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This research involved interviewing three people who had experienced self-injury. They were accessed from the voluntary sector as I felt that if I had accessed them from the National Health Service their views might not be honest, due to their possible perceptions of threats to their care. It was not intended that the views of these people would be representative, my aim was that their views, as well as areas highlighted in the literature, would inform me of areas pertinent to the topic, when seeking staff views. The views of staff, of which there were 15 self-selecting clinicians, formed the main focus of the study. The aims of the research were designed to highlight potentially contrasting perceptions of self-injury as a means of illuminating a current clinical problem. The results showed that staff on the whole agreed with the perceptions of people who have experienced self-injury; that they are often viewed negatively, though this is changing. It was recognized that care was dependent on where the person entered the service. Staff recognized that the service is under pressure and provision may not be available in the voluntary sector for these clients. [ABSTRACT FROM AUTHOR]

1. The cardiovascular effects of the proprietary cold remedies, Mu-cron and Boots Cold Relief tablets were compared with 'placebo' Boots Pain Relief tablets in a double-blind study involving 16 healthy volunteers. Measurements (impedance cardiography, forearm plethysmography) were made over 4 h after oral drug administration. 2. Two Mu-cron tablets (containing phenylpropanolamine [(1R,2S)- plus (1S,2R)-norephedrine] 50 mg) increased blood pressure (maximal effect 18 +/- 1/8 +/- 1 mm Hg (mean +/- s.e. mean), P less than 0.001), stroke volume (4.9 +/- 0.8 ml m-2, P less than 0.05), total peripheral resistance (243 +/- 27 dyn s cm-5 m2, P less than 0.001) and forearm vascular resistance (1.3 +/- 0.3 mm Hg ml-1 min, P less than 0.01) and reduced the ratio of pre- ejection period to ventricular ejection time (-0.031 +/- 0.003, P less than 0.05) and forearm blood flow (-2.6 +/- 0.5 ml min-1, P less than 0.05) but did not affect heart rate or cardiac index. 3. Two Boots Cold Relief tablets (containing phenylephrine 10 mg and caffeine 60 mg) caused a small and short-lived increase in total peripheral resistance but did not have consistent effects on other measurements. Two Boots Pain Relief tablets (containing caffeine 60 mg) did not have important cardiovascular effects. 4. The cardiovascular effects of phenylpropanolamine, including vasoconstriction and an increase in cardiac performance, are consistent with its alpha- and beta 1- adrenoceptor agonist action. While it may help the symptoms of rhinitis, its use in patients with heart disease or hypertension is hazardous.(ABSTRACT TRUNCATED AT 250 WORDS) [ABSTRACT FROM AUTHOR]

1. Intraocular pressure and cardiovascular responses to metipranolol 0.1% and 0.3% and timolol 0.25% eyedrops were measured in a balanced single dose placebo-controlled crossover study in eight healthy volunteers aged 34-58 years. 2. Timolol 0.25% and metipranolol 0.3% reduced intraocular pressure throughout the 6 h period of observation to a similar extent. Metipranolol 0.1% was marginally less effective, significantly reducing pressure up to 4 h only. 3. No drug treatment significantly altered resting heart rate or blood pressure. Timolol 0.25% significantly reduced exercise tachycardia (P less than 0.05), an effect which was not shown by metipranolol 0.1 or 0.3%. Exertional pain in the legs occurred more frequently after timolol 0.25% and metipranolol 0.3% than after metipranolol 0.1% or placebo eyedrops. 4. Octan-1-ol/pH 7.4 buffer distribution coefficients at 37 degrees C were found to be: metipranolol 5.19, timolol 0.84, indicating that metipranolol has an approximately 6-fold greater lipid solubility. 5. It is concluded that, by comparison with timolol, metipranolol in eyedrop concentrations up to 0.3%, despite its greater lipid solubility, reaches concentrations in the systemic circulation which are less likely to affect the heart. [ABSTRACT FROM AUTHOR]

