"Important but risky": attitudes of global thought leaders towards cost and value research in health professions education.

Studies of cost and value can inform educational decision making, yet our understanding of the barriers to such research is incomplete. To address this gap, our aim was to explore the attitudes of global thought leaders in HPE towards cost and value research. This was a qualitative virtual interview study underpinned by social constructionism. In telephone or videoconference interviews in 2018-2019, we asked global healthcare professional thought leaders their views regarding HPE cost and value research, outstanding research questions in this area and why addressing these questions was important. Analysis was inductive and thematic, and incorporated review and comments from the original interviewees (member checking). We interviewed 11 thought leaders, nine of whom gave later feedback on our data interpretation (member checking). We identified four themes: Cost research is really important but potentially risky (quantifying and reporting costs provides evidence for decision-making but could lead to increased accountability and loss of autonomy); I don't have the knowledge and skills (lack of economic literacy); it's not what I went into education research to do (professional identity); and it's difficult to generate generalizable findings (the importance of context). This study contributes to a wider conversation in the literature about cost and value research by bringing in the views of global HPE thought leaders. Our findings provide insight to inform how best to engage and empower educators and researchers in the processes of asking and answering meaningful, acceptable and relevant cost and value questions in HPE.

AMEE Guide No. 123 - How to read studies of educational costs.

Healthcare and health professions education share many of the same problems in decision making. In both cases, there is a finite amount of resources, and so choices need to be made between alternatives. To navigate the options available requires effective decision making. Choosing one option requires consideration of its opportunity cost - the benefit forgone of the other competing options. The purpose of this abridged AMEE guide is to introduce educational decision-makers to the economic concept of cost, and how to read studies about educational costs to inform effective cost-conscious decision-making. This guide leads with a brief review of study designs commonly utilized in this field of research, followed by an overview of how study findings are commonly presented. The tutorial will then offer a four-step model for appraising and considering the results of an economic evaluation. It asks the questions: (1) Can I trust the results? (2) What are the results telling me? (3) Could the results be transferred to my context? (4) Should I change my practice?

Electrodeposition from supercritical fluids.

Recent studies have shown that it is possible to electrodeposit a range of materials, such as Cu, Ag and Ge, from various supercritical fluids, including hydrofluorocarbons and mixtures of CO2 with suitable co-solvents. In this perspective we discuss the relatively new field of electrodeposition from supercritical fluids. The perspective focuses on some of the underlying physical chemistry and covers both practical and scientific aspects of electrodeposition from supercritical fluids. We also discuss possible applications for supercritical fluid electrodeposition and suggest some key developments that are required to take the field to the next stage.

Simulation-based training in anaesthesiology: a systematic review and meta-analysis.

Simulation has long been integrated in anaesthesiology training, yet a comprehensive review of its effectiveness is presently lacking. Using meta-analysis and critical narrative analysis, we synthesized the evidence for the effectiveness of simulation-based anaesthesiology training. We searched MEDLINE, ERIC, and SCOPUS through May 2011 and included studies using simulation to train health professional learners. Data were abstracted independently and in duplicate. We included 77 studies (6066 participants). Compared with no intervention (52 studies), simulation was associated with moderate to large pooled effect sizes (ESs) for all outcomes (ES range 0.60-1.05) except for patient effects (ES -0.39). Compared with non-simulation instruction (11 studies), simulation was associated with moderate effects for satisfaction and skills (ES 0.39 and 0.42, respectively), large effect for behaviours (1.77), and small effects for time, knowledge, and patient effects (-0.18 to 0.23). In 17 studies comparing alternative simulation interventions, training in non-technical skills (e.g. communication) and medical management compared with training in medical management alone was associated with negligible effects for knowledge and skills (four studies, ES range 0.14-0.15). Debriefing using multiple vs single information sources was associated with negligible effects for time and skills (three studies, ES range -0.07 to 0.09). Our critical analysis showed inconsistency in measurement of non-technical skills and consistency in the (ineffective) design of debriefing. Simulation in anaesthesiology appears to be more effective than no intervention (except for patient outcomes) and non-inferior to non-simulation instruction. Few studies have clarified the key instructional designs for simulation-based anaesthesiology training.

