Global challenges, local impact

[EN] In 2015, the UN set 17 global goals, the so-called Sustainable Development Goals (SDGs) for the year 2030, “a universal call to action to end poverty, protect the planet and ensure that all people enjoy peace and prosperity”. Although these challenges are global, their impact manifests itself on a local level. An inspiring challenge for HU UAS Utrecht is to educate self-confident (upcoming) professionals who contribute to the realization of these global goals by creating local impact. In our opinion such professionals are socially involved, cope with complexity, think systemic and work trans-disciplinary. Furthermore, they ‘mix and match’ personal, societal and professional development, which will not be confined to formal education but lasts a lifetime. This complex challenge forges us to transform our thinking about education and how to organize learning, and about how, where and with whom we educate. UAS’s will have to cooperate with private, public and research partners and create communities in which all participants work, learn and develop themselves while facing new challenges.Schröder, I.; De Jonge, E.; Mooij, E.; Evers, F. (2019). Global challenges, local impact. En Proceedings 5th CARPE Conference: Horizon Europe and beyond. Editorial Universitat Politècnica de València. 67-72. https://doi.org/10.4995/CARPE2019.2019.10564OCS677

A Prediction Model for Neonatal Mortality in Low- and Middle-income Countries: An Analysis of Data from Population Surveillance Sites in India, Nepal and Bangladesh

Background: In poor settings, where many births and neonatal deaths occur at home, prediction models of neonatal mortality in the general population can aid public-health policy-making. No such models are available in the international literature. We developed and validated a prediction model for neonatal mortality in the general population in India, Nepal and Bangladesh. Methods: Using data (49 632 live births, 1742 neonatal deaths) from rural and urban surveillance sites in South Asia, we developed regression models to predict the risk of neonatal death with characteristics known at (i) the start of pregnancy, (ii) start of delivery and (iii) 5 minutes post partum. We assessed the models’ discriminative ability by the area under the receiver operating characteristic curve (AUC), using cross-validation between sites. Results: At the start of pregnancy, predictive ability was moderate {AUC 0.59 [95% confidence interval (CI) 0.58–0.61]} and predictors of neonatal death were low maternal education and economic status, short birth interval, primigravida, and young and advanced maternal age. At the start of delivery, predictive ability was considerably better [AUC 0.73 (95% CI 0.70–0.76)] and prematurity and multiple pregnancy were strong predictors of death. At 5 minutes post partum, predictive ability was good [AUC: 0.85 (95% CI 0.80–0.89)]; very strong predictors were multiple birth, prematurity and a poor condition of the infant at 5 minutes. Conclusions: We developed good performing prediction models for neonatal mortality. Neonatal deaths are highly concentrated in a small group of high-risk infants, even in poor settings in South Asia. Risk assessment, as supported by our models, can be used as a basis for improving community- and facility-based newborn care and prevention strategies in poor settings

The association between presenting complaints and clinical outcomes in emergency department patients of different age categories

BACKGROUND AND IMPORTANCE: Although aging societies in Western Europe use presenting complaints (PCs) in emergency departments (EDs) triage systems to determine the urgency and severity of the care demand, it is unclear whether their prognostic value is age-dependent. OBJECTIVE: To assess the frequency and association of PCs with hospitalization and mortality across age categories. METHODS: An observational multicenter study using all consecutive visits of three EDs in the Netherlands Emergency department Evaluation Database. Patients were stratified by age category (0-18; 19-50; 51-65; 66-80; >80 years), in which the association between PCs and case-mix adjusted hospitalization and mortality was studied using multivariable logistic regression analysis (adjusting for demographics, hospital, disease severity, comorbidity and other PCs). RESULTS: We included 172  104 ED-visits. The most frequent PCs were 'extremity problems' [range across age categories (13.5-40.8%)], 'feeling unwell' (9.5-23.4%), 'abdominal pain' (6.0-13.9%), 'dyspnea' (4.5-13.3%) and 'chest pain' (0.6-10.7%). For most PCs, the observed and the case-mix-adjusted odds for hospitalization and mortality increased the higher the age category. The most common PCs with the highest adjusted odds ratios (AORs, 95% CI) for hospitalization were 'diarrhea and vomiting' [2.30 (2.02-2.62)] and 'feeling unwell' [1.60 (1.48-1.73)]. Low hospitalization risk was found for 'chest pain' [0.58 (0.53-0.63)] and 'palpitations' [0.64 (0.58-0.71)]. CONCLUSIONS: Frequency of PCs in ED patients varies with age, but the same PCs occur in all age categories. For most PCs, (case-mix adjusted) hospitalization and mortality vary across age categories. 'Chest pain' and 'palpitations,' usually triaged 'very urgent', carry a low risk for hospitalization and mortality

Small Nuclear RNAs Encoded by Herpesvirus saimiri Upregulate the Expression of Genes Linked to T Cell Activation in Virally Transformed T Cells