The influence of vagal and sympathetic efferent activity on sinus arrhythmia in man has been studied in six healthy subjects by administration of hyoscine butylbromide and/or various beta- adrenoceptor blocking drugs using a microcomputer-linked electrocardiogram system. Sinus arrhythmia was quantitated as the s.d. of the R-R interval. Sinus arrhythmia was almost abolished by hyoscine butylbromide irrespective of the absence or presence and nature of the beta-adrenoceptor blocking drug. Atenolol and metoprolol alone prolonged the mean R-R interval and increased sinus arrhythmia. Oxprenolol, a drug with modest partial agonist or intrinsic sympathomimetic activity (ISA), prolonged the mean R-R interval to a lesser extent but had no effect on sinus arrhythmia. Xamoterol, which has high ISA, shortened the mean R-R interval but had no effect on sinus arrhythmia. These data yielded a non-linear relationship between sinus arrhythmia and mean R-R interval. Exaggerated sinus arrhythmia appears to accompany beta-adrenoceptor blockade only in the absence of ISA when bradycardia ensues. These findings are consistent with the hypothesis that the exaggeration in sinus arrhythmia is due to a central vagotonic effect secondary to the action of the drugs in the periphery. Changes in R-R interval induced by the adrenoceptor blocking drugs were altered to some extent by vagal blockade. This observation is consistent with the hypothesis that changes in heart rate induced by such drugs are determined in part by a change in vagal tone. [ABSTRACT FROM AUTHOR]

Plasma concentrations of oxprenolol have been measured in six healthy volunteers following single-dose oral administration of the drug in conventional and Oros dosage forms in fasting and postprandial states. After the Oros system, plasma concentrations reached peaks in most subjects at 3-8 h after dosing and were approximately 25% of those achieved with the conventional tablet. Plasma concentrations were well sustained for at least 24 h. A secondary peak occurred consistently at 12 h, possibly reflecting a transient change in clearance and/or distribution of the drug following the evening meal. With each formulation, plasma drug concentration profiles following administration in the fasting state did not differ significantly from those obtained when the drug was given postprandially. Drug absorption in vivo corresponded reasonably closely with in vitro drug release from the Oros system. [ABSTRACT FROM AUTHOR]

Plasma metoprolol concentrations and haemodynamic effects have been measured in six healthy male volunteers during once daily dosing with a 19/285 Oros system and twice daily dosing with 100 mg conventional tablets, on two separate occasions. Plasma drug concentrations throughout the day varied less with the Oros than with the conventional tablet regimen. Predosing concentrations were also higher with Oros but areas under the curve, after correcting for the differences in dose, were similar for the two preparations. Inhibition of exercise tachycardia was drug concentration dependent and was smoothly controlled through the day only with the Oros preparation. Predosing effects at steady-state were also greater for the Oros regimen. The decline in mean blood pressure, however, showed the same daily pattern for both regimens, and no significant differences were detected between Oros and conventional tablet treatments. The smoothness of the plasma profiles after Oros confirmed the controlled-release performance of the system in vivo and indicates its potential in the treatment of angina, cardiac arrhythmias and wherever it is important not to jeopardize steady selective beta-adrenoceptor blockade. [ABSTRACT FROM AUTHOR]

Heart-rate responses to intravenous hyoscine butylbromide, atropine and physiological saline in cumulative dosage regimens have been recorded in six healthy subjects. Atropine sulphate induced bradycardia at low, and tachycardia at higher, dose levels whereas hyoscine butylbromide caused only tachycardia but with a flatter dose-response relationship. Exact potency ratios could not be calculated because of the differing dose-response curves. However, an approximate estimate from a comparison of equiactive doses at the upper part of the curve yielded a value less than one half that obtained from the drugs' affinity constants in guinea-pig ileum. The findings suggest that, in addition to its action as a muscarinic antagonist, hyoscine butylbromide is a ganglion blocker in man as it is in animals. [ABSTRACT FROM AUTHOR]

