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Background: Due to emergency care overcrowding, right care at the right place and time is necessary. Uniform triage of patients contacting different emergency care settings will improve quality of care and communication between health care providers., Objective: Validation of the computer-based Netherlands Triage System (NTS) developed for physical triage at emergency departments (EDs) and telephone triage at general practitioner cooperatives (GPCs)., Methods: Prospective observational study with patients attending the ED of a university-affiliated hospital (September 2008 to November 2008) or contacting an urban GPC (December 2008 to February 2009). For validation of the NTS, we defined surrogate urgency markers as best proxies for true urgency. For physical triage (ED): resource use, hospitalization and follow-up. For telephone triage (GPC): referral to ED, self-care advice after telephone consultation or GP advice after physical consultation. Associations between NTS urgency levels and surrogate urgency markers were evaluated using chi-square tests for trend., Results: We included nearly 10 000 patients. For physical triage at ED, NTS urgency levels were associated with resource use, hospitalization and follow-up. For telephone triage at GPC, trends towards more ED referrals in high NTS urgency levels and more self-care advices after telephone consultation in lower NTS urgency levels were found. The association between NTS urgency classification and GP advice was less explicit. Similar results were found for children; however, we found no association between NTS urgency level and GP advice., Conclusions: Physically and telephone-assigned NTS urgency levels were associated with majority of surrogate urgency markers. The NTS as single triage system for physical and telephone triage seems feasible.

Objectives: Migrants originating from countries with a high HIV prevalence account for a large number of heterosexually acquired HIV infections in western European countries. These migrants may be infected before migrating and they may engage in unsafe sexual practices both in the country of residence and in their country of origin. This report investigates how patterns of migration may affect the heterosexual HIV epidemic in The Netherlands., Methods: A mathematical model was used that describes the transmission of HIV in heterosexual partnerships between African migrants, Caribbean migrants and the local Dutch population. Infection of migrants before migrating to The Netherlands and during trips to their country of origin was also accounted for., Results: The incidence of HIV infection among adult heterosexuals in 2010 was 1.50 new infections per 100,000 individuals per year. If the number of migrants entering the country increases, then the incidence of HIV will increase, although this change among Dutch individuals will be negligible. Moreover, if HIV prevalence among those migrating to The Netherlands (at the time of entry to the country) is higher, then incidence in the respective ethnic group will increase; among other ethnic groups, the increase will be very small., Conclusions: Heterosexual transmission of HIV in The Netherlands occurs mostly within migrant communities. Limiting migration and introducing travel restrictions would probably have no effect on HIV incidence in countries with low HIV prevalence among heterosexuals. Policy making should focus on targeted interventions, to reduce the burden of disease in migrant communities in Europe.

Objective: To assess hospitalisation rate as a proxy for the ability of the Manchester Triage System (MTS) to identify less urgent paediatric patients. We also evaluated general practitioner (GP) services to determine if they met patients' needs compared to emergency department care., Methods: Self-referred children triaged as less urgent by the MTS in two emergency departments in the Netherlands were included in a prospective observational study. Therapeutic interventions during emergency department consultation, hospitalisation after consultation and determinants for hospitalisation were assessed using logistic regression analysis., Results: During emergency department consultation, extensive therapeutic interventions were performed more often in patients with extremity problems (n=175, 19%) and dyspnoea (n=30, 15%). 191 (3.5%) of 5425 patients were hospitalised. Age and presenting problem remained statistically significant in multivariable logistic analysis, predicting hospitalisation with ORs of 3.0 (95% CI 2.2 to 4.1) for age <1 year, 2.5 (1.5 to 4.1) for dyspnoea, 3.5 (2.5 to 4.9) for gastrointestinal problems and 2.8 (1.1 to 7.2) for patients with fever without identified source compared to all other patients. 3975 (76%) of 5234 patients were contacted for follow-up after discharge. Six (0.15%) patients were hospitalised after emergency department discharge., Conclusion: In the MTS less urgent categories, overall hospitalisation is low, although children <1 year of age or with dyspnoea, gastrointestinal problems or fever without identified source have an increased risk for hospitalisation. Except for these patient groups, the MTS identifies less urgent patients safely. It may not be optimal for GP services to treat patients with extremity problems.