Simulation training for breast and pelvic physical examination: a systematic review and meta-analysis.

BACKGROUND: Breast and pelvic examinations are challenging intimate examinations. Technology-based simulation may help to overcome these challenges. OBJECTIVE: To synthesise the evidence regarding the effectiveness of technology-based simulation training for breast and pelvic examination. SEARCH STRATEGY: Our systematic search included MEDLINE, EMBASE, CINAHL, PsychINFO, Scopus, and key journals and review articles; the date of the last search was January 2012. SELECTION CRITERIA: Original research studies evaluating technology-enhanced simulation of breast and pelvic examination to teach learners, compared with no intervention or with other educational activities. DATA COLLECTION AND ANALYSIS: The reviewers evaluated study eligibility and abstracted data on methodological quality, learners, instructional design, and outcomes, and used random-effects models to pool weighted effect sizes. MAIN RESULTS: In total, 11 272 articles were identified for screening, and 22 studies were eligible, enrolling 2036 trainees. In eight studies comparing simulation for breast examination training with no intervention, simulation was associated with a significant improvement in skill, with a pooled effect size of 0.86 (95% CI 0.52-1.19; P < 0.001). Four studies comparing simulation training for pelvic examination with no intervention had a large and significant benefit, with a pooled effect size of 1.18 (95% CI 0.40-1.96; P = 0.003). Among breast examination simulation studies, dynamic models providing feedback were associated with improved outcomes. In pelvic examination simulation studies, the addition of a standardised patient to the simulation model and the use of an electronic model with enhanced feedback improved outcomes. AUTHOR'S CONCLUSIONS: In comparison with no intervention, breast and pelvic examination simulation training is associated with moderate to large effects for skills outcomes. Enhanced feedback appears to improve learning.

Cricoid pressure training using simulation: a systematic review and meta-analysis.

Cricoid pressure (CP) is commonly applied during rapid sequence intubation and may be protective during induction of anaesthesia; however, CP application by untrained practitioners may not be performed optimally. The objective of this systematic review was to synthesize the evidence regarding effectiveness of technology-enhanced simulation training to improve efficacy of CP application. Electronic databases from inception through May 11, 2011 were searched. Eligible studies evaluated CP simulation training. Independent reviewers working in duplicate extracted study characteristics, validity, and outcomes data. Pooled effect size (ES) with 95% confidence intervals (CIs) were estimated from each study that compared technology-enhanced simulation with no intervention or with other methods of CP training using random-effects model. Twelve studies (772 trainees) evaluated CP training as an outcome. Nine studies reported information on baseline skill, with 23% of providers being able to achieve the target CP before training. In a meta-analysis of 10 studies (570 trainees), CP training resulted in a large favourable impact on skills among trainees compared with no intervention (pooled ES 1.18; 95% CI 0.85-1.51; P<0.0001). Four studies found evidence of skills retention for CP application after training, but for a limited time (<4 weeks). Comparative effectiveness research shows beneficial effects to force feedback training over training without feedback. Simulation training significantly improves the efficacy of CP application. Future studies might evaluate the clinical impact of training on CP application during rapid sequence intubation, and the comparative effectiveness of different training approaches.

Primary cervical cancer screening with HPV testing compared with liquid-based cytology: results of round 1 of a randomised controlled trial -- the HPV FOCAL Study.

