RCSIsmj report

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Inside: Changing needs in medicine

RCSIsmjfeature

RCSI Medical imaging in the 21st century

Volume 3: Number 1. 2010 ISSN 2009-0838

smj Royal College of Surgeons in Ireland Student Medical Journal


RCSIsmjcontents Royal College of Surgeons in Ireland student medical journal Director Vice-Director Chief Editor Senior Editor Faculty Editor Junior Editor

– – – – – –

Kristl Vidya Dorschner James Young Erik Vakil Rowena Almeida Professor Tom Fahey Amrita Roy

Staff writers Aideen Henry Hugh McGregor Aoife Morris Lucky Sekhon Peer Review Director Atish Chopra Peer reviewers Wei Lyn Chung (PMC) Julian Davis Ashley Freeman Arvin Kapoor Emily Kuhlman Paul O’Mahoney Mohammed Sarhan Amber Waits Dustin Williams Sponsorship Co-ordinator Eva Forman Public relations Gurleen Bhatia (MUB) Mark Kiak Min Tan (PMC) Poster design Buthaina Bin Turkeya Website design and maintenance Sandford Kong Hong Kuan Kok Special thanks Mr Fintan Foy Dean Cathal Kelly Professor Gerry McElvaney Faculty advisors Professor Marie Cassidy Professor Tom Fahey Dr Joe Galvin Professor Gerry McElvaney Professor Alf Nicholson Professor David Smith Dr Muirne Spooner Sponsors The RCSI Alumni Office and Louise Sherwin Published on behalf of RCSI by

Th!nk Th nkMedia

3 3

Editorial Director’s welcome

Prizes 4 5

RCSIsmj ECG Challenge 2010 RCSIsmj Ethics Challenge 2010

RCSI on the outside 6

Commissioning the King Hamad General Hospital

RCSI people 8 10

Mixing sport and medicine – interview with Felipe Contepomi An interesting life – interview with Mr Harold Browne

Career opportunities 13 17

Oral and maxillofacial surgery in Ireland The United Kingdom Foundation Programme

RCSIsmj Ethics Prize 20

RCSIsmj Ethics Challenge winner 2009

Original articles 25 29 33

An audit of primary care referrals to the Ophthalmic Accident and Emergency Department of the Royal Victoria Eye and Ear Hospital, Dublin Prescribing patterns and administration of intravenous paracetamol: a clinical audit Assessment of the mental health of Irish adolescents in the community

Case reports 36 39

A case of elevated troponins Signal change following posterior fossa tumour resection: evidence of hydrocephalus

Topic reviews 42 47

Cardiology review: Sudden cardiac death in the young: causes and prevention Paediatrics review: Making Europe a better place for our children

Review articles 51 56

Anatomy of a pandemic: influenza A (H1N1) 2009 Understanding metastasis: current paradigms and therapeutic challenges in breast cancer progression

Staff reviews 61 65 70

Changing patient needs: issues and ethics of maternal requested caesarean delivery Editors’ pick: Medical imaging in the 21st century: the promise and the challenges ‘Wii-habilitation’ and robotic exoskeletons: technology in physiotherapy

Staff feature 75

The provision of healthcare in a changing Ireland

Electives 79 81

Liberian HEARTT: post-conflict emergency medicine Reaching out to rural communities

83 Staff picks

PROFESSIONAL PUBLISHING SERVICES

Abstract The Malthouse, 537 NCR, Dublin 1. T: 01-856 1166 F: 01-856 1169 www.thinkmedia.ie Design: Tony Byrne, Tom Cullen and Ruth O’Sullivan Editorial: Ann-Marie Hardiman and Paul O’Grady

84

Molecular interactions of Staphylococcus aureus-induced osteomyelitis

Awards 85 86 87

Upjohn Medal in Molecular Medicine 2009: Sheryl Ramdass Kane Medal: Amrita Roy Norman Rae Dissertation Medal: Tristan Tham

Please email comments to editorsmj@RCSI.ie or join our Facebook page and discuss journal articles. Submissions to submissionssmj@RCSI.ie Page 2 | Volume 3: Number 1. 2010


RCSIsmjeditorial Addressing changing needs in medicine The virus that causes the flu has a very peculiar genome. It is composed of ssRNA that codes for an unstable configuration of haemagglutinin (H) and neuraminidase (N) genes. This allows the virus to constantly evolve in one of two ways: genetic drift and genetic shift. Genetic drift is a collection of small changes in HN assortment that maintains its ability to be infective, whereas genetic shift is a single event that changes the virus so much, it can start a pandemic: a case in point is swine flu (p. 51). Progress in medicine is perhaps more akin to drift rather than shift. It isn’t without hope that we await a shift – perhaps a cure for cancer, or an end to heart disease – but in the meantime we continue to make the small changes that keep us effective. We cannot despair at this war of attrition because as we endeavour to progress, we live on to await a shift. In this edition we present the theme of ‘Changing Needs in Medicine’, an update on the latest drifts. In the wake of global financial collapse, new life has been breathed into the healthcare debate. Even without a mind for the details, America can be applauded for its effort to reform its notoriously inequitable system. And for better or worse, the HSE has also recalculated its health delivery platform. The success of these reforms is yet to be determined and the collective grumblings against any HSE action may have you thinking that change is not a good thing. But we must drift on. The latest HSE saga has been the development and implementation of new NCHD working hour contracts and consultant terms of employment. In this edition, Aoife Morris helps set the record straight as she breaks down the ongoing battle for satisfactory reform (p. 75). She also spends time with the RCSI’s distinguished and beloved Mr Harold Browne in an interview that cuts across generations of surgeons in America, the UK and Ireland (p. 10). For those of you less concerned with the talk and more about the walk, Hugh McGregor and Aideen Henry present us with the latest in medical imaging technology and physical rehabilitation (pp. 65 and

70). As the squabbles continue about how to better implement our healthcare, and as the fantasy of supreme medical technology slowly unfolds into reality, we cannot lose sight of the question of what kind of medicine should we be practising? Medical ethics is the ultimate forum for this debate and we are excited to include some rumblings on these matters as well. In a comprehensive review, Lucky Sekhon confronts the difficult question of elective caesarean section on maternal request (p. 61). We are also delighted to present the winning 2009 Ethics Challenge essay by Adwait Mehta and Janso Padickakudi (p. 20). We hope other students will follow their lead and start thinking critically about the ethical scenarios they encounter, and perhaps even try their hand at the 2010 Ethics Challenge (p. 5), due in the autumn. If ethics isn’t your thing, we are excited to introduce a new ECG Challenge (p. 4), due April 16, 2010. As we enter a new decade, and as the students of today become the doctors of tomorrow, we hope that the pursuit of medical excellence will continue with the same enthusiasm as it has in the past. I would like to extend a very warm thank you to all our contributors and participants, who have without doubt applied that enthusiasm to help fill this edition with the latest in original research, political musings, clinical landmarks and medical commentary. We invite our readers to keep the RCSIsmj close at hand and enjoy drifting through its diverse and stimulating content for the year to come!

Erik Vakil – Chief Editor

Director’s welcome Welcome to the third edition of the RCSIsmj! This issue represents the last issue that will be directed by a founding editor, and as I look back on the last three years, I realise how far we have come. The RCSIsmj is now a well-established publication, not only within the RCSI, but throughout the medical schools of Ireland, and among RCSI graduates around the world. Every year our readership and our involvement have grown by leaps and bounds to represent a diverse section of the RCSI community from Junior Cycle Medicine to Physiotherapy, from Dublin to Bahrain, and more. Each of the last three years has brought more students to the fore, eager to participate in this publication and to present the research they have done. When Gavin Falk first founded this journal in 2007, he wrote of it that he wanted a forum for students to share their work through publication. Moreover, he hoped

that: “The RCSIsmj will increase student interest in research and scientific writing by providing both a formal structure and staff mentorship to facilitate these pursuits”. This goal has been achieved through continued interest and support from RCSI faculty and staff, and student involvement. As we publish this issue and begin to look towards next year, I am encouraged to think of the students who value this journal as a learning resource, as a forum for their own work, and as a way to introduce themselves to the world of medical research and publication. With this fine base, there is no doubt in my mind that the RCSIsmj will continue to grow and improve in the coming years, and I look forward to every future edition. Kristl Vidya Dorschner – Director

Volume 3: Number 1. 2010 | Page 3


RCSIsmjprize

ECG Challenge 2010 Welcome to the RCSIsmj ECG Challenge!

Think you know the diagnosis? Try answering the questions and send your answers to editorsmj@rcsi.ie. Please include your name(s), year and faculty with your attachment. The winner will recieve a brand new copy of the eminent cardiology text

Braunwald’s Heart Disease, 8th Edition. Please direct any enquiries to editorsmj@rcsi.ie. The closing date for entires is April 16, 2010. Keep up to date on our website – www.rcsismj.com – for the latest on the due date and prizes. Good luck!

Questions 1. 2. 3. 4.

Describe the ECG (rate, rhythm, axis, intervals). What is the diagnosis? Describe the pathophysiology of this condition. What is the significance of the wave indicated by the black arrow?

Disclaimer RCSIsmj is the official student publication of the Royal College of Surgeons in Ireland. The opinions expressed in the journal are, however, those of the authors and cannot be construed as reflecting the College’s views, or those of the editorial committee. The editor

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5. Discuss the classification of this syndrome. 6. What is the emergency treatment of arrhythmias within this condition? 7. What is the long-term treatment of this syndrome? reserves the right to edit all copy submitted to RCSIsmj. Publication of an advertisement does not necessarily imply that the College, or the editorial committee, agrees with or supports the claims therein. For guidelines for authors, please see: www.RCSIsmj.com.


RCSIsmjprize

Ethics Challenge 2010 This is the second instalment of the RCSIsmj Ethics Challenge. The editorial staff would like to congratulate Adwait Mehta and Janso Padickakudi for their winning essay for the 2009 Challenge. Please see p. 20 for their submission. Once again, we invite all students to submit an essay discussing the ethical questions raised in the case study presented here. Medical ethics is an essential aspect of the medical curriculum and we hope to encourage RCSI students to think critically about ethical situations that arise during their education and their careers in healthcare. All essays will be reviewed by a faculty panel of experts and the winning essay will be published in the 2011 print edition of the RCSIsmj.

The deadline for submission of entries will be the same as the general submission deadline for the 2011 RCSIsmj. Please keep up to date by visiting our website – www.rcsismj.com.

parenteral nutrition because her GI tract was non-functional. She developed fungaemia due to fungal endocarditis and required pressors most of the time because of almost continuous sepsis. A very large and very deep sacral decubitus ulcer further complicated her care. Although she would open her eyes and visually follow people in her room, she made no response to any sort of verbal or tactile stimulus. The nurses noted, however, that she would moan softly when they changed her dressings. Despite the worsening prognosis, the patient’s daughter insisted on continued aggressive care. She stated that her mother had survived the Nazi concentration camps and would survive this illness. She further said that although her mother had no written advance directives or a healthcare proxy, she had on several occasions commanded her daughter: “Don’t let anything happen to me”, which the daughter interpreted as an order to make sure everything was done to keep her mother alive. By the fourth month of her ICU stay, the patient’s physicians felt that there was no chance that she would leave the hospital alive, and requested a medical ethics consultation and review by the hospital ethics committee.

Any questions? Email us at editorsmj@rcsi.ie.

Key questions to be addressed:

This is a perfect opportunity to be published, and is the only officially guaranteed publication in the RCSIsmj.

The case Can doctors say ‘enough’? A 77-year-old woman was admitted to New York Presbyterian Hospital, Columbia Division, with intestinal obstruction. The patient had a history of multiple prior abdominal surgeries for resection of colonic polyps, partial colostomy for bowel incarceration, and small bowel obstruction. The patient had undergone coronary artery bypass surgery and valve replacement three years prior to admission. She was very obese, was diabetic, and had peripheral vascular disease. Her mental status was normal. She was a Holocaust survivor, was married, and had one daughter. The patient underwent bowel resection for a large villous adenoma. One month postoperatively she developed septic shock and was re-explored. An anastomotic leak was found along with multiple intra-abdominal abscesses, which were drained. She went to the surgical ICU postop. Her subsequent hospital course was marked by severe complications. She developed multiple enterocutaneous fistulas, required ventilator support because of respiratory failure, needed regular haemodialysis, and was alimented intravenously with total

1. Identify the ethical issues involved in this case. 2. How would you address them? 3. Discuss your course of action and justify it within the framework you have established. 4. Consider weaknesses in your position and address potential challenges to your decision.

Submission guidelines Please construct a lucid, structured and well-presented argument for your course of action in this case. Please ensure that you have addressed all the questions highlighted and discuss these ethical issues academically, making sure to reference when necessary.

Your paper should not exceed 2,000 words. Your essay will be evaluated on three major criteria: 1. Ability to identify the ethical issues raised by the case. 2. Fluency of your arguments (note that there is no penalty for which side you discuss; just be sure to develop your arguments). 3. Academic quality with regard to depth of research, appropriateness of references and quality of sources.

Volume 3: Number 1. 2010 | Page 5


RCSI on the outside COMMISSIONING THE

King Hamad General Hospital SAMEER S KASSIM, GURLEEN BHATIA and ZEESHAN IJAZ present an inside look at Bahrain’s first university teaching hospital. Introduction The students at the RCSI-Medical University of Bahrain (MUB) have been unusually fortunate in that they have had the privilege to witness the opening of their university and their new university teaching hospital. We were given the unique opportunity to interview the RCSI Commissioning Team leaders in Bahrain and talk with them about the development of the King Hamad General Hospital (KHGH). There is currently only one large government-run secondary care hospital in Bahrain and the KHGH will help to meet the increasing demand for healthcare services. It will also increase the capacity for training medical and nursing students from the RCSI-MUB and other universities in the country.1

Commissioning Planning for the KHGH began with a feasibility study, and the master plan was drawn up by the French hospital consultant agency INGEROP. The Australian Hospital Design Group was then contracted to finalise the hospital infrastructure in December 2003.2 The facility design was defined by the RCSI Clinical Working Group under the direction of Professor Cathal Kelly and the Bahraini Government, and was to become RCSI-MUB’s main teaching site. Thus, the KHGH will be a specialised facility for the delivery of stateof-the-art healthcare, teaching and research, as well as fulfilling the national agenda defined in Bahrain Vision 2030.3,4 The scope of the RCSI Commissioning Team is to oversee design, construction and post-construction of the new facility.5 The Team also acts as an intermediary between other agencies involved in specific aspects of development, and equipment and service suppliers. It must balance the needs of the hospital’s sponsors with the need to implement health services that meet standards of best practice. This helps to ensure that the most recent hospital service models and guidelines are applied, thus meeting the international standards for hospital care should the institution choose to seek

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international accreditation.5,6 In the final phase, the Commissioning Team guides the hospital management team to ensure that those processes designed for the hospital are implemented as intended.5 The estimated building cost of the hospital is an impressive 100,000,000 Bahraini Dinars (€180,000,000).2 The complex will cover 64,000m2 and consist of three four-storey buildings linked by enclosed courtyards, containing 312 secondary care beds, and situated adjacent to the RCSI-MUB campus in Busaiteen. It will also have several specialty units including obstetrics and gynaecology, paediatrics, ophthalmology, ENT, accident and emergency, physiotherapy, occupational therapy, outpatient facilities and an intensive care unit. The maternity unit will replace the current facilities in Muharraq.1,2 In addition to providing hospital services, the KHGH will also provide teaching facilities for medical and nursing students from the RCSI-MUB and other universities. It will provide a 200-seat lecture theatre, conference rooms for faculty and students, and strong information technology infrastructure similar to that provided at the RCSI-MUB campus.1,2

Illustration of the King Hamad Hospital showing its three-block design, internal open courtyards and upper level connecting bridges.


RCSI on the outside

The twin towers of the Bahrain Financial Harbour in the capital city, Manama.

Accreditation The hospital will be accredited by Accreditation Canada, which will help to improve the safety and quality of services delivered to patients. In order to meet the external standards, the RCSI Commissioning Team worked to establish clear evidence-based protocols for all aspects of hospital activity, ranging from patient management to waste disposal.

There is currently only one large government-run secondary care hospital in Bahrain and the KHGH will help to meet the increasing demand for healthcare services. The accreditation process at the KHGH will take three years to complete and the process will begin after one year of hospital operations. During this time, hospital management and staff will also collaborate to identify key strengths and weaknesses. The Canadian approach to

accreditation is a rigorous peer review process comprising selfassessment against a set of standards, an on-site survey, and follow-up action on recommendations made in the survey.7,8

Conclusion The challenges for the RCSI Commissioning Team will continue as they review the newly implemented policies and management procedures. This is an ongoing process and the Team’s evaluation will feed directly into the accreditation process. The faculty and students are anxiously awaiting their new facility and the RCSI continues to grow as an international clinical cohort.

Acknowledgments The authors offer their sincere thanks to Professor Niall O’Higgins (Chair, Department of Surgery, RCSI-Bahrain) for his help and support. We would also like to thank Marian Noone (Director, RCSI Hospital Projects Board) and Olive Schmidt-Flynn (Project Director Commissioning) for the opportunity to talk about the KHGH project.

References 1. King Hamad General Hospital at Muharraq. Manama: Ministry of Works, Kingdom of Bahrain, 2009. Updated 2009. Cited May 30, 2009. Available from: http://www.works.gov.bh/default.asp?action=article&id=331. 2. King Hamad General Hospital. Manama: Health Information Directorate; 2009. Updated 2009. Cited May 30, 2009. Available from: http://www.moh.gov.bh/EN/AboutMOH/MOHProjects/KingHamad.aspx. 3. Kingdom of Bahrain. From Regional Pioneer to Global Contender: The Economic Vision 2030 for Bahrain, 2009. 4. Iglehart JK. The American healthcare system. Teaching hospitals. New Engl J Med 1993; 329 (14): 1052-6.

5. Toombs KE (ed.). Commissioning Hospital Construction. National Conference on Building Commissioning: May 2-4, 2007; Chicago, Il, USA. Portland Energy Conservation, Inc. 6. Chappel D, Miller P, Parkin D, Thomson R. Models of commissioning health services in the British National Health Service: a literature review. J Pub Health Med 1999; 21 (2): 221-7. 7. Morrow L. Preparing for a successful accreditation: strategies for engaging staff. Journal (serial on the Internet), 2009 Date; 2. 8. Robblee JA, Heidemann EG. Hospital accreditation and the surgeon: the Canadian experience. Surgeon 2004; 2 (6): 321-6.

Volume 3: Number 1. 2010 | Page 7


RCSI people 2008/2009 RCSI Rugby Captain MIKE WILLIAMS spoke to RCSI graduate and international rugby sensation Felipe Contepomi.

Mixing sport and medicine Felipe Contepomi is one of the RCSI’s best known alumni. He is both a medical doctor and has had a dramatically successful rugby career. He has captained his home country, Argentina, in international fixtures, has played in three World Cups, was nominated for International Rugby Player of the Year in 2007, was a fan favourite while playing for Leinster, and is now trying to make his mark for his new club in Toulon. In 2007 he graduated with a Bachelor’s in Medicine from the RCSI and began his internship in Beaumont Hospital. This interview was conducted in early October 2008.

On rugby Why did you choose Leinster when you left Bristol – you had offers from a lot of clubs? Playing with Leinster provided me with the opportunity to play with one of the best teams in Europe and to study at the College of Surgeons at the same time. If you have just one of those chances, you consider yourself lucky, and I had the opportunity to take both of them. It was an easy choice to make looking back, but at the time very little was known about how the Celtic League would progress, and in retrospect I consider myself very lucky. How do you feel about playing against your former Leinster team mates when you take to the field for Argentina against Ireland? I definitely don’t enjoy playing against them, because I know how good they are. I would rather play with Brian O’Driscoll than against him. The same goes for Girvan Dempsey, Shaggy [Shane Horgan] or Rob [Kearney].

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Surely you’re at an advantage having an insight into their game and how they play? Yes, but they know my game too. I know how good they are but it’s a team sport, and I’m playing with 14 other people who don’t play with them week in week out, so you still have to do your homework. And with the technology nowadays, you can see exactly what they do in different situations in the game. How do you feel about putting in a big hit against one of your club mates? The same way as if I play against Argentinian players when I am playing for Leinster. You give 100% for the team you are playing with, but especially so when you are playing for your country. But I think that whoever you play against, you should play with honesty and within the laws of the game; there should be no dirty play in that sense, so if a big hit is within the law, it’s welcome and part of the game. You play hard but you look after your team mates whether you’re playing for or against them, and that’s how you earn their respect. I wouldn’t be at all angry if I take a good hit, I would probably congratulate them. It’s part of rugby and the sport you play. You seem to have a great relationship with the Leinster fans. When you got your 100th Cap, the supporters made a presentation to you. That must have been a touching gesture considering you are so far from home. It was really nice. Since I’ve been here with my family they always treat us very well. It’s hard to come as a foreigner to a totally different culture, a totally different place, especially in Ireland, where players still play for their local club. Normally there are many more foreign players. Here, most of the Leinster players are from the Leinster area, which is great for the team but makes it very hard for a foreign player coming in.


RCSI people You’ve played rugby now in three countries, two professionally, and

On working with Professor Hill

captained your own national team, as well as playing alongside

I understand that you’re currently doing your internship under Professor Hill. How do you find working for him, having had him as a lecturer during your time at RCSI? Well, as a Professor, you know, he can be strict. When he works with his colleagues he is very good, he will demand quality and he looks after his team, and on a one-to-one basis he gets the best out of you. If you are lazy he may put you on the spot, but that’s no bad thing; although you may not enjoy it at the time, it’s good for you in the long run.

your brother. What would you say was your favourite moment in your rugby career? It would have to be playing with my twin brother in three World Cups; that was unbelievable, especially the last one. In terms of where we come from in Argentina, it was a dream. I wonder if we will ever be able to do as well again. We may not have won the World Cup, but people can see that Argentina was a successful team. It is not always the result that dictates success, but how you reach it.

On medicine How do you think the values you have learnt from playing top-level rugby will benefit you in your medical career? It’s not only rugby that gives you values. I’m a strong believer that playing a team sport teaches you different things, but you are also part of a team in your job as a doctor. So you are continuously working in a team, and whether you learn it in sport or in medicine it is no different. It is not something that you only learn from playing at a professional level:

On life Did you have many problems with the language barrier when you first came over from Argentina? I studied English at home in Argentina, and I went to an Irish school called Cardinal Newman College. I lived in Bristol for three years before I came here but I lived with three Argentinians, so that didn’t really help as I spoke Spanish all day. But coming here and having a life outside of the training camp helped a lot, especially working and studying in the College where I had to speak English all day, every day. And although I may get confused for a French guy with my pronunciation, I don’t see the language as a problem anymore.

any team that you are involved in where you strive to be the best you can be, but at the same time understanding that you are doing something for the good of many other people, teaches you the same thing. You will see that every day of your life, where there is an error or something that is not done properly, some people have the attitude that someone else will fix it, rather than taking responsibility and making sure it is corrected, and most importantly that it doesn’t happen again. And in sport it happens all the time. In rugby you don’t lay blame, you make up for the mistake and try and turn it around. The trouble is that often in medicine an error is seen as weakness and not an opportunity to learn. But we are human and we will all make errors, and if you learn from

How do you find juggling study with playing rugby and family life? Well obviously it is not easy. It required an understanding position from the Club and from College, both of whom were unbelievable. And then of course there is the support from your family. I have always said that my family is the most important thing in my life. Probably, though, this last three to four years is the least time I’ve spent with them, but I presume they understand that it is what I have to do, and they are always very supportive. If things go well in rugby or College I would not take all the credit. Yes you have to do certain things on your own but it is not always a one-man effort, and without the support of your family you would never achieve as much.

them they will happen less and less. And I think that in everything we see errors as weakness, but particularly so in medicine. But you should recognise your mistakes and not make excuses for them. Do you think you would’ve chosen orthopaedics if you didn’t have a background in rugby? Yes. I started my career thinking I was going to do that from the first minute. At home, when you qualify you go and do your residency, so you already know what you want to do when you finish college. But throughout my career I liked other disciplines as well; I like gastroenterology and general surgery as well, so at points that made me question my choice, but my intention has always been to stick with orthopaedics. Having been so successful in your rugby career, do you feel you’re putting extra pressure on yourself to be equally successful in medicine? Pressure is for the man who has to get up at 4.00am to shift sacks of potatoes for 12 hours each day and still not make enough money to feed his wife and children, that’s pressure. I don’t feel pressure in that way. I think you build your own pressure. In my career I want to be successful as a doctor, but for me success is not about being the best, but instead about reaching your potential. I will try to be the best doctor I can be, and if I achieve that, then I can consider myself successful.

Are you and Paula still enjoying Ireland? The weather is hard to cope with. The city itself, Dublin, is not huge, but it’s big enough to be active and lively. It’s beautiful to come and visit, but it’s the kind of city where you get more from living there than from visiting, I would think. Unlike London or Paris; they are beautiful to go and visit but to live there is pretty hectic. Finally Felipe, now that you are qualified as a doctor, do you have any plans to retire from rugby like your brother? The decisions are very personal: it is not an easy decision I can tell you. I’ve never thought about it really, but it is hard for people who have played rugby for a long time and they will tell you in particular how difficult it is. With Manuel, I tried to be more supportive of his decision rather than telling him what to do. It was important that whatever he decided, I made him feel like it was the right choice. I’ve always said when I stop enjoying rugby I will quit, if my body does not quit before that. Even being paid, you are putting your body on the line each training session, so no matter what you’re getting paid, if you stop enjoying it then there’s just no point. Felipe is yet to play his first game, after suffering an ACL injury in the semi-final of the Heineken Cup against Munster. His partner Paula has just given birth to their second child and he is working in the Orthopaedic Department of the Clinique Saint-Roch under Dr Jose Gadea.

Volume 3: Number 1. 2010 | Page 9


RCSI people

An interesting life AOIFE MORRIS spoke to Mr Harold Browne about his career as a surgeon and anatomist. As a witness to the vast changes in the medical and surgical professions, and indeed the RCSI, there are few who have seen more than Mr Harold Browne. Many will know and remember Mr Browne from their days in the Anatomy Room, where he has been teaching since 1953. His enthusiasm and witty approach has instilled a respect, if not a love, for the subject in many of his students.

When I came here, in late 1953, the teaching of anatomy was somewhat unstructured. A light approach Mr Browne has honed his approach to lecturing over the years. “Anatomy is a rather dull subject; basically, you must enlighten the atmosphere with a few risqué stories, if you don’t mind me saying so. You need to spice it up, make it interesting by talking about the pathology, the surgical and medical aspects. That’s the way I teach anatomy, and did teach it then.” Indeed, any RCSI student will know that, “as Moses led the Jews to the Promised Land, the gubernaculum leads the testes to the promised land of the scrotum”.

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Humour aside, Mr Browne is well aware of the challenges that anatomy can pose to the new medical student, particularly where the modern curriculum is concerned. “I feel, now that I’m at the end of my teaching career, that students are taught too much detailed anatomy. One forgets anatomy very quickly; personally I forget anatomy at times. It is necessary to refer to the books periodically. We often have discussions here [in the Surgeon Prosector’s Room] on the finer points of anatomy… no doubt we should make allowances for students learning such detailed material. If one teaches them solid, basic anatomy, they’ll remember it.” Teaching anatomy has evolved a great deal while Mr Browne has been at the RCSI. “When I came here, in late 1953, the teaching of anatomy was somewhat unstructured. There were no organised designated tables like today, but we still taught basic anatomy and I used to give lectures on standard and applied anatomy. Of course, we had demonstrations as they exist today, but there weren’t as many students as there are today.”

A distinguished faculty Mr Browne has personally witnessed the contribution and legacy of many professors of anatomy. When he first started teaching, Gilbert Marshall Irvine was Professor of Anatomy, assisted by Mr


RCSI people Tom Garry “who could be quite eccentric at times, and is alleged to have stated that only one person knew more anatomy than him … and that was God!” Professor Irvine was then succeeded by Professor Rooney. “In their time, Professors Irvine and Rooney, and Mr Garry, made great contributions to the progress of anatomy in the RCSI.” “In 1987, Professor [Stanley] Monkhouse reorganised the whole system of teaching. He initiated the table teaching, allotting one demonstrator to each two tables. He wrote the two reference books on anatomy, one for the first and one for the second years, with directions and questions on the day’s anatomy, and then specimen questions at the end of each topic. They really are most beneficial. Professor Monkhouse also spent a lot of time in the Anatomy Room and had great empathy with the students. I should also state that Professor Monkhouse wrote an anatomy book for students.” When Professor Monkhouse made a career change, he was succeeded by Professor Clive Lee. “He too has made a marvellous contribution to the Anatomy Department. He has developed and established an extensive research department, with their main research on stress in bones. Not alone has he himself obtained a PhD for his own work in this specialty; he has a large staff and, more recently, three of his graduates have obtained PhDs for their work with him. Professor Lee has recently introduced a dissection programme for students, and Professor Harold Ellis of Cambridge is a great advocate of this system.” Today, Mr Browne lectures and demonstrates as part of a team of surgeon prosectors. “As a group of retired consultants, we bring a great skill mix to the department, which we understand, going by end-of-term evaluations, is very much appreciated by the students.”

“In their time, Professors Irvine and Rooney, and Mr Garry, made great contributions to the progress of anatomy in the RCSI.” Bodies of work One constant during Mr Browne’s teaching tenure has been the use of cadavers for dissection. “I don’t believe one can learn anatomy from plastic specimens. One cannot beat hands-on. I presume there may come a time when the supply of cadavers may diminish and we may have to rely on plastic specimens, but as long as the supply lasts, I will be a great advocate of the use of cadavers. It’s the same with bones; I dislike these artificial bones – they just don’t have the same detail. One sees a lot of congenital abnormalities with the use of cadavers; ductus arteriosus, abnormalities of arteries, the bile ducts, the renal vascular supply, the ureters, horseshoe kidney. Plastic models can never resemble accurately the human body and its great detail.”

Changing times The number of students passing through the Anatomy Room has increased significantly over the years. “When I returned in 1987 [after he retired], there were only about 90 students in a class, as compared to the present when there are about 285. There were also three distinct groups: Irish one-third, Third World countries onethird and a middle group of Americans, Canadians, English and Scandinavians.” Similarly, when it comes to the number of women, Mr Browne notes that “it has changed very significantly. In my time, when I qualified from UCD [in 1946], it would have been the same proportion [as it was] here. I think it would have been about 70:30 [male: female], if not more”.

“I feel, now that I’m at the end of my teaching career, that students are taught too much detailed anatomy. One forgets anatomy very quickly.” Some of his more fundamentalist mentors and colleagues may have theorised that the growing numbers of women entering surgical specialties will have a negative impact on the previously maledominated arena, but Mr Browne is convinced otherwise. “A few of my female registrars are now surgeons and I know three, in particular, who are first-class surgeons. They are well able to hold their own, I can tell you. In my time, surgery of all types was purely a male-dominated specialty. I remember there was a famous surgeon I worked with one time and he said to me: ‘I shouldn’t be stitching this wound, the nurse here beside me is a much better seamstress than I!’”

Career and education Mr Browne undertook a fellowship in general surgery at the Mayo Clinic, and was awarded an MS degree by the University of Minnesota in 1953. “I spent four years there and my knowledge and technique of surgery was greatly enhanced. During that time I did general surgery and orthopaedics followed by six months of pathology, which was a great advantage to my surgical career. There were 23 operating theatres at St Mary’s Hospital (one of the three hospitals which make up the integrated centre that is the Mayo Clinic), and all the specimens following the surgeries of the day were laid out on tables in the pathology department. There was a lunch hour session given by Dr Docherty, who was a Canadian, and he gave expert teaching, grossly and microscopically, on all these various specimens. He was a marvellous teacher. I always remember that ‘common diseases are common!’” Considering the wealth of his own experience, he is a strong advocate of training overseas. “There was a huge volume of patients and the first day I worked with a very urbane man, Dr Gray, he did six partial gastrectomies. You wouldn’t see six partial gastrectomies here in 12 weeks. Ireland has a small population and there’s just not the volume here to learn all the techniques. It is mandatory that trainees should go abroad to these centres of excellence, not only in

Volume 3: Number 1. 2010 | Page 11


RCSI people America, but also Australia, Canada, the UK and Europe, and one must spend at least two or three years there.” On his return to Ireland, Mr Browne was a consultant surgeon in The Richmond Hospital. He practised there for 32 years, retiring in 1987. Surgery, in practice, was quite different during Mr Browne’s career. “There were very few specialists in those days. I did renal surgery, neck surgery, gastric and colon surgery. I had to do a lot of orthopaedic surgery because there would be no orthopaedic surgeon available in our hospital. The interns and students who worked with us got a tremendous all-round experience. Students today are with consultants who are all very specialised; they just don’t get that all-round education that the students did in my time.”

Surgical challenges Mr Browne considers the specialisation of surgeons to be one of the greatest challenges to our generation. He is optimistic about the improved patient care pathways that are part of specialist centres or ‘centres of excellence’, but is cautionary at the same time. “Specialisation has demanded a new population of specialists. In ways, it is good for the profession, because one can’t be generalised in everything, one can’t be good at everything, and it’s certainly better for the patients.” Mr Browne does not like the term ‘centre of excellence’, though, having worked in such centres where patients still died. From his experience, they will improve baseline standards of care because of the large volumes of patients being treated. He does, however, lament the demise of the generalist. “It is better to have specialists, but not too specialised. In those days, we had general surgeons and general physicians; they’re now a dying breed. It’s a pity really.” The finely-honed clinical skills and surgical techniques that Mr Browne would have used on a daily basis have been largely replaced by more technologically advanced investigations and minimally invasive procedures. “When I was a surgeon, it was purely clinical. One took a very careful history, carried out a hands-on examination of the patient, and ordered the appropriate x-rays. There were none of these CT scans or MRIs until late in my career. One depended on the radiologist to show one barium x-rays of the gastrointestinal tract, or whatever one was concerned with. Laparoscopic surgery came in after my time. I often wonder why one should do laparoscopic hernia operations when it’s a beautiful anatomical operation by open surgery. One of the great successes of laparoscopic surgery is the laparoscopic cholecystectomy. Professor David Bouchier Hayes performed the first such operation in Ireland and it has been extended to many other fields of surgery. I can’t comment on laparoscopic surgery; I’ve my own views about it but it certainly is the practice of today.”

Other issues Patients, too, play a different role in healthcare today, becoming more involved in their own management. Patient autonomy, however, is a double-edged sword; Ireland has seen a sharp increase in litigation and malpractice suits in recent years. With increased patient consultation and input, it seems that there are often unrealistic expectations from the patients despite the best efforts of

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their doctors. Mr Browne observed this trend as his own career progressed. “I was a Governor of the American College of Surgeons for six years, way back in the eighties, and we met every year at the American College of Surgeons Meeting. At one session, there were a hundred governors in the room and they asked anyone who had been sued to put their hands up and 80% put their hands up. I didn’t put my hand up and they said: ‘Why didn’t you put your hand up?’ and I said: ‘I’ve never been sued’. To this, another doctor remarked: ‘If you haven’t been sued at least three times, you’re not doing your operations properly!’ Now litigation in Ireland has increased markedly, it’s caught up with America. Surgeons here are very conscious of the fact. Some people are of the opinion that litigation makes surgeons more accountable. I feel it has potentially destroyed the patient–doctor relationship.”

