Identifying stressor criteria that hinder or challenge junior clinical medical student learning.

INTRODUCTION: What makes something a stressor within clinical students' education is unclear. Medical students moving from a predominantly protected classroom environment to a situated-work environment provided an ideal transition point to explore the criteria that might make a learning experience a stressor and whether these stressors hinder or challenge learning. METHOD: Data on the stressors associated with learning experiences in clinical education were collected from New Zealand undergraduate medical students. Free text comments, in a survey-based questionnaire were supplemented by focus group data. Using inductive thematic analysis with grounded theory, themes were generated about the characteristics of stressors; referred to here as stressor criteria. These stressor criteria were then classified according to their impact on perceived learning. RESULTS: Under the broad headings of the nature of the learning task, external factors, internal factors, and social interaction; 12 stressor criteria groupings were defined. Some of these criteria were a positive challenge to learning (e.g. legitimacy of the task, novelty of the learning, social interactions) and others a hindrance. DISCUSSION: Not all stressors hinder learning. Instead, and depending on their nature, many result in perceived assistance to learning. Stressors hindering learning need to be recognised by the teacher, especially those that can be converted from a hindrance to an assistance.

Relationships among perceived learning, challenge and affect in a clinical context.

BACKGROUND: Challenge, sometimes perceived as stress, may be beneficial or detrimental to learning but the circumstances when it may be beneficial are not clear. This study looks at the association of challenge with perceived learning and how this might be influenced by affect, context or the type of learning. METHOD: The participants, medical students in their first years of experiential clinical exposure, rated specified learning episodes (LEs) on the perceived learning (low to high), challenge (low to high) and affect (feeling positive to negative). Such learning episodes were self-identified or identified by course organisers. Correlations, using Kendall's tau-b test, were conducted to explore the associations among learning, challenge and affect. In the second stage the types of LEs were then thematically classified in order to determine those that were positive for learning and challenging and/or associated with positive affect. RESULT: There were positive correlations between perceived learning and challenge, and between perceived learning and affect for both types of LEs. The circumstances in which challenge (stress) promoted learning were authentic environments, authentic tasks and simulated clinical activities; most requiring a degree of social interaction. CONCLUSION: Challenge and positive affect are beneficial in the perception of discrete learning, but are two separate constructs. Ideally both challenge and affect need to operate alongside authentic supportive clinical activities, that by their nature involve others, to maximise perceived learning.

Student belief about the value of challenge.

BACKGROUND: The undergraduate curriculum tends to focus on how individuals can cope with stress especially when transitioning from the classroom to the clinical workplace environment. Often this carries the message that stress is bad, yet little attention has been paid to the influence of one's belief regarding the value of stress for learning. Because stress is often perceived as bad, we chose to use the term 'challenge' in exploring the associations amongst belief of the value of challenge, the challenge experienced, the perceived learning, affect and staff support. METHODS: At the end of each clinical module within a medical curriculum, medical students rated the perceived learning, degree of challenge, affect, support and the value of challenge for learning. The value and associations amongst these variables were analysed. RESULTS: The challenge for students varied according to the type of module. Students generally considered that challenge promoted rather than hindered learning. The level of challenge experienced may influence the perception of the value of challenge for learning. However, when challenge was regarded as beneficial, this was strongly, positively associated with perceived learning, positive affect and support. DISCUSSION: Students who believe challenge is positive also perceive that such challenges promote learning. Likewise students who regard challenge as negative are less likely to learn from such challenges. The positive relationship between the belief of the value of challenge with affect and support may have positive implications for well-being. It is contended that curriculum planners should acknowledge the potential positive influence of stressors in clinical education and that challenge can be seen as valuable when there is student support and measures associated with maintaining a positive affect.

Certainty and safe consequence responses provide additional information from multiple choice question assessments.

