Genetic Aspects of the Estrogen Signaling Pathway

__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

Knowledge about systemic inflammatory response syndrome and sepsis: a survey among Dutch emergency department nurses

__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

An experimental study on the effects of a simulation game on students’ clinical cognitive skills and motivation

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

Emergency Department visits due to intoxications in a Dutch university hospital: Occurrence, characteristics and health care costs

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

Predicting 30-day mortality using point-of-care testing; an external validation and derivation study

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

Estrogen receptor polymorphism predicts the onset of natural and surgical menopause

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

Oromandibular dystonia: A serious side effect of capecitabine

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

Predicting mortality in patients with suspected sepsis at the Emergency Department; A retrospective cohort study comparing qSOFA, SIRS and National Early Warning Score

Objective In hospitalized patients, the risk of sepsis-related mortality can be assessed using the quick Sepsis-related Organ Failure Assessment (qSOFA). Currently, different tools that predict deterioration such as the National Early Warning Score (NEWS) have been introduced in clinical practice in Emergency Departments (ED) worldwide. It remains ambiguous which screening tool for mortality at the ED is best. The objective of this study was to evaluate the predictive performance for mortality of two sepsis-based scores (i.e. qSOFA and Systemic Inflammatory Response Syndrome (SIRS)-criteria) compared to the more general NEWS score, in patients with suspected infection directly at presentation to the ED. Methods We performed a retrospective cohort study. Patients who presented to the ED between June 2012 and May 2016 with suspected sepsis in a large tertiary care center were included. Suspected sepsis was defined as initiation of intravenous antibiotics and/or collection of any culture in the ED. Outcome was defined as 10-day and 30-day mortality after ED presentation. Predictive performance was expressed as discrimination (AUC) and calibration using Hosmer-Lemeshow goodness-of-fit test. Subsequently, sensitivity, and specificity were calculated. Results In total 8,204 patients were included of whom 286 (3.5%) died within ten days and 490 (6.0%) within 30 days after presentation. NEWS had the best performance, followed by qSOFA and SIRS (10-day AUC: 0.837, 0.744, 0.646, 30-day AUC: 0.779, 0.697, 0.631). qSOFA (�2) lacked a high sensitivity versus SIRS (�2) and NEWS (�7) (28.5%, 77.2%, 68.0%), whilst entailing highest specificity versus NEWS and SIRS (93.7%, 66.5%, 37.6%). Conclusions NEWS is more accurate in predicting 10- and 30-day mortality than qSOFA and SIRS in patients presenting to the ED with suspected sepsis

Preparing Residents Effectively in Emergency Skills Training with a Serious Game

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 measur