Optimising Multi-stakeholder Practices in Patient Engagement: A Gap Analysis to Enable Focused Evolution of Patient Engagement in the Development and Lifecycle Management of Medicines.

BACKGROUND: The PARADIGM consortium aimed to make patient engagement in the development and lifecycle management of medicines easier and more effective for all, with the development of new tools that fulfil robustly defined gaps where engagement is suboptimal. AIMS: To generate an inventory of gaps in patient engagement practices and process from existing global examples. METHODS: A large set of criteria for effective patient engagement previously defined via a multi-stakeholder Delphi method, were mapped under fourteen overarching themes. A gap analysis was then performed by twenty-seven reviewers against the resulting forty-six mapped criteria, on a sample of seventy initiatives from global databases. RESULTS: An inventory of gaps was identified including contextual information as to why the gaps exist. Our work identified general patterns where patient engagement was suboptimal-defined as; fragmented reporting and dissemination of patient engagement activities, and the fundamental principles defined in frameworks or guidance being poorly adhered to in actual practice. Specific gaps were identified for sixteen criteria. Additionally, it was also common to observe primary aspects of a process were addressed for a given criteria (i.e. training for roles and responsibilities) but a secondary context element was lacking (i.e. making training material accessible/understandable/meaningful to all participants). CONCLUSION: The results show that the evolution towards meaningful and systematic patient engagement is occurring, yet more importantly they provide clear directional insights to help enhance collaborative practices and co-design solutions. This targeted impact to catalyse a needs-oriented health system that integrates patient engagement at its core is essential.

Urodynamic changes in mice with experimental autoimmune encephalomyelitis correlate with neurological impairment.

AIMS: Neurogenic bladder dysfunction is a major issue in Multiple Sclerosis (MS). High intravesical pressure should be treated early. Available therapies are insufficient and there is need for drug development and investigation of pathogenesis. Experimental Autoimmune Encephalomyelitis (EAE) in rodents is a well validated model to study MS. Previous research has shown that these animals develop urinary symptoms. However, from clinical studies, we know that symptoms do not necessarily reflect changes in bladder pressure. This paper aims to provide a complete overview of urodynamic changes in a model for detrusor overactivity in MS. METHODS: Female C57Bl/6J mice, injected with MOG35-55 and control mice, injected with vehicle (Complete Freund's adjuvant), were monitored daily for neurologic symptoms. Within 1 month after symptom development, mice were used for cystometry or histology of the bladder. RESULTS: Increasing disease score correlated with increased micturition frequency, basal pressure, and average pressure, and with a decrease in functional bladder capacity, voiding amplitude, and maximum pressure. CONCLUSIONS: This paper provides a detailed description of bladder function in C57Bl/6J mice with Myelin Oligodendrocyte Glycoprotein peptide (MOG35-55 ) induced EAE. This EAE model induces detrusor overactivity in close relationship to neurological impairment. EAE in mice is a suitable model to study detrusor overactivity in MS. Neurourol. Urodynam. 35:450-456, 2016. © 2015 Wiley Periodicals, Inc.

Transient receptor potential channels in bladder function.

The transient receptor potential (TRP) superfamily of cationic ion channels includes proteins involved in the transduction of several physical and chemical stimuli to finely tune physiological functions. In the urinary bladder, they are highly expressed in, but not restricted to, primary afferent neurons. The urothelium and some interstitial cells also express several TRP channels. In this review, we describe the expression and the known roles of some members of TRP subfamilies, namely TRPV, TRPM and TRPA, in the urinary bladder. The therapeutic interest of modulating the activity of TRP channels to treat bladder dysfunctions is also discussed.

Rhopalia are integrated parts of the central nervous system in box jellyfish.

In cubomedusae, the central nervous system (CNS) is found both in the bell (the ring nerve) and in the four eye-bearing sensory structures (the rhopalia). The ring nerve and the rhopalia are connected via the rhopalial stalks and examination of the structure of the rhopalial stalks therefore becomes important when trying to comprehend visual processing. In the present study, the rhopalial stalk of the cubomedusae Tripedalia cystophora has been examined by light microscopy, transmission electron microscopy, and electrophysiology. A major part of the ring nerve is shown to continue into the stalk and to contact the rhopalial neuropil directly. Ultrastructural analysis of synapse distribution in the rhopalial stalk has failed to show any clustering, which indicates that integration of the visual input is probably spread throughout the CNS. Together, the results indicate that cubomedusae have one coherent CNS including the rhopalia. Additionally, a novel gastrodermal nerve has been found in the stalk; this nerve is not involved in visual processing but is likely to be mechanosensory and part of a proprioceptory system.