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Item does not contain fulltext, OBJECTIVES: Early Warning Scores (EWSs) have a great potential to assist clinical decision-making in the emergency department (ED). However, many EWS contain methodological weaknesses in development and validation and have poor predictive performance in older patients. The aim of this study was to develop and externally validate an International Early Warning Score (IEWS) based on a recalibrated National Early warning Score (NEWS) model including age and sex and evaluate its performance independently at arrival to the ED in three age categories (18-65, 66-80, > 80 yr). DESIGN: International multicenter cohort study. SETTING: Data was used from three Dutch EDs. External validation was performed in two EDs in Denmark. PATIENTS: All consecutive ED patients greater than or equal to 18 years in the Netherlands Emergency department Evaluation Database (NEED) with at least two registered vital signs were included, resulting in 95,553 patients. For external validation, 14,809 patients were included from a Danish Multicenter Cohort (DMC). MEASUREMENTS AND MAIN RESULTS: Model performance to predict in-hospital mortality was evaluated by discrimination, calibration curves and summary statistics, reclassification, and clinical usefulness by decision curve analysis. In-hospital mortality rate was 2.4% ( n = 2,314) in the NEED and 2.5% ( n = 365) in the DMC. Overall, the IEWS performed significantly better than NEWS with an area under the receiving operating characteristic of 0.89 (95% CIs, 0.89-0.90) versus 0.82 (0.82-0.83) in the NEED and 0.87 (0.85-0.88) versus 0.82 (0.80-0.84) at external validation. Calibration for NEWS predictions underestimated risk in older patients and overestimated risk in the youngest, while calibration improved for IEWS with a substantial reclassification of patients from low to high risk and a standardized net benefit of 5-15% in the relevant risk range for all age categories. CONCLUSIONS: The IEWS substantially improves in-hospital mortality predict

01 juli 2023, Contains fulltext : 296067.pdf (Publisher’s version ) (Open Access), BACKGROUND: Guidelines and textbooks assert that tachycardia is an early and reliable sign of hypotension, and an increased heart rate (HR) is believed to be an early warning sign for the development of shock, although this response may change by aging, pain, and stress. OBJECTIVE: To assess the unadjusted and adjusted associations between systolic blood pressure (SBP) and HR in emergency department (ED) patients of different age categories (18-50 years; 50-80 years; > 80 years). METHODS: A multicenter cohort study using the Netherlands Emergency department Evaluation Database (NEED) including all ED patients ≥ 18 years from three hospitals in whom HR and SBP were registered at arrival to the ED. Findings were validated in a Danish cohort including ED patients. In addition, a separate cohort was used including ED patients with a suspected infection who were hospitalized from whom measurement of SBP and HR were available prior to, during, and after ED treatment. Associations between SBP and HR were visualized and quantified with scatterplots and regression coefficients (95% confidence interval [CI]). RESULTS: A total of 81,750 ED patients were included from the NEED, and a total of 2358 patients with a suspected infection. No associations were found between SBP and HR in any age category (18-50 years: -0.03 beats/min/10 mm Hg, 95% CI -0.13-0.07, 51-80 years: -0.43 beats/min/10 mm Hg, 95% CI -0.38 to -0.50, > 80 years: -0.61 beats/min/10 mm Hg, 95% CI -0.53 to -0.71), nor in different subgroups of ED patient. No increase in HR existed with a decreasing SBP during ED treatment in ED patients with a suspected infection. CONCLUSION: No association between SBP and HR existed in ED patients of any age category, nor in ED patients who were hospitalized with a suspected infection, even during and after ED treatment. Emergency physicians may be misled by traditional concepts about HR disturbances because tachycardia may be absent in hypotension.

Item does not contain fulltext, BACKGROUND: Appropriate interpretation of vital signs is essential for risk stratification in the emergency department (ED) but may change with advancing age. In several guidelines, risk scores such as the Systemic Inflammatory Response Syndrome (SIRS) and Quick Sequential Organ Failure Assessment (qSOFA) scores, commonly used in emergency medicine practice (as well as critical care) specify a single cut-off or threshold for each of the commonly measured vital signs. Although a single cut-off may be convenient, it is unknown whether a single cut-off for vital signs truly exists and if the association between vital signs and in-hospital mortality differs per age-category. AIMS: To assess the association between initial vital signs and case-mix adjusted in-hospital mortality in different age categories. METHODS: Observational multicentre cohort study using the Netherlands Emergency Department Evaluation Database (NEED) in which consecutive ED patients ≥18 years were included between 1 January 2017 and 12 January 2020. The association between vital signs and case-mix adjusted mortality were assessed in three age categories (18-65; 66-80; >80 years) using multivariable logistic regression. Vital signs were each divided into five to six categories, for example, systolic blood pressure (SBP) categories (≤80, 81-100, 101-120, 121-140, >140 mm Hg). RESULTS: We included 101 416 patients of whom 2374 (2.3%) died. Adjusted ORs for mortality increased gradually with decreasing SBP and decreasing peripheral oxygen saturation (SpO(2)). Diastolic blood pressure (DBP), mean arterial pressure (MAP) and heart rate (HR) had quasi-U-shaped associations with mortality. Mortality did not increase for temperatures anywhere in the range between 35.5°C and 42.0°C, with a single cut-off around 35.5°C below which mortality increased. Single cut-offs were also found for MAP <70 mm Hg and respiratory rate >22/min. For all vital signs, older patients had larger increases in absolute mortality co

Item does not contain fulltext, 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.