1 Antipyrine elimination kinetics have been determined in fifteen patients before and after 4 weeks treatment with monoamine oxidase inhibitors and in five patients after treatment only. 2 Antipyrine elimination was slightly but significantly slowed by 28 days treatment with phenelzine but the degree of slowing was uninfluenced by acetylator phenotype or dosage of phenelzine administered. 3 The findings suggest that at the dosage used phenelzine is a weak inhibitor of hepatic microsomal mixed function oxidase in man and it is concluded that this is likely to provide an important source of drug interaction in some patients. [ABSTRACT FROM AUTHOR]

Introduction: Healthcare systems worldwide are facing a workforce crisis; meanwhile, refugee doctors throughout the world face difficulties in accessing work. The aims of this review were to explore the integration needs of refugee doctors into host healthcare systems from the refugee perspective, synthesise the literature to construct a theory of refugee doctor integration needs and explore how these needs are met or challenged on the pathway to full integration., Methods: In this integrative literature review, 11 databases and eight grey literature sources were searched by combining terms for refugee doctor and social integration and limiting to research published in or after 2003. Data were extracted, and quality scoring was completed independently by two researchers. This study utilised template analysis to perform a qualitative synthesis of the data. The multidimensional template included a pre-defined template based on a theoretical framework and a concurrent fully inductive template., Results: Twenty-two papers were included, incorporating the views of 339 doctors from 30 different home countries and 10 different host countries. The resultant theory included 'foundations' (rights and responsibilities) and three pillars. The 'learning' pillar included required knowledge and skills acquisition. The 'being' pillar encompassed necessary identity work. The 'connecting' pillar comprised social connections, which impacted all other domains. The random and non-linear path to integration faced by refugee doctors was also presented as a serious game., Discussion: This study produced a theory exploring refugee doctors' integration needs and how these are met or challenged. Medical educators developing courses for refugee doctors should attend not only to knowledge and skills acquisition but also social connections, identity work and rights and responsibilities. The theory highlights the central importance of social connections. Medical educators can therefore have a transformative impact on refugee doctors' integration. This may also contribute to society by helping to alleviate the workforce crisis., (© 2023 Association for the Study of Medical Education and John Wiley & Sons Ltd.)

Introduction: Health professional identity transitions involve a dynamic period of liminality prompting a time of considerable uncertainty and self-doubt. For postgraduate trainees in the United Kingdom, the transition to medical registrar can be a significant deterrent to recruitment and retention. Narrative analysis offers insight into identity work during transitions with potential to inform strategies for developing professional identities. This study aimed to use narrative analysis to explore trainees' experiences and their sense of agency during the liminal phase of this transition., Methods: Following ethical approval, internal medicine (IM) trainees in their second year of IM training were interviewed. Transcripts were audio recorded, transcribed verbatim and analysed to identify narratives describing liminality during the transition to the role of medical registrar, including examples of rejecting and claiming identity grants. Narrative analysis, as described by Riessman and influenced by James Gee's units of discourse, was undertaken, with an agentive lens applied to the data., Results: Between January 2021 and February 2022, 19 IM trainees were interviewed. Given the in-depth analysis, four narratives were purposively selected to present, including trainees rejecting and claiming the medical registrar role. Trainees tended to describe negative experiences, but those with a higher sense of agency demonstrated positive reflection and identity construction through narrative. There was often identity dissonance between how trainees defined their stage in the transition to medical registrar and how their narrative illustrated their identity work., Conclusion: This study exemplifies narrative analysis' linguistic and agentive lenses in exploring the experience of the liminal identity transitional period. The findings reflect the identity dissonance experienced by trainees during this time and sheds light on their sense of agency throughout. It heralds a need to acknowledge the significant liminality experienced during transitions throughout medical training and to empower a sense of agency to support identity work., (© 2022 Association for the Study of Medical Education and John Wiley & Sons Ltd.)

