cerebral venous thrombosis after vaccination against COVID-19 in the UK: a multicentre cohort study

BackgroundA new syndrome of vaccine-induced immune thrombotic thrombocytopenia (VITT) has emerged as a rare side-effect of vaccination against COVID-19. Cerebral venous thrombosis is the most common manifestation of this syndrome but, to our knowledge, has not previously been described in detail. We aimed to document the features of post-vaccination cerebral venous thrombosis with and without VITT and to assess whether VITT is associated with poorer outcomes.MethodsFor this multicentre cohort study, clinicians were asked to submit all cases in which COVID-19 vaccination preceded the onset of cerebral venous thrombosis, regardless of the type of vaccine, interval between vaccine and onset of cerebral venous thrombosis symptoms, or blood test results. We collected clinical characteristics, laboratory results (including the results of tests for anti-platelet factor 4 antibodies where available), and radiological features at hospital admission of patients with cerebral venous thrombosis after vaccination against COVID-19, with no exclusion criteria. We defined cerebral venous thrombosis cases as VITT-associated if the lowest platelet count recorded during admission was below 150 × 109 per L and, if the D-dimer was measured, the highest value recorded was greater than 2000 μg/L. We compared the VITT and non-VITT groups for the proportion of patients who had died or were dependent on others to help them with their activities of daily living (modified Rankin score 3–6) at the end of hospital admission (the primary outcome of the study). The VITT group were also compared with a large cohort of patients with cerebral venous thrombosis described in the International Study on Cerebral Vein and Dural Sinus Thrombosis.FindingsBetween April 1 and May 20, 2021, we received data on 99 patients from collaborators in 43 hospitals across the UK. Four patients were excluded because they did not have definitive evidence of cerebral venous thrombosis on imaging. Of the remaining 95 patients, 70 had VITT and 25 did not. The median age of the VITT group (47 years, IQR 32–55) was lower than in the non-VITT group (57 years; 41–62; p=0·0045). Patients with VITT-associated cerebral venous thrombosis had more intracranial veins thrombosed (median three, IQR 2–4) than non-VITT patients (two, 2–3; p=0·041) and more frequently had extracranial thrombosis (31 [44%] of 70 patients) compared with non-VITT patients (one [4%] of 25 patients; p=0·0003). The primary outcome of death or dependency occurred more frequently in patients with VITT-associated cerebral venous thrombosis (33 [47%] of 70 patients) compared with the non-VITT control group (four [16%] of 25 patients; p=0·0061). This adverse outcome was less frequent in patients with VITT who received non-heparin anticoagulants (18 [36%] of 50 patients) compared with those who did not (15 [75%] of 20 patients; p=0·0031), and in those who received intravenous immunoglobulin (22 [40%] of 55 patients) compared with those who did not (11 [73%] of 15 patients; p=0·022).InterpretationCerebral venous thrombosis is more severe in the context of VITT. Non-heparin anticoagulants and immunoglobulin treatment might improve outcomes of VITT-associated cerebral venous thrombosis. Since existing criteria excluded some patients with otherwise typical VITT-associated cerebral venous thrombosis, we propose new diagnostic criteria that are more appropriate