Title: Designing a prediction model to identify people witH PArkinson’s who May be at risk of deveLoping dETrusor underactivity (HAMLET)
Funder: Health Education England

Abstract: Can a prediction model stratify the risk of people with Parkinson's (PwP) developing detrusor underactivity? Lower urinary tract (LUT) symptoms are the most common non-motor symptom in Parkinson's affecting between 27-85% of PwP and have a considerable impact on quality of life. LUT symptoms are more common and present earlier in PwP than in age-matched controls. Video-urodynamic studies determine an objective measure of bladder filling and voiding parameters. PwP typically present with storage symptoms (nocturnal enuresis and detrusor overactivity). However, recent work has linked PwP to a high prevalence of voiding dysfunction or specifically detrusor underactivity. PwP who do not empty their bladders or require catheterisation are at a higher risk of developing urine infections, which can develop into kidney infections and sepsis. The aim of this research is to develop a predictive model of factors for the risk stratification of PwP developing detrusor underactivity. The objectives of this study are: Review the literature for risk factors of developing detrusor underactivity in PwP compared with the general population Prospectively evaluate consecutive PwP reporting LUT symptoms to estimate the prevalence of detrusor underactivity in a tertiary care centre To establish a prediction model for the clinical and urodynamic risk factors of developing detrusor underactivityA systematic review will be performed to investigate the prevalence of detrusor underactivity in PwP and other neurological disorders. The findings of the systematic review will be used to inform the factors used in the prospective cohort study. Validated cognitive, motor and bladder questionnaires, mobility tests and a video-urodynamic assessment of bladder function will be completed. All the assessment methods are part of the routine care pathway in the management of bladder symptoms in PwP and no additional tests used during this study. Statistical analysis will be performed using univariable analyses to investigate the relationship between each predictor and the outcome. Significant predictors will be included in a multivariable logistic regression to predict the risk of detrusor underactivity. The systematic review will be completed in the first six months and published in year one. The prospective cohort study will be completed over the following 24-months. The predictive model will be developed over the final six months of the award. The use of antimuscarinics or Botulinum toxin to manage urinary incontinence in PwP who may have underlying detrusor underactivity could lead to urinary retention. A prediction model would help clinicians adopt a more cautious approach, reducing the risk for iatrogenic urinary retention, along with the risk for catheterisation. This would ensure PwP affected by this condition gets the necessary treatment at the earliest stage possible, ultimately improving their quality of life. This study is supported by the host organisations, Parkinson's UK, Age UK, Marie Curie, The Urology Foundation and Core Charity. Beyond conference presentations and journal articles, the study outcomes will be communicated using the supporting organization's Twitter, Facebook, newsletters and websites. We also plan to disseminate the outcomes through the Parkinson's nurses' network and Parkinson's UK Engagement Network.

Lay abstract: Building a better picture of why people with Parkinson's develop problems passing urine. Aim of this Research: We would like to develop a model that helps to predict if people with Parkinson's (PwP) are at risk of developing problems passing urine due to a weak bladder. Background to the Research: Parkinson's is a progressive neurological condition (causes problems in the brain that get worse over time). Parkinson's occurs when a chemical called dopamine is no longer being produced in the brain. Over time this results in symptoms that include tremor (involuntary shaking of parts of the body) and difficulty walking. A variety of symptoms which are not linked to movement also occur, the most common being bladder problems. Individuals may talk of an urgent need to pass urine and urine incontinence. Sometimes, however, they may have problems passing urine. We previously have identified a group of PwP who could only pass urine when suddenly urgent. They were unaware that they were not completely emptying their bladder when urinating. People who do not completely empty their bladders are at a higher risk of developing urine infections. Sometimes urine infections can develop into kidney infections and sepsis. Sepsis is a serious complication of an infection which can be life-threatening. Design and Methods: In the first part of this study, we will perform a 'systematic review' to find out how common it is for PwP to develop problems passing urine due to weak bladder contractions. A 'systematic review' is a way of summarising what other studies have found on the same topic. We will use the results of the review to help identify the reasons why PwP are at risk of developing problems passing urine. In the second part of this study, we will use a way of predicting (called a model) the risk for developing problems passing urine using questionnaires, and different ways of measuring their mobility and how their bladder function. We will study bladder function using methods (assessments) that have already been proven to work. This will be done as part of a routine assessment for bladder function in PwP who have problems passing urine. Analysing the results of these different assessments will help to identify the reasons that may predict the risk of PwP developing problems emptying their bladder. Patient and Public Involvement (PPI): This proposal was developed in collaboration with Parkinson's UK through a Research Involvement Award engaging with PwP who were interested in being involved in designing clinical research projects. The PPI Group helped to design the study, confirmed that the lay summary of the study was clear and easy to understand and that the research question reflected their concerns. We plan to meet as a group every six months to monitor the progress of the project, evaluate its impact, and maximise the dissemination of the study. Dissemination: We plan to share the results of the project through conference presentations and journal articles. We will also be sharing the results through the Parkinson's Facebook groups, Parkinson's nurses' network and Parkinson's UK Engagement Network. The study is supported by different host organisations, Parkinson's UK, Age UK, Marie Curie, The Urology Foundation and Core Charity. We plan to use the supporting organisations' social media, twitter and websites to share the findings of the study. We believe this will maximise the dissemination to the wider community of PwP, their carers, the NHS and the wider population.

Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: NEUROLOGICAL