Objectives: To investigate how the sexual behaviour of migrants originating from HIV-endemic countries affects the spread of HIV among heterosexuals in low-endemic countries., Methods: A mathematical model is developed describing the transmission of HIV in heterosexual partnerships between African migrants, Caribbean migrants, and local natives. The model accounts for infection of migrants before migration and during trips to their home country. The model is parameterized using data from the Netherlands., Results: Among new and newly imported, heterosexually acquired, infections in 2010 in the Netherlands, the individual acquiring HIV is an African in 53% of cases, a Caribbean in 26% of cases, and a Dutch native in 21% of cases. The percentage of new infections acquired outside the Netherlands is 40% among African migrants and 32% among Caribbean migrants; these are mostly acquired before migration to the Netherlands. The prevalence of HIV in the Netherlands is hardly affected by changes in risk behaviour of migrants during trips to their home country after migration. If migrants mix more with the Dutch in forming partnerships, then HIV prevalence among migrants will decrease. The more initiating antiviral therapy is delayed among migrants, the higher the resulting prevalence in their own ethnic group and among the Dutch., Conclusion: The serostatus of individuals migrating to low-prevalence countries as well as their sexual behaviour in the country of residence affect considerably the spread of HIV. Preventive measures should focus on targeted interventions, promoting safe sex practices, HIV testing, and entry to specialized HIV care among migrants.

Objective: The authors aimed to assess the repeatability of the Manchester Triage System (MTS) in children., Methods: All emergency department nurses (n=43) from a general teaching hospital and a university children's hospital in The Netherlands triaged 20 written case scenarios using the Manchester Triage system. Second, at two emergency departments (EDs), real-life simultaneous triage of patients (<16 years) was performed by ED nurses and two research nurses. The written case scenarios and the patients included in the real-life simultaneous triage study were representative of children attending the ED, in age, problem and urgency level. The authors assessed inter-rater agreement using quadratic weighted kappa values., Results: The weighted kappa between the nurses, triaging the case scenarios, was 0.83 (95% CI 0.74 to 0.91). In total, 88% (N=198) of the eligible ED patients were triaged simultaneously, with a weighted kappa of 0.65 (95% CI 0.56 to 0.72)., Conclusions: The MTS showed good to very good repeatability in paediatric emergency care.

Background: Triage in paediatric emergency care is an important tool to prioritize seriously ill children. Triage can also be used to identify patients who do not need urgent care and who can safely wait. The aim of this review was to provide an overview of the literature on reliability and validity of current triage systems in paediatric emergency care, Methods: We performed a search in Pubmed and Cochrane on studies on reliability and validity of triage systems in children, Results: The Manchester Triage System (MTS), the Emergency Severity Index (ESI), the Paediatric Canadian Triage and Acuity Score (paedCTAS) and the Australasian Triage Scale (ATS) are common used triage systems and contain specific parts for children. The reliability of the MTS is good and reliability of the ESI is moderate to good. Reliability of the paedCTAS is moderate and is poor to moderate for the ATS.The internal validity is moderate for the MTS and confirmed for the CTAS, but not studied for the most recent version of the ESI, which contains specific fever criteria for children., Conclusion: The MTS and paedCTAS both seem valid to triage children in paediatric emergency care. Reliability of the MTS is good, moderate to good for the ESI and moderate for the paedCTAS. More studies are necessary to evaluate if one triage system is superior over other systems when applied in emergency care.

