Effect on hospital incentive payments and quality performance of a hospital pay for performance (P4P) programme in Belgium.

BACKGROUND: Belgium initiated a hospital pay for performance (P4P) programme after a decade of fixed bonus budgets for "quality and safety contracts". This study examined the effect of P4P on hospital incentive payments, performance on quality measures, and the association between changes in quality performance and incentive payments over time. METHODS: The Belgian government provided information on fixed bonus budgets in 2013-2017 and hospital incentive payments as well as hospital performance on quality measures for the P4P programmes in 2018-2020. Descriptive analyses were conducted to map the financial repercussion between the two systems. A difference-in-difference analysis evaluated the association between quality indicator performance and received incentive payments over time. RESULTS: Data from 87 acute-care hospitals were analyzed. In the transition to a P4P programme, 29% of hospitals received lower incentive payments per bed. During the P4P years, quality performance scores increased yearly for 55% of hospitals and decreased yearly for 5% of hospitals. There was a significant larger drop in incentive payments for hospitals that scored above median with the start of the P4P programme. CONCLUSIONS: The transition from fixed bonus budgets for quality efforts to a new incentive payment in a P4P programme has led to more hospitals being financially impacted, although the effect is marginal given the small P4P budget. Quality indicators seem to improve over the years, but this does not correlate with an increase in reward per bed for all hospitals due to the closed nature of the budget.

The FlaQuM-Quickscan: A starting point to include primary care professionals' perspectives in the evaluation of hospital quality priorities.

INTRODUCTION: Today, primary care professionals' (PCPs) perspectives on hospital quality are unknown when evaluating hospital quality priorities. The aims of the present study were to identify key healthcare quality attributes from PCPs' perspective, to validate an instrument that measures PCPs' experiences of healthcare quality multidimensionally and to define hospital quality priorities based on PCPs' experiences. MATERIAL AND METHODS: Focus groups with PCPs were conducted to identify quality attributes through a qualitative in-depth analysis. A multicentre study of 18 hospitals was used to quantitatively assess construct, discriminant and criterion validity of the FlaQuM-Quickscan, an instrument that measures 'Healthcare quality for patients and kin' (part 1) and 'Healthcare quality for professionals' (part 2). To set quality priorities, scores on quality domains were analyzed descriptively and between-hospital variation was examined by evaluating differences in hospitals' mean scores on the quality domains using one-way Analysis of Variance (ANOVA). RESULTS: Identified key attributes largely corresponded with Lachman's multidimensional quality model. Including 'Communication' as a new quality domain was recommended. The FlaQuM-Quickscan was completed by 550 PCPs. Confirmatory factor analyses showed reasonable to good fit, except for the Root Mean Square Error of Approximation (RMSEA) in part 2. The 'Equity' domain scored the highest in parts 1 and 2. Domains 'Kin-centred care' and 'Accessibility and timeliness' scored the lowest in part 1 and 'Resilience' and 'Partnership and co-production' in part 2. Significant variation in hospitals' mean scores was observed for eleven domains in part 1 and sixteen domains in part 2. CONCLUSIONS: The results gained a better understanding of PCPs' perspective on quality. The FlaQuM-Quickscan is a valid instrument to measure PCPs' experiences of hospital quality. Identified priorities indicate that hospital management should focus on multifaceted quality strategies, including technical domains, person-and kin-centredness, core values and catalysts.

Advanced drinking water production by 1 kDa hollow fiber nanofiltration - Biological activated carbon filtration (HFNF - BACF) enhances biological stability and reduces micropollutant levels compared with conventional surface water treatment.