BACKGROUND: Round 1 data of human papillomavirus (HPV) FOCAL, a three-arm, randomised trial, which aims to establish the efficacy of HPV DNA testing as a primary screen for cervical cancer, are presented. METHODS: The three arms are: Control arm - liquid based cytology with atypical squamous cells of unknown significance (ASC-US) triage with hrHPV testing; Intervention Arm - hrHPV at entry with liquid-based cytology (LBC) triage of hrHPV positives, with exit screen at 4 years; Safety check arm - hrHPV at entry with LBC triage of hrHPV positives with exit screen at 2 years. RESULTS: A total of 6154 women were randomised to the control arm and 12 494 to the HPV arms (intervention and safety check). In the HPV arm, the baseline cervical intraepithelial neoplasia (CIN)2+ and CIN3+ rate was 9.2/1000 (95%CI; 7.4, 10.9) and 4.8/1000 (95%CI; 3.6, 6.1), which increased to 16.1/1000 (95%CI 13.2, 18.9) for CIN2+ and to 8.0/1000 (95%CI; 5.9, 10.0) for CIN3+ after subsequent screening of HPV-DNA-positive/cytology-negative women. Detection rate in the control arm remained unchanged after subsequent screening of ASC-US-positive/hrHPV DNA-negative women at 11.0/1000 for CIN2+ and 5.0/1000 for CIN3+. CONCLUSION: After subsequent screening of women who were either hrHPV positive/cytology negative or ASC-US positive/HPV negative, women randomised to the HPV arms had increased CIN2+ detection compared with women randomised to the cytology arm.

Targeting acute ischemic stroke with a calcium-sensitive opener of maxi-K potassium channels.

During ischemic stroke, neurons at risk are exposed to pathologically high levels of intracellular calcium (Ca++), initiating a fatal biochemical cascade. To protect these neurons, we have developed openers of large-conductance, Ca++-activated (maxi-K or BK) potassium channels, thereby augmenting an endogenous mechanism for regulating Ca++ entry and membrane potential. The novel fluoro-oxindoles BMS-204352 and racemic compound 1 are potent, effective and uniquely Ca++-sensitive openers of maxi-K channels. In rat models of permanent large-vessel stroke, BMS-204352 provided significant levels of cortical neuroprotection when administered two hours after the onset of occlusion, but had no effects on blood pressure or cerebral blood flow. This novel approach may restrict Ca++ entry in neurons at risk while having minimal side effects.

Audit of ten years of donation after circulatory death experience in Queensland: observations of agonal physiology following withdrawal of cardiorespiratory support.

An audit of ten years' experience in all patients undergoing withdrawal of cardiorespiratory support (WCRS) in the context of donation after circulatory death (DCD) was conducted in Queensland, Australia (2008 to 2017). One hundred and seventy-one patients proceeded to donation after declaration of death by circulatory criteria with loss of pulsatile arterial blood pressure (circulatory arrest) for five minutes. The demographics, times and haemodynamic observations were abstracted, de-identified and collated. The average age of patients was 43 years (standard deviation 16.1 years) and 63% were male. The median and mean times to an agonal systolic blood pressure below 50 mmHg were 10 and 11 minutes and the median and mean times from WCRS to circulatory arrest were 14 and 16 minutes. After systolic blood pressure fell to 50 mmHg or lower, 33 patients (19.3%) had spontaneous return of systolic pressure to above 50 mmHg. Following periods of circulatory arrest, five patients were documented to have spontaneous return of pulsatile arterial pressure. Two patients had return of circulation after two minutes, but less than five minutes of circulatory arrest and three patients had return of circulation where circulatory arrest had been documented for less than two minutes. Following WCRS, transient restoration of circulation following circulatory arrest may occur, even following two minutes of circulatory asystole, albeit rarely.

LRRK2 levels in immune cells are increased in Parkinson's disease.