“There were very few specialists in those days. I did renal surgery, neck surgery, gastric and colon surgery. I had to do a lot of orthopaedic surgery because there would be no orthopaedic surgeon available in our hospital.” The administration of hospitals and consultants has been revolutionised but, in Mr Browne’s opinion, not for the better: “In the present system, I feel that consultants have lost the influence we had when I was a surgeon. We participated in the boards of the hospital; we had a great input into the running of the hospital. From a satisfaction point of view, I feel that consultants today are not in charge of their own destiny. The system at present, in my opinion, is very unsatisfactory, despite the highly skilled doctors. They just do not have enough resources to care for their patients. For example, accident and emergency remains seriously overcrowded on a daily basis, a percentage of elective surgery is cancelled daily and lengthy waiting lists still exist. Despite the funding of the system, medicine is a well with no bottom to it”. As we sat down to chat in July 2009, ‘The System’ had just given us the Blasphemy Act, quite the source of bemusement to Mr Browne: “Does it mean we’re not allowed curse anymore?” At this stage in the game, Mr Browne has truly seen it all. From UCD to the Mayo Clinic, to the RCSI and the Richmond, a Fellow of the American College of Surgeons, a former president of the Medical Council, an Honorary Fellow of the RCSI, a Recipient of the College Medal, an eponymous lecture theatre in the hallowed halls of the Department of Anatomy … as he says himself, professionally and personally, he’s had an interesting life.

Acknowledgements The author would like to thank Mr Browne for his time and insights, and Ms Amanda Campbell and Mrs Vivienne Nash Browne for their assistance in completing this article.


RCSI career opportunity Oral and maxillofacial surgery in Ireland

Introduction Oral and maxillofacial surgery (OMFS) is one of the nine surgical specialties and is unique in that it requires qualifications in both medicine and dentistry. To become a specialty training registrar (StR) or consultant, it is necessary to obtain a fellowship in surgery, and most people will also complete a fellowship in dental surgery or equivalent. Registration with the Irish Medical Council and the Irish Dental Council is required. Despite the long training period, it offers a diverse professional life that is both challenging and rewarding for those who take the leap and return to pursue their second degree towards this specialty. Royal College of Surgeons in Ireland Student Medical Journal 2010; 3: 13-16.

What do oral and maxillofacial surgeons do? Oral and maxillofacial surgeons provide a variety of treatments in a well-defined anatomical area – the head and neck. They deal with the diagnosis, evaluation and treatment of conditions arising around the face, jaws, mouth and their environment, including the maxilla, mandible, nose, neck and salivary glands. The scope of the specialty and the management of the pathology encountered ranges from the surgical removal of teeth and facial pain

management, to excision and free flap reconstruction of oral-facial malignancy, facial trauma, and cleft lip and palate surgery (Table 1). The wide scope provides the opportunity to treat patients from different age groups and affords a varied and exciting practice. Oral and maxillofacial surgeons ideally work in teams and alongside other specialists including ENT surgeons, plastic surgeons, neurosurgeons, ophthalmologists, orthodontists, restorative dentists, clinical oncologists, radiotherapists and radiation oncologists, and pain specialists.

Table 1: Spectrum of conditions managed by oral and maxillofacial surgeons. Mark HL Wilson1, Dr Tom WM Walker2,

■ Cranial and maxillofacial trauma (soft and hard tissues)

Prof. Leo FA Stassen3

■ Cancer of the head and neck region and its reconstruction

1RCSI medical student

■ Disease of the salivary glands

2Registrar in Oral & Maxillofacial

Surgery, University College Hospital Galway 3Professor of Oral & Maxillofacial

Surgery, St James’s Hospital/Dublin Dental School and Hospital

■ Surgical correction of facial disproportion – both congenital and acquired ■ Cleft lip and palate surgery ■ Facial pain ■ Disorders of the temporomandibular joint ■ Surgical removal of impacted and buried teeth, cysts and benign tumours of the jaws ■ Placement of osseointegrated dental and extra-oral implants ■ Management of infections of the head and neck, including life-threatening fascial space infection ■ Conditions of the oral mucosa such as mouth ulcers, white patches and dentoalveolar infection

Volume 3: Number 1. 2009/2010 | Page 13


RCSI career opportunity Undergraduate dental degree (BDS) – five years

Clockwise from top left: FIGURE 1: A 3D reconstructed facial CT demonstrating severe maxillofacial injury. FIGURE 2: An ortho-pantomogram (OPG) of a patient who underwent open reduction and internal fixation. This was to correct a right-sided parasymphyseal fracture of the mandible that had subsequently sustained a second fracture, at his left angle, left condyle and right parasymphysis. Of note, the patient has three impacted wisdom teeth and an impacted upper right canine. FIGURE 3: Squamous cell carcinoma of the right lateral margin of the tongue. FIGURE 4: Right submandibular abscess secondary to a dental cause (impacted wisdom tooth).

History of oral and maxillofacial surgery World War II saw a large number of young men returning from combat with severe facial injuries. In the United Kingdom and Ireland ‘plastic surgery and jaw injury’ units were established in the Queen Victoria Hospital in East Grinstead, the Ballochmyle Hospital in Ayrshire, Scotland, and later in Dr Steeven’s Hospital in Dublin. In these units, consultant dental surgeons worked with plastic surgeons to reconstruct the faces of those soldiers who returned. Since then, dental surgeons have been increasingly involved in the reconstruction and rehabilitation of the head and neck. Since 1995 it has become compulsory for surgeons to be dually qualified to practice OMFS. OMFS has now established itself as a leader in several fields such as facial and craniofacial trauma, head and neck oncology and its reconstruction (including microvascular surgery), oral surgery and cleft palate/lip repair, and craniofacial surgery (Figures 1-4).

Training There are currently two routes to become an oral and maxillofacial surgeon (Figures 5-7). One option is to complete medicine as a first degree, then return to dental school after completing basic surgical training (BST) and the MRCS exam or an equivalent. In the UK, some trainees return to dental school after their two-year foundation programme (equivalent to intern and SHO 1 years). Irish medical graduates are at an advantage to finance themselves and pursue their interest in the specialty during their dental degree with BST/MRCS. It might be advantageous to obtain a year as an SHO in OMFS in the UK or

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Vocational training (dental VT) – year 1 OMFS experience (SHO) – year 2 (Membership of the Faculty of Dental Surgery at one of the royal colleges during this period, e.g., MFD RCSI)

Undergraduate medical degree (MB, BCh, BAO) – five or six years

Pre-registration year/internship

Basic surgical training scheme (BST). Surgical membership of one of the royal colleges, e.g., MRCSI Undergraduate medical degree – three to five years (MB, BCh, BAO)

Undergraduate dental degree (BDS) – three to five years. Pre-registration year/internship

Experience in OMFS – SHO/Reg. Basic surgical training (BST) – two years Surgical membership of one of the royal colleges, e.g., MRCSI

Higher surgical training scheme in OMFS – five years Intercollegiate FRCS (OMFS) Completion certificate of surgical training (CCST/CCT) Subspecialisation.

Consultant in oral and maxillofacial surgery

Higher surgical training scheme in OMFS – five years Membership of the Faculty of Dental Surgery at one of the royal colleges during this period, e.g., MFD RCSI Intercollegiate FRCS (OMFS) Completion certificate of surgical training (CCST/CCT)

Consultant in oral and maxillofacial surgery

FIGURE 5: Sequence of training pathways in oral and maxillofacial surgery.


RCSI career opportunity Ireland before starting dental school to gain firsthand experience in the specialty. Some dental schools either offer a shortened degree (three to four years) or offer graduate dental programmes as in the UK. After completing a dental degree, trainees with OMFS experience should apply for a surgical training three (ST3) post in OMFS and aim to complete their postgraduate dental membership examinations (MFDS/MJDF) during ST3 or ST4 year. It is important to ensure eligibility to apply for any Irish training scheme or ST3 (SpR1 in the UK). Most often, applicants are considered ineligible because of inadequate proof of completion of foundation competencies, which are available on the Internet and can be verified. Those who complete undergraduate dental training as a primary degree can then return to medical school after gaining a broadbased dental, oral surgery and basic OMFS experience. This can be achieved within two years of qualifying as a dentist, usually accompanied by sitting the postgraduate dental examinations and obtaining the Membership of the Faculty of Dental Surgery at one of the royal colleges (e.g., MFD/MFDS/MJDF or equivalent). Some medical schools now offer a three-year course specifically for dental graduates or a four-year graduate entry course. After a year of internship they apply for the RCSI BST in Ireland, or in core training one (CT1) in OMFS or surgery in general in the UK. Thereafter, they apply for ST3 in OMFS in the UK.

consultant level as the main factor for deficient service provision. Some of the key recommendations outlined by the report were to increase consultant numbers from six to 24 posts in the long term, develop academic posts in OMFS, and to regain recognition for training in OMFS in Ireland as a priority. Since 2003, four new oral and maxillofacial surgeons have been appointed in Ireland in the public hospitals and continued expansion at the consultant level is expected, with two posts advertised in the near future.

Internship

Core surgical training (CST) – two years

MRCS, courses, web-based learning, logbook/eportfolio

CCBST

Higher surgical training (specialty training) Higher surgical training (HST) is five years that is simultaneously taken with the intercollegiate FRCS (three to five years). Unfortunately, HST in OMFS was lost from Ireland in early 2000 and there is currently no HST in OMFS. However, it is hoped that a HST programme will be available by 2010. Training in OMFS is currently available in the UK, Europe, the USA and Australia. In the UK the first three years of the specialty training are general and competency based, while the next two years are specialised. The curriculum for HST in the UK and Ireland is available online via the Intercollegiate Surgical Curriculum Programme website (http://www.iscp.ac.uk). Currently, there is a trend towards a post-certificate of completion of training (CCT CST) fellowship in one of the sub-specialties (cleft, head and neck, craniofacial). It is expected that fellowships will become available in trauma and aesthetics in the near future (Figures 5-7).

Basic specialty training (clinical research)

MCh

Higher surgical training Five years – FRCS (MaxFac) undertaken between year three and year five

FRCS (MaxFac)

Satisfactory RITA

Oral and maxillofacial services in Ireland Over the last 20 years, OMFS has established itself as an important and accessible hospital service in many countries worldwide. Unfortunately, Ireland lags behind. A statutory government body, Comhairle na nOspidéal, which is now part of the HSE, stated in a report released in 2005 that oral and maxillofacial services in the Republic of Ireland had developed slowly and were largely underdeveloped in comparison to international standards.2 The report cited understaffing at

Completion certificate of specialist training (CCST)

FIGURE 6: Training pathway for oral and maxillofacial surgery in Ireland.

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RCSI career opportunity Conclusion

Further advice and links

OMFS offers diverse scope of practice in a specialty that is heavily dependent on surgical treatment of conditions. It offers the skills of dentistry and surgery in modifying the facial skeleton, managing dental occlusion, and reconstructing and rehabilitating the oral cavity. It is this balance of hard and soft tissue practice, as well as the broad range of congenital and acquired conditions, which present themselves to oral and maxillofacial surgeons. It makes for a demanding and rewarding career, working closely with other medical, dental and surgical specialties, as well as with allied health professionals.

British Association of Oral & Maxillofacial Surgeons – www.baoms.org.uk Association of British Academic Oral & Maxillofacial Surgeons – www.abaoms.org.uk Intercollegiate Surgical Curriculum Programme – www.iscp.ac.uk Post Graduate Medical Education & Training Board Report on OMFS Training – www.pmetb.org.uk/index.php?id=omfs

Oral and maxillofacial surgery training pathways Selection into medical school

Selection into surgery

Selection into OMFS specialty training

FY1

1

FY2

1

Specialty training

Core surgical training

2 CT1

CT2

1

ST3 Introduction to specialty** ST4

10-12 years

Route 1

2

MFDS EXAM*

*Optional Route 1

First degree dentistry

Route 2

First degree medicine

Undergraduate Dentistry (five years for a first degree or three years for a second degree) + Dental Foundation Year 1 Year 2/SHO*

ST5 ST6

2

ST7

Specialty/ special interest modules 8T8

FRCS examination

(five years for a first degree or three years for a second degree)

Foundation training

Route 2

Undergraduate medical training

11-12 years

MRCS examination (required for entry to specialty training)

**Required competencies may be achieved in Dental Foundation years 1 or 2

2 1

Certificate of completion of training (CCT)

Selection into dentistry

FIGURE 7: Training pathway for oral and maxillofacial surgery in the United Kingdom.1

Reference heading 1. Intercollegiate Surgical Curriculum Programme. Oral and

2. Comhairle na nOspidéal. Oral & Maxillofacial Surgery

maxillofacial surgery: the training pathway. Cited September

Services, June 2005. Cited September 1, 2009. Available from:

1, 2009. Available from: http://www.iscp.ac.uk/Syllabus/

http://www.lenus.ie/hse/handle/10147/44533.

Overview.aspx?Spec=OMF2.

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RCSI career opportunity The United Kingdom Foundation Programme

Royal College of Surgeons in Ireland Student Medical Journal 2010; 3: 17-19.

Table 1: Glossary of abbreviations. AFP

Academic Foundation Programme

EEA

European Economic Area

EMQ

Extended matching questions

EU

European Union (in the context of the article, interpret as ‘EU/EEA/Swiss’)

GMC

General Medical Council

GP

General practice

IMG

International medical graduate

MCCEE

Medical Council of Canada Evaluating Examination

MCQ

Multiple choice questions

MTAS

Medical Training Application Service

NHS

National Health Service

OSCE

Objective structured clinical examination

PLAB

Professional and Linguistic Assessments Board

RCSI

Royal College of Surgeons in Ireland

UK

United Kingdom

Division of Cardiovascular and

UKFPO

United Kingdom Foundation Programme Office

Medical Sciences; Academic

USMLE

United States Medical Licensing Examination

Janso Padickakudi1, Matthew Walters2, Alice McGarvey3 1Royal College of Surgeons in

Ireland; Academic Foundation Doctor 2010-2012, NHS Scotland, University of Glasgow 2Reader in Medicine and

Honorary Consultant Physician,

Foundation Programme Director, University of Glasgow 3Senior Lecturer in Anatomy; Vice

Dean for Student Affairs, Royal College of Surgeons in Ireland

The Royal College of Surgeons in Ireland (RCSI) Medical School has a significant international student population; therefore, it is natural for RCSI’s graduates to consider global career paths and opportunities. The United States and Canada are well-advertised options, with most students

familiar with the difficulties of writing the United States Medical Licensing Examination (USMLE) and the Medical Council of Canada Evaluating Examination (MCCEE). But have you ever considered a career with the National Health Service (NHS) of the United Kingdom (UK)?

Volume 3: Number 1. 2010 | Page 17


RCSI career opportunity This article aims to inform students of the internship opportunities that are available in the UK. In particular, this article aims to point out the exceptional opportunities offered by the Academic Foundation Programmes (AFPs). It will be of particular interest to European Union/European Economic Area/Swiss students for whom the transition is quite simple. The EEA is comprised of the 27 EU Member States, Iceland, Lichteinstein and Norway. For simplicity, the term ‘EU’ in this article is used to represent the EU, the EEA and the Swiss. It can be noted here that in order to apply for AFPs, international medical graduates (IMGs) need to write the Professional and Linguistic Assessments Board (PLAB) examination and obtain a right to work. However, once the candidate is deemed eligible to apply, applications are considered regardless of nationality and PLAB score.

Background In 2006, the Irish Department of Health endorsed the ‘Fottrell Report’ (‘Medical Education in Ireland: A new direction’) and its recommendation to decrease non-EU graduates at Irish medical schools from 60% of the student population (2003/2004 intake) to 25%. To achieve this, they proposed a variety of complex models that range from increasing EU student numbers to reducing non-EU spaces. The eventual target was to produce 700-740 EU graduates per year (up from 305 EU graduates), who will hopefully stay in Ireland. In contrast, non-EU students “generally return to their country of origin upon graduation”.1 In this context, the UK may become an increasingly interesting option for RCSI graduates.

National Health Service The NHS is the public healthcare service of the UK. It was established after World War II on the premise that good healthcare should be universally accessible. The NHS is government funded and the vast majority of services (from GP consultations to open heart surgery) are free to all residents of the UK at the point of service delivery.2

Foundation Programme Upon graduation from medical school in the UK, doctors embark on a two-year internship entitled the ‘Foundation Programme’. The first year of the Programme aims to be a “bridge between medical school and speciality training”,3 and includes compulsory rotations in both medicine and surgery. At the end of this year, trainees are registered with the General Medical Council (GMC). The second year aims to introduce the doctor to disease management. The Foundation Programme’s focus on outcomes is unique. A defined Foundation Programme curriculum outlines competencies that should be attained by trainees at the end of their training. The equivalent of such an extensive compendium for interns in Ireland does not yet exist.

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The NHS is government funded and the vast majority of services (from GP consultations to open heart surgery) are free to all residents of the UK at the point of service delivery. Application process Entry into the Foundation Programme is co-ordinated by the United Kingdom Foundation Programme Office (UKFPO) via a centralised process called the Medical Training Application Service (MTAS). For EU students, the application is simple. The main process takes place between July and October in the year before the student intends to start their Foundation Programme (for example a student would apply in 2010 for a programme that starts in 2011). Each application on MTAS is scored out of 100 points, with 40 points allocated to academic ranking and 60 to answers to standardised questions.4

Passing the PLAB does not guarantee employment. In addition, a number of eligibility criteria need to be met before an application is considered. The UK is divided into 27 regions, each having its own ‘foundation school’, which administers all of the Foundation Year jobs in its area. All applicants rank the foundation schools in order of preference. In turn, the applicants are ranked based on their application scores. An electronic algorithm then matches students to foundation schools.

Eligibility EU students are eligible to apply through the UKFPO subject to confirmation of their eligibility status. This is a simple application form that is completed by the Medical School Dean or Vice Dean, in combination with a photocopy of the student’s passport. Non-EU students are required to sit Step 1 and Step 2 of the Professional and Linguistic Assessments Board (PLAB) examination. Step 1 is a three-hour 200-EMQ/MCQ examination set at a level commensurate with Foundation Year 1. Step 2 is an objective structured clinical examination (OSCE). Passing the PLAB does not guarantee employment. In addition, a number of eligibility criteria need to be met before an application is considered. For 2010 programmes, applicants had to be an EU passport holder, a student of a UK medical school in their final year of study, or have the right to work as a doctor in training in the UK. Applicants who are unable to submit a valid right to work are only considered if there are insufficient eligible applicants who have the right to work in the UK.


RCSI career opportunity Foundation Programme 2010 match The UKFPO match for 2009/2010 graduates was completed in December 2009. The results of the match were that over 90% of EU applicants were allocated to their first choice of foundation school. In a second round of matching, all candidates who were eligible apart from the right to work (i.e., all international graduates who had completed their PLABs and had applied in time) were allocated to programmes that still had vacancies. The proportion of international applicants who obtained a job in the second round of matching has not been disclosed.

There is a variety of programmes on offer. For example, Hull/York has a fourmonth block of clinical or laboratory research, including HIV and genito-urinary medicine. Academic Foundation Programmes The AFP is a ‘Foundation Programme Plus’ and offers exceptional opportunities to successful candidates. It provides the regular foundation training, with additional structured opportunities for candidates to get involved with research, medical education or leadership/management. These programmes are becoming more competitive as awareness about them increases among UK medical students. Only 5% of UK graduates obtain an AFP. In contrast to the centralised applications for the mainstream foundation programme, AFPs are recruited by each foundation school individually. In addition to the application process outlined above, supplementary questionnaires and interviews form the admissions process. There is a wide variety of academic programmes on offer. For example, the Hull/York programme has a dedicated four-month block of clinical or laboratory research, including an exciting programme in HIV and genito-urinary medicine (HIV/GUM). By contrast, most Scottish and Welsh programmes offer academic training as a longitudinal theme throughout the two years, with

Only 5% of UK graduates obtain an AFP. In contrast to the centralised applications for the mainstream foundation programme, AFPs are recruited by each foundation school individually. In addition to the application process, supplementary questionnaires and interviews form the admissions process. didactic teaching in year one and research assignments and teaching responsibilities in year two. Leicester offers the largest cohort of academic foundation posts and stands out with an exceptional emergency medicine/clinical educator programme. If research, teaching or leadership/management are of interest, then the AFP is an opportunity to develop skills and competencies early in one’s career. Applications for AFPs need to be submitted early (some as early as May 2010 for August 2011 entry), and students who pursue this route must commit to attending interviews from June to August 2010. Phone interviews are available at most schools for students on electives. The benefit of the AFP, apart from the opportunities it presents, is that the student can then start final med with job security.

Conclusion The UK offers an interesting career option for graduates from the RCSI, particularly EU students. It offers a simple transition from medical school in Ireland to the highly structured, goal-oriented Foundation Programme in the UK. For non-EU students, it is of interest if they commit to the process of obtaining eligibility. It is often difficult for students to navigate the plethora of opportunities available in the global medical community. The UK Foundation Programme is one route.

Bibliography 1. Working Group on Undergraduate Medical Education and Training. Medical Education in Ireland: A new direction (the ‘Fottrell Report’). Cited 2006. Available from: http://www.dohc.ie /publications/ fottrell.html?lang=en. 2. National Health Service. About the National Health Services. Cited 2009. Available from: http://www. nhs.uk/NHSEngland /aboutnhs/Pages/About.aspx.

3. Moore C (ed.). The UK Foundation Programme Office. Rough Guide to the Foundation Programme. Cited 2007. Available from: http://www.foundationprogramme.nhs.uk. 4. The UK Foundation Programme Office. Foundation Applicant’s Handbook 2010. Cited September 2009. Available from: http://www.foundation programme.nhs.uk.

Volume 3: Number 1. 2010 | Page 19


RCSIsmjethics challenge RCSIsmj Ethics Challenge winner 2009

“Whatever in connection with my professional practice … I see or hear, in the life of men … I will not divulge.” – Hippocratic Oath (5th Century BC)

Royal College of Surgeons in Ireland Student Medical Journal 2010; 3: 20-24.

Introduction

Adwait Mehta1, Janso Padickakudi1 1RCSI medical students

Page 20 | Volume 3: Number 1. 2010

The RCSIsmj Ethics Challenge 2009 presented the case of a rural GP in Ireland who has diagnosed one of his patients, Richard, as HIV positive. Given a troublesome marriage in which Richard and his wife Sheila have stopped any form of intimacy, the GP is threatened with litigation should Richard’s HIV status become known to Sheila. The age-old notion of patient confidentiality is, clearly, at the centre of this ethical dilemma. This article aims to identify the ethical issues raised by the case, to address

these academically and to suggest how the situation might be addressed in a satisfactory manner.1 Throughout the article weaknesses of the arguments are also identified. The underlying question that is posed is of interest to medical students who will encounter ethical dilemmas throughout their careers: how is it possible for a GP to reconcile his professional duty of confidentiality with protecting the welfare and health of another patient and of society in general?


RCSIsmjethics challenge Ethical issues The case raises key ethical issues, which merit academic discussion. The core issues are: ■ Richard’s autonomy and right to confidentiality; ■ Sheila’s autonomy and right to health; ■ the GP’s dilemma in respecting Richard’s confidentiality while simultaneously safeguarding the health of Sheila and of society at large; ■ the GP’s “duty to warn”; ■ the GP’s choice of method of disclosure; ■ Richard’s and the GP’s responsibility to prevent transmission; and, ■ the GP’s responsibility to notify authorities.

Background – ethics Before the case is tackled it is important to establish basic principles of ethics and law that can be referred to in our line of argument. There are four basic principles of ethics (the “Belmont principles”) that must form the basis of all medical decisions for doctors: ■ beneficence: an obligation to provide the most beneficial treatment; ■ non-maleficence: the duty to protect persons from harm; ■ autonomy: the patient’s right to an informed, uncoerced decision with regard to their diagnosis and treatment (informed consent and patient confidentiality are extrapolations of this principle); and, ■ justice: the physician’s responsibility to provide equal medical care to all.2 The main conflict for the GP in this situation is the balance between Richard’s autonomy in terms of confidentiality, and nonmaleficence towards Sheila, who is at a potential risk of contracting HIV.

Background – Irish Medical Council guidelines According to the Irish Medical Council (IMC), there are four circumstances in which exceptions to confidentiality may be justified without the patient’s consent:3 1. When ordered by a judge in a court of law, or by a tribunal established by an act of the Oireachtas. 2. When necessary to protect the interests of the patient. 3. When necessary to protect the welfare of society. 4. When necessary to safeguard the welfare of another individual or patient. The IMC further stipulates that in cases where one of the above is satisfied, notifications to third parties should, if possible, be made with the informed consent of the patient.3 In accordance with point 4 of the IMC framework, the GP is obliged to safeguard Sheila’s welfare by informing her of Richard’s diagnosis. Although the couple is currently not intimate with each other, a legitimate potential risk of transmission exists

due to the nature of their relationship (i.e., marriage).4 Also, the IMC guideline to protect the welfare of society is pertinent to this case and will be explored in more detail shortly. Does the GP need to be concerned about the welfare of society? Are there any guidelines that require him to alert the authorities to prevent local transmission?

Legal issues and physician litigation Despite such guidelines, physician liability and potential legal cases must still be addressed. To illustrate physician immunity, a case in India (where the Medical Council employs almost identical ethical guidelines)5 is used here. The ‘Mr X vs. Hospital Z’ case involved a man’s claim for damages against a hospital whose staff informed his future wife’s family of his HIV status. The court held that the future wife’s right to health, and the provision of the Indian Penal Code, which makes it an offence to knowingly risk spread of an infectious disease, legally negated the patient’s right to confidentiality. Furthermore, the Indian Code of Medical Ethics permits the disclosure of otherwise confidential information when there is a health risk to another person.6 Thus, the GP in this case should receive a favourable verdict if a legal case is filed against him. Naturally, this conclusion must be drawn cautiously since it is based on the assumption that no other factors confound the case.

The Tarasoff case and the “duty to warn” The Tarasoff case was a landmark trial in the USA in which Prosenjit Poddar had informed counsellors of a fantasy to harm an unnamed love interest, who was readily identifiable as Tatiana Tarasoff. Poddar’s healthcare providers raised concern but efforts to commit him as an inpatient were dropped as authorities found him to be “rational”. Two months later, Poddar stabbed Tarasoff to death. The courts ruled that counsellors had had the “duty to warn” Tarasoff. The conclusion of the trial has altered the practice of healthcare. It is now widely accepted that a patient’s “protective privilege ends where the public peril begins”.7 Applying both current Irish legal requirements and the Tarasoff case to our dilemma, there seems to be an obligation on the GP to inform Sheila. The weakness of this argument, however, is that the breach of confidentiality and consequent repercussions are based on assumptions of how Richard will act, not on his actions themselves. We assume that he will have intercourse with his wife. But how can the GP justify pre-emptively disrupting Richard’s life despite knowing that Richard and Sheila are not sexually intimate? From an academic perspective, the literature shows that anywhere between 40 and 65% of HIV-positive individuals (both heterosexual and homosexual) fail to disclose their condition to all of their sexual partners.8,9,10 For argument’s sake, if we assume that Richard will fall into this category, then we must further examine disclosure, reasons for non-disclosure and the benefits of disclosure of HIV status in order to obtain the best outcome for all those involved.

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RCSIsmjethics challenge Disclosure HIV status disclosure has long been recognised as a complex interaction of individual beliefs, social support, and relationship types and their sexual nature.11 In the current biopsychosocial model of healthcare, it is paramount to recognise these factors in the prevention of further HIV transmission.12,13,14,15 Thus, the following question arises: to whom does the patient need to disclose their HIV status? Is it only to sexual partners? Or is it also to friends, family, employers, healthcare providers or even strangers? Commonly cited reasons for non-disclosure include stigma, need for privacy, fear of rejection by sexual partners, denial, low viral load, type of sex, location of sexual encounter, legal reprisal (fear of arrest), and condom use (no need to disclose).9,16,17 Interestingly, research shows that individuals who self-identify as homosexuals, ethnic minorities, sex workers, or those who report depression, are less likely to disclose.17,18 Open disclosure has been found to lower infection rates, as persons are motivated to adopt safer sex practices.12 It is also recognised that non-disclosure plays a central role in global HIV transmission and is associated with greater sexual risk taking.13,14 Social analysis has shown that HIV disclosure to one’s family, friends, and lovers – although potentially socially detrimental – was also found to be positively related to social support and the use of more adaptive coping strategies.19 The implications of this literature on our case are that these are the issues that Richard needs to have addressed before he can disclose his status to his wife. His main concern is further marital discord, perhaps even separation from his wife. Undeniably, Sheila is at risk of infection. However, being the immediate patient, the GP’s role would be to address Richard’s underlying concerns. The communication involved in this type of counselling would ensure that the GP has done everything in his power to gain informed consent from Richard before informing Sheila. This step is not strictly necessary – it is merely humane.

HIV in stable relationships With an increasing number of HIV infections occurring in stable relationships, the burden of coping with HIV notification and its economic, emotional and physical impacts is well established. In contrast, little has been written on the impact of HIV disclosure on partnership durability or dissolution. The literature, using cohorts from Northern Thailand, Uganda and Malawi, identifies the following six factors that determine marital stability in couples in which only one partner is HIV positive:20,21,22 ■ gender (males are more likely to divorce an HIV-positive wife than vice versa); ■ duration of partnership before disclosure; ■ economic constraints; ■ the role of the extended family for social support; ■ fear of stigmatisation by community; and, ■ the existence of children, which is strongly correlated with a decision to stay in the marriage.

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The weakness of this approach is that the presence of risk factors predisposes to, but does not predetermine, individual behaviour. Consequently, although Sheila is a female and the couple has two children, it would be impossible to judge Sheila’s reaction. Furthermore, a particular weakness of this argument is that conclusions based on this literature need to be drawn with caution because of differences in cultural, economic and religious circumstances.

Partner notification The next issue that we explore is the role of the GP and how he can best address this situation. The literature suggests three methods of partner notification. Partners may be notified: by index case – “patient/self-referral”; by a healthcare worker – “provider referral”;23 or, by “contract referral”, in which healthcare workers encourage index patients to notify their partners.24 Although all three approaches have been shown to be successful methods of disclosure,25 researchers in North America have shown that provider referral generally ensures that more partners are notified and medically evaluated than self-referral does.26,27,28 In the last decade, literature has been published regarding recommendations and guidelines for breaking bad news.29 However, it is important to note that there is little evidence about the best approach, so most guidelines are based on opinion.30 Buckman developed a six-step protocol that the GP may employ in this circumstance. The model is based on private meetings with no time constraints, in which both partners can have all their ideas, expectations, concerns and questions addressed.29 This academic point addresses one of the core issues in our case, and suggests that the GP should inform Sheila personally in order to ensure her safety. A compromise solution between the methods of disclosure could be a combination of the three approaches. For example, the GP could encourage Richard to notify Sheila during a joint consultation in his practice. This method would change the dynamics of confidentiality between the GP and his patients and ensure that accurate information is conveyed to Sheila. The session may also be used to answer any medical questions that Sheila may have.

Transmission prevention Viral load, the chief predictor of HIV transmission, is dramatically reduced by successful antiretroviral treatment.31,32 Promoting both condom use and antiretrovirals will further reduce the chances of transmission.33 It is important to keep in mind that the risk of transmission increases both with increasing number of encounters and the nature of encounters. Encouraging abstinence is a possible measure; however, it is generally less utilised in the setting of serodiscordant couples.34,35 Recently, international research has made it clear that male circumcision can be efficacious in reducing the risk of HIV transmission from men to women.36


RCSIsmjethics challenge In keeping with non-maleficence, it is essential for the GP to address prevention of HIV transmission between Richard and Sheila. Whatever the result of the marriage, it is crucial that the GP educates both Richard and Sheila on HIV prevention for the benefit of Sheila and all their future potential sexual partners.

Disease notification In a broader sense, the GP’s responsibility for reporting Richard’s HIV status to public authorities is disputable. In Ireland37 and the United Kingdom,38 in contrast to the USA,39 HIV is not a notifiable disease. This is despite evidence that many Irish healthcare professionals believe that HIV should be notifiable.40 Reports recognise that the current status of notification in Ireland has significant implications for epidemiological studies and causes considerable underestimation of the prevalence of HIV.40 The GP’s approach in this case should be to keep Richard’s HIV status confidential in terms of the broader community. Unless he has occupational exposure that may put others at risk, there is no utilitarian benefit of disclosing his status to the community. The weakness of this approach is that HIV surveillance and epidemiology is impeded, but its strength is that it upholds the patient’s confidentiality and dignity.

Conclusion Breach of confidentiality is a contentious issue that requires ethical sensibilities and a thorough understanding of current legal

guidelines. Both of these must then be synthesised into a plan of action for the GP involved in the case. Given the information presented, we therefore suggest that the GP take the following approach: ■ applying the Belmont principle of non-maleficence, the IMC guideline of disclosure to safeguard the well-being of a third party, and the “duty to warn”, the GP should set out to inform Sheila of Richard’s HIV status; ■ the GP should address Richard’s reasons for non-disclosure and counsel him on the benefits of disclosure. This is in line with the Belmont principle of beneficence; ■ the GP must progress to inform Sheila; he may do this himself, or by encouraging Richard to do so. This needs to happen in private, with sufficient time for both Richard and Sheila to ask questions and voice concerns; ■ Richard and Sheila should both be counselled in the prevention of HIV transmission and safe sex practices; and, ■ as HIV is not notifiable in Ireland, authorities need not be informed in this instance. In conclusion, it is evident that the management of a couple in which one partner has been diagnosed as HIV positive is a complex issue. The Hippocratic Oath, in which doctors swear to confidentiality, should be implemented with consideration for the ethical and legal context.

References 1. Royal College of Surgeons in Ireland. Ethics Challenge. Royal College of Surgeons in Ireland Student Medical Journal 2008; 2 (1): 5. 2. The Belmont Report. Ethical principles and guidelines for the protection of human subjects of research. Cited October 12, 2009. Available from: http://ohsr.od.nih.gov/guidelines/belmont.html. 3. Irish Medical Council. A Guide to Ethical Conduct and Behaviour (6th ed.). Cited October 12, 2009. Available from: http://www.medicalcouncil.ie/_fileupload/standards/Ethical_Guide_6th_Edition.pdf. 4. Van Der Straten A, Gómez CA, Saul J, Quan J, Padian N. Sexual risk behaviours among heterosexual HIV serodiscordant couples in the era of post-exposure prevention and viral suppressive therapy. AIDS 2000; 14 (4): F47-54. 5. NO. MCI-211 (2)/2003-Ethical/ MEDICAL COUNCIL OF INDIA. NEW DELHI-110002. Cited October 15, 2009. Available from: http://www.mciindia.org/meetings/Ethics/2003/Ethical%20Minu tes%2022%20&%2023%20.11.2003.pdf.

6. Dickens BM, Cook RJ. Ethical and legal issues in reproductive health law and ethics in conflict over confidentiality? International Journal of Gynecology & Obstetrics 2000; 70 (3): 385-91. 7. Bayer R, Toomey KE. HIV prevention and the two faces of partner notification. Am J Public Health 1992; 82 (8): 1158-64. 8. Ainslie DC. AIDS and sex: is warning a moral obligation? Health Care Analysis 2002; 10 (1): 49-66. 9. Garbach PM, Galea JT, Aman B, Shin A, Celum C, Kerndt P et al. Don’t ask, don’t tell: patterns of HIV disclosure among HIV positive men who have sex with men with recent STI practising high risk behaviour in Los Angeles and Seattle. Sexually Transmitted Infections 2004; 80 (6): 512-7. 10. Simbayi LC et al. Disclosure of HIV status to sex partners and sexual risk behaviours among HIV-positive men and women, Cape Town, South Africa. Sexually Transmitted Infections 2007; 83: 29-34. 11. Sullivan KM. Male self-disclosure of HIV positive serostatus to sex partners: a review of the literature. J Assoc Nurses AIDS Care 2005; 16: 33-65.