This study comprehensively investigates the quality of drinking water produced by novel advanced treatment encompassing 1 kDa hollow fiber nanofiltration (HFNF) - Biological Activated Carbon Filtration (BACF) from (reservoir) surface water, and compares this with drinking water after conventional 'CSF' pretreatment (coagulation - flocculation - sedimentation - media filtration - UV-disinfection) - BACF. The objective of HFNF - BACF treatment is to enhance the drinking water's quality in increased biological stability, reduced concentrations of organic micropollutants (OMP), and improvement in other chemical-physical parameters, whilst maintaining sufficient hardness to avoid subsequent remineralization. For this study a large suite of quality parameters was extensively monitored in pilot plants during nearly two years, enabling the incorporation of seasonal effects. HFNF - BACF treatment accomplished a similarly high level of biological stability as regrowth-free drinking waters (total organic carbon (DOC) 0.6 mg/L, assimilable organic carbon (AOC) 4 µg/L Ac-C and <1 µg/L biopolymer-C, total microbial growth potential (MGP) as BPC14 50 ng d/L and as BGP 170 × 103 cells/mL), unlike the conventional treatment (1.9 mg/L, 10 µg/L, 9 µg/L, 130 ng d/L and 170 × 103 cells/mL, respectively) where regrowth occurred in its distribution network. Average OMP removal, including perfluoro-alkyl substances (PFAS), by HFNF - BACF (54%) was higher than conventional treatment (37%). This improvement was mainly attributable to rejection in the HFNF membrane step, indicating that the DOC concentration after HFNF pretreatment was not yet sufficiently low to eliminate competitive adsorption and/or preloading in the BACF (confirmed by laboratory experiments). The advanced treatment also performed better in turbidity, particulates and most trace metals. Importantly, hardness retention by HFNF was only moderate, rendering remineralization unnecessary. Overall, this study demonstrates the superior performance in water quality of advanced HFNF - BACF treatment compared to conventional treatment.

Achieving quadruple aim goals through clinical networks: A systematic review.

INTRODUCTION: Clinical Networks are complex interventions that enable healthcare professionals from various disciplines to work in a coordinated manner in the context of multiple care settings, to provide a high quality response to a specific disease. The aim of this study was to evaluate if clinical networks are able to improve effectiveness, efficiency, patients' satisfaction and professionals' behavior in the health care settings, namely the "quadruple aim" quality goals. MATERIALS AND METHODS: A systematic review of documents published until February 28, 2018, in Medline, Embase and CINAHL was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses approach. A specific research strategy was created to identify studies evaluating effectiveness, efficiency, patient satisfaction and professionals well-being obtained through clinical networks implementation. RESULTS: 14249 studies were identified; 12 of these were eligible to the evaluation of "Quadruple Aim" outcomes. 9 studies focused on patients' outcomes improvement and 4 on network efficiency. Professionals' and patients' experience were not considered in any study. CONCLUSIONS: There are some evidences that clinical network can improve patients' outcomes and health funds allocation in a small number of moderate-low quality studies. Further rigorous studies are needed to confirm these findings and to evaluate patients' and professionals' experience, taking into account also networks' structural features that could influence outcomes achievement.

Citizen approval of nudging interventions promoting healthy eating: the role of intrusiveness and trustworthiness.

BACKGROUND: Nudging interventions have lately been widely adopted by policy makers to increase the welfare of society and to help citizens make better choices. Hence, it has become important to understand the conditions under which they are approved. While most research has looked into whether professionals approve of nudging interventions, surprisingly the opinion of the target group has been widely ignored. This study investigated citizens' level of approval of nudging in the realm of healthy eating promotion, as well as its boundary conditions. METHODS: Participants (N = 1441) from the US and seven European countries were probed for their level of approval of nudges. Moreover, we investigated whether these levels of approval were dependent on the level of intrusiveness of the nudge and on the type and trustworthiness of the source (policy makers, experts, industry) implementing the nudge. RESULTS: People revealed moderate to high levels of approval with nudging across all countries. Intrusiveness and nudging approval were negatively associated. Nudges implemented by experts received more approval than those by policy makers. In general, approval increased with the trustworthiness of the source. CONCLUSIONS: These results provide information for European and American policy makers considering using nudging in their policy repertoire.

Differential electrophysiological correlates of panic disorder in non-pulsatile tinnitus.

