Using Mixed Reality Simulation to Improve Junior Medical Trainees' Preparedness to Manage High-Acuity Trauma.

High-acuity trauma necessitates experienced and rapid intervention to prevent patient harm. However, upskilling junior trainees through hands-on management of real trauma cases is rarely feasible without compromising patient safety. This quality education report sought to investigate whether a simulation course operated via mixed reality (MR) headset devices (Microsoft HoloLens) could enhance the clinical knowledge recall and preparedness to practice of junior trainees with no prior experience managing trauma.The Plan-Do-Study-Act quality improvement method was used to refine six emergency trauma vignettes compatible with an MR teaching platform. Each vignette was curated by a multidisciplinary team of orthopaedic surgeons, clinical fellows and experts in simulation-based medical education. As a baseline assessment, a 2-hour emergency trauma course was delivered using traditional didactic methods to a cohort of pre-registration medical students with no clinical exposure to high-acuity trauma (n=16). Next, we delivered the MR simulation to an equivalent cohort (n=32). Clinical knowledge scores derived from written test papers were recorded for each group during and 2 weeks after each course. Each attendee's end-of-rotation clinical supervisor appraisal grade was recorded, as determined by a consultant surgeon who supervised participants during a 2-week placement on a major trauma ward. Balancing measures included participant feedback and validated cognitive load questionnaires (National Aeronautics and Space Administration-Task Load Index).Overall, attendees of the MR simulation course achieved and sustained higher clinical knowledge scores and were more likely to receive a positive consultant supervisor appraisal. This project serves as a proof of concept that MR wearable technologies can be used to improve clinical knowledge recall and enhance the preparedness to practice of novice learners with otherwise limited clinical exposure to high-acuity trauma.

Effectiveness of short, personalised student assistantships: an evaluative study across eight London hospitals.

OBJECTIVES: Student assistantships are recommended to prepare medical graduates for clinical practice. Traditionally, assistantships have consisted of longer placements, often up to 15 weeks. However, within the constraints of the final year, medical schools need to carefully balance the time required for specialty placements, assessments and the risk of student burnout. We set out to evaluate the effectiveness of shorter, personalised student assistantships. DESIGN: An evaluative study on the changes in final year student confidence in preparedness for practice after a 3-week assistantship with defined learning objectives and learning needs assessment. SETTING: Eight hospitals affiliated with Imperial College School of Medicine. OUTCOMES: Student confidence in 10 learning outcomes including organising ward rounds, documentation, communication with colleagues, communication with patients and relatives, patient handover, practical procedures, patient management, acute care, prioritisation and out-of-hours clinical work. RESULTS: Two hundred and twenty final year medical students took part in the student assistantship, of whom 208 completed both the pre-assistantship and post-assistantship confidence rating questionnaires (95% completion rate). After the assistantship, 169 (81%) students expressed increased confidence levels in one or more learning objectives. For each individual learning objective, there was a significant change in the proportion of students who agreed or strongly agreed after the assistantship (p<0.0001). CONCLUSION: Overall, the focused 3-week, personalised student assistantships led to significant improvement across all learning objectives related to preparedness for practice. The use of the pre-assistantship confidence rating questionnaire allowed students to identify and target areas of learning needs during their assistantship.

The Vanishing Adrenal Glands: A Transient Regression of Adrenal Lymphoma After a Single Dose of 1 mg Dexamethasone.

OBJECTIVE: Dexamethasone is a known treatment for lymphoma, but the potency and rapidity of its effect have not been recognized. We present a case of bilateral adrenal lymphoma that significantly reduced in size after a single dose of dexamethasone. METHODS: We present the clinical course and investigations, including adrenocorticotropic hormone, cortisol, short synacthen test, computed tomography (CT), and adrenal biopsy results. RESULTS: A 52-year-old man had a fall and was incidentally found to have bilateral adrenal masses (left, 6 cm; right, 5 cm) on CT. His adrenal function tests included plasma metanephrines (normetanephrine, 830 pmol/L [normal, <1180]; metanephrine, <100 pmol/L [<510]; 3-methoxytyramine, <100 pmol/L [<180]); aldosterone, 270 pmol/L( 90-700); and random cortisol, 230 nmol/L (160-550). An overnight dexamethasone suppression test with 1 mg of dexamethasone showed cortisol of <28 nmol/L (0-50). A repeat CT scan 8 days thereafter showed adrenal masses of 4.5 and 3.5 cm on the left and right, respectively. He had a follow-up CT scan 3 months later that showed adrenal lesions measuring 8 cm (left) and 9 cm (right). He subsequently presented with fatigue and dizziness. Morning cortisol of 201 nmol/L (160-550) with adrenocorticotropic hormone of 216 ng/L (10-30) indicated primary adrenal insufficiency. Mineralocorticoid and glucocorticoid replacement therapy commenced. An adrenal biopsy showed abnormal enlarged B cells, consistent with a diagnosis of diffuse large B-cell lymphoma. CONCLUSION: A diagnosis of lymphoma should be considered when adrenal lesions shrink following even a single low dose of dexamethasone administered as a part of a diagnostic test.