Item does not contain fulltext, BACKGROUND: Treatment and the clinical course during Emergency Department (ED) stay before Intensive Care Unit (ICU) admission may affect predicted mortality risk calculated by the Acute Physiology and Chronic Health Evaluation (APACHE)-IV, causing lead-time bias. As a result, comparing standardized mortality ratios (SMRs) among hospitals may be difficult if they differ in the location where initial stabilization takes place. The aim of this study was to assess to what extent predicted mortality risk would be affected if the APACHE-IV score was recalculated with the initial physiological variables from the ED. Secondly, to evaluate whether ED Length of Stay (LOS) was associated with a change (delta) in these APACHE-IV scores. METHODS: An observational multicenter cohort study including ICU patients admitted from the ED. Data from two Dutch quality registries were linked: the Netherlands Emergency department Evaluation Database (NEED) and the National Intensive Care Evaluation (NICE) registry. The ICU APACHE-IV, predicted mortality, and SMR based on data of the first 24 h of ICU admission were compared with an ED APACHE-IV model, using the most deviating physiological variables from the ED or ICU. RESULTS: A total of 1398 patients were included. The predicted mortality from the ICU APACHE-IV (median 0.10; IQR 0.03-0.30) was significantly lower compared to the ED APACHE-IV model (median 0.13; 0.04-0.36; p < 0.01). The SMR changed from 0.63 (95%CI 0.54-0.72) to 0.55 (95%CI 0.47-0.63) based on ED APACHE-IV. Predicted mortality risk changed more than 5% in 321 (23.2%) patients by using the ED APACHE-IV. ED LOS > 3.9 h was associated with a slight increase in delta APACHE-IV of 1.6 (95% CI 0.4-2.8) compared to ED LOS < 1.7 h. CONCLUSION: Predicted mortality risks and SMRs calculated by the APACHE IV scores are not directly comparable in patients admitted from the ED if hospitals differ in their policy to stabilize patients in the ED before ICU admission. Future research s

Item does not contain fulltext, INTRODUCTION: In the first wave, thrombotic complications were common in COVID-19 patients. It is unknown whether state-of-the-art treatment has resulted in less thrombotic complications in the second wave. METHODS: We assessed the incidence of thrombotic complications and overall mortality in COVID-19 patients admitted to eight Dutch hospitals between September 1st and November 30th 2020. Follow-up ended at discharge, transfer to another hospital, when they died, or on November 30th 2020, whichever came first. Cumulative incidences were estimated, adjusted for competing risk of death. These were compared to those observed in 579 patients admitted in the first wave, between February 24th and April 26th 2020, by means of Cox regression techniques adjusted for age, sex and weight. RESULTS: In total 947 patients with COVID-19 were included in this analysis, of whom 358 patients were admitted to the ICU; 144 patients died (15%). The adjusted cumulative incidence of all thrombotic complications after 10, 20 and 30 days was 12% (95% confidence interval (CI) 9.8-15%), 16% (13-19%) and 21% (17-25%), respectively. Patient characteristics between the first and second wave were comparable. The adjusted hazard ratio (HR) for overall mortality in the second wave versus the first wave was 0.53 (95%CI 0.41-0.70). The adjusted HR for any thrombotic complication in the second versus the first wave was 0.89 (95%CI 0.65-1.2). CONCLUSIONS: Mortality was reduced by 47% in the second wave, but the thrombotic complication rate remained high, and comparable to the first wave. Careful attention to provision of adequate thromboprophylaxis is invariably warranted.

Contains fulltext : 245692.pdf (Publisher’s version ) (Open Access), INTRODUCTION: In the first wave, thrombotic complications were common in COVID-19 patients. It is unknown whether state-of-the-art treatment has resulted in less thrombotic complications in the second wave. METHODS: We assessed the incidence of thrombotic complications and overall mortality in COVID-19 patients admitted to eight Dutch hospitals between September 1st and November 30th 2020. Follow-up ended at discharge, transfer to another hospital, when they died, or on November 30th 2020, whichever came first. Cumulative incidences were estimated, adjusted for competing risk of death. These were compared to those observed in 579 patients admitted in the first wave, between February 24th and April 26th 2020, by means of Cox regression techniques adjusted for age, sex and weight. RESULTS: In total 947 patients with COVID-19 were included in this analysis, of whom 358 patients were admitted to the ICU; 144 patients died (15%). The adjusted cumulative incidence of all thrombotic complications after 10, 20 and 30 days was 12% (95% confidence interval (CI) 9.8-15%), 16% (13-19%) and 21% (17-25%), respectively. Patient characteristics between the first and second wave were comparable. The adjusted hazard ratio (HR) for overall mortality in the second wave versus the first wave was 0.53 (95%CI 0.41-0.70). The adjusted HR for any thrombotic complication in the second versus the first wave was 0.89 (95%CI 0.65-1.2). CONCLUSIONS: Mortality was reduced by 47% in the second wave, but the thrombotic complication rate remained high, and comparable to the first wave. Careful attention to provision of adequate thromboprophylaxis is invariably warranted.

