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Background Early risk stratification for guiding treatment priority in the emergency department (ED) is becoming increasingly important. Existing prediction models typically use demographics, vital signs and laboratory parameters. Laboratory-based models require blood testing, which may cause substantial delay. However, these delays can be prevented by the use of point-of-care testing (POCT), where results are readily available. We aimed to externally validate a laboratory-based model for mortality and subsequently assessed whether a POCT model yields comparable performance. Methods All adult patients visiting the ED of a university hospital between January 1st, 2012 and December 31st, 2016 were retrospectively reviewed for inclusion. Primary outcome was defined as 30-day mortality after ED presentation. We externally validated one existing prediction model including age, glucose, urea, sodium, haemoglobin, platelet count and white blood cell count. We assessed the predictive performance by discrimination, expressed as Area under the Curve (AUC). We compared the existing model to an equivalent model using predictors that are available with POCT (i.e. glucose, urea, sodium and haemoglobin). Additionally, we internally validated these models with bootstrapping. Results We included 34,437 patients of whom 1,942 (5.6%) died within 30 days. The AUC of the laboratory-based model was 0.794. We refitted this model to our ED population and found an AUC of 0.812, which decreased only slightly to 0.790 with only POCT parameters. Conclusions Our POCT-model performs similar to existing laboratory-based models in identifying patients at high risk for mortality, with results available within minutes. Although the model needs further validation and evaluation, it shows the potential of POCT for early risk stratification in the ED.

The physical and social distancing measures that have been adopted worldwide because of COVID-19 will probably remain in place for a long time, especially for senior adults, people with chronic conditions, and other at-risk populations. Teleconsultations can be useful in ensuring that patients continue to receive clinical care while reducing physical crowding and avoiding unnecessary exposure of health care staff. Implementation processes that typically take months of planning, budgeting, pilot testing, and education were compressed into days. However, in the urgency to deal with the present crisis, we may be forgetting that the introduction of digital health is not exclusively a technological issue, but part of a complex organizational change problem. This viewp

_Objective:_ Non-adherence to antimicrobial guidelines in patients with bloodstream infection can result in undertreatment, overtreatment, or equivalent treatment, and could lead to suboptimal care. Our aim was to examine the association between non-adherence and appropriate coverage as well as to assess the impact of non-adherence on 30-day mortality. _Methods:_ We conducted a retrospective cohort study between 2012 and 2017 at a tertiary university hospital. Adult patients attending the emergency department with a bloodstream infection were included. Adherence was defined as guideline-recommended antibiotic therapy. Non-adherence was either undertreatment (too narrow-spectrum), overtreatment (too broad-spectrum), or equivalent treatment. Outcomes were appropriate coverage (i.e. antibiotic therapy that matches in vitro susceptibility of the isolated bacteria) and 30-day mortality. _Results:_ We included 909 patients of whom 395 (43.5%) were treated adherently, 355 (39.1%) were undertreated, 87 (9.6%) were overtreated, and 72 (7.9%) received an equivalent treatment. Overtreated patients were more severely ill, whilst undertreated patients had more favorable patient characteristics. Overtreatment did not result in higher appropriate coverage, whereas undertreatment was associated with lower coverage (OR[95%CI]: 0.18 [0.12; 0.26]). Overtreatment and undertreatment were not associated with 30-day mortality. _Conclusions:_ Guideline adherence likely depends on disease severity, because overtreatment was more often observed in patients with high disease severity and undertreatment in less severely ill patients. Undertreatment was associated lower appropriate coverage but not with higher mortality. However, this can be the result of residual confounding. Overtreatment did not result in higher appropriate antibiotic coverage nor a survival benefit. Therefore, overtreatment seems not justifiable.

BACKGROUND: Urgency triage in the emergency department (ED) is important for early identification of potentially lethal conditions and extensive resource utilization. However, in older patients, urgency triage systems could be improved by taking geriatric vulnerability into account. We investigated the association of geriatric vulnerability screening in addition to triage urgency levels with 30-day mortality in older ED patients. DESIGN: Secondary analysis of the observational multicenter Acutely Presenting Older Patient (APOP) study. SETTING: EDs within four Dutch hospitals. PARTICIPANTS: Consecutive patients, aged 70 years or older, who were prospectively included. MEASUREMENTS: Patients were triaged using the Manchester Triage System (MTS). In addition, the APOP screener was used as a geriatric screening tool. The primary outcome was 30-day mortality. Comparison was made between mortality within the geriatric high- and low-risk screened patients in every urgency triage category. We calculated the difference in explained variance of mortality by adding the geriatric screener (APOP) to triage urgency (MTS) by cal

