The Womb Cancer Awareness Measure (WCAM): development of an instrument to assess public awareness of endometrial cancer.

OBJECTIVE: To develop and test a novel instrument to assess public awareness of endometrial cancer symptoms and risk factors in a UK population. METHODS: A 36-item questionnaire was developed through literature review and extraction from cancer awareness materials. The Womb Cancer Awareness Measure (WCAM) was tested for content validity in 65 self-identified female research participants and 10 endometrial cancer experts prior to UK-wide field testing using social media. Test-retest reliability was assessed over 2 weeks, construct validity was assessed by comparing womb cancer experts and non-medical academics, and sensitivity to change was assessed by comparing scores of participants who read an endometrial cancer leaflet with those given a control leaflet. RESULTS: Fifty-two percent of the items in the test-retest reliability showed >80% agreement. Construct validity was demonstrated; endometrial cancer experts achieved higher scores (median 79 (IQR 18)) than non-medical academics (median 50 (IQR 18)) (p<0.001). The WCAM was sensitive to change; volunteers who read an endometrial cancer leaflet showed greater awareness (median 73 (IQR 9)) than those who read the control leaflet (median 59 (IQR 9)) (p<0.001). Knowledge of endometrial cancer red flag symptoms and risk factors was poor in the 847 UK-based participants. CONCLUSIONS: Our findings support the validity and reliability of the Womb Cancer Awareness Measure in assessing public awareness of endometrial cancer. In a UK population sample, knowledge of warning symptoms and risk factors was low, highlighting the need for public awareness campaigns.

How pre-registration nursing students acquire delegation skills: A systematic literature review.

AIM: To discover what is known about how nursing students acquire delegation skills. DESIGN: A systematic search was conducted utilising databases: CINAHL, AMED, MedLine, PsycINFO, Web of Science, PsychArticles, PubMed Central and Science Direct. The objectives were to: conduct a systematic literature review of the available literature on how nursing students acquire delegation skills; to identify factors that promote synthesis of delegation skills into clinical practice and understand how students learn these skills; and to identify any gaps in the literature. RESULTS: Fifteen papers, which use a range of methodologies, were included in the review. The author identified that acquiring delegation skills is an ongoing process and cannot be fully learnt during a single intervention. Furthermore that there are multiple factors that may promote the acquisition of this skill. These include simulation, clinical practice and theoretical curriculum. Delegation links to other skills such as critical thinking, decision making, prioritisation and communication. CONCLUSION: Delegation should not be considered in isolation to these underpinning skills. Furthermore, it is evident that delegation is an often-misunderstood concept and something that newly qualified nurses feel unprepared for. It is therefore vital that preregistration nursing education (as well as other pre- and post-qualification training) incorporate the development of this essential skill.

Arteriovenous malformation as a cause for acute confusion and gastrointestinal bleeding in a primigravida pregnancy.

Acute confusion in pregnancy is generally uncommon, given the relatively young and healthy population obstetricians care for. We present an unusual and rare case of acute confusion in a term pregnancy with antecedent history of gastrointestinal (GI) bleeding. A primigravida with no medical history of note, was found to have a haemoglobin of 67 g/L at booking and was commenced on oral iron supplementation. In the third trimester, she presented with haematochezia and had several admissions, requiring 18 units of red blood cells during her pregnancy. At term, she was admitted with acute confusion and GI bleeding, and was subsequently delivered by caesarean section to facilitate ongoing investigation and management of her symptoms. She was diagnosed postnatally with an arteriovenous malformation in the jejunum which required interventional radiology and surgical management for symptom resolution. Her confusion was attributed to hyperammonaemic levels secondary to her high protein load.

UK guidelines for the medical and laboratory procurement and use of sperm, oocyte and embryo donors (2019).