Contains fulltext : 199462.pdf (publisher's version ) (Open Access)

Contains fulltext : 195155.pdf (Publisher’s version ) (Open Access)

Contains fulltext : 199462.pdf (publisher's version ) (Open Access)

Contains fulltext : 195155.pdf (Publisher’s version ) (Open Access)

Contains fulltext : 195155.pdf (Publisher’s version ) (Open Access)

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Item does not contain fulltext, OBJECTIVE: To describe the effect of implementation of a rapid response system on the composite endpoint of cardiopulmonary arrest, unplanned ICU admission, or death. DESIGN: Pragmatic prospective Dutch multicenter before-after trial, Cost and Outcomes analysis of Medical Emergency Teams trial. SETTING: Twelve hospitals participated, each including two surgical and two nonsurgical wards between April 2009 and November 2011. The Modified Early Warning Score and Situation-Background-Assessment-Recommendation instruments were implemented over 7 months. The rapid response team was then implemented during the following 17 months. The effects of implementing the rapid response team were measured in the last 5 months of this period. PATIENTS: All patients 18 years old and older admitted to the study wards were included. MEASUREMENTS AND MAIN RESULTS: In total, 166,569 patients were included in the study representing 1,031,172 hospital admission days. No differences were observed in patient demographics between periods. The composite endpoint of cardiopulmonary arrest, unplanned ICU admission, or death per 1,000 admissions was significantly reduced in the rapid response team versus the before phase (adjusted odds ratio, 0.847; 95% CI, 0.725-0.989; p = 0.036). Cardiopulmonary arrests and in-hospital mortality were also significantly reduced (odds ratio, 0.607; 95% CI, 0.393-0.937; p = 0.018 and odds ratio, 0.802; 95% CI, 0.644-1.0; p = 0.05, respectively). Unplanned ICU admissions showed a declining trend (odds ratio, 0.878; 95% CI, 0.755-1.021; p = 0.092), whereas severity of illness at the moment of ICU admission was not different between periods. CONCLUSIONS: In this study, introduction of nationwide implementation of rapid response systems was associated with a decrease in the composite endpoint of cardiopulmonary arrests, unplanned ICU admissions, and mortality in patients in general hospital wards. These findings support the implementation of rapid response systems in

Item does not contain fulltext, OBJECTIVE: To describe the effect of implementation of a rapid response system on the composite endpoint of cardiopulmonary arrest, unplanned ICU admission, or death. DESIGN: Pragmatic prospective Dutch multicenter before-after trial, Cost and Outcomes analysis of Medical Emergency Teams trial. SETTING: Twelve hospitals participated, each including two surgical and two nonsurgical wards between April 2009 and November 2011. The Modified Early Warning Score and Situation-Background-Assessment-Recommendation instruments were implemented over 7 months. The rapid response team was then implemented during the following 17 months. The effects of implementing the rapid response team were measured in the last 5 months of this period. PATIENTS: All patients 18 years old and older admitted to the study wards were included. MEASUREMENTS AND MAIN RESULTS: In total, 166,569 patients were included in the study representing 1,031,172 hospital admission days. No differences were observed in patient demographics between periods. The composite endpoint of cardiopulmonary arrest, unplanned ICU admission, or death per 1,000 admissions was significantly reduced in the rapid response team versus the before phase (adjusted odds ratio, 0.847; 95% CI, 0.725-0.989; p = 0.036). Cardiopulmonary arrests and in-hospital mortality were also significantly reduced (odds ratio, 0.607; 95% CI, 0.393-0.937; p = 0.018 and odds ratio, 0.802; 95% CI, 0.644-1.0; p = 0.05, respectively). Unplanned ICU admissions showed a declining trend (odds ratio, 0.878; 95% CI, 0.755-1.021; p = 0.092), whereas severity of illness at the moment of ICU admission was not different between periods. CONCLUSIONS: In this study, introduction of nationwide implementation of rapid response systems was associated with a decrease in the composite endpoint of cardiopulmonary arrests, unplanned ICU admissions, and mortality in patients in general hospital wards. These findings support the implementation of rapid response systems in