Ovarian small-cell carcinoma of the hypercalcemic type is a rare and highly malignant tumor. In two thirds of the patients, the tumor is associated with asymptomatic paraneoplastic hypercalcemia. The diagnosis may be impeded; the tumor must be distinguished from other tumors with similar features.This tumor occurs predominantly in young women and is merely lethal. The 1-year survival is solely 50%, with an overall 5-year survival rate of approximately 10%. It is believed that the empirical treatment characterized by combination of radical surgery, chemotherapy, and radiotherapy results in the most favorable outcome in terms of survival. However, the outcome remains extremely poor despite this aggressive approach.Alternatively, these poor survival rates may justify a less aggressive fertility sparing approach without compromising the outcome. Such an approach is illustrated by a case report involving a patient with ovarian small-cell carcinoma of the hypercalcemic type, FIGO stage IIIC. A fertility-sparing approach was used, consisting of conservative surgery followed by induction chemotherapy, interval debulking surgery, and local radiotherapy. During follow-up of 60 months, there was no evidence of disease and the normal menstrual cycle resumed.In addition to this case report, histopathological features, different therapeutic modalities, and outcome of ovarian small-cell carcinoma of the hypercalcemic type is reviewed. This report suggests that a fertility-sparing approach may be just as feasible as the generally applied aggressive approach.

Objective: To validate use of the Manchester triage system in paediatric emergency care., Design: Prospective observational study., Setting: Emergency departments of a university hospital and a teaching hospital in the Netherlands, 2006-7., Participants: 17,600 children (aged <16) visiting an emergency department over 13 months (university hospital) and seven months (teaching hospital)., Intervention: Nurses triaged 16,735/17,600 patients (95%) using a computerised Manchester triage system, which calculated urgency levels from the selection of discriminators embedded in flowcharts for presenting problems. Nurses over-ruled the urgency level in 1714 (10%) children, who were excluded from analysis. Complete data for the reference standard were unavailable in 1467 (9%) children leaving 13,554 patients for analysis., Main Outcome Measures: Urgency according to the Manchester triage system compared with a predefined and independently assessed reference standard for five urgency levels. This reference standard was based on a combination of vital signs at presentation, potentially life threatening conditions, diagnostic resources, therapeutic interventions, and follow-up. Sensitivity, specificity, and likelihood ratios for high urgency (immediate and very urgent) and 95% confidence intervals for subgroups based on age, use of flowcharts, and discriminators., Results: The Manchester urgency level agreed with the reference standard in 4582 of 13,554 (34%) children; 7311 (54%) were over-triaged and 1661 (12%) under-triaged. The likelihood ratio was 3.0 (95% confidence interval 2.8 to 3.2) for high urgency and 0.5 (0.4 to 0.5) for low urgency; though the likelihood ratios were lower for those presenting with a medical problem (2.3 (2.2 to 2.5) v 12.0 (7.8 to 18.0) for trauma) and in younger children (2.4 (1.9 to 2.9) at 0-2 months [corrected] v 5.4 (4.5 to 6.5) at 8-16 years)., Conclusions: The Manchester triage system has moderate validity in paediatric emergency care. It errs on the safe side, with much more over-triage than under-triage compared with an independent reference standard for urgency. Triage of patients with a medical problem or in younger children is particularly difficult.

Two girls developed symptoms of wheezing which started shortly after birth. The symptoms did not respond to bronchodilators. At the age of 5 months, the first infant developed severe respiratory distress with decreased left-sided breathing sounds on auscultation. The chest X-ray showed left-sided hyperinflation. Bronchoscopy revealed isolated malacia of the left main stem bronchus. The second patient, who had a history ofcor vitium, was referred to a paediatric pulmonologist in an academic hospital for chronic coughing and wheezing. Bronchoscopy and CT angiogram, performed at the age of 14 months, revealed tracheal malacia due to compression from a right descending aortic arch. Broncho- and tracheomalacia are disorders which may rarely result in severe respiratory distress. These disorders should be considered when unexplained symptoms of wheezing or coughing are present in young infants, especially if the symptoms start shortly after birth and persist without signs of viral infection.