Mutations associated with leucine-rich repeat kinase 2 are the most common known cause of Parkinson's disease. The known expression of leucine-rich repeat kinase 2 in immune cells and its negative regulatory function of nuclear factor of activated T cells implicates leucine-rich repeat kinase 2 in the development of the inflammatory environment characteristic of Parkinson's disease. The aim of this study was to determine the expression pattern of leucine-rich repeat kinase 2 in immune cell subsets and correlate it with the immunophenotype of cells from Parkinson's disease and healthy subjects. For immunophenotyping, blood cells from 40 Parkinson's disease patients and 32 age and environment matched-healthy control subjects were analyzed by flow cytometry. Multiplexed immunoassays were used to measure cytokine output of stimulated cells. Leucine-rich repeat kinase 2 expression was increased in B cells (p = 0.0095), T cells (p = 0.029), and CD16+ monocytes (p = 0.01) of Parkinson's disease patients compared to healthy controls. Leucine-rich repeat kinase 2 induction was also increased in monocytes and dividing T cells in Parkinson's disease patients compared to healthy controls. In addition, Parkinson's disease patient monocytes secreted more inflammatory cytokines compared to healthy control, and cytokine expression positively correlated with leucine-rich repeat kinase 2 expression in T cells from Parkinson's disease but not healthy controls. Finally, the regulatory surface protein that limits T-cell activation signals, CTLA-4 (cytotoxic T-lymphocyte-associated protein 4), was decreased in Parkinson's disease compared to HC in T cells (p = 0.029). In sum, these findings suggest that leucine-rich repeat kinase 2 has a regulatory role in immune cells and Parkinson's disease. Functionally, the positive correlations between leucine-rich repeat kinase 2 expression levels in T-cell subsets, cytokine expression and secretion, and T-cell activation states suggest that targeting leucine-rich repeat kinase 2 with therapeutic interventions could have direct effects on immune cell function.

Mechanisms of cerebral vasospasm in subarachnoid haemorrhage.

Cerebrovascular spasm is a slowly developing constriction of the cerebral arteries, which frequently follows subarachnoid haemorrhage and is associated with considerable morbidity and mortality. The condition has been studied by use of models of subarachnoid haemorrhage in the whole animal and examination of isolated blood vessels or vascular smooth muscle cells in culture. The condition probably arises from the action of haemoglobin released from erythrocytes trapped in the subarachnoid clots, although the mechanism of action of haemoglobin remains uncertain. Systemic pharmacotherapy to avert or reverse vasospasm is still experimental.

Clinical effects of the use of a bipolar vessel sealing device for soft palate resection and tonsillectomy in dogs, with histological assessment of resected tonsillar tissue.

OBJECTIVE: To investigate whether soft palate resection and tonsillectomy with a bipolar vessel sealing device (BVSD) improves clinical respiratory score. To document histopathological changes to tonsillar tissue following removal with a BVSD. METHODS & RESULTS: Case series of 22 dogs with clinical signs of upper respiratory obstruction related to brachycephalic airway syndrome. Soft palate and tonsils were removed using a BVSD. Alarplasty and saccullectomy were also performed if indicated. A clinical respiratory score was assigned preoperatively, 24-h postoperatively and 5 weeks postoperatively. Excised tonsillar samples were measured and then assessed histologically for depth of tissue damage deemed to be caused by the device. Depth of tissue damage was compared between two power settings of the device. Soft palate resection and tonsillectomy with a BVSD lead to a significant improvement in respiratory scores following surgery. Depth of tissue damage was significantly less for power setting 1 compared with power setting 2. Using power setting 1, median calculated depth of tonsillar tissue damage was 3.4 mm (range 1.2-8.0). One dog experienced major complications. CONCLUSION: Soft palate resection and tonsillectomy with a BVSD led to significant improvement in clinical respiratory score.

Balloon occlusion of the caudal vena cava for vascular contrast studies as an aid to intravascular coil embolisation for the treatment of intrahepatic portosystemic shunts in three dogs.

CASE REPORT: Three dogs were treated with fluoroscopically guided coil embolisation of intrahepatic portosystemic shunts. A large-diameter vascular occlusion balloon was used to improve the vascular contrast studies required to perform this procedure. This technique improved identification of vascular structures and allowed completion of the procedures without the need for digital subtraction angiography. CLINICAL SIGNIFICANCE: Interventional radiological procedures are an emerging area of veterinary medicine and procedural modifications may help expand their use in clinical practice.

Common Genetic Variant Association with Altered HLA Expression, Synergy with Pyrethroid Exposure, and Risk for Parkinson's Disease: An Observational and Case-Control Study.