Item does not contain fulltext, OBJECTIVE: To describe the effect of implementation of a rapid response system on the composite endpoint of cardiopulmonary arrest, unplanned ICU admission, or death. DESIGN: Pragmatic prospective Dutch multicenter before-after trial, Cost and Outcomes analysis of Medical Emergency Teams trial. SETTING: Twelve hospitals participated, each including two surgical and two nonsurgical wards between April 2009 and November 2011. The Modified Early Warning Score and Situation-Background-Assessment-Recommendation instruments were implemented over 7 months. The rapid response team was then implemented during the following 17 months. The effects of implementing the rapid response team were measured in the last 5 months of this period. PATIENTS: All patients 18 years old and older admitted to the study wards were included. MEASUREMENTS AND MAIN RESULTS: In total, 166,569 patients were included in the study representing 1,031,172 hospital admission days. No differences were observed in patient demographics between periods. The composite endpoint of cardiopulmonary arrest, unplanned ICU admission, or death per 1,000 admissions was significantly reduced in the rapid response team versus the before phase (adjusted odds ratio, 0.847; 95% CI, 0.725-0.989; p = 0.036). Cardiopulmonary arrests and in-hospital mortality were also significantly reduced (odds ratio, 0.607; 95% CI, 0.393-0.937; p = 0.018 and odds ratio, 0.802; 95% CI, 0.644-1.0; p = 0.05, respectively). Unplanned ICU admissions showed a declining trend (odds ratio, 0.878; 95% CI, 0.755-1.021; p = 0.092), whereas severity of illness at the moment of ICU admission was not different between periods. CONCLUSIONS: In this study, introduction of nationwide implementation of rapid response systems was associated with a decrease in the composite endpoint of cardiopulmonary arrests, unplanned ICU admissions, and mortality in patients in general hospital wards. These findings support the implementation of rapid response systems in

Marga Kool en Jan Veenstra zijn beiden schrijver van een gedeeltelijk Drentstalig oeuvre. Tijdens een culturele avond in het Strokasteel in Veenhuizen, hoorde ik hen voor het eerst voorlezen, in het Drents. Door de prachtige klanken en de mooie droge humor werd ik meteen een fan. Else de Jong sprak met hen: over schrijven in de streektaal, het zelfbewustzijn van Drenten en het belang van een eigen plek in tijden van globalisering.

Op bezoek bij een bevlogen biologisch-dynamische stadsimker. Edwina Brinckmann-Rouffaer woont met gezin in haar ouderlijk huis in Amersfoort. In de ruime stadstuin staan -al naar gelang het seizoen- een of meer volken.

Contains fulltext : 77189.pdf (publisher's version ) (Open Access), achtergrond In de forensische psychiatrie is het zo betrouwbaar mogelijk inschatten van de recidiverisico's van patiënten cruciaal. Het risicotaxatie-instrument hkt-30 brengt zowel statische als dynamische risicofactoren in kaart. De dynamische risicofactoren zouden door behandeling ten goede moeten veranderen. doel Onderzoeken of dynamische factoren veranderen tijdens tbs-behandeling. methode De hkt-30 werd in totaal 984 maal gescoord bij tbs-patiënten in 3 verschillende forensisch psychiatrische centra, medio 2003-november 2006. Voor 513 patiënten gebeurde dat ten minste 1 maal, voor 313 2 maal of meer en voor 158 in 3 opeenvolgende jaren. Opdeling van de onderzoeksgroep in 'nieuwe', 'oude' en 'overgeplaatste' patiënten maakte het mogelijk te onderzoeken in welke fase van de behandeling de meeste verandering in scores plaatsvond. resultaten Een groot deel van de scores op de dynamische risicofactoren, en daarmee ook de totaalscore, namen statistisch significant af, maar de absolute verschillen waren klein. De drie groepen patiënten verschilden niet veel van elkaar in mate van verandering. conclusie De scores op de in theorie als veranderbaar veronderstelde risicofactoren verminderden naarmate de behandeling vorderde. Daarmee staat echter nog niet vast of dit ook daadwerkelijk een vermindering van het recidiverisico betekent.

Contains fulltext : 77189.pdf (publisher's version ) (Open Access), achtergrond In de forensische psychiatrie is het zo betrouwbaar mogelijk inschatten van de recidiverisico's van patiënten cruciaal. Het risicotaxatie-instrument hkt-30 brengt zowel statische als dynamische risicofactoren in kaart. De dynamische risicofactoren zouden door behandeling ten goede moeten veranderen. doel Onderzoeken of dynamische factoren veranderen tijdens tbs-behandeling. methode De hkt-30 werd in totaal 984 maal gescoord bij tbs-patiënten in 3 verschillende forensisch psychiatrische centra, medio 2003-november 2006. Voor 513 patiënten gebeurde dat ten minste 1 maal, voor 313 2 maal of meer en voor 158 in 3 opeenvolgende jaren. Opdeling van de onderzoeksgroep in 'nieuwe', 'oude' en 'overgeplaatste' patiënten maakte het mogelijk te onderzoeken in welke fase van de behandeling de meeste verandering in scores plaatsvond. resultaten Een groot deel van de scores op de dynamische risicofactoren, en daarmee ook de totaalscore, namen statistisch significant af, maar de absolute verschillen waren klein. De drie groepen patiënten verschilden niet veel van elkaar in mate van verandering. conclusie De scores op de in theorie als veranderbaar veronderstelde risicofactoren verminderden naarmate de behandeling vorderde. Daarmee staat echter nog niet vast of dit ook daadwerkelijk een vermindering van het recidiverisico betekent.

