Does simulation training in final year make new graduates feel more prepared for the realities of professional practice?

Introduction: The transition from medical student to doctor has long been a source of concern, with widespread reporting of new graduates' lack of preparedness for medical practice. Simulation has been suggested as a way to improve preparedness, particularly due to the difficulties in allowing full autonomy for patient care for undergraduate medical students. Few studies look at simulation alone for this purpose, and no studies have compared different simulation formats to assess their impact on preparedness. Methods: This mixed-method study looked at two different simulation courses in two UK universities. Data were collected in two phases: immediately after the simulation and 3-4 months into the same students' postgraduate training. Questionnaires provided quantitative data measuring preparedness and interviews provided a more in-depth analysis of experiential learning across final year and how this contributed to preparedness. Results: There were no significant differences between the two courses for overall preparedness, stress or views on simulation, and no significant differences in opinions longitudinally. Although the study initially set out to look at simulation alone, emergent qualitative findings emphasised experiential learning as key in both clinical and simulated settings. This inter-relationship between simulation and the student assistantship prepared students for practice. Longitudinally, the emphasis on experiential learning in simulation was maintained and participants demonstrated using skills they had practised in simulation in their daily practice as doctors. Nevertheless, there was evidence that although students felt prepared, they were still scared about facing certain scenarios as foundation doctors. Discussion: The results of this study suggest that simulation may positively affect students' preparedness for practice as doctors. Simulation will never be a replacement for real clinical experience. However, when used prior to and alongside clinical experience, it may have positive effects on new doctors' confidence and competence, and, therefore, positively impact patient care.

Experiences of Patients with Mental Illness' Interactions with Medical Students: A Systematic Review.

OBJECTIVES: Mental health is a key area for learning within undergraduate medical education. Given the nature of mental illness, interactions may have the potential to uniquely affect patients. This study set out to systematically review studies reporting experiences and perceptions of patients with mental illness' clinical interactions with medical students. This includes which factors encourage patients to interact with medical students and if patients perceive negative and positive effects from these interactions. METHOD: Studies reporting patient experiences of involvement in undergraduate medicine were included. A standardised search of online databases was carried out independently by 2 authors and consensus reached on the inclusion of studies. Data extraction and quality assessment were also completed independently, after which a content analysis of interventions was conducted and key themes extracted. Studies were included from peer-reviewed journals, in any language. RESULTS: Eight studies from 5 countries were included, totaling 1088 patients. Most patients regarded interacting with medical students as a positive experience. Patients described feeling comfortable with medical students, and the majority believed it is important for students to 'see real patients'. Patients described benefits to them as enjoyment, being involved in student education, and developing an illness narrative. CONCLUSIONS: Results suggest that most patients with mental illness want to interact with medical students, and this should be encouraged during student placements. Further research, however, is required to understand in more depth what else can be done to improve the comfort and willingness for patients to interact with students, including barriers to this.

The role of cytokine expression in different subgroups of subfertile men.

PROBLEM: The aim of this study was to evaluate the levels of seminal plasma cytokines interleukin 6 (IL-6), interleukin 8 (IL-8), interleukin 10 (IL-10), interleukin 11 (IL-11), interleukin 12 (IL-12), tumour necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma) in male subfertility. METHOD OF STUDY: A total of 73 male partners of an infertile couple attending a regional andrology unit were recruited into this prospective study and subdivided into the various groups based on semen analysis. Concentrations of cytokines such as IL-6, IL-8, IL-10, IL-11, IL-12, TNF-alpha and IFN-gamma in the seminal plasma were determined using enzyme linked immunosorbent assay (ELISA). RESULTS: Significant higher concentrations (P < 0.05) of IL-6 in the mild and severe oligospermic group, IL-8 and IL-10 in the asthenospermic group and IL-6, IL-10, TNF-alpha and IFN-gamma in the obstructed azoospermic group were determined. IL-10 concentrations correlated significantly with other cytokines in the obstructed azoospermic group and the asthenospermic group. CONCLUSION: Our study confirms that cytokines rarely act in isolation, but rather in a network of other cytokines and may affect sperm function directly or indirectly. The presence of increased levels of cytokines in the obstructed azoospermic group suggests that the cytokines may not originate from the testis.

Phenytoin but not valproate directly affected in vitro trophoblast differentiation.