BACKGROUND/OBJECTIVES: The common non-coding single nucleotide polymorphism (SNP) rs3129882 in HLA-DRA is associated with risk for idiopathic Parkinson's disease (PD). The location of the SNP in the major histocompatibility complex class II (MHC-II) locus implicates regulation of antigen presentation as a potential mechanism by which immune responses link genetic susceptibility to environmental factors in conferring lifetime risk for PD. METHODS: For immunophenotyping, blood cells from 81 subjects were analyzed by qRT-PCR and flow cytometry. A case-control study was performed on a separate cohort of 962 subjects to determine association of pesticide exposure and the SNP with risk of PD. RESULTS: Homozygosity for G at this SNP was associated with heightened baseline expression and inducibility of MHC class II molecules in B cells and monocytes from peripheral blood of healthy controls and PD patients. In addition, exposure to a commonly used class of insecticide, pyrethroids, synergized with the risk conferred by this SNP (OR = 2.48, p = 0.007), thereby identifying a novel gene-environment interaction that promotes risk for PD via alterations in immune responses. CONCLUSIONS: In sum, these novel findings suggest that the MHC-II locus may increase susceptibility to PD through presentation of pathogenic, immunodominant antigens and/or a shift toward a more pro-inflammatory CD4+ T cell response in response to specific environmental exposures, such as pyrethroid exposure through genetic or epigenetic mechanisms that modulate MHC-II gene expression.

Fecal characteristics in healthy young adults consuming defined liquid diets or a free-choice diet.

Fat and nitrogen absorption and fecal characteristics were studied in 10 healthy, young adults who ingested a free-choice diet for 12 days and then isocaloric amounts of one of two nutritionally complete liquid defined formula diets during a succeeding 12-day period. Apparent fat absorption was 98 to 99% of intake with both defined formula diets and 95% of intake on the free-choice diet. Nitrogen digestibility was determined during the liquid diet period, and averaged 95 to 98% of intake. There were no statistically significant differences between the liquid diets and the free-choice diets with respect to fecal wet or dry weight, transit time, or stool frequency. Individual stool weights averaged 83 to 96 g on the free-choice or liquid formula diets and were comparable to other values reported in the literature. These results support the theory that a critical volume of feces must accumulate in the colon before defecation occurs, regardless of diet composition.

Method for assessing food intakes in terms of servings based on food guidance.

We describe a method for comparing food intakes reported in surveys with recommendations given in the US Department of Agriculture's food guide pyramid. Such comparison was previously difficult because many foods are eaten as mixtures that cannot be categorized into pyramid food groups and because food intake data and food recommendations are expressed in different units of measurement. We developed a recipe file showing ingredients at multiple levels of breakdown and used it to disaggregate food mixtures into their ingredients so that they could be placed into pyramid food groups. Food-specific weight consistent with the pyramid definitions for serving sizes were derived from the food code book of the 1989-1991 Continuing Survey of Food Intakes by Individuals and used to develop a serving-weight file. Data collected from 8181 adults aged > or = 20 y in the survey were used to estimate the mean number of servings from pyramid food groups and percentages of the population meeting pyramid recommendations. The mean numbers of servings were close to the minimum recommendations for the grain, vegetable, and meat groups and well below the minimum recommendations for the fruit and dairy groups. large proportions of adults (43-72%) failed to meet the dietary recommendations. Our method has several nutrition monitoring and nutrition education applications.

Characterizing food intake patterns of American adults.

Food-pattern analysis provides a way to examine diets in a multidimensional context. This study examined the diets of 8181 adults in the 1989-1991 Continuing Survey of Food Intakes by Individuals and evaluated whether they met the federal recommendations for each of five food groups. The sample was partitioned among 32 different food-intake patterns, six of which represented 44% of the population. Nutrient profiles associated with each of the patterns indicated that failure to meet one or more of the food-group recommendations was associated with nutrient inadequacy, macronutrient imbalance, or both. A reexamination of the data to account for low energy reporters did not alter these findings. The pattern of meeting all five of the food-group recommendations was among the least common, accounting for only 1% of adults' intakes.

Blockade by phenoxybenzamine of the contractor response produced by agonists in the isolated ileum of the guinea-pig.