Contains fulltext : 77189.pdf (Publisher’s version ) (Open Access), achtergrond In de forensische psychiatrie is het zo betrouwbaar mogelijk inschatten van de recidiverisico's van patiënten cruciaal. Het risicotaxatie-instrument hkt-30 brengt zowel statische als dynamische risicofactoren in kaart. De dynamische risicofactoren zouden door behandeling ten goede moeten veranderen. doel Onderzoeken of dynamische factoren veranderen tijdens tbs-behandeling. methode De hkt-30 werd in totaal 984 maal gescoord bij tbs-patiënten in 3 verschillende forensisch psychiatrische centra, medio 2003-november 2006. Voor 513 patiënten gebeurde dat ten minste 1 maal, voor 313 2 maal of meer en voor 158 in 3 opeenvolgende jaren. Opdeling van de onderzoeksgroep in 'nieuwe', 'oude' en 'overgeplaatste' patiënten maakte het mogelijk te onderzoeken in welke fase van de behandeling de meeste verandering in scores plaatsvond. resultaten Een groot deel van de scores op de dynamische risicofactoren, en daarmee ook de totaalscore, namen statistisch significant af, maar de absolute verschillen waren klein. De drie groepen patiënten verschilden niet veel van elkaar in mate van verandering. conclusie De scores op de in theorie als veranderbaar veronderstelde risicofactoren verminderden naarmate de behandeling vorderde. Daarmee staat echter nog niet vast of dit ook daadwerkelijk een vermindering van het recidiverisico betekent.

Sinds de opkomst van digitale en interactieve kaarten is het Centraal Bureau voor de Statistiek (CBS) actief met het kartografisch ontsluiten en visualiseren van statistieken. Voorbeelden zijn Buurt in Beeld (2001) en de kartografische toegang tot databank StatLine (2004). Door informatie uit registraties te gebruiken, is het CBS meer dan in het verleden in staat om informatie over kleine gebieden samen te stellen en te publiceren. Kartografische mogelijkheden faciliteren dit. Sinds de beschrijving van de achtergronden bij regionaal statistische informatie [Beeckman 2006] heeft het CBS twee nieuwe initiatieven ontwikkeld: een kaartlaag met CBS-buurtcijfers in Google Earth en de website CBSinuwbuurt.nl. Statistieken tot in de achtertuin.

Binnenkort verschijnt de tweede roman van Albertina Soepboer. Een boek over de waarde van verhalen, hoe ze ontstaan en zich verplaatsen. ‘Verhalen worden vaak misbruikt als exclusief onderdeel van een nationaal erfgoed – daar hebben de Friezen ook een handje van.’ Dit artikel geeft de relatie weer die Soepboer heeft met landschap, stilte en verhalend schrijven

Contains fulltext : 71100.pdf (publisher's version ) (Open Access), BACKGROUND: Plasmodium falciparum Apical Membrane Antigen 1 (PfAMA1) is a candidate vaccine antigen expressed by merozoites and sporozoites. It plays a key role in red blood cell and hepatocyte invasion that can be blocked by antibodies. METHODOLOGY/PRINCIPAL FINDINGS: We assessed the safety and immunogenicity of recombinant PfAMA1 in a dose-escalating, phase Ia trial. PfAMA1 FVO strain, produced in Pichia pastoris, was reconstituted at 10 microg and 50 microg doses with three different adjuvants, Alhydrogel, Montanide ISA720 and AS02 Adjuvant System. Six randomised groups of healthy male volunteers, 8-10 volunteers each, were scheduled to receive three immunisations at 4-week intervals. Safety and immunogenicity data were collected over one year. Transient pain was the predominant injection site reaction (80-100%). Induration occurred in the Montanide 50 microg group, resulting in a sterile abscess in two volunteers. Systemic adverse events occurred mainly in the AS02 groups lasting for 1-2 days. Erythema was observed in 22% of Montanide and 59% of AS02 group volunteers. After the second dose, six volunteers in the AS02 group and one in the Montanide group who reported grade 3 erythema (>50 mm) were withdrawn as they met the stopping criteria. All adverse events resolved. There were no vaccine-related serious adverse events. Humoral responses were highest in the AS02 groups. Antibodies showed activity in an in vitro growth inhibition assay up to 80%. Upon stimulation with the vaccine, peripheral mononuclear cells from all groups proliferated and secreted IFNgamma and IL-5 cytokines. CONCLUSIONS/SIGNIFICANCE: All formulations showed distinct reactogenicity profiles. All formulations with PfAMA1 were immunogenic and induced functional antibodies. TRIAL REGISTRATION: (Clinicaltrials.gov) NCT00730782.

Contains fulltext : 71100.pdf (publisher's version ) (Open Access), BACKGROUND: Plasmodium falciparum Apical Membrane Antigen 1 (PfAMA1) is a candidate vaccine antigen expressed by merozoites and sporozoites. It plays a key role in red blood cell and hepatocyte invasion that can be blocked by antibodies. METHODOLOGY/PRINCIPAL FINDINGS: We assessed the safety and immunogenicity of recombinant PfAMA1 in a dose-escalating, phase Ia trial. PfAMA1 FVO strain, produced in Pichia pastoris, was reconstituted at 10 microg and 50 microg doses with three different adjuvants, Alhydrogel, Montanide ISA720 and AS02 Adjuvant System. Six randomised groups of healthy male volunteers, 8-10 volunteers each, were scheduled to receive three immunisations at 4-week intervals. Safety and immunogenicity data were collected over one year. Transient pain was the predominant injection site reaction (80-100%). Induration occurred in the Montanide 50 microg group, resulting in a sterile abscess in two volunteers. Systemic adverse events occurred mainly in the AS02 groups lasting for 1-2 days. Erythema was observed in 22% of Montanide and 59% of AS02 group volunteers. After the second dose, six volunteers in the AS02 group and one in the Montanide group who reported grade 3 erythema (>50 mm) were withdrawn as they met the stopping criteria. All adverse events resolved. There were no vaccine-related serious adverse events. Humoral responses were highest in the AS02 groups. Antibodies showed activity in an in vitro growth inhibition assay up to 80%. Upon stimulation with the vaccine, peripheral mononuclear cells from all groups proliferated and secreted IFNgamma and IL-5 cytokines. CONCLUSIONS/SIGNIFICANCE: All formulations showed distinct reactogenicity profiles. All formulations with PfAMA1 were immunogenic and induced functional antibodies. TRIAL REGISTRATION: (Clinicaltrials.gov) NCT00730782.

