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Volume 49: Issue 2: 2019
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J R Coll Physicians Edinb 2019; 49: 171–4



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Radial artery spasm during cardiac angiography: the impact of endothelial dysfunction and anxiety

The radial artery is a common access site for coronary catheterisation owing to reduced risk of bleeding complications.1 However, the procedure is often complicated by the occurrence of radial artery vasospasm, which necessitates patients to be exposed to the alternative, less preferential femoral route catheterisation. This increases the duration of the procedure, and may increase vascular complications.2 In a study of 379 patients undergoing radial artery catheterisation, the outer sheath diameter of the catheter along with radial artery diameter were among the independent predictors of vasospasm.3 Furthermore, administration of vasodilator agents glyceryl trinitrate and sodium nitroprusside did not reduce the risk of vasospasm. Indeed, there is a possibility that the catheter may cause disruption of the endothelial cell lining resulting in endothelial dysfunction – an inflammatory response characterised by the loss of the vasodilator, nitric oxide, along with concomitant increase in vasoconstrictive factors, such as endothelin-1 or thromboxane.4 However, despite administering potent vasodilators, vasospasm still occurred, suggesting that factors other than loss of vasodilatation could contribute to the vasoconstrictive effect.

A recent line of enquiry has concerned the impact of patient anxiety on the clinical severity of spasm. In their study of 81 patients indicated for coronary angiography, Ercan et al.5 reported that higher anxiety (using Hamilton Anxiety Scale) was associated with radial artery vasospasm, particularly in females. Other studies report that anxiety is common before, during and after coronary angiography procedures.6–8 Moreover, showing informative videos before coronary angiography reduces anxiety levels,9 and guided imagery before surgery can reduce mean anxiety levels.10 Indeed, there has been much research since the 1980s evidencing the anxiety-ameliorating potential of psychological intervention both in pre- and post-operative environments.11–13 Collectively, these findings suggest that alternative mechanisms might impact on the vasculature, and it seems plausible that anxiety (or any form of stress) will increase sympathetic innervation to the vessel via activation of α-adrenoreceptors located in the vessel.14 It is our view that further prospective studies are required to elucidate the mechanisms responsible for vasospasm in patients undergoing coronary angiography. Such studies need to incorporate robust methodology, including assessments of endothelial function in the microvasculature and large vessels, examination of anxiety and inclusion of large sample size. Furthermore, appropriately powered randomised control trials could examine the long-term impact of techniques used to reduce anxiety on the vasculature.

Hussain Ibrahem Hussain1, Chetan Upadhyaya2, Aaron W Pritchard3, Aamer Sandoo4
1University Hospital of Wales, Heath Park, Cardiff, UK
2North Wales Cardiac Centre, Ysbyty Glan Clwyd, Bodelwyddan, UK
3Research and Development Department, Betsi Cadwaladr University Health Board, Ysbyty Gwynedd, Bangor, UK
4School of Sport Health and Exercise Sciences, Bangor University, Bangor, UK
doi: 10.4997/JRCPE.2019.220


1 Carvalho MS, Calé R, Gonçalves P de A et al. Predictors of conversion from radial into femoral access in cardiac catheterization. Arq Bras Cardiol 2015; 104: 401–8.

2 Hetherington SL, Adam Z, Morley R et al. Primary percutaneous coronary intervention for acute ST-segment elevation myocardial infarction: changing patterns of vascular access, radial versus femoral artery. Heart 2009; 95: 1612–8.

3 Coppola J, Patel T, Kwan T et al. Nitroglycerin, nitroprusside, or both, in preventing radial artery spasm during transradial artery catheterization. J Invasive Cardiol 2006; 18: 155–8.

4 Sandoo A, Veldhuijzen van Zanten JJCS, Metsios GS et al. The endothelium and its role in regulating vascular tone. Open Cardiovasc Med J 2010; 4: 302–12.

5 Ercan S, Unal A, Altunbas G et al. Anxiety score as a risk factor for radial artery vasospasm during radial interventions: a pilot study. Angiology 2014; 65: 67–70.

6 Piegza M, Pudlo R, Badura-Brzoza K et al. Dynamics of anxiety in women undergoing coronary angiography. Kardiol Pol 2014; 72: 175–80.

7 Ozdemir PG, Selvi Y, Boysan M et al. Relationships between coronary angiography, mood, anxiety and insomnia. Psychiatry Res 2015; 228: 355–62.

8 Rutledge T, Kenkre TS, Bittner V et al. Anxiety associations with cardiac symptoms, angiographic disease severity, and healthcare utilization: the NHLBI-sponsored Women’s Ischemia Syndrome Evaluation. Int J Cardiol 2013; 168: 2335–40.