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RCSIsmjethics challenge 12. Sturdevant MS, Belzer M, Weissman G, Friedman LB, Sarr M, Muenz LR et al. Relationship of unsafe sexual behaviour and the characteristics of sexual partners of HIV infected and HIV uninfected adolescent females. Journal of Adolescent Health 2001; 29 (3 Suppl.): 64-71. 13. De Rosa CJ, Marks G. Preventive counselling of HIV-positive men and self-disclosure of serostatus to sex partners: new opportunities for prevention. Health Psychology 1998; 17 (3): 224-31. 14. Hyde J, Appleby PR, Weiss G, Bailey J, Morgan X. Group-level interventions for persons living with HIV: a catalyst for individual change. AIDS Education and Prevention 2005; 17 (Suppl. A): 5365. 15. Smith RC. The biopsychosocial revolution. Interviewing and provider-patient relationships becoming key issues for primary care. Gen Intern Med 2002; 17 (4): 309-10. 16. Carr RL, Gramling LF. Stigma: a health barrier for women with HIV/AIDS. Journal of the Association of Nurses in AIDS Care 2004; 15 (5): 30-9. 17. Derlega V, Winstead B, Greene K, Serovich J, Elwood WN. Perceived HIV-related stigma and HIV disclosure to relationship partners after finding out about the seropositive diagnosis. Journal of Health Psychology 2002; 7 (4): 415-32. 18. Knight KR, Purcell D, Dawson-Rose C, Halkitis PN, Gomez CA, Team SUIS. Sexual risk taking among HIV-positive injection drug users: contexts, characteristics, and implications for prevention. AIDS Education and Prevention 2005; 17 (Suppl. A): 76-88. 19. Simoni JM, Demas P, Mason HR, Drossman JA, Davis ML. HIV disclosure among women of African descent: associations with coping, social support, and psychological adaptation. AIDS and Behavior 2000; 4 (2). 20. Boileau C et al. Sexual and marital trajectories and HIV infection among ever-married women in rural Malawi. Sex Transm Infect 2009; 85 (Suppl_1): i27-i33. 21. Tangmunkongvorakul A, Celentano DD, Burke JG, de Boer MA, Wongpan P, Suriyanon V. Factors influencing marital stability among HIV discordant couples in northern Thailand. AIDS Care 1999; 11 (5): 511-24. 22. Amanyire MB. Discordant couples! A silent high-risk group in HIV transmission, a case of Uganda. Int Conf AIDS 1998; 12: 374 (abstract no. 23165). Available at: http://gateway.nlm.nih.gov/MeetingAbstracts/ma?f=102228795 .html. 23. Hogben M et al. The effectiveness of HIV partner counselling and referral services in increasing identification of HIV-positive individuals: a systematic review. American Journal of Preventive Medicine 2007; 33 (2): S89-S100. 24. Mathews C et al. Strategies for partner notification for sexually transmitted diseases (review). Cochrane Database Syst Rev 2001; 4: CD002843.

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25. HIV Partner Counselling and Referral Services. Cited October 12, 2009. Available from: http://www.cdc.gov/hiv/topics/prev_prog/AHP/resources/guidel ines/Interim_partnercounsel.htm. 26. Macke BA, Maher JE. Partner notification in the United States: an evidence-based review. Am J Prev Med 1999; 17: 230-42. 27. Oxman AD, Scott EA, Sellors JW et al. Partner notification for sexually transmitted diseases: an overview of the evidence. Can J Public Health 1994; 85 (Suppl. 1): S41-7 (abstract). 28. West GR, Stark KA. Partner notification for HIV prevention: a critical reexamination. AIDS Education Prevention: official publication of the International Society for AIDS education 1997; 9 (3, Suppl.): 68-78. 29. Farber NJ et al. The good news about giving bad news to patients. J Gen Intern Med 2002; 17 (12): 914-22. 30. Walsh RA, Girgis A, Sanson-Fisher RW. Breaking bad news. 2: what evidence is available to guide clinicians? Behav Med 1998; 24: 61-72. 31. Quinn TC, Wawer MJ, Sewankambo N et al. Viral load and heterosexual transmission of human immunodeficiency virus type 1. N Engl J Med 2000; 342: 921-9. 32. Vernazza PL, Troiani L, Flepp MJ et al. Potent antiretroviral treatment of HIV infection results in suppression of the seminal shedding of HIV. AIDS 2000; 14: 117-21. 33. Garnett GP, Gazzard B. Risk of HIV transmission in discordant couples. Lancet 2008; 372 (9635): 270-1. 34. Bunnell RE et al. Living with discordance: knowledge, challenges, and prevention strategies of HIV-discordant couples in Uganda. AIDS Care 2005; 17 (8): 999-1012. 35. Allen S et al. Sexual behavior of HIV discordant couples after HIV counselling and testing. AIDS 2003; 17 (5): 733-40. 36. Sullivan PS, Kilmarx PH, Peterman TA et al. Male circumcision for prevention of HIV transmission: what the new data mean for HIV prevention in the US. PLoS Med 2007; 4 (7): e223. 37. Notifiable Diseases Sub-Committee of the Scientific Advisory Committee, National Disease Surveillance Centre. Review of Notifiable Diseases and the Process of Notification. Cited October 13, 2009. Available from: http://www.hpsc.ie/hpsc/NotifiableDiseases/NotificationLegislati onandProcess/ReviewofNotifiableDiseasesandtheProcessofNotific ation/File,3550,en.pdf. 38. List of Notifiable Diseases. Cited October 13, 2009. Available from: http://www.hpa.org.uk/HPA /Topics/InfectiousDiseases/InfectionsAZ/1234432664900/. 39. Summary of Notifiable Diseases – United States, 2006. Cited October 12, 2009. Available from: http://www.cdc.gov/mmwr/ preview/mmwrhtml/mm5553a1.htm. 40. Health Protection Surveillance Centre. HIV and AIDS in Ireland. Cited October 12, 2009. Available from: http://www.hpsc.ie/hpsc/A-Z/HepatitisHIVAIDSandSTIs/HIVand AIDS/SurveillanceReports/File,3276,en.pdf.


RCSIsmjoriginal article An audit of primary care referrals to the Ophthalmic Accident and Emergency Department of the Royal Victoria Eye and Ear Hospital, Dublin Abstract Aims: The objective of this audit was to determine the pattern of general practitioner referrals to the ophthalmic casualty department and to make recommendations to improve the service. Methods: Clinical data were collected from the Accident and Emergency Department (A&E) case notes regarding patient demographics, reason for referral by GP, triage group, diagnosis and course of management. Results: A total of 2,015 patients attended the A&E during the one-month study period, of whom 335 (16.6%) were GP referred. A total of 271 (80.9%) of these patients were non-urgent referrals. Non-painful and non-sight threatening conditions accounted for 172 (51.3%) referrals. The consistency of ocular examinations in the GP letters was poor, with only 16.4% recording visual acuity and 49.9% recording any examination findings. Conclusion: There is a high rate of non-emergency referrals to the ophthalmic A&E. There is a need for better ophthalmic training for GPs, either as part of the existing training scheme or as part of continued education programmes. The introduction of a standard GP referral form with focused questions would allow better triage of these patients on arrival in the A&E department. The expansion of the role of the casualty nurse specialist would also help to alleviate pressure on this overburdened system. Keywords: Ophthalmic, audit, accident and emergency, primary care.

Royal College of Surgeons in Ireland Student Medical Journal 2010; 3: 25-28.

Introduction Hammed Al-Arrayedh1, Maeve O’Doherty2, Conor Murphy1,2,3, Fran O’Reilly1 1RCSI medical students 2Royal Victoria Eye and Ear

Hospital, Adelaide Road, Dublin 3Professor of Ophthalmology,

Royal College of Surgeons Ireland

The Royal Victoria Eye and Ear Hospital is a specialised hospital for ophthalmic and ear, nose and throat conditions. The ophthalmic division of the hospital provides a 24-hour, seven day per week, ‘walk-in’ accident and emergency service. There were over 30,000 patient attendances in 2008 with an average of 100 patients per day. The Accident and Emergency (A&E) Department is staffed by one full-time casualty doctor and one or two rostered senior house officers. The high number of patients presenting to the A&E poses

great challenges for the efficiency of the service. All of these patients are first seen and categorised by a triage nurse and are then assessed by a nonconsultant hospital doctor (NCHD). The patients either self refer or are referred by their general practitioner (GP), optometrist or another hospital. The aim of this audit was to determine the nature and outcome of GP referrals to the A&E Department. We assessed the urgency of these referrals and analysed patient demographics, reason for referral, diagnosis and management plan.

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RCSIsmjoriginal article Table 1: Baseline demographics of study participants (n=335). 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0%

97.61%

Characteristic

Number of patients Percentage

Sex (no.) (%) Male Female

49.85%

171 164

51% 49%

24 235 76

7% 70% 23%

254 41 40

76% 12% 12%

Age (no.) (%)

16.42%

History stated

History stated

Ocular findings stated

Ocular findings stated

Visual acuity stated Visual acuity stated

FIGURE 1: Characteristics of the GP referral letter.

Methods This prospective audit was undertaken in the Royal Victoria Eye and Ear Hospital A&E from July 17, 2009, to August 17, 2009. All patients attending the ophthalmic A&E with a letter from their GP were enrolled in the study. Patients who were self-, hospital- or opticianreferred, or attending for ear, nose and throat complaints, were excluded. The following information was collected from the case notes and referral letter: patient demographics; reason for referral by the GP (assessed from the documentation of relevant ophthalmic history, eye examination and visual acuity in the GP letter); triage time; triage category; diagnosis by NCHD; and, follow-up outcome. The data collected was categorised into predetermined categories and entered into an electronic database. This audit did not require ethical committee approval and patient confidentiality was ensured by strictly excluding the collection of patient personal data.

Results The total attendance at the ophthalmic A&E during the course of this study was 2,015 patients. Some 335 (16.6%) of these patients were referred by their GP. An ophthalmic history was provided in 327 (97.6%) of these referrals, whereas ocular examination findings and visual acuity were documented in 167 (49.9%) and 55 (16.4 %), respectively (Figure 1). Patient demographic data showed a 1:1 male to female ratio, with a mean age of 46.5 years (standard deviation 20.4, range 26-67). Some 254 (76%) patients attended A&E during the hours of 9.00am to 5.00pm (Table 1). On arrival in A&E, the patients were triaged and categorised into four groups by the ophthalmic nurse specialist using the Manchester Triage System (Table 2). The average triage time was 21 minutes. Some 271 (80.9%) patients did not require urgent consultation following triage. Those requiring urgent (should be seen in less than 60 minutes) and extremely urgent (should be seen in less than 10 minutes) attention made up 16.7% and 0.6% of the attendees, respectively (Figure 2). As shown in Table 3, a wide range of conditions was diagnosed by the NCHD. No

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0-18 yrs 18-64 yrs 65+ yrs Time of arrival (no.) (%) 9.00am to 5.00 pm 5.00pm to 10.00pm 10.00pm to 9.00am

Table 2: The Manchester Triage System. Red – less than 10 minutes

Green – less than 60 minutes

Blue – waiting Yellow – for availability return for review

1. Penetrating injury

1. Corneal abrasion

1. Painless diplopia

2. Chemical burn

2. Corneal conjunctiva, foreign body

2. Flashes and floaters

3. Headache, sudden loss of visual acuity, elderly, frail, giant cell arthritis

3. Orbital cellulites

3. Recent non-specific blurred vision

4. Painful third cranial nerve palsy, diplopic

4. Infectious conditions, adenovirus

4. Non-specific eye pain

5. Acute glaucoma

5. Corneal ulcer, abscess

5. Mild conjunctivitis

6. Crying babies with cloudy cornea

6. Welding flash

6. Trichiasis

7. Hypopyon

7. Retinal detachment

7. Cyst (except in children)

8. Severe eye pain 8. Hyphema

8. Blepharitis

9. Intraocular foreign body

9. Dry eyes

9. Recent surgery with complications 10. Mental and physical disability 11. Rx in other hospital 12. Severe conjunctivitis 13. Children <5 years


RCSIsmjoriginal article A&E Triage groups 0.60%

■ Red (must be seen in less than 10min)

1.79%

■ Treated and discharged

Patient Course 12.5%

8.7% 1.8% 0.6%

16.72%

■ Yellow (return for review)

■ Requiring no treatment and discharged

13.4%

■ Treated and referred to OPD

■ Green (must be seen in than 60min)

80.90%

■ Treated and referred to A&E

■ Treated and referred elsewhere

■ Blue (non-urgent waiting on availability)

17.6% 45.4%

■ Admitted ■ Not treated and referred

FIGURE 2: The Manchester Triage System.

FIGURE 3: Patient management course after being seen by a nonconsultant hospital doctor.

Table 3: Ophthalmic diagnoses of the study participants by the senior house officers.

Table 4: Diagnosis groups of the study participants (n=335) by the non-consultant hospital doctor.

Diagnosis

Cases (n=335)

%

Group*

Group

Description

Percentage

Other No abnormality detected Conjunctivitis Foreign body Cyst Dry eye Uveitis Cataract Blepharitis Corneal abrasion Subconjunctival haemorrhage Posterior vitreous detachment Trauma Herpes zoster ophthalmics Pterygium Macular degeneration Scleritis Glaucoma Chemical injury Migraine Pre-septal cellulites Contact lens-related Diabetes Retinal vascular disease Third nerve palsy Retinal detachment Cerebro-vascular accident Corneal disease Optic neuritis Squint Giant cell arteritis

36 35 35 31 29 23 17 17 14 11 9 9 7 7 6 5 5 5 4 3 3 3 3 2 2 2 2 2 1 1 1

10.7% 10.4% 10.4% 9.3% 8.7% 6.9% 5.1% 5.1% 4.2% 3.3% 2.7% 2.7% 2.1% 2.1% 1.8% 1.5% 1.5% 1.5% 1.2% 0.9% 0.9% 0.9% 0.9% 0.6% 0.6% 0.6% 0.6% 0.6% 0.3% 0.3% 0.3%

5 4 4 2 4 4 3 4 4 2 4 1 3 3 4 1 3 3 3 4 3 3 1 1 1 1 3 3 1 4 3

1

Sight-threatening

7.2%

2

Painful

14.0%

3

Painful and sight-threatening

16.7%

4

Neither

51.3%

5

Other

10.7%

*Abbreviations: 1: Sight-threatening; 2: Painful; 3: Painful and sight-threatening; 4: Neither; and, 5: Other.

abnormality was detected in 34 (10.4%) patients. Only 119 (35.5%) patients were found to have either a painful or sight-threatening condition (Table 4). A total of 152 (45.4 %) patients were treated in A&E and discharged, 59 (17.6%) were treated and followed up in A&E, 45 (13.4%) were discharged without any treatment, and 42 (12.5%) were referred to the outpatient department. Patients with acute ocular emergencies requiring admission constituted only 1.8% of total referrals (Figure 3).

Discussion The Ophthalmic A&E Department at the Royal Victoria Eye and Ear Hospital provides a dedicated round the clock emergency service. Patients attending the service by GP referral present with a wide variety of diagnoses and 80.9% of these cases were found to be non-urgent. As in all areas of clinical medicine, successful triage of referrals depends on the provision of adequate details regarding history and examination findings by the referring doctor. Only 16.4% of patients had a record of their visual acuity on the referral letter and the majority of these cases had been seen by an optometrist prior to visiting their GP. Similarly, an attempt to examine the eye had been documented by the referring GP in only 49.9% of cases. The introduction of an ophthalmic standard referral form, including patient and GP details and simple objective questions such as patient complaint, visual acuity and external eye signs, might encourage ophthalmic examination by GPs, provide better information for the triage nurse and facilitate speedier assessment.

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RCSIsmjoriginal article A similar study was undertaken in 2001 by Fenton et al, which showed similar data where 17% of the patients referred to A&E were GP referred, while non-urgent referrals constituted 60-70% of patients. This is comparable to the results found in this audit, where only 16.6% were GP referred, of which 80.9% were non-urgent referrals.1 Since their study, the A&E service has introduced an A&E triage system and a GP liaison office. The GP liaison office in the Royal Victoria Eye and Ear Hospital, which employs one GP liaison officer, was set up in November 2005 in order to facilitate communication between the A&E service and primary care. The GP liaison office has been a positive addition to the hospital’s service, where GPs have direct access to the feedback given to patients sent to the A&E. It is important to strengthen the communication between the GP and the GP liaison office to facilitate an efficient system. The role of ophthalmic education for GPs must also be addressed. Currently, ophthalmology is not part of postgraduate GP training in Ireland. Consequently, GPs may lack confidence in the diagnosis and management of eye conditions. With appropriate training and supervision, GPs could develop their interest in ophthalmology. They can thereafter assist in the management of many patients with nonsight threatening eye conditions, which currently constitute a significant part of a GP’s workload. A number of ophthalmology study days have been set up previously by the GP liaison office, but reintroduction of these ophthalmology study days for GPs would facilitate their continuing education. Community ophthalmologists provide general ophthalmic care in wide areas of the country. By expanding this service, more non-emergency cases could be appropriately managed in the community. Not only would this decrease the burden on A&E but it would also benefit patients who will no longer have to travel significant distances to attend the Royal Victoria Eye and Ear Hospital in Dublin. The evolving role of the ophthalmic nurse specialist ensures effective time management and patient satisfaction, and decreases the workload of medical staff. After initial assessment by the triage nurse, simple ophthalmic cases such as meibomium cysts can be managed and discharged by the nurse without doctor involvement. A study by Buchen et al in 2003 showed that 22% of patients presenting to the eye casualty clinic were treated and discharged successfully, with 2.5% of patients returning unplanned. The study also showed that non-sight threatening external eye diseases that could be treated successfully by a trained specialist ophthalmic nurse were the most common presenting conditions.2 These conditions include

foreign bodies, corneal abrasions, blepharitis, lid cysts, sub-conjunctival haemorrhages, conjunctivitis and dry eye. These conditions constituted 45% of the cases presenting to the Royal Victoria Eye and Ear Hospital in this audit, and therefore expansion of this service by ophthalmic nurse specialists in the Royal Victoria Eye and Ear Hospital A&E could lead to a decrease in waiting times and workload for medical staff and an increase in patient satisfaction. However, as demonstrated in a follow-up study by Buchan et al, the importance of clinical governance measures such as audit, risk management, clinical management protocols and continued medical education of ophthalmic nurse specialists would be required in order to maintain a high standard of clinical care in this model.3 Recently, a study in Scotland highlighted the impact of direct electronic optometric referral with ocular imaging to a hospital eye service.4 It has shown that electronic referral with images to the hospital eye service is a safe, speedy, efficient and clinically accurate system that avoids unnecessary consultation in 37% of cases. This scheme can potentially decrease transportation costs and waiting time for patients, and is associated with a direct financial saving, as outpatient appointments cost from £108 to £307 in Scotland. The limitation of the system has been demonstrated in four cases, where the diagnosis was wrong using imaging alone. Consideration should be given to the development of an electronic referral system for GPs referring patients to the Royal Victoria Eye and Ear Hospital A&E Department. In summary, this audit shows that a large percentage of patients attending the ophthalmic A&E following GP referral are non-urgent. These patients should be treated by GPs or ophthalmic nurse specialists, or referred to the outpatients department in order to decrease the burden on A&E. This study shows that more effort should be directed towards GP education, the development of management guidelines for common ophthalmic conditions, the introduction of a standard referral form and an increase in ophthalmic nurse specialist involvement in patient assessment and management. These changes would aid the development of a more efficient emergency service and significant improvements in patient satisfaction.

Acknowledgments This project was supported by the 2009 Award of Alumni Student Research Fund in Ophthalmology awarded by the RCSI research office. I would like to acknowledge the support of Professor Conor Murphy, Consultant Ophthalmic Surgeon and Professor of Ophthalmology, RCSI, and supervisor for the project.

References 1. Fenton S, Jackson E, Fenton M. An audit of the ophthalmic division of the accident and emergency department of the Royal Victoria Eye and Ear Hospital Dublin. Ir Med J 2001: 94 (9): 265-6. 2. Buchan JC, Saihan Z, Reynolds AG. Nurse triage, diagnosis and treatment of eye casualty patients: a study of quality and utility. Accid Emerg Nurs 2003; 11 (4); 226-8.

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3. Buchan JC, Ashiq A, Kitson N, Dixon J, CasselsBrown A, Bradbury JA. Nurse specialist treatment of eye emergencies: five-year follow-up study of quality and effectiveness. Int Emerg Nurs 2009; 17 (3): 149-54. 4. Cameron JR, Ahmed S, Curry P, Forrest G, Sanders R. Impact of direct electronic optometric referral with ocular imaging to a hospital eye service. Eye 2009; 23 (5): 1134-40.


RCSIsmjoriginal article Prescribing patterns and administration of intravenous paracetamol: a clinical audit Abstract Background: Intravenous (IV) paracetamol was authorised by the Irish Medicines Board in 2003. Thereafter, the Drugs and Therapeutics Committee (DTC) in the study hospital added the IV preparation to the hospital formulary in September 2005. The DTC policy allows for IV administration only when the oral (PO), rectal (PR) and enteral routes are not available. Aim: To identify the prescribing and administration patterns of IV paracetamol, to assess its appropriateness and to identify the associated opportunity cost. Methods: A retrospective survey was conducted on patients who were prescribed paracetamol on adult medical and surgical wards. The patients were randomly selected and their healthcare charts were reviewed over a two-week period in September 2008. Results: A total of 1,934 administrations were surveyed. Compliance with policy was demonstrated in 94.3% of administrations. The opportunity cost of using IV instead of PO tablets was found to be in excess of â‚Ź23,000 per annum for the study hospital. Conclusion: The majority of paracetamol administration was compliant with hospital policy. The cost implications for inappropriate administration were identified by calculating the difference incurred when IV was chosen over the equally efficacious PO/PR routes. Current findings and recommendations can be presented to relevant stakeholders (doctors, nurses and pharmacists) in order to review the usage of IV paracetamol and improve adherence with policy guidelines. Key words: Intravenous paracetamol, clinical audit, audit cycle, prescribing guidelines. Royal College of Surgeons in Ireland Student Medical Journal 2010; 3: 29-32.

Introduction

Linda Fitzharris1, Tamasine Grimes2 1RCSI pharmacy student 2Pharmacy Department, AMNCH

In 2003, Intravenous (IV) paracetamol (PerfalganÂŽ) was authorised for the Irish market by the Irish Medicines Board (IMB). It is indicated for the short-term treatment of moderate and severe pain following surgery and for the treatment of fever.1 Oral (PO) or rectal (PR) administration of paracetamol is as effective as IV administration, and should therefore be used as first-line routes of administration.1 The bioavailability of paracetamol varies depending on the route of

administration. IV paracetamol provides onset of pain relief within five to 10 minutes after administration.1 PO preparations are completely absorbed from the gastrointestinal tract with a peak plasma concentration in 30 to 60 minutes. The bioavailability of suppositories is approximately 80% of that of tablets.1 Clinical trials to date have concentrated on the morphine-sparing effects of IV paracetamol and have indicated that although morphine consumption was reduced, pain control was no greater.2

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RCSIsmjoriginal article The Drugs and Therapeutics Committee (DTC) in the study hospital added the IV preparation to the hospital formulary in September 2005. The DTC policy states that IV paracetamol may only be prescribed by the acute pain team, intensive care team or by anaesthetists, and is justified only when the PO and PR routes are unavailable.3 The availability of PO administration can be determined by whether the patient is pre-operative and ‘nil per mouth’. Factors such as dysphagia and vomiting are additional considerations. The PR route is unavailable if the patient is non-mobile (e.g., post-operative) or has gastro-intestinal symptoms (e.g., diarrhoea). The IV route of administration is associated with a higher incidence of anaphylactic reactions.2 Also, the therapeutic value of the parenteral route is not supported by a thorough comparative evaluation.4 There is a significant cost difference between the IV and either the PO or PR preparations of paracetamol available in the Irish market. These differences highlight the potential saving in choosing a cheaper but equally efficacious oral tablet over the IV route, which is over 200 times the cost.5 The acquisition cost associated with a 1g dose of an oral tablet is four cents; for an oral soluble tablet is 55 cents; for a suppository is €2.30; and, for an IV solution is €8.28. In addition, the IV solution requires the use of IV administration sets and constitutes an invasive procedure. The aim of this paper is to identify the prescribing and administration patterns of IV paracetamol, to evaluate adherence to hospital policy standards, to identify reasons for nonadherence and to identify the associated opportunity costs.

Methods The study design was a clinical audit conducted as a retrospective cohort survey. Clinical pharmacists were asked to identify patients on the general medical and surgical wards who were prescribed IV paracetamol during a two-week period (September 15-26, 2008). Patient identification numbers were randomised and 198 patients were selected. Data were collected on 108 patients (80%) for whom records were successfully retrieved from the Medical Records Department; the remainder of the records were not available. The data collection form was designed to collect information on patient demographics (gender, age, length of hospital stay, clinical indication for paracetamol, bowel status, fluid status, mobility status) and procedural details (surgical procedure undertaken, date, time and type of procedure). Information was also collected on each dose of paracetamol administered to the patient, the route of administration and the availability of the PO or PR routes at the time of each administration. Data were collected retrospectively by reviewing healthcare records, and adherence to policy for each administration was ascertained by the availability of the PO or PR routes when IV

Page 30 | Volume 3: Number 1. 2010

paracetamol was administered. Targeted parameters included patient mobility, and bowel and fluid status. Details of whether the patient was ‘nil per mouth’ were noted, along with medicines administered by a non-IV route. Data were entered into SPSS v. 15 and descriptive and inferential statistics are reported. The opportunity cost for paracetamol was calculated per annum and quantifies the monetary difference incurred when IV was chosen over the PO/PR routes.

Results Some 51.9% of the study population analysed was male, the median age was 59 years (range 16-91) and the majority (81.5%) received surgical care. Greater than one-third (37%) of patients were under the care of general surgery, followed by orthopaedics (26%), medical (19%), and vascular surgery (7%), and the remainder were a mixture of gynaecology, urology and ear, nose or throat (10%). The majority (69.4%) underwent a minor or major procedure during their stay as an inpatient. A total of 1,934 administrations were surveyed for the 108 patients. The most common prescription (87.2%) included IV plus another route. The other routes available were PO or PR and the choice of route rested with the nurse administering the medication. The route administered in the majority was PO (91.1%), IV (7.4%), PR (0.7%), or via enteral feeding tube (0.8%). The factors associated with selection of route are described below.

Adherence with prescribing policy Review by the acute pain team was documented in the healthcare record for 18.5% of patients, and a recommendation to use IV paracetamol was documented in the healthcare record for one patient (0.9%). The prescriber was not discernible in the majority of cases and so it could not be determined if the prescription was generated by intensivists or anaesthetists. The prescription was co-signed by the pharmacist in 85% of cases, and in 47.2% of cases they added a qualifying comment to the drug prescription and administration chart (the Kardex) to advise use of PO or PR routes as first-line therapy. In eight patients, the choice of IV/PO/PR paracetamol was prescribed but not administered.

Adherence with administration policy Adherence with hospital DTC administration policy was demonstrated in 94.3% of administrations. Of the IV doses administered, the OR route was available in 53.8% and the PR route was available in 92.7% of the cases.

Exploring reasons for non-adherence There was a statistically significant association between the ward in which the patient received care and adherence to policy, indicating that adherence was more likely on some wards than others (χ2=19.38, df=9, p=0.022). Also, there was an association between the prescription type and adherence, i.e., doses


RCSIsmjoriginal article 25,000.00

Table 1: Association between prescription type (regular, once off, or as required) and compliance with DTC administration policy (χ2=8.746, p<0.05).

Regular

Compliance (%) Yes

No

n

95.1

4.9

1,534

Euro (€)

Prescription type

20,000.00 15,000.00 10,000.00 5,000.00

Once off

As required

n

100

91.3

109

0

8.7

1,825

7

393

1,934

prescribed ‘as required’ were less compliant than those for regular or once-off administration (χ2=8.746, df=2, p=0.013) (Table 1). There was no association between adherence and doses administered day time (07:00-21:00) or night time (21:00-07:00) (χ2=0.238, df=1, p=0.328). There was a weak association between adherence and endorsement of the qualifying comment on the Kardex by the clinical pharmacist, although this was not statistically significant (χ2=0.238, df=1, p=0.09). Of those patients who underwent a procedure, there was an association between non-adherence and the time from procedure to administration. The results indicate that non-adherence was greatest on the day of procedure after the PO route became available (χ2=141.6, df=5, p<0.001) (Table 2). There was no association between the specialty team overseeing patient care and adherence (χ2=1.608, df=4, p=0.807) (χ2=0.792, df=1, p=0.272), or between patient gender and adherence (χ2=0.298, df=1, p=0.397).

Calculating costs During the two-week study period, a total of 1,934 administrations of paracetamol were recorded, which extrapolates to 50,284 administrations annually. Considering that 5.7% of the total 1,934 administrations were administered as IV when other routes were available, this would result in 2,866 non-adherent administrations per annum. The cost difference incurred by choosing the more expensive IV formulation over the cheaper but equally efficacious and safe PO formulation was found to be €23,615.84 per annum for the study hospital (Figure 1).

Discussion The high level of adherence (94.3%) to policy is encouraging because of its implication for patient safety and cost effectiveness. However, there is a 200-fold difference between the ingredient cost of an IV versus a PO dose of paracetamol.5 This difference may vary depending on the market but it generally holds that IV solutions are considerably more expensive. For example, in Australian hospitals,

0.00

IV

PO-tablet PO-soluble PR Preparation Cost of administration Potential savings

FIGURE 1: Cost of IV paracetamol per annum against PO and PR formulations. Unit cost per 1g of paracetamol: IV (€8.28); PO-tablet (€0.04); PO-soluble (€0.55); and, PR (€2.30).5 Ghiculescu et al found that IV formulation is 100-fold the cost of PO and two-fold the cost of PR.6 Advantages of IV are accuracy of dose delivered to the patient and targeted peak analgesic effect (Figure 1).7 To date, there has been no published data to justify the cost of IV over other routes.8 It should be expected, therefore, that restrictions on IV use form part of hospital policy.6,7,8 Indentifying conditions associated with non-adherence may provide an opportunity for implementing effective change. For example, wards that were shown to have lower compliance can be targeted for education and training. The finding that non-adherence was greatest on the day of a procedure may reflect a misperception that IV administration is more potent than other routes or a reluctance to use the PR route, either on the part of the patient or staff member. This is important to consider as the vast majority of patients audited received surgical care. IV paracetamol was most often administered post-operatively, even after the patient food intake restrictions were lifted (Table 2). The duration of IV use was not noted in the medical chart, nor was a recommendation to review the method of administration. This may have resulted in the administration of IV beyond when other routes may have become suitable. Despite the prescribing restrictions, it is possible that junior medical staff may have prescribed the drug. This was unclear because the prescriber did not include their training level beside the prescription, and therefore it cannot be ascertained if the acute pain team, anaesthetist, or other medical staff on call made the recommendation. Clinical pharmacists aim to maximise the appropriate use of IV paracetamol by labelling the drug Kardex with “Use PO or PR first line, as effective as IV”. It is unclear whether or not this influences compliance and it may be worthwhile to consider alternative strategies, such as implementing an automatic stop on IV paracetamol beyond 48 hours unless reviewed by the pain team or anaesthetist. Another consideration could be to empower the clinical pharmacist to amend the Kardex, as appropriate, on their review.

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RCSIsmjoriginal article Table 2: Association of the duration between procedure and administration with compliance to DTC administration policy (χ2=141.6, p<0.05). Time of IV paracetamol administration with respect to procedure

Compliance (%)

Yes

No

n

Day before

99.1

0.9

228

Day of

72.6

27.4

106

Day after

87.2

12.8

179

Two days after

93.8

6.3

160

Three days after

97.9

2.1

143

Four+ days after

97.9

2.1

625

n

1361

80

1441

Non-compliance with “as required” prescriptions might be overcome by discontinuing the choice of the IV route once PO/PR routes become available. Ideally, PO should replace IV once the patient is able to eat solids and swallow oral drugs. Lamb et al highlighted the problem of idiosyncratic ordering and administration of paracetamol. They concluded that hospital guidelines for paracetamol should be more specific in terms of indication for use and to ensure that the medical staff is precise in what their prescription of paracetamol means.9 IV paracetamol is a relatively new preparation and there is limited safety data available to date, and so its use should strictly follow formulary guidelines.9 Most published studies have concentrated on whether its use results in a reduction in morphine consumption and little has been published comparing IV to PO or PR for either pain control or the treatment of fever.10 Clinical trials to date have had small sample sizes and this may contribute to the lack of statistical significance of their results.4 We recognise the limitations of this study, but for the future we recommend that this type of audit be performed in a greater number of patients and in additional hospitals and medical centres.

Conclusion We recommend that prescribing IV paracetamol should be restricted to the pain, intensive care and anaesthetic teams. It should be prescribed only for short-term treatment and reviewed after 48 hours by the authorised prescribers. This audit found that the majority of IV paracetamol administered in general medical and surgical adult patients was compliant with DTC policy. Nonadherence was associated with specific wards, prescription type and the duration between procedure and administration. The annual cost of administering IV over PO preparations was in excess of €23,000.

Acknowledgments I would like to thank the members of the Pharmacy Department of the Adelaide and Meath Hospital and the National Children’s Hospital (AMNCH) for their co-operation and support.

References 1. Summary of product characteristics, Perfalgan® solution for infusion, 10mg/ml. 2. Topol A. London New Drugs Group Briefing Document. 2004. Updated 2004. Cited. Available from: http://www.nelm. nhs.uk/en/NeLMArea/Evidence/Drug-Specific-Reviews /495087/Post.aspx?query=%2520Intravenous%2520paracetamol&rank=5. 3. Adult Medicines Guide, AMNCH and Naas General Hospital 2008/9. 4. Anon. Paracetamol for injection. New formulation: why so widely used? Prescrire Int 2003; 12 (67): 178. 5. United Drug wholesaler purchase costs. November 2008.

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6. Ghiculescu RA, Kubler PA, Gleeson P. Drug utilisation evaluation of i.v. paracetamol at a large teaching hospital. Internal Medicine Journal 2007; 37: 620-3. 7. Livingstone HL, Marcus RJ. Which preparation of paracetamol? An audit of usage and costs. Paediatric Anesthesia 2007; 17: 1006-15. 8. New South Wales Therapeutic Advisory Group. IV paracetamol – where does it sit in hospital practice? Curr Opin 2005; 10: 1-8. 9. Lamb SA, Henry RL. Paracetamol pro re nata orders: an audit. J Paediatr Child Health 2004; 40: 213-6. 10. Keys CD. The drug cupboard. British Journal of Anaesthetic and Recovery Nursing 2008; 9 (3): 79.


RCSIsmjoriginal article Assessment of the mental health of Irish adolescents in the community

Abstract Aim: This study aims to assess a community of Irish adolescents using the Strengths and Difficulties Questionnaire (SDQ) for behavioural difficulties and mental health disorders. Method: All fifth and sixth class pupils attending eight primary schools were eligible to participate. The self-report version of the SDQ was administered to the pupils in the classroom. Results: Thirty participants (8.7%) had an abnormal SDQ score and 53 (15.3%) had a borderline abnormal SDQ score. Abnormal SDQ scores were more common among females (9.7%; mean score = 11.86; sd = 5.4) than among males (7.6%; mean score = 10.96; sd = 5.26). The difference was most pronounced on the emotional symptoms subscale (females received a mean score of 4.03 [sd = 2.1] compared to a mean male score of 2.90 [sd = 2.1]). Conclusions: Mental health problems are widespread among Irish adolescents. The SDQ is a useful preliminary assessment tool of the mental health profile of Irish adolescents and highlights the need for childhood mental health promotion in schools. The SDQ could also be used in a primary care setting to screen adolescents for mental disorders. Key words: Psychiatry, behaviour, mental disorders, adolescence, questionnaires, schools, Ireland. Royal College of Surgeons in Ireland Student Medical Journal 2010; 3: 33-35. Paula Greally1, Ian Kelleher2, Jennifer Murphy2, Mary Cannon2 1RCSI medical student 2Department of Psychiatry,

Education and Research Centre, Beaumont Hospital, Dublin

Introduction Adolescence is a period of physical, psychological, emotional and personality change, which can lead to stress, and emotional and behavioural problems. Studies have shown that there is a 10% overall prevalence of mental disorders among five- to 15-year-olds and this figure may be as high as 25% among children and adolescents who attend primary care services in the UK.1 Standardised assessment of mental

health difficulties in a primary care setting is commonplace in the US; however, this practice is not prevalent in Ireland.2 The Strengths and Difficulties Questionnaire (SDQ) (Goodman, 1997)3 is a useful tool that could be applied in a community setting to assess emotional and behavioural problems.2 It has been found to effectively predict the presence of conduct, hyperactivity, emotional, and psychiatric disorders.4 Previously, it has been used in Britain

Volume 3: Number 1. 2009/2010 | Page 33


RCSIsmjoriginal article to screen a community cohort for child psychiatric disorders and it identified over 70% of individuals with conduct, hyperactivity, depressive and some anxiety disorders.5 Numerous studies have been conducted to examine the rates of psychiatric disorders among young people worldwide,6,7 and these describe an increase in particular psychiatric disorders, such as conduct and emotional problems.8 There is little epidemiological data on the prevalence of psychiatric disorders among Irish adolescents, although data will soon be available from the national longitudinal study ‘Growing Up in Ireland’. Prior to this, Dr Fionnuala Lynch of the Mater Misericordiae Hospital in Dublin and Professor Carol Fitzpatrick of University College Dublin conducted an epidemiological investigation of mental health problems among Dublin adolescents aged 12 to 15 years.9 In this project we propose to assess a community of Irish adolescents, using the SDQ for behavioural difficulties and mental health disorders.

