De Do-Not-Reanimate-code in het medisch handelen rond de uitbehandelde patiënt. Een brug van cure naar comfort.

Intensieve Geneeskunde is het specialisme dat zich toelegt op de behandeling en observatie van kritiek zieke patiënten. Bij patiënten met een slechte prognose kan een ‘Do-Not-Reanimate-code’ (DNR-code) worden ingesteld. Er wordt dan op een zo objectief mogelijke manier een schatting gemaakt van de toekomstperspectieven waarbij wordt gekeken of bepaalde bijkomende behandelingen nog zinvol zijn of therapeutische hardnekkigheid in de hand werken. Belangrijk in deze discussie is het verschil in het onthouden versus onttrekken van therapie. Het onttrekken van reeds begonnen levensondersteunende behandeling (withdrawal of therapy) is niet hetzelfde als het onthouden (withholding) van nog niet begonnen therapie. Het eerste is een actieve en het tweede een passieve daad. Het gevaar bestaat dat het objectieve beeld van de pathologie de overhand heeft in de beslissing tot het uitschrijven van de DNR-code, waarbij het individuele (subjectieve) aspect van de zieke verloren gaat. In de praktijk wordt een DNR-code meestal toegekend aan de oudere en ziekere patiënt. Vanuit het medisch gezichtspunt moet duidelijkheid bestaan over het doel van een DNR-code: het is in de ‘care’ een overgang van ‘cure’ naar ‘comfort’. In het medisch handelen van de eenentwintigste eeuw behoren de factoren ‘cure’, ‘care’ en ‘comfort’ samen te gaan.Karin Janssen van Doorn (Zetten 1968) studeerde geneeskunde aan de VU Brussel en specialiseerde zich in interne geneeskunde (nefrologie) en intensieve geneeskunde. Haar doctoraatswerk omvat onderzoek naar acuut nierfalen bij kritiek zieke patiënten. Sinds 2003 studeert zij moraalwetenschappen aan dezelfde universiteit. In het kader van het vak ‘Ethische problemen; medicalisering van de dood’ deed zij onderzoek naar het gebruik van de Do-Not-Reanimate-code op de afdeling Intensieve Geneeskunde

Acute Kidney Injury in the Critically Ill Still Remains A Challenge

Acute kidney injury (AKI) is a common complication of critical illness and is associated with high morbidity and mortality. The epidemiology and pathogenesis of AKI and changes in renal function and preventive strategies are areas of interest. Although the aetiology of AKI is often multifactorial, sepsis has been consistently found to be a leading contributing factor in AKI during critical illness. Despite revised guidelines and better haemodynamic management, the outcome of AKI is still a reason for concern. Critically ill patients with AKI have significantly improved short-time prognosis with current treatment standards but are more prone to develop increased morbidity in the near future

Acute stress response in children with meningococcal sepsis: important differences in the growth hormone/insulin-like growth factor I axis between nonsurvivors and survivors

Septic shock is the most severe clinical manifestation of meningococcal disease and is predominantly seen in children under 5 yr of age. Very limited research has been performed to elucidate the alterations of the GH/IGF-I axis in critically ill children. We evaluated the GH/IGF-I axis and the levels of IGF-binding proteins (IGFBPs), IGFBP-3 protease, glucose, insulin, and cytokines in 27 children with severe septic shock due to meningococcal sepsis during the first 3 d after admission. The median age was 22 months (range, 4-185 months). Eight patients died. Nonsurvivors had extremely high GH levels that were significant different compared with mean GH levels in survivors during a 6-h GH profile (131 vs. 7 mU/liter; P &lt; 0.01). Significant differences were found between nonsurvivors and survivors for the levels of total IGF-I (2.6 vs. 5.6 nmol/liter), free IGF-I (0.003 vs. 0.012 nmol/liter), IGFBP-1 (44.3 vs. 8.9 nmol/liter), IGFBP-3 protease activity (61 vs. 32%), IL-6 (1200 vs. 50 ng/ml), and TNFalpha (34 vs. 5.3 pg/ml; P &lt; 0.01). The pediatric risk of mortality score correlated significantly with levels of IGFBP-1, IGFBP-3 protease activity, IL-6, and TNFalpha (r = +0.45 to +0.69) and with levels of total IGF-I and free IGF-I (r = -0.44 and -0.55, respectively). Follow-up after 48 h in survivors showed an increased number of GH peaks, increased free IGF-I and IGFBP-3 levels, and lower IGFBP-1 levels compared with admission values. GH levels and IGFBP-1 levels were extremely elevated in nonsurvivors, whereas total and free IGF-I levels were markedly decreased and were accompanied by high levels of the cytokines IL-6 and TNFalpha. These values were different from those for the survivors. Based on these findings and literature data a hypothetical model was constructed summarizing our current knowledge and understanding of the various mechanisms.</p

Public participation in mission-oriented innovation projects

Mission-oriented innovation policy is currently gaining renewed interest as an approach for addressing societal challenges. One of the promises is that missions can mobilise and align diverse stakeholders around a shared goal. Recent literature underlines the importance of public participation (e.g. municipalities and civil society organisations) in the socioeconomic transformations required for attaining missions. We ask how public participation differs among (non-)mission-oriented innovation projects. Drawing on a database containing Dutch government-funded innovation projects, we investigate whether mission-oriented projects are associated with earlier, more open, and more influential forms of public participation than conventional projects. Although the results suggest that mission-oriented projects indeed correspond with earlier participation of more public actors, we find little evidence that they also coincide with increased diversity and financial influence of public participants. We conclude by discussing how policymakers and intermediaries may engage in strategies to make missions more inclusive