Maternal mortality continues to be an issue globally despite advances in technology and pharmacotherapy. Pregnancy can lead to complications that necessitate immediate action to prevent severe morbidity and mortality. Patients may need escalation to the ICU setting for close monitoring and administration of advanced therapies not available elsewhere. Obstetric emergencies are rare but high-stakes events that require clinicians to have prompt identification and management. The purpose of this review is to describe complications of pregnancy and provide a focused resource of pharmacotherapy considerations that clinicians may encounter. For each disease state, the epidemiology, pathophysiology, and management are summarized. Brief descriptions of non-pharmacological (e.g., cesarean or vaginal delivery of the baby) interventions are provided. Mainstays of pharmacotherapy highlighted include oxytocin for obstetric hemorrhage, methotrexate for ectopic pregnancy, magnesium and antihypertensive agents for preeclampsia and eclampsia, eculizumab for atypical hemolytic uremic syndrome, corticosteroids, and immunosuppressive agents for thrombotic thrombocytopenic purpura, diuretics, metoprolol, and anticoagulation for peripartum cardiomyopathy, and pulmonary vasodilators for amniotic fluid embolism., (© 2023 Pharmacotherapy Publications, Inc.)

Safe and thoughtful medication management of pregnant patients requiring intensive care unit (ICU) level of care is key to optimizing outcomes for both mother and fetus. Pregnancy induces physiologic alterations that closely mirror the changes expected in a critically ill patient. These changes can be predictable depending on the gestational age and trimester and will directly impact the pharmacokinetic profile of medications commonly used in the ICU; examples include decreased gastric emptying, increased blood and plasma volume, increased glomerular filtration, and increased cardiac output. When pregnant patients require ICU care, the resulting impact on drug absorption, distribution, metabolism, and elimination can be difficult to predict. In addition, there are many nuances of medication metabolism and interface with the placental barrier that should be considered when selecting pharmacotherapy for the pregnant patient. Critical care clinicians need to be aware of medication interactions with the placenta and weigh the risk versus benefit profile of medication use in this patient population. Obstetric critical care admissions have increased over the years, especially during the coronavirus waves. Therefore, understanding the interplay between pregnancy and critical illness to optimize pharmacotherapy selection is crucial to improving health outcomes of mother and fetus. This review highlights pharmacotherapy considerations in the pregnant ICU patient for the following topics: physiologic alterations, categorizing medication risk, supportive care, sepsis, cardiogenic shock, acute respiratory distress syndrome, and venous thromboembolism., (© 2023 Pharmacotherapy Publications, Inc.)

Context: Non-technical skills (NTS) training should be incorporated into medical students' education and simulation-based approaches are often utilised to facilitate this. Such experiences have the potential to foster transformative learning by facilitating a reassessment of one's prior assumptions and a significant shift in one's outlook, referred to as the process of perspective transformation. The aim of this research was to explore how NTS training might facilitate transformative learning in final-year medical students., Methods: Following ethical approval, medical student volunteers from four medical schools (Aberdeen, Dundee, Edinburgh and Glasgow) participated in simulation sessions, were debriefed with an emphasis on NTS using a behavioural marker system and then took part in focus groups. Focus group discussions were semi-structured and questions were based on the phases of perspective transformation identified by Jack Mezirow. Focus group discussions were audiorecorded, transcribed verbatim, anonymised and analysed using template analysis., Results: A total of 33 medical students took part in five focus groups. There was evidence of the following stages of perspective transformation: Phase 2 (self-examination with emotional disturbance, including fear, anxiety, guilt, shame and frustration); Phase 3 (critical assessment of assumptions, including the undervaluing of NTS, recognising that technical skills alone are insufficient, and recognising that it is possible to improve one's NTS); Phase 5 (exploring options for new roles, relationships and actions), and Phase 6 (planning a course of action for future simulations, as a medical student and as a doctor)., Conclusions: This study deepens our understanding of how exposure to NTS training in simulation-based education influences the learning of medical students and shows that such exposure can result in the cognitive phases of transformative learning. It provides us with valuable insights into medical students' perspectives on their learning of NTS at a pivotal stage in training and represents an interesting way of assessing the educational impact of such sessions., (© 2020 John Wiley & Sons Ltd and The Association for the Study of Medical Education.)