Background: Many countries have centralized and dedicated trauma centres with high volumes of trauma patients. However, the volume-outcome relationship in severely injured patients (Injury Severity Score (ISS) > 15) remains unclear. The aim of this study was to determine the association between hospital volume and outcomes in Major Trauma Centres (MTCs). Methods: A retrospective observational cohort study was conducted using the Trauma Audit and Research Network (TARN) consisting of all English Major Trauma Centres (MTCs). Severely injured patients (ISS > 15) admitted to a MTC between 2013 and 2016 were included. The effect of hospital volume on outcome was analysed with random effects logistic regression models with a random intercept for centre and was tested for nonlinearity. Primary outcome was in-hospital mortality. Results: A total of 47,157 severely injured patients from 28 MTCs were included in this study. Hospital volume varied from 69 to 781 severely injured patients per year. There were small between-centre differences in mortality after adjusting for important demographic and injury severity characteristics (adjusted 95% odds ratio range: 0.99-1.01). Hospital volume was found to be linear and not associated with in-hospital mortality (adjusted odds ratio (aOR) 1.02 per 10 patients, 95% confidence interval (CI) 0.68-1.54, p = 0.92). Conclusions: Despite the large variation in volume of the included MTCs, no relationship between hospital volume and outcome of severely injured patients was found. These results suggest that centres with similar structure and processes of care can achieve comparable outcomes in severely injured patients despite the number of severely injured patients they treat.

Background: Intoxications with alcohol and drugs are common in the Emergency Department. This study aimed to describe the occurrence and characteristics of intoxications (alcohol, Drugs of Abuse (DOA), pharmaceutical and chemical) presented to the Emergency Department and the health care costs of these intoxications. Methods: This was a retrospective medical record study of all patients (≥ 16 years) who presented to the Emergency Department of an inner-city academic hospital in the Netherlands due to single or multiple intoxication(s) as the primary or secondary reason in the year 2016. An intoxication was reported as present if the attending physician described the intoxication in the patient's medical record. Results: A total of 783 patients were included, accounting for 3.2% of the adult Emergency Department population (age ≥ 16 year). In 30% more than one substance was used. Intoxications with alcohol, Drugs of Abuse and pharmaceuticals was reported in respectively 62%, 29% and 21% of the intoxicated patients. The mean costs per patient presenting with an intoxication to the Emergency Department was € 1,490. The mean costs per patient were highest for pharmaceutical intoxications (€ 2,980), followed by Drugs of Abuse (€ 1,140) and alcohol (€ 1,070). Conclusions: Intoxications among patients aged 16 years and older are frequently seen at the Emergency Department and are frequently caused by multiple substances. Alcohol is the most common intoxication. Substantial healthcare costs are involved. Therefore, this study suggests that further research into hazardous alcohol consumption and DOA abuse is warranted. Copyright

Objective Clinical practice universally assumes that appropriate empirical antibiotic therapy improves survival in patients with bloodstream infection. However, this is not generally supported by previous studies. We examined the association between appropriate therapy and 30-day mortality, while minimizing bias due to confounding by indication. Methods We conducted a retrospective cohort study between 2012 and 2017 at a tertiary university hospital in the Netherlands. Adult patients with bloodstream infection attending the emergency department were included. Based on in vitro susceptibility, antibiotic therapy was scored as appropriate or inappropriate. Primary outcome was 30-day mortality. To control for confounding, we performed conventional multivariable logistic regression and propensity score methods. Additionally, we performed an analysis in a more homogeneous subgroup (i.e. antibiotic monotherapy). Results We included 1.039 patients, 729 (70.2%) received appropriate therapy. Overall 30-day mortality was 10.4%. Appropriately treated patients had more unfavorable characteristics, indicating more severe illness. Despite adjustments, we found no association between appropriate therapy and mortality. For the antibiotic monotherapy subgroup (n = 449), patient characteristics were more homogeneous. Within this subgroup, appropriate therapy was associated with lower mortality (Odds Ratios [95% Confidence Intervals] ranging from: 0.31 [0.14; 0.67] to 0.40 [0.19; 0.85]). Conclusions Comparing heterogeneous treatment groups distorts associations despite use of common methods to prevent bias. Consequently, conclusions of such observational studies should be interpreted with care. If possible, future investigators should use our method of attempting to identify and analyze the most homogeneous treatment groups nested within their study objective, because this minimizes residual confounding.