A Case Series of Patients with Isolated IgG4-related Hypophysitis Treated with Rituximab.

CONTEXT: The acute presentation of immunoglobulin G4 (IgG4)-related hypophysitis can be indistinguishable from other forms of acute hypophysitis, and histology remains the diagnostic gold standard. The high recurrence rate necessitates long-term immunosuppressive therapy. Rituximab (RTX) has been shown to be effective in systemic IgG4-related disease (IgG4-RD), but experience with isolated pituitary involvement remains limited. CASE DESCRIPTION: We report 3 female patients with MRI findings suggestive of hypophysitis. All patients underwent transsphenoidal biopsy and fulfilled diagnostic criteria for IgG4-related hypophysitis. Treatment with glucocorticoids (GCs) resulted in good therapeutic response in Patients 1 and 2, but the disease recurred on tapering doses of GCs. GC treatment led to emotional lability in Patient 3, necessitating a dose reduction. All 3 patients received RTX and Patients 2 and 3 received further courses of treatment when symptoms returned and B-cells repopulated. Patient 3 did not receive RTX until 12 months from the onset of symptoms. Patient 1 was not able to have further RTX treatments due to an allergic reaction when receiving the second dose. Rituximab treatment resulted in sustained remission and full recovery of anterior pituitary function in Patients 1 and 2, with complete resolution of pituitary enlargement. By contrast, Patient 3 only showed a symptomatic response following RTX treatment, but pituitary enlargement and hypofunction persisted. CONCLUSION: Rituximab treatment for IgG4-related hypophysitis resulted in sustained remission in 2 patients treated early in the disease process but only achieved partial response in a patient with chronic disease, suggesting that early therapeutic intervention may be crucial in order to avoid irreversible changes.

Animated stories of medical error as a means of teaching undergraduates patient safety: an evaluation study.

BACKGROUND: Storytelling is a powerful form of communication which can improve attention and lead to lasting behavioural changes. Addressing the need to incorporate patient safety teaching into undergraduate medical curricula, it was hypothesized that medical students could benefit from hearing clinician stories of medical error. The medium of animation was considered to be a potentially engaging means of presenting stories of error to a large audience. METHODS: Three animated videos were developed to accompany audio recordings of junior doctors describing their experiences of a serious incident or near-miss event. The videos were delivered to 200 final-year medical students with a subsequent large-group discussion directed at understanding contributory factors. An evaluative questionnaire exploring learners' reactions and modification of beliefs and perception was distributed. The questionnaire included questions rated on a modified Likert scale and a free-text box. A mixed-methods analysis was conducted with descriptive statistics and qualitative content analysis of the free-text responses. RESULTS: Of the 200 students who attended, 104 completed the questionnaire and 83 completed free-text feedback. Most students responded positively to hearing stories of medical error and felt that the animated videos improved their engagement while the voice recordings helped bring the cases to life. The majority of students agreed the session would impact on their future practice. CONCLUSION: This pilot study confirmed that undergraduate students consider animated, personal stories of medical error an effective, engaging means of learning about patient safety. Longitudinal studies are required to confirm if measurable behaviour change is achieved.

Association of p16 expression with prognosis varies across ovarian carcinoma histotypes: an Ovarian Tumor Tissue Analysis consortium study.