The appropriate level of sedation in patients with an open abdomen following damage control laparotomy (DCL) is debated. Chemical paralysis with neuromuscular blocking agents (NMBAs) has been used to decrease time to abdominal closure. We sought to evaluate the effect of NMBA use on sedation requirements in patients with an open abdomen and to determine the effect of sedation on patient outcomes. A retrospective cohort study was conducted at an American College of Surgeons' verified level 1 trauma center. Adult trauma patients who underwent DCL between 2009 and 2015 were included. Patients with an intensive care unit length of stay of less than 48 hours and those who died before abdominal closure were excluded. The NMBA+ group received continuous NMBA within 24 hours of DCL; the NMBA- group did not. The primary outcome was cumulative sedation dose during the 7 days following DCL. Secondary outcomes included Richmond Agitation-Sedation Scale (RASS) score, mechanical ventilation-free days, and delirium-coma-free days. Delirium-coma-free days were analyzed with linear regression. A total of 222 patients were included (NMBA+ 125; NMBA- 97). Demographics were similar between groups including age, Injury Severity Score, and mechanism of injury. The median time to closure in the overall cohort was 2 days (interquartile range [IQR] 1-2 days). Propofol and fentanyl were the primary sedatives used. The NMBA+ group received higher cumulative doses of propofol (NMBA+ 5405 mg, IQR 3103-10,573 mg; NMBA- 3601 mg, IQR 1605-6887 mg; p=0.007), but not of fentanyl. Time to abdominal closure, but not NMBA use, was associated with a higher cumulative propofol dose on multivariate analysis. The NMBA+ group had significantly lower RASS scores on the first 3 days following DCL. Mechanical ventilation-free days (NMBA+ 20 days vs NMBA- 18 days, p=0.960) and delirium-coma-free days (NMBA+ 18 days vs NMBA- 18 days, p=0.610) were similar between the groups. On linear regression, cumulative propofol dose was associated with fewer delirium-coma-free days (β-coefficient -0.007, 95% confidence interval -0.015 to -0.003). In trauma patients managed with DCL, higher cumulative sedative doses were administered in patients who received adjunctive NMBA, although NMBA therapy was not associated with a higher cumulative propofol dose on multivariate analysis. Consideration must be given to the potential effect of sedation on delirium and awakening following DCL., (© 2019 Pharmacotherapy Publications, Inc.)

Latent transforming growth factor binding proteins (LTBP) are a family of extracellular matrix glycoproteins that play an important role in the regulation of transforming growth factor beta (TGF-ß) activation. Dysregulation of the TGF-ß pathway has been implicated in the pathogenesis of inherited disorders predisposing to thoracic aortic aneurysms syndromes (TAAS) including Marfan syndrome (MFS; FBN1) and Loeys-Dietz syndrome (LDS; TGFBR1, TGFBR2, TGFB2, TGFB3, SMAD2, SMAD3). While these syndromes have distinct clinical criteria, they share clinical features including aortic root dilation and musculoskeletal findings. LTBP1 is a component of the TGF-ß pathway that binds to fibrillin-1 in the extracellular matrix rendering TGF-ß inactive. We describe a three-generation family case series with a heterozygous ∼5.1 Mb novel contiguous gene deletion of chromosome 2p22.3-p22.2 involving 11 genes, including LTBP1. The deletion has been identified in the proband, father and grandfather, who all have a phenotype consistent with a TAAS. Findings include thoracic aortic dilation, ptosis, malar hypoplasia, high arched palate, retrognathia, pes planus, hindfoot deformity, obstructive sleep apnea, and low truncal tone during childhood with joint laxity that progressed to reduced joint mobility over time. While the three affected individuals did not meet criteria for either MFS or LDS, they shared features of both. Although the deletion includes 11 genes, given the relationship between LTBP1, TGF-ß, and fibrillin-1, LTBP1 stands out as one of the possible candidate genes for the clinical syndrome observed in this family. More studies are necessary to evaluate the potential role of LTBP1 in the pathophysiology of TAAS., (© 2018 Wiley Periodicals, Inc.)

