Comparing the effectiveness and costs of Bevacizumab to Ranibizumab in patients with Diabetic Macular Edema: A randomized clinical trial (the BRDME study)

Background: The effectiveness of ranibizumab in the treatment of diabetic macular edema has been proven with large clinical trials. For bevacizumab only two clinical trials have been published and a head-to-head comparison is lacking to date. However, if proved non-inferior to ranibizumab, use of the off-label bevacizumab could reduce costs enormously without a loss in visual acuity. A cost-effectiveness study has been designed to substantiate this hypothesis. Aim: To compare the effectiveness and costs of 1.25 mg of bevacizumab to 0.5 mg ranibizumab given as monthly intravitreal injections during 6 months in patients with diabetic macular edema. It is hypothesized that bevacizumab is non-inferior to ranibizumab regarding its effectiveness. Design: This is a randomized, controlled, double masked, clinical trial in 246 patients in seven academic trial centres in The Netherlands. Outcomes: The primary outcome measure is the change in best-corrected visual acuity (BCVA) in the study eye from baseline to month 6. Secondary outcomes are the proportions of patients with a gain or loss of 15 letters or more or a BCVA of 20/40 or more at 6 months, the change in leakage on fluorescein angiography and the change in foveal thickness by optical coherence tomography at 6 months, the number of adverse events in 6 months, and the costs per quality adjusted life-year of the two treatments

City-to-City Learning to Enhance Urban Water Management: The Contribution of the City Blueprint Approach

Cities face several water challenges which ask for more pro-active governance approaches. One option that cities have is to start networking and build learning alliances with other cities. Forming meaningful alliances however asks for clear and easily accessible city-matching methodologies which are based on a standardised assessment approach and the presence of structured and large databases. The City Blueprint Approach is an example of such a methodology. Aim of this paper is to show the potential of this approach as a substantive methodology for enhancing urban water management. This is done by illustrating the use of the approach in four cities, which were studied in the H2020 project POWER (Political and sOcial awareness on Water EnviRonmental challenges) and by comparing the results found with good practises present in the City Blueprint database. These good practises however cannot simply be copy-pasted from one city to another. We therefore outline in what way more in-depth city to city learning results can be achieved and be tailored to best-fit particular urban areas. The paper concludes with some suggestions for enhancing the potential for city-to-city learning in urban water governance networks

City-to-city learning to enhance urban water management: The contribution of the City Blueprint Approach

Cities face several water challenges which ask for more pro-active management approaches. One option that cities have is to start networking and build learning alliances with other cities. Forming meaningful alliances however asks for clear and easily accessible city-matching methodologies which are based on a standardised assessment approach and the presence of structured and large databases. The City Blueprint Approach is an example of such a methodology. Aim of this paper is to demonstrate the potential of this approach as a substantive methodology for enhancing learning on urban water management. This is done by illustrating the use of the approach in four cities, which were studied in the H2020 project POWER (Political and sOcial awareness on Water EnviRonmental challenges) and by comparing the results found with good practices present in the City Blueprint database. These good practices however cannot simply be copy-pasted from one city to another. We therefore outline in what way more in-depth city-to-city (C2C) learning results can be achieved and be tailored to best-fit particular urban areas. The paper concludes with some suggestions for enhancing the potential for C2C learning in urban water management networks

From subthalamic local field potentials to the selection of chronic deep brain stimulation contacts in Parkinson's disease - A systematic review

Background: Programming deep brain stimulation (DBS) of the subthalamic nucleus for optimal symptom control in Parkinson's Disease (PD) requires time and trained personnel. Novel implantable neurostimulators allow local field potentials (LFP) recording, which could be used to identify the optimal (chronic) stimulation contact. However, literature is inconclusive on which LFP features and prediction techniques are most effective. Objective: To evaluate the performance of different LFP-based physiomarkers for predicting the optimal (chronic) stimulation contacts.Methods: A literature search was conducted across nine databases, resulting in 418 individual papers. Two independent reviewers screened the articles based on title, abstract, and full text. The quality of included studies was assessed using a modified Joanna Briggs Institute Critical Appraisal Checklist for Case Series. Results were categorised in four classes based on the predictive performance with respect to the a priori chance. Results: Twenty-five studies were included. Single-feature beta-band predictions demonstrated positive performance scores in 94 % of the outcomes. Predictions based on single non-beta-frequency features yielded positive scores in only 25 % of the outcomes, with positive results mainly for high frequency oscillations. Multi-feature predictions (e.g. machine learning) achieved accuracy scores within the two highest performance classes more often than single beta-based predictions (100 % versus 39 %). Conclusion: Predicting the optimal stimulation contact based on LFP recordings is feasible and can improve DBS programming efficiency in PD. Single beta-band predictions show more promising results than non-beta-frequency features alone, but are outperformed by multi-feature predictions. Future research should further explore multi-feature predictions for optimal contact identification.</p