9 Ruffinengo C, Versino E, Renga G. Effectiveness of an informative video on reducing anxiety levels in patients undergoing elective coronarography: an RCT. Eur J Cardiovasc Nurs 2009; 8: 57–61.

10 Foji S, Tadayonfar M, Mohsenpour M et al. The study of the effect of guided imagery on pain, anxiety and some other hemodynamic factors in patients undergoing coronary angiography. Complement Ther Clin Pract 2015; 21: 119–23.

11 Anderson KO, Masur FT. Psychological preparation for cardiac catheterization. Advances 1989; 6: 8–10.

12 Anderson EA. Preoperative preparation for cardiac surgery facilitates recovery, reduces psychological distress, and reduces the incidence of acute postoperative hypertension. J Consult Clin Psychol 1987; 55: 513.

13 Mumford E, Schlesinger HJ, Glass GV. The effect of psychological intervention on recovery from surgery and heart attacks: an analysis of the literature. Am J Public Health 1982; 72: 141–51.

14 Sheng Y, Zhu L. The crosstalk between autonomic nervous system and blood vessels. Int J Physiol Pathophysiol Pharmacol 2018; 10: 17–28.


Behçet’s disease and bipolar disorder

Hibberd et al. emphasise bipolar disorder as an associated feature of Behçet’s disease (BD).1 Talarico et al. recently reported on psychiatric involvement in 116 patients with BD and compared them to a control group of patients with systemic lupus erythematosus (SLE) and chronic hypertension.2 The BD cohort was divided in two groups depending on the presence or otherwise of neurological features. The frequency of bipolar disorder was significantly higher in the BD cohort than in disease controls (p < 0.001). However, there was no significant difference in unipolar depression and insomnia in the BD, SLE and chronic arterial hypertension groups. In addition, the presence of bipolar disorder in BD patients (mainly hypomanic episodes) was not related to the presence of neurological involvement; however, the presence of manic bipolar disorder was associated with active disease.

The higher frequency of psychiatric manifestations in BD adds to the importance of a multidisciplinary approach to patients. A clinical psychologic or psychiatric input is important. The recently published EULAR recommendations for the management of BD need to be updated to include management of psychological aspects of the disease.3

Ali SM Jawad
Royal London Hospital, London, UK
doi: 10.4997/JRCPE.2019.221


1 Hibberd O, Bhomra P, Ahmad A. Radiological neuro-Behçet’s associated with bipolar disorder: first presentation of a multisystem disease. J R Coll Physicians Edinb 2018; 48: 323–7.

2 Talarico R, Palagini L, Elefante E et al. Behçet’s syndrome and psychiatric involvement: is it a primary or secondary feature of the disease? Clin Exp Rheumatol 2018; 36: S125–8.

3 Hatemi G, Christensen R, Bang D et al. 2018 update of the EULAR recommendations for the management of Behçet’s syndrome. Ann Rheumat Dis 2018; 77: 808–18.

Liquorice (Glycyrrhiza glabra): the journey of the sweet root from Mesopotamia to England

The beguiling story of liquorice in its many aspects as told by Lee1 struck several chords with this correspondent, partly because of a boyhood fondness for Liquorice Allsorts, partly because of the previous use of liquorice in asthma treatment, but principally because of recently visiting the old ducal town of Uzes in the Gard department of south western France. Uzes is the source of the Roman aqueduct whose UNESCO World Heritage stretch is the Pont du Gard. Uzes may have had knowledge of liquorice since the Arab–Islamic extension from Spain into France in the eight century.2 The town has a liquorice factory, set up by Henry Lafont in 1862. It has been owned by the German company Haribo since 1985 and now also boasts the Haribo liquorice museum. Among the artists who created posters to advertise the liquorice products in the 1880–1910 period were Henri Toulouse-Lautrec and poster designer and painter Leonetto Capiello, reputedly the father of the modern advertising poster. Nowadays, however, Capiello, unlike Toulouse-Lautrec, appears to have almost disappeared into the ether of art history. It is noted also that Haribo now owns a liquorice factory in Pontefract, an ironic twist of history considering the destructive impact of the Luftwaffe on the Ewbank’s factory. As Lee shows the sweet root (and the industry of which it is the raison d’etre) is indeed well travelled. It had the capacity to survive, as it endured the long hazardous return from Mesopotamia to medieval France and England. The outward leg of this journey was well documented by the explorer and historian Tim Severin,3 who followed on horseback the route of the great crusader Godfrey de Bouillon, first ruler of the Kingdom of Jerusalem. Liquorice also survived the dissolution of the monasteries, as well as assault from the air in the Second World War, and assault on the ground by government regulation as happened in Britain in 1939. The liquorice industry also survived allegations in 2017 of exploitation of carnuaba wax workers in BraziI. Carnauba wax is a resin derived from the leaves of the palm tree Copernicia prunifera and is sometimes used as a surface smoothing and antisticking agent in liquorice and other gums. Accordingly, the task of trekking with the sweet root from Mesopotamia, and its preservation from the eleventh into the twenty-first century, appears to have been a sometimes not very sweet experience. Nevertheless the images evoked by this historic story, such as horseback Crusaders and siege towers at the gates of Jerusalem,3 as well as that of the intrepid monks of Cluny carting (and sailing) their precious booty all the way from the banks of the Euphrates to Pontefract, are well worth savouring.