Marleen Felius (Hillegersberg,1948) is veeschilder. Zij woont en werkt in Rotterdam. Naast een impressie van haar werk volgt hier een interview met haar over werk, in de provincie Friesland. Ze trof 25 rassen aan, maar het originele zwart-bonte stamboekvee trof ze nauwelijks nog aan. Een tentoonstelling van haar werk is te vinden in Harlingen (Galerie de Vis) en in Leeuwarden (Friesland Bank), daarbij is een boerderijenroute beschikbaar langs 12 van de 25 in beeld gebrachte rassen

Item does not contain fulltext, Randomized clinical trials (RCTs) are prospective empirical studies used to investigate the effect of a particular medical intervention. The design of a clinical trial is a delicate decision process, as each of the decisions that are taken in this process influences the eventual result of the clinical trial. Despite the efforts that are put into trial design, many trials fail to show an effect of the intervention. In some of these situations the intervention may be truly ineffective, however, more often this is caused by problems with the inclusion of patients and a resulting lack of statistical power to show the effect. To avoid this problem, in the design of a trial, the statistical power that can be achieved with the current design choices is calculated and balanced with economic considerations. In the choice of the entry criteria however, an important step in the design process, the influence of the chosen criteria on statistical power and number of eligible patients is not quantified. As these criteria influence the characteristics of the study population and the number of patients that will be eligible for the trial, and thereby the chances of finding an effect of the intervention, we believe that also in the choice of entry criteria explicit estimates of the number of eligible patients should be made. This paper presents a method to arrive at precise, objective estimates of statistical power and the number of eligible patients, using a registry database. Furthermore, we describe how this method is incorporated in the process of choosing entry criteria for a clinical trial. We illustrate the method with an example in the area of severe sepsis.

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Contains fulltext : 52407.pdf ( ) (Open Access), INTRODUCTION: The aim of the study was to assess the influence of annual volume and factors related to intensive care unit (ICU) organization on in-hospital mortality among patients admitted to the ICU with severe sepsis. METHODS: A retrospective cohort study was conducted using the database of the Dutch National Intensive Care Evaluation (NICE) registry. Analyses were based on consecutive patients admitted between 1 January 2003 and 30 June 2005 who fulfilled criteria for severe sepsis within the first 24 hours of admission. A 13-item questionnaire was sent to all 32 ICUs across The Netherlands that participated in the NICE registry within this period in order to obtain information on ICU organization and staffing. The association between in-hospital mortality and factors related to ICU organization was investigated using logistic regression analysis, combined with generalized estimation equations to account for potential correlations of outcomes within ICUs. Correction for patient-related factors took place by including Simplified Acute Physiology Score II, age, sex and number of dysfunctioning organ systems in the analyses. RESULTS: Analyses based on 4,605 patients from 28 ICUs (questionnaire response rate 90.6%) revealed that a higher annual volume of severe sepsis patients is associated with a lower in-hospital mortality (P = 0.029). The presence of a medium care unit (MCU) as a step-down facility with intermediate care is associated with a higher in-hospital mortality (P = 0.013). For other items regarding ICU organization, no independent significant relationships with in-hospital mortality were found. CONCLUSION: A larger annual volume of patients with severe sepsis admitted to Dutch ICUs is associated with lower in-hospital mortality in this patient group. The presence of a MCU as a step-down facility is associated with greater in-hospital mortality. No other significant associations between in-hospital mortality and factors related to ICU organization were

Item does not contain fulltext, Randomized clinical trials (RCTs) are prospective empirical studies used to investigate the effect of a particular medical intervention. The design of a clinical trial is a delicate decision process, as each of the decisions that are taken in this process influences the eventual result of the clinical trial. Despite the efforts that are put into trial design, many trials fail to show an effect of the intervention. In some of these situations the intervention may be truly ineffective, however, more often this is caused by problems with the inclusion of patients and a resulting lack of statistical power to show the effect. To avoid this problem, in the design of a trial, the statistical power that can be achieved with the current design choices is calculated and balanced with economic considerations. In the choice of the entry criteria however, an important step in the design process, the influence of the chosen criteria on statistical power and number of eligible patients is not quantified. As these criteria influence the characteristics of the study population and the number of patients that will be eligible for the trial, and thereby the chances of finding an effect of the intervention, we believe that also in the choice of entry criteria explicit estimates of the number of eligible patients should be made. This paper presents a method to arrive at precise, objective estimates of statistical power and the number of eligible patients, using a registry database. Furthermore, we describe how this method is incorporated in the process of choosing entry criteria for a clinical trial. We illustrate the method with an example in the area of severe sepsis.

