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Background: Serious games have the potential to teach complex cognitive skills in an engaging way, at relatively low costs. Their flexibility in use and scalability makes them an attractive learning tool, but more research is needed on the effectiveness of serious games compared to more traditional formats such e-modules. We investigated whether undergraduate medical students developed better knowledge and awareness and were more motivated after learning about patient-safety through a serious game than peers who studied the same topics using an e-module., Methods: Fourth-year medical students were randomly assigned to either a serious game that included video-lectures, biofeedback exercises and patient missions (n = 32) or an e-module, that included text-based lectures on the same topics (n = 34). A third group acted as a historical control-group without extra education (n = 37). After the intervention, which took place during the clinical introduction course, before the start of the first rotation, all students completed a knowledge test, a self-efficacy test and a motivation questionnaire. During the following 10-week clinical rotation they filled out weekly questionnaires on patient-safety awareness and stress., Results: The results showed patient safety knowledge had equally improved in the game group and e-module group compared to controls, who received no extra education. Average learning-time was 3 h for the game and 1 h for the e-module-group. The serious game was evaluated as more engaging; the e-module as more easy to use. During rotations, students in the three groups reported low and similar levels of patient-safety awareness and stress. Students who had treated patients successfully during game missions experienced higher self-efficacy and less stress during their rotation than students who treated patients unsuccessfully., Conclusions: Video-lectures (in a game) and text-based lectures (in an e-module) can be equally effective in developing knowledge on specific topics. Although serious games are strongly engaging for students and stimulate them to study longer, they do not necessarily result in better performance in patient safety issues.

Background: Sepsis has a high mortality. Early recognition and timely treatment are essential for patient survival. The aim of this study is to examine the factors that influence the knowledge and recognition of systemic inflammatory response syndrome (SIRS) criteria and sepsis by emergency department (ED) nurses., Methods: A prospective, multi-center study including 216 ED nurses from 11 hospitals and academic medical centers in The Netherlands was conducted in 2013. A validated questionnaire was used to evaluate ED nurses' knowledge about SIRS and sepsis. Questions about demographic characteristics were also included, to investigate factors that may contribute to the knowledge about SIRS and sepsis., Results: The mean total score was 15.9 points, with a maximum possible score of 29 points. ED nurses employed at hospitals with a level 3 intensive care unit (ICU) scored significantly higher than their colleagues employed at hospitals with a level 1 or 2 ICU. Recently completed education in sepsis was associated with a higher score. The employees in low ICU level hospitals who reported recent education did not score significantly lower than their ICU level 3 colleagues. ED nurses over the age of 50 scored significantly lower than their younger colleagues., Conclusions: The knowledge of ED nurses concerning SIRS and sepsis rises proportionally with the level of ICU in hospitals. Recent education in sepsis raises knowledge level as well. We recommend that when there is a low exposure rate to SIRS and sepsis, more emphasis should be placed on regular education.

Background: Fever is a common symptom in the emergency department(ED). Fever can be caused by bacterial infections, which are treated with antibiotics. Often, bacterial infections cannot be ruled out in the ED using standard diagnostics, and empiric antibiotic treatment is started. Procalcitonin(PCT) is a biomarker for bacterial infections, but its role in an undifferentiated ED population remains unclear. We hypothesize that PCT-guided therapy may reduce antibiotics prescription in undifferentiated febrile ED patients. The primary objectives of this study are to determine a) the efficacy, b) the safety of PCT-guided therapy, and c) the accuracy of the biomarker PCT for bacterial infections. The secondary objective is to study the cost-effectiveness of PCT-guided therapy., Methods/design: This is a multicenter noninferiority randomized controlled trial. All adult ED patients with fever(≥38.2 °C) are randomized between standard care with and without the addition of a PCT level, after written informed consent. a) For efficacy, the reduction of patients receiving antibiotics is calculated, using a superiority analysis: differences between the PCT-guided group and control group are assessed using a Fisher's exact test, and a multivariable logistic regression analysis to account for the effects of demographic and medical variables on the percentage of febrile patients receiving antibiotics. b) Safety consists of a composite endpoint, defined as mortality, intensive care admission and ED return visit within 14 days. Noninferiority of PCT will be tested using a one-sided 95 % confidence interval for the difference in the composite safety endpoint between the PCT-guided and control groups using a noninferiority margin of 7.5 %. c) Accuracy of PCT and CRP for the diagnosis of bacterial infections will be reported, using the sensitivity, specificity, and the area under the receiver-operating-characteristic curve in the definitive diagnosis of bacterial infections. The sample size is 550 patients, which was calculated using a power analysis for all primary objectives. Enrollment of patients started in August 2014 and will last 2 years., Discussion: PCT may offer a more tailor-made treatment to the individual ED patient with fever. Prospective costs analyses will reveal the economic consequences of implementing PCT-guided therapy in the ED., This Trial Is Registered in the Dutch Trial Register: NTR4949.