Charles P Bredin
Clinical Senior Lecturer, Respiratory Medicine, University College Cork, Ireland
doi: 10.4997/JRCPE.2019.222


1 Lee MR. Liquorice (Glycyrrhiza glabra): the journey of the sweet root from Mesopotamia to England. J R Coll Physicians Edinb 2018; 48: 378–82.

2 Gleize Y, Mendisco F, Permonge M et al. Early medieval graves in France: first archaeological and palaeogenomic evidence. PLoS One 2016; 11: e014853.

3 Severin T. Crusader: by Horse to Jerusalem. London: Arrow Books; 1990.

‘Working diagnosis’ as a means to reduce cognitive bias

O’Sullivan and Schofield gave an excellent summary of the problem of cognitive bias in the diagnostic process.1 Metacognition and use of Bayesian theory were highlighted as means to mitigate the effect of bias. We suggest that the routine use of the term ‘working diagnosis’ would draw attention to these strategies by emphasising the uncertainty that prevails. Even when all relevant tests have been made, some uncertainty may remain. The task of the clinician is, therefore, not necessarily to attain certainty, but rather to reduce the level of diagnostic uncertainty enough to make optimal therapeutic decisions.2 It is accepted clinical practice to compile a list of differential diagnoses – these each have varying degrees of plausibility. The ‘working diagnosis’ is simply the differential with the greater probability. By using the term ‘working diagnosis’, the clinician is challenged to re-evaluate the diagnosis in light of new evidence. In this way, anchoring bias, confirmation bias and premature closure bias may be avoided. Clinicians should embrace uncertainty whilst avoiding decision paralysis in the face of uncertainty.

Stuart J Sullivan1, Martin B Whyte2
1University of Warwick Medical School, Warwick, UK
2University of Surrey, Guildford, UK
doi: 10.4997.JRCPE.2019.223


1 O’Sullivan ED, Schofield SJ. Cognitive bias in clinical medicine. J R Coll Physicians Edinb 2018; 48: 225–32.

2 Kassirer JP. Our stubborn quest for diagnostic certainty. A cause of excessive testing. N Engl J Med 1989; 320: 1489–91.

Positive facets of simulation-based learning: patient safety, risk management, synergy with e-learning and its use in life support courses

I read with interest, Simulation in Medical Education by So et al.1 in which the authors have advocated in favour of using simulation-based learning (SBL) as a delivery method in medical education. I would like to bring certain interesting points regarding SBL to the reader’s attention. SBL has been used as a risk management strategy in different healthcare systems around the globe and evaluations have indicated favourable outcomes to support its use in this regard.2 SBL can be applied as learning modality to improve patient safety in healthcare settings and has a benefit of being able to be tailored to the needs of learners, whilst allowing for deliverable positive outcomes and cost effectiveness.3 SBL is being used around the world but there has been a special emphasis on its use in the NHS in the UK, as it has been seen as a way of delivering patient-centred high-quality education to NHS staff to improve patient safety and risk manage serious incidents.4,5 Certain education centres in the UK have even won international awards in recognition of their success in delivering world-class simulation training in healthcare.5 Simulation has been widely used in the delivery of life support courses, such as basic life support, advanced life support, advanced cardiac life support, advanced trauma life support and paediatrics advanced life support by Resuscitation Council UK [RC (UK)], European Resuscitation Council (ERC) and American Heart Association (AHA), as simulation improves learner confidence, performance and communication.6 It will be very interesting to note if RC (UK), ERC and AHA could come forward with some results from the wealth of data available to them to further confirm the findings available in the literature regarding SBL. Another interesting facet of SBL is its association with e-learning that has shown to improve the utilisation and outcomes of SBL when used jointly with e-learning modules.7 This approach of using e-learning in conjunction with simulation training has been used by many mainstream organisations utilising SBL during their standardised courses, for example during life support courses organised by RC (UK), ERC and AHA.8–10

Bilal Haider Malik
Health Education England East of England, Cambridge, UK
doi: 10.4997/JRCPE.2019.224


1 So HY, Chen PP, Wong GKC et al. Simulation in medical education. J R Coll Physicians Edinb 2019; 49: 52–7.

2 Jolly J, Bowie P, Dawson L et al. Evaluation of a simulation-based risk management and communication masterclass to reduce the risk of complaints, medicolegal and dentolegal claims. BMJ Stel 2019; [Epub ahead of print].