AIMS: The prevalence of panic disorder (PD) reportedly is up to fivefold higher in people with tinnitus than it is in the general population. The brain networks in the two conditions overlap but the pathophysiological link remains unclear. In this study the electrophysiological brain activity is investigated in adults with non-pulsatile tinnitus with and without concurrent PD. METHODS: Resting-state EEGs of 16 participants with non-pulsatile tinnitus and PD were compared with those of 16 peers with non-pulsatile tinnitus without PD and as many healthy controls. The sLORETA technique was used to identify group-specific electrophysiological frequencies in the brain and to approximate the brain regions where differences occurred. The influence of distress was investigated and functional connectivity charted using the Region-of-Interest (ROI) approach (amygdala, anterior cingulate cortex (ACC), insula, precuneus). RESULTS: The comorbid group showed significantly diminished theta activity (p < 0.05) in the precuneus (BA7) compared to the tinnitus group without PD as well as in another region of the precuneus (BA31) as compared to the controls. Higher levels of distress influenced results in the tinnitus group without PD, while in those with PD a diminished connectivity was observed between the dorsal ACC and the other three ROIs as contrasted to the controls. CONCLUSIONS: Adults with non-pulsatile tinnitus and concurrent PD show differential brain activity patterns to tinnitus only sufferers and healthy controls. Higher levels of distress may modulate brain activity in the absence of PD. Screening for distress is recommended in both clinical and research settings.

Nudging at the checkout counter - A longitudinal study of the effect of a food repositioning nudge on healthy food choice.

Objective The current study is a longitudinal conceptual replication and aimed to investigate the effect of a food repositioning nudge on healthy food choice in a kiosk. Design During eight weeks, sales data were collected. The former four weeks formed the baseline phase and the latter four weeks formed the nudge phase where healthy food products were repositioned at the checkout counter display, while unhealthy alternatives remained available elsewhere in the store. Main Outcome Measures The main variable of interest was the proportion of healthy food products (selected to be repositioned) sold per day. Also exit interviews were administered to gather individual level data about purchases, and awareness and opinions of the nudge. Results Results showed that the proportion of selected healthy food products in total food sales was higher in all four nudge weeks than in all four baseline weeks. Individual level data showed that more customers had bought a selected healthy food product in the nudge phase and that customers generally approved of the nudge. Conclusion The current study strengthened the empirical evidence base of repositioning healthy food products as an effective and well-accepted nudge.

Mapping, modeling, and characterization of protein-protein interactions on a proteomic scale.

Proteins effect a number of biological functions, from cellular signaling, organization, mobility, and transport to catalyzing biochemical reactions and coordinating an immune response. These varied functions are often dependent upon macromolecular interactions, particularly with other proteins. Small-scale studies in the scientific literature report protein-protein interactions (PPIs), but slowly and with bias towards well-studied proteins. In an era where genomic sequence is readily available, deducing genotype-phenotype relationships requires an understanding of protein connectivity at proteome-scale. A proteome-scale map of the protein-protein interaction network provides a global view of cellular organization and function. Here, we discuss a summary of methods for building proteome-scale interactome maps and the current status and implications of mapping achievements. Not only do interactome maps serve as a reference, detailing global cellular function and organization patterns, but they can also reveal the mechanisms altered by disease alleles, highlight the patterns of interaction rewiring across evolution, and help pinpoint biologically and therapeutically relevant proteins. Despite the considerable strides made in proteome-wide mapping, several technical challenges persist. Therefore, future considerations that impact current mapping efforts are also discussed.

Solifenacin is effective and well tolerated in patients with neurogenic detrusor overactivity: Results from the double-blind, randomized, active- and placebo-controlled SONIC urodynamic study.