Study Objectives: The primary objective was to determine the impact of hematologic malignancies and/or conditioning regimens on the risk of developing Clostridium difficile infection (CDI) in patients undergoing hematopoietic stem cell transplantation (HSCT). Secondary objectives were to determine if traditional CDI risk factors applied to patients undergoing HSCT and to determine the presence of CDI markers of severity of illness among this patient population., Design: Single-center retrospective case-control study., Setting: Quaternary care academic medical center., Patients: A total of 105 patients who underwent HSCT between December 2009 and December 2014; of these patients, 35 developed an initial episode of CDI (HSCT/CDI group [cases]), and 70 did not (controls). Controls were matched in a 2:1 ratio to cases based on age (± 10 yrs) and date of HSCT (± 6 mo)., Measurements and Main Results: Baseline characteristics of the two groups were well balanced regarding age, sex, race, ethnicity, and type of HSCT. No significant differences in conditioning regimen, hematologic malignancy, total body irradiation received for HSCT, use of antibiotics within 60 days of HSCT, or use of prophylactic antibiotics after HSCT were noted between the two groups. Patients in the control group were 10.57 (95% confidence interval 1.24-492.75) more likely to have received corticosteroids prior to HSCT than patients in the HSCT/CDI group (p=0.01). Use of proton pump inhibitors at the time of HSCT was greater among the control group than among patients in the HSCT/CDI group (97% vs 86%, p=0.048). No significant difference in mortality was noted between the groups at 3, 6, and 12 months after HSCT. Metronidazole was frequently prescribed for patients in the HSCT/CDI group (34 patients [97%]). Severe CDI was not common among patients within the HSCT/CDI group (13 patients [37%]); vancomycin was infrequently prescribed for these patients ([31%] 4/13 patients)., Conclusion: Hematologic malignancies and a conditioning regimen administered for HSCT were not significant risk factors for the development of CDI after HSCT. Use of corticosteroids prior to HSCT and use of proton pump inhibitors at the time of HSCT were associated with a significantly decreased risk of CDI., (© 2017 Pharmacotherapy Publications, Inc.)

Rearrangement of MYC is associated with a poor prognosis in patients with diffuse large B cell lymphoma (DLBCL) and B cell lymphoma unclassifiable (BCLU), particularly in the setting of double hit lymphoma (DHL). However, little is known about outcomes of patients who demonstrate MYC rearrangement without evidence of BCL2 or BCL6 rearrangement (single hit) or amplification (>4 copies) of MYC. We identified 87 patients with single hit lymphoma (SHL), 22 patients with MYC-amplified lymphoma (MYC amp) as well as 127 DLBCL patients without MYC rearrangement or amplification (MYC normal) and 45 patients with DHL, all treated with either R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) or intensive induction therapy. For SHL and MYC amp patients, the 2-year progression-free survival rate (PFS) was 49% and 48% and 2-year overall survival rate (OS) was 59% and 71%, respectively. SHL patients receiving intensive induction experienced higher 2-year PFS (59% vs. 23%, P = 0·006) but similar 2-year OS as compared with SHL patients receiving R-CHOP. SHL DLBCL patients treated with R-CHOP, but not intensive induction, experienced significantly lower 2-year PFS and OS (P < 0·001 for both) when compared with MYC normal patients. SHL patients appear to have a poor prognosis, which may be improved with receipt of intensive induction., Competing Interests: The authors have declared no conflicts of interest., (© 2016 John Wiley & Sons Ltd.)