BACKGROUND: Clinicians making decisions require the ability to self-monitor and evaluate their certainty of being correct while being mindful of the potential consequences of alternative actions. For clinical students, this ability could be inferred from their responses to multiple-choice questions (MCQ) by recording their certainty in correctness and avoidance of options that are potentially unsafe. METHODS: Response certainty was assessed for fifth year medical students (n = 330) during a summative MCQ examination by having students indicate their certainty in each response they gave on the exam. Incorrect responses were classified as to their inherent level of safeness by an expert panel (response consequence). Analyses compared response certainty, response consequence across student performance groupings. RESULTS: As students' certainty in responses increased, the odds they answered correctly increased and the odds of giving unsafe answers decreased. However, from some ability groups the odds of an incorrect response being unsafe increased with high certainty. CONCLUSIONS: Certainty in, and safeness of, MCQ responses can provide additional information to the traditional measure of a number correct. In this sample, even students below standard demonstrated appropriate certainty. However, apart from those scoring lowest, student's incorrect responses were more likely to be unsafe when they expressed high certainty. These findings suggest that measures of certainty and consequence are somewhat independent of the number of correct responses to MCQs and could provide useful extra information particularly for those close to the pass-fail threshold.

NVP-QBE170: an inhaled blocker of the epithelial sodium channel with a reduced potential to induce hyperkalaemia.

BACKGROUND AND PURPOSE: Inhaled amiloride, a blocker of the epithelial sodium channel (ENaC), enhances mucociliary clearance (MCC) in cystic fibrosis (CF) patients. However, the dose of amiloride is limited by the mechanism-based side effect of hyperkalaemia resulting from renal ENaC blockade. Inhaled ENaC blockers with a reduced potential to induce hyperkalaemia provide a therapeutic strategy to improve mucosal hydration and MCC in the lungs of CF patients. The present study describes the preclinical profile of a novel ENaC blocker, NVP-QBE170, designed for inhaled delivery, with a reduced potential to induce hyperkalaemia. EXPERIMENTAL APPROACH: The in vitro potency and duration of action of NVP-QBE170 were compared with amiloride and a newer ENaC blocker, P552-02, in primary human bronchial epithelial cells (HBECs) by short-circuit current. In vivo efficacy and safety were assessed in guinea pig (tracheal potential difference/hyperkalaemia), rat (hyperkalaemia) and sheep (MCC). KEY RESULTS: In vitro, NVP-QBE170 potently inhibited ENaC function in HBEC and showed a longer duration of action to comparator molecules. In vivo, intratracheal (i.t.) instillation of NVP-QBE170 attenuated ENaC activity in the guinea pig airways with greater potency and duration of action than that of amiloride without inducing hyperkalaemia in either guinea pig or rat. Dry powder inhalation of NVP-QBE170 by conscious sheep increased MCC and was better than inhaled hypertonic saline in terms of efficacy and duration of action. CONCLUSIONS AND IMPLICATIONS: NVP-QBE170 highlights the potential for inhaled ENaC blockers to exhibit efficacy in the airways with a reduced risk of hyperkalaemia, relative to existing compounds.

Variability in the assessment of advanced life support skills.

The number of short 'life support' and emergency care courses available are increasing. Variability in examiner assessments has been reported previously in more traditional types of examinations but there is little data on the reliability of the assessments used on these newer courses. This study evaluated the reliability and consistency of instructor marking for the Resuscitation Council UK Advanced Life Support Course. Twenty five instructors from 15 centres throughout the UK were shown four staged video recorded defibrillation tests (one repeated) and three cardiac arrest simulation tests in order to assess inter-observer and intra-observer variability. These tests form part of the final assessment of competence on an Advanced Life Support course. Significant levels of variability were demonstrated between instructors with poor levels of agreement of 52-80% for defibrillation tests and 52-100% for cardiac arrest simulation tests. There was evidence of differences in the observation/recognition of errors and rating tendencies of instructors. Four instructors made a different pass/fail decision when shown defibrillation test 2 for a second time leading to only moderate levels of intra-observer agreement (kappa=0.43). In conclusion there is significant variability between instructors in the assessment of advanced life support skills, which may undermine the present assessment mechanisms for the advanced life support course. Validation of the assessment tools for the rapidly growing number of life support courses is required with urgent steps to improve reliability where required.

The effect of differing support surfaces on the efficacy of chest compressions using a resuscitation manikin model.