OBJECTIVE: Epilepsy has been associated with poor obstetric outcomes that could be the result of the epilepsy itself or a direct effect of anti-epileptic medication on placentation. The aim of this study was to investigate any direct effect of anti-epileptic drugs on an established, in vitro bioassay of trophoblast differentiation. STUDY DESIGN: Primary extravillous trophoblast cells were cultured in the presence of phenytoin and sodium valproate at a range of concentrations with appropriate solvent controls. The formation of multinuclear giant cells was used as a marker of trophoblast differentiation. RESULTS: Phenytoin inhibited giant multinuclear cell formation in a dose-dependent manner; in contrast sodium valproate had no effect (p=0.011). CONCLUSIONS: This study found that two anti-epileptic medications induced different effects on an in vitro trophoblast bioassay, suggesting that further research should be aimed at elucidating which anti-epileptic medication is most suitable for pregnant women.

Androgen receptors are expressed in a variety of human fetal extragenital tissues: an immunohistochemical study.

AIM: To investigate the expression of androgen receptors in the extragenital tissues of developing human embryo. METHODS: Using immunohistochemistry, we investigated the distribution of androgen receptor (AR) in the extragenital tissues of paraffin-embedded tissue sections of first trimester (8-12 weeks gestation) human embryos. Gender was determined by polymerized chain reaction. RESULTS: There were no differences in the expression and distribution of AR in male and female embryos at any stage of gestation. AR expression was seen in the thymus gland. The bronchial epithelium of the lungs showed intense positive staining with surrounding stroma negative. Furthermore, positive staining for androgen receptor was exhibited in the spinal cord with a few positive cells in the surrounding tissues. Cardiac valves also showed strong positive staining but with faint reactivity of the surrounding cardiac muscle. There was no staining in kidney, adrenal, liver or bowel. CONCLUSION: This study demonstrates that immunoreactive AR protein is present in a wide variety of human first trimester fetal tissues and shows the potential for androgen affecting tissues, which are mostly not considered to be androgen dependent. Moreover, it implies that androgen might act as a trophic factor and affect the early development of these organs rather than simply sexual differentiation.

Electrical potential difference across the nasal epithelium is reduced in premature infants with chronic lung disease but is not associated with lower airway inflammation.

Airway liquid content and insufficient absorptive airway ion transport at birth are potentially important factors in the development and severity of neonatal respiratory disease. The role of deficient absorptive airway ion transport in the development of chronic lung disease of prematurity is unknown. Additionally, lung inflammatory mediators modulate airway ion transport. Their effect on preterm lung ion transport and absorptive capacity is not established. We performed serial nasal potential difference studies and broncho-alveolar lavage in preterm infants born less than 30 wk postmenstrual age over the first four postnatal weeks. Our study aims were to: 1) compare nasal potential difference between preterm infants developing chronic lung disease and babies of similar gestation who do not; and 2) examine for an association between airway inflammation and ion transport parameters. We found that potential difference across the nasal epithelium increased with gestation, remained low and unchanged in infants developing chronic lung disease over the first four postnatal weeks, was significantly lower at four weeks in chronic lung disease infants, and was not associated with lower airway inflammation at any time point. We conclude that infants with chronic lung disease postnatally have a persistently reduced absorptive airway ion transport capacity.

Prednisolone reduces preconceptual endometrial natural killer cells in women with recurrent miscarriage.

OBJECTIVE: To test the hypothesis that high numbers of uterine natural killer (uNK) cells in the endometrium of women with recurrent miscarriage (RM) could be reduced with prednisolone. DESIGN: A before and after study. SETTING: A tertiary referral teaching hospital. PATIENT(S): Eighty-five women with idiopathic RM recruited from all over the UK and 18 women attending for sterilization (controls). INTERVENTION(S): An endometrial sample was taken on day 21 +/- 2 of the menstrual cycle. Immunohistochemistry was used to identify uNK (CD56+, CD16-, CD3-). Twenty-nine women with RM and >5% uNK agreed to take 20 mg oral prednisolone daily from day 1 to 21 of their menstrual cycle, when a second biopsy was obtained and analyzed. MAIN OUTCOME MEASURE(S): The percentage of stromal cells that were uNK. The normal range was defined using control samples as <5%. RESULT(S): Women with RM had significantly more uNK than the controls (P=.008). Prednisolone treatment significantly reduced the number of CD56 cells in the endometrium, from a median of 14% (before) to 9% (after) (P=.0004). CONCLUSION(S): We have demonstrated that high numbers of uNK in preimplantation endometrium of women with recurrent miscarriage can be reduced with administration of prednisolone.

Antiphospholipid antibodies prevent extravillous trophoblast differentiation.