SummarySeven small nuclear RNAs of the Sm class are encoded by Herpesvirus saimiri (HVS), a γ Herpesvirus that causes aggressive T cell leukemias and lymphomas in New World primates and efficiently transforms T cells in vitro [1–4]. The Herpesvirus saimiri U RNAs (HSURs) are the most abundant viral transcripts in HVS-transformed, latently infected T cells but are not required for viral replication or transformation in vitro [5]. We have compared marmoset T cells transformed with wild-type or a mutant HVS lacking the most highly conserved HSURs, HSURs 1 and 2. Microarray and Northern analyses reveal that HSUR 1 and 2 expression correlates with significant increases in a small number of host mRNAs, including the T cell-receptor β and γ chains, the T cell and natural killer (NK) cell-surface receptors CD52 and DAP10, and intracellular proteins—SKAP55, granulysin, and NKG7—linked to T cell and NK cell activation. Upregulation of three of these transcripts was rescued after transduction of deletion-mutant-HVS-transformed cells with a lentiviral vector carrying HSURs 1 and 2. These changes indicate an unexpected role for the HSURs in regulating a remarkably defined and physiologically relevant set of host targets involved in the activation of virally transformed T cells during latency

Compliance to Screening Protocols for Multidrug-Resistant Microorganisms at the Emergency Departments of Two Academic Hospitals in the Dutch-German Cross-Border Region

Infections caused by multidrug-resistant organisms (MDROs) are associated with prolonged hospitalization and higher risk of mortality. Patients arriving in the hospital via the emergency department (ED) are screened for the presence of MDROs in compliance with the screening protocols in order to apply the correct isolation measures. In the Dutch-German border region, local hospitals apply their own screening protocols which are based upon national screening protocols. The contents of the national and local MDRO screening protocols were compared on vancomycin-resistant enterococci (VRE), methicillin-resistant Staphylococcus aureus (MRSA), and carbapenemase-producing and carbapenem-resistant Enterobacteriaceae (CPE/CRE). The practicality of the screening protocols was evaluated by performing an audit. As a result, the content of the MDRO screening protocols differed regarding risk factors for MDRO carriage, swab site, personal protective equipment, and isolation measures. The observations and questionnaires showed that the practicality was sufficient; however, the responsibility was not designated clearly and education regarding the screening protocols was deemed inappropriate. The differences between the MDRO screening protocols complicate patient care in the Dutch-German border region. Arrangements have to be made about the responsibility of the MDRO screening, and improvements are necessary concerning education regarding the MDRO screening protocols

Abyssal food-web model indicates faunal carbon flow recovery and impaired microbial loop 26 years after a sediment disturbance experiment

Due to the predicted future demand for critical metals, abyssal plains covered with polymetallic nodules are currently being prospected for deep-seabed mining. Deep-seabed mining will lead to significant sediment disturbance over large spatial scales and for extended periods of time. The environmental impact of a small-scale sediment disturbance was studied during the ‘DISturbance and reCOLonization’ (DISCOL) experiment in the Peru Basin in 1989 when 10.8 km2 of seafloor were ploughed with a plough harrow. Here, we present a detailed description of carbon-based food-web models constructed from various datasets collected in 2015, 26 years after the experiment. Detailed observations of the benthic food web were made at three distinct sites: inside 26-year old plough tracks (IPT, subjected to direct impact from ploughing), outside the plough tracks (OPT, exposed to settling of resuspended sediment), and at reference sites (REF, no impact). The observations were used to develop highly-resolved food-web models for each site that quantified the carbon (C) fluxes between biotic (ranging from prokaryotes to various functional groups in meio-, macro-, and megafauna) and abiotic (e.g. detritus) compartments. The model outputs were used to estimate total system throughput, i.e., the sum of all C flows in the food web (the ‘ecological size’ of the system), and microbial loop functioning, i.e., the C-cycling through the prokaryotic compartment for each site. Both the estimated total system throughput and the microbial loop cycling were significantly reduced (by 16% and 35%, respectively) inside the plough tracks compared to the other two sites. Site differences in modelled faunal respiration varied among the different faunal compartments. Overall, modelled faunal respiration appeared to have recovered to, or exceeded reference values after 26-years. The model results indicate that food-web functioning, and especially the microbial loop, have not recovered from the disturbance that was inflicted on the abyssal site 26 years ago

Long-term outcomes after endoscopic treatment for Barrett's neoplasia with radiofrequency ablation +/- endoscopic resection:results from the national Dutch database in a 10-year period

