Reduction in PA28αβ activation in HD mouse brain correlates to increased mHTT aggregation in cell models

Huntington’s disease is an autosomal dominant heritable disorder caused by an expanded CAG trinucleotide repeat at the N-terminus of the Huntingtin (HTT) gene. Lowering the levels of soluble mutant HTT protein prior to aggregation through increased degradation by the proteasome would be a therapeutic strategy to prevent or delay the onset of disease. Native PAGE experiments in HdhQ150 mice and R6/2 mice showed that PA28αβ disassembles from the 20S proteasome during disease progression in the affected cortex, striatum and hippocampus but not in cerebellum and brainstem. Modulating PA28αβ activated proteasomes in various in vitro models showed that PA28αβ improved polyQ degradation, but decreased the turnover of mutant HTT. Silencing of PA28αβ in cells lead to an increase in mutant HTT aggregates, suggesting that PA28αβ is critical for overall proteostasis, but only indirectly affects mutant HTT aggregation

Terecht en onterecht gebruik van urinekatheters

Many hospitalized patients receive a urinary catheter during their stay. In 21-54% of patients, however, there is no appropriate indication for this. The most significant complication caused by the use of urinary catheters is the development of a urinary tract infection (UTI), one of the most common nosocomial infections. In 71-80% of hospital acquired UTIs a urinary catheter is present. The duration of the presence of a catheter is the major risk factor for catheter-associated UTI. Reducing the number of inappropriate catheterisations is an effective way of preventing catheter-related UTIs. Inappropriate use of indwelling urinary catheters can be reduced by maintaining strict guidelines on justifiable indications for inserting a urinary catheter, verifying daily whether the indication still applies, and by timely removal of the catheter when it is not or no longer neede

Reduction of unnecessary use of indwelling urinary catheters

The most effective way to reduce catheter-associated urinary tract infections (CA-UTIs) is to avoid unnecessary urinary catheterisation and to minimise the duration of catheterisation. To implement and assess the effect of an intervention to reduce the duration of urinary tract catheterisation. This quality improvement project was set up as a before-after comparison consisting of a 2-month pre-intervention period, a period in which the intervention was implemented and a 2-month post-intervention period. The intervention included educational sessions to increase physicians' awareness and the daily reassessment of catheter use. The primary endpoint was the duration of catheterisation. Secondary endpoints were the catheter utilisation ratio, the length of hospital stay, the number of hospital-acquired symptomatic CA-UTIs and the number of appropriate indications for catheterisation. During the total study period, 149 patients (18.3%) were catheterised at some time during their hospital stay. There was a statistically significant decrease in the duration of catheterisation (median 7 vs 5 days; p <0.01), length of hospital stay (median 13 vs 9 days; p <0.01), and number of hospital-acquired CA-UTIs (4 vs 0, p=0.04) in the pre-intervention versus post-intervention period. An intervention to raise more awareness of the risks of inappropriate catheterisation can reduce the duration of catheterisation along with the length of hospital stay and the number of hospital-acquired symptomatic CA- UTIs, even in a short period of tim

A qualitative participatory study to identify experiences of coronary heart disease patients to support the development of online self-management services

Web-based self-management services remain underutilized in current practice. Our aim was to gain insight into disease and self-management experiences of patients in early and progressive stages of coronary heart disease (CHD), to understand moderating effects of daily life experiences on the utilization of web-based self-management services and preconditions for use. We applied generative research techniques, which stem from the field of product design and are characterized by the use of creative processes. Three groups of patients with CHD received a sensitizing package to document and reflect on their health, and were subsequently either interviewed or participated in a focus group session. In total, 23 patients participated in this study. Emerging themes were (1) fear for recurrent events, (2) experiences with professional care, (3) the perceived inability to prevent disease progression, (4) the desire to go on living without thinking about the disease every day, (5) the social environment as a barrier to or facilitator for self-management, and (6) the need for information tailored to personal preferences. How patients experience their disease varies between stable and post-acute stages, as well as between early and progressive stages of CHD. Patients in post-acute stages of the disease seem to be most amenable to support, while patients in stable stages want to live their life without being reminded of their disease. In the context of self-management, web-based services should be adapted to the variation in needs that occur in the different stages of CHD and new strategies to fit such services to these needs should be developed. Furthermore, they should be tailored to patients' individual health situation and preferences, support patient empowerment, and manage expectations regarding the progression of their diseas