Methods The study population The study was carried out in Maynooth, Lucan, Leixlip, Celbridge, Carragh and Dunboyne, in Ireland. The study population consisted of fifth and sixth class pupils attending eight primary schools in these towns, aged between 10 and 13 years.

The Strengths and Difficulties Questionnaire The SDQ is a user-friendly screening questionnaire, which can be used to assess behavioural problems and mental health disorders. It can be administered to the parents and teachers of four- to 16year-olds and to the 11- to 16-year-olds themselves. Goodman, Ford, Simmons, Gatward and Meltzer reported the scale’s internal reliability to be acceptable, with a Cronbach alpha coefficient of 0.73.5,10 The questionnaire consists of 25 questions subdivided into five categories: conduct; hyperactivity; peer problems; emotional; and, prosocial, with five questions in each scale. A sample item from the SDQ is: “I am restless, I cannot stay still for long”. The participant chooses between three boxes and ticks their response. The boxes are labelled “not true”, “somewhat true” or “certainly true”. Each of the categories is given a score and then summed to get a total difficulties score, except the prosocial score, which is assigned a separate score. The scores can then be used to make separate predictions for conduct–oppositional disorders, hyperactivity–inattention disorders, and anxiety–depressive disorders.

The screening procedure After obtaining approval from the Beaumont Hospital Ethics Committee, permission was sought from the principals of each of the selected schools to recruit students for the study. An information sheet and consent form was sent to each parent. The consent form was to be signed by a parent or guardian and returned to the school. The questionnaires were distributed to the pupils as a group in their classrooms during a pre-arranged time.

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Each pupil who had returned a consent form was given a copy of the questionnaire for completion. The pupils were asked to read the questionnaire and answer it to the best of their ability. Every effort was made to ensure that the pupils had privacy when completing the questionnaire. Researchers were available to answer any of the pupils’ questions or to clarify instructions. The pupils were also asked to include their name, class and age.

Statistical analysis Data were analysed using the Statistical Package for the Social Sciences (SPSS) and established cut-off scores indicated high risk for mental health problems.11

Results A group of 346 pupils aged 10 to 13 years, which consisted of 171 boys and 175 girls attending the eight participating schools, participated in the screening study. The mean age of the study population was 11.57 years. Thirty participants (8.7%) received an abnormal SDQ score. A further 53 (15.3%) received a borderline abnormal SDQ score. Abnormal and borderline abnormal scores are shown in Table 1. The most common abnormal scores were on the hyperactivity and conduct problems subscales (13.6% had abnormal scores on each of these subscales). A total of 2.9% of the population tested had abnormal scores on the emotional symptoms subscale versus 2.3% on the peer problems subscale. Only 0.3% of the total population scored abnormally on the prosocial subscale.

Sex differences Abnormal SDQ scores were more common among females (9.7%; mean score = 11.86; sd = 5.4) than among males (7.6%; mean score = 10.96; sd = 5.26). The difference was most pronounced on the emotional symptoms subscale, with females receiving a mean score of 4.03 (sd = 2.1) compared to a mean male score of 2.9 (sd = 2.1). Males, however, had higher (more abnormal) mean scores on the conduct problems subscale (2.72 vs. 2.13 mean female score), as well as lower (more abnormal) mean scores on the prosocial behaviour subscale (7.85 vs. 8.78 mean female score).

Discussion The main objective of this study was to provide a generalised assessment of Irish adolescents aged 10 to 13 years using the SDQ. This study showed that 8.7% of the participants studied had an abnormal SDQ score, which would suggest that they were likely to suffer from some degree of mental health issues. Of these participants, 9.7% were female and 7.6% were male. Normative data has not been published for Ireland but has been published in Britain (n=4,228). Some 5.2% of British males and 5.1% of British females aged 11-15 received abnormal scores on the SDQ.5 This would indicate that the Irish participants were perhaps more at risk of developing mental health difficulties than their British


RCSIsmjoriginal article counterparts. However, socio-economic differences and the fact that the British study had a bigger cohort would have to be taken into account when comparing these two groups. SDQs are a useful tool to identify participants who may have emotional problems (females more than males in this study) and conduct problems (males more than females in this study). However, it has been shown that, on the whole, SDQs completed by parents and teachers are better indicators than SDQs completed by adolescents themselves.5 The socio-economic class of the participants is not known, nor is the population norm of the geographical area. Prior research indicates that respondents to questionnaires and those who agree to participate in research tend to be of a higher social class.12 As a consequence, there could have been an under- or overrepresentation of psychopathology in the study sample. This was a school-based sample. Children may not legally leave school in Ireland until the age of 16; however, some may not attend until that age. Among those registered with the school, a number will be absent on any one day. The dropouts and absent adolescents are likely to be from a vulnerable section of society and have potentially high levels of emotional and behavioural problems.13,14 Additionally, the schools who participated in the study were all mainstream schools and special schools for those who have intellectual and physical disabilities were not included. Students in these settings are known to have higher rates of emotional and behavioural problems when compared to the general population.15 As a consequence, the prevalence rates indicated in this study are liable to be an inaccurate estimate of the true prevalence of psychiatric disorders in young adolescents in the community.

Conclusion Mental health problems are common among the general adolescent population in Ireland. Early intervention should be a focus of health policy; however, more resources are necessary if childhood mental health problems are to be addressed. From the analysis of all the data and results it can be concluded that the SDQ gives a practical assessment of the mental health profile of young Irish adolescents. It is a short, simple questionnaire, which could be utilised in a general practice setting to screen adolescents for mental distresses.

Acknowledgements I wish to acknowledge financial support from the Royal College of Surgeons in Ireland 2009 Alumni Student Research Fund in General Practice.

Table 1: SDQ scoring values. Normal

Borderline

Abnormal

Total difficulties score

0-15

16-19

20-40

Emotional symptoms score

0-5

6

7-10

Conduct problems score

0-3

4

5-10

Hyperactivity score

0-5

6

7-10

Peer problems score

0-4

5

6-10

Prosocial behaviour score

6-10

5

0-4

References 1. Martinez R, Reynolds S, Howe A. Factors that influence the detection of psychological problems in adolescents attending general practices. Br J Gen Pract 2006; 56: 594-9. 2. Warnick EM, Weersing VR, Scahill L, Woolston JL. Selecting measures for use in child mental health services: a scorecard approach. Adm Policy Ment Health 2009; 36: 112-22. 3. Goodman R. The strengths and difficulties questionnaire: a research note. J Child Psychol Psychiatry 1997; 38: 582-6. 4. Goodman R, Renfrew D, Mullick M. Predicting type of psychiatric disorder from Strengths and Difficulties Questionnaire (SDQ) scores in child mental health clinics in London and Dhaka. Eur Child Adolesc Psychiatry 2000; 9: 129-34. 5. Goodman R, Ford T, Simmons H, Gatward R, Meltzer H. Using the Strengths and Difficulties Questionnaire (SDQ) to screen for child psychiatric disorders in a community sample. Br J Psychiatry 2000; 177: 534-9. 6. Bird H. Epidemiology of childhood disorders in a cross-cultural context. J Child Psychol Psychiatry 1996; 37: 35-49. 7. Costello E. Developments in child psychiatric epidemiology. J Am Acad Child Adolesc Psychiatry 1989; 28: 837-41. 8. Collishaw S, Maughan B, Goodman R, Pickles A. Time trends in adolescent mental health. J Child Psychol Psychiatry 2004; 45 (8): 1350-62.

9. Lynch F, Mills C, Daly I, Fitzpatrick C. Challenging times: prevalence of psychiatric disorders and suicidal behaviours in Irish adolescents. J Adolesc 2006; 29: 555-73. 10. Lynch F, Mills C, Daly I, Fitzpatrick C. Challenging times: a study to detect Irish adolescents at risk of psychiatric disorders and suicidal ideation. J Adolesc 2004; 27: 441-51. 11. SDQ: Information for researchers and professionals about the Strengths & Difficulties Questionnaires. Youth in Mind. June 2, 2008. Cited October 1, 2009. Available from: http://www.sdqinfo.com/b4.html. 12. Boyle M, Offord D, Racine Y, Catlin G. Ontario child health study follow-up: evaluation of sample loss. J Am Acad Child Adolesc Psychiatry 1991; 30 (3): 449-56. 13. Barker L, Adelman H. Mental health and help seeking among ethnic minority adolescents. J Adolesc 1994; 17: 251-63. 14. Kellam S, Branch M, Brown C, Russel G. Why teenagers come for treatment: a ten-year prospective epidemiological study in Woodlawn. J Am Acad Child Adolesc Psychiatry 1981; 20: 477-95. 15. Fombonne E. The Chartres study, I. Prevalence of psychiatric disorder among French schoolchildren. Br J Psychiatry 1994; 1634: 69-79.

Volume 3: Number 1. 2010 | Page 35


RCSIsmjcase report A case of elevated troponins Royal College of Surgeons in Ireland Student Medical Journal 2010; 3: 36-38.

The case A 77-year-old woman was referred to our cardiology service from a local emergency department for further evaluation of palpitations and elevated troponins. The presumed diagnosis was a non-ST elevation myocardial infarction (NSTEMI). Her past medical history included a pre-syncopal event in 1998, which resulted in some outpatient investigations. She conveyed to us that a treadmill exercise test and coronary angiogram had been normal. She had suboptimally controlled hypertension, but no other cardiovascular risk factors. Four days prior to presentation, she experienced an episode of palpitations. This lasted for one to two minutes and resolved spontaneously. The palpitations re-occurred several more times throughout the day. She felt quite weak intermittently for the next three days, but did not experience any additional palpitations.

On the day of her admission, she experienced new symptoms after making lunch. When she sat down to eat, she began to feel very weak, and felt that she was breathing rapidly. She denied any chest pain or pressure, or any pain in her arms, neck or jaw at any time during these episodes. She also denied sweating, pallor, nausea or vomiting. Of note, she did report decreased exercise tolerance recently, as she had been inactive for the previous two months. This was on a background history of lumbar disc herniation with associated severe sciatica in her left leg, which limited her to sitting, or lying in bed for most of the time. She initially presented to her local emergency department. At this time her serum troponin was found to be elevated. An ECG demonstrated sinus tachycardia and some non-specific T-wave abnormalities in leads V1 and V2. As per their NSTEMI protocol, she received metoprolol, heparin and aspirin. She was then transferred to us.

On examination Vital signs

Pulse: 113 beats/minute, regular rhythm Blood pressure: 141/65mmHg Respirations: 20 breaths/minute Temperature: 36.7ÂşC O2 saturation: 98% on 2L O2 by nasal cannula

General inspection The patient appeared well and was resting comfortably in bed. No apparent pain, clinical distress or dyspnoea.

James Young RCSI medical student and Vice-Director, RCSIsmj

Body mass index

29.8kg/m2

Neck

No jugular venous distention. Normal carotid upstroke. No audible carotid bruits.

Heart

Palpable heave at the upper left sternal border. No chest wall tenderness on palpation. S1/S2 normal. Audible S4 at the left mid-sternum. No murmurs, clicks or rubs.

Lungs

Good air entry bilaterally. Breath sounds vesicular. No adventitious sounds.

Abdomen

Soft and non-tender, with no organomegaly, masses or pulsations. Bowel sounds present and normal. No renal artery bruits.

Extremities

Trace oedema to the ankle bilaterally. Dorsalis pedis pulses palpable and equal. No lumps or swellings.

We re-evaluated her troponin T, which was high at 0.21ng/ml (normal <0.01ng/ml). Coagulation studies revealed her D-dimers to be >2,000ng/ml (DVT rule out threshold ≤250ng/ml). Her ECG was essentially unchanged as compared to the ECG performed in her local emergency department. A chest x-ray was

Page 36 | Volume 3: Number 1. 2009/2010

uninformative. We calculated her modified Wells score for pulmonary embolism (PE) to be 6, indicating a high probability of PE. In light of her presentation, the results of the D-dimers made us highly suspicious for a PE. A contrast CT scan of the chest was ordered. A few hours later we had our


RCSIsmjcase report answer: bilateral pulmonary emboli were present in the right and left pulmonary arteries extending into multiple lobar and segmental arteries (Figures 1a, b, c and d). Furthermore, there was enlargement of the right heart, and reflux of contrast into the hepatic veins, suggestive of acute right heart strain. The patient was anticoagulated with heparin and warfarin, and received physical and occupational therapy. She did well in hospital and was discharged to a skilled care facility for further reconditioning support before returning home.

Discussion PE is very common and a comprehensive discussion of diagnosis, management and follow-up can be found elsewhere. In this discussion, the emphasis will be on a few important learning points from this case. The relevance of this case discussion lies in the fact that PE is common and therefore important to recognise. The diagnosis of PE can be challenging, yet early diagnosis and treatment are necessary to reduce mortality. The mortality of untreated PE is 30% while mortality with treatment is between 2 and 8%.1,2 The incidence of non-classical symptoms of acute coronary syndrome (ACS) is high in women. In a study of early warning symptoms of acute myocardial infarction in women, the most frequent acute symptoms were shortness of breath (57.9%), weakness (54.8%) and fatigue (42.9%). Acute chest pain was absent in 43%.3 Given this fact, the non-specific symptoms in our patient’s history, along with her elevated troponins, made it prudent to consider ACS. However, PE is a crucial diagnosis to make and should have been in the differential prior to her referral. The most common symptoms of PE in the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) study are shown in Table 1.4 Despite this, PE may be asymptomatic. While our patient did not initially suffer any of the symptoms of PE outlined in Table 1, she did exhibit tachypnoea, tachycardia and a fourth heart sound (S4). She also had a palpable right ventricular (RV) heave from the straining right ventricle. Her S4 was a right-sided S4, representing an atrial kick against the stiff, straining RV. These findings underscore the fact that careful attention to clinical examination is warranted in these patients. The elevation in her troponins was probably the major misleading factor in the early cardiac focus of her workup. While elevated troponins are very specific for myocyte damage, in this case the myocyte damage was secondary to her right heart straining to pump blood into thrombus-clogged vessels. Thus, the first important point here is that an elevation in troponins should not automatically focus the differential on primary cardiac pathology. The second important point is that elevated troponins carry a significantly worse prognosis. In a meta-analysis by Becattini et al, 31% of PE cases involved elevated troponins. The mortality rate for patients with elevated troponins was 19.7% vs. 3.7% for those with PE without elevated troponins. It is important to note that the high mortality rate also included the subset of patients who were haemodynamically stable (odds ratio 5.46).5 Thus, these patients need to be monitored closely for any signs of acute decompensation. The ECG in this patient was not particularly helpful as it revealed only sinus tachycardia (which in itself does not require an ECG for diagnosis). This certainly illustrates the rule rather than the exception. Sinus tachycardia is the only finding in most cases of PE.6 There was T-wave flattening/inversion in leads V1 and V2,

FIGURE 1: Contrast-enhanced CT images of the thorax (clockwise from top left): a) coronal view, demonstrating large hyperdensities consistent with pulmonary emboli at the bifurcation of the right pulmonary artery, and some clot in the left pulmonary artery; b) axial view, demonstrating hyperdense clot in branches of the right pulmonary arteries; c) axial view, demonstrating hyperdense clot in the left pulmonary artery; and, d) axial view, demonstrating hyperdense clot extending into the right and left lobar and segmental arteries.

Table 1: Most common symptoms/physical findings of PE in patients without pre-existing cardiopulmonary disease in the PIOPED Study.4 Symptoms

Signs

Dyspnoea (73%)

Tachypnoea (70%)

Pleuritic chest pain (66%)

Rales (crackles) (51%)

Cough (37%)

Tachycardia (30%)

Haemoptysis (13%)

S4 (24%) Loud P2 (23%)

which was probably, in retrospect, related to her PE, but no old ECGs were available for comparison. There are a few ECG changes that may be helpful in diagnosing PE. These include new right axis deviation, new right bundle branch block, new atrial fibrillation or flutter, or definite Twave inversion in the right praecordial leads (V1 and V2). These findings are suggestive of RV dysfunction and may carry a worse prognosis.7 The classic pattern of an S-wave in lead I, a Q-wave in lead III and T-wave inversion in lead III (the so-called S1Q3T3 pattern) is highly suggestive of RV strain when present, but is only seen in about 12% of massive PEs

Volume 3: Number 1. 2010 | Page 37


RCSIsmjcase report (i.e., those associated with systemic arterial hypotension).8 The key laboratory finding in this case was the D-dimer elevation. D-dimers are elevated in 95% of patients with PE. The drawback is that they are highly non-specific, and can be elevated in patients without PE. For CTexperienced institutions (most institutions these days), the Christopher study validated a very simple and effective approach to working up a PE. The modified Wells score is used as a metric for stratifying patients into low or high clinical probability of PE prior to ordering investigations (Figure 2). In the study, out of 1,028 patients who had PE ruled out and received no anticoagulation, only five (0.5%) were found to have venous thromboembolism in the subsequent three months, none of which were fatal.9 As a final point, our patient was scheduled for follow-up malignancy screening. In older patients from the community presenting with their first PE, up to 20% will have an occult malignancy.10

In summary, PE may present with non-specific findings, which may hinder early diagnosis. Particularly in older women, the symptoms of PE overlap considerably with those of acute myocardial infarction. A careful history and physical examination is crucial. Elevated troponins are a common feature of acute PE and should be taken seriously, as they are associated with a significantly greater mortality rate, even in haemodynamically stable patients. A simple approach to diagnosis involves the use of the modified Wells score and D-dimers to guide the use of contrast-enhanced helical CT scan. Follow-up in older patients with first onset PE should include a screen for occult malignancy.

Acknowledgments I would like to thank my patient who very generously allowed me to use these case details. I would also like to thank Dr Paul Sorajja and the residents at the Mayo Clinic who guided me through this case.

Suspected pulmonary embolus

Score 4 or less

Calculate modified Wells score

Score 5 or more

Check D-dinner

D-dimer >500ng/ml

Proceed to contrastenhanced spiral CT Scan

D-dimer <500ng/ml

Pulmonary embolus ruled out

FIGURE 2: An approach to the diagnosis of PE as outlined by the Christopher Study.9 The modified Wells score influences the use of D-dimers. The results of these two investigations guide the use of contrast-enhanced CT scanning.

References 1. Goldhaber SZ, Visani L, De Rosa M. Acute pulmonary embolism: clinical outcomes in the International Co-operative Pulmonary Embolism Registry (ICOPER). Lancet 1999; 353 (9162): 1386-9. 2. Nijkeuter M, Sohne M, Tick LW, Kamphuisen PW, Kramer MH, Laterveer L et al. The natural course of haemodynamically stable pulmonary embolism: clinical outcome and risk factors in a large prospective cohort study. Chest 2007; 131 (2): 517-23. 3. McSweeney JC, Cody M, O’Sullivan P, Elberson K, Moser DK, Garvin BJ. Women’s early warning symptoms of acute myocardial infarction. Circulation 2003; 108 (21): 2619-23. 4. The PIOPED Investigators. Value of the ventilation/perfusion scan in acute pulmonary embolism. Results of the prospective investigation of pulmonary embolism diagnosis (PIOPED). JAMA 1990; 263 (20): 2753-9. 5. Becattini C, Vedovati MC, Agnelli G. Prognostic value of troponins in acute pulmonary embolism: a meta-analysis. Circulation 2007; 116 (4): 427-33.

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6. Hamptom JR. The ECG in Practice (4th ed.). London: Churchill Livingstone, 2003. 7. Sanchez O, Trinquart L, Colombet I, Durieux P, Huisman MV, Chatellier G et al. Prognostic value of right ventricular dysfunction in patients with haemodynamically stable pulmonary embolism: a systematic review. Eur Heart J 2008; 29 (12): 1569-77. 8. Harrigan RA, Jones K. ABC of clinical electrocardiography. Conditions affecting the right side of the heart. BMJ 2002; 324 (7347): 1201-4. 9. van Belle A, Buller HR, Huisman MV, Huisman PM, Kaasjager K, Kamphuisen PW et al. Effectiveness of managing suspected pulmonary embolism using an algorithm combining clinical probability, D-dimer testing, and computed tomography. JAMA 2006; 295 (2): 172-9. 10. Heit JA, O’Fallon WM, Petterson TM, Lohse CM, Silverstein MD, Mohr DN et al. Relative impact of risk factors for deep vein thrombosis and pulmonary embolism: a population-based study. Arch Intern Med 2002; 162 (11): 1245-8.


RCSIsmjcase report Signal change following posterior fossa tumour resection: evidence of hydrocephalus Key words: Posterior fossa tumour, hydrocephalus, fourth ventricle, mutism, children.

Royal College of Surgeons in Ireland Student Medical Journal 2010; 3: 39-41.

This report discusses two patients who had neuro-imaging changes suggestive of uncontrolled hydrocephalus following the removal of a fourth ventricle tumour. Patient one had a low-density change on a computed tomography (CT) scan and patient two had increased signal intensity on a T2-weighted magnetic resonance (MR) scan. Both patients were treated for hydrocephalus and subsequently improved with complete resolution of these signal changes. Progressive signal change in the region surrounding the resection bed following removal of fourth ventricular tumours may be due to evolving hydrocephalus. This finding might be a useful indicator of disordered cerebrospinal fluid (CSF) circulation that requires treatment.

Patient 1

Brian Drake1, Ash Singhal1, D Douglas Cochrane1 1Division of Pediatric

Neurosurgery, The University of British Columbia, Vancouver, British Columbia, Canada

A 13-year-old boy presented to the emergency department with a one-month history of nausea and vomiting. On neurological exam he had diminished gag reflex bilaterally. There was no papilloedema. An MR scan showed a posterior fossa mass occupying the fourth ventricle and extending through the foramen magnum, suggestive of an ependymoma (Figure 1a and 1b). There was no evidence of metastatic disease. An uncomplicated posterior fossa craniotomy was performed with gross total excision of the mass, and pathological analysis confirmed an ependymoma. He became acutely hypertensive shortly after his arrival in the intensive care unit. A CT scan showed a tumour bed haemorrhage with extension into the third and fourth ventricles, and hydrocephalus. An external ventricular drain (EVD) was inserted

and the operative site re-explored. Following the second procedure, the patient was noticed to have cranial nerve palsies affecting cranial nerves (CN) V (loss of sensation, right side of face), VII (bilateral facial motor weakness), IX (no cough, gag or swallow) and XII (inability to protrude tongue completely and fasciculations), and was aphonic after extubation. In addition to the ventriculomegaly that had developed as a result of the tumour bed haemorrhage, low-density changes on CT were found in the resection bed and in the walls of the fourth ventricle (Figure 2a). No other periventricular low density was seen. The EVD was maintained and, over the course of 10 days, several attempts were made to wean him from the drain by gradual elevation. In all attempts, his level of consciousness deteriorated and his ventricles increased in size. It was decided that longer term CSF drainage was required and a ventriculoperitoneal shunt was inserted. Two days later, a CT scan was performed that showed reduction in the size of the lateral ventricles and reversal of the tumour bed low-density change (Figure 2b). The patient has recovered speech but bulbar cranial nerve dysfunction remains.

Patient 2 A nine-year-old girl presented to the emergency department with a one-week history of progressive headache, nausea and vomiting, and a two-day history of worsening vision and unsteady gait. On physical examination she was alert and oriented while showing left-directed horizontal nystagmus and congruent lateral deviation to the left. She had bilateral papilloedema, a positive Romberg’s

Volume 3: Number 1. 2010 | Page 39


RCSIsmjcase report Patient 1

FIGURE 1a and 1b: MR head scan of patient 1 (white arrow), showing the posterior fossa lesion, which was confirmed to be an ependymoma. a (left): axial plane; and, b (right): sagittal plane.

FIGURE 2a: CT head scan of patient 1 showing low density around the fourth ventricle.

FIGURE 2b: CT head scan of patient 1 (white arrow), showing reversal of low-density change.

Patient 2

FIGURE 3: MR head scan of patient 2 (white arrow), showing the midline fourth ventricular posterior fossa tumour, which was confirmed to be a medulloblastoma.

FIGURE 4a: MR head scan of patient 2 (white arrow), showing signal change around the fourth ventricle.

sign, an ataxic gait and mild sitting ataxia. MR (Figure 3) and CT scans of the brain showed a midline fourth ventricular mass lesion with accompanying hydrocephalus. Periventricular signal change was present adjacent to the frontal and occipital horns of the lateral ventricles. There was no evidence of metastatic disease. An uncomplicated posterior fossa craniotomy was performed with gross total excision of the mass. Pathological analysis confirmed medulloblastoma. The patient was kept intubated overnight and was extubated the following day. A CT scan on the first postoperative day showed decreased ventricular size and no residual tumour. Aside from a mild left facial weakness suggestive of lower motor neuron damage, she displayed no abnormal behaviour, was appropriately responsive and exhibited normal spontaneous speech. Her extraocular movements were normal. On the second postoperative day, the patient complained of severe headaches, developed a left-sided CN VI palsy and a right internuclear ophthalmoplegia. A CT scan showed ventricular

Page 40 | Volume 3: Number 1. 2010

Figure 4b: MR head scan of patient 2, showing reversal of the fourth ventricle signal change.

dilatation and an EVD was inserted. Approximately 72 hours after the patient’s operation, she was noted to be aphonic. During the next 24 hours, the measured intracranial pressure was low. The patient continued to be aphonic and demonstrated limb and truncal ataxia. The EVD was removed on the eighth postoperative day. On the fourteenth postoperative day, a surveillance MR scan showed that her lateral ventricles were increasing in size and there was significant signal change in the lateral and posterior walls of the resection bed (Figure 4a). The periventricular signal change seen around the lateral ventricles pre-operatively had resolved. An endoscopic third ventriculostomy (ETV) was performed 18 days after the excision of the tumour. By the seventh day post ETV, the signal change around the fourth ventricle had improved (Figure 4b). Within 24 hours, the patient’s speech partially returned and she was able to understand and answer questions using two- to five-word sentences.


RCSIsmjcase report Discussion The most common solid tumours in the paediatric population are brain neoplasms, accounting for 16% of all malignancies, 43% of which occur in the posterior fossa.1,2 The most common tumours include astrocytomas (52%), medulloblastoma/primitive neuroectodermal tumours (21%) and ependymomas (9%). The current overall five-year survival for all brain tumours in childhood is 67%.2 Hydrocephalus is a common complication of posterior fossa tumours and results from derangement of CSF production, circulation, or drainage. Non-communicating hydrocephalus results from obstruction within the ventricular system while communicating hydrocephalus results from decreased CSF reabsorption or increased production.3 Diagnosis is suspected by characteristic clinical signs and confirmed with imaging studies. The clinical picture varies with age but typical symptoms include irritability, headache, vomiting, poor appetite, lethargy, change in personality and deterioration in school performance. Infants (whose fontanelle is open and cranial sutures have not fused) often present with accelerated head growth, a bulging anterior fontanelle and, occasionally, prominent veins. Clinical signs include papilloedema, muscle weakness, brisk deep tendon reflexes, spasticity, clonus and a Babinski reflex. The ‘sun-setting’ sign is also classically observed when the dilated suprapineal recess impinges on the tectum, forcing the eyes to deviate downward. Imaging studies confirm the diagnosis and can help to identify the underlying pathology and the severity of the hydrocephalus. CT, MRI and transcranial ultrasonography in the infant (through a patent fontanelle) are the most common diagnostic studies. Plain film x-rays of the skull may show separation of the cranial sutures.3 Treatment of hydrocephalus depends on the underlying pathology. Diuretic medications (furosemide and acetazolamide) and EVD insertion can provide temporary relief, but long-term treatment usually requires extracranial shunting of CSF with a ventriculoperitoneal or ventriculo-atrial shunt, or a ventriculostomy. Major complications of shunts are occlusion and infection requiring shunt revision.3 Hydrocephalus secondary to brain tumours, in particular those occupying the fourth ventricle, are managed in a variety of ways. The

most effective treatment is gross total resection of the tumour in order to restore normal CSF circulation. However, obstructive hydrocephalus may remain in 15-30% of patients and requires further treatment.4 In the early postoperative period, it is not always apparent that the hydrocephalus has resolved. In this period, clinical signs and any changes in ventricular size or draining CSF are used to determine if further treatment is needed. Periventricular low densities on CT are often seen in the lateral ventricles in hydrocephalus. It is thought to represent transependymal flow of CSF associated with increased diffusion.5 It is less commonly seen in the fourth ventricle. Using pre-treatment clinical features, Riva-Cambrin et al have devised a model to predict the need for hydrocephalus treatment following tumour resection. The parameters are age <2 (score of 2), papilloedema (score of 1), moderate to severe hydrocephalus (score of 2), cerebral metastases (score of 3), and specific tumour pathologies (score of 1). Patients with a score of 0-4 are deemed low risk, while those at 5-10 are high risk.6 Pre-operatively, both patients in this report were considered to be at low risk for hydrocephalus intervention following resection of the tumour (a score of 3 for patient 1, and 4 for patient 2). Subsequently, their postoperative hydrocephalus was treated conservatively via EVD with the expectation that it would resolve without further treatment. CT low density or T2 signal change is not normally seen around the tumour site following resection of a posterior fossa tumour. The observed effect of CT low density is presumed to be interstitial fluid, which is likely to be an indication of locally obstructed CSF flow. This is either due to blockage of interstitial fluid flow back into the ventricular system, or the influx of CSF from pressurised ventricles into the periventricular tissues. Thus, the phenomenon of signal change surrounding the posterior fossa tumour bed in the setting of postresection hydrocephalus suggests that the CSF circulation disturbance is not controlled. Establishing risk of hydrocephalus pre- and postoperatively is valuable in counselling families and outlining treatment plans. Such marked signal changes in the tumour bed following resection of a posterior fossa tumour may be another sign of ongoing hydrocephalus requiring intervention.

References 1. Kinsman S, Johnston M. Congenital anomalies of the central nervous system. In: Bergman RE, Kliegman R, Jenson HB (eds.). Nelson Textbook of Pediatrics (18th ed.). Philadelphia: Saunders Elsevier, 2007: pp. 2443-56. 2. Sklar CA. Childhood brain tumours. Journal of Paediatric Endocrinology and Metabolism 2002; 15 (2 Suppl.): 669-73. 3. Kuttesch J, Ater J. Brain Tumors in Childhood. Philadelphia: Saunders Elsevier, 2007: pp. 2128-37. 4. Morelli D, Pirotte B, Lubansu A, Detemmerman D, Aeby A, Fricx C et al. Persistent hydrocephalus after early surgical management of posterior fossa tumours in

children: is routine preoperative endoscopic third ventriculostomy justified? Journal of Neurosurgery 2005; 103: 247-52. 5. Ulug A, Truong T, Filippi C, Lee J, Yang C, Souweidane M et al. Diffusion imaging in obstructive hydrocephalus. American Journal of Neuroradiology 2003; 14: 1171-6. 6. Riva-Cambrin J, Detsky AS, Lamberti-Pasculli M, Sargent MA, Armstrong D, Moineddin R et al. Predicting postresection hydrocephalus in paediatric patients with posterior fossa tumours. Journal of Neurosurgical Pediatrics 2009; 3 (5): 378-85.

Volume 3: Number 1. 2010 | Page 41


RCSIsmjcardiology review Sudden cardiac death in the young: causes and prevention Abstract Sudden cardiac death (SCD) in the young is a tragic event that can occur in infants, children, adolescents and young adults alike. In a lot of cases, sudden death is the first manifestation of an undetected fatal heart abnormality, with no previous symptoms or warning signs during the victim’s life. Although we know many pathological heart conditions that give rise to SCD in the young, the frequently ‘silent’ nature of these conditions means that identifying individuals who are susceptible is difficult. Strategies aimed at reducing the incidence of SCD in the young mainly focus on risk stratification through screening programmes, followed by the institution of preventive management in those discovered to be at risk. The role of genetic testing in SCD is constantly advancing, particularly in screening relatives of young people with known heart conditions, or of young people who have tragically succumbed to SCD. This paper gives a broad overview of the causes of SCD in the young, with extra consideration given to infants and young athletes. This is followed by discussion of both current and future prevention strategies. Key words: Sudden cardiac death, sudden infant death syndrome, young adult, adolescent, children. Royal College of Surgeons in Ireland Student Medical Journal 2010; 3: 42-46.

Introduction Sudden cardiac death (SCD) in the young is a rare but tragic event that deeply affects families and communities. It is broadly defined as death from a cardiac cause or no identifiable cause occurring within one hour of symptom onset, in individuals at or under 35 years.1 SCD in the young may include sudden infant death syndrome (SIDS), which is defined as sudden unexpected death occurring without identifiable abnormality on post-mortem in an individual less than one year.1 In Ireland in 2005, there were 69 post-mortem confirmed cases of SCD in the young,1 while in the UK it is estimated that there are at least eight cases per week.2

Causes of SCD in the young

Rory Kelly1, Dr Joseph Galvin2 1RCSI medical student 2Consultant Cardiologist,

James Connolly Memorial Hospital, Dublin

Page 42 | Volume 3: Number 1. 2010

The final event in SCD is usually a fatal arrhythmia such as ventricular fibrillation or ventricular tachycardia.3 The pathophysiological processes leading up to such an event are frequently complex. While a causative structural heart abnormality is usually identified at post-mortem, no structural defect can be found in 10-30% of cases.4 Sudden death in these instances is potentially due to a primary electrical condition such as an ion channel disorder or an accessory pathway. Structural abnormalities most frequently identified are hypertrophic cardiomyopathy (HCM), arrhythmogenic right ventricular cardiomyopathy

(ARVC), coronary artery anomalies, and myocarditis. Where no structural defect is found, potential causes include long QT syndrome (LQTS), Brugada syndrome, and catecholaminergic polymorphic ventricular tachycardia (CPVT). In 69 confirmed cases of SCD in the young in Ireland in 2005, the most common autopsy findings were: no detectable heart abnormality (41.4%); and, HCM (14.5%).1

Hypertrophic cardiomyopathy HCM is the most common cause of SCD in young athletes and non-athletes in the USA5 and is the leading structural cause of SCD in the young in Ireland.1 In most cases inheritance is autosomal dominant, involving gene mutations of cardiac sarcomere proteins. The pathophysiology of sudden death in HCM involves a complex arrhythmogenic substrate formed by myocyte disarray, fibrosis, and calcium regulation abnormalities, which predisposes the individual to fatal ventricular fibrillation.6

Arrhythmogenic right ventricular cardiomyopathy ARVC is characterised by fibro-fatty replacement of ventricular myocardium (usually the right ventricle), resulting in ventricular dysfunction and arrhythmias. Inheritance is usually autosomal dominant with variable phenotype.7 Up to 20% of SCD may be attributable to ARVC.8


RCSIsmjcardiology review

FIGURE 1: 12-lead ECG of a young male with hypertrophic cardiomyopathy demonstrating voltage criteria for LV hypertrophy and repolarisation changes.