AIM: External chest compression (ECC) efficacy is influenced by factors including the surface supporting the patient. Air-filled support surfaces are deflated for cardiopulmonary resuscitation, with little evidence to substantiate this. We investigated the effect that differing support surfaces had on ECC efficacy using a CPR manikin model. METHODOLOGY: Four participants carried out four cycles of ECC with an assistant ventilating. The subjects were blinded to the seven support surfaces and the order was randomised. For each participant/surface combination, ECC variables and the participants' perceptions were measured. RESULTS: Participants produced effective ECC with the manikin on the floor (mean proportion correct, 94.5%; mean depth, 42.5 mm). Compared with the floor: the proportion of correct ECC was less for the overlay inflated (P<0.05); the depth of ECC was less effective (30-37 mm) for the overlay inflated/deflated and low-air-loss inflated and foam mattresses (P<0.05). The foam mattress, overlay inflated/deflated, and low-air-loss inflated were perceived as being less stable and as having reduced ECC efficacy compared with the floor. There was no difference or agreement, regarding subjects' perceptions or ECC variables, between the support surfaces or between inflated/deflated air-filled support surfaces. CONCLUSION: The efficacy of ECC is affected by the support surfaces. There seems little evidence to substantiate deflating all air-filled support surfaces for CPR.

The face validity of a final professional clinical examination.

OBJECTIVE: To develop new methods of evaluating face validity in the context of a revised final professional examination for medical undergraduates, organized on three sites, over 2 days. METHODS: The opinion of the students and examiners was surveyed by Likert-style questionnaires, with additional open comments. Expert opinion was gathered from external examiner reports and a recent Quality Assurance Agency (QAA) Subject Review Report. RESULTS: The questionnaires had an overall response rate of 84%. Internal reliability, assessed by comparing responses to appropriate questions, was good with an equivalence of 45% (weighted kappa 0.54) for the students and 33% (weighted kappa 0.41) for the assessors. There was little evidence of inconsistency between days or sites. The majority of the opinions from the students, examiners and external experts were positive. Negative comments related to time pressure and case mix. CONCLUSION: The measurement of face validity proved feasible and valuable and will assist in the further development of the course and the examination.

The design and synthesis of thrombin inhibitors: analogues of MD805 containing non-polar surrogates for arginine at the P1 position.

A series of monocyclic and bicyclic amino acids have been synthesised and incorporated into thrombin inhibitors based on CGH728, an analogue of the Mitsubishi compound MD805. Benzthiazolylalanine (Bta) was found to be a good non-polar substitute for arginine at the P1 position, yielding compounds with low nanomolar potency and good selectivity for thrombin.

The design and synthesis of thrombin inhibitors: the introduction of in vivo efficacy and oral bioavailability into benzthiazolylalanine inhibitors.

The further optimisation of the novel lead compound CGH752 (Fig. 1) is described. By introducing various substituents into the 6-position of the 3,3-dimethyltetrahydroquinoline (DMTHQS) ring we have been able to favourably affect the in vitro and in vivo activity, and the pharmacokinetics of such compounds. One of the inhibitors synthesised (CGH1484) is bioavailable and shows efficacy in animal models of thrombosis.

The discovery of orally available thrombin inhibitors: optimisation of the P1 pharmacophore.

Thrombin inhibitors have been designed with the replacement of the strongly basic guanidine P1 pharmocophore with a group that exploits the lipophilicity of the S1 pocket. The approach has lead to the discovery of potent thrombin inhibitors demonstrating good intra-duodenal absorption.

Studies towards the identification of potent, selective and bioavailable thrombin inhibitors.

The application of selection criteria, based on potency and physicochemical parameters, to a candidate library of thrombin inhibitors is described. The utility of the approach is exemplified by the discovery of a potent, selective and bioavailable thrombin inhibitor 62.

The discovery of orally available thrombin inhibitors: studies towards the optimisation of CGH1668.

The chemical optimisation of CGH1668 1 is described employing an in vivo model of absorption to determine the influence on bioavailability of single point modifications to five key molecular templates. The discovery of an orally bioavailable and selective thrombin inhibitor, 24, highlights the utility of this approach.

Attenuation of arteriolar alpha 2-adrenoceptor sensitivity during endotoxemia.

