Perineural injections of incobotulinumtoxin-A for diabetic neuropathic pain of the lower extremities: protocol for a phase II, single-centre, double-blind, randomised, placebo-controlled trial (the PINBOT study).

INTRODUCTION: Diabetic neuropathic pain (DNP) is a debilitating complication affecting 15-20% of people with diabetes and is a predictor of depression, poor sleep and decreased quality of life. Current pharmacological treatments are often insufficient and have significant side-effects. Subcutaneous or intradermal botulinumtoxin-A (BonT-A) is an effective and safe treatment for neuropathic pain but is limited by the need to cover the entire affected area with injections. For large cutaneous areas, infiltration of the sensory nerve supply with BonT-A could provide similar effects, with a single injection. We aim to investigate the safety, efficacy, and effects on quality of life, physical activity, depressive symptoms and activities of daily living of perineural injections of BonT-A in patients with DNP of both lower extremities. METHODS: This study is a double-blind, randomised, placebo-controlled clinical trial. 80 participants with moderate to severe DNP of both legs will be randomised 1:1 to receive injections of either 100 units incobotulinumtoxin-A or a saline placebo around each distal sciatic nerve for two cycles of 12 weeks. Average daily pain scores will be recorded once a day from 1 week prior to the first treatment and through the entire study period. Primary outcomes are differences between groups in daily and weekly mean pain scores. Secondary outcomes are levels of physical activity, depression scores, health-related quality of life, activities of daily living, sensory profiles and motor function, recorded at baseline, 4, 12, 16 and 24 weeks. The use of rescue medication and adverse events will be recorded throughout the study period. ETHICS AND DISSEMINATION: The study is approved by the Danish Committee on Health Research Ethics and the Danish Medicines Agency. EU-Clinical Trial Information System (EU: 2022-500727-68-01), clinicaltrials.gov (ID: NCT05623111). Results will be published in peer-reviewed journals in open-access formats and data made available in anonymised form. TRIAL REGISTRATION NUMBER: NCT05623111.

Life with Parkinson's Disease During the COVID-19 Pandemic: The Pressure Is "OFF".

People with Parkinson's disease (PwP) have been suggested to be more vulnerable to negative psychological and psycho-social effects of the COVID-19 pandemic. Our aim was to assess the potential impact of the COVID-19 pandemic in PwP. A Danish/Swedish cohort of 67 PwP was analysed. Health-related quality of life (HRQL), depression, anxiety, apathy, sleep and motor symptom-scores were included in the analysis. Additionally, the Danish participants provided free-text descriptions of life during the pandemic. Overall, the participants reported significantly better HRQL during the COVID-19 period compared with before. Reduced social pressure may be part of the explanation. Despite worsened anxiety, night sleep improved.

"Does the Response to Morning Medication Predict the ADL-Level of the Day in Parkinson's Disease?"

BACKGROUND: Individuals with Parkinson's Disease (PD) have bradykinesia during mobility tasks in the morning before intake of dopaminergic treatment and have difficulties managing Activities of Daily Living (ADLs). Early morning off (EMO) refers to off-states in the morning where the severity of bradykinesia is increased and causes a decrease in mobility related to wearing off of effects of medication. Measurements from devices capable of continuously recording motor symptoms may provide insight into the patient's response to medication and possible impact on ADLs. OBJECTIVES: To test whether poor or slow response to medication in the morning predicts the overall ADL-level and to assess the association between change in bradykinesia score (BKS) and the risk of having disabilities within three selected ADL-items. METHODS: In this cross-sectional study, the sample consists of 34 patients with light to moderate PD. Data collection encompasses measurements from the Parkinson KinetiGraph, and the ADL-limitations are assessed by the Movement Disorder Society Unified Parkinson Disease Rating Scale (MDS-UPDRS) Part II. RESULTS: The association between UPDRS- II and BKS from the algorithm was -0.082 (p < 0.01), 95% CL:-0.113; -0.042). The individuals experienced disabilities in performing "Speech" (p=0.004) and "Doing hobbies" (p=0.038) when being slow or poor responders to dopaminergic therapy. The PD patients' L-dopa equivalent dose seems to be a strong predictor of the ADL-level in the morning. CONCLUSION: Slow response to the medication dosages in the morning is correlated with disabilities in the overall ADL-level in PD. The combination of PD-drugs and precise, timely dosages must be considered in the improvement of the ADL-level in PD patients.