Stephanie C. E. Schuit

Estrogen Receptor α Gene Variation Is Associated With Risk of Myocardial Infarction in More Than Seven Thousand Men From Five Cohorts

Understanding the mechanisms by which estrogens affect cardiovascular disease risk, including the role of variation in the gene for estrogen receptor α (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).

Estrogen Receptor β (ESR2) Polymorphisms in Interaction With Estrogen Receptor α (ESR1) and Insulin-Like Growth Factor I (IGF1) Variants Influence the Risk of Fracture in Postmenopausal Women†

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.

How to Systematically Assess Serious Games Applied to Health Care

The usefulness and effectiveness of specific serious games in the medical domain is often unclear. This is caused by a lack of supporting evidence on validity of individual games, as well as a lack of publicly available information. Moreover, insufficient understanding of design principles among the individuals and institutions that develop or apply a medical serious game compromises their use. This article provides the first consensus-based framework for the assessment of specific medical serious games. The framework provides 62 items in 5 main themes, aimed at assessing a serious game’s rationale, functionality, validity, and data safety. This will allow caregivers and educators to make balanced choices when applying a serious game for healthcare purposes. Furthermore, the framework provides game manufacturers with standards for the development of new, valid serious games.

Variations in estrogen receptor ? gene and risk of dementia, and brain volumes on MRI.

The role of estrogens in Alzheimers disease (AD) is controversial. We investigated the association between well-recognized, and potentially functional, polymorphisms in the estrogen receptor (ER) α 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 ERα, 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.

Estrogen receptor alpha gene polymorphisms and anxiety disorder in an elderly population.

SIR—Estrogens act on various monoamine systems in the brain, affect synaptogenesis and have neuroprotective properties. Previously, estrogen receptor (ER) polymorphisms have been related to personality traits. We found that in women ERa haplotypes created by the PvuII (c.454–397T4C) and the XbaI (c.454–351A4G) polymorphisms increased the likelihood of having an anxiety but not of having a depressive disorder; no relation between mood or anxiety disorders and ERa haplotypes was observed in men. This study is based on data from the Rotterdam Study, a population-based cohort of persons over 55 years. A random selection of 2468 participants of a Caucasian origin filled in the Hospital Anxiety and Depression Scale (HADS) during the second examination and was genotyped. Anxiety was defined as a score of 11 or more on the HADS-anxiety subscale, which traditionally denotes probable anxiety disorder. We found a probable anxiety disorder in 148 (6.0%) persons. Additionally, we defined a more homogenous group with anxiety and no comorbid depression. This group (n1⁄484) was restricted to those with a HADS-depression score of less than 11. Depressive disorders were assessed with the Center for Epidemiological Studies Depression scale (CES-D) in 4098 persons participating in the third examination (1997–1999). Screen-positive subjects (cut-off score was 16) had a psychiatric interview with the present state examination to classify depression according to DSM-IV criteria. In total, 321 (7.8%) screened positive for depressive symptoms and of these, 132 had a DSM-IV depressive disorder. We studied two single nucleotide polymorphisms (SNP) identified in the ERa gene, the c.454–397T4C (also known as PvuII) and the c.454–351A4G (also known as XbaI), to define haplotypes as described previously. All SNPs were genotyped with Taqman Assays-by-Design SNP Genotyping Service and ABI PRISM 7900HT Sequence Detection System (both: Applied Biosystems). The association of the ERa haplotype with depressive symptoms, and depressive disorders, and anxiety was assessed separately in men and women using logistic regression and testing an allele–dose model. Only the results of the ERa PvuII– XbaI haplotype 1 (frequency 52.8%) are reported as the haplotype alleles are closely related. Genotype distribution was in Hardy–Weinberg equilibrium. The ERa haplotype 1 was associated with the likelihood of having anxiety in women, but not in

Variation in the Estrogen Receptor α Gene and Risk of Stroke The Rotterdam Study

Background and Purpose— Variations in the −397T>C (rs2234693) and −351A>G (rs9340799) single nucleotide polymorphisms of the estrogen &agr; receptor (ESR1) gene were found to be strongly associated with risk of ischemic heart disease, although not all studies could replicate this finding. One study also reported an association with stroke. We assessed whether variations in the ESR1 gene are associated with the risk of stroke in the general population. Methods— This prospective population-based study was based on 6229 Rotterdam Study participants who at baseline (1990–1993) were aged 55 years or older, free from stroke, and had assessment of the ESR1 rs2234693 and rs9340799 single nucleotide polymorphisms. Follow-up for incident stroke was complete until January 1, 2005. Data were analyzed with Cox proportional hazards models for men and women separately with adjustment for age. Results— During an average follow-up time of 10.1 years, 659 strokes occurred, of which 386 were ischemic. Three common haplotypes were identified: −397T/−351A (carried by 78% of all participants), −397C/−351G (carried by 57%), and −397C/−351A (carried by 22%). Although we had at least 89% power to detect a relative risk of 1.5 (&agr;=0.05) in all subgroups, we did not find any association between ESR1 haplotype carriership and risk of stroke and ischemic stroke. Conclusions— We have not been able to replicate the previously reported association between variations in the ESR1 gene and risk of stroke.