Background: Patients with major trauma might benefit from treatment in a trauma centre, but early identification of major trauma (Injury Severity Score (ISS) over 15) remains difficult. The aim of this study was to undertake an external validation of existing prognostic models for injured patients to assess their ability to predict mortality and major trauma in the prehospital setting. Methods: Prognostic models were identified through a systematic literature search up to October 2017. Injured patients transported by Emergency Medical Services to an English hospital from the Trauma Audit and Research Network between 2013 and 2016 were included. Outcome measures were major trauma (ISS over 15) and in-hospital mortality. The performance of the models was assessed in terms of discrimination (concordance index, C-statistic) and net benefit to assess the clinical usefulness. Results: A total of 154 476 patients were included to validate six previously proposed prediction models. Discriminative ability ranged from a C-statistic value of 0·602 (95 per cent c.i. 0·596 to 0·608) for the Mechanism, Glasgow Coma Scale, Age and Arterial

Background/Objectives Cognitive impairment is a frequent problem among older patients attending the Emergency Department (ED) and can be the result of pre-existing cognitive impairment, delirium, or neurologic disorders. Another cause can also be acute disturbance of brain perfusion and oxygenation, which may be reversed by optimal resuscitation. This study aimed to assess the relationship between vital signs, as a measure of acute hemodynamic changes, and cognitive impairment in older ED patients. Design Prospective cohort study Setting ED’s of two tertiary care and two secondary care hospitals in the Netherlands. Participants 2629 patients aged 70-years and older Measurements Vital signs were measured at the moment of ED arrival as part of routine clinical care. Cognition was measured using the Six-Item Cognitive Impairment Test (6-CIT). Results The median age of patients was 78 years (IQR 74–84). Cognitive impairment was present in 738 patients (28.1%). When comparing lowest with highest quartiles, a systolic blood pressure of <129 mmHg (OR 1.30, 95% confidence interval (95%CI) 0.98–1.73)was associated with increased risk of cognitive impairment. A higher respiratory rate (>21/min) was associated with increased risk of impaired cognition (OR 2.16, 95% CI 1.58–2.95) as well as oxygen saturation of <95% (OR 1.64, 95%CI 1.24–2.19). Conclusion Abnormal vital signs associated with decreased brain perfusion and oxygenation are also associated with cognitive impairment in older ED patients. This may partially be explained by the association between disease severity and delirium, but also by acute disturbance of brain perfusion and oxygenation. Future studies should establish whether normalization of vital signs will also acutely improve cognition.

BACKGROUND The volume-outcome relationship in severely injured patients remains under debate and this has consequences for the designation of trauma centers. OBJECTIVES The aim of this study was to evaluate the relationship between hospital or surgeon volume and health outcomes in severely injured patients. METHODS Six electronic databases were searched from 1980 up to January 30, 2018, to identify studies that describe the relationship between hospital or surgeon volume and health outcomes in severely injured patients (preferably Injury Severity Score above 15). Selection of relevant studies, data extraction, and critical appraisal of the methodological quality were performed by two independent reviewers. Pooled adjusted and unadjusted estimates of the effect of volume on in-hospital mortality, only in study populations with Injury Severity Score greater than 15, were calculated with a random-effects meta-analysis. A mixed effects linear regression model was used to assess hospital volume as continuous parameter. RESULTS Eighteen observational cohort studies were included. The majority (13 [72%] of 18) reported an association between higher hospital or surgeon volume and lower mortality rate. Overall, the quality of the included studies was reasonable, with insufficient adjustment as one of the most common limitations. Eight studies were included in the meta-analysis with a total of 222,418 patients. High hospital volume (>240 admitted severely injured patients per year) was associated with a lower risk of mortality (adjusted odds ratio, 0.85; 95% confidence interval, 0.76-0.94). Four studies were included in the regression model, providing a beta of-0.17 per 10 patients (95% CI,-0.27 to-0.07). There was no clear association between surgeon volume and mortality rates based on three available studies. CONCLUSION Our systematic overview of the literature reveals a modest association between high-volume centers and lower mortality in severely injured patients, suggest

Introduction Training emergency care skills is critical for patient safety but cost intensive. Serious games have been proposed as an engaging self-directed learning tool for complex skills. The objective of this study was to compare the cognitive skills and motivation of medical residents who only used a course manual as preparation for classroom training on emergency care with residents who used an additional serious game. Methods This was a quasi-experimental study with residents preparing for a rotation in the emergency department. The "reading" group received a course manual before classroom training; the "reading and game" group received this manual plus the game as preparation for the same training. Emergency skills were assessed before training (with residents who agreed to participate in an extra pretraining assessment), using validated competency scales and a global performance scale. We also measure