1. The effects of various concentrations of phenoxybenzamine (dibenzyline) on the contractor response of the isolated ileum of the guinea-pig were investigated. The agonists tested were histamine, 5-hydroxytryptamine (5-HT), acetycholine and potassium chloride.2. In addition, uptake of (14)C-phenoxybenzamine into the ileum was determined as a function of antagonist concentration. The uptake increases sharply at concentrations above 10(-6) g/ml, (3x10(-6)M) and was not saturable at any concentration tested.3. In the presence of low concentrations of phenoxybenzamine, the dose-response curve for histamine undergoes a parallel shift of about 0.5 log units. At higher concentrations of phenoxybenzamine the maximum response is depressed. In the case of the other agonists, the maximum response is depressed as soon as any blockade becomes apparent.4. The ease of blockade with phenoxybenzamine is 5-HT >/= histamine>> acetylcholine >/= potassium chloride.5. These results do not lend support to the ;spare-receptor' hypothesis and may be better explained by the ;two-site' hypothesis of Moran & Triggle (1970).6. It may further be concluded that the successful antagonism of potassium-induced contractions in this preparation lies in the ability of phenoxybenzamine to prevent the action of released acetylcholine. In the case of the contraction induced by 5-HT, phenoxybenzamine probably interferes with the 5-HT receptor responsible for neuronal release of acetycholine.

Responses of rabbit portal vein to histamine.

1 Histamine produced a dose-dependent contraction of the isolated portal vein of the rabbit. This contraction was not antagonized by atropine, methysergide, indomethacin, cocaine or 6-hydroxy-dopamine, nor by pretreatment of the rabbit with reserpine. 2 The response to histamine was blocked by H1-receptor antagonists only when the blocking agent was used in very high concentrations, and was not antagonized by the H2-receptor blocking agent, metiamide, H1-receptor antagonists did not block the effects of 5-hydroxytryptamine. 3 The contractions elicited by histamine, 5-hydroxytryptamine and noradrenaline were blocked by phentolamine. 4 Desensitization to high doses of 5-hydroxytryptamine caused a concomitant depression in the response to histamine but not to noradrenaline or acetylcholine. 5 The results suggest that the contractions of rabbit portal vein elicited by histamine are not mediated by receptors of the H1- or the H2-type, but may involve an action of histamine at a receptor which is also involved in the action of 5-hydroxytryptamine.

The polycationic aminoglycosides modulate the vasoconstrictive effects of endothelin: relevance to cerebral vasospasm.

1. The vasoactive peptide endothelin (ET) has been implicated in the pathogenesis of cerebral vasospasm following subarachnoid haemorrhage. In these studies we investigated the involvement of protein kinase C (PKC) in sustained vasoconstriction induced by ET-1 in canine cerebral arteries. We also examined the ability of the aminoglycoside antibiotics to reverse the effects mediated by ET-1 in canine cerebrovascular smooth muscle cells (CVSMC). 2. The ET(A) receptor antagonist, BQ-123, showed a competitive inhibition of the ET-1 responses. 3. The vasoconstrictor action of both ET-1 (0.5 nM) and phorbol myristate acetate (PMA) (160 nM) was reversed by a selective PKC inhibitor, Ro-32-0432. 4. In cerebral arteries precontracted with ET-1 the aminoglycosides caused a concentration-dependent relaxation. The EC(50s) for the relaxation were as follows: 0.54+/-0.05, 0.63+/-0.01, 1.88+/-0.46 and 2.3+/-0.92 mM for gentamicin, neomycin, streptomycin and kanamycin, respectively. 5. Gentamicin caused a concentration-dependent decrease of the PMA-induced responses in calcium free medium. 6. PKC activity was elevated in CVSMC exposed to ET-1 (170%) and PMA (167%) for a period of time (60 min) corresponding to maximum tonic contraction induced by these agents in arterial rings. 7. The administration of the aminoglycosides to CVSMC, in concentrations corresponding to the EC(50s) from contractility studies, reduced the effects of both ET-1 and PMA on PKC activity to the levels not different from controls. 8. These results show that the aminoglycosides are able to inhibit sustained vasoconstriction induced by ET-1, an effect which is due, at least in part, to the inhibition of PKC.