AIMS: To investigate the effect on urodynamics of 4 weeks treatment with solifenacin succinate in patients with neurogenic detrusor overactivity (NDO) due to multiple sclerosis (MS) or spinal cord injury (SCI). METHODS: SONIC was a prospective, multicenter, double-blind, phase 3b/4 study investigating the efficacy and safety of solifenacin 10 mg in patients with NDO due to MS or SCI. Patients (n = 189) were randomized to placebo or active treatment (solifenacin 5 mg, 10 mg or oxybutynin hydrochloride 15 mg) for 4 weeks, after a 2-week, single-blind, placebo run-in period. The primary endpoint was change in maximum cystometric capacity (MCC) from baseline to end of treatment. The primary analysis compared solifenacin 10 mg versus placebo; all other comparisons were considered secondary. Secondary endpoints included changes in urodynamic parameters, patient-reported outcomes, and safety assessments. RESULTS: In the primary analysis, solifenacin 10 mg significantly improved mean change from baseline MCC versus placebo (P < 0.001) and was associated with improvements in bladder volume at first contraction and at first leak as well as detrusor pressure at first leak. Similar results were obtained for oxybutynin versus placebo. Patient perception of bladder condition significantly improved with solifenacin 10 mg versus placebo (P = 0.041). There was a clear improvement in quality of life (QoL) in the solifenacin arms versus placebo. The overall incidence of adverse events was low. CONCLUSIONS: In patients with NDO due to MS and SCI, 4 weeks of treatment with solifenacin 10 mg improved urodynamic variables and QoL versus placebo and was well tolerated. Neurourol. Urodynam. 36:414-421, 2017. © 2015 Wiley Periodicals, Inc.

Preferred frequencies and waveforms for spinal cord stimulation in patients with complex regional pain syndrome: A multicentre, double-blind, randomized and placebo-controlled crossover trial.

BACKGROUND: Conventional tonic spinal cord stimulation (SCS) is an effective treatment for patients with therapy-resistant complex regional pain syndrome (CRPS). Although the therapeutic effect of SCS can diminish over time due to tolerance, pain control can be regained by changing the pulse width and the amplitude and/or by increasing the stimulation frequency. This multicentre, double-blind, randomized and placebo-controlled crossover trial was conducted to investigate whether more effective pain reduction is achieved with different frequencies (trial registration, current controlled trials, ISRCTN 36655259). METHODS: The investigated settings are as follows: standard 40, 500, 1200 Hz, burst and placebo stimulation. All five were programmed in random order during the 10-week crossover period (2 weeks/setting). The primary outcome parameters were scores on the visual analogue scale (VAS), McGill Pain Questionnaire (MPQ) and the Global Perceived Effect (GPE); at the end of the crossover period, patients decided which SCS setting they preferred. A linear mixed models analysis was performed in 29 patients who completed the crossover trial. RESULTS: Significant pain reduction and GPE satisfaction was achieved with four SCS settings compared with placebo stimulation, and these four settings did not differ significantly from each other. Standard stimulation was preferred by 48% of the patients, while 52% preferred non-standard stimulation. Other than pain reduction, factors such as user-friendliness, comfort and recharging time may have influenced the patient's final decision for the preferred stimulation setting. CONCLUSIONS: Apparently, for various reasons, patients have a preference for different SCS setting. Therefore, future neuromodulation should aim to implement customized individual patient care by incorporating all stimulation options in one device. SIGNIFICANCE: This study demonstrates that standard frequency SCS is an effective therapy for patients with CRPS. However, it also demonstrates that patients can often gain better pain reduction with non-standard frequencies of SCS. Furthermore, it shows that the preferred stimulation setting is not solely driven by the amount of pain reduction, but is also influenced by which stimulation setting feels most comfortable and provides the best user-friendliness. Therefore, we strive to maximize the therapeutic effects of SCS in as many patients as possible. This can be achieved with customized individual patient care by incorporating the various frequencies and waveforms into one single device.

Consumers' choice-blindness to ingredient information.

Food manufacturers and policy makers have been tailoring food product ingredient information to consumers' self-reported preference for natural products and concerns over food additives. Yet, the influence of this ingredient information on consumers remains inconclusive. The current study aimed at examining the first step in such influence, which is consumers' attention to ingredient information on food product packaging. Employing the choice-blindness paradigm, the current study assessed whether participants would detect a covertly made change to the naturalness of ingredient list throughout a product evaluation procedure. Results revealed that only few consumers detected the change on the ingredient lists. Detection was improved when consumers were instructed to judge the naturalness of the product as compared to evaluating the product in general. These findings challenge consumers' self-reported use of ingredient lists as a source of information throughout product evaluations. While most consumers do not attend to ingredient information, this tendency can be slightly improved by prompting their consideration of naturalness. Future research should investigate the reasons for consumers' inattention to ingredient information and develop more effective strategies for conveying information to consumers.

