In-Hospital Production of Medicines: Preparing for Disruption.

In-hospital production of affordable medicines holds potential to address problems of drug accessibility. However, expanding the scope of magistral preparation to include high-cost drugs and complex biologicals gives rise to new challenges. We discuss ethical and regulatory complexities faced by Dutch initiatives defying the current pharmaceutical system through magistral preparation.

Responsible Reporting: Neuroimaging News in the Age of Responsible Research and Innovation.

Besides offering opportunities in both clinical and non-clinical domains, the application of novel neuroimaging technologies raises pressing dilemmas. 'Responsible Research and Innovation' (RRI) aims to stimulate research and innovation activities that take ethical and social considerations into account from the outset. We previously identified that Dutch neuroscientists interpret "responsible innovation" as educating the public on neuroimaging technologies via the popular press. Their aim is to mitigate (neuro)hype, an aim shared with the wider emerging RRI community. Here, we present results of a media-analysis undertaken to establish whether the body of articles in the Dutch popular press presents balanced conversations on neuroimaging research to the public. We found that reporting was mostly positive and framed in terms of (healthcare) progress. There was rarely a balance between technology opportunities and limitations, and even fewer articles addressed societal or ethical aspects of neuroimaging research. Furthermore, neuroimaging metaphors seem to favour oversimplification. Current reporting is therefore more likely to enable hype than to mitigate it. How can neuroscientists, given their self-ascribed social responsibility, address this conundrum? We make a case for a collective and shared responsibility among neuroscientists, journalists and other stakeholders, including funders, committed to responsible reporting on neuroimaging research.

Exploring Responsible Neuroimaging Innovation: Visions From a Societal Actor Perspective.

Apart from the scientific unknowns and technological barriers that complicate the development of medical neuroimaging applications, various relevant actors might have different ideas on what is considered advancement or progress in this field. We address the challenge of identifying societal actors and their different points of view concerning neuroimaging technologies in an early phase of neuroimaging development. To this end, we conducted 16 semistructured interviews with societal actors, including governmental policy makers, health professionals, and patient representatives, in the Netherlands. We show how the contextual aspects of applications and underlying features of the ideal health system determine the desirability. Neuroimaging developments are perceived as innovations that will optimize the current health system or as opportunities to change existing structures and practices of the current health system more radically. Insights into and understanding of these visions show incongruence between visions regarding desirable medical neuroimaging use and potential conflicting visions regarding the embedding of neuroimaging applications. We conclude that it is possible to prospectively identify incongruent visions and analyze when these visions will most likely come into conflict with each other. Such an analysis might provide a reflective space, beyond personal and political interest, suitable as a starting point for joint reflection and mutual learning in order to manage medical neuroimaging innovations towards more responsible applications.

The effect of oxybutynin on structural changes of the obstructed guinea pig bladder.

PURPOSE: Oxybutynin is used clinically to lower intravesical pressure and detrusor overactivity. In vitro it inhibits stretch induced bladder smooth muscle cell proliferation. We tested whether oxybutynin also prevents hypertrophic bladder changes in vivo in a model of partial bladder obstruction. MATERIALS AND METHODS: Subvesical obstruction was induced in immature guinea pigs by a silver ring around the urethra. Eight animals received 0.4 mg oxybutynin per kg body weight per day in 2 doses. Control groups were obstructed without oxybutynin treatment or sham operated. Urodynamic pressure flow studies were performed at 1-week intervals for 10 weeks in all animals under anesthesia with ketamine/xylazine. After 10 weeks the animals were sacrificed and the bladder was removed for structural analysis with periodic acid-Schiff stain, in which the number of glycogen granules was also scored as a measure of previous ischemia. RESULTS: Compared to the sham treated group obstructed animals had significantly higher intravesical pressure and detrusor overactivity, lower compliance and increased contractility. Obstructed animals that received oxybutynin retained normal intravesical pressure, detrusor overactivity and compliance. Their bladder contractility increased as in obstructed animals. The oxybutynin group showed less collagen infiltration in the detrusor and fewer glycogen granules compared to those in obstructed animals. CONCLUSIONS: Our results demonstrate that oxybutynin has a protective effect on bladder function and structure. Prevention of hypertrophic and ischemic bladder changes is an argument for an early start of oxybutynin treatment in children with inborn neurogenic bladder dysfunction, such as spina bifida, or in patients with urethral valves.

Detrusor glycogen reflects the functional history of bladders with partial outlet obstruction.

OBJECTIVE: To assess the relationship between glycogen content in bladder detrusor tissue and historical bladder function in a guinea-pig model of partial bladder outlet obstruction (PBOO). MATERIALS AND METHODS: In male immature guinea pigs PBOO was created with a silver ring around the proximal urethra; a control group had a sham operation for comparison. Longitudinal individual urodynamic data were obtained weekly, so that guinea pigs were killed at different levels of bladder dysfunction. Bladder sections were stained with periodic acid-Schiff (PAS) to assess overall morphology and glycogen granule density, scored from 0 (no glycogen) to 3. Glycogen scores were related to both the end-stage and historical extremes of bladder function values. RESULTS: Glycogen granules were seen only in the detrusor; as their number increased their location expanded from only close to the serosa (glycogen score 1), through the detrusor (score 2) up to the urothelium (score 3). A glycogen score of 0 correlated with normal values for all urodynamic variables. Compared with a glycogen score of 0 a score of 1 correlated with significant (P < 0.05) changes in end-stage compliance (decrease) and contractility (increase) and significantly higher historical values for contractility, pressure and number of unstable contractions (NUC). In the group with a glycogen score of 2 there were significant changes in both the end-stage values and historical extremes for compliance, pressure, contractility and NUC (all P < 0.05). In the group with a glycogen score of 3 all these changes were even more dramatic, except for the end-stage contractility, for which the increase was not significant. From glycogen score 0 to score 3 all changes increased in magnitude. CONCLUSION: A high glycogen content reflects a history of abnormal urodynamic function. This finding exemplifies the added value of structural analysis to urodynamic studies. Further studies are needed to relate bladder structure to the potential for functional recovery.