3 Walsh K. Simulation is the way to bring risk management and patient safety together. Acad Med 2011; 86: 1193.

4 Health Education England. Simulation. (accessed 05/04/19).

5 MacEachen J. ‘World first’ award for Scots clinical skills network. 2018.‘world-first’-award-for-scots-clinical-skills-network.aspx (accessed 05/04/19).

6 Han JE, Trammell AR, Finklea JD et al. Evaluating simulation-based ACLS education on patient outcomes: a randomized, controlled pilot study. J Grad Med Educ 2014; 6: 501–6.

7 The power of simulation-based e-learning (SIMBEL). (accessed 05/04/19).

8 Resuscitation Council UK. e-ALS – Advanced Life Support e-learning course. (accessed 05/04/19).

9 American Heart Association eLearning. HeartCode® ACLS. (accessed 05/04/19).

10 European Resuscitation Council. Advanced Life Support. (accessed 05/04/19).

Authors’ reply

We are happy to see the letter from Malik with supplementary information of how simulation can lead to effective medical education. We agree that there are many ways in which simulation can be applied to improve the quality and safety of healthcare. Although our paper1 focused on education and training, simulation is a very effective form of assessment as demonstrated by the popularity of objective structured clinical examinations in both postgraduate and undergraduate education.2 Simulation can be used for research into topics that are difficult to study in an authentic clinical environment. One good example is the demonstration of the effectiveness of using surgical-crisis checklists.3 Finally, simulation can be used for evaluating how different elements of a system interact with each other, such as whether facilities or equipment are well designed for human use.4,5 We agree that simulation should be used more frequently to enhance quality and safety in healthcare.

Hing Yu So, Phoon Ping Chen, George Kwok Chu Wong, Tony Tung Ning Chan
Hong Kong Jockey Club Innovative Learning Centre for Medicine Consultant in Intensive Care, Prince of Wales Hospital, Hong Kong
doi: 10.4997/JRCPE.2019.225


1 So HY, Chen PP, Wong GKC et al. Simulation in medical education. J R Coll Physicians Edinb 2019; 49: 52–7.

2 Khan KZ, Ramachandran S, Gaunt K et al. The objective structured clinical examination (OSCE): AMEE Guide No. 81. Part 1: an historical and theoretical perspective. Med Teach 2013; 35: e1437–46.

3 Arriaga AF, Bader AM, Wong JM et al. Simulation-based trial of surgical-crisis checklists. N Engl J Med 2013; 368: 246–53.

4 Chen PP, Tsui NTK, Fung ASW et al. In-situ medical simulation for pre-implementation testing of clinical service in a regional hospital in Hong Kong. Hong Kong Med J 2017; 23: 404–10.

5 Or C, Chan FY, So HY et al. Human factors evaluation and simulated use testing of infusion pumps to inform pump selection decision making. Int J Med Informatics Submitted.

Relationship between acute asthma, pneumomediastinum and pulmonary embolism

When acute asthma is complicated by pneumomediastinum, as in the recently reported case1 and in one other report,2 symptoms such as retrosternal chest tightness1 and pleuritic chest pain2 may simulate those documented in pulmonary embolism (PE). Furthermore, PE can present with severe wheezing simulating acute severe asthma,3 and asthma appears to increase the risk of pulmonary thromboembolism.4 The latter observation was made in a nationwide case–control study that included 114,366 Swedish-born patients with a first hospital admission of PE, 76,494 with deep vein thrombosis (DVT) and 6,854 with combined DVT and PE, between 1981 and 2010. In each group asthma was included as a comorbidity. Each case was matched with five controls for age, sex and educational level. Asthma was found to be associated with an adjusted odds ratio for PE amounting to 1.43 [95% confidence interval (CI), 1.37–1.50), for DVT amounting to 1.56 (95% CI, 1.47–1.65) and for combined DVT and PE 1.60 (95% CI, 1.32–1.93).4 PE may, itself, be complicated by pneumomediastinum, due to septic cavitation of a pulmonary infarct situated adjacent to the mediastinal pleura.5 In the latter context the management of pneumomediastinum includes antibiotics to mitigate the risk of mediastinitis.5 Accordingly, in the event of the occurrence of PE-related pneumomediastinum in a patient with asthma the strategy of watchful expectancy employed in some cases of pneumomediastinum1,2 needs to be complemented by prophylactic antibiotics to mitigate risk of mediastinitis.