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.

Durable improvements in urinary incontinence and positive treatment response in patients with idiopathic overactive bladder syndrome following long-term onabotulinumtoxinA treatment: Final results of 3.5-year study.

OBJECTIVES: Here we present the final results from an extension study assessing long-term onabotulinumtoxinA treatment (3.5 years) in patients with idiopathic overactive bladder. METHODS: Patients who completed either of 2 Phase III trials were eligible to enter a 3-year extension study in which they received multiple onabotulinumtoxinA (100 U) treatments. Data were analyzed for the overall population of patients who received 100 U in any treatment cycle (n=829) and within discrete subgroups of patients who received exactly 1 (n=105), 2 (n=118), 3 (n=117), 4 (n=83), 5 (n=46), or 6 (n=33) treatments of the 100 U dose throughout the study (n=502). RESULTS: Of the 829 patients enrolled, 51.7 % completed the study. Discontinuations due to AEs/lack of efficacy were low (5.1/5.7 %); other reasons were not treatment-related. Mean reductions from baseline in urinary incontinence (UI) episodes/day (week 12; co-primary endpoint) were consistent among discrete subgroups who received 1 (-3.1), 2 (-2.9, -3.2), 3 (-4.1 to -4.5), 4 (-3.4 to -3.8), 5 (-3.0 to -3.6), or 6 (-3.1 to -4.1) treatments. A consistently high proportion of patients reported improvement/great improvement on the Treatment Benefit Scale (week 12; co-primary endpoint) in the discrete subgroups across all treatments (70.0-93.5 %). Median time to request retreatment was ≤6 months for 34.2 %, >6-≤12 months for 37.2 %, and >12 months for 28.5 % of patients. Most common AE was UTI, with no changes in safety profile over time. CONCLUSION: Long-term onabotulinumtoxinA treatment resulted in consistent reductions in UI and high proportions of patients reporting improvement after each treatment, with no new safety findings.

Chromosomal Copy Number Variation in Saccharomyces pastorianus Is Evidence for Extensive Genome Dynamics in Industrial Lager Brewing Strains.

Lager brewing strains of Saccharomyces pastorianus are natural interspecific hybrids originating from the spontaneous hybridization of Saccharomyces cerevisiae and Saccharomyces eubayanus. Over the past 500 years, S. pastorianus has been domesticated to become one of the most important industrial microorganisms. Production of lager-type beers requires a set of essential phenotypes, including the ability to ferment maltose and maltotriose at low temperature, the production of flavors and aromas, and the ability to flocculate. Understanding of the molecular basis of complex brewing-related phenotypic traits is a prerequisite for rational strain improvement. While genome sequences have been reported, the variability and dynamics of S. pastorianus genomes have not been investigated in detail. Here, using deep sequencing and chromosome copy number analysis, we showed that S. pastorianus strain CBS1483 exhibited extensive aneuploidy. This was confirmed by quantitative PCR and by flow cytometry. As a direct consequence of this aneuploidy, a massive number of sequence variants was identified, leading to at least 1,800 additional protein variants in S. pastorianus CBS1483. Analysis of eight additional S. pastorianus strains revealed that the previously defined group I strains showed comparable karyotypes, while group II strains showed large interstrain karyotypic variability. Comparison of three strains with nearly identical genome sequences revealed substantial chromosome copy number variation, which may contribute to strain-specific phenotypic traits. The observed variability of lager yeast genomes demonstrates that systematic linking of genotype to phenotype requires a three-dimensional genome analysis encompassing physical chromosomal structures, the copy number of individual chromosomes or chromosomal regions, and the allelic variation of copies of individual genes.

The role of bladder neck suspension in the era of mid-urethral sling surgery.