We aimed to validate the prognostic association of p16 expression in ovarian high-grade serous carcinomas (HGSC) and to explore it in other ovarian carcinoma histotypes. p16 protein expression was assessed by clinical-grade immunohistochemistry in 6525 ovarian carcinomas including 4334 HGSC using tissue microarrays from 24 studies participating in the Ovarian Tumor Tissue Analysis consortium. p16 expression patterns were interpreted as abnormal (either overexpression referred to as block expression or absence) or normal (heterogeneous). CDKN2A (which encodes p16) mRNA expression was also analyzed in a subset (n = 2280) mostly representing HGSC (n = 2010). Association of p16 expression with overall survival (OS) was determined within histotypes as was CDKN2A expression for HGSC only. p16 block expression was most frequent in HGSC (56%) but neither protein nor mRNA expression was associated with OS. However, relative to heterogeneous expression, block expression was associated with shorter OS in endometriosis-associated carcinomas, clear cell [hazard ratio (HR): 2.02, 95% confidence (CI) 1.47-2.77, p < 0.001] and endometrioid (HR: 1.88, 95% CI 1.30-2.75, p = 0.004), while absence was associated with shorter OS in low-grade serous carcinomas (HR: 2.95, 95% CI 1.61-5.38, p = 0.001). Absence was most frequent in mucinous carcinoma (50%), and was not associated with OS in this histotype. The prognostic value of p16 expression is histotype-specific and pattern dependent. We provide definitive evidence against an association of p16 expression with survival in ovarian HGSC as previously suggested. Block expression of p16 in clear cell and endometrioid carcinoma should be further validated as a prognostic marker, and absence in low-grade serous carcinoma justifies CDK4 inhibition.

Clinical and biochemical characteristics of patients presenting with pituitary apoplexy.

PURPOSE: To review the clinical and biochemical characteristics and clinical outcome of patients presenting with pituitary apoplexy to a tertiary centre. METHODS: We retrospectively reviewed the clinical features, predisposing factors, biochemistry and clinical outcome of patients presenting with pituitary apoplexy to Imperial College Healthcare NHS Trust between 1991 to 2015. RESULTS: We identified 64 patients with pituitary apoplexy (more complete clinical records were available in 52 patients). The median age at presentation was 46.7 years (IQR 31.5-57.0 years). Pituitary apoplexy was the first presentation of pituitary disease in 38/52 of patients and predisposing factors were identified in 28/52. Pituitary apoplexy predominantly occurred in patients with non-functioning pituitary adenomas (47/52). Headache was most commonly described as sudden-onset, severe, lateralising to the frontal or temporal regions. Symptoms of meningeal irritation were reported in 7/18 and visual abnormalities in 22/35. A pre-treatment serum cortisol <100nmol/l was recorded in 12/31 of patients. All patients with visual disturbance had some resolution of their visual symptoms whether managed surgically (14/14) or conservatively (5/5), although pituitary endocrine function did not fully recover in any patient. CONCLUSIONS: In conclusion, these data describe the clinical features of pituitary apoplexy to aid the clinician in diagnosing this rare emergency presentation of pituitary disease. Prospective multicentre studies of the presentation of pituitary apoplexy are required to further characterise presentation and outcomes.

Interpretation of Serum Gonadotropin Levels in Hyperprolactinaemia.

BACKGROUND/AIMS: Hyperprolactinaemia is a common cause of amenorrhoea due to hypogonadotropic hypogonadism. Prolactin is hypothesised to impede the reproductive axis through an inhibitory action at the hypothalamus. However, limited data exist to aid the interpretation of serum gonadotropins in the context of hyperprolactinaemia. METHODS: Serum gonadotropin values were reviewed in 243 patients with elevated serum monomeric prolactin due to discrete aetiologies at a tertiary reproductive endocrine centre between 2012 and 2015. The cause of hyperprolactinaemia was categorised by an experienced endocrinologist/pituitary multidisciplinary team, unless superseded by histology. The most frequently encountered diagnoses were microprolactinoma (n = 88), macroprolactinoma (n = 46), non-functioning pituitary adenoma (NFPA) (n = 72), drug-induced hyperprolactinaemia (n = 22) and polycystic ovarian syndrome (PCOS) (n = 15). RESULTS: In patients with prolactinoma and modestly raised serum prolactin levels (< 4,000 mU/L), increasingly FSH-predominant gonadotropin values were observed with rising prolactin level, consistent with a progressive reduction in hypothalamic gonadotropin-releasing hormone (GnRH) pulsatility. Patients with prolactinoma and higher prolactin values (> 4,000 mU/L) were more likely to have a reduction in serum levels of both FSH and LH, consistent with direct pituitary gonadotrope dysfunction. Patients with macroadenoma and extremes of serum gonadotropin values (either serum FSH or LH > 8 IU/L) were more likely to have NFPA than prolactinoma. Patients with PCOS and hyperprolactinaemia had LH-predominant secretion in keeping with increased GnRH pulsatility despite a raised prolactin level. CONCLUSION: The pattern of gonadotropin secretion in patients with hyperprolactinaemia reflects the underlying aetiology.