Context: Previous research has suggested that as medical students become more senior, they should increasingly take on the roles they will enact as newly qualified doctors by contributing to patient care. However, student contribution to patient care carries inherent risks to patient safety. This study aimed to provide students with a new opportunity to contribute to patient care and to use this as a platform from which to explore the influence of contributing to patient care on medical student learning., Methods: This study took place in the context of final-year medical student prescribing education at the University of Edinburgh, Edinburgh, UK. Students on attachment at a district general hospital were afforded a unique opportunity to learn prescribing by completing in-patient drug charts in a process termed 'pre-prescribing'. All students were invited to participate in focus groups conducted by the principal researcher. Focus group discussions were audio-recorded, transcribed verbatim and thematically analysed., Results: Six focus groups, each lasting 20-50 minutes, were conducted with four to seven participants (33 students in total). The emerging themes took the form of developmental outcomes and learning processes. Developmental outcomes included ability to perform the task, modification of attitudes towards the task, formation of a professional identity, and development of relationships within the team. The central feature of the experience which influenced all developmental outcomes, was making mistakes. The themes interact in complex ways and all contribute towards development as a professional., Conclusions: This study has demonstrated that contributing to patient care enhances students' development as professionals. Some of these developmental outcomes, such as improvements in knowledge and skills, may be achievable to some extent within the classroom. Other changes, such as developing relationships, forming a sense of professional identity and modifying attitudes, might arguably be achievable only within the context of contributing to patient care., (© 2013 John Wiley & Sons Ltd.)

Norrie disease (ND) is an X-linked recessive disorder characterized by congenital blindness, progressive sensorineural hearing loss and cognitive impairment. The ocular phenotype has been well described, while the extraocular manifestations of the disorder are not well understood. We present the data from the Norrie Disease Registry, which consists of 56 patients with detailed clinical histories and genotype data. This study represents the largest, detailed investigation into the phenotypic spectrum of ND to date and more importantly expands knowledge of the extraocular clinical manifestations. We identify several novel aspects of the syndrome that will improve the management of these patients. In particular, we expand our understanding of the neurologic manifestations in ND and identify a chronic seizure disorder in approximately 10% of all patients. In addition, details of the hearing phenotype are described including the median age of onset (12 years of age) and how genotype affects onset. Moreover, we find vascular disease to be a significant component of ND; and vascular health should be, in the future, a component of patient clinical care. In summary, the results expand our understanding of the phenotypic variability and genotypic heterogeneity in ND patients., (Copyright © 2012 Wiley Periodicals, Inc.)

Various workplace-based assessment tools are available, but none have been shown to improve performance in procedural skills. This study aimed to assess the impact of using one such tool, cumulative sum charts, on procedural skill ability. A single-blind randomised controlled trial was conducted on 82 final year medical students. Control group students received the usual teaching; in addition to this, intervention group students were provided with cumulative sum charts to log their cannulation attempts over a 7-month period. At the end of the year, students from both groups undertook a validated test of automaticity of cannulation skill. Students in the intervention group obtained median (IQR [range]) scores of 68.2 (60.5-74.3 [42.7-81.1]) vs 62.2 (52.2-68.8 [40.7-80.5]) for the control group (p = 0.013). The effect size was moderate (Cohen's d = 0.608). This study therefore provides support for the hypothesis that use of cumulative sum charts improves performance when learning procedural skills., (Anaesthesia © 2012 The Association of Anaesthetists of Great Britain and Ireland.)