OBJECTIVE: We investigated the hypothesis that antiphospholipid antibodies (aPL) have a detrimental effect on human extravillous trophoblast (EVT) differentiation into giant multinucleated cells "in vitro." DESIGN: The EVT were isolated from the placental chorion using enzymatic digestion and Percoll gradient centrifugation. After 24, 36, and 48 hours in culture, giant multinuclear cells (GMC) were identified by immunohistochemistry using antibodies to cytokeratin 7 and counted. SETTING: An academic research laboratory. PATIENT(S): Placentas were donated by women having an elective cesarean section for a normal pregnancy at term. MAIN OUTCOME MEASURE(S): This model was then used to investigate the effect of two different monoclonal aPL to beta2-glycoprotein 1 (IIC5 and ID2), and control mouse IgG antibody on EVT differentiation. RESULT(S): Freshly isolated EVT were nonproliferative but moved together losing their intervening cell walls and differentiated into GMC. Maximal numbers of GMC were detected after 48 hours of culture. The aPL, IIC5, and ID2 significantly inhibited GMC formation, whereas the mouse IgG control had no effect. CONCLUSION(S): Antiphospholipid antibodies can inhibit EVT differentiation and GMC formation "in vitro" suggesting that a failure of trophoblast differentiation and subsequent uteroplacental development may be an underlying pathology in antiphospholipid syndrome-associated pregnancy loss.

Trophoblast invasion.

Trophoblast invasion can be seen as a tightly regulated battle between the competing interests of the survival of the fetus and those of the mother. Successful pregnancy is dependent on the trophoblast invading the mother, attaching the pregnancy to the uterus and securing an adequate supply of oxygen and nutrient to the fetus. For successful invasion to occur, extravillous trophoblast has to perform a range of functions; transformation of the maternal spiral arteries, tolerate hypoxia, proliferate and die by apoptosis (programmed cell death), differentiate, adhere to and digest the extracellular matrix, move and interact with the maternal immune system. Each of these functions has multiple overlapping control systems so that trophoblast invasion is a finely controlled balance of competing mechanisms.

Immunohistochemical localization of androgen receptors in the urogenital tracts of human embryos.

The aim of this study was to investigate androgen receptor (AR) expression in the developing human urogenital tract. The distribution of AR was examined in paraffin-embedded tissue sections of the lower urogenital tract using 55 human embryos of 8-12 weeks of gestation. Immunohistochemistry was performed for AR detection and gender was determined by polymerized chain reaction. There were no differences in the distribution of AR in male and female embryos at any stage of gestation. AR was present only in the mesenchymal tissues of the urogenital sinus at 8 weeks whilst the epithelium was negative, but after 9 weeks the epithelium also showed progressively more positive staining. In the phallus, AR staining was prominent. There was far less staining in the epithelium of the urethral groove from 8 to 10 weeks, whilst the mesenchyme of the urethral folds showed positive staining. At 11 and 12 weeks, both the urethral groove and folds showed uniform staining. The genital tubercle, genital swelling and bulbourethral gland precusors were also positively stained, although paramesonephric ducts were negative. Staining was observed in the mesonephric duct from 9 weeks. There was an absence of staining in the rectum at all stages of gestation. The expression of AR in an epithelium may be dependent upon the mesenchyme. Mesenchymal-epithelial interactions played an important role in development, as has been described in experimental animals. AR expression could play a part in the growth of the genital organs.

Effects of low-molecular-weight and unfractionated heparin on trophoblast function.

OBJECTIVE: Unfractionated and low-molecular-weight heparin and low-dose aspirin are used for the prevention of pregnancy loss in pregnant women with thrombophilia. We investigated the effect of these drugs on in vitro models of human extravillous trophoblast motility and differentiation. METHODS: Chorion from term placentas was digested and extravillous trophoblast isolated. Extravillous trophoblast formed giant multinuclear cells that were counted after 24, 36, and 48 hours of culture. This model was then used to investigate the effect of unfractionated, low-molecular-weight heparin and aspirin on in vitro extravillous trophoblast differentiation at both therapeutic and supratherapeutic doses. In addition, the effect of unfractionated and low-molecular-weight heparin on hepatocyte growth factor-stimulated SGHPL-4 cell (extravillous trophoblast cell line) motility was determined by time-lapse microscopy. RESULTS: At therapeutic doses unfractionated heparin promoted extravillous trophoblast differentiation. However, low-molecular-weight heparin inhibited giant multinuclear cells formation. At supratherapeutic doses, both low-molecular-weight and unfractionated heparin promoted extravillous trophoblast differentiation. Low-dose aspirin had minimal effects on the extravillous trophoblast differentiation. Both unfractionated and low-molecular-weight heparin inhibited hepatocyte growth factor-stimulated extravillous trophoblast motility at supratherapeutic doses. At a therapeutic dose of 0.25 IU/mL, only unfractionated heparin inhibited hepatocyte growth factor-stimulated motility, whereas low-molecular-weight heparin had no effect. CONCLUSION: Our data suggest that unfractionated and low-molecular-weight heparin have differing effects on trophoblast differentiation and motility at therapeutic doses. This finding may be one of many factors that contribute to the clinical scenario.