OBJECTIVE: Radiofrequency ablation (RFA)±endoscopic resection (ER) is the preferred treatment for early neoplasia in Barrett’s oesophagus (BE). We aimed to report short-term and long-term outcomes for all 1384 patients treated in the Netherlands (NL) from 2008 to 2018, with uniform treatment and follow-up (FU) in a centralised setting. DESIGN: Endoscopic therapy for early BE neoplasia in NL is centralised in nine expert centres with specifically trained endoscopists and pathologists that adhere to a joint protocol. Prospectively collected data are registered in a uniform database. Patients with low/high-grade dysplasia or low-risk cancer, were treated by ER of visible lesions followed by trimonthly RFA sessions of any residual BE until complete eradication of BE (CE-BE). Patients with ER alone were not included. RESULTS: After ER (62% of cases; 43% low-risk cancers) and median 1 circumferential and 2 focal RFA (p25-p75 0–1; 1–2) per patient, CE-BE was achieved in 94% (1270/1348). Adverse events occurred in 21% (268/1386), most commonly oesophageal stenosis (15%), all were managed endoscopically. A total of 1154 patients with CE-BE were analysed for long-term outcomes. During median 43 months (22–69) and 4 endoscopies (1–5), 38 patients developed dysplastic recurrence (3%, annual recurrence risk 1%), all were detected as endoscopically visible abnormalities. Random biopsies from a normal appearing cardia showed intestinal metaplasia (IM) in 14% and neoplasia in 0%. A finding of IM in the cardia was reproduced during further FU in only 33%, none progressed to neoplasia. Frequent FU visits in the first year of FU were not associated with recurrence risk. CONCLUSION: In a setting of centralised care, RFA±ER is effective for eradication of Barrett’s related neoplasia and has remarkably low rates of dysplastic recurrence. Our data support more lenient FU intervals, with emphasis on careful endoscopic inspection. Random biopsies from neosquamous epithelium and cardia are of questionable value. NETHERLANDS TRIAL REGISTER NUMBER: NL7039

Incidence and outcomes of poor healing and poor squamous regeneration after radiofrequency ablation therapy for early Barrett's neoplasia

BACKGROUND: Although endoscopic eradication therapy with radiofrequency ablation (RFA) is effective in most Barrett's Esophagus (BE) patients, some might experience poor healing (PH) and/or poor squamous regeneration (PSR). We aimed to evaluate PH/PSR incidence and treatment outcomes. METHODS: We included all patients treated with RFA for early BE neoplasia, from a nationwide Dutch registry based on a joint treatment protocol. PH was defined as active inflammatory changes or visible ulcerations ≥3 months post-RFA, PSR as <50% squamous regeneration, and treatment success as complete eradication of BE (CE-BE). Results 1,386 patients (median BE C2M5) underwent RFA with baseline low-grade dysplasia (27%), high-grade dysplasia (30%), or early cancer (43%). In all 134 patients with PH (10%), additional time and acid suppression resulted in complete esophageal healing. 67/134 (50%) had normal regeneration with 97% CE-BE. In total, 74 patients had PSR (5%). As compared to patients with normal squamous regeneration, PSR patients had a higher risk for treatment failure (64% versus 2%, RR 27 [95% CI 18-40]) and progression to advanced disease (15% versus <1%, RR 30 [95% CI 12-81]). Higher BMI, longer BE, reflux esophagitis, and <50% squamous regeneration after baseline endoscopic resection were independently associated with PSR in multivariable logistic regression. Conclusions In half of the patients with PH, additional time and acid suppression may lead to normal squamous regeneration and excellent treatment outcomes. However, if patients experience PSR, the risk for treatment failure and progression to advanced disease is significantly increased with a relative risk of 27 and 30, respectively

Development and external validation of a model to predict complex treatment after RFA for Barrett's esophagus with early neoplasia

Background & Aims: Endoscopic eradication therapy for Barrett's esophagus (BE)-related neoplasia is safe and leads to complete eradication in the majority of patients. However, a subgroup will experience a more complex treatment course with a risk for failure or disease progression. Early identification of these patients may improve patient counseling and treatment outcomes. We aimed to develop a prognostic model for a complex treatment course. Methods: We collected data from a nationwide registry that captures outcomes for all patients undergoing endoscopic eradication therapy for early BE neoplasia. A complex treatment course was defined as neoplastic progression, treatment failure, or the need for endoscopic resection during the radiofrequency ablation treatment phase. We developed a prognostic model using logistic regression. We externally validated our model in an independent registry. Results: A total of 1386 patients were included, of whom 78 (6%) had a complex treatment course. Our model identified patients with a BE length of 9 cm or longer with a visible lesion containing high-grade dysplasia/cancer, and patients with less than 50% squamous conversion after radiofrequency ablation were identified as high risk for a complex treatment. This applied to 8% of the study population and included 93% of all treatment failures and 76% of all patients with advanced neoplastic progression. The model appeared robust in multiple sensitivity analyses and performed well in external validation (area under the curve, 0.84). Conclusions: We developed a prognostic model that identified patients with a BE length of 9 cm or longer and high-grade dysplasia/esophageal adenocarcinoma and those with poor squamous regeneration as high risk for a complex treatment course. The good performance in external validation suggests that it may be used in clinical management (Netherlands Trial Register: NL7039)