Introduction: Costs are one of the factors determining physicians' choice of medication to treat patients in specific situations. However, usually only the drug acquisition costs are taken into account, whereas other factors such as the use of disposable materials, the drug preparation time and the staff workload are insufficiently taken into consideration. We therefore decided to assess true overall costs of intravenous (IV) antibiotic administration by performing an activity-based costing approach., Methods: A prospective survey on costs and workload by means of a time and motion analysis and activity-based costing was performed in a 605-bed secondary referral centre with 20 intensive care unit beds. The subjects were 50 consecutive patients admitted to our hospital with community-acquired pneumonia or intra-abdominal infections requiring treatment with IV antibiotics. A time and motion analysis of 103 routine acts of preparing and administering IV antibiotics was performed in the intensive care unit and in the Department of Internal Medicine. To measure the entire process an inventory and work flowchart were made using detailed questionnaires completed by members of the nursing staff, the medical staff and the pharmacy staff. In addition, questionnaires were distributed to management and secretarial staff to determine additional overhead costs. The average costs for different methods of IV antibiotic administration were then compared by timing all steps in the process. Four different methods of drug administration were used: administration by volumetric pump, administration by syringe pump, administration by 'unaided' infusion bag, and administration by direct IV injection., Results: The average times required for each of these procedures, including preparation and administration of the drug, were 4:49 +/- 2:37, 4:56 +/- 2:03, 5:51 +/- 3:33 and 9:21 +/- 2:16 min (mean minutes:seconds +/- standard deviation), respectively. When the costs for expended staff time and materials (not including drug costs) were calculated this resulted in average costs of 5.65, 7.28, 5.36 and 3.83, respectively, for administration of each dose of antibiotics. These costs represent between 11% and 53% of the total daily costs of antibiotic therapy. Compared with the acquisition costs, these indirect costs ranged from 13% to 113%. Not included in this comparison is the time required for insertion of an IV catheter, which was found to be 10:15 +/- 6:31 min with an average calculated cost of 9.17., Conclusions: Total costs of IV antibiotic administration are formed not only by the costs of the drugs themselves, but also, to a substantial degree, by the time expended by medical and nursing staff, costs of disposable materials and overhead costs. Physicians making decisions regarding the use of specific medications in intensive care unit patients should take these factors into account. Use of IV antibiotics is associated with considerable workload and additional costs that can exceed the acquisition costs of the medications themselves.

The tetranuclear aggregate (enH(2))[Fe(4)(mu(3)-O)(heidi)(4)(mu-O,O'-O(2)CNHC(2)H(4)NH(3))] x 4H(2)O contains a novel bidentate zwitterionic carbamic acid ligand. Magnetic studies indicate that the unsymmetrical Fe(4) core is ferrimagnetic with an S=4 ground state. Similar ligands have been obtained on rectangular tetranuclear aggregates [M(4)(mu-O)(mu-OH)(hpdta)(2)(mu-X)(2)](n-) (M[double bond]Fe, Al, Ga). The carbamic acid ligands are considered to result from the hydrolytic activation (fixation) of atmospheric CO(2) by the aggregate precursor to give a carbonato intermediate, which then reacts with the organic diamine used as base in the synthesis. Similar aggregates with acetate ligands result from hydrolytic activation of the DMA used as cosolvent. Closely related mechanisms for these two activation processes are proposed, which are also related to the accepted mechanisms for carbonic anhydrase and urease.

Two studies are reported which aimed to examine the relationship between phonological sensitivity and the acquisition of new words that systematically differed in the familiarity of their sound structures. In the first study measures of phonological sensitivity, phonological short-term memory, vocabulary, and nonverbal ability were administered to forty-one 5-year-old children. Phonological sensitivity was related to the paired-associate learning of phonologically unfamiliar words, but not to the learning of familiar words. In the second study a group of 14 nonreading 5-year-old children received phonological sensitivity training. A control group was trained in semantic categorization. After the training, the phonological sensitivity group did perform better on measures of letter knowledge and phonological sensitivity (rhyme and first-sound categorization) and appeared to learn phonologically unfamiliar words more easily. The findings of both studies suggest that phonological sensitivity can support the acquisition of novel words., (Copyright 2000 Academic Press.)