Successful pregnancy outcome following 19 consecutive miscarriages: case report.

No cause can be found in 50% of patients with recurrent miscarriage. Recent research has shown that high levels of natural killer (NK) cells within the endometrium may be associated with idiopathic recurrent miscarriage. This case report describes a patient in whom an excessive number of uterine NK cells were found. She received preconceptual prednisolone and delivered a live baby. This is a novel observation of untested significance.

Endometrial integrin expression in women undergoing in vitro fertilization and the association with subsequent treatment outcome.

OBJECTIVE: To study the endometrial expression of three integrins (alpha v beta 3, alpha 4 beta 1, and alpha 1 beta 1) in women undergoing IVF-intracytoplasmic sperm injection (ICSI) treatment and assess whether they could be used to predict subsequent treatment success.Prospective observational study. Healthy volunteers in a large teaching hospital. PATIENT(S): Sixty-six patients attending for IVF-ICSI treatment. INTERVENTION(S): Timed endometrial biopsies were taken, during the implantation window at LH + 7-9 days, from women before IVF-ICSI treatment. MAIN OUTCOME MEASURE(S): Histological dating of endometrium and immunohistochemical staining intensity of alpha 4 beta 1, alpha v beta 3, and alpha 1 beta 1 integrins. The integrin levels were correlated with subsequent success rates. RESULT(S): There was a statistically significantly greater expression of alpha v beta 3 in the luminal epithelium of those patients who had successful treatment. However, treatment was successful in some patients with negative expression. CONCLUSION(S): Integrins are important markers of endometrial receptivity. There is an association between an in-phase endometrial biopsy, with positive luminal alpha v beta 3 integrin expression, and subsequent treatment success. However, the clinical value of assessing the endometrium before treatment has drawbacks, and further work needs to be done before this can be considered a clinically useful test.

Recurrent miscarriage: a defect in nature's quality control?

Recent data on recurrent miscarriage (RM) is discussed in the framework of the selection failure hypothesis which states, 'Recurrent miscarriage is the result of failure of the prevention of 'poor quality' embryos implanting, allowing embryos that are destined to fail to implant and present clinically as recurrent miscarriage. Thus, recurrent miscarriage is a failure of nature's quality control.' The assumption that RM results from the maternal rejection of normal fetuses is challenged and evidence reviewed regarding the contribution of abnormal embryos and endometrial receptivity. Further research is needed to understand the mechanisms of maternal tract-embryo interaction and move towards improved management of recurrent pregnancy loss.

Leukocyte populations in interstitial cystitis and idiopathic reduced bladder storage.

OBJECTIVES: Mast cells and leukocyte populations in bladder biopsies from women with interstitial cystitis (IC) or idiopathic reduced bladder storage (sensory urgency [SU]) were compared to determine whether any evidence of a common etiology between these conditions could be found. METHODS: Biopsies from 40 patients (9 meeting the National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases criteria [IC] and 31 who did not [SU]) and 20 controls (having colposuspension for stress incontinence) were stained with monoclonal antibodies against leukocyte antigens and mast cell tryptase. The median cell counts from 10 high power fields were calculated and compared between cases and controls. The clinical and urodynamic data were also compared. RESULTS: Nocturia (odds ratio 26.7; 95% confidence interval 3.3 to 245.5) and bladder pain (odds ratio 18.5; 95% confidence interval 1.8 to 193.1) were associated with significant odds ratios for disease (IC or SU compared with controls) in logistic regression analysis. Patients with IC were significantly older than those with SU (P = 0.05). Leukocyte populations showed only increased CD20+ cells in patients with IC compared with the others (P = 0.03). CONCLUSIONS: The analysis of the clinical, urodynamic, and cystoscopic data showed no differences between patients with IC and those with SU, except for age. Nocturia or bladder pain discriminated between patients and controls. The lymphocytic infiltrate in SU is similar to that seen in IC but with fewer CD20+ cells. These data support the work of others and may indicate that SU has a common etiology with IC.