Context: A particularly onerous aspect of the transition from medical student to practising doctor concerns the necessity to be able to rapidly identify acutely unwell patients and initiate appropriate resuscitation. These are skills in which many graduates feel poorly prepared and are considered by some to be best learned on the job. This constructivist study investigated the factors that influence the behaviour of junior doctors in this context and initiated the development of a framework that promotes understanding of this important area., Methods: Focus groups involving 36 clinicians with a variety of clinical experience were conducted and analysed using a qualitative, grounded theory approach. The complex relationships between emergent themes guided the development of a framework that was refined and validated by further interviews with participants., Results: Six main themes, grouped under three broad headings, emerged from the data: 'transferring knowledge into practice' and 'decision making and uncertainty' (cognitive challenges); 'acts and omissions' and 'identity and expectations' (roles and responsibilities), and, finally, 'the medical hierarchy' and 'performing under stress' (environmental factors). The framework presented within this paper illustrates the complex relationships between these factors., Conclusions: Although the potential of metacognitive strategies to reduce medical error is acknowledged, the framework promotes looking beyond the individual to consider the contributions to patient safety of identity issues, role uncertainty and the hierarchical clinical environment. A more distributed approach to situation awareness may help junior doctors to better tolerate complexity and uncertainty. The efficacy of simulation as an educational strategy may be improved by finding ways to recreate the hierarchical and stressful environment in which junior doctors practise. Junior doctors should be aware of the impact of affect and emotion on behaviour, and clinical supervisors should strive to ensure that roles and responsibilities are explicitly discussed., (© Blackwell Publishing Ltd 2011.)

Problem: Are the effects of ruminant trophoblast interferon-tau (IFN-tau) on uterine prostaglandin (PG) secretion a specific action of this cytokine and what are the effects of IFN-tau on expression of uterine genes not generally associated with pregnancy maintenance?, Methods: The effects of IFN-tau and IFN-alpha on bovine uterine explant and epithelial cell production of PGF2 alpha and PGE2 were determined in the presence and absence of oxytocin (OT). The effects of intrauterine administration of IFN-tau were determined on uterine expression of retinol-binding protein (RBP) and transforming growth factor-beta (TGF-beta) isoforms., Results: IFN-tau attenuated uterine endometrial secretion of PGF2 alpha and PGE2 in vitro and diminish PG stimulation by OT. IFN-tau and IFN-alpha were observed to be equipotent. Intrauterine infusion of IFN-tau resulted in a significant decrease in steady-state RBP mRNA levels and expression of TGF-beta 1, 2, and 3 mRNA levels were lowest in IFN-tau treated animals., Conclusion: Negative regulation of gene expression may be a general strategy in IFN activity. This may explain the similar activities of IFN-tau and IFN-alpha on a broad variety of cell types, including ruminant uterine endometrium.

1 Mydriatic and cycloplegic effects of tropicamide in the normal and in the guanethidine-treated human eye have been recorded following prolonged exposure of the eye to drug solutions. 2 Marked effects and satisfactory dose-response relationships were observed at drug concentrations within the range 1.25-40 μg/ml, by comparison with concentrations of 5-10 mg/ml usually applied as eye-drops. 3 The findings are discussed in relation to drug concentrations which produce cholinergic antagonism in vitro.

1. Television pupillometry was used to measure the effect of six topically applied cholinomimetic drugs on the resting diameter and light reflex amplitude of the human pupil. Drug potency was obtained from dose response curves. 2. The tertiary amines arecoline, aceclidine and pilocarpine were considerably more effective miotics than the choline esters carbachol, methacholine and acetylcholine. 3. All the drugs which caused miosis also reduced light reflex amplitude proportionally. 4. The in vitro potency of these drugs was also measured on preparations of rabbit iris sphincter and guinea pig ileum. 5. Dose response relationships for pilocarpine in man and in vitro showed evidence of partial agonist activity on the rabbit iris only. 6. A comparison of the in vivo and in vitro results showed that three factors influenced the potency of topically applied miotics: accessibility to the iris; sensitivity to cholinesterase; and cholinoceptor agonist potency.

1 Plasma drug concentrations in eight volunteer subjects following oral administration of six preparations of paracetamol have been studied. 2 Significant interindividual differences in plasma paracetamol concentration were found within 1 h but there were no consistent differences between the different drug preparations. The results indicate that all the preparations have equivalent bioavailability. 3 In four subjects, tested with the same preparation on two occasions, the findings suggest that drug absorption may differ from one occasion to another.