It is well documented that adrenergic responses after endotoxin (ENDT) administration are greatly reduced. The hypothesis of this study is that either alpha 1- or alpha 2-receptor activity is attenuated and the other receptor type is minimally affected during ENDT shock. Reactivity of the arterioles of left cremaster muscles of male Wistar rats anesthetized with pentobarbital sodium was studied using videomicroscopy. Femoral mean arterial pressure and first-, second-, third-, and fourth-order arteriolar diameters were measured. In group I, the decreases in arteriolar diameter and half-maximal effective dose (ED50) values with increasing phenylephrine concentration (alpha 1-adrenergic receptor agonist) were similar in all four branching orders before and after ENDT. In group II, the decreases in arteriolar diameter with increasing clonidine concentrations (alpha 2-adrenergic receptor agonist) were effectively attenuated by ENDT, and ED50 values were increased above control in all four branching orders. In group III, idazoxan (alpha 2-receptor antagonist) effectively blocked the vasoconstrictor effects of clonidine but did not affect the responses to phenylephrine before or after ENDT in all four arteriolar orders. In group IV, prazosin (alpha 1-adrenergic receptor antagonist) blocked the vasoconstrictor effects of phenylephrine before and after the administration of ENDT. However, vasoconstriction due to clonidine post-ENDT even at maximal dosage (10(-3) M), was greatly attenuated in all four branching orders as in group II. It is concluded that during endotoxemia the reduced adrenergic vasoconstrictor response of cremaster muscle arterioles is the result of attenuated activity of alpha 2-adrenergic receptors with minimal if any effects on alpha 1-adrenergic receptor activity.(ABSTRACT TRUNCATED AT 250 WORDS)

The characterisation of thrombus development in an improved model of arterio-venous shunt thrombosis in the rat and the effects of recombinant desulphatohirudin (CGP 39393), heparin, and iloprost.

An existing arterio-venous shunt thrombosis model in the rat has been modified to increase its usefulness for the testing of anti-thrombotic agents and characterised using morphological and radiometric techniques. The thrombus formed on the cotton thread held in the shunt was found to be composed of platelet aggregates surrounded by red thrombus. After 30 min of blood flow there was a 15-fold increase in the platelet content of the thrombus and a 4-fold increase in the fibrin(ogen) content compared with an equivalent weight of whole blood. Use of the anticoagulants recombinant desulphatohirudin (CGP 39393, 4 mg/kg, s.c.) and unfractionated heparin (800 IU/kg, s.c.) showed that approx. 90% inhibition of thrombus weight and approx. 80% inhibition of fibrin(ogen) content could be achieved without significant effect on the platelet content. Conversely, using the platelet inhibitor Iloprost (1 microgram kg-1 min-1), a reduction in thrombus weight of 50% was associated with 75% inhibition of platelet content and only 20% inhibition of fibrin(ogen). These observations suggest that the growth of this type of thrombus is largely the result of continued fibrin formation rather than continued platelet recruitment and activation.

The effects of recombinant desulphatohirudin on arterial thrombosis in rats.

The role of thrombin in the formation of arterial thrombi is poorly understood. With the new availability of the specific thrombin inhibitor, recombinant desulphatohirudin, in large quantities this is now under investigation. A new model of arterial thrombosis in rats is described where a thrombus is formed on a mechanically injured vessel in vivo. Both platelet and fibrin deposition is inhibited by a recombinant hirudin (CGP 39393) at doses which prolong the activated partial thromboplastin time (APTT) to no more than 3-4 times the control level. In contrast, both unfractionated heparin and Fragmin only inhibit thrombosis when the APTT is excessively prolonged (i.e. to greater than 15 times the control value). It is concluded that CGP 39393 is an effective antithrombotic in arterial thrombosis at lower levels of anticoagulation than either heparin or Fragmin.

Recombinant desulphatohirudin (CGP 39393) anticoagulant and antithrombotic properties in vivo.

The effects of the newly available biotechnology product, recombinant desulphatohirudin (CGP 39393) have been investigated in rats. This highly potent and selective thrombin inhibitor exhibited marked anticoagulant properties with controllable titration of anticoagulant effect, as measured by activated partial thromboplastin time (APTT), up to nearly four times control values. Furthermore, CGP 39393 exhibited impressive antithrombotic activity in vivo. In an arteriovenous shunt model of thrombus formation on a cotton-thread, the compound was capable of complete inhibition of thrombus development (ED50 = 0.3 mg/kg i.v. and 1.0 mg/kg s.c.). Venous stasis thrombosis was also highly susceptible to inhibition by CGP 39393 (ED50 = 0.01 mg/kg i.v. and 0.45 mg/kg s.c.). Comparison of the anticoagulant and antithrombotic activities of the compound shows that potent antithrombotic effects (83-97% inhibition in the rat shunt model) are achieved within the generally acceptable range of anticoagulation. These results suggest a clear potential for this new agent in the clinical treatment of thrombotic disease.