Adrenal venous sampling as a diagnostic procedure for primary hyperaldosteronism: experience from a tertiary referral centre.

CONTEXT: Adrenal vein sampling (AVS) is recommended in all patients with hyperaldosteronism to whom surgery would be offered if the results indicated unilateral hypersecretion. OBJECTIVE: To assess the performance of AVS against radiological findings and to evaluate the Endocrine Society's Practice Guidelines for diagnostic cut-offs. PATIENTS: Retrospective study of 41 patients with hyperaldosteronism who underwent both AVS and computed tomography (CT) imaging. RESULTS: CT and AVS results were concordant in 73.7%. Unilateral lesions on CT had a greater positive predictive value (85%) than non-unilateral lesions (50%). In patients with subsequently confirmed adrenal adenomas, a lateralisation ratio >2 when comparing cortisol-corrected aldosterone ratios from the affected versus unaffected side was 100% sensitive. Patients who were managed surgically experienced significant reductions in blood pressure and medication burden and 46% were cured. CONCLUSIONS: AVS is important in establishing unilateral or bilateral adrenal secretion of aldosterone in patients with primary hyperaldosteronism. However, it may not be essential for the work-up in patients below the age of 40, in whom adrenal incidentalomas adrenal incidentalomas are known to be rarer, and a unilateral lesion on CT therefore has a greater positive predictive value.

Primary sellar neuroblastoma presenting with syndrome of inappropriate secretion of anti-diuretic hormone.

A 29-year-old Ethiopian man presented with marked bilateral visual loss, headache, hypopituitarism and significant hyponatraemia (115 mmol/L). A brain MRI scan demonstrated a large, lobulated, sellar and suprasellar mass, elevating the floor of the 3rd ventricle and compressing the optic chiasm. The patient underwent a transphenoidal resection of the mass followed by a craniotomy 10 days later. Histological examination demonstrated a Hyams' grade III neuroblastoma with ectopic expression of vasopressin. He underwent fractionated radiotherapy at a dose of 60 Gy in 30 fractions. Fourteen months after the onset, he is well with no neuroimaging evidence of tumour recurrence. His serum and urine sodium are completely normalised.

Catecholamine-induced transient myocardial dysfunction.

This report presents an interesting case of acute myocardial stunning secondary to catecholamine surge from a phaeochromocytoma. A 39-year-old British Asian man was admitted with chest pain, labile blood pressure, dynamic ECG changes and positive troponin I level. Echocardiogram showed severe global impairment of his left ventricular systolic function but sparing of the basal segments. Portable renal ultrasonography revealed a 6 cm mass in the left adrenal gland. The clinical suspicion was of catecholamine-induced acute myocardial dysfunction secondary to underlying phaeochromocytoma. Intravenous alpha blockade resulted in a dramatic clinical improvement and near resolution of the echocardiographic abnormalities. Subsequent coronary angiography confirmed normal coronary arteries. He was discharged, well, on oral alpha-adrenergic and beta-adrenergic blockade. Outpatient metaiodobenzylguanidine scanning was consistent with the diagnosis and a left phaeochromocytoma was successfully removed laparoscopically.

A legacy of tinnitus: multiple head and neck paragangliomas.

We describe the case of a patient who presented with a right-sided glomus jugulare tumor and bilateral glomus vagale tumors. These proved to be nonmalignant paragangliomas on histopathological analysis. Genetic analysis revealed a germline heterozygous missense mutation (Pro81Leu) in the succinate dehydrogenase subunit D (SDHD) gene. We discuss the clinical presentations of the familial paraganglioma syndrome type 1, which is caused by mutations in SDHD, and the implications for the clinical diagnosis and care of such patients.