FIGURE 2: Left: ECG showing classic epsilon wave seen in patients with arrhythmogenic right ventricular cardiomyopathy (right ventricular cardiomyopathy). Right: Signal averaged ECG showing low voltage, high frequency electrograms at the terminal end of the summated, filtered QRS complex.

Coronary artery anomalies

the most widely reported. In recent studies, post-mortem testing has revealed LQTS-associated mutations in 9.5% of 201 SIDS victims,19 and in 8.3% of 200 SIDS victims.20 The pathophysiological mechanisms of SIDS remain poorly understood, and discovery of currently unknown cardiac causes may represent the greatest challenge for researchers of SCD in the young.

In addition to cardiomyopathies, anatomical anomalies of the coronary circulation are frequently implicated in SCD in the young, and have been described in detail.9 Ventricular arrhythmia leading to sudden death is usually linked to sudden myocardial ischaemia or to scarring.9

Ion channelopathies No structural abnormalities can be identified at autopsy in 10-30% of sudden deaths in previously healthy children and adolescents.4,10 The finding of a morphologically normal heart at post-mortem therefore suggests an ion channelopathy, such as LQTS, Brugada syndrome, and CPVT. LQTS comprises a distinct group of cardiac channelopathies, which usually follow autosomal dominant inheritance.8 Approximately 75% of LQTS cases are caused by mutations in five specific ion channel genes.11 The characteristic features are delayed myocardial repolarisation and QT prolongation, with increased risk for syncope, seizures and SCD.11 Brugada syndrome is an inheritable arrhythmia syndrome associated with sodium channel mutations. It poses an inherent risk of SCD due to episodes of polymorphic ventricular arrhythmias. It is more common in young males; however, it can occur in children.8 CPVT, which usually involves mutations in a ryanodine receptor gene, is increasingly recognised as a cause of SCD in the young.4 This condition closely mimics LQTS but appears to be far more lethal.12

Other causes of SCD in the young Various other causes of SCD in the young have been described including short QT syndrome,8 Wolff-Parkinson-White (WPW) syndrome,13 myocarditis,1 restrictive cardiomyopathy,14 congenital heart disease,1,4 coronary atherosclerosis,15 valvular disease,2 and blunt chest trauma (commotio cordis).16

Sudden infant death syndrome While the causes of sudden death in infants under one year are multifactorial,17 molecular studies have shown that 10% of cases of SIDS may result from an ion channelopathy,18,19,20 of which LQTS is

SCD in young athletes The sudden death of a young athlete often receives increased publicity, perhaps because athletes are perceived as one of the healthiest subpopulations of society. The risk of SCD in young athletes has been estimated as 2.8 times greater than the risk in non-athletes.21 HCM is considered the most frequent cause of SCD in young competitive athletes,22,23 and is implicated in one-third of fatal cases in the USA.21,24,25 However, geographical variations exist, as the leading cause of SCD in young athletes in Veneto, Italy, is ARVC.26 Other causes of SCD in young athletes include coronary anomalies, premature atherosclerotic coronary disease, mitral valve prolapse, WPW syndrome,13 and ion channelopathies.26 It is believed that intense exercise may act as an external trigger of SCD in athletes who harbour an underlying structural or arrhythmogenic heart disease. Exercise imposes a combination of physical, metabolic and endocrine stresses on the heart, which could trigger a fatal arrhythmia.22 Evidence exists to support this idea,24,25,27 including a recent study of SCD in UK athletes in which over 80% of fatal events occurred during or immediately following exercise.22 Specific sports have been pinpointed in certain instances; for example, SCD due to LQTS and CPVT has been strongly associated with swimming.28,29,30 Exercise, however, is by no means a prerequisite for SCD. Nearly 20% of athletes in the UK study who died suddenly were not exercising at the time,22 while some reports have found that SCD due to HCM often occurs during mild or sedentary activity.31,32,33 The role of exercise in triggering SCD is highlighted when considering preventive measures to reduce the incidence of SCD in the young.

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FIGURE 3: The ECG findings in long QT syndrome are an abnormally long corrected QT interval (QTc). In the context of a suspicious history this warrants consideration of long QT syndrome as a potential culprit. Long QT patients are diagnosed and risk stratified according to symptoms as well as the actual length of their QTc interval, with longer QTc values indicating higher risk.

FIGURE 4: The classic ECG findings in Brugada syndrome include coved or saddle-shaped ST segment elevation and partial RBBB pattern in V1-V3. There are three subtypes of Brugada, shown above, each with slightly different ECG changes.

Prevention of SCD in the young

Family screening and genetic testing

Sudden death is often the first symptomatic manifestation of cardiovascular disease, which makes prevention of SCD in the young very difficult. The key to minimising the incidence of SCD in the young lies in identifying those individuals who are at risk for sudden fatal arrhythmias, thus allowing directed preventive management to be instituted. Major prevention strategies can be divided broadly into two main areas: the first is a national or population-based screening programme for specific groups; and, the second involves screening in families with suspected or known genetic cardiac abnormalities.

In the 10-30% of SCD cases that reveal no obvious structural explanation at autopsy, identifying a possible arrhythmogenic cause is the next step. The role of genotyping in this instance is constantly advancing, and has been advocated in the analysis of cases of sudden death where the post-mortem was inconclusive.17 Identification of disease-causing mutations in the deceased can enable screening of family members, and initiate preventive management in relatives with mutations. One recent study established an identifiable mutation in over 30 relatives of a cohort of 49 SCD victims with LQTS.11 However, a major hurdle in genetic testing is that many inherited cardiac disorders have incomplete penetrance and variable expressivity, and thus may escape detection.

Population screening There is currently no population screening for heart disease in the young in Ireland.1 Research on screening programmes is limited, and to date has largely focused on young competitive athletes in the USA and Europe. Currently, the American Heart Association recommends that history and physical examination alone should constitute basic preparticipation screening of young athletes, while ECG testing remains optional.34 However, in Italy a landmark study26 showed that a screening programme consisting of history, physical examination and 12-lead ECG reduced the incidence of SCD in young athletes by 89% over a 26-year period. The addition of ECG was viewed as pivotal to the success of this screening programme, being deemed a “lifesaving strategy”.13 The European Society of Cardiology has duly adopted the recommendation that the 12-lead ECG be included in the pre-participation screening for young athletes.35 ECG is a relatively cheap and simple test, and should form the basis of any screening programme for SCD in both athletes and non-athletes.36 ECG changes, for example, are evident in 85% of cases of HCM,15 with specific ECG predictors of sudden death identified.37,38 ECG screening also has the potential to unmask other undetected heart conditions such as coronary anomalies,15 SQTS,39 ARVC and Brugada syndrome.26 With regard to SIDS prevention, the knowledge that 10% of SIDS may be due to ion channelopathies such as LQTS has strengthened the case for infant screening. Accordingly, some European countries are considering the introduction of national neonatal ECG screening programmes,40 with some authors recommending screening between two and four weeks of age.41 Such programmes can be cost effective, and can successfully identify asymptomatic infants as well as guide further investigation of family members for ‘silent’ LQTS.17

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Preventive management Preventive measures in those young people with known risk of SCD vary depending on the underlying condition. In addition to antiarrhythmic medications and invasive techniques, restriction of activity and use of defibrillation devices form the cornerstone of preventive management. Exercise curtailment is an obvious prevention strategy, considering the significant incidence of SCD that occurs during or immediately after physical activity. The diagnosis of HCM, for example, generally necessitates disqualification from most competitive sports,42 with some individual exceptions made.43 However, this approach is certainly not exhaustive because many cases of SCD occur during mild or sedentary activity. Indeed, rather than unnecessarily exclude participation in all sports, the goal should be to adapt the activity in accordance with each individual’s specific risk.26 The advent of implantable cardioverter-defibrillator (ICD) devices has prompted huge advances in SCD prevention in the young, particularly in HCM where ICD implantation is recommended for patients who satisfy particular criteria.44 ICD therapy may also have a preventive role in coronary disease,43 congenital heart disease4 and LQTS.13 Additionally, the presence of automated external defibrillator (AED) devices at sporting events has been advocated.26 This, along with an increased provision of AEDs in all public places, may reduce the time between an event and life-saving intervention, and therefore potentially reduce SCD rates.


RCSIsmjcardiology review

FIGURE 5: The classical appearance of the QRS complex in WPW syndrome. Instead of the expected abrupt upstroke of a normal QRS, in WPW there is a slurred upstroke, which represents early depolarisation of the accessory pathway. This slurring also causes the PR interval to be shorter, and the QRS complex to be widened. Further information about the anatomical location of the pathway can be deduced from the QRS axis and dominant QRS deflections in V1 and V2.

Implications for the future In addition to screening programmes for the young, much of the scope for preventing SCD lies in the genetic screening of surviving relatives of young victims. Provision of cardiac genetic services, where families can avail of screening as well as education and genetic counselling, should be a major focus for national health departments. In Ireland, the Family Heart Screening Clinic was set up in the Mater Hospital in Dublin in 2007, providing such services to the relatives of young SCD victims. Prevention of SCD may also be facilitated by the increased availability of national epidemiological data on SCD incidence, trends and postmortem findings. To this end there is a need to implement national SCD registries. Cardiac arrest registries could aid the improvement of

cardiac arrest response strategies,1 while prospective post-mortem registries have also been advocated.1,36 Comprehensive epidemiological information may strengthen the case for funding of national SCD screening programmes, and allow better risk stratification across various cohorts. Future success in reducing the burden of SCD in the young depends on several factors, not least the implementation of screening programmes in at-risk populations, and the availability of formalised epidemiological data. Furthermore, as research increases our understanding of the genetic basis of SCD in the coming years, improved management and prevention of SCD in the young can surely be expected.

References 1. Morris VB, Keelan T, Leen E et al. Sudden cardiac death in the young: a one-year post-mortem analysis in the Republic of Ireland. Ir J Med Sci 2009; 178 (3): 257-61. 2. Fishbein MC. Cardiac disease and risk of sudden death in the young: the burden of the phenomenon. Cardiovasc Pathol 2009. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19740679. 3. Hofman N, Tan HL, Clur S et al. Contribution of inherited heart disease to sudden cardiac death in childhood. Pediatrics 2007; 120 (4): e967-e973. 4. Bar-Cohen Y, Silka MJ. Sudden cardiac death in pediatrics. Curr Opin Pediatr 2008; 20 (5): 517-21. 5. Maron BJ. Sudden death in young athletes. N Engl J Med 2003; 349 (11): 1064-75. 6. Seggewiss H, Blank C, Pfeiffer B, Rigopoulos A. Hypertrophic cardiomyopathy as a cause of sudden death. Herz 2009; 34 (4): 305-14. 7. RodrĂ­guez-Calvo MS, Brion M, Allegue C, Concheiro L, Carracedo A. Molecular genetics of sudden cardiac death. Forensic Sci Int 2008; 182 (1-3): 1-12. 8. Tester DJ, Ackerman MJ. Cardiomyopathic and channelopathic causes of sudden unexplained death in infants and children. Annu Rev Med 2009; 60 (1): 69-84. 9. Cheitlin MD, MacGregor J. Congenital anomalies of coronary arteries: role in the pathogenesis of sudden cardiac death. Herz 2009; 34 (4): 268-79.

10. Tan HL, Hofman N, van Langen IM, van der Wal AC, Wilde AAM. Sudden unexplained death: heritability and diagnostic yield of cardiological and genetic examination in surviving relatives. Circulation 2005; 112 (2): 207-13. 11. Tester DJ, Ackerman MJ. Postmortem long QT syndrome genetic testing for sudden unexplained death in the young. Journal of the American College of Cardiology 2007; 49 (2): 240-6. 12. Tester DJ, Kopplin LJ, Will ML, Ackerman MJ. Spectrum and prevalence of cardiac ryanodine receptor (RyR2) mutations in a cohort of unrelated patients referred explicitly for long QT syndrome genetic testing. Heart Rhythm 2005; 2 (10): 1099-105. 13. Corrado D, Migliore F, Bevilacqua M, Basso C, Thiene G. Sudden cardiac death in athletes: can it be prevented by screening? Herz 2009; 34 (4): 259-66. 14. Hayashi T, Tsuda E, Kurosaki K et al. Electrocardiographic and clinical characteristics of idiopathic restrictive cardiomyopathy in children. Circ J 2007; 71 (10): 1534-9. 15. Wisten A, Andersson S, Forsberg H, Krantz P, Messner T. Sudden cardiac death in the young in Sweden: electrocardiogram in relation to forensic diagnosis. J Intern Med 2004; 255 (2): 213-20. 16. Maron BJ, Poliac LC, Kaplan JA, Mueller FO. Blunt impact to the chest leading to sudden death from cardiac arrest during sports activities. N Engl J Med 1995; 333 (6): 337-42. 17. Schwartz PJ, Crotti L. Can a message from the dead save lives? J Am Coll Cardiol 2007; 49 (2): 247-9.

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RCSIsmjcardiology review 18. Ackerman MJ, Siu BL, Sturner WQ et al. Postmortem molecular analysis of SCN5A defects in sudden infant death syndrome. JAMA 2001; 286 (18): 2264-9. 19. Tester DJ, Ackerman MJ. Sudden infant death syndrome: how significant are the cardiac channelopathies? Cardiovasc Res 2005; 67 (3): 388-96. 20. Arnestad M, Crotti L, Rognum TO et al. Prevalence of long-QT syndrome gene variants in sudden infant death syndrome. Circulation 2007; 115 (3): 361-7. 21. Corrado D, Basso C, Rizzoli G, Schiavon M, Thiene G. Does sports activity enhance the risk of sudden death in adolescents and young adults? J Am Coll Cardiol 2003; 42 (11): 1959-63. 22. de Noronha SV, Sharma S, Papadakis M et al. Aetiology of sudden cardiac death in athletes in the United Kingdom: a pathological study. Heart 2009; 95 (17): 1409-14. 23. Sharma S, Whyte G, McKenna WJ. Sudden death from cardiovascular disease in young athletes: fact or fiction? Br J Sports Med 1997; 31 (4): 269-76. 24. Maron BJ, Doerer JJ, Haas TS, Tierney DM, Mueller FO. Sudden deaths in young competitive athletes: analysis of 1866 deaths in the United States, 1980-2006. Circulation 2009; 119 (8): 1085-92. 25. Corrado D, Basso C, Pavei A et al. Trends in sudden cardiovascular death in young competitive athletes after implementation of a preparticipation screening program. JAMA 2006; 296 (13): 1593-601. 26. Corrado D, Basso C, Schiavon M, Pelliccia A, Thiene G. Preparticipation screening of young competitive athletes for prevention of sudden cardiac death. J Am Coll Cardiol 2008; 52 (24): 1981-9. 27. Corrado D, Basso C, Schiavon M, Thiene G. Screening for hypertrophic cardiomyopathy in young athletes. N Engl J Med 1998; 339 (6): 364-9. 28. Moss AJ, Robinson JL, Gessman L et al. Comparison of clinical and genetic variables of cardiac events associated with loud noise versus swimming among subjects with the long QT syndrome. Am J Cardiol 1999; 84 (8): 876-9. 29. Ackerman MJ, Tester DJ, Porter CJ. Swimming, a gene-specific arrhythmogenic trigger for inherited long QT syndrome. Mayo Clin Proc 1999; 74 (11): 1088-94. 30. Choi G, Kopplin LJ, Tester DJ et al. Spectrum and frequency of cardiac channel defects in swimming-triggered arrhythmia syndromes. Circulation 2004; 110 (15): 2119-24. 31. Corrado D, Pelliccia A, Bjørnstad HH et al. Cardiovascular preparticipation screening of young competitive athletes for prevention of sudden death: proposal for a common European protocol. Consensus Statement of the Study Group of Sport Cardiology of the Working Group of Cardiac Rehabilitation and Exercise Physiology and the Working Group of Myocardial and Pericardial Diseases of the European Society of Cardiology. Eur Heart J 2005; 26 (5): 516-24. 32. Maron BJ, Chaitman BR, Ackerman MJ et al. Recommendations for physical activity and recreational sports participation for young patients with genetic cardiovascular diseases. Circulation 2004; 109 (22): 2807-16.

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33. Maron BJ, Kogan J, Proschan MA, Hecht GM, Roberts WC. Circadian variability in the occurrence of sudden cardiac death in patients with hypertrophic cardiomyopathy. J Am Coll Cardiol 1994; 23 (6): 1405-9. 34. Maron BJ, Thompson PD, Ackerman MJ et al. Recommendations and considerations related to pre-participation screening for cardiovascular abnormalities in competitive athletes: 2007 update: a scientific statement from the American Heart Association Council on Nutrition, Physical Activity, and Metabolism: endorsed by the American College of Cardiology Foundation. Circulation 2007; 115 (12): 1643-55. 35. Pelliccia A, Fagard R, Bjørnstad HH et al. Recommendations for competitive sports participation in athletes with cardiovascular disease: a consensus document from the Study Group of Sports Cardiology of the Working Group of Cardiac Rehabilitation and Exercise Physiology and the Working Group of Myocardial and Pericardial Diseases of the European Society of Cardiology. Eur Heart J 2005; 26 (14): 1422-45. 36. Tanaka Y, Yoshinaga M, Anan R et al. Usefulness and cost effectiveness of cardiovascular screening of young adolescents. Medicine & Science in Sports & Exercise 2006; 38 (1): 2-6. 37. Bongioanni S, Bianchi F, Migliardi A et al. Relation of QRS duration to mortality in a community-based cohort with hypertrophic cardiomyopathy. Am J Cardiol 2007; 100 (3): 503-6. 38. Ostman-Smith I, Wettrell G, Keeton B et al. Echocardiographic and electrocardiographic identification of those children with hypertrophic cardiomyopathy who should be considered at high risk of dying suddenly. Cardiol Young 2005; 15 (6): 632-42. 39. Gussak I, Brugada P, Brugada J et al. Idiopathic short QT interval: a new clinical syndrome? Cardiology 2000; 94 (2): 99-102. 40. Quaglini S. Cost-effectiveness of neonatal ECG screening for the long QT syndrome. European Heart Journal 2006; 27 (15): 1824-32. 41. Schwartz PJ, Garson A, Paul T et al. Guidelines for the interpretation of the neonatal electrocardiogram. A task force of the European Society of Cardiology. Eur Heart J 2002; 23 (17): 1329-44. 42. Pelliccia A, Corrado D, Bjørnstad HH et al. Recommendations for participation in competitive sport and leisure-time physical activity in individuals with cardiomyopathies, myocarditis and pericarditis. Eur J Cardiovasc Prev Rehabil 2006; 13 (6): 876-85. 43. Seggewiss H, Blank C, Pfeiffer B, Rigopoulos A. Hypertrophic cardiomyopathy as a cause of sudden death. Herz 2009; 34 (4): 305-14. 44. Zipes DP, Camm AJ, Borggrefe M et al. ACC/AHA/ESC 2006 guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death – executive summary: A report of the American College of Cardiology/American Heart Association Task Force and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Develop Guidelines for Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death) Developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society. Eur Heart J 2006; 27 (17): 2099-140.


RCSIsmjpaediatrics review Making Europe a better place for our children “By spending itself for the benefit of its children, the human race ensures the progressive development of all.� James Connolly

Royal College of Surgeons in Ireland Student Medical Journal 2010; 3: 47-50.

Sarah Cook1, Natalya Azadeh1, Mary Neville1,

The true measure of a nation’s standing is how well it attends to its children; their health and safety, their education, and their sense of being loved, valued and included in the society into which they are born.1,2,3,4,5 Child poverty rates vary from under 3% to more than 25% in Europe. Whether measured by physical and mental development, health and survival rates, educational achievements or job prospects, incomes or life expectancies, those who spend their childhood in poverty of income and expectation are at a marked and measurable disadvantage. They are more likely to have learning difficulties, to drop out of school, to resort to drugs, to commit crimes, to be out of work, to become pregnant at an early age, and to live lives that perpetuate poverty and disadvantage into succeeding generations.6

Professor Alf Nicholson2 1RCSI medical students 2Professor of Paediatrics,

RCSI, and Consultant Paediatrician, Temple Street Hospital, Dublin

Indicators of health and safety of children across Europe The infant mortality rate (IMR) is a standard indicator of child health. IMR ranges from under three per 1,000 births in Iceland to over six per 1,000 in Hungary and Poland. A society that can effectively reduce infant mortality to

below five per 1,000 live births is one that has the capacity and commitment to deliver critical components of child health (Figure 1).7 Immunisation rates serve as a measure of national commitment to primary healthcare for children. Failure to reach high levels of immunisation reduces herd immunity, which means that more children may fall victim to disease. Furthermore, immunisation rates may be indicative of the effort made by each nation to provide each child, and particularly the children of marginalised groups, with basic preventive health services (Figure 2).8 Sweden, the United Kingdom, the Netherlands and Italy are the four countries that have reduced the incidence of deaths from accidents and injuries to a remarkably low level, fewer than 10 per 100,000. The likelihood of a child being injured or killed is also associated with poverty, single parenthood, low maternal education, low maternal age at birth, poor housing, weak family ties, and parental drug or alcohol abuse (Table 1). Other indicators of child well-being (Table 2) include:

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15 80

Infant mortality in Ireland

Q1 2008 –

Q3 2007 –

Q1 2007 –

Q3 2006 –

Q1 2006 –

Q3 2005 –

Q1 2005 –

Q3 2004 –

Q1 2004 –

Q3 2003 –

Q1 2003 –

Q3 2002 –

– – – – – – – – – – – – – – – – – – – – – – – – – – –

0

0

Q1 2002 –

3

20 Q3 2001 –

6

40

Q1 2001 –

9

60

Q3 2000 –

Percentage uptake

12

1980 1981 1982 1983 1984 1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006

Deaths per 1,000 live births

100

Quarter

Infant mortality in EU-15

Men C

MMR

Diptheria

Hib

Source: European Health for all Database (November 2007), WHO Regional Office for Europe The uptake levels, where applicable, are for fully completed courses of vaccination. Source: HPSC.

FIGURE 1: Infant mortality rates in Ireland and the EU 15, 1908-2006.

FIGURE 2: Quarterly immunisation uptake rates at 24 months of age, Q3 2000 to Q1 2008.

Table 1: Comparisons of social policies and poverty rates with Scandinavian countries.28 Country

Average ranking position for all six dimensions of child well-being

Child poverty rate

% GDP spent on social protection

Expenditure per capita in PPS

General government contributions

Social contributions

The Netherlands Sweden Denmark Ireland The United Kingdom

4.2 5.0 7.2 10.2 18.2

7.7% 2.6% 2.4% 16.8% 19.8%

29.3 30.7 29.1 18.2 26.4

9 8 8 6 7

20.1 48.9 62.8 53.2 50.4

69.5 48.7 30.8 41.8 47.9

■ educational achievement (average achievement in reading, mathematical and science literacy, the percentage of 15- to 19-yearolds remaining in education and the percentage of 15-year-olds expecting to find low-skilled work);6 ■ family structure (percentage of children living in single parent families, percentage of children who report eating the main meal of the day with parents more than once a week and percentage of 11-, 13- and 15-year-olds who report finding their peers “kind and helpful”);6 ■ health behaviours and risks (includes the percentage of children who eat breakfast daily, are physically active and not overweight);6 ■ risk behaviours (percentage of 15-year-olds who smoke, who have been drunk more than twice, who use cannabis, who have sex by age 15, who use condoms, or who may have experienced violence in the last 12 months);6 and, ■ subjective well-being.6 In particular, eating habits in childhood and adolescence are indicators of both present and future well being. Those who eat

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099 998 601 321 410

unhealthily during the early years of life are more likely to continue the pattern into adulthood and to be at increased risk of diabetes, heart disease and cancer.

Effects of poverty and lessons from Europe A child living in a household with either no working adult or only one working adult is more likely to fall below the poverty line than a child in a two-income household. There is a clear link between child poverty rates and the percentage of full-time workers who are low paid (defined as earning less than twothirds of the national median wage).5 Children from poor households are much more likely to have low educational achievement, to become teenage parents, to serve a prison sentence, and to have less success in the labour market. Recent evidence from Germany shows that children from the poorest fifth of households (assessed by averaging the income over their childhood years of 6-13) are only one-quarter as likely to attend a gymnasium secondary school – the best route to university – as


RCSIsmjpaediatrics review Table 2(a): Child well-being: EU comparisons.28 Dimension 1

Dimension 2

Dimension 3

Dimension 4

Dimension 5

Dimension 6

Dimension of child well-being

Average ranking position (for all 6 dimensions)

Material well-being

Health and safety

Educational well-being

Family and peer relationships

Behaviours and risks

Subjective well-being

Netherlands

4.2

10

2

6

3

3

1

Sweden

5.0

1

1

5

15

1

7

Denmark

7.2

4

4

8

9

6

12

Finland

7.5

3

3

4

17

7

11

Spain

8.0

12

6

15

8

5

2

Switzerland

8.3

5

9

14

4

12

6

Norway

8.7

2

8

11

10

13

8

Italy

10.0

14

5

20

1

10

10

Ireland

10.2

19

19

7

7

4

5

Belgium

10.7

7

16

1

5

19

16

Germany

11.2

13

11

10

13

11

9

Canada

11.8

6

13

2

18

17

15

Greece

12.3

15

18

16

11

8

3

Poland

12.3

21

15

3

14

2

19

Czech Republic

12.5

11

10

9

19

9

17

France

13.0

9

7

18

12

14

18

Portugal

13.7

16

14

21

2

15

14

Austria

13.8

8

20

19

16

16

4

Hungary

14.5

20

17

13

6

18

13

United States

18.0

17

21

12

20

20

-

United Kingdom

18.2

18

12

17

21

21

20

those from the richest fifth.5 For practical purposes, poverty is usually interpreted as those whose incomes fall below half of the average income, as measured by the median, for the nation in which they live. For the best part of 20 years the Nordic countries of Denmark, Finland, Norway and Sweden have held child poverty at around 5%. These consistently low rates, even in the face of economic recession and rising unemployment during the early 1990s, suggest that these countries share effective policies that offer lessons for elsewhere.6 Scandinavian policy places emphasis on helping people into paid work. This is complemented by a wide range of social policies aimed at redistributing income to reduce inequalities. One element of the drive for high employment rates has been the focus on promoting gender equality and stimulating a more

equal share of responsibility for childcare between men and women. Nordic countries have legislated in favour of extended parental leave schemes, which allow one parent to care for a child at home until the age of three without losing their job. Daycare is universal in all Scandinavian countries except Norway.9 High investment in family policy means high social expenditure. Tax and social contributions in Denmark, Finland and Sweden averaged 52% of GDP compared to an average of 41% in other European Union (EU) Member States. It is clear, however, that higher government spending on family and social benefits is associated with lower child poverty rates. Most EU countries that devote 10% or more of GDP to social transfers have child poverty rates lower than 10%, of which the notable exceptions are Ireland and the United Kingdom. Comparatively,

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RCSIsmjpaediatrics review Table 2(b): Overview. ■ Child poverty rates in the world’s wealthiest nations vary from under 3% to over 25%. ■ One in every six children in the EU is living in poverty. ■ There is a close relationship between child poverty rates and the percentage of households with children in which there is no adult in work. ■ Countries with the lowest child poverty rates (especially the Scandanavian countries) allocate the highest proportion of GNP to social expenditure.

no country devoting less than 5% of GDP to social transfers has a child poverty rate of less than 15%.10 Interestingly, there appears to be little relationship between levels of employment and levels of child poverty. Rather, the distribution of employment among different households, the proportion of those in low paying jobs, and the level of state benefits for the unemployed, are the factors that contribute most to these differences.10 International variation in the proportion of children growing up in single-parent families also does not correlate with poverty rates. Sweden, for example, has a higher proportion of its children living in single-parent families than the United States or the United Kingdom but has a much lower child poverty rate.6 Single-parent households, distribution of employment, wage inequality and state transfers to the unemployed and low paid are all contributory to childhood poverty, but no one cause predominates. One-fifth of Britain’s children live in poverty, a rate more than twice as high as France or the Netherlands and five times higher than in Norway and Sweden.12 About half of Britain’s poor

children live in households where parents are unavailable for work, through sickness, disability or because a child is below school age. Many children continue to depend on state benefits that currently leave them well below the poverty line. The best performing countries have child benefit systems with certain common characteristics. These include comparatively generous universal child and unemployment benefits, adequate social assistance, lower childcare costs, guaranteed child support, and housing benefits that help a large proportion of families on low incomes.5 An Irish anti-poverty strategy involves a process of building and sustaining a national consensus. The main challenges are to first create an awareness of poverty and its effects, to debunk myths and to demonstrate the need for action. Regardless of a country’s economic status, policy interventions can significantly lessen the burden of poverty.12 The statistics outlined in this article indicate that most of the variation in child poverty levels among EU countries can be attributed to government policy. A realistic target for all EU countries would be to reduce child poverty rates to below 10% and, for those countries who have already achieved this, to emulate the four Nordic countries in bringing child poverty rates below 5%.

Conclusions Child poverty is clearly linked to child health and well-being. Successful strategies to reduce poverty seek a balance between improved child benefits while maintaining incentives to work. Countries with low child poverty rates have common policies that include jobs with sufficient pay, flexible hours and leave, parental leave arrangements, skills training for parents and excellent childcare. These aspirations have been consistently achieved in Scandinavian countries as a result of national social policies. If we wish to eradicate child poverty across Europe we need to emulate these policies.

References 1. Aaberge A, Bjorklung M, Jantti P, Pedersen N, Smith N, Wennemo T. Unemployment shocks and income distribution: how did the Nordic countries fare during their crises? Scandinavian Journal of Economics 2000; (102): 77-99. 2. Bradbury B, Jenkins S, Micklewright J. The Dynamics of Child Poverty in Industrialized Countries: Innocenti Working paper 78. Available from: http://www.unicef-icdc.org. 3. Targeting poverty: lessons from Ireland on setting a national poverty target. New Economy 1999; (6): 44-9. 4. Bradshaw JA. Child poverty and deprivation. In: Bradshaw J, Mayhew W (eds.). The Well-being of Children in the United Kingdom. London: Save the Children, 2005. 5. Bradshaw JA. A review of the comparative evidence on child poverty 2006. Joseph Rowntree Foundation.

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6. 2007 UNICEF Innocenti Research Centre, Florence p. 4 Public Health Reports/July-August 2005/Volume 120. 7. WHO Regional Office for Europe. European Health for All Database, November 2007. 8. HPSC Health Protection Surveillance Centre. Immunisation Uptake Report. Available from: www.hpsc.ie. 9. Innocenti report card 1: p.8 10. Innocenti report card 1: p.14 figure 8 11. Child poverty in rich nations 2005. Innocenti Report Card 7: UNICEF Research Centre 12. Whiteford P, Adema W. What works best in reducing child poverty: a benefit or work strategy? OECD Social, employment and migration working papers 2007; 1-51.


RCSIsmjreview Anatomy of a pandemic: influenza A (H1N1) 2009 Abstract The H1N1 2009 influenza A virus has reached pandemic status and is currently infecting hundreds of thousands of people, spreading efficiently since being isolated in Mexico in April 2009. In this review, the current pandemic state of H1N1 will be discussed along with the symptoms and severity of illness caused by the virus and how they compare to previous pandemics. A number of diagnostic tests are available for the rapid detection of the H1N1 2009 infection and are discussed, along with management of infection and the emergence of antiviral resistance. A vaccine has currently been licensed for use against the H1N1 2009 virus and its effectiveness will be addressed, along with prevention measures that should be taken to hinder further spread of the virus. Keywords: Influenza A virus, H1N1 subtype, disease outbreaks, influenza, human, virus replication, virus shedding, influenza vaccines, oseltamivir, zanamivir. Royal College of Surgeons in Ireland Student Medical Journal 2010; 3: 51-55.

Introduction

Adam C Brady RCSI medical student

Influenza A viruses have long caused human pandemics. The current pandemic virus is a direct descendent of the influenza A H1N1 outbreak of 1918 (the ‘Spanish flu’), which killed an estimated 50 million people worldwide.1 In April 2009, a novel triple-reassortment swine-origin influenza A virus was isolated from a patient in Mexico, and quickly spread worldwide. This is the first influenza A virus pandemic since the H3N2 Hong Kong influenza outbreak of 1968, which killed an estimated one to two million people.1 As of November 15, 2009, 206 countries have reported 6,770 deaths due to H1N1 2009 to the World Health Organisation (WHO).2 In contrast, seasonal influenza A epidemics result in three to five million severe infections worldwide, with 250,000-500,000 deaths annually.3 Ireland has reported 3,914 confirmed cases, with 16 deaths due to H1N1 2009 as of November 14, 2009.4

The current influenza outbreak has been classified as phase 6 by the WHO, indicating that the virus has reached full pandemic status and has the capability to cause sustained outbreaks in populations across the globe. All WHO pandemic phases are illustrated in Figure 1.5 H1N1 2009 infections had been steadily increasing worldwide until reaching a peak in late October 2009. Decreases in infection indices were observed in many countries throughout November, with the amount of hospitalised cases of H1N1 2009 decreasing by 50% in Ireland.4,1 Although the drop in influenza cases may appear to indicate that the worst of the pandemic has passed, this may in fact be due to the natural progression of the pandemic. Influenza pandemics typically progress in waves, and a decrease in the amount of cases may indicate the end of a wave of infections, with potentially more outbreaks to come.6

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RCSIsmjreview PHASES 1-3

PHASE 4

PHASE 5-6/ PANDEMIC

POST PEAK

POST PANDEMIC

Predominantly animal infections; few human infections

Sustained human to human transmission

Widespread human infection

Possibility of recurrent events

Disease activity at seasonal levels

Time

FIGURE 1: Pandemic influenza phases. Source: WHO.

Influenza A virus

Pathogenicity of the virus

Influenza viruses are classified by their core proteins as influenza A, B, or C.1 Influenza A is a negative sense RNA orthomyxovirus containing eight

It is of great benefit to use previous pandemics as models to assess the potential of the H1N1 2009 virus for widespread infection and loss of life. Pathogenicity of viruses is often determined by the reproduction number (R0), which indicates the average number of infections caused by a single person with the illness. The reproduction number for H1N1 2009 is estimated to be between 1.4 and 1.6.14 This is more transmissible than the seasonal influenza virus, which has a mean R0 of 1.3, and less transmissible than the 1918 pandemic, which at its peak had an estimated mean R0 of 2.0.15

genetic segments, which code for 10 different proteins7 (Table 1).1,8-10 Influenza A is further classified by the surface antigens haemagglutinin (H) and neuraminidase (N). Sixteen H and nine N alleles exist, coding for 144 possible unique surface antigen combinations.11 In addition, mutations in the influenza genome can result in antigenic drift, introducing new viral subtypes into the population and altering the pathogenicity of individual virus strains. When two viral subtypes co-infect the same host, genetic shift can occur. Genetic shift results from the swapping of one or both genomic segments encoding H and N between two different influenza subtypes. Pigs are frequently infected with human and avian influenza strains, and

Table 2: Influenza pandemics. Year/name Strain

Estimated deaths

thus are thought to be prime organisms for facilitating the creation of new strains of influenza via genetic drift. In the case of H1N1 2009, the virus was originally endemic in swine and adapted to cause widespread infection in humans.12 Pandemics arise when a virus undergoes genetic shift resulting in a novel H surface protein. Rapid spread through large populations occurs due to an absence of previous immunity to the new

1918 ‘Spanish flu’

H1N1

20-50 million

1957-‘58 ‘Asian flu’

H2N2

2-4 million

1968-‘69 ‘Hong Kong flu’

H3N2

1-2 million

H antigen, which contributed to the 1918, 1957 and 1968 pandemics, and is implicated in the current H1N1 2009 outbreak.10 An overview of previous pandemics is detailed in Table 2.11,13

1977 ‘Russian flu’

H1N1

0.7 million

2009 Pandemic flu

H1N1

Under review

Table 1: Influenza gene segments and functions. Protein(s) Gene segment

Function

Lineage

NA

Neuraminidase

Viral progeny release and spread

Eurasian swine

M

Matrix protein 1 Matrix protein 2

Structural

Eurasian swine

*HA

Haemagglutinin

Binds to sialic acid receptors on host cell surface

Classical swine

NP

Nucleoprotein

Encapsidation of viral genome

Classical swine

*NS

Non-structural protein 1 NEP

Inhibits host interferon response; inhibits apoptosis

Classical swine

Viral polymerase complex

Viral RNA replication

Swine triple ressortant

*PB1, PB2, PA *Virulence factors

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RCSIsmjreview Table 3: Diagnostic tests for H1N1 2009. Test

Time to complete

Sensitivity

Specificity

PPV

NPV

Rapid antigen detection

15 minutes

17.8

93.6

77.4

47.9

Direct fluorescent antibody

2.5 hours

46.7

94.5

91.3

58.9

Viral cell culture

2-3 days

88.9

100

100

87.9

Polymerase chain reaction

Up to 6 hours

97.8

100

100

97.3

PPV: positive predictive value; NPV: negative predictive value.