This article updates the 2008 UK guidelines for the medical and laboratory screening of sperm, egg and embryo donors. This was achieved by a working group composed of representatives from: the Association of Biomedical Andrologists, the Association of Clinical Embryologists, the British Andrology Society and the British Fertility Society, with subsequent review and commentary from their respective memberships. Information and guidance on core facts which should be made evident to all parties involved in donation are provided. Changes with regard to transmissible disease screening include: (i) extended guidance regarding history taking, risk factors and deferral periods; (ii) recommended quarantine period for donors screened by Nucleic Acid Testing (NAT) and serology is now 3 months; (iii) recommended quarantine period for donors screened by serology alone is legally required to be 6 months; (iv) if donor oocytes, or embryos created with donor oocytes, are cryopreserved then the quarantine period should be observed as best practice. We further recommend that consideration be given to HPV vaccination of women who outside of insemination may not be exposed to HPV. For heritable diseases, the discussion and assessment of genetic risk have been fundamentally reviewed in light of technological advances. After review of scientific evidence, it has also been deemed acceptable for men to donate sperm up to their 46th birthday.

Evaluation of agreement of placental growth factor (PlGF) tests and the soluble FMS-like tyrosine kinase 1 (sFlt-1)/PlGF ratio, comparison of predictive accuracy for pre-eclampsia, and relation to uterine artery Doppler and response to aspirin.

OBJECTIVES: The objective of this study is to evaluate agreement between PlGF and sFlt-1/PlGF ratio tests and compare their predictive accuracy for pre-eclampsia in high-risk women. Also, to examine for associations of abnormal PlGF or sFlt-1/PlGF ratio with abnormal uterine artery Doppler and platelet response to aspirin. METHODS: Prospective cohort study, 150 pregnant women at high risk of pre-eclampsia prescribed 75 mg aspirin daily. Uterine artery Dopplers were assessed at 20+0-23+6 weeks. At 33+0-35+6 weeks platelet function aspirin metabolites, PlGF and the sFlt-1/PlGF ratio were measured. OUTCOME: Measures were all pre-eclampsia and pre-eclampsia requiring delivery prior to 37 weeks. RESULTS: Overall percent agreement was 89.3% for PlGF tests but 74.7-78% for PlGF tests and the sFlt-1/PlGF ratio. AUCs were 0.70-0.75 for prediction of any pre-eclampsia and 0.92-0.99 for preterm pre-eclampsia. We found a significant association between abnormal PlGF or sFlt-1/PlGF ratio and abnormal uterine artery Doppler (χ2 5.47, p = .019), but no association with platelet response to aspirin (χ2 0.12, p = .913). There were no associations between suboptimal aspirin adherence and either abnormal angiogenic markers or uterine artery Dopplers (χ2 0.144, 0.038, p = .704, .846, respectively). CONCLUSIONS: There was good agreement between PlGF tests and limited agreement between PlGF tests and the sFlt-1/PlGF ratio. All tests have heightened predictive accuracy for preterm pre-eclampsia. Abnormal PlGF or sFlt-1/PlGF ratio relates to abnormal uterine artery Doppler but not platelet response to aspirin.

Oncological outcomes of abdominoperineal resection for the treatment of low rectal cancer: A retrospective review of a single UK tertiary centre experience.