INTRODUCTION: Mid-urethral slings are currently considered to be the gold standard for the surgical treatment of stress urinary incontinence, replacing bladder neck suspension techniques which previously occupied this position. In recent years, however, there have been concerns with regard to the use of synthetic material in vaginal surgery. METHODS: We performed a review of the literature to discuss the role of bladder neck suspension techniques in the current clinical setting. CONCLUSIONS: Bladder neck suspension techniques consist of vaginal techniques, needle suspension techniques and retropubic techniques. The latter two techniques have been proven to offer durable outcomes for stress urinary incontinence. As compared to autologous slings, the long-term success rates may be considered inferior, but so is the rate of complication, resulting in higher patient satisfaction. Bladder neck suspension techniques may have a role in treating recurrent and/or persisting stress urinary incontinence after (failed) sling surgery and remain of particular interest in patients with stress urinary incontinence when performing concomitant surgery, for example for prolapse.

Olfactomedin 4 Serves as a Marker for Disease Severity in Pediatric Respiratory Syncytial Virus (RSV) Infection.

BACKGROUND: Respiratory viral infections follow an unpredictable clinical course in young children ranging from a common cold to respiratory failure. The transition from mild to severe disease occurs rapidly and is difficult to predict. The pathophysiology underlying disease severity has remained elusive. There is an urgent need to better understand the immune response in this disease to come up with biomarkers that may aid clinical decision making. METHODS: In a prospective study, flow cytometric and genome-wide gene expression analyses were performed on blood samples of 26 children with a diagnosis of severe, moderate or mild Respiratory Syncytial Virus (RSV) infection. Differentially expressed genes were validated using Q-PCR in a second cohort of 80 children during three consecutive winter seasons. FACS analyses were also performed in the second cohort and on recovery samples of severe cases in the first cohort. RESULTS: Severe RSV infection was associated with a transient but marked decrease in CD4+ T, CD8+ T, and NK cells in peripheral blood. Gene expression analyses in both cohorts identified Olfactomedin4 (OLFM4) as a fully discriminative marker between children with mild and severe RSV infection, giving a PAM cross-validation error of 0%. Patients with an OLFM4 gene expression level above -7.5 were 6 times more likely to develop severe disease, after correction for age at hospitalization and gestational age. CONCLUSION: By combining genome-wide expression profiling of blood cell subsets with clinically well-annotated samples, OLFM4 was identified as a biomarker for severity of pediatric RSV infection.

Urgency and other lower urinary tract symptoms in men aged ≥ 40 years: a Belgian epidemiological survey using the ICIQ-MLUTS questionnaire.

BACKGROUND AND AIMS: The aim of this study was to assess prevalence and associated bother of male lower urinary tract symptoms (LUTS), especially of urgency and other storage symptoms, since these are generally assumed to be underdiagnosed/undertreated in men. METHODS: Data on bladder condition of men ≥ 40 years were prospectively collected by 124 general practitioners (GPs) during a regular visit for any reason, using the validated ICIQ-MLUTS questionnaire. For 13 symptoms, prevalence (scale 0-4) and bother (scale 0-10) were scored. General bladder-related quality of life (scale 0-3) was also assessed. RESULTS: Data from 5890 men (mean age: 61.2 years) were analysed. A total of 7.7% had urgency most or all of the time (score ≥ 3) and 6.2% had bothersome urgency (score ≥ 3 + bother score ≥ 5). Nocturia (69.2%) and urgency (58.3%) were the most prevalent and bothersome symptoms. Both prevalence and bother of all LUTS increased with age. Additionally, 28.9% of men reported to be a little bothered by their bladder condition in everyday life, while 11.9% were bothered a lot/very much (2.5% in age group 40-49 years increasing to 29.2% in those > 80 years). CONCLUSIONS: In the general population of men ≥ 40 years who visited a GP for any reason, 41% indicated to be at least a little bothered by their bladder condition. The prevalence of LUTS, especially nocturia and urgency, is high and a significant number of men indicated to be seriously bothered. Increasing awareness of male LUTS, and storage symptoms in particular, is warranted to discuss management options that could increase quality of life.

Performance of different culture methods and of a commercial molecular assay for the detection of carbapenemase-producing Enterobacteriaceae in nursing homes and rehabilitation centers.