Although the reproduction number of H1N1 2009 is closer to that of the seasonal flu virus than the devastating 1918 influenza pandemic, it carries the potential to develop mutations that could allow more efficient spread between humans, increasing its replication number.

Symptoms of pandemic H1N1 H1N1 2009 is spread through respiratory droplets, with an incubation time of two to seven days.16 This is considerably longer than the incubation time of the seasonal influenza A virus, which has been estimated at 1.4 days.17 Models have shown that shedding of the virus is observed as soon as one day after infection and lasts seven days,18 allowing for asymptomatic spread. Symptoms of infection are similar to symptoms of the seasonal influenza virus, including fever (94%), cough (92%) and sore throat (66%). Vomiting and diarrhoea are also present in 25% of cases, and potential faecal–oral spread of the virus must be investigated.1,16 The majority of previously healthy patients who acquire H1N1 2009 will fully recover in one week. In a study of 272 patients hospitalised with H1N1 2009 infection, 73% had underlying medical conditions, including asthma, diabetes, pregnancy, and neurological disease. Nineteen (7%) died, with a median time from onset of illness to death of 15 days. Hospitalisations were seen more frequently in younger patients, with only 5% of admissions consisting of patients over 65 years old.19 This is in contrast with seasonal influenza, in which the majority of hospitalisations occur in the elderly population and children under two years of age.20

Diagnosis of pandemic H1N1 Many different variables contribute to making a diagnosis. Clinical suspicion based on current pandemic trends in the community must be high to cost-effectively carry out diagnostic testing. There are many techniques readily available to confirm a diagnosis, including rapid antigen testing, direct fluorescent antibody testing, polymerase chain reaction (PCR), and cell culture methods. Characteristics of each test are shown in Table 3.21 PCR remains the most robust test for diagnosing pandemic influenza, yielding the most sensitive and specific results within a reasonable time period. Other tests may be quicker, but are much less sensitive.

Treatment strategies The earlier antiviral therapy is started, the more effective the treatment is at reducing influenza viral load and the duration of viral shedding.19,22 Current antiviral treatments include N inhibitors (oseltamivir and zanamivir) and adamantane derivatives (amantadine and rimantidine). Oseltamivir and zanamivir function by blocking progeny virion release from infected cells, while adamantane and its derivatives interfere with intracellular viral uncoating.23 While most strains of pandemic H1N1 have remained susceptible to N inhibitors, adamantane-based drug resistance has been described and these drugs are not considered to be treatment options for acute infection.16,24 Due to its effectiveness against H1N1 2009, many countries have stockpiled vast quantities of oseltamivir to combat the global pandemic. Unfortunately, resistance to oseltamivir has recently emerged in 31 cases of H1N1 2009 infection.25 Peravimir, an N inhibitor that is currently undergoing Phase 3 clinical trials, was authorised for emergency use by the Centers for Disease Control (CDC) on October 23, 2009. It has been approved for use in severe cases of H1N1 2009, which are not responsive to oseltamivir or zanamivir.26 Zanamivir has shown similar efficacy and safety to oseltamivir with no resistance reported to date, and is effective in treating oseltamivir-resistant strains.27,28 Zanamivir is contraindicated in patients with chronic obstructive pulmonary disease (COPD), and is delivered using an inhaler, which is difficult to administer correctly to children and elderly patients.27 Countries are now adding zanamivir to their antiviral stockpiles (which are dominated by oseltamivir stores); however, a large number of children, COPD patients, and the elderly are currently vulnerable to oseltamivirresistant H1N1 2009.27 New research has shown that a synergy of oseltamivir, amantadine and ribavirin (a widely available antiviral drug) has a two- to 13fold increase in antiviral activity against influenza A when compared to any two of the agents used together in vitro.30 Additional studies of antiviral treatments for oseltamivir-resistant H1N1 must be undertaken to ensure the safety and preparedness of the general population in the event of a multidrug-resistant influenza pandemic.

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RCSIsmjreview Vaccination

Prevention and infection control

Vaccination continues to be the most important primary prevention measure against influenza spread.31 Both live attenuated and inactivated vaccines providing protection from H1N1 2009 have been manufactured for general use, with the first batches administered to the public in early October 2009. The pandemic H1N1 vaccine is being manufactured in the same way as the annual influenza vaccine, using hen’s eggs to grow both the pandemic H1N1 virus and an inactive laboratory strain. Hybrid virions containing surface proteins of the pandemic strain with an inactivated genome are isolated and become the main constituent of the inactive vaccine.32 A single dose influenza H1N1 vaccine is immunogenic in adults with sufficient protective antibodies produced 14-21 days post vaccination.33 Children aged six months to nine years should receive two doses of vaccine separated by 21 days to ensure sufficient production of antibodies.34 Side effects are similar to those of the seasonal influenza vaccine, consisting of injection site tenderness and mild headaches. No serious adverse events have been consistently reported. However, there is widespread public concern over the vaccine’s safety,35 which is based on fears of rare complications from the vaccine, namely Guillain-Barré syndrome. Thus far, in the population who have been vaccinated, the incidence of Guillain-Barré syndrome has not increased over the baseline rates that are observed in the general population. This is also true for other serious medical conditions.36 Careful vaccine safety surveillance must be undertaken to detect increases in adverse vaccine reactions over background incidences. Since availability of the vaccine will be limited, selected countries have initiated prioritisation schedules for vaccine recipients in the event of a vaccine shortage. The CDC has advised that populations at risk of serious complications should be vaccinated. This includes all children and young adults between the ages of six months and 24 years of age, all people between the ages of 25 and 64 who have underlying health conditions, healthcare and emergency service workers, pregnant women, and people who care for children under the age of six months.37

Prevention of the spread of H1N1 2009 can also be facilitated by community interventions. Simple measures such as covering coughs and sneezes, washing hands, staying home when sick, and avoiding close contact with people who are ill can have enormous effects on reducing the spread of disease. Households that initiate the use of facemasks and hand hygiene within the first 36 hours after the onset of flu-like symptoms in a family member have a reduced incidence of household transmission of influenza.38 This illustrates the importance of non-medical measures for controlling infection and can also be translated to the hospital setting, where the use of facemasks, gloves and aprons is recommended when treating infected patients. The use of negative pressure rooms and fit-tested ventilators has been advised by the CDC, but may not be possible in all centres due to facility and financial limitations.30,39

Conclusion Past pandemics have shown that influenza A viruses have great potential to cause widespread infections and deaths worldwide. It is important to stay vigilant in the surveillance and detection of influenza strains so that future pandemics can be predicted and prevented before they reach advanced stages. While the current H1N1 2009 virus has not been as devastating as some had forecast, the capability for further, and perhaps more virulent and lethal mutations, still exists.1 Vaccine production must be increased so that new pandemic strains of influenza can quickly be vaccinated against. A combination of public awareness of the pandemic threat, increased vaccine production technologies, and further development of antiviral treatments is the key to being prepared for current and future influenza pandemics.

References 1. Michaelis M, Doerr HW, Cinatl Jr J. An Influenza A H1N1 Virus Revival – Pandemic H1N1/09 Virus. Infection 2009; 37 (5): 3819. 2. World Health Organisation. Pandemic (H1N1) 2009 – update 75. Cited 2009. Available from: www.who.int/csr/don/2009_11_20a/en/index.html, 2009. 3. World Health Organisation. Fact Sheet: Influenza (Seasonal). Cited April 2009. Available from: www.who.int/mediacentre/factsheets/fs211/en/index.html. 4. Health Protection Surveillance Centre. Influenza Weekly Surveillance Report. Cited November 19, 2009. Available from:. http://www.hpsc.ie/hpsc/AZ/EmergencyPlanning/AvianPandemicInfluenza/SwineInfluenza/S urveillance%20Reports/File,3749,en.pdf.

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5. World Health Organisation. Current WHO Phase of Pandemic Alert. Available from: www.who.int/csr/disease/avian_influenza/ phase/en/index.html. 6. Glezen WP. Emerging infections: pandemic influenza. Epidemiol Rev 1996; 18 (1): 64-76. 7. Strauss JH, Strauss EG. Viruses and Human Disease. San Diego: Academic Press, 2002. 8. Ghate AA, Air GM. Site-directed mutagenesis of catalytic residues of influenza virus neuraminidase as an aid to drug design. Eur J Biochem 1998; 258 (2): 320-31. 9. Portela A, Digard P. The influenza virus nucleoprotein: a multifunctional RNA-binding protein pivotal to virus replication. J Gen Virol 2002; 83 (Pt 4): 723-34. 10. Garten RJ, Davis CT, Russell CA, Shu B, Lindstrom S, Balish A et al. Antigenic and genetic characteristics of swine-origin 2009 A (H1N1) influenza viruses circulating in humans. Science 2009; 325 (5937): 197-201.


RCSIsmjreview 11. Michaelis M, Doerr HW, Cinatl Jr J. Novel swine-origin influenza A virus in humans: another pandemic knocking at the door. Med Microbiol Immunol 2009; 198 (3): 175-83. 12. Cinatl Jr J, Michaelis M, Doerr HW. The threat of avian influenza A (H5N1). Part I: Epidemiologic concerns and virulence determinants. Med Microbiol Immunol 2007; 196 (4): 181-90. 13. National Institute of Allergy and Infectious Diseases. Flu (Influenza): Timeline of Influenza Pandemics. Available at: www3.niaid.nih.gov/topics/Flu/Research/Pandemic/TimelineHum anPandemics.htm. 14. Fraser C, Donnelly CA, Cauchemez S, Hanage WP, Van Kerkhove MD, Hollingsworth TD et al. Pandemic potential of a strain of influenza A (H1N1): early findings. Science 2009; 324 (5934): 1557-61. 15. Coburn BJ, Wagner BG, Blower S. Modelling influenza epidemics and pandemics: insights into the future of swine flu (H1N1). BMC Med 2009; 7: 30. 16. Dawood FS, Jain S, Finelli L, Shaw MW, Lindstrom S, Garten RJ et al. Emergence of a novel swine-origin influenza A (H1N1) virus in humans. N Engl J Med 2009; 360 (25): 2605-15. 17. Lessler J, Reich NG, Brookmeyer R, Perl TM, Nelson KE, Cummings DA. Incubation periods of acute respiratory viral infections: a systematic review. Lancet Infect Dis 2009; 9 (5): 291300. 18. Munster VJ, de Wit E, van den Brand JM, Herfst S, Schrauwen EJ, Bestebroer TM et al. Pathogenesis and transmission of swineorigin 2009 A (H1N1) influenza virus in ferrets. Science 2009; 325 (5939): 481-3. 19. Jain S, Kamimoto L, Bramley AM, Schmitz AM, Benoit SR, Louie J et al. Hospitalised patients with 2009 H1N1 influenza in the United States, April-June 2009. N Engl J Med 2009; 361 (20): 1935-44. 20. Thompson WW, Shay DK, Weintraub E, Brammer L, Bridges CB, Cox NJ et al. Influenza-associated hospitalisations in the United States. JAMA 2004; 292 (11): 1333-40. 21. Ginocchio CC, Zhang F, Manji R, Arora S, Bornfreund M, Falk L et al. Evaluation of multiple test methods for the detection of the novel 2009 influenza A (H1N1) during the New York City outbreak. J Clin Virol 2009; 45 (3): 191-5. 22. Lee N, Chan PK, Hui DS, Rainer TH, Wong E, Choi KW et al. Viral loads and duration of viral shedding in adult patients hospitalised with influenza. J Infect Dis 2009; 200 (4): 492-500. 23. Moscona A. Neuraminidase inhibitors for influenza. N Engl J Med 2005; 353 (13): 1363-73. 24. Wang JF, Wei DQ, Chou KC. Insights from investigating the interactions of adamantane-based drugs with the M2 proton channel from the H1N1 swine virus. Biochem Biophys Res Commun 2009; 388 (2): 413-7. 25. World Health Organisation. Pandemic (H1N1) 2009 – update 70. Cited 2009. Online. Available from: www.who.int/csr/don/2009_10_16/en/index.html, 2009.

26. Silver Spring, MD: Food and Drug Administration, 2009. Emergency Use Authorization of peramivir: fact sheet for health care providers. Cited November 24, 2009. Accessed November 24, 2009. Available from: http://www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDr ugSafetyInformationforPatientsandProviders/UCM187811.pdf. 27. Khazeni N, Bravata DM, Holty JE, Uyeki TM, Stave CD, Gould MK. Systematic review: safety and efficacy of extended-duration antiviral chemoprophylaxis against pandemic and seasonal influenza. Ann Intern Med 2009; 151 (7): 464-73. 28. Update: influenza activity – United States, September 28, 2008January 31, 2009. MMWR Morb Mortal Wkly Rep 2009; 58 (5): 115-9. 29. Diggory P, Fernandez C, Humphrey A, Jones V, Murphy M. Comparison of elderly people’s technique in using two dry powder inhalers to deliver zanamivir: randomised controlled trial. BMJ 2001; 322 (7286): 577-9. 30. Nguyen JT, Hoopes JD, Smee DF, Prichard MN, Driebe EM, Engelthaler DM et al. Triple combination of oseltamivir, amantadine, and ribavirin displays synergistic activity against multiple influenza virus strains in vitro. Antimicrob Agents Chemother 2009; 53 (10): 4115-26. 31. Barry JM. Pandemics: avoiding the mistakes of 1918. Nature 2009; 459 (7245): 324-5. 32. World Health Organisation. Pandemic (H1N1) 2009 briefing note 7: Pandemic influenza vaccine manufacturing process and timeline. Available from: www.who.int/csr/disease/swineflu/notes/h1n1_vaccine_2009080 6/en/index.htm. 33. Clark TW, Pareek M, Hoschler K, Dillon H, Nicholson KG, Groth N et al. Trial of Influenza A (H1N1) 2009 Monovalent MF59-Adjuvanted Vaccine – Preliminary Report. N Engl J Med 2009; 361 (25): 2424-35. 34. Wise J. Children are likely to need two doses of swine flu vaccine. BMJ 2009; 339: b3969. 35. Greenberg ME, Lai MH, Hartel GF, Wichems CH, Gittleson C, Bennet J et al. Response after one dose of a monovalent influenza A (H1N1) 2009 vaccine – preliminary report. N Engl J Med 2009; 361 (25): 2405-13. 36. Black S, Eskola J, Siegrist CA, Halsey N, Macdonald N, Law B et al. Importance of background rates of disease in assessment of vaccine safety during mass immunisation with pandemic H1N1 influenza vaccines. Lancet 2009; 374 (9707): 2115-22. 37. Update on influenza A (H1N1) 2009 monovalent vaccines. MMWR Morb Mortal Wkly Rep 2009; 58 (39): 1100-1. 38. Cowling BJ, Chan KH, Fang VJ, Cheng CK, Fung RO, Wai W et al. Facemasks and hand hygiene to prevent influenza transmission in households: a cluster randomised trial. Ann Intern Med 2009; 151 (7): 437-46. 39. Gordon SM. Update on 2009 pandemic influenza A (H1N1) virus. Cleve Clin J Med 2009; 76 (10): 577-82.

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RCSIsmjreview Understanding metastasis: current paradigms and therapeutic challenges in breast cancer progression

Abstract Metastasis is the terminal event in carcinogenesis and the principal contributor to mortality in breast cancer patients. However, relatively little is known about the molecular mechanisms of this complex, multi-step process. Consequently, management of metastatic breast cancer (MBC) is far less successful than the treatment of primary disease. Research in the field is very active, resulting in the development of numerous models of metastasis and the identification of key factors implicated in the process. Thus it is hoped that with continued research into the mechanisms driving cancer progression and metastasis, insights will be gained that will facilitate earlier diagnosis and improved treatment of MBC. Key words: Breast cancer, metastasis, metastatic regulators, targeted therapies. Abbreviations – MBC: metastatic breast cancer; EMT: epithelial-mesenchymal transition; MET: mesenchymal-epithelial transition; EGF: epidermal growth factor; VEGF: vascular endothelial growth factor; PDGF: platelet-derived growth factor; RNAi: RNA interference; miRNA: microRNA; ESMO: European Society of Medical Oncology; CTC: circulating tumour cell. Royal College of Surgeons in Ireland Student Medical Journal 2010; 3: 56-60.

Introduction

Sharon F. McGee RCSI medical student

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Breast cancer is the most common female malignancy in the developed world, with over 60,000 women in the EU succumbing to the disease each year.1 The Irish National Cancer Registry predicts that by 2020, the number of cases in this country could increase from the current yearly average of 1,895 to almost 5,000 cases per annum.2 Over the past two decades, the management of breast cancer has evolved dramatically due to an increased awareness of the disease, advances in mammographic screening, improved surgical techniques and the increased use of adjuvant therapy.3 Current treatment strategies are based on the grade, stage and hormone/growth factor receptor status of the disease. Treatments typically rely on surgery combined with adjuvant radiotherapy and systemic medical therapy, including both chemotherapy and endocrine

therapy.4 Owing to these strategies, the treatment of primary breast cancer is extremely effective when detected at an early stage. Indeed, much of this success can be attributed to novel and targeted therapies that have resulted from years of focused research into the molecular basis of breast cancer. Thus, breast cancer management is the archetypal example of personalised medicine. A brief overview of these therapies is provided in Table 1. However, as with most other malignancies, the main cause of death in breast cancer patients is not the primary tumour but metastases to different sites, with death arising as a result of direct organ damage by the growing lesions, paraneoplastic syndromes or complications following treatment.5 Despite this fact, relatively little is known about the key molecular mechanisms and determinants driving this terminal stage of the disease. Thus far, no


RCSIsmjreview doctrine akin to Hanahan and Weinberg’s “Hallmarks of Cancer”6 has yet been compiled for the metastatic process. Consequently, current diagnostic and treatment strategies for metastatic breast cancer are much less successful. Our lack of in-depth knowledge regarding metastasis is partly attributed to the complex and multifaceted nature of the process, which encompasses various dynamic physiological activities. These include invasion of the local tissue and entry into the circulatory or lymphatic systems, which transport the metastatic cells to distant sites where they may extravasate and enter the surrounding microenvironment. At this point, colonisation and continued development is typically dependent on favourable interactions with the secondary microenvironment (Figure 1).7

Table 1: Role of molecular research in the development of targeted breast cancer therapies. Targeted treatment strategies in primary breast cancer ■ Endocrine therapy arose from a specific understanding of the role oestrogen plays in mammary gland development and the promotion of breast cancer growth. ■ The monoclonal antibody trastuzumab (Herceptin) was developed to treat HER2/neu-positive tumours following the discovery that over-expression of the receptor resulted in constitutive activation and thus increased tumour cell proliferation.29 ■ These tumours may also be treated with the dual HER2/neu and EGFR tyrosine kinase inhibitor lapatinib (Tyverb/Tykerb), which is currently in trials for use both as monotherapy and in combination with other therapeutic regimes.30 ■ A recent addition is PARP inhibitors, which are under trial for the treatment of mutant BRCA1/2 breast tumours. Theses agents inhibit ss DNA repair, which triggers selective tumour cell death when coupled with the cells’ existing ds DNA repair deficit.31 ■ Deciding the best treatment strategy can, however, be challenging, especially when it comes to the use of adjuvant chemotherapy in lymph node negative patients. Thus, gene profiling techniques are used to stratify patients on the basis of their predicted prognosis in an effort to guide treatment. ■ The two main molecular profiling tools currently available are the RT-PCR assay, oncotype DX™, and the DNA microarray assay, MammaPrint®, both of which are under investigation in the TAILORx32 and MINDACT trials,33 respectively. Abbreviations – HER2/neu: human epidermal growth factor receptor 2 (ERBB2); EGFR: epidermal growth factor receptor; PARP: poly(ADP-ribose) polymerase; BRCA1/2: breast cancer susceptibility gene 1/2; ss DNA: single-stranded DNA; ds DNA: double-stranded DNA; RT-PCR: reverse transcriptase polymerase chain reaction; TAILORx: Trial Assigning Individualized Options for Treatment; MINDACT: Microarray in Node-Negative Disease May Avoid Chemotherapy.

Classical models of metastasis One of the first and most enduring metastasis models was proposed in 1889 by Stephen Paget, who was struck by the propensity of some cancers to yield metastatic growths in specific organs. He believed that their distribution was not random, but was the result of the complementary interactions between the tumour cells and host environment. He compared this interaction to that of a seed and the soil stating: “When a plant goes to seed, its seeds are carried in all directions; but they can only live and grow if they fall on congenial soil”.8 The “seed and soil” theory was later disputed by James Ewing, who suggested that the circulatory patterns between primary tumours and ectopic growths were sufficient to account for organ-specific metastasis.9 However, through a series of autopsy studies, Leonard Weiss lent credence to Paget’s theory by demonstrating that the site of many metastatic growths could not be accounted for by mechanical blood flow patterns alone.10

New paradigms in metastasis Metaplasia More recently, epithelial-to-mesenchymal transition (EMT), and the reverse process of mesenchymal-to-epithelial transition

FIGURE 1: Overview of the key molecular events in metastasis. During the metastatic process, cancer cells proceed through a series of distinct, rate-limiting steps to form an overt, secondary tumour. In the initial stages, cells detach from the primary tumour mass, invade adjacent tissue and then enter the lymphatic or circulatory systems, which transport them to distant sites, where they extravasate and enter the surrounding microenvironment. At this point, specific factors determine if the cells may proliferate to form a clinically detectable metastasis or if they are to remain dormant as single cells or micrometastases. (Figure reproduced with authors’ permission.28)

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RCSIsmjreview (MET), have been implicated in the dissemination of tumour cells and their subsequent growth at distant sites. EMT describes a series of events during which cells lose many of their classic epithelial characteristics and take on properties typical of mesenchymal cells. Central to this transition is the reduction of cell-cell adherence as a result of the transcriptional repression and delocalisation of cadherins (adherens junctions), occludin and claudins (tight junctions) and desmoplakin (desmosomes). These changes allow the cells to separate and trigger alterations in shape and adhesion, facilitating movement.11 Cycles of EMT and MET play critical roles in embryogenesis, where they are tightly regulated by various growth/transcription factors and interaction with the surrounding environment. In cancer, EMT is thought to enhance dissemination by facilitating the acquisition of a more motile, invasive phenotype while also protecting the cells in circulation. Conversely, MET is believed to allow diseminated tumour cells to re-establish their epithelial characteristics and facilitate proliferation and colonisation at the secondary site.12,13

Microenvironment and inflammation Of note with regard to the EMT model is the emphasis it places on the surrounding microenvironment, which is thought to initiate and maintain EMT-mediated tumour progression and metastasis. This is reminiscent of Paget’s seed and soil hypothesis, a theory that has seen a revival in recent years. Researchers have realised that they may have been too focused on the intrinsic properties of the tumour cell (the seed) and thus failed to recognise the role of the microenvironment (the soil). The importance of this contribution was recently highlighted by Finak et al, who successfully used DNA microarray analysis to define a stroma-derived prognostic predictor (SDPP) that could stratify disease outcome independently of standard clinical prognostic factors.14 Examination of the 26-gene SDPP revealed many encoded proteases, chemokines and cell surface receptors associated with immune cells, emphasising the important role the inflammatory response plays in tumour progression. This observation was recently reinforced by Lisa Coussens and colleagues at UCSF, who demonstrated a metastasis-promoting role for TH2-CD4+ T-lymphocytes in a pre-clinical mouse model of mammary carcinoma.15

Dormancy Dormancy is another intriguing aspect of metastasis and is particularly common in breast cancer, where between 20 and 45% of patients relapse years or even decades after their initial diagnosis.16 During this asymptomatic interim, minimal residual disease is thought to exist as pre-angiogenic micrometastases or solitary dormant cells. The latter are typically quiescent, while micrometastases are actively proliferating, their growth balanced by apoptosis and thus resulting in no net increase in size.17 Dissemination to a non-permissive microenvironment is thought to be an important factor in dormancy. However, the specific

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physiological and/or pathological influences that determine whether tumour cells remain in this dormant state or actively proliferate to form an overt macrometastasis are not yet known. However, activation of a so-called ‘angiogenic switch’ is thought to be necessary, whereby the balance between the proangiogenic (e.g., VEGF and PDGF) and anti-angiogenic (e.g., thrombospondin and angiostatin) factors necessary to maintain dormancy is tipped in favour of the former.17 As such, antiangiogenic therapies may prove beneficial in maintaining disseminated tumour cells in a dormant, sub-clinical state in the future.

Metastatic mediators It is evident that it will take some time to reconcile the various theories of metastatic mechanisms, such that an integrative model of tumour progression can be developed. However, research has also been focused on the identification of key mediators that could serve as novel points for therapeutic intervention. These mediators can be classified as either effectors or regulators, where the former are factors that promote or inhibit a specific step in the metastatic cascade (i.e., invasion and migration), but cannot by themselves direct the entire process. However, given that each step in metastasis is rate limiting, the disruption of these effectors should be sufficient to block the formation of distant metastases. Many of the metastatic effectors identified to date inhibit specific stages in the process and are referred to as metastasis suppressor genes. These genes are typically lost or down-regulated in aggressive metastatic cancers and their suppression in preclinical mouse models results in an increase in the formation of metastatic foci. However, unlike tumour suppressor genes, which inhibit tumourigenesis, metastasis suppressors only inhibit metastasis and have no effect on the growth of the primary tumour.18 Interestingly, many of these genes function by inhibiting the growth of cells at ectopic sites and thus may play a role in dormancy (e.g., KISS1 and BRMS1).19,20 The identification of key regulators of metastasis is, however, far more challenging, as these genes must be capable of orchestrating all the disparate processes required for a tumour cell to disseminate and grow at an ectopic site. Nevertheless, a breakthrough was recently made on this front with the identification of the transcription factor SATB1, which regulates the expression of multiple genomic loci by modulating higherorder chromatin structure.21 Down-regulation of the gene in an aggressive metastatic breast cancer cell line restored cell polarity in vitro while inhibiting tumour growth and metastasis in mice. Furthermore, immunohistochemical analysis of a large cohort of breast tumour samples found SATB1 expression to be an independent prognostic factor for breast cancer metastasis.21 Also emerging as key regulators of the metastatic process are miRNAs, which are a class of small, non-coding RNA molecules that have the ability to co-ordinate global changes in gene


RCSIsmjreview expression by inhibiting the translation of multiple mRNA transcripts via the RNAi pathway.22 They have been shown to play a key role in numerous physiological processes from embryogenesis to tumourigenesis, and now metastasis. A recent study identified miRNA-335 as a potent metastasis suppressor whose expression was lost in both metastatic cell lines and tumours, resulting in a dramatic increase in metastases through up-regulation of the transcription factor SOX4, which directs the expression of numerous genes implicated in tumour progression and metastasis.23

Managing metastatic breast cancer Compared with early-stage breast cancer, there are few proven standards of care for the management of MBC. However, current clinical recommendations from the European Society of Medical Oncology (ESMO) advocate the use of an interdisciplinary team of healthcare professionals to provide patients with personalised psychosocial, supportive and symptom-related interventions.24 A brief overview of the different treatment strategies for MBC is provided in Table 2. Patients with resistant or unresponsive disease may be considered for inclusion in appropriate clinical trials, which in Ireland are largely co-ordinated by the Irish Clinical Oncology Research Group (ICORG). One of the main challenges with respect to metastases is the fact that most are discovered at such an advanced stage in their development that they are often incurable. However, new techniques are emerging, which have the ability to detect disseminating tumour cells present at the single-cell level in bone marrow and peripheral blood.25 Although much success has been achieved with the detection of disseminating tumour cells in bone marrow,26 efforts are now being directed towards the detection of circulating tumour cells (CTCs) in peripheral blood. A novel system called CellSearch™(Veridex), which detects CTCs via immunocytochemistry, has just been approved by the US Food and Drug Administration for use in the management of advanced breast cancer patients.27

Conclusion Metastasis is the major contributor to mortality in patients with breast cancer, and most other malignancies. However, in comparison with tumourigenesis, relatively little is known about the molecular mechanisms or determinants of this complex process. Consequently, early stage breast cancer is typically managed very successfully, while metastasis remains a significant challenge. Although research in the field is very active, it will take some time before these hypotheses are integrated to yield a definitive model of breast cancer progression and metastasis. These studies are crucial as they provide an insight into the molecular basis of the disease process. This is not only important as a means of identifying novel points for therapeutic intervention, but for the discovery of new biomarkers that could be used to determine prognosis or response to therapy.

Table 2: Overview of current ESMO clinical recommendations for treatment of main metastatic breast cancer sub-types: luminal-type (hormone receptor-positive); HER2/neu positive breast cancer; and, basal-type (hormone receptor-negative).24

Luminal-type breast cancer (hormone receptor-positive) ■ Endocrine therapy is the preferred option except if clinically aggressive disease mandates a quicker response or if resistance is suspected. ■ The choice of endocrine agent should be individualised according to the patient’s safety profile, co-morbidities and tumour biology. ■ Tamoxifen with ovarian ablation is typically recommended for premenopausal patients, while third-generation aromatase inhibitors are advised for postmenopausal patients.

HER2/neu-positive breast cancer ■ Patients should be treated with trastuzumab (Herceptin) with/without chemotherapy, and cardiac monitoring should be performed before/after commencement to monitor for cardiotoxicity. ■ Lapatinib (Tyverb/Tykerb) may also be used and has shown a significant increase in time to progression in combination with capecitabine (Xeloda) in patients progressing after trastuzumab (Herceptin) treatment. ■ Other anti-HER2/neu agents such as pertuzumab (Omnitarg) are currently under investigation. ■ Combinations of trastuzumab (Herceptin) with other biological agents with/without chemotherapy to tackle the problem of resistance to trastuzumab (Herceptin) are currently under investigation.

Basal-type breast cancer (hormone receptor-negative) ■ Patients with hormone receptor-negative tumours are candidates for cytotoxic chemotherapy, of which taxanebased regimens are the only ones where level one evidence is available. ■ In the absence of the need for a rapid and significant response for symptom control or life-threatening disease, preference is given to the sequential use of a single cytotoxic agent, as it is associated with reduced toxicity and improved quality of life in comparison with combination chemotherapy. ■ The duration and number of regimens should be tailored to each individual patient; however, high-dose chemotherapy should not be proposed.

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RCSIsmjreview References 1. Levi F, Lucchini F, Negri E, La Vecchia C. Trends in mortality from major cancers in the European Union, including acceding countries, in 2004. Cancer 2004; 101 (12): 2843-50. 2. National Cancer Registry Ireland. Cancer in Ireland 1994-2005: a summary. National Cancer Registry Ireland 2006. Cited October 16, 2009. Available from: http://ncri.ie/pubs/pubfiles/summary2007.pdf. 3. Heneghan HM, Prichard RS, Devaney A et al. Evolution of breast cancer management in Ireland: a decade of change. BMC Surg 2009; (9): 15. 4. Kataja V, Castiglione M. ESMO Guidelines Working Group. Primary breast cancer: ESMO clinical recommendations for diagnosis, treatment and follow-up. Ann Oncol 2009; 20 (Suppl. 4): 10-4. 5. Harris JR, Lippman ME, Morrow M, Osborne CK. Diseases of the Breast (3rd ed.). Lippincott Williams & Wilkins, 2004. 6. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell 2000; 100 (1): 57-70. 7. Welch DR, Steeg PS, Rinker-Schaeffer CW. Molecular biology of breast cancer metastasis. Genetic regulation of human breast carcinoma metastasis. Breast Cancer Res 2000; 2 (6): 408-16. 8. Paget S. The distribution of secondary growths in cancer of the breast. Lancet 1889; 1: 99-101. 9. Ewing J. Neoplastic Diseases. A Treatise on Tumours (6th ed.). W.B. Saunders Co.; Philadelphia & London, 1928. 10. Weiss L. Comments on haematogenous metastatic patterns in humans as revealed by autopsy. Clin Exp Metastasis 1992; 10 (3): 191-9. 11. Hay ED. An overview of epithelio-mesenchymal transformation. Acta Anat (Basel) 1995; 154 (1): 8-20. 12. Thiery JP, Sleeman JP. Complex networks orchestrate epithelialmesenchymal transitions. Nat Rev Mol Cell Biol 2006; 7 (2): 13142. 13. Tse JC, Kalluri R. Mechanisms of metastasis: epithelial-tomesenchymal transition and contribution of tumour microenvironment. J Cell Biochem 2007; 101 (4): 816-29. 14. Finak G, Bertos N, Pepin F et al. Stromal gene expression predicts clinical outcome in breast cancer. Nat Med 2008; 14 (5): 518-27. 15. DeNardo DG, Barreto JB, Andreu P et al. CD4(+) T cells regulate pulmonary metastasis of mammary carcinomas by enhancing protumour properties of macrophages. Cancer Cell 2009; 16 (2): 91-102. 16. Allan AL, Vantyghem SA, Tuck AB, Chambers AF. Tumour dormancy and cancer stem cells: implications for the biology and treatment of breast cancer metastasis. Breast Dis 2007; 26: 87-98. 17. Aguirre-Ghiso JA. Models, mechanisms and clinical evidence for cancer dormancy. Nat Rev Cancer 2007; 7 (11): 834-46. 18. Stafford LJ, Vaidya KS, Welch DR. Metastasis suppressor genes in cancer. Int J Biochem Cell Biol 2008; 40 (5): 874-91.