Improving Health Literacy Responsiveness:A Randomized Study on the Uptake of Brochures on Doctor-Patient Communication in Primary Health Care Waiting Rooms

Presenting attractive and useful health education materials in waiting rooms can help improve an organization's health literacy responsiveness. However, it is unclear to what extent patients may be interested in health education materials, such as brochures. We conducted a three-week field study in waiting rooms of three primary care centers in Groningen. Three versions of a brochure on doctor-patient communication were randomly distributed, 2250 in total. One version contained six short photo stories, another version was non-narrative but contained comparable photos, and the third version was a traditional brochure. Each day we counted how many brochures were taken. We also asked patients (N = 471) to participate in a brief interview. Patients who consented (N = 390) were asked if they had noticed the brochure. If yes (N = 135), they were asked why they had or had not browsed the brochure, and why they had or had not taken it. Interview responses were categorized by two authors. Only 2.9% of the brochures were taken; no significant association with brochure version was found. Analysis of the interview data showed that the version with the photo narrative was noticed significantly more often than the non-narrative version or the traditional version. These results suggest that designing attractive and comprehensible health materials is not enough. Healthcare organizations should also create effective strategies to reach their target population

Combining HPAEC-PAD, PGC-LC-MS, and 1D ¹H NMR to Investigate Metabolic Fates of Human Milk Oligosaccharides in 1-Month-Old Infants:A Pilot Study

A solid-phase extraction procedure was optimized to extract 3-fucosyllactose and other human milk oligosaccharides (HMOs) from human milk samples separately, followed by absolute quantitation using high-performance anion-exchange chromatography-pulsed amperometric detection and porous graphitized carbon-liquid chromatography-mass spectrometry, respectively. The approach developed was applied on a pilot sample set of 20 human milk samples and paired infant feces collected at around 1 month postpartum. One-dimensional 1H nuclear magnetic resonance spectroscopy was employed on the same samples to determine the relative levels of fucosylated epitopes and sialylated (Neu5Ac) structural elements. Based on different HMO consumption patterns in the gastrointestinal tract, the infants were assigned to three clusters as follows: complete consumption; specific consumption of non-fucosylated HMOs; and, considerable levels of HMOs still present with consumption showing no specific preference. The consumption of HMOs by infant microbiota also showed structure specificity, with HMO core structures and Neu5Ac(α2-3)-decorated HMOs being most prone to degradation. The degree and position of fucosylation impacted HMO metabolization differently. </p

The Coax Dipole: A fully flexible coaxial cable dipole antenna with flattened current distribution for body imaging at 7 Tesla

Purpose: The coax dipole antenna, a flexible antenna for body imaging at 7T is presented. Similar to the high impedance coil, this coaxial cable antenna is fed on the central conductor and through gaps in the shield, the current passes to the outside of the antenna to generate B1 field. This could achieve more favorable current distributions and better adaptation to the body curvature. Methods: Finite difference time domain (FDTD) simulations are performed to optimize the positions of the gaps in the shield for a flat current profile. Lumped inductors are added to each end to reduce losses. The performance of a single antenna is compared to a fractionated dipole using B1 maps and MR thermometry. Finally, an array of eight coax dipoles is evaluated in simulations and used for in-vivo scanning. Results: An optimal configuration is found with gaps located at 10 cm from the center and inductor values of 28 nH. In comparison to the fractionated dipole antenna, in single antenna phantom measurements the coax dipole achieves similar B1 amplitude with 18% lower peak temperature. In simulations, the eight-channel array of coax dipoles improved B1 homogeneity by 18%, along with small improvements in transmit efficiency and specific absorption rate (SAR). MRI measurements on three volunteers show more consistent performance for the coax dipoles. Conclusion: The coax dipole is a novel antenna design with a flattened current distribution resulting in beneficial properties. Also, the flexible design of the coax dipoles allows better adaptation to the body curvature and can potentially be used for a wide range of imaging targets