Over the last several years, carbapenemase-producing Enterobacteriaceae (CPE) have been increasingly detected not only among patients in acute care hospitals, but also in long-term care facilities. In this point prevalence survey, residents from three nursing homes and patients in one rehabilitation center were screened for asymptomatic intestinal carriage of CPE by rectal swabs. The first objective was to evaluate the hypothesis of the establishment of a CPE reservoir in a geriatric/chronic care population. Secondly, we evaluated the comparative performances of different culture methods (chromID(®) CARBA, chromID(®) OXA-48, MacConkey with temocillin/meropenem, ertapenem enrichment broth) and a commercial molecular assay (Check-Direct CPE). From the 257 included residents, only one had evidence for CPE carriage. From the rectal swabs of this resident, an OXA-48-producing Klebsiella pneumoniae could be isolated and was confirmed by a molecular assay both on the strain and on the rectal swab. The specificity of the different culture methods and Check-Direct CPE was at least 97 %. Neither enrichment broth nor prolonged incubation up to 48 h increased the yield of CPE. This point prevalence survey shows a low CPE prevalence of 0.39 %. Larger scaled studies are needed in order to confirm the role of chronic care settings as secondary CPE reservoirs and to adjust the infection control and prevention recommendations.

TRP channels in lower urinary tract dysfunction.

Lower urinary tract dysfunction (LUTd) represents a major healthcare problem. Although it is mostly not lethal, associated social disturbance, medical costs, loss of productivity and especially diminished quality of life should not be underestimated. Although more than 15% of people suffer from a form of LUTd to some extent, pathophysiology often remains obscure. In the past 20 years, transient receptor potential (TRP) channels have become increasingly important in this field of research. These intriguing ion channels are believed to be the main molecular sensors that generate bladder sensation. Therefore, they are intensely pursued as new drug targets for both curative and symptomatic treatment of different forms of LUTd. TRPV1 was the first of its class to be investigated. Actually, even before this channel was cloned, it had already been targeted in the bladder, with clinical trials of intravesical capsaicin instillations. Several other polymodally gated TRP channels, particularly TRPM8, TRPA1 and TRPV4, also appear to play a prominent role in bladder (patho)physiology. With this review, we provide a brief overview of current knowledge on the role of these TRP channels in LUTd and their potential as molecular targets for treatment.

Regulated genes in psoriatic skin during treatment with fumaric acid esters.

BACKGROUND: Fumaric acid esters (FAEs) are widely used in Europe for the treatment of psoriasis because of their clinical efficacy and favourable safety profile. However, the mechanisms of action by which FAEs improve psoriasis remain largely unknown. OBJECTIVES: To identify pathways and mechanisms affected by FAE treatment and to compare these with pathways affected by treatment with the antitumour necrosis factor (anti-TNF)-α biologic etanercept. METHODS: In a prospective cohort study, 50 patients with plaque psoriasis were treated with FAEs for 20 weeks. Nine patients were randomly selected for gene expression profiling of plaque biopsies from week 0 and week 12. The groups consisted of FAE responders [> Psoriasis Area and Severity Index (PASI)-75 improvement] and nonresponders (< PASI-50 improvement). Changes in gene expression profiles were analysed using Ingenuity Pathway Analysis (IPA) and the outcome was compared with gene expression affected by etanercept. RESULTS: Response to FAE treatment was associated with a ≥ 2-fold change (P < 0.05) in the expression of 458 genes. In FAE responders the role of interleukin-17A in the psoriasis pathway was most significantly activated. Glutathione and Nrf2 pathway molecules were specifically induced by FAE treatment and not by etanercept treatment, representing an FAE-specific effect in psoriatic skin. In addition, FAE treatment specifically induced the transcription factors PTTG1, NR3C1, GATA3 and NFκBIZ in responding patients. CONCLUSIONS: FAE treatment induces glutathione and Nrf2 pathway genes in lesional skin of patients with psoriasis. In responders, FAEs specifically regulate the transcription factors PTTG1, NR3C1, GATA3 and NFκBIZ, which are important in normal cutaneous development, and the T-helper (Th)2 and Th17 pathways, respectively.