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19. Lee JH, Miele ME, Hicks DJ et al. KiSS-1, a novel human malignant melanoma metastasis-suppressor gene. J Natl Cancer Inst 1996; 88 (23): 1731-7. 20. Seraj MJ, Samant RS, Verderame MF, Welch DR. Functional evidence for a novel human breast carcinoma metastasis suppressor, BRMS1, encoded at chromosome 11q13. Cancer Res 2000; 60 (11): 2764-9. 21. Han HJ, Russo J, Kohwi Y, Kohwi-Shigematsu T. SATB1 reprogrammes gene expression to promote breast tumour growth and metastasis. Nature 2008; 452 (7184): 187-93. 22. Nicoloso MS, Spizzo R, Shimizu M, Rossi S, Calin GA. MicroRNAs – the micro steering wheel of tumour metastases. Nat Rev Cancer 2009; 9 (4): 293-302. 23. Tavazoie SF, Alarcón C, Oskarsson T et al. Endogenous human microRNAs that suppress breast cancer metastasis. Nature 2008; 451 (7175): 147-52. 24. Cardoso F, Castiglione M. ESMO Guidelines Working Group. Locally recurrent or metastatic breast cancer: ESMO clinical recommendations for diagnosis, treatment and follow-up. Ann Oncol 2009; 20 (Suppl. 4): 15-8. 25. Pantel K, Alix-Panabières C, Riethdorf S. Cancer micrometastases. Nat Rev Clin Oncol 2009; 6 (6): 339-51. 26. Braun S, Pantel K, Müller P et al. Cytokeratin-positive cells in the bone marrow and survival of patients with stage I, II, or III breast cancer. N Engl J Med 2000; 342 (8): 525-33. 27. Riethdorf S, Fritsche H, Müller V et al. Detection of circulating tumour cells in peripheral blood of patients with metastatic breast cancer: a validation study of the CellSearch system. Clin Cancer Res 2007; 13 (3): 920-8. 28. McGee SF, Lanigan F, Gilligan E, Groner B. Mammary gland biology and breast cancer. Conference on Common Molecular Mechanisms of Mammary Gland Development and Breast Cancer Progression. EMBO Rep 2006; 7 (11): 1084-8. 29. Baselga J, Perez EA, Pienkowski T, Bell R. Adjuvant trastuzumab: a milestone in the treatment of HER-2-positive early breast cancer. Oncologist 2006; 11 (Suppl. 1): 4-12. 30. Collins D, Hill AD, Young L. Lapatinib: a competitor or companion to trastuzumab? Cancer Treat Rev 2009; 35 (7): 574-81. 31. Fong PC, Boss DS, Yap TA et al. Inhibition of poly(ADPribose) polymerase in tumours from BRCA mutation carriers. N Engl J Med 2009; 361 (2): 123-34. 32. Ross JS, Hatzis C, Symmans WF, Pusztai L, Hortobágyi GN. Commercialised multigene predictors of clinical outcome for breast cancer. Oncologist 2008; 13 (5): 477-93. 33. Cardoso F, Piccart-Gebhart M, Van’t Veer L, Rutgers E; TRANSBIG Consortium. The MINDACT trial: the first prospective clinical validation of a genomic tool. Mol Oncol 2007; 1 (3): 246-51.


RCSIsmjstaff review Changing patient needs: issues and ethics of maternal requested caesarean delivery Royal College of Surgeons in Ireland Student Medical Journal 2010; 3: 61-64.

Caesarean deliveries are one of the most common surgical procedures performed in the developed world. Although complications are known to occur, the rates of adverse events continue to decline. The longstanding evidence that women who choose vaginal delivery over a scheduled caesarean have a substantially lower risk of death is becoming increasingly tenuous. As a result, primary and repeat caesarean deliveries have reached their highest levels.1,2 Caesarean delivery on maternal request is defined as a primary caesarean delivery performed at the request of the mother in the absence of any medical or obstetric indication.3 The American College of Obstetrics and Gynecology (ACOG) estimates that 2.5% of all births in the United States are caesarean delivery on maternal request.4 In a 2000 editorial, the former president of the ACOG wrote that perhaps the time had come when the risks, benefits and costs between vaginal and caesarean births are so balanced that women can choose both how and when to have their babies.5

Why do women request an elective caesarean delivery?

Lucky Sekhon, RCSI medical student

The increasing prevalence of elective caesarean sections may be accounted for by the perceived advantages of the procedure for mothers, babies, and healthcare providers. A mother may request a caesarean section with the belief that there is real benefit to herself and her baby, or as result of anxiety over labour, the birthing process and its potential consequences.6 A planned caesarean procedure eliminates the chance that a woman will require an emergency caesarean, which is associated with an increased risk of morbidity and mortality.7 Lilford et al reported a relative risk of 1.7 (95% CI, 0.5-6.0) for death attributable to emergency caesarean section compared to elective procedures. The increased mortality was attributed to a greater incidence of

postoperative sepsis and thromboembolism.8 Similar findings by Yokoe et al showed that emergency caesarean deliveries were associated with a greater incidence of postpartum infection than elective procedures.9 General anaesthesia is also more likely to be used for emergency caesarean versus elective caesarean and is known to increase the risk to the patient.7 Given these increased risks of emergency caesarean, a woman may view an elective procedure as a pro-active approach to reduce risk. Many women desire caesarean births to avoid the potential for perineal trauma associated with normal and assisted vaginal delivery.10 Importantly, such injuries are known to compromise the integrity of the pelvic floor.11 The incidence of urinary incontinence after a vaginal birth may range from 22% in spontaneous vaginal births to 33% following forceps-assisted delivery.12 Most observational studies assert that caesarean delivery is protective against a pelvic floor injury, associated pelvic organ prolapse, and urinary incontinence.13 Rorteveit et al suggested that prophylactic caesarean delivery might reduce a woman’s risk of moderate to severe urinary incontinence by 5%.14 A planned caesarean section may also be viewed by the mother as a safer mode of delivery because it may reduce the risk of intrapartum death, hypoxia and birth trauma.7 In 2003, an Irish retrospective study involving infants weighing 2,500g or more demonstrated a significantly lower perinatal mortality rate in babies born by caesarean section. However, the study design failed to control for confounding factors such as antepartum, intrapartum and neonatal care.15 Elective caesarean delivery also eliminates the risk of detrimental intrapartum events such as shoulder dystocia or failure to progress, which may be associated with neonatal intracranial injury.13 It may also protect against the risk of meconium aspiration and the possibility of intubation, which is more likely

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RCSIsmjstaff review to occur after 39 weeks’ gestation.16 Conversely, a planned vaginal delivery has been hypothesised to place neonates at an increased risk of intracranial haemorrhage, asphyxia, encephalopathy and infection.10 A retrospective study by McFarland et al emphasised the protective effect of caesarean section against birth injury, demonstrating a 50% reduction in the rates of fractures and nerve palsies among neonates delivered by caesarean section compared with those that underwent assisted vaginal delivery.17 Irrespective of the benefits or concerns with elective caesarean deliveries, anxious patients often just wish to gain control over the unpredictable nature of labour and vaginal birth.11 Obstetricians may accommodate these requests, despite a medical opinion to the contrary, since the medical-legal standpoint is that elective caesarean birth is a fairly standard procedure associated with less risk than vaginal delivery.11 A survey of 243 obstetricians in England and Wales revealed that 69% would perform an elective caesarean section on maternal request due to fear of litigation and pressure from their patients.18 In addition to reducing liability, scheduling these procedures may help to balance staffing levels with clinical volume.16 Arguably, optimal scheduling may also alleviate the issues of insufficient staff and fatigue in healthcare professionals, which can contribute to maternal and neonatal morbidity.19

What are the concerns regarding elective caesarean birth becoming a ‘standard of care’ procedure? Advances in surgical and anaesthetic techniques, antibiotic therapy and blood product availability have led to the evolution of the benefit–risk calculus associated with caesarean deliveries. Nevertheless, vaginal delivery is still considered the safest mode of delivery in the uncomplicated low-risk patient.3 The relative risk of maternal death after caesarean delivery versus vaginal birth in the United States has been reported as 3.5.20 Schuitemaker et al asserts that up to 130 annual maternal deaths in the US might be attributed to the high rate of surgical delivery.20 However, as maternal death has become rare, this inference may be largely based on older data using patients whose care was not provided according to current obstetric standards. As the risks of surgery have decreased over time, the exact degree of maternal mortality that would occur if elective caesarean birth became standard of care is unknown. Cases of maternal mortality secondary to caesarean birth have been attributed mainly to haemorrhage, thromboembolism and infection risks that are associated with all types of major abdominal surgery.21 Extensive blood loss is a rare complication but may occur due to laceration of uterine vessels during inadvertent extension of the uterine incision angles.22,7 A greater decline in postnatal haemoglobin from occult blood loss and haematoma formation within the broad ligament are also potential complications. Excessive blood loss, combined with dehydration and post-operative immobility, contribute to the increased risk of thromboembolism.7 This risk is further increased by anaemia, infection, postpartum haemorrhage and reactive thrombocytosis, which is a prominent feature in caesarean births compared to vaginal delivery.23 There have also been rare case reports describing air and amniotic fluid embolism during caesarean section,7 which may be related to a prolonged uterine incision-to-delivery interval.24

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The most common maternal post-operative complication is infection and this is responsible for significant postnatal morbidity and prolonged hospital stay.25 Despite the routine use of prophylactic antibiotics, infection is thought to occur in up to 10% of women.13 However, the incidence of maternal infection may be under-reported. A 2001 retrospective cohort study of women in the United States found that 94% of all postpartum infections occur after hospital discharge.26 Early recovery from a caesarean section takes more time than recovery from an uncomplicated vaginal delivery.10 A study by Liu et al showed that women with planned caesarean delivery required longer hospital stay than women with planned vaginal delivery, with an adjusted mean difference of 1.47 days in hospital (95% CI; 2.7-3.4).27 Restricted mobility may have personal, social and economic consequences as it may interfere with the patient’s ability to care for her newborn and older children, and delay the patient’s return to work.7 Although elective caesarean is increasingly perceived to be associated with decreased mortality and morbidity over time, the fact remains that it is an open abdominal procedure with risks of damage to urinary and gastrointestinal organs. Incidence of bladder or ureteric injury during surgical delivery is estimated at 0.03-0.1%.28 Bladder injury is often immediately recognised and managed, and rarely leads to long-term complications.29 In contrast, injury to the ureter is often not recognised until the post-operative period. The ureter may be inadvertently ligated during lateral extension of the uterine incision or while trying to achieve haemostasis. A damaged ureter must be repaired in conjunction with a urologist, with the outcome depending on the site and nature of injury.28,29 The incidence of injury to the bowel during caesarean section is reported as 0.05%.29 Postoperative ileus is more common and is more likely to occur in the presence of adhesions, excess handling of the bowel during surgery, blood remaining in the abdominal cavity, and when caesarean is performed under general anaesthetic.30 With regard to neonatal health, delivery by caesarean section may be associated with compromised respiratory function.31 The physiological process of labour and vaginal birth promotes adaptation of the respiratory system to extrauterine life. In particular, physical compression of the chest during labour stimulates epinephrine release in the foetal circulation, which decreases the amount of fluid in the lungs.11 A retrospective analysis comparing the neonatal outcomes of infants born after 35 weeks’ gestation via caesarean delivery demonstrated higher frequency of persistent pulmonary hypertension, transient tachypnoea of the newborn and respiratory distress compared with neonates born vaginally.31 In addition, transient foetal respiratory acidosis has been linked to maternal hypotension, a common side effect of anaesthesia during surgery.32 One of the most controversial issues surrounding caesarean without medical indication is the long-term consequences it may have on a woman’s reproductive health. A history of previous uterine incision predisposes a woman to placental abnormalities in subsequent pregnancies. For example, it more than doubles the risk of developing placenta praevia,8 a condition where the placenta partly or fully occludes the internal cervical os. It also increases the risk of placental abruption, a condition where the placenta prematurely separates from the uterine wall.24 Both these conditions are associated with increased rates of


RCSIsmjstaff review antepartum haemorrhage. The pathogenesis of placenta praevia involves impaired decidualisation at the uterine scar site, which enables the trophoblast to morbidly invade the myometrium such that it cannot migrate away from the cervix as the uterus grows.24 An abnormally sited placenta is also more likely to invade the uterine scar and develop into placenta accreta, a condition where the placenta becomes morbidly adherent to the uterine wall. In addition to an increased risk of haemorrhage, treatment of a placenta accreta requires a hysterectomy.24 The weakening of the uterine wall and risk of uterine rupture in subsequent pregnancies is another major concern. Studies have shown that the incidence of uterine rupture is greater with attempted vaginal birth after previous caesarean than with elective repeat caesarean.33,34 In addition to the proposed risk to future pregnancies, possible associations with fertility decline, miscarriage, stillbirth and an ectopic pregnancy have been proposed. Although reliable data are limited, these complications relate to a hypothesis that the caesarean procedure alters the blood supply of the uterus.35

Ethical issues The issue of performing caesarean delivery on maternal request is at the centre of an ongoing and controversial bioethical debate. It highlights the struggle to balance patient autonomy with the duty of the physician to uphold the principles of beneficence, non-maleficence and justice. Patients may view their request for delivery by caesarean section as exercising their right to individual choice and self-governance.36 The principle of autonomy can only be satisfied when true informed consent is obtained37 and this involves discussion of the relative risks and benefits of the procedure, including a realistic assessment of the potential complications and outcomes.13 However, the evidence provided in the current literature is confounded by variables that influence outcome such that it is impossible to precisely predict the sequelae of caesarean section. Due to this relative lack of reliable data, a physician is neither ethically obligated to initiate a discussion of elective caesarean birth, nor required to perform an intervention in the absence of a medical indication.38,39 In fact, the decision to undertake major surgery to circumvent what is a normal physiological event challenges the principles of beneficence and non-maleficence.40 By considering a caesarean section to be an invasive procedure in the absence of medical or obstetric indication, non-

maleficence may thereby outweigh a patient’s autonomy. Finally, a physician’s ethical duty to uphold justice involves ensuring the fair treatment of patients and allocation of health resources. It has been shown that the total cost of caesarean delivery is twice that of a vaginal delivery,41 due to the costs of using an operating theatre, anaesthesia, increased length of stay in hospital, and treatment of wound infections.41 The foundation of the ethical relationship between a woman and her physician requires the exchange of accurate information and effective communication. Patients’ requests should be met with non-directive counselling, which incorporates the woman’s values and cultural context with sensitivity to her concerns.36 The dialogue should aim to maximise the patient’s understanding of the issues and focus on individual needs, including future reproductive plans, medical risk factors, and psychological concerns.3 After a thorough discussion and review, caesarean delivery on maternal request may be agreed upon as a reasonable alternative to planned vaginal delivery. Where a physician cannot support this request based on their ethical standpoint, it may be appropriate to refer the patient to another healthcare provider.38 The increase in maternal request for caesarean delivery may be related to socio-cultural change. In developed countries, women live longer and have fewer children, rendering quality of life issues such as the risk of incontinence more prominent and the risks associated with having multiple subsequent caesarean deliveries less prominent. Despite the frequency of the procedure, the evidence concerning the risk–benefit paradigm of vaginal delivery and caesarean delivery on maternal request is inconclusive. The interpretation of many relevant studies on the subject is often limited by study design and conflicting conclusions. There are no randomised control trials and few prospective long-term studies that evaluate the outcomes of elective caesarean delivery compared with vaginal birth. Robust prospective studies of women undergoing caesarean section under regional anaesthesia, with routine antibiotic therapy and appropriate thromboprophylaxis, are needed to assess the true risks. These studies should particularly focus on the incidence of maternal mortality and placental problems in future pregnancies. Until quality evidence is available, the decision to perform a caesarean delivery on maternal request should be carefully individualised and consistent with ethical principles.

References 1. Declercq E, Menacker F, MacDorman MF. Rise in “no indicated risk” primary caesareans in the United States, 1991-2001: cross sectional analysis. BMJ 2005; 330: 71-2. 2. Meikle SF, Steiner CA, Zhang J, Lawrence WL. A national estimate of the elective primary caesarean delivery rate. Obstet Gynecol 2005; 105 (4): 751-6. 3. Kalish RB, McCullough LB, Chervenak FA. Patient choice caesarean delivery: ethical issues. Curr Opin Obstet Gynecol 2008; 20 (2): 116-9. 4. ACOG Committee Opinion. Caesarean delivery on maternal request. Obstet Gynecol 2007; 386: 1209-12.

5. Benson Harer W. Patient choice caesarean. ACOG Clin Rev 2000; 5: 1-15. 6. Bewley S, Cockburn J. The unfacts of ‘request’ caesarean section. Br J Obstet Gynecol 2002; 109: 597-605. 7. Jackson N, Paterson-Brown S. Physical sequelae of caesarean section. Best Pract Res Clin Obstet Gynaecol 2001; 15: 49-61. 8. Lilford RJ, van Coeverden de Groot HA, Moor PJ, Bingham P. The relative risks of caesarean section (intrapartum and elective) and vaginal delivery: a detailed analysis to exclude the effects of medical disorders and other acute pre-existing physiological disturbances. British Journal of Obstetrics and Gynaecology 1990; 97: 883-92.

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RCSIsmjstaff review 9. Yokoe DS, Christiansen RJ, Sands KE, Livingston J, Shtatland ES, Platt R. Epidemiology of and surveillance of postpartum infections. Emerg Infect Dis 2001; 7: 837-41. 10. National Institutes of Health. NIH State-of-the-Science Conference: Caesarean Delivery on Maternal Request. NIH Consens State Sci Statements 2006; 29; 23 (1): 1-29. 11. McFarlin BL. Elective caesarean birth: issues and ethics of an informed decision. J Midwifery Womens Health 2004; 49: 421-9. 12. Farrell SA, Allen VM, Baskett TF. Parturition and urinary incontinence in primiparas. Obstet Gynecol 2001; 97: 350-6. 13. Minkoff H, Chervenak FA. Elective primary caesarean delivery. N Engl J Med 2003; 348 (10): 946-50. 14. Rortveit G, Dalveit AK, Hannestad YS, Hunskaar S. Urinary incontinence after vaginal delivery or caesarean section. N Engl J Med 2003; 348: 900-7. 15. Matthews TG, Crowley P, Chong A, McKenna P, McGarvey C, Regan M. Rising caesarean section rates: a cause for concern? BJOG 2003; 11, 346-9. 16. Saunders N, Paterson C. Effect of gestational age on obstetric performance: when is ‘term’ over? Lancet 1991; 338: 1190-2. 17. McFarland LV, Raskin M, Daling JR, Benedetti TJ. Erb/Duchenne’s palsy: a consequence of foetal macrosomia and method of delivery. Obstet Gynecol 1986; 68: 784-8. 18. Cotzias CS, Paterson-Brown S, Fisk NM. Obstetricians say yes to maternal request for elective caesarean section: a survey of current opinion. Eur J Obstet Gynecol Reprod Biol 2001; 97: 15-6. 19. Tucker J, UK Neonatal Staffing Study Group. Patient volume, staffing, and workload in relation to risk-adjusted outcomes in a random stratified sample of UK neonatal intensive care units: a prospective evaluation. Lancet 2002; 359: 99-107. 20. Schuitemaker N, van Roosmalen J, Dekker G, van Dongen P, van Geijn H, Gravenhorst JB. Maternal mortality after caesarean section in The Netherlands. Acta Obstet Gynecol Scand 1997; 76: 332-4. 21. Why mothers die. Report on confidential enquiries into maternal deaths in the United Kingdom 1994-96. London: Stationery Office, 1998. 22. Lilantha W, Macleod M, Murphy D. Use of oxytocin to prevent haemorrhage at caesarean section – a survey of practice in the United Kingdom. European Journal of Obstetrics Gynecology and Reproductive Biology 2008; 137 (1): 27-30. 23. Atalla RK, Thompson JR, Oppenheimer CA et al. Reactive thrombocytosis after caesarean section and vaginal delivery: implications for maternal thromboembolism and its prevention. British Journal of Obstetrics and Gynecology 2000; 107: 411-4. 24. Hemminki E, Merilainen J. Long-term effects of caesarean sections: ectopic pregnancies and placental problems. American Journal of Obstetrics and Gynecology 1996; 174: 1569-74. 25. Henderson EJ, Love EJ. Incidence of hospital-acquired infections associated with caesarean section. Journal of Hospital Infection 1995; 29: 245-55.

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26. Lydon-Rochelle M, Holt VL, Martin DP, Easterling TR. Association between method of delivery and maternal rehospitalisation. JAMA 2000; 283: 2411-6. 27. Liu S, Liston RM, Joseph KS, Heaman M, Sauve R, Kramer MS. Maternal mortality and severe morbidity associated with low-risk planned caesarean delivery versus planned vaginal delivery at term. Canadian Medical Association Journal 2007: 176 (4): 455-60. 28. Eisenkop SM, Richman R, Platt LD, Paul RH. Urinary tract injury during caesarean section. Obstetrics and Gynecology 1982; 60: 591-6. 29. Davis JD. Management of injuries to the urinary and gastrointestinal tract during caesarean section. Obstetrics and Gynecology Clinics of North America 1999; 26: 469-80. 30. Irion O, Luzuy F, Beguin F. Nonclosure of the visceral and

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parietal peritoneum at caesarean delivery. Obstetrics and Gynecology 1991; 77: 818-21. Hook B, Kiwi R, Amini SB et al. Neonatal morbidity after elective repeat caesarean section and trial of labour. Pediatrics 1997; 100: 348-53. Corke BC, Datta S, Ostheimer GW, Weiss JB, Alper MH. Spinal anaesthesia for caesarean section: the influence of hypotension on neonatal outcome. Anaesthesia 1982; 37: 65862. McMahon MJ, Luther ER, Bowes WA Jr, Olshan AF. Comparison of a trial of labour with an elective second caesarean section. New England Journal of Medicine 1996; 335: 689-95. Landon MB, Hauth JC, Leveno KJ et al. Maternal and perinatal outcomes associated with a trial of labour after prior caesarean delivery. N Engl J Med 2004; 351 (25): 2581-9. Smith GC, Pell JP, Dobbie R. Caesarean section and risk of unexplained stillbirth in subsequent pregnancy. Lancet 2003; 362 (9398): 1779-84. Minkoff H, Powderly KP, Chervenak F, McCollough LB. Ethical dimensions of elective primary caesarean delivery. Obstet Gynecol 2004; 103: 387-92. O’Neill O. Autonomy and Trust in Bioethics. Cambridge; Cambridge University Press, 2002. Nygaard I, Cruikshank DP. Should all women be offered elective caesarean delivery? Obstet Gynecol 2003; 102 (2): 217-9. International Federation of Gynecology and Obstetrics (FIGO). Ethical Aspects Regarding Caesarean Delivery for Nonmedical Reasons, vol. 2003. London: FIGO, 1998. American College of Obstetricians and Gynecologists Committee Opinion. Surgery and patient choice: the ethics of decision making. Obstet Gynecol 2003; 102: 1101-6. Allen VM, O’Connell CM, Baskett TF. Cumulative economic implications of initial method of delivery. Obstet Gynecol 2006; 108 (3 Pt 1): 549-55.


RCSIsmjstaff review Editors’ pick Medical imaging in the 21st century: the promise and the challenges Royal College of Surgeons in Ireland Student Medical Journal 2010; 3: 65-69.

Introduction The latter part of the 20th century saw the practical application of computer technology and molecular biology, while the early 21st century is seeing the merging of these technologies and the application of bioinformatics to medical imaging. The development of computed tomography (CT) and magnetic resonance imaging (MRI) over the past two decades, and the more recent emergence of molecular imaging, has created diagnostic capabilities that will dramatically change the way medicine is practised. As well as providing new diagnostic modalities, advanced imaging will improve our understanding of disease processes and facilitate tailored patient treatment and follow-up. Although imaging technology requires major capital investment, costs may be offset by eliminating unnecessary procedures, improving outcomes, and optimising care.1 This article discusses two emerging imaging technologies: molecular imaging (MI); and, computed tomography angiography (CTA).

Hugh McGregor, RCSI medical student

Molecular imaging History Molecular imaging dates back to the 1940s and gained momentum with the successful use of radioactive iodine to treat thyroid cancer.2 This

was followed by the development of positron emission tomography (PET) technology in the 1950s and the synthesis of fluorine 18 flouro-2deoxy-D-glucose (FDG) in the 1970s.3 Although the field has a seemingly long history, it was only in the last decade that researchers and physicians have been able to exploit the potential of molecular imaging. Growth in the understanding of basic cell and molecular biology has elucidated many of the key molecular pathways, signal transduction cascades, and receptor alteration abnormalities that lead to disease. This has led to the development of relevant molecular targets for existing imaging systems.

Principles MI is defined as the in vivo characterisation and measurement of biologic processes at the cellular and molecular level. Traditional imaging modalities (x-ray, CT, MRI) are successful in obtaining anatomic and physiologic information but lack the ability to assess disease at a molecular level. The ability to measure metabolic processes with MI is beginning to change practice in oncology, cardiology, neurology, rheumatology, and infectious diseases. A number of imaging modalities (ultrasound, CT, MRI) now take advantage of newer biomarkers of disease.4

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RCSIsmjstaff review Far left: FIGURE 1: PET-CT fusion images of splenic lesions in lymphoma. Left: FIGURE 2: CTA three-dimensional reconstruction exhibiting a proximal stenosis of the left anterior descending coronary artery. The basic concepts of molecular imaging are illustrated by the use of FDG as a positron emitting radioactive isotope used in PET. Neoplastic cells show an increased rate of glycolysis and glucose metabolism.5 The initial step in glucose metabolism is the phosphorylation of glucose to glucose-6-phosphate by the enzyme hexokinase.6 FDG, a glucose analogue, is initially converted to FDG6-phosphate, but cannot be further metabolised. Furthermore, due to its negative charge, it is trapped within cells. Thus FDG is a biomarker for a rate-limiting step of glycolysis. The 18F incorporated in FDG generates signal by positron emission radioactive beta decay, creating gamma photons whose energy is captured by a ring scanner and used to construct an image.7 Neoplastic cells will emit more signal than normal cells, enabling comparison between the two on a metabolic level.8 MI is not limited to FDG and the basic concept of labelling biomarkers to capture their location and activity holds vast potential.

Clinical application: oncology Thus far, oncology is the area of greatest success in molecular imaging. FDG use in PET for staging of cancers (breast, colorectal, oesophageal, melanoma, lymphoma) and monitoring response to treatment has been approved by the United States Food and Drug Administration (FDA) and is the standard practice in many centres.9 Ralph Weissleder of Harvard Medical School, a leader in the field of molecular imaging, described in 2006 the goals of clinical molecular imaging as: “(i) the detection of molecular or physiological alterations that signal the presence of cancer when it is still at a curable stage; (ii) the ability to evaluate and adjust treatment protocols in real time; and, (iii) the ability to streamline the drug development process�.10 Currently, the most frequently used cancer imaging agent is FDG (Figure 1). Smith et al demonstrated that after a single pulse of chemotherapy, FDG PET was able to predict breast tumour response with a sensitivity of 90% and a specificity of 74% based on a decline in FDG uptake compared to non-responsive tumours.11 Another example utilises lymphotropic superparamagnetic nanoparticles and MRI to image lymph node metastasis in prostate cancer. Harisinghani et al were able to detect millimetre-sized metastases and correctly identified patients with nodal metastases with a sensitivity of 90.5% compared to 35.4% with conventional MRI.12 Drug development is another area of advancement. Imaging molecular processes will enable researchers to identify and validate

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potential targets and efficiently monitor metabolic effects of drugs at therapeutic doses. For example, Wu et al describe the use of bioluminescence imaging of reporter genes to quantify efficacy of epothilones, a class of chemotherapeutic drugs that disrupt mitosis in vivo.13 In addition, pharmacokinetic and pharmacodynamic data can be efficiently collected by radiolabelling cancer drugs.14 These applications of MI allow more accurate diagnosis, staging and prediction of tumour response of many cancers, allowing individualisation of therapy, thus improving cost-effectiveness and clinical outcomes.15

Clinical application: cardiovascular Conventional cardiac imaging methods such as echocardiography, CT and MRI are effective at visualising anatomic and physiologic properties of the myocardium, but lack the ability to capture metabolic processes.16 PET, by utilising 82Rb, a potassium analogue and substrate for myocardial uptake via Na/K ATPase, can image myocardial perfusion and metabolic activity but lacks anatomic resolution. By combining techniques, PET-CT enables the construction of single images characterising anatomic, physiologic, and metabolic properties of the myocardium.17 Coronary artery disease (CAD) is an atherosclerotic process in which narrowing of the vessel lumen or complete obstruction of the lumen by a ruptured plaque results in tissue hypoxia and myocardial necrosis and apoptosis.18 Invasive coronary angiography (ICA), directly injecting contrast into the coronary arteries to characterise vessel diameter, has been the principal diagnostic procedure to identify and predict the course of CAD. Unfortunately, acute coronary syndromes (ACS) often result from plaque rupture at sites not significantly stenosed.19 Additionally, 50% of men and 64% of women who die suddenly because of CAD have no previous symptoms.20 Other factors contributing to the risk of plaque rupture include plaque inflammation,21 macrophage infiltration,22 degree of apoptosis,23 matrix degradation,24 angiogenesis,25 thrombosis, and smooth muscle proliferation.26 Thus, molecular imaging provides the opportunity for a more detailed analysis of the structure and biology of the atherosclerotic process in coronary arteries. For example, the use of lymphotropic superparamagnetic iron oxide nanoparticles to label macrophages enables MR imaging to characterise plaque macrophage infiltration.22 Radiolabelled Z2D3 antibody is currently used as a marker for smooth muscle cell proliferation.27


RCSIsmjstaff review MI is currently used to predict acute coronary events, allowing for pre-emptive management and co-ordinated treatment plans.28 Future developments will allow risk assessment for ventricular arrhythmias (neuronal imaging),29 identify ‘pre-disease’ states enabling earlier treatment,30 and target the biomechanisms associated with cardiac remodelling and the development of heart failure.31

Computed tomography angiography History The first CT scanner was developed in 1972 by Sir Godfrey Hounsfield32 and independently by Allen Cormack.33 At this stage, each tomographic slice required hours of scan time and days of computation to construct images. The early 1990s saw the introduction of continuous helical scanners, reducing scan times. Images were still not captured fast enough to view contrast, and clinical applications of CTA were limited by high slice thickness and low image resolution. The emergence of multirow detector scanners in the late 1990s allowed for many images to be acquired during a

Table 1: Thrombosis In Myocardial Infarction (TIMI) risk score for unstable angina and non-ST segment elevation myocardial infarction (NSTEMI). Each factor is awarded one point. The low-risk group is defined by a score of 0 or 1 while the high-risk group is defined by a score of 6 or 7. Individuals at high risk are usually admitted and are candidates for PCI: ■ age ≥65 years; ■ history of known coronary artery disease (documented prior coronary artery stenosis ≥50%); ■ ≥3 conventional cardiac risk factors (age, male sex, family history, hyperlipidaemia, diabetes mellitus, smoking, obesity); ■ use of aspirin in the past seven days; ■ ST-segment deviation (persistent depression or transient elevation); ■ increased cardiac biomarkers (troponins); and, ■ ≥2 anginal events in the preceding 24 hours. Table 2: Patient selection criteria for TRO CTA: ■ ■ ■ ■ ■ ■ ■

clinical presentation: low to moderate risk of ACS; clinical presentation: non-ACS diagnosis considered; normal ECG or non-specific changes; no history to suggest extensive coronary calcium; not recommended for patients with bypass or stents; patient able to tolerate CT and hold breath; cardiac rhythm acceptable for ECG-gated scan; and, ■ adequate renal function.

single helical revolution of the scanner. This further reduced scan times and slice thickness and enabled visualisation of contrast using CT.34 Technology has improved over the past 10 years with the development of 16-, 32-, 64-, 128- and 256-row scanners, further reducing scan times significantly and increasing the resolution of CTA images.35 Detailed analysis of coronary and peripheral vasculature is now possible and research efforts continue to increase the resolution of CTA studies.36

Principles CTA is a minimally invasive technique using peripheral infusion of intravenous contrast for visualisation of blood vessels, most commonly the coronary arteries (Figure 2). A typical scan usually requires a breath hold of 10 seconds and 60-80ml of contrast media. To avoid high radiation exposure, automated bolus timing can be used. CTA commonly images from the level of the carina superiorly to the apex inferiorly and has spatial resolution of 0.4mm3 (64-slice).37 Recent evidence shows that 64-slice CTA can accurately detect coronary lesions with a sensitivity of 99% and a specificity of 96% per coronary segment, with a negative predictive value of 99%.38,39 ICA remains the ‘gold standard’ for detection of coronary artery stenosis40 but requires cardiac catheterisation with its attendant complications, including stroke, local bleeding and vessel perforation.41 The information provided by ICA is limited to luminal diameter, which is only one of many factors that contribute to cardiac risk. CTA provides a more rapid, less resource intensive, minimally invasive alternative with reduced complications and costs.42

Clinical application: acute chest pain A major clinical application of CTA is the evaluation of acute chest pain in the emergency department. This accounted for more than six million emergency department visits in the United States in 2006,43 with between 30% and 72% of patients admitted to hospital.44 Approximately 15-25% of admitted patients were eventually diagnosed with ACS, with 44% having significant pathology ruled out.45 The cost of chest pain-related hospital admissions in the United States approaches US$8 billion.46 The missed diagnosis of ACS is a major reason for litigation against emergency department physicians (accounting for up to 20% of emergency department malpractice dollar losses) and consequently the threshold for hospital admission is low.47 The need for a definitive, cost-effective test to distinguish between life-threatening (acute coronary syndrome, pulmonary embolism, aortic dissection) and non-immediate life-threatening (pneumonia, pulmonary neoplasm, pericarditis) conditions is essential.48 Patients complaining of chest pain in the emergency room are risk stratified for ACS, with the Thrombosis In Myocardial Infarction (TIMI) risk score commonly used (Table 1). Management of low-risk patients includes serial biomarkers, observation in a telemetry setting and cardiac stress testing. However, this remains suboptimal, with an inappropriate discharge rate of 2-8% despite the expenditure of significant resources.37 A triple-rule-out (TRO) CTA procedure is useful in such low-risk patients with a differential diagnosis of ACS in addition to non-cardiac causes (Table 2).

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RCSIsmjstaff review In stable patients where clinical evaluation primarily indicates chest pain of cardiac origin, dedicated cardiac CTA can be used to exclusively evaluate the coronary vessels. TRO CTA is an ECG-gated application of CTA intended to evaluate the aorta, coronary circulation, pulmonary arteries and the middle to lower portion of the chest with a single scan.49 ECG-gating refers to the triggering of image acquisition by the ECG signal that coincides with the heart phase with least motion. This decreases motion artefacts, allowing for clearer images. Takakuwa et al demonstrated that TRO CTA is an effective tool for evaluating chest pain in low to moderate risk ACS patients, avoiding additional testing in 75% of patients. At 30-day follow-up, the negative predictive value of TRO CTA was 99.4%.50 Although CTA will not replace ICA for investigation of high-risk cardiac patients (as coronary intervention can often be done simultaneously during ICA), data suggests a significant role in the assessment of lowrisk patients, and potentially for population screening.51

Conclusions Molecular imaging and CTA are two of many emerging imaging technologies that will greatly impact medical care. Advances in bioinformatics and improved acquisition and resolution of images will facilitate the continued expansion of MI. The high capital costs of commissioning imaging equipment and the need for multidisciplinary involvement will require large centres to allow MI to reach its full potential. Unfortunately, these technologies have progressed faster than the ability to validate their use and clinical evaluation of their effectiveness and the concurrent development of practice guidelines are essential. Ensuring cost effectiveness by avoiding use with little or no indication is an important factor in facilitating the success of these technologies, especially in the current economic climate. Although great progress has already been made, the potential for imaging to further improve patient care is significant. Medical imaging will continue to shape the practice of medicine in the 21st century.

References 1. Ehman RL, Hendee WR, Welch MJ et al. Blueprint for imaging in biomedical research. Radiology 2007; 244 (1): 12-27. 2. Curtis GM, Fertman MB. Radioiodine in thyroid disease. J Int Coll Surg 1949; 12 (3): 254-60. 3. Ter-Pogossian MM, Phelps ME, Hoffman EJ et al. A positronemission transaxial tomograph for nuclear imaging (PETT). Radiology 1975; 114 (1): 89-98. 4. Weissleder R, Pittet MJ. Imaging in the era of molecular oncology. Nature 2008; 452 (7187): 580-9. 5. Warburg O. The Metabolism of Tumors. New York: Richard R. Smith, 1931: 1-129. 6. Weber G. Enzymology of cancer cells. N Engl J Med 1977; 296 (10): 541-51. 7. Phelps ME, Huang SC, Hoffman EJ et al. Tomographic measurement of local cerebral glucose metabolic rate in humans with (F-18)2-fluoro-2-deoxy-D-glucose: validation of method. Ann Neurol 1979; 6 (5): 371-88. 8. Hoffman JM, Gambhir SS. Molecular imaging: the vision and opportunity for radiology in the future. Radiology 2007; 244 (1): 39-47. 9. Juweid ME, Cheson BD. Positron-emission tomography and assessment of cancer therapy. N Engl J Med 2006; 354 (5): 496-507. 10. Weissleder R. Molecular imaging in cancer. Science 2006; 312 (5777): 1168-71. 11. Smith IC, Welch AE, Hutcheon AW et al. Positron emission tomography using [(18)F]-fluorodeoxy-D-glucose to predict the pathologic response of breast cancer to primary chemotherapy. J Clin Oncol 2000; 18 (8): 1676-88. 12. Harisinghani MG, Barentsz J, Hahn PF et al. Non-invasive detection of clinically occult lymph-node metastases in prostate cancer. N Engl J Med 2003; 348 (25): 2491-9.