BACKGROUND: The use of abdominoperineal resection (APR) in the management of low rectal cancer has received criticism over high rates of incomplete resection due to tumour involvement at the circumferential resection margin. Extralevator abdominoperineal resection has been advocated as a means of improving complete resection. However, Extralevator abdominoperineal resection can result in increased cost, morbidity and reduced quality of life.This study aims to assess the histological features and long-term outcomes of patients undergoing standard abdominoperineal resection and discusses the potential role of Extralevator abdominoperineal resection in this cohort. METHOD: A retrospective review of a prospectively maintained database of rectal cancer patients at a single centre. Patients undergoing standard APR were included from 01/06/2007 to 31/05/2012 to allow a minimum 2-year follow-up. Data was collected on age, gender, co-morbidity, pre-operative stage, neo-adjuvant therapy, histology, recurrence and mortality. RESULTS: Seventy patients were identified (45 (64%) male, median age 67; (range 36-85)). 12 (17.1%) patients had a positive circumferential resection margin; 4 (6.1%) tumours were located anteriorly, 8 (11%) were located posteriorly or laterally and may potentially have been completely resected with extralevator abdomino-perineal resection, Number-needed to treat = 9. Positive circumferential resection margin was more common in advanced tumours (p < 0.001). Local recurrence was more common with positive circumferential resection margins (16.7% Vs 0%, p = 0.027), with no statistically significant difference in 5-year survival, although there was a tendency towards worse survival in these patients. CONCLUSION: Positive circumferential resection margin following APR resulted in significantly increased local recurrence with a trend towards poorer survival outcomes. Extralevator abdomino-perineal resection may have benefited some of these patients with locally advanced tumours and postero-lateral recurrences. However, this has to be balanced against exposing patients to increased risk of adverse events. We would recommend selective use of Extralevator abdominoperineal resection for locally advanced and node-positive tumours although further studies to help refine selection criteria are required with long-term follow-up.

Discovery of a novel dominant mutation in the REN gene after forty years of renal disease: a case report.

BACKGROUND: Heterozygous mutations in the gene encoding renin (REN) cause autosomal dominant tubulointerstitial kidney disease (ADTKD), early-onset anaemia and hyperuricaemia; only four different mutations have been described in the published literature to date. We report a novel dominant REN mutation discovered in an individual after forty years of renal disease. CASE PRESENTATION: A 57 year old Caucasian woman with chronic kidney disease stage five was reviewed in a regional joint renal genetics clinic. She had initially been diagnosed with chronic pyelonephritis in adolescence, around the same time that she was investigated for anaemia out of keeping with her degree of renal impairment. Hyperuricaemia was identified in her twenties following an episode of gout. A diagnosis of ADTKD was not made until the age of 37 years, when her mother was also found to have kidney disease and commenced haemodialysis. The patient's renal function continued to slowly deteriorate and, twenty years later, her sister was worked up as a potential donor for kidney transplantation. Revisiting the maternal family history during the transplant work up prompted a referral to clinical genetics and urgent REN genetic testing was requested for the patient, leading to discovery of a heterozygous mutation in the REN gene: c.49 T > C, p.(Trp17Arg). This variant was not identified in her otherwise healthy sister, allowing pre-emptive live renal transplantation to take place shortly afterwards. CONCLUSIONS: In an era where genetic testing is becoming much more readily available, this case highlights the importance of considering a genetic aetiology in all patients with long-standing renal disease and a relevant family history. Establishing a genetic diagnosis of ADTKD-REN in this individual with chronic anaemia, hyperuricaemia and slowly progressive renal impairment helped to identify a suitable live kidney donor and allowed successful pre-emptive transplantation to take place.

An Unusual Cause of Subacute Headache in a Patient Undergoing Chemotherapy for Advanced Testicular Nonseminomatous Germ Cell Tumour.

Testicular (germ cell) cancer is a model of a chemocurable malignancy and tends to have a favourable prognosis even in advanced stages due to exquisite sensitivity to platinum-based chemotherapy. However, both acute and longer-term toxicities of multiagent chemotherapy remain significant as causes of morbidity, very occasionally mortality, and impaired quality-of-life. Here, we report a case of acute cerebral venous sinus thrombosis occurring within 10 days of chemotherapy initiation in a young patient without comorbidities, whose only predisposing factors were malignancy, chemotherapy, and perhaps mild dehydration. The clinical presentation was also unusual with headache of moderate severity only without focal or global neurologic deficits. We suspect that cisplatin may have had direct vasculotoxic effects. The patient recovered fully after short-duration anticoagulation but oncologists must remain aware of unusual and unpredictable complications of cytotoxic treatment.

Sperm DNA fragmentation, recurrent implantation failure and recurrent miscarriage.