Objective: To monitor liver regeneration following partial hepatectomy, liver cell proliferation can be measured by assaying in vivo [3H]thymidine incorporation into liver cell DNA. We hypothesized that [3H]thymidine incorporation into whole liver tissue parallels [3H]thymidine incorporation into liver cell DNA, both in high proliferating and low proliferating liver., Study Design: Liver cell proliferation in rats after partial hepatectomy or a sham operation was studied by measuring incorporation of [3H]thymidine into various fractions of liver tissue on days 1, 2, 3, 4 and 10 after surgery., Results: [3H]thymidine incorporation into whole liver tissue and in the protein fraction correlated well with DNA-specific [3H]thymidine incorporation into regenerating (r > .80, P < .0001) and nonregenerating liver (r > .69, P < .005). [3H]thymidine incorporation into DNA was < 5% of the total amount of administered [3H]thymidine in both sham-operated and hepatectomized rats. Significant differences in [3H]thymidine incorporation into partially hepatectomized livers as compared to sham-operated rat livers were found on days 1 and 2 (whole liver tissue and protein fraction) or day 1 (DNA) after surgery., Conclusion: [3H]thymidine incorporation into whole liver tissue is a simple technique that can be used for the study of liver cell proliferation after partial hepatectomy in rats.

The characterization of fluoresceinphosphatidylethanolamine (FPE) as a real-time indicator of the electrostatic nature of a membrane surface is described. The conditions appropriate for the labelling of membranes and the implementation of FPE as a tool to monitor the interactions of various peptides with model membranes are outlined. It is shown that of the membrane-active peptides studied, Naja naja kaouthia cardiotoxin and pyrularia thionin bind to certain model membranes without insertion. Whereas the leader sequence of the nuclear encoded subunit IV of mammalian cytochrome c oxidase (E.C. 1.9.3.1), known as p-25, and melittin appear to bind and then partially insert into the membrane. It seems evident also that melittin does not adopt a fully transmembrane configuration. Melittin is known to promote membrane lysis and by employing a rapid-kinetic technique it is shown that the time-course of such lysis does not appear to correlate with peptide binding, but following binding a significant proportion of melittin must become inserted into the membrane before lysis appears to commence.

Reconstitution of the anion exchange protein from human erythrocytes (band 3) into phospholipid vesicles was shown to have a protective effect on melittin lysis of the vesicles when compared to pure lipid vesicles. Low salt buffer was found to cause an inhibition of lysis in both proteoliposomes and pure lipid vesicles compared to salt buffer. High phosphate concentration did not seem to cause inhibition of lysis in the reconstituted system. However, an inhibition is observed in pure lipid vesicle control, which is contradictory to previous reports.

The present paper is concerned with the question whether cells of the mononuclear phagocyte system (MPS) function as a transport system for doxorubicin (DXR)-containing liposomes into solid tumors. The investigations were performed in solid IgM immunocytoma bearing Lou/M Wsl rats. In this tumor system macrophage accumulation was observed during DXR and cisplatin induced tumor regression. Tumor-bearing rats were treated i.v. with 1 mg/kg DXR (either free or entrapped in liposomes) for 4 consecutive days. Changes in the cellular composition of the tumor were studied by histology and cytology comparing free and liposomal DXR treatment. Therapy with DXR-liposomes (lip DXR) induced macrophage accumulation similar to free DXR. No differences in cellular changes in the tumor between both types of treatment were found. The DXR-content of tumor-associated cells was measured at various times during treatment with free or lip DXR by means of flow cytometry. Most DXR-fluorescence was associated with dead cells and cellular debris. No clear-cut differences in DXR-content were found between macrophages isolated from tumors of free DXR treated animals and those isolated from lip DXR treated animals. In order to investigate whether DXR-liposomes are taken up by tumor tissue (either via macrophages or directly by the tissue itself), [3H]inulin-labeled DXR-liposomes were administered to tumor-bearing rats. The distribution of radiolabeled lip DXR in non-treated rats was compared with that in rats which were pretreated with non-radiolabeled lip DXR to induce macrophage accumulation. In both untreated and pretreated animals most of the administered 3H-dose was recovered in liver and spleen. Only a minor fraction was recovered from the tumor and other tissues. This fraction was not higher than that obtained when a comparable amount of free [3H]inulin was injected. In conclusion, this study suggests that DXR-liposomes do not enter the solid IgM immunocytoma, even when during therapy macrophages pass the endothelial barrier. Therefore, it is unlikely that macrophage-mediated transportation of DXR-liposomes into the tumor is involved in the mechanism of tumor regression induced by liposome-entrapped DXR.