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13. Wu KD, Cho YS, Katz J et al. Investigation of anti-tumour effects of synthetic epothilone analogues in human myeloma models in vitro and in vivo. Proc Natl Acad Sci USA 2005; 102 (30): 10640-5. 14. Kelloff GJ, Krohn KA, Larson SM et al. The progress and promise of molecular imaging probes in oncologic drug development. Clin Cancer Res 2005; 11 (22): 7967-85. 15. Jaffer FA, Weissleder R. Molecular imaging in the clinical arena. JAMA 2005; 293 (7): 855-62. 16. Wu JC, Bengel FM, Gambhir SS. Cardiovascular molecular imaging. Radiology 2007; 244 (2): 337-55. 17. Bengel FM, Higuchi T, Javadi MS et al. Cardiac positron emission tomography. J Am Coll Cardiol 2009; 54 (1): 1-15. 18. Naghavi M, Libby P, Falk E. From vulnerable plaque to vulnerable patient: a call for new definitions and risk assessment strategies: Part I. Circulation 2003; 108 (14): 1664-72. 19. Fuster V, Badimon L, Badimon JJ et al. The pathogenesis of coronary artery disease and the acute coronary syndromes (1). N Engl J Med 1992; 326 (4): 242-50. 20. Myerburg RJ, Interian A Jr, Mitrani RM et al. Frequency of sudden cardiac death and profiles of risk. Am J Cardiol 1997; 80 (5B): 10F-19F. 21. Rudd JH, Warburton EA, Fryer TD et al. Imaging atherosclerotic plaque inflammation with [18F]fluorodeoxyglucose positron emission tomography. Circulation 2002; 105 (23): 2708-11. 22. Litovsky S, Madjid M, Zarrabi A et al. Superparamagnetic iron oxide-based method for quantifying recruitment of monocytes to mouse atherosclerotic lesions in vivo: enhancement by tissue necrosis factor-alpha, interleukin-1beta, and interferon-gamma. Circulation 2003; 107 (11): 1545-9.


RCSIsmjstaff review 23. Kietselaer BL, Reutelingsperger CP, Heidendal GA et al. Noninvasive detection of plaque instability with use of radiolabeled annexin A5 in patients with carotid artery atherosclerosis. N Engl J Med 2004; 350 (14): 1472-3. 24. Schäfers M, Riemann B, Kopka K et al. Scintigraphic imaging of matrix metalloproteinase activity in the arterial wall in vivo. Circulation 2004; 109 (21): 2554-9. 25. Sadeghi MM, Krassilnikova S, Zhang J et al. Detection of injuryinduced vascular remodelling by targeting activated alphavbeta3 integrin in vivo. Circulation 2004; 110 (1): 84-90. 26. Narula J, Petrov A, Bianchi C et al. Non-invasive localisation of experimental atherosclerotic lesions with mouse/human chimeric Z2D3 F(ab’)2 specific for the proliferating smooth muscle cells of human atheroma. Imaging with conventional and negative charge-modified antibody fragments. Circulation 1995; 92 (3): 474-84. 27. Khaw BA, Tekabe Y, Johnson LL. Imaging experimental atherosclerotic lesions in ApoE knockout mice: enhanced targeting with Z2D3-anti-DTPA bispecific antibody and 99mTc-labelled negatively charged polymers. J Nucl Med 2006; 47 (5): 868-76. 28. Sinusas AJ, Bengel F, Nahrendorf M et al. Multimodality cardiovascular molecular imaging, part I. Circ Cardiovasc Imaging 2008; 1 (3): 244-56. 29. Sasano T, Abraham MR, Chang KC et al. Abnormal sympathetic innervation of viable myocardium and the substrate of ventricular tachycardia after myocardial infarction. J Am Coll Cardiol 2008; 51 (23): 2266-75. 30. Nahrendorf M, Zhang H, Hembrador S et al. Nanoparticle PETCT imaging of macrophages in inflammatory atherosclerosis. Circulation 2008; 117 (3): 379-87. 31. Dilsizian V, Eckelman WC, Loredo ML et al. Evidence for tissue angiotensin-converting enzyme in explanted hearts of ischaemic cardiomyopathy using targeted radiotracer technique. J Nucl Med 2007; 48 (2): 182-7. 32. Ambrose J, Hounsfield G. Computerised transverse axial tomography. Br J Radiol 1973; 46 (542): 148-9. 33. Montgomery BJ. CT scanning recognised with Nobel Prize. JAMA 1979; 242 (22): 2380. 34. Kalender WA. CT: the unexpected evolution of an imaging modality. Eur Radiol 2005; 15 (Suppl. 4): D21-4. 35. Wink O, Hecht HS, Ruijters D. Coronary computed tomographic angiography in the cardiac catheterisation laboratory: current applications and future developments. Cardiol Clin 2009; 27 (3): 513-29. 36. Burgstahler C, Reimann A, Brodoefel H et al. Quantitative parameters to compare image quality of non-invasive coronary angiography with 16-slice, 64-slice and dual-source computed tomography. Eur Radiol 2009; 19 (3): 584-90. 37. Bastarrika G, Thilo C, Headden GF et al. Cardiac CT in the assessment of acute chest pain in the emergency department. Am J Roentgenol 2009; 193 (2): 397-409.

38. Pugliese F, Mollet NR, Runza G et al. Diagnostic accuracy of noninvasive 64-slice CT coronary angiography in patients with stable angina pectoris. Eur Radiol 2006; 16 (3): 575-82. 39. Raff GL, Gallagher MJ, O’Neill WW et al. Diagnostic accuracy of non-invasive coronary angiography using 64-slice spiral computed tomography. J Am Coll Cardiol 2005; 46 (3): 552-7. 40. Miller JM, Rochitte CE, Dewey M et al. Diagnostic performance of coronary angiography by 64-row CT. N Engl J Med 2008; 359 (22): 2324-36. 41. Batyraliev T, Ayalp MR, Sercelik A et al. Complications of cardiac catheterisation: a single-centre study. Angiology 2005; 56 (1): 75-80. 42. Mowatt G, Cook JA, Hillis GS et al. 64-slice computed tomography angiography in the diagnosis and assessment of coronary artery disease: systematic review and meta-analysis. Heart 2008; 94 (11): 1386-93. 43. Selker HP, Zalenski RJ, Antman EM et al. An evaluation of technologies for identifying acute cardiac ischaemia in the emergency department: a report from a National Heart Attack Alert Program Working Group. Ann Emerg Med 1997; 29 (1): 13-87. 44. Graff LG, Dallara J, Ross MA et al. Impact on the care of the emergency department chest pain patient from the chest pain evaluation registry (CHEPER) study. Am J Cardiol 1997; 80 (5): 563-8. 45. Pozen MW, D’Agostino RB, Selker HP et al. A predictive instrument to improve coronary-care-unit admission practices in acute ischaemic heart disease. A prospective multicenter clinical trial. N Engl J Med 1984; 310 (20): 1273-8. 46. Fineberg HV, Scadden D, Goldman L. Care of patients with a low probability of acute myocardial infarction. Cost effectiveness of alternatives to coronary-care-unit admission. N Engl J Med 1984; 310 (20): 1301-7. 47. Pope JH, Aufderheide TP, Ruthazer R et al. Missed diagnoses of acute cardiac ischaemia in the emergency department. N Engl J Med 2000; 342 (16): 1163-70. 48. Stillman AE, Oudkerk M, Ackerman M et al. Use of multidetector computed tomography for the assessment of acute chest pain: a consensus statement of the North American Society of Cardiac Imaging and the European Society of Cardiac Radiology. Int J Cardiovasc Imaging 2007; 23 (4): 415-27. 49. Halpern EJ. Triple-rule-out CT angiography for evaluation of acute chest pain and possible acute coronary syndrome. Radiology 2009; 252 (2): 332-45. 50. Takakuwa KM, Halpern EJ. Evaluation of a “triple rule-out” coronary CT angiography protocol: use of 64-Section CT in lowto-moderate risk emergency department patients suspected of having acute coronary syndrome. Radiology 2008; 248 (2): 438-46. 51. Mowatt G, Cummins E, Waugh N et al. Systematic review of the clinical effectiveness and cost-effectiveness of 64-slice or higher computed tomography angiography as an alternative to invasive coronary angiography in the investigation of coronary artery disease. Health Technol Assess 2008; 12 (17): iii-iv, ix-143.

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RCSIsmjstaff review ‘Wii-habilitation’ and robotic exoskeletons: technology in physiotherapy

The Lokomat® – a robotic gait exoskeleton, body weight support system, treadmill, and screen mounted at eye level to provide patient with motivation. (Picture courtesy of Hocoma.)

Abstract

Aideen Henry1, Aileen Barrett2 1RCSI physiotherapy student 2Practice Education Co-ordinator,

School of Physiotherapy, RCSI

For mobility-impaired patients, gait retraining is an integral part of the rehabilitation programme. Manual assisted body weight support treadmill training (BWSTT) has been a major focus of research and is considered one of the primary methods of gait retraining. In recent years the focus of research has shifted to robotic assisted treadmill training, which is as efficacious as manual assisted BWSTT but is considered more cost-effective with respect to personnel and labour. The Lokomat® is a machine that provides robotic assisted treadmill training by means of a robotic gait orthosis, body weight support system and treadmill. Manufactured by Hocoma in Switzerland, it has been the subject of intense media attention since it was introduced to the US in 2001. Similar attention has been given to the Nintendo Wii™ gaming system for its potential role in rehabilitation. Although not specifically designed for use in the medical arena, the Nintendo Wii™ has been linked with functional rehabilitation benefits in a variety of patient groups. The aim of this paper is to review the clinical applications of the Lokomat® and Nintendo Wii™, and to provide an analysis of the advantages and disadvantages associated with each as a physiotherapy modality in rehabilitation. Keywords: Physiotherapy, treadmill training, Lokomat®, virtual reality, Nintendo Wii™, gait re-education. Royal College of Surgeons in Ireland Student Medical Journal 2010; 3: 70-74.

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RCSIsmjstaff review Introduction Almost 650 million people around the world live with a disability, most of whom require ongoing and intensive physiotherapy and rehabilitation.1 The most common neurological causes of debilitation include stroke, Parkinson’s disease, cerebral palsy, multiple sclerosis and spinal cord injury. The figures for each of these diseases are striking. In the United States there are 5.5 million stroke survivors, the majority of whom suffer with a stroke-related permanent disability.2 This can cost up to $140,000 in healthcare per patient over the course of their lifetime.3 Parkinson’s disease affects more than one million people in the US, at least four million people worldwide, and approximately 7,000 people in Ireland.4 An estimated 8,000 babies will be affected by cerebral palsy this year, and approximately 800,000 people have the condition in the US.5 Multiple sclerosis is one of the most common causes of neurological debilitation, affecting more than 30 per 100,000 of the population in the US.6 Finally, the incidence of spinal cord injury in the US is estimated at 40 per million, with approximately 12,000 new cases annually.7 Patients suffering from these neurological conditions generally experience impairments with balance and proprioception,8 cardiovascular fitness,9 co-ordination, motor control,10 sensation and muscle strength.11 All of these compromise an independent lifestyle and limit self efficacy, mobility and participation in an active social life.12 Therefore, rehabilitation that optimises functional capabilities and can return some ambulatory independence is of the utmost importance. Studies have shown that rehabilitation that is intensive, repetitive and task specific can enhance neuro-plasticity13 and improve motor performance in patients with neurological or orthopaedic lesions.14 Unfortunately, the high costs of rehabilitation limit its application in the clinical setting.14 However, many of these techniques can become automated due to their repetitive and mechanical nature, which would make them ideal candidates for technological innovations that play an ever increasing role in rehabilitation.15 The restoration of gait is often one of the primary goals in rehabilitation of patients with injury to their neurological system.16 Gait retraining is based on activating the plasticity of the nervous system. The afferent receptors of the lower limbs are stimulated, which then generates the necessary sensory feedback to train the central pattern receptors in the spinal cord that seem to regulate locomotion.17 Exercise such as BWSTT involves the gait rehabilitation of the patient on a moving treadmill, while strapped into a harness suspended over the machine, providing support to their trunk. It is vital to the production of neurotrophin 3 (NT3) and BDNF (brain derived neurotrophic factor), which are believed to play an integral role in synaptic plasticity.18 The exercise of practising a gait cycle on the treadmill results in the generation of sensory feedback and production of the aforementioned factors. Manual assisted BWSTT has also proven to be beneficial to a patient’s progress.16,19 This technique is similar to BWSTT, with the added component of at least two therapists, who assist in manually moving the patient’s limbs in a physiologically correct gait pattern, as the treadmill is in operation. A primary advantage of this method is that little or no ambulatory function is required by the patient to begin gait retraining, leading to improvements in overground gait such as

symmetry, endurance and speed post stroke, and an increase in motor impairment and balance scores.19,20 These improvements have also been maintained at six months following locomotor rehabilitation.21 Unfortunately, manual assist BWSTT is limited by high operating costs and a risk of injury to therapists, and is not consistent in delivering a repetitive gait pattern.22

Lokomat® The introduction of the Lokomat® has been greeted with widespread enthusiasm since this operating system is expected to overcome the shortcomings of BWSTT. Manufactured in Switzerland by Hocoma AG, the Lokomat® consists of a robotic gait orthosis, a body weight support system and a treadmill.23 The patient’s legs are strapped into a motorised exoskeleton, which then simulates walking by generating passively guided and symmetrical lower extremity trajectories that are consistent with a typical physiological gait pattern.15 The reproduced movements include interlimb co-ordination and gait cycle timing (stance versus swing phase).23 The software incorporated into the Lokomat® is the distinguishing feature of this machine as it allows precise adjustments of gait pattern as required by the patient. It also maintains constant supervision of the interaction between the patient and the treadmill by means of force transducers placed at each hip and knee. Patient motivation is provided by both the physiotherapist and a screen mounted at eye level that provides an estimate of performance and encourages a reduction in performance error. The body weight support system used by the Lokomat® is called the ‘Levi’, which is influenced by various fluctuations in order to encourage a more physiological and vertical gait.23 This weight support allows the patient to train at higher speeds, which may accelerate recovery.24 The Lokomat® differs from other gait retraining technologies in that it provides the level of support necessary to begin training at the earliest possible stage. This is particularly important for recovery in stroke patients.25 The Lokomat® increases the duration of the gait retraining session, minimises the labour-intensive assistance provided by the physiotherapists and reduces the number of personnel required. Depending on how often it is used, it also has the capacity to allow the patient to be as active as possible throughout the therapy session, which can maximise the activity-dependant plasticity of the spinal cord.26 Improvements have also been recorded in patients’ cardiorespiratory function, bone density, and even bowel motility and tissue health.27 There are currently two Lokomats® in operation in Ireland, one at the National Rehabilitation Hospital in Dublin and the second at the First Steps Rehabilitation Clinic in Limerick. Although the settings are different, the physiotherapists using these machines have unanimously supported the use of Lokomat® as a vital component in their neurorehabilitation programme. Disadvantages of the Lokomat® include limitations placed on the upper extremities, pelvis and trunk, which may alter the muscular work required for propulsion and, in turn, lead to a reduced metabolic cost of the exercise.28,29 The reduction in the metabolic cost of the exercise

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RCSIsmjstaff review Effective unloading during gait training

Unloading (kg)

Patient bodyweight Treadmill speed Selected unloading

75kg 3.2km/h 30kg

Unloading

Levi Counterweights 40 30 20

Levi Time

FIGURE 2 (above): Unloading of body weight during training by the Lokomat® body weight support system – the Levi. (Picture courtesy of Hocoma.) FIGURE 3 (left): A paediatric Lokomat®. (Picture courtesy of Hocoma.) limits the aerobic benefits that the patient may gain from it. The passive guidance provided by the Lokomat® is a vital component in the initial stages of gait retraining. The patient’s limbs are controlled by the robotic exoskeletons, which ‘passively guide’ the limbs through a physiological gait pattern. However, this assistance may compromise motor learning due to the lack of ‘error signals’ experienced throughout the gait cycle, thus leading to excessive hip abduction.25 In other words, the patient does not experience the feeling of mistakes during their training session, and their learning may therefore be limited. Despite these limitations, the feedback from researchers, physiotherapists and patients has been positive. Patients have reported that the functional gains achieved over the course of their treatment have made a dramatic difference to their daily lives.27 The official launch of the Lokomat® at the First Steps Rehabilitation Clinic took place on September 14, 2009. Already, the positive effects, both physical and psychological, can be seen in the patients who have used it. In the future, the Lokomat® could potentially be used in conjunction with other therapies to assist in the recovery of a variety of dysfunctions.

Nintendo Wii™ Virtual reality (VR) technology has been used for several years for psychosocial purposes,30 but interest has now increased in the role that VR technology and gaming may play in the treatment of people with physical disabilities.31 The interactive rehabilitation exercise programme (IREX), which uses motion capture technology, illustrates the application of a VR system designed specifically for rehabilitation. Unfortunately, this and other VR systems designed for this purpose are either expensive or not commercially available.32 Focus has therefore shifted to the use of low cost gaming systems as a method of performing task-specific and repetitive exercises in a physiotherapy programme.33 Of emerging interest is a system that bears no resemblance to the Lokomat® but has found a role as a rehabilitation platform. The Nintendo Wii™ gaming system has been shown to encourage a task-specific, repetitive exercise programme and has already been trialled in many rehabilitation clinics since it was introduced in November 2006. The Wii™ offers a low cost, commercially available alternative to VR and its application may prove to

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be useful across a variety of medical disciplines. The Wii™ is unique among other gaming systems in that it is based on motion and a spatially sensitive wireless controller, which uses accelerometers in three axes and an infrared sensor bar to recognise and interpret gestures in the environment.34 The system provides rich multi-sensory feedback such as auditory, haptic and visual components that are often lacking in other VR systems.32 The Wii Sports™ programme incorporates five different sports activities: tennis; bowling; baseball; golf; and, boxing. In order to play each game, the player needs to respond with specific physical movements that are translated to the movements of the player on screen. These movements are similar to those prescribed in physiotherapy exercises and have a beneficial effect on balance, arm movement, hand–eye co-ordination and posture.36 This was confirmed by a study at Longwood University that investigated the use of Wii™ in the rehabilitation of arthritis patients. They found that the Wii™ can be a beneficial part of exercise since it employs similar movements to conventional rehabilitation exercises.37 Physiotherapists in England are also using the Wii™ in the treatment of burns patients to improve flexibility during recovery. The Wii Fit Balance Board™ has also been used in the treatment of patients with neurological disorders and lower limb amputations. This system incorporates a touch sensitive board into the original console and controller version. The player stands on the board, which detects slight changes in movement and pressure, and allows for the participation of the player in games such as yoga and skiing. Studies are currently underway to assess the role of the Wii Fit Balance Board™ in the reduction of falls and increased confidence in the elderly. Wii Fit™ games are also physically strenuous, which may have a positive impact on a patient’s aerobic health, and levels of obesity and inactivity in children.38 They also allow the patient to play the game in either the sitting or standing positions, which encourages the participation of wheelchair users. A Nintendo Wii™ is now regularly being used in Hospital 2, St James’s Hospital in Dublin. It is used primarily in the rehabilitation of stroke patients, the majority of whom seem to enjoy the games while simultaneously receiving rehabilitation benefits. According to Sinead Coleman, Senior Physiotherapist in Care of the Elderly,


RCSIsmjstaff review Rehabilitation Unit at St James’s Hospital, the boxing and bowling games are the most popular, and also the most efficacious in improving balance, trunk control and general upper extremity movements. Scope for the Wii™ to gain a permanent position in conventional rehabilitation programmes remains unclear. In its favour, many studies conclude that the majority of long-term rehabilitation patients spend a significant amount of time in inactive situations without directed or self-directed exercise.39,40,41 Therefore, the Wii™ may be a useful method of optimising the visual perception, postural control and functional mobility of certain patients. As a means of therapy it is considerably cost-effective, requiring only one physiotherapist to supervise, which depends on the patient, and has a multi-player option.32 The Wii™ appeals to a broad demographic of people and patients generally report that they enjoy playing the games, which may increase compliance with their programmes and encourage continued use in their homes. Despite its emerging popularity, current research suggests that the Wii™ is not a suitable replacement for more conventional therapies. The movements incorporated by patients while playing the Wii™ are generally more complex than those in a conventional physiotherapy programme. This can complicate attempts to standardise a treatment regimen since patients would perform different motions using different amounts of force.36 Wii™ Fit games include a number of built-in levels of difficulty. It is not possible to adjust these levels, which may rule out the participation of certain patients.42 There have also been reports of injuries received while playing the Wii™, such as patellar dislocation, which indicates the need for proper safety precautions.43 Although the Wii™ certainly allows for more diversity and variety within therapy, further research needs to be done to fully assess its effects with specific patient groups and to standardise a method of playing.

Conclusion Physiotherapy practices are constantly evolving in conjunction with advances in technology, ultimately producing new ideas and equipment that enhance the effectiveness of therapeutic interventions such as the Lokomat® and the Nintendo Wii™. There are many benefits attributed to the Lokomat®, although the long-term effects of its use remain unclear.16 Despite limitations such as restriction of movement and alteration of muscle work patterns, the Lokomat® allows patients to execute practised movements in a consistent manner,17 reduces staffing demands and may prevent injury to therapists. The use of the Nintendo Wii™ in physiotherapy adds excitement and a unique stimulus to rehabilitation. It is capable of providing similar benefits to VR rehabilitation but without the associated cost and complications.35 Although not suitable for every patient, the Wii™ has the potential to assist in the rehabilitation of patients with physical and possibly cognitive impairments. Overall, these new modalities offer a promising new direction for rehabilitation and will hopefully promote the continued integration of technology into physiotherapy. Further research is necessary to better understand the long-term efficacy of the Lokomat® and the Nintendo Wii™, but the field of rehabilitation technology is likely to expand in the near future and maybe even make rehabilitation fun.

Acknowledgements I would like to thank Aileen Barrett, RCSI, the staff of the National Rehabilitation Hospital, Dublin, Sinead Coleman, Senior Physiotherapist, St James’s Hospital, and Jane Evans for their assistance and advice in the writing of this paper.

References 1. Howard G, Howard VJ, Katholo C, Oli MK, Huston S. Decline in US stroke mortality: an analysis of temporal patterns by sex, race and geographic region. Stroke 2001; 32: 2214-20. 2. Rosamund W, Flegal K, Furie K et al. Heart disease and stroke statistics 2008 update: a report from the American Heart Association statistics subcommittee. Circulation 2008; 117: e25e146. 3. Parkinson’s Disease Stages and Symptoms. Cited July 21, 2009. Available from: http://www.stagesofparkinsonsdisease.com/understandingparkinsons-disease-statistics.php. 4. 4 my child – Cerebral palsy facts and statistics. Cited July 21, 2009. Available from: http://www.cerebralpalsy.org/what-iscerebral-palsy/statistics/. 5. The Neurology Channel – Multiple Sclerosis. Cited July 21, 2009. Available from: http://www.neurologychannel.com /multiplesclerosis/index.shtml.

6. The Spinal Cord Injury Information Network. Spinal Cord Injury Facts and Stats page. Cited July 21, 2009. Available from: http://www.spinalcord.uab.edu/show.asp?durki=119513. 7. Tyson S, Selley A. A content analysis of physiotherapy for postural control in people with stroke: an observational study. Disabil Rehabil 2006; 28: 865-72. 8. Potempa K, Lopez M, Braun LT, Szidon JP, Fogg L, Tincknell T. Physiological outcomes of aerobic exercise training in hemiparetic stroke patients. Stroke 1995; 26: 101-5. 9. Duncan P, Studenski S, Richards L et al. Randomised clinical trial of therapeutic exercise in subacute stroke. Stroke 2003; 34: 2173-80. 10. Duncan P, Richards L, Wallace D et al. A randomised, controlled pilot study of a home based exercise program for individuals with mild and moderate stroke. Stroke 1998; 29: 2055-60. 11. Rimmer JH, Riley BB. A new measure for assessing the physical activity behaviours of persons with disabilities and chronic health conditions: the physical activity and disability survey. Am J Health Promot 2001; 16: 34-42.

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RCSIsmjstaff review 12. Meyer-Heim A, Ammann-Reiffer C, Schmartz A et al. Improvement of walking abilities after robotic-assisted locomotion training in children with cerebral palsy. Arch Dis Child 2009; 94: 615-20. 13. Riener R, Lunenburger L, Jezernik S, Anderschitz M, Columbo G, Dietz V. Patient-co-operative strategies for robotaided treadmill training: first experimental results. IEEE Transactions on Neural Systems and Rehabilitation Engineering 2005; 13: 380-94. 14. Hornby GT, Zemon DH, Campbell D. Robotic assisted bodyweight supported treadmill training in individuals following motor incomplete spinal cord injury. Phys Ther 2005; 85: 52-66. 15. Danielsson A, Stribrant Sunnerhagen K. Oxygen consumption during treadmill walking with and without body weight support in patients with hemiparesis after stroke and in healthy subjects. Arch Phys Med Rehabil 2000; 81: 953-7. 16. Hidler JM, Wall AE. Alterations in muscle activation patterns during robotic-assisted walking. Clinical Biomechanics 2005; 20: 184-93. 17. Hutchinson KJ, Gomez-Pinilla F, Crowe MJ, Ying Z, Basso M. Three exercise paradigms differentially improve sensory recovery after spinal cord contusion in rats. Brain 2004; 127: 1403-14. 18. McCain KJ, Pollo FE, Baum BS, Coleman SC, Baker S, Smith PS. Locomotor treadmill training with partial body weight support before overground gait in adults with acute stroke: a pilot study. Arch Phys Med Rehabil 2008; 89: 684-91. 19. Visintin M, Barbeau H, Korner-Bittensky N, Mayo NE. A new approach to retrain gait in stroke patients through body weight support and treadmill stimulation. Stroke 1998; 29: 1122-8. 20. Sullivan KJ, Knowlton BJ, Dobkin BH. Step training with body weight support: effect of treadmill speed and practice paradigms on poststroke locomotor recovery. Arch Phys Med Rehabil 2002; 83: 683-91. 21. Westlake KP, Patten C. Pilot study of Lokomat versus manualassisted treadmill training for locomotor recovery post stroke. Journal of Neuroengineering and Rehabilitation 2009; 6: 18. 22. The Hocoma Website. Hocoma Features and functions of the Lokomat page. Cited July 10, 2009. Available from: http:// www.hocoma.ch/en/products/lokomat/features-functions/. 23. Pohl M, Mehrholz J, Ritschel C, Ruckriem S. Speed-dependant treadmill training in ambulatory hemiparetic stroke patients: a randomised control trial. Stroke 2002; 33: 553-8. 24. Horn SD, DeJong G, Smout RJ, Gassaway J, James R, Conroy B. Stroke rehabilitation patients, practice and outcomes: is earlier and more aggressive therapy better? Arch Phys Med Rehabil 2005; 85: s101-s14. 25. Huang H, Ferris DP. Neural coupling between upper and lower limbs during recumbent stepping. J Appl Physiol 2004; 97: 1299-1308. 26. Edgerton VR, Roy RR. Paralysis recovery in humans and model systems. Current Opin Neurobiol 2002; 12: 658-67. 27. Gottschall JS, Kram R. Energy cost and muscular activity required for propulsion during walking. J Appl Physiol 2003; 94: 1766-72.

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28. Macko RF, Ivey FM, Forrester LW. Treadmill exercise rehabilitation improves ambulatory function and cardiovascular fitness in patients with chronic stroke. Stroke 2005; 36: 2206-11. 29. Keshner EA. Virtual reality and physical rehabilitation: a new toy or a new research and rehabilitation tool? Journal of Neuroengineering and Rehabilitation 2004; 1: 13. 30. Cobb SVG, Sharkey PM. A decade of research and development in disability, virtual reality and associated technologies: review of ICDVRAT 1996-2006. The International Journal of Virtual Reality 2007; 6: 51-68. 31. Deutsch JE, Borbely M, Filler J, Huhn K, Guarrera-Bowlby P. Use of a low cost, commercially available gaming console (Wii) for rehabilitation of an adolescent with cerebral palsy. Phys Ther 2008; 88: 1196-207. 32. Flynn S, Palma P, Bender A. Feasibility of using the Sony Playstation 2 gaming platform for an individual post stroke: a case report. Journal of Neurologic Physical Therapy 2007; 31: 180-9. 33. Halton J. Virtual rehabilitation with video games: a new frontier for occupational therapy. Occupational Therapy Now 2008. Cited August 5, 2009. Available from: http://www.caot.ca/otnow/jan%2008/virtual.pdf. 34. Crosbie J, Lennon S, Basford JR, McDonough SM. Virtual reality in stroke rehabilitation: still more virtual than real. Disabil and Rehabil 2007; 29: 1139-46. 35. Peltier M. Wii can work it out. Nursing Homes: Long Term Care Management 2007; 56: 72-3. 36. Sutton MA. New technologies gain popularity with older adults. Adult Development and Aging News 2008. 37. Daley A. Can exergaming contribute to improving physical activity levels and health outcomes in children? Pediatrics 2009; 124: 763-71. 38. Tinson DJ. How stroke patients spend their days, an observational study of the treatment regime offered to patients with movement disorders in hospitals following stroke. Int Disabil Studies 1989; 11: 45-9. 39. Lincoln NB, Gamlen R, Thomason H. Behavioural mapping of patients on a stroke unit. Int Disabil Studies 1989; 11: 149-54. 40. Esmonde T, McGinley J, Goldie P et al. Stroke rehabilitation: patient activity during non-therapy time. Austral J Physio-ther 1997; 43: 43-51. 41. Flynn SM, Lange BS, Yeh SC, Rizzo AA. Virtual reality rehabilitation – what do users with disabilities want? Cited August 5, 2009. Available from: http://playpen.icomtek.csir.co.za/~acdc/assistive%20devices /Artabilitation2008/archive/2008/papers/ICDVRAT2008_S03 _N03_Flynn_Lange_Yeh_Rizzo.pdf. 42. Hirpara KM, Abouazza OA. The “Wii Knee”: a case of patellar dislocation secondary to computer video games. Injury Extra 2008; 39: 86-7.


RCSIsmjstaff feature THE PROVISION OF HEALTHCARE

in a changing Ireland

AOIFE MORRIS discusses the changes to Ireland’s healthcare systems during the boom years, and the implications of economic downturn. Volume 3: Number 1. 2010 | Page 75


RCSIsmjstaff feature Described by The Economist in 1988 as “easily the poorest country in rich north-west Europe”, Ireland underwent an unprecedented economic transformation during the 1990s. From a country marred by chronic budget deficits, high levels of unemployment and widespread emigration, it became the European Union’s success story. Over a period of only a few years, Ireland emerged as an economic frontrunner, with sustained economic growth, and was seemingly ‘getting richer’ all the time.1 Ironically, the aetiology of this revolution has ultimately become its downfall; the phenomenon of globalisation. Ireland’s geographic position on the periphery of Europe, combined with competitive taxation policies and corporate incentive schemes, made it the ideal base for US companies to bridge the Atlantic and target the European market.1,2 The influx of large multinational investment placed Ireland at the heart of this new global economy and provided the financial stimulus and momentum for what was, in economic and real terms, a dramatic turning point in Irish interests. However, Ireland’s open market economy was, and remains, reliant on global trade and investment, particularly from the US. In 2007, the credit and housing boom in the United States crumbled, triggering a banking and financial market crisis that infected their economy and, by proxy, that of Ireland. The Irish success story received a rude awakening and a sharp reversal in its fortunes. Health expenditure trends in Ireland have naturally followed the national economic position. Strict economising in the earlier part of the 1990s gave way to exponential increases in expenditure between 1996 and 2002.3 The publication of the 2001 Health Strategy ‘Quality and Fairness: A Health System for You’ reaffirmed the governing principles of Irish health policy: equity, quality and accountability, with the additional focus of placing the patient at the centre of future reform.4 This strategy centred on six key areas: strengthening primary care provision; developing the acute hospital system; improving funding; better planning and training for the healthcare workforce; review of the current healthcare structures; and, improving health information systems. This strategy paved the way for a number of reports that changed the landscape of Irish healthcare. For the most part, this change has been quite visible.

Structural and departmental change The Prospectus Report5 proposed the Health Service Executive (HSE) as a means of establishing a unitary approach to health service delivery and management. Following the enactment of the Health Act 2004, the HSE was established in 2005 and charged with managing the health service as a single entity. The HSE has control over all executive, managerial and budgetary decisions. Prior to this, the administration and provision of services fell to a number of regional health boards and various government authorities. This system was fragmented and inefficient, with multiple departments lacking clarity of roles and underdeveloped functions. Both the Prospectus and Brennan` reports identified the need for separate operational and policy functions. Following the establishment of the HSE, the Department of Health and Children (DoHC) was restructured. This enabled it to refocus its activities on strategic overview, analysis and evaluation, and to advise the government on health policy. Finally, the Health Information and Quality Authority (HIQA) was established, with the aim of supporting

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the delivery of high quality services based on evidence-based best practice. Its mandate includes the development of health information, health promotion, the implementation of quality assurance programmes and overseeing health technology assessment.3

Health expenditure trends in Ireland have naturally followed the national economic position. Strict economising in the earlier part of the 1990s gave way to exponential increases in expenditure between 1996 and 2002. While the need for a more streamlined approach to delivering healthcare services was clearly evident, the HSE has been the focus of much dissatisfaction. It has been widely criticised for being too concerned with its own structures and centralised methods of working and for not engaging with those who experience the challenges of running the health service on a daily basis.6 Where enhanced patient care was a core objective of health strategies, it is felt that such improvement has been only in high profile areas, such as cancer care and the private sector. Other critical issues of hospital overcrowding and community services are being overlooked.7 The economic context notwithstanding, the HSE’s lack of partnership and willingness to harness the experience and expertise that is found at the front line has been detrimental. This was witnessed in the implementation of revised working practices and costeffectiveness measures. Such unilateral action, particularly where the National Service Plan 20098 is concerned, is widely regarded as being unaware of the realities of providing safe and efficient patient care. It has resulted in numerous industrial relations issues, some requiring the involvement of the Labour and High Courts for resolution. Despite an attempt to clearly delineate the roles and responsibilities of the DoHC and the HSE, there remain grey areas, and of particular concern are budgetary issues. No single agency is accountable for ensuring efficient use of resources,5 which is critical for managing the health service effectively, especially in the current economic climate. Although this ‘managerial vacuum’ was identified by the Brennan Report, action based on its recommendations has been nominal and remains controversial. Recently, however, almost reneging on their stance for the past five years, the HSE has announced that it is to make “significant changes to its organisational structure”, reflecting the need to bring decision-making closer to where the service is delivered.9 This restructuring involves establishing four regional teams and an integrated services directorate accountable to HSE headquarters. Regional teams will be responsible for identifying and setting performance targets, and budgets needed to achieve these will be allocated by the Government. The difficult questions that now need to be answered are whether this will actually be an effective method of resolving current problems or are the issues more complex than simply organisational. Also, it is most important to consider whether this restructuring will be effectively conducted in a budget-neutral fashion.


RCSIsmjstaff feature The Hanly Report The National Task Force on Medical Staffing was created to introduce the 48-hour working week for non-consultant hospital doctors (NCHDs) by 2009. This was in accordance with the requirements of the European Working Time Directive (EWTD).3 However, it was also charged with “devising