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Contains fulltext : 52407.pdf ( ) (Open Access), INTRODUCTION: The aim of the study was to assess the influence of annual volume and factors related to intensive care unit (ICU) organization on in-hospital mortality among patients admitted to the ICU with severe sepsis. METHODS: A retrospective cohort study was conducted using the database of the Dutch National Intensive Care Evaluation (NICE) registry. Analyses were based on consecutive patients admitted between 1 January 2003 and 30 June 2005 who fulfilled criteria for severe sepsis within the first 24 hours of admission. A 13-item questionnaire was sent to all 32 ICUs across The Netherlands that participated in the NICE registry within this period in order to obtain information on ICU organization and staffing. The association between in-hospital mortality and factors related to ICU organization was investigated using logistic regression analysis, combined with generalized estimation equations to account for potential correlations of outcomes within ICUs. Correction for patient-related factors took place by including Simplified Acute Physiology Score II, age, sex and number of dysfunctioning organ systems in the analyses. RESULTS: Analyses based on 4,605 patients from 28 ICUs (questionnaire response rate 90.6%) revealed that a higher annual volume of severe sepsis patients is associated with a lower in-hospital mortality (P = 0.029). The presence of a medium care unit (MCU) as a step-down facility with intermediate care is associated with a higher in-hospital mortality (P = 0.013). For other items regarding ICU organization, no independent significant relationships with in-hospital mortality were found. CONCLUSION: A larger annual volume of patients with severe sepsis admitted to Dutch ICUs is associated with lower in-hospital mortality in this patient group. The presence of a MCU as a step-down facility is associated with greater in-hospital mortality. No other significant associations between in-hospital mortality and factors related to ICU organization were

Contains fulltext : 52407.pdf ( ) (Open Access), INTRODUCTION: The aim of the study was to assess the influence of annual volume and factors related to intensive care unit (ICU) organization on in-hospital mortality among patients admitted to the ICU with severe sepsis. METHODS: A retrospective cohort study was conducted using the database of the Dutch National Intensive Care Evaluation (NICE) registry. Analyses were based on consecutive patients admitted between 1 January 2003 and 30 June 2005 who fulfilled criteria for severe sepsis within the first 24 hours of admission. A 13-item questionnaire was sent to all 32 ICUs across The Netherlands that participated in the NICE registry within this period in order to obtain information on ICU organization and staffing. The association between in-hospital mortality and factors related to ICU organization was investigated using logistic regression analysis, combined with generalized estimation equations to account for potential correlations of outcomes within ICUs. Correction for patient-related factors took place by including Simplified Acute Physiology Score II, age, sex and number of dysfunctioning organ systems in the analyses. RESULTS: Analyses based on 4,605 patients from 28 ICUs (questionnaire response rate 90.6%) revealed that a higher annual volume of severe sepsis patients is associated with a lower in-hospital mortality (P = 0.029). The presence of a medium care unit (MCU) as a step-down facility with intermediate care is associated with a higher in-hospital mortality (P = 0.013). For other items regarding ICU organization, no independent significant relationships with in-hospital mortality were found. CONCLUSION: A larger annual volume of patients with severe sepsis admitted to Dutch ICUs is associated with lower in-hospital mortality in this patient group. The presence of a MCU as a step-down facility is associated with greater in-hospital mortality. No other significant associations between in-hospital mortality and factors related to ICU organization were

Item does not contain fulltext, Randomized clinical trials (RCTs) are prospective empirical studies used to investigate the effect of a particular medical intervention. The design of a clinical trial is a delicate decision process, as each of the decisions that are taken in this process influences the eventual result of the clinical trial. Despite the efforts that are put into trial design, many trials fail to show an effect of the intervention. In some of these situations the intervention may be truly ineffective, however, more often this is caused by problems with the inclusion of patients and a resulting lack of statistical power to show the effect. To avoid this problem, in the design of a trial, the statistical power that can be achieved with the current design choices is calculated and balanced with economic considerations. In the choice of the entry criteria however, an important step in the design process, the influence of the chosen criteria on statistical power and number of eligible patients is not quantified. As these criteria influence the characteristics of the study population and the number of patients that will be eligible for the trial, and thereby the chances of finding an effect of the intervention, we believe that also in the choice of entry criteria explicit estimates of the number of eligible patients should be made. This paper presents a method to arrive at precise, objective estimates of statistical power and the number of eligible patients, using a registry database. Furthermore, we describe how this method is incorporated in the process of choosing entry criteria for a clinical trial. We illustrate the method with an example in the area of severe sepsis.