Do patients’ disruptive behaviours influence the accuracy of a doctor's diagnosis? A randomised experiment

Background Literature suggests that patients who display disruptive behaviours in the consulting room fuel negative emotions in doctors. These emotions, in turn, are said to cause diagnostic errors. Evidence substantiating this claim is however lacking. The purpose of the present experiment was to study the effect of such difficult patients’ behaviours on doctors’ diagnostic performance. Methods We created six vignettes in which patients were depicted as difficult (displaying distressing behaviours) or neutral. Three clinical cases were deemed to be diagnostically simple and three deemed diagnostically complex. Sixty-three family practice residents were asked to evaluate the vignettes and make the patients diagnosis quickly and then through deliberate reflection. In addition, amount of time needed to arrive at a diagnosis was measured. Finally, the participants rated the patients likability. Results Mean diagnostic accuracy scores (range 0–1) were significantly lower for difficult than for neutral patients (0.54 vs 0.64; p=0.017). Overall diagnostic accuracy was higher for simple than for complex cases. Deliberate reflection upon the case improved initial diagnostic, regardless of case complexity and of patient behaviours (0.60 vs 0.68, p=0.002). Amount of time needed to diagnose the case was similar regardless of the patients behaviour. Finally, average likability ratings were lower for difficult than for neutral-patient cases. Conclusions Disruptive behaviours displayed by patients seem to induce doctors to make diagnostic errors. Interestingly, the confrontation with difficult patients does however not cause the doctor to spend less time on such case. Time can therefore not be considered an intermediary between the way the patient is perceived, his or her likability and diagnostic performance.

Why patients’ disruptive behaviours impair diagnostic reasoning: a randomised experiment

Background Patients who display disruptive behaviours in the clinical encounter (the so-called ‘difficult patients’) may negatively affect doctors’ diagnostic reasoning, thereby causing diagnostic errors. The present study aimed at investigating the mechanisms underlying the negative influence of difficult patients’ behaviours on doctors’ diagnostic performance. Methods A randomised experiment with 74 internal medicine residents. Doctors diagnosed eight written clinical vignettes that were exactly the same except for the patients’ behaviours (either difficult or neutral). Each participant diagnosed half of the vignettes in a difficult patient version and the other half in a neutral version in a counterbalanced design. After diagnosing each vignette, participants were asked to recall the patients clinical findings and behaviours. Main measurements were: diagnostic accuracy scores; time spent on diagnosis, and amount of information recalled from patients’ clinical findings and behaviours. Results Mean diagnostic accuracy scores (range 0–1) were significantly lower for difficult than neutral patients’ vignettes (0.41 vs 0.51; p<0.01). Time spent on diagnosing was similar. Participants recalled fewer clinical findings (mean=29.82% vs mean=32.52%; p<0.001) and more behaviours (mean=25.51% vs mean=17.89%; p<0.001) from difficult than from neutral patients. Conclusions Difficult patients’ behaviours induce doctors to make diagnostic errors, apparently because doctors spend part of their mental resources on dealing with the difficult patients’ behaviours, impeding adequate processing of clinical findings. Efforts should be made to increase doctors’ awareness of the potential negative influence of difficult patients’ behaviours on diagnostic decisions and their ability to counteract such influence.

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 measured motivation. Results All groups had comparable important characteristics (eg, experience with acute care). Before training, the reading and game group felt motivated to play the game and spent more self-study time (+2.5 hours) than the reading group. Game-playing residents showed higher scores on objectively measured and self-assessed clinical competencies but equal scores on the global performance scale and were equally motivated for training, compared with the reading group. After the 2-week training, no differences between groups existed. Conclusions After preparing training with an additional serious game, residents showed improved clinical competencies, compared with residents who only studied course material. After a 2-week training, this advantage disappeared. Future research should study the retention of game effects in blended designs.

Assessing the Assessment in Emergency Care Training

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.