Oscar MP Jolobe
Manchester Medical Society, Manchester, UK
doi: 10.4997/JRCPE.2019.226


1 Mohamed W, Exley C, Sutcliffe IM, Dwarakananth A. Spontaneous pneumomediastinum(Hamman’s syndrome): presenting as acute severe asthma. J R Coll Physicians Edinb 2019; 49: 31–3.

2 Aleemuddin NM, Bahmed F. Spontaneous pneumomediastinum in acute severe asthma. Indian J Crit Care Med 2010; 14: 92–4.

3 Bansal DP, Maazuddin M, Viquasuddin M. Pulmonary embolism mimicking acute severe asthma. J Assoc Physicians India 2018; 66: 84–5.

4 Zoller B, Pirouzifard M, Memon AA et al. Risk of pulmonary embolism and deep vein thrombosis in patients with asthma: nationwide case-control study from Sweden. Eur Respir J 2017; 49: 1601014.

5 Maldjian PD, Petscavage JM. Intracardiac thrombus and pulmonary embolism with cavitation and pneumomediastinum in a patient with protein S deficiency. J Thorac Imaging 2006; 21: 222–4.

Authors’ reply

We thank Dr Jolobe for his interest in our recent paper1 and highlighting the link between airways disease and thrombosis. It is true that recent studies have shown that asthma is a risk factor for pulmonary embolism2–4 and can pose a diagnostic challenge in clinical practice, especially when patients present with acute asthma symptoms. It is not entirely clear about the mechanism of the association, but both local and systemic inflammation inducing prothrombotic effects5–8 and the use of steroids that leads to endothelial dysfunction are hypothesised.9,10 Further studies are needed to evaluate the various mechanisms in hypercoagulability in asthma patients.

Pneumomediastinum secondary to a pulmonary embolism and subsequent acute mediastinitis is extremely rare and usually is a sequelae of septic cavitation complicated by pulmonary infarction. However, this seldom leads to chronic or fibrosing mediastinitis.

Waddah Mohamed, Claire Exley, Ian Michael Sutcliffe, Akshay Dwarakanath
Mid Yorkshire Hospitals NHS Trust, Wakefield, UK
doi: 10.4997/JRCPE.2019.227


1 Mohamed W, Exley C, Sutcliffe IM et al. A spontaneous pneumomediastinum (Hamman’s syndrome): presenting as acute severe asthma. J R Coll Physicians Edinb 2019; 49: 31–3.

2 Majoor CJ, Kamphuisen PW, Zwinderman AH et al. Risk of deep vein thrombosis and pulmonary embolism in asthma. Eur Respir J 2013; 42: 655–61.

3 Chung W-S, Lin C-L, Ho F-M et al. Asthma increases pulmonary thromboembolism risk: a nationwide population cohort study. Eur Respir J 2014; 43: 801–7.

4 Zoller B, Pirouzifard M, Memon AA et al. Risk of pulmonary embolism and deep vein thrombosis in patients with asthma: nationwide case-control study from Sweden. Eur Respir J 2017; 49: 1601014

5 Ramagopalan SV, Wotton CJ, Handel AE et al. Risk of venous thromboembolism in people admitted to hospital with selected immune-mediated diseases: record-linkage study. BMC Med 2011; 9: 1–8.

6 Zöller B, Li X, Sundquist J et al. Risk of pulmonary embolism in patients with autoimmune disorders: a nationwide follow-up study from Sweden. Lancet 2012; 379: 244–9.

7 Zöller B, Li X, Sundquist J et al. Autoimmune diseases and venous thromboembolism: a review of the literature. Am J Cardiovasc Dis 2012; 2: 171–83.

8 Martinez FD, Vercelli D. Asthma. Lancet 2013; 382: 1360–72.

9 Sneeboer MM, Majoor CJ, de Kievit A et al. Prothrombotic state in patients with severe and prednisolone-dependent asthma. J Allergy Clin Immunol 2016; 137: 1727–32.

10 Coelho MC, Santos CV, Vieira Neto L et al. Adverse effects of glucocorticoids: coagulopathy. Eur J Endocrinol 2015; 173: M11–21.