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Portret van Groningse schrijfster Aafke Steenhuis. Haar leven op het Groningse platteland en haar huidige houding ten aanzien van het platteland: na een tijdelijk verblijf in het buitenland, kijkt ze met andere ogen naar Groningen. Voorafgaand aan het verschijnen van haar boek "Verhalen van het Groninger Ommeland" volgt hier een interview en een voorpublicatie van een fragment

Item does not contain fulltext, OBJECTIVE: To understand the impact of patient selection criteria used in recent sepsis trials on baseline mortality risk and number of eligible patients. DESIGN: Observational cohort study, with retrospective analysis of prospectively collected data. METHODS AND MAIN RESULTS: Using a MEDLINE search, we selected recent randomized controlled trials in patients with severe sepsis and studied the mortality rate in the control groups of these trials. Nine articles fulfilled the search criteria and were used in our analyses. The 28-day mortality rate in the control groups of these trials varied between 28.0% and 89.0%. Differences in this mortality rate might be due to the use of different entry criteria but also to other factors that vary between the trials. To eliminate the influence of these confounding factors when studying the effect of the use of entry criteria on baseline mortality risk and number of eligible patients, we projected the entry criteria of these nine trials on a large independent database of >70,000 Dutch intensive care patients admitted between 1996 and 2003. This yielded nine groups of patients who would have been eligible for the respective trials. The percentage of patients who would have been eligible for these trials varied between 1.5% and 6.0%. Six of these groups had a similar intensive care mortality rate (between 25.0% and 28.9%). The projection of the entry criteria of the three other trials onto the database resulted in groups of patients with considerably higher intensive care mortality. For in-hospital mortality rate in these groups, similar results were found. CONCLUSIONS: The majority of the trials we studied used entry criteria that select patients with a similar mortality risk. This suggests that differences in baseline mortality risk reported in recent sepsis trials are to be attributed to other factors that vary between trials rather than to differences in entry criteria. However, entry criteria do have an important influence on

Item does not contain fulltext, OBJECTIVE: To understand the impact of patient selection criteria used in recent sepsis trials on baseline mortality risk and number of eligible patients. DESIGN: Observational cohort study, with retrospective analysis of prospectively collected data. METHODS AND MAIN RESULTS: Using a MEDLINE search, we selected recent randomized controlled trials in patients with severe sepsis and studied the mortality rate in the control groups of these trials. Nine articles fulfilled the search criteria and were used in our analyses. The 28-day mortality rate in the control groups of these trials varied between 28.0% and 89.0%. Differences in this mortality rate might be due to the use of different entry criteria but also to other factors that vary between the trials. To eliminate the influence of these confounding factors when studying the effect of the use of entry criteria on baseline mortality risk and number of eligible patients, we projected the entry criteria of these nine trials on a large independent database of >70,000 Dutch intensive care patients admitted between 1996 and 2003. This yielded nine groups of patients who would have been eligible for the respective trials. The percentage of patients who would have been eligible for these trials varied between 1.5% and 6.0%. Six of these groups had a similar intensive care mortality rate (between 25.0% and 28.9%). The projection of the entry criteria of the three other trials onto the database resulted in groups of patients with considerably higher intensive care mortality. For in-hospital mortality rate in these groups, similar results were found. CONCLUSIONS: The majority of the trials we studied used entry criteria that select patients with a similar mortality risk. This suggests that differences in baseline mortality risk reported in recent sepsis trials are to be attributed to other factors that vary between trials rather than to differences in entry criteria. However, entry criteria do have an important influence on

Item does not contain fulltext, OBJECTIVE: To understand the impact of patient selection criteria used in recent sepsis trials on baseline mortality risk and number of eligible patients. DESIGN: Observational cohort study, with retrospective analysis of prospectively collected data. METHODS AND MAIN RESULTS: Using a MEDLINE search, we selected recent randomized controlled trials in patients with severe sepsis and studied the mortality rate in the control groups of these trials. Nine articles fulfilled the search criteria and were used in our analyses. The 28-day mortality rate in the control groups of these trials varied between 28.0% and 89.0%. Differences in this mortality rate might be due to the use of different entry criteria but also to other factors that vary between the trials. To eliminate the influence of these confounding factors when studying the effect of the use of entry criteria on baseline mortality risk and number of eligible patients, we projected the entry criteria of these nine trials on a large independent database of >70,000 Dutch intensive care patients admitted between 1996 and 2003. This yielded nine groups of patients who would have been eligible for the respective trials. The percentage of patients who would have been eligible for these trials varied between 1.5% and 6.0%. Six of these groups had a similar intensive care mortality rate (between 25.0% and 28.9%). The projection of the entry criteria of the three other trials onto the database resulted in groups of patients with considerably higher intensive care mortality. For in-hospital mortality rate in these groups, similar results were found. CONCLUSIONS: The majority of the trials we studied used entry criteria that select patients with a similar mortality risk. This suggests that differences in baseline mortality risk reported in recent sepsis trials are to be attributed to other factors that vary between trials rather than to differences in entry criteria. However, entry criteria do have an important influence on

Contains fulltext : 58186.pdf (publisher's version ) (Closed access)

Contains fulltext : 58188.pdf (publisher's version ) (Closed access)

Contains fulltext : 58186.pdf (publisher's version ) (Closed access)

Contains fulltext : 58188.pdf (publisher's version ) (Closed access)

Contains fulltext : 58186.pdf (publisher's version ) (Closed access)

Item does not contain fulltext

Item does not contain fulltext