Acute stress response in children with meningococcal sepsis: important differences in the growth hormone/insulin-like growth factor I axis between nonsurvivors and survivors

Septic shock is the most severe clinical manifestation of meningococcal disease and is predominantly seen in children under 5 yr of age. Very limited research has been performed to elucidate the alterations of the GH/IGF-I axis in critically ill children. We evaluated the GH/IGF-I axis and the levels of IGF-binding proteins (IGFBPs)

Phosphate-containing dialysis solution prevents hypophosphatemia during continuous renal replacement therapy

Background: Hypophosphatemia occurs in up to 80% of the patients during continuous renal replacement therapy (CRRT). Phosphate supplementation is time-consuming and the phosphate level might be dangerously low before normophosphatemia is re-established. This study evaluated the possibility to prevent hypophosphatemia during CRRT treatment by using a new commercially available phosphate-containing dialysis fluid. Methods: Forty-two heterogeneous intensive care unit patients, admitted between January 2007 and July 2008, undergoing hemodiafiltration, were treated with a new Gambro dialysis solution with 1.2 mM phosphate (Phoxilium) or with standard medical treatment (Hemosol B0). The patients were divided into three groups: group 1 (n=14) receiving standard medical treatment and intravenous phosphate supplementation as required, group 2 (n=14) receiving the phosphate solution as dialysate solution and Hemosol B0 as replacement solution and group 3 (n=14) receiving the phosphate-containing solution as both dialysate and replacement solutions. Results: Standard medical treatment resulted in hypophosphatemia in 11 of 14 of the patients (group 1) compared with five of 14 in the patients receiving phosphate solution as the dialysate solution and Hemosol B0 as the replacement solution (group 2). Patients treated with the phosphate-containing dialysis solution (group 3) experienced stable serum phosphate levels throughout the study. Potassium, ionized calcium, magnesium, pH, pCO(2) and bicarbonate remained unchanged throughout the study. Conclusion: The new phosphate-containing replacement and dialysis solution reduces the variability of serum phosphate levels during CRRT and eliminates the incidence of hypophosphatemia

Environmentally sustainable food consumption : a review and research agenda from a goal-directed perspective

The challenge of convincing people to change their eating habits toward more environmentally sustainable food consumption (ESFC) patterns is becoming increasingly pressing. Food preferences, choices and eating habits are notoriously hard to change as they are a central aspect of people's lifestyles and their socio-cultural environment. Many people already hold positive attitudes toward sustainable food, but the notable gap between favorable attitudes and actual purchase and consumption of more sustainable food products remains to be bridged. The current work aims to (1) present a comprehensive theoretical framework for future research on ESFC, and (2) highlight behavioral solutions for environmental challenges in the food domain from an interdisciplinary perspective. First, starting from the premise that food consumption is deliberately or unintentionally directed at attaining goals, a goal-directed framework for understanding and influencing ESFC is built. To engage in goal-directed behavior, people typically go through a series of sequential steps. The proposed theoretical framework makes explicit the sequential steps or hurdles that need to be taken for consumers to engage in ESFC. Consumers need to positively value the environment, discern a discrepancy between the desired versus the actual state of the environment, opt for action to reduce the experienced discrepancy, intend to engage in behavior that is expected to bring them closer to the desired end state, and act in accordance with their intention. Second, a critical review of the literature on mechanisms that underlie and explain ESFC (or the lack thereof) in high-income countries is presented and integrated into the goal-directed framework. This contribution thus combines a top-down conceptualization with a bottom-up literature review; it identifies and discusses factors that might hold people back from ESFC and interventions that might promote ESFC; and it reveals knowledge gaps as well as insights on how to encourage both short- and long-term ESFC by confronting extant literature with the theoretical framework. Altogether, the analysis yields a set of 33 future research questions in the interdisciplinary food domain that deserve to be addressed with the aim of fostering ESFC in the short and long term

Functional Characterization of the Disease-associated N-Terminal complement Factor H Mutation W198R

Dysregulation of the complement alternative pathway is involved in the pathogenesis of several diseases, including the kidney diseases atypical hemolytic uremic syndrome (aHUS) and C3 glomerulopathy (C3G). In a patient, initially diagnosed with chronic glomerulonephritis, possibly C3G, and who 6 years later had an episode of aHUS, a heterozygous missense mutation leading to a tryptophan to arginine exchange (W198R) in the factor H (FH) complement control protein (CCP) 3 domain has previously been identified. The aim of this study was to clarify the functional relevance of this mutation. To this end, wild-type (FH1-4(WT)) and mutant (FH1-4(W198R)) CCPs 1-4 of FH were expressed as recombinant proteins. The FH1-4(W198R) mutant showed decreased C3b binding compared with FH1-4(WT). FH1-4(W198R) had reduced cofactor and decay accelerating activity compared with the wild-type protein. Hemolysis assays demonstrated impaired capacity of FH1-4(W198R) to protect rabbit erythrocytes from human complement-mediated lysis, and also to prevent lysis of sheep erythrocytes in human serum induced by a monoclonal antibody binding in FH CCP5 domain, compared with that of FH1-4(WT). Thus, the FH W198R exchange results in impaired complement alternative pathway regulation. The heterozygous nature of this mutation in the index patient may explain the manifestation of two diseases, likely due to different triggers leading to complement dysregulation in plasma or on cell surfaces