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 spec

__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.

Simulation games are becoming increasingly popular in education, but more insight in their critical design features is needed. This study investigated the effects of fidelity of open patient cases in adjunct to an instructional e-module on students’ cognitive skills and motivation. We set up a three-group randomized post-test-only design: a control group working on an e-module; a cases group, combining the e-module with low-fidelity text-based patient cases, and a game group, combining the e-module with a high-fidelity simulation game with the same cases. Participants completed questionnaires on cognitive load and motivation. After a 4-week study period, blinded assessors rated students’ cognitive emergency care skills in two mannequin-based scenarios. In total 61 students participated and were assessed; 16 control group students, 20 cases students and 25 game students. Learning time was 2 h longer for the cases and game groups than for the control group. Acquired cognitive skills did not differ between groups. The game group experienced higher intrinsic and germane cognitive load than the cases group (p = 0.03 and 0.01) and felt more engaged (p < 0.001). Students did not profit from working on open cases (in adjunct to an e-module), which nonetheless challenged them to study longer. The e-module appeared to be very effective, while the high-fidelity game, although engaging, probably distracted students and impeded learning. Medical educators designing motivating and effective skills training for novices should align case complexity and fidelity with students’ proficiency level. The relation between case-fidelity, motivation and skills development is an important field for further study.

__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

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. A diagnosis of oromandibular dystonia due to capecitabine use was made. After the anticholinergic drug biperiden (Akineton) was given intravenously, complaints disappeared within twenty minutes. Due to an early discontinuation of biperiden, however, the symptoms of oromandibular dystonia recurred. Again, she was successfully treated with an anticholinergic drug. Capecitabine was permanently discontinued. Three days after the initial presentation the anticholinergic drug was stopped after which symptoms did not reappear. 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.

The estrogen receptor alpha gene (ESR1) is known to be involved in metabolic pathways influencing growth. We have performed two population-based association studies using three common polymorphisms within this candidate gene to determine whether these are associated with variation in adult stature. In 607 women, aged 55-80 yr, from the Rotterdam Study, the ESR1 PvuII-XbaI haplotype 1 (px) and the L allele of the TA repeat polymorphism (<18 TA repeats) were significantly

__Abstract__ Estradiol, one of the sex hormones responsible for gender dimorphism and reproduction, is a pleitropic hormone with widespread biological actions far beyond human reproduction alone. For example, withdrawal of the effects of estradiol at menopause from non-reproductive tissues like the skeleton, the cardiovascular system, and the brain, is a major risk factor for the development of osteoporosis, coronary artery disease, stroke, and perhaps neurodegenerative diseases like Alzheimer’s disease. On the other hand, continuous exposure of reproductive tissues to estrogen during the post reproductive part of life is a risk factor for the development of breast, and uterine cancer.

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) 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, 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.

This study investigates the influence of genetic variation of the estrogen receptor alpha (ESR1) gene locus on several bone parameters in 2042 individuals of The Rotterdam Study, a prospective population-based cohort study of elderly subjects. We analysed three polymorphic sites in the 5' region of the ESR1 gene; a (TA)(n)-repeat in the promoter region, and molecular haplotypes of the PvuII and XbaI RFLPs in intron 1, and inferred long-range haplotypes (LRH) thereof. We observed only three of the possible four PvuII-XbaI haplotypes in our population. A comparison with other Caucasian populations showed similar haplotype frequencies, while in Asian and African populations these were different. Linkage disequilibrium (LD) analysis between the PvuII-XbaI haplotype and the (TA)(n) repeat showed strong LD between the two sites. Reconstruction of long range haplotypes over the entire 5' region, revealed six frequent LRH. In men, we did not observe an association between the ESR1 polymorphisms studied a

Age at menopause and risk of hysterectomy have strong genetic components, but the genes involved remain ill defined. We investigated whether genetic variation at the estrogen receptor (ER) gene contributes to the variability in the onset of menopause in 900 postmenopausal women, aged 55-80 yr, of the Rotterdam Study, a population-based cohort study in The Netherlands. Gynecological information was obtained, and if women reported surgical menopause, validation of type and indication of surgery was accomplished by checking medical records. The ER genotypes (PP, Pp, and pp) were assessed by PCR using the PvuII endonuclease. Compared with women carrying the pp genotype, homozygous PP women had a 1.1-yr (P < 0.02) earlier onset of menopause. Furthermore, an allele dose effect was observed, corresponding to a 0.5-yr (P < 0.02) earlier onset of menopause per copy of the P allele. The risk of surgical menopause was 2.4 (95% confidence interval, 1.5-3.8) times higher for women carrying the PP genotype compared to those in the pp group, with the most prominent effect in women who underwent hysterectomy due to fibroids or menorrhagia. We conclude that genetic variations of the ER gene are related to the onset of natural menopause and the risk of surgical menopause, especially hysterectomy.