Appendix JResearch recommendations

J.1. Safety and efficacy of antimuscarinics

J.1.1. What is the safety and efficacy of more recently developed antimuscarinics compared with a) placebo/usual care b) other antimuscarinics in the treatment of neurogenic lower urinary tract dysfunction?

Why this is important: No high quality clinical trials, looking at the use of the newer antimuscarinic drugs in the population with neurogenic LUT dysfunction, have been carried out. Both placebo-controlled and comparative studies are lacking. This is important because the more recently developed medications are inevitably more expensive whilst claiming (in the non-neurogenic population) to be freer of adverse side effects. The adverse effects of antimuscarinics are mostly due to that same action at sites other than the bladder (e.g. a dry mouth) but there is now increasing concern that central antimuscarinic effects may adversely impact on cognitive function in both children with brain damage (cerebral palsy or hydrocephalus) and adults with impaired cognition (due to cerebral involvement by Multiple Sclerosis or neurodegenerative diseases).

J.2. Safety and efficacy of botulinum toxin

J.2.1. What is the safety and efficacy of Botulinum toxin compared with a) usual care b) antimuscarinics c) augmentation cystoplasty in people with incontinence in neurological disease?

Why this is important: Further research is required to determine whether repeated intradetrusor injections of Botulinum toxin type A (BTX) have long term efficacy. The efficacy in terms of continence and upper urinary tract preservation should be studied.

BTX injection into the detrusor is an effective means of managing continence, and improves urodynamic measures of bladder storage with the potential to protect the kidneys from the effects of high intravesical pressures. It is well tolerated in a spectrum of conditions and ages. However, the longer term efficacy over many injections has not been established.

A clinical trial is required to study the outcome in terms of continence and renal preservation over many cycles of repeated injection. Quality of life is an important outcome. This should enrol children and adults. The indications for BTX need not be modified for inclusion, but entrants into a trial must have anatomically normal kidneys (on imaging) and have normal renal function.

J.2.2. What is the safety and efficacy of Botulinum toxin compared with a) usual care b) antimuscarinics c) augmentation cystoplasty in people with primary cerebral conditions with lower urinary tract dysfunction?

Why this is important: The effects of intradetrusor Botulinum toxin type A injection (BTX) should be investigated in groups of patients with underlying cerebral conditions that are associated with lower urinary tract dysfunction, as well as those with spinal cord injury, spinal dysraphism and multiple sclerosis. Reports of its use in other conditions are limited to small numbers of patients within case series studies that include heterogeneous groups of patients. Potential benefits of successful treatment in cerebral disease may include the avoidance of cognitive impairment which can be seen as a side effect of antimuscarinic medication.

A trial should include patients with primary cerebral conditions including (but not restricted to) stroke, head injury and cerebral palsy, but excluding multiple sclerosis. Children and adults should be recruited. Tolerability and acceptability are important outcomes, as well as the primary outcomes of continence, preservation of the upper urinary tracts and quality of life. Measurement of carer burden and quality of life is also important.

J.3. Management strategies to reduce the risk of symptomatic UTIs

J.3.1. In patients with neurogenic lower urinary tract dysfunction, which management strategies (including the use of prophylactic antibiotics and various invasive and non-invasive techniques to aid bladder drainage) reduce the risk of symptomatic urinary tract infections?

Why this is important: Recurrent UTIs in patients with neurogenic bladder dysfunction are a cause of considerable morbidity. UTIs may exacerbate incontinence, cause symptoms of malaise and may progress to involve the upper urinary tract with possible loss of renal function. In the population with neurological diseases such as Multiple Sclerosis (MS), Parkinson’s Disease and Dementia, the rise in temperature with UTI can cause deterioration in neurological function and even a relapse of MS. There are therefore numerous reasons why patients with neurogenic LUT dysfunction should avoid UTIs.

The causes for the high prevalence of UTIs in such patients include loss of physiological bladder function and high intravesical pressures. Intermittent or permanent catheterisation inevitably exacerbate the problem but incomplete bladder emptying is also a predisposing factor for UTI.

Research in this area is faced by methodological difficulties, not least because it may be difficult to distinguish between bladder colonisation (asymptomatic bacteriuria) and true infection.

In view of the considerable clinical burden of UTI and the global problem of antibiotic resistance, it is important to establish whether or not any infection prevention strategies, including patient training or the provision of information relating to prophylactic antibiotics are effective in reducing symptomatic UTIs.

J.4. Bladder management strategies

J.4.1. What are the long-term risks and effects on quality of life of different bladder management strategies for lower urinary tract dysfunction in people with neurological disease?

Why is this important: The range of bladder management strategies available to manage LUTD in neurological disease include, permanent urethral catheterisation and suprapubic catheterisation, intermittent self-catheterisation, penile sheath collection systems and pads. However, there is very sparse evidence about which strategies are most acceptable to patients and their carers. The current research base relates mainly to the spinal injury population but may be relevant to people with other neurological diseases.

Bladder management strategies are a long term treatment with implications for maintaining health and quality of life. In order to make informed choices about the most appropriate method of bladder management, patients and their carers require information about the risks and benefits of the available options. There is currently little evidence about which methods are most likely to produce long-term complications (renal impairment, urinary stones and infections, hydronephrosis, bladder malignancy). The effect on quality of life for patients and their carers of different bladder management strategies is not known. There are methodological difficulties due to the heterogeneity of the population with neurological disease, the long time course of treatments and the presence of cognitive impairment in some sub-populations.

Proposed studies could include prospective cohort studies of disease-specific populations examining the effect of each method on quality of life using both generic and disease-specific assessment methods. In addition prospective screening for complications including renal impairment, stone formation and infection should be carried out and comparisons made for each bladder management method. Particular emphasis should be placed on quality of life outcomes for carers, especially for those looking after patients with cognitive impairment.