Evidence is increasing that the integrity of sperm DNA may also be related to implantation failure and recurrent miscarriage (RM). To investigate this, the sperm DNA fragmentation in partners of 35 women with recurrent implantation failure (RIF) following in vitro fertilization, 16 women diagnosed with RM and seven recent fathers (control) were examined. Sperm were examined pre- and post-density centrifugation by the sperm chromatin dispersion (SCD) test and the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. There were no significant differences in the age of either partner or sperm concentration, motility or morphology between three groups. Moreover, there were no obvious differences in sperm DNA fragmentation measured by either test. However, whilst on average sperm DNA fragmentation in all groups was statistically lower in prepared sperm when measured by the SCD test, this was not seen with the results from the TUNEL assay. These results do not support the hypothesis that sperm DNA fragmentation is an important cause of RIF or RM, or that sperm DNA integrity testing has value in such patients. It also highlights significant differences between test methodologies and sperm preparation methods in interpreting the data from sperm DNA fragmentation tests.

ACE consensus meeting report: culture systems.

The UK Association of Clinical Embryologists held a workshop on Culture Systems for assisted conception in Sheffield on 22 May 2013. The meeting was organised in the light of the availability of numerous commercial products for the culture of human preimplantation embryos in vitro and the absence of data comparing the performance of these products. Expert opinions were presented, along with survey data provided by participating IVF Centres. The workshop highlighted the lack of a sound evidence base to support the selection of any one commercial product over another, and raised concerns over the lack of information defining precisely the composition of media, and the potential for adverse long-term effects of such products following their use in assisted conception.

ACE consensus meeting report: oocyte and embryo cryopreservation Sheffield 17.05.11.

The UK Association of Clinical Embryologists (ACE) held a consensus workshop on Oocyte and Embryo Cryopreservation in Sheffield, UK, on May 17th, 2011. This was organized in response to a number of considerations including the increasing prevalence of vitrification for oocyte and embryo cryopreservation in the UK and worldwide, coupled with an apparent lack of consensus over which methods of cryopreservation are optimal. The workshop included expert opinion and survey data on current practice provided by participating clinics. The workshop highlighted that an increasing number of clinics in the UK are choosing vitrification rather than controlled rate freezing, particularly for the storage of oocytes and blastocysts. It was evident that a variety of solutions are used in conjunction with open and closed containers. Data supplied by the participating clinics suggest that both freezing and vitrification can lead to similar outcomes in early embryos and blastocysts and at the moment there is no evidence base to recommend either method over the other. The delegates arrived at a number of consensus points which reflected current practice in the UK, but recognized the need for well-designed trials with careful follow up of the children born before optimal methods can be agreed.

Donor HO-1 expression inhibits intimal hyperplasia in unmanipulated graft recipients: a potential role for CD8+ T-cell modulation by carbon monoxide.

BACKGROUND: Induction of heme oxygenase (HO)-1 expression protects transplanted organs from humoral rejection and ischemia-reperfusion injury, but induction in recipient immune cells also has direct immunomodulatory effects. Although many studies have examined the impact of HO-1 after transplantation, it is still unclear whether HO-1 expression solely in the donor tissue can influence the recipient T-cell response. METHODS: Donor mice were treated with hemin to transiently upregulate HO-1. Control or HO-1-expressing aortas were transplanted into fully mismatched, completely unmanipulated recipients, and harvested at 6 weeks to assess neointimal area and T-cell infiltration. T cells were isolated from draining lymph nodes to assess cytokine production. In vitro, T-cell proliferative and cytokine responses to allogeneic donor dendritic (DC) and endothelial cells expressing HO-1 were examined. RESULTS: Neointimal area was significantly (P<0.01) reduced in HO-1-expressing grafts. Hemin pretreated endothelial cells significantly inhibited proliferation (P<0.01) and interferon (IFN)-gamma production (P =0.01) in allogeneic CD8 T cells. This effect was mimicked by a carbon monoxide-releasing molecule. No phenotypic or functional changes were observed after incubation of T cells with hemin-treated dendritic cells. T-cell infiltration of HO-1-expressing donor aortas was significantly reduced (P<0.001), but proportions of IFN-gamma-producing T cells harvested from regional lymph nodes were similar. CONCLUSIONS: Organs expressing cytoprotective HO-1 have a direct influence on the recipient immune response. Given the important role of CD8 T cells and IFN-gamma in chronic rejection, these data suggest that donor HO-1 expression may be useful to augment other immunosuppressive therapies to prolong graft survival and inhibit intimal hyperplasia.