Accelerating the transition from a linear to a circular healthcare sector: ESCH-R:study design and methodology

Due to the significant environmental impact of healthcare, there is an urgent need to accelerate its circular transition. We provide an overview of the ESCH-R project study design and methodology for accelerating the transition from a linear to a circular healthcare sector through the development and implementation of circular interventions in the Netherlands. Using a transdisciplinary approach, we will apply the 10-R ladder framework for a circular economy to hospitals. Methods are presented to analyze current clinical practices, policies and requirements for sustainable behavioral change, from material flows and operations to policy and regulations. We describe methods for the development of circular interventions, including business models, contract templates, and product redesigns. Finally, our approach to dissemination and education is presented. The described study design and methods can be used by other hospital (settings) to identify environmental hotspots for circular interventions in their own healthcare practice and for the cross-transfer of knowledge and anticipated challenges in implementing circular strategies. Ultimately, the ESCH-R project will deliver innovative, scalable approaches for hospitals to reduce procurement of raw materials, retain value of medical products, and reduce waste streams, CO2 emissions and pollution

Stargardt disease:monitoring incidence and diagnostic trends in the Netherlands using a nationwide disease registry

PURPOSE: To assess the incidence of Stargardt disease (STGD1) and to evaluate demographics of incident cases. METHODS: For this retrospective cohort study, demographic, clinical and genetic data of patients with a clinical diagnosis of STGD1 were registered between September 2010 and January 2020 in a nationwide disease registry. Annual incidence (2014-2018) and point prevalence (2018) were assessed on the basis of this registry. RESULTS: A total of 800 patients were registered, 56% were female and 83% were of European ancestry. The incidence was 1.67-1.95:1,000,000 per year and the point prevalence in 2018 was approximately 1:22,000-1:19,000 (with and without 10% of potentially unregistered cases). Age at onset was associated with sex (p = 0.027, Fisher's exact); 1.9x more women than men were observed (140 versus 74) amongst patients with an age at onset between 10 and 19 years, while the sex ratio in other age-at-onset categories approximated one. Late-onset STGD1 (≥45 years) constituted 33% of the diagnoses in 2014-2018 compared to 19% in 2004-2008. Diagnostic delay (≥2 years between the first documentation of macular abnormalities and diagnosis) was associated with older age of onset (p = 0.001, Mann-Whitney). Misdiagnosis for age-related macular degeneration (22%) and incidental STGD1 findings (14%) was common in patients with late-onset STGD1. CONCLUSION: The observed prevalence of STGD1 in real-world data was lower than expected on the basis of population ABCA4 allele frequencies. Late-onset STGD1 was more frequently diagnosed in recent years, likely due to higher awareness of its phenotype. In this pretherapeutic era, mis- and underdiagnosis of especially late-onset STGD1 and the role of sex in STGD1 should receive special attention

Accelerating the transition from a linear to a circular healthcare sector: ESCH-R: study design and methodology

Due to the significant environmental impact of healthcare, there is an urgent need to accelerate its circular transition. We provide an overview of the ESCH-R project study design and methodology for accelerating the transition from a linear to a circular healthcare sector through the development and implementation of circular interventions in the Netherlands. Using a transdisciplinary approach, we will apply the 10-R ladder framework for a circular economy to hospitals. Methods are presented to analyze current clinical practices, policies and requirements for sustainable behavioral change, from material flows and operations to policy and regulations. We describe methods for the development of circular interventions, including business models, contract templates, and product redesigns. Finally, our approach to dissemination and education is presented. The described study design and methods can be used by other hospital (settings) to identify environmental hotspots for circular interventions in their own healthcare practice and for the cross-transfer of knowledge and anticipated challenges in implementing circular strategies. Ultimately, the ESCH-R project will deliver innovative, scalable approaches for hospitals to reduce procurement of raw materials, retain value of medical products, and reduce waste streams, CO2 emissions and pollution