Pituitary macroadenomas: are combination antiplatelet and anticoagulant therapy contraindicated? A case report.

BACKGROUND: Pituitary apoplexy is a life-threatening endocrine emergency that is caused by haemorrhage or infarction of the pituitary gland, commonly within a pituitary adenoma. Patients classically present with headache, ophthalmoplegia, visual field defects and altered mental state, but may present with a typical symptoms such as fever and altered conscious level. CASE PRESENTATION: A 57-year-old female with a known pituitary macroadenoma was treated for suspected acute coronary syndrome with aspirin, clopidogrel and full dose enoxaparin. She developed a severe and sudden headache, nausea and vomiting and visual deterioration. A CT scan showed haemorrhage into the pituitary macroadenoma. She underwent neurosurgical decompression. Post-operatively her visual fields and acuity returned to baseline. She was continued on hydrocortisone and thyroxine replacement on discharge. CONCLUSION: This case illustrates the risks of anticoagulation in a patient with a known pituitary macroadenoma, and raises the issue of whether these tumours present a relative contraindication to the use of dual antiplatelet and anticoagulation in acute coronary syndrome.

Spatial and temporal variations in parasite prevalence and infracommunity structure in herring (Clupea harengus L.) caught to the west of the British Isles and in the North and Baltic Seas: implications for fisheries science.

Herring Clupea harengus L. viscera were examined for endoparasitic infections as part of a multidisciplinary stock identification project (WESTHER, EU Contract no. Q5RS-2002-01 056) which applied a range of stock discrimination techniques to the same individual fishes to obtain comparable results for multivariate analysis. Spawning and non-spawning adults, and juvenile herring were caught, over 3 years, by commercial and research vessels from numerous locations to the west of the UK and Ireland, along with control samples of spawning fish from the eastern Baltic Sea, and juveniles from sites in the eastern and western North Sea, and the north of Norway. The metacercariae of two renicolid digeneans (Cercaria pythionike and Cercaria doricha), one larval nematode (Anisakis simplex s.s.) and one larval cestode (Lacistorhynchus tenuis) were selected as tag species. Results were compared with those from herring collected between 1973 and 1982, which suggested remarkable stability in the parasite fauna of herring in the study area. These species were used to compare the parasite infracommunities of spawning herring. A significant variation in infracommunity structure was observed between different spawning grounds. These results suggest that the parasite fauna of herring are spatially variable but remain temporally stable in both the short and long term. Significant differences in prevalence and abundance of infections and comparisons of parasite infracommunity enabled the separation of putative herring stocks west of the British Isles. Distinctive patterns of parasite infection in two different spawning groups off the north coast of Scotland suggest that this area is occupied by two spawning populations, one recruiting from the west of Scotland, the other from outside this area, and most likely from the eastern North Sea. The distribution patterns of L. tenuis, C. doricha and C. pythionike suggest the potential for fish that spawn in three distinct International Council for the Exploration of the Seas (ICES) management units to be present in mixed aggregations found over the Malin Shelf, with significant implications for management in this area.

Biocomplexity in a highly migratory pelagic marine fish, Atlantic herring.

The existence of biologically differentiated populations has been credited with a major role in conferring sustainability and in buffering overall productivity of anadromous fish population complexes where evidence for spatial structure is uncontroversial. Here, we describe evidence of correlated genetic and life history (spawning season linked to spawning location) differentiation in an abundant and highly migratory pelagic fish, Atlantic herring, Clupea harengus, in the North Sea (NS) and adjacent areas. The existence of genetically and phenotypically diverse stocks in this region despite intense seasonal mixing strongly implicates natal homing in this species. Based on information from genetic markers and otolith morphology, we estimate the proportional contribution by NS, Skagerrak (SKG) and Kattegat and western Baltic (WBS) fish to mixed aggregations targeted by the NS fishery. We use these estimates to identify spatial and temporal differences in life history (migratory behaviour) and habitat use among genetically differentiated migratory populations that mix seasonally. Our study suggests the existence of more complex patterns of intraspecific diversity than was previously recognized. Sustainability may be compromised if such complex patterns are reduced through generalized management (e.g. area closures) that overlooks population differences in spatial use throughout the life cycle.