Establishing quality control in the new IVF laboratory.

The ability to create an optimal environment for the culture of oocytes and embryos is important to ensure that embryo viability, and therefore pregnancy outcome, is not compromised. Laboratory performance can be monitored using a quality control system. In setting up a new IVF unit, a comprehensive quality control programme was established to monitor laboratory performance and to detect any problems that potentially may have resulted in a sub-optimal service. The measures employed were designed to optimize the environment for human embryo culture by providing aseptic conditions and security for the gametes and embryos, whilst providing a safe working environment for laboratory staff. Equipment function, consumables and environmental parameters were assessed prior to the commencement of treatment in the new unit. A mouse embryo bioassay was used to assess the ability of the new laboratory and equipment to support mammalian embryo development. Prior to the start of clinical treatments a quality control program highlighted equipment that was functioning sub-optimally, which had the potential to cause problems had it been left undetected. Once clinical treatment commenced, quality control monitoring was continued to ensure that the laboratory functioned to a consistently high standard.

The big idea: clients' perspectives of change processes in cognitive therapy.

This study reports on analyses carried out by the authors on five 'end of therapy' evaluations conducted with clients who had received a brief course of cognitive therapy for depression. The clients' evaluation was based on Elliott's (1996) Change Interview Schedule. The transcripts were then analysed using grounded theory methods, and arranged into 10 categories and three category clusters. The category clusters included 'the listening therapist', 'the big idea' and 'feeling more comfortable with self'. Clients' reported cognitive and emotional processes fit with Stiles et al.'s (1990) assimilation model.

Ras antagonist farnesylthiosalicylic acid (FTS) reduces glomerular cellular proliferation and macrophage number in rat thy-1 nephritis.

Targeting the Ras family of monomeric GTPases has been suggested as a therapeutic strategy in proliferative renal diseases. This article reports the effects of Ras antagonist farnesylthiosalicylic acid (FTS) in rat thy-1 nephritis, a model in which cytokine-driven glomerular cell proliferation and invasion is likely to involve Ras signaling pathways. FTS in vitro specifically inhibits the binding of Ras to discrete membrane sites, thereby downregulating several Ras-dependent signaling functions and accelerating Ras degradation. Forty-four Lewis rats were given nephritis by day zero injection of a monoclonal thy-1 antibody ER4 (2.5mg/kg body wt). Twenty-two rats were then treated with daily intraperitoneal injection of FTS (5 mg/kg body wt) until sacrifice, and the remaining control rats were given vehicle alone (C). Six rats from each group were sacrificed at day 1 to establish equal injury; other sacrifice points were day 7 and day 10. Bromo-deoxyuridine (BrdU) was injected 1 h before sacrifice, after which sections were used for immunohistochemistry, which included detection of Ras expression, BrdU+ cells and macrophages/monocytes (ED1+). Thy-1 nephritis was associated with an increase in glomerular expression of Ki-Ras and N-Ras isoforms, which was almost fully prevented by FTS. FTS treatment was associated with: (a) a 54% reduction in the mean number of BrdU+ cells per glomerulus (P < 0.01), (b) a 50% reduction in macrophages/monocytes (ED1+) per glomerulus (P < 0.01), and (c) a reduction in 24-h proteinuria at day 10 (P < 0.05). These results show that Ras inhibition can reduce both glomerular cell proliferation and glomerular macrophage cell number in the thy-1 model and justify further study of FTS as a potential therapeutic in proliferative nephritis.