Intentional or accidental intoxications are common in the emergency department, but are not always sufficiently recognised. When intoxication is suspected, the causative agent or combination of agents often remain unclear, making these patients a diagnostic challenge. We present here a 45-year-old woman who was admitted due to altered consciousness. The clinical presentation fitted the anticholinergic toxidrome and an intoxication with venlafaxine (her known prescribed medication) was suspected. Plasma venlafaxine concentrations, however, were very low. After 24 hours the patient recovered completely. Further testing after discharge revealed high concentrations of promethazine, confirming the suspected diagnosis. This case illustrates the importance of knowledge of toxidromes and good collaboration with the hospital pharmacist. Because of the thorough testing the patient could receive proper treatment.

Background: Capecitabine has activity against several types of cancer. In 10-15% of patients treated with capecitabine, treatment is discontinued because of serious adverse reactions, mostly within the first weeks of treatment., Case Presentation: A 56 year-old female patient presented at the emergency department after ten days of chemotherapy with progressive airway obstruction and complaints of numbness of the tongue. She also had difficulty swallowing and was unable to speak. Laboratory findings were completely normal and no co-medication was used, in particular no dopamine antagonists., Conclusion: The case highlights the need for awareness that capecitabine may potentially lead to severe life-threatening complaints of oromandibular dystonia. We hypothesize that capecitabine passed the blood brain barrier which led to a disruption within the basal ganglia in this case. Prompt treatment with an anticholinergic drug and cessation of capecitabine in the patient case led to disappearance of complaints.

Objective: Each year over 1.5 million health care professionals attend emergency care courses. Despite high stakes for patients and extensive resources involved, little evidence exists on the quality of assessment. The aim of this study was to evaluate the validity and reliability of commonly used formats in assessing emergency care skills., Methods: Residents were assessed at the end of a 2-week emergency course; a subgroup was videotaped. Psychometric analyses were conducted to assess the validity and inter-rater reliability of the assessment instrument, which included a checklist, a 9-item competency scale and a global performance scale., Results: A group of 144 residents and 12 raters participated in the study; 22 residents were videotaped and re-assessed by 8 raters. The checklists showed limited validity and poor inter-rater reliability for the dimensions "correct" and "timely" (ICC = .30 and.39 resp.). The competency scale had good construct validity, consisting of a clinical and a communication subscale. The internal consistency of the (sub)scales was high (α = .93/.91/.86). The inter-rater reliability was moderate for the clinical competency subscale (.49) and the global performance scale (.50), but poor for the communication subscale (.27). A generalizability study showed that for a reliable assessment 5-13 raters are needed when using checklists, and four when using the clinical competency scale or the global performance scale., Conclusions: This study shows poor validity and reliability for assessing emergency skills with checklists but good validity and moderate reliability with clinical competency or global performance scales. Involving more raters can improve the reliability substantially. Recommendations are made to improve this high stakes skill assessment.

Unlabelled: In this large population-based cohort study, variants in ESR2 were associated with increased risk of vertebral and incident fragility fracture in postmenopausal women. Interaction of ESR2 with ESR1 and IGF1 was determined and revealed a deleterious genetic combination that enhances the risk of osteoporotic fracture., Introduction: Osteoporosis is a complex disease with strong genetic influence, but the genes involved are ill-defined. We examined estrogen receptor beta (ESR2) polymorphisms in interaction with estrogen receptor alpha (ESR1) and insulin-like growth factor I (IGF1) variants in relation to the risk of osteoporotic fracture, BMD, and bone geometry., Materials and Methods: In the Rotterdam study, a prospective population-based cohort of elderly white individuals, we studied six single nucleotide polymorphisms (SNPs) in ESR2 (n = 6343, 60% women). We analyzed the genetic variants in the form of haplotypes reconstructed by a statistical method. Results refer to the most frequent ESR2 haplotype 1 estimated from two SNPs in intron 2 and the 3'-untranslated region (UTR). Outcomes included vertebral and incident nonvertebral fractures, BMD, and hip structural analysis (HSA). We also studied the interaction with (the most frequent) ESR1 haplotype 1 estimated from the PvuII and XbaI polymorphisms and an IGF1 promoter CA-repeat., Results: Compared with ESR2 haplotype 1 noncarriers, female homozygous carriers had a 1.8- and 1.4-fold increased risk of vertebral and fragility fractures. HSA showed that ESR2 haplotype 1 homozygote women had 2.6% thinner cortices, 1.0% increased neck width, and 4.3% higher bone instability (buckling ratios). For testing the gene interaction, we assumed a recessive model of ESR2 haplotype 1. Female homozygous carriers of ESR2 haplotype 1 and noncarriers of ESR1 haplotype 1 had a 3.5- and 1.8-fold increased risk of vertebral and fragility fractures (p(interaction) = 0.10). Such effects and interactions were stronger in women homozygous for the IGF1 192-bp allele, with 9.3-fold increased risk (p(interaction) = 0.002) for vertebral and 4.0-fold increased risk (p(interaction) = 0.01) for fragility fractures. Multilocus interaction analyses of fracture endured correction for multiple testing using Monte-Carlo simulations (p(interaction) = 0.02 for vertebral and p(interaction) = 0.03 for fragility fractures). Similar patterns of interaction were observed for BMD, cortical thickness, bone strength (section modulus), and instability (buckling ratio). In men, no such effects were observed., Conclusions: Variants of ESR2 alone and in interaction with ESR1 and IGF1 influence the risk of fracture in postmenopausal women. These findings reinforce the polygenic and complex character of osteoporosis.

Understanding the mechanisms by which estrogens affect cardiovascular disease risk, including the role of variation in the gene for estrogen receptor alpha (ESR1), may be key to new treatment strategies. We investigated whether the CC genotype at ESR1 c.454-397T>C is associated with increased risk among men. Study of more than 7000 whites in 5 cohorts from 4 countries provided evidence that genotype CC, present in roughly 20% of individuals, is a risk factor for nonfatal acute myocardial infarction (odds ratio=1.44; P<0.0001), after adjustment for established cardiovascular risk factors. After exclusion of younger subjects from 2 cohorts, because of age interaction, the odds ratio increased (to 1.63).

The role of estrogens in Alzheimer's disease (AD) is controversial. We investigated the association between well-recognized, and potentially functional, polymorphisms in the estrogen receptor (ER) alpha gene and the risk of AD in a prospective study of 6056 Caucasian older men and women aged 55 years and over. In a subset of 468 participants, we assessed volumes of the hippocampus and amygdala, which have a high density of ER alpha, with brain magnetic resonance imaging (MRI) (1.5 T MR unit). During a total of 35 405 person-years of follow-up (mean per persons 5.8 years), 312 new cases of dementia were detected, of whom 230 were diagnosed with AD. Neither the PvuII nor the XbaI polymorphism or haplotypes thereof were associated with the risk of all-cause dementia or AD. In contrast, we found that nondemented women who carried the PvuII p allele or haplotype 'px' had smaller amygdalar volumes on MRI in an allele-dose-dependent fashion. Total amygdalar volume was 4.50 (SE 0.10) in PP genotype, 4.45 (SE 0.06) in Pp genotype, and 4.18 ml (SE 0.08) in pp genotype (P trend=0.008). Further studies are required to investigate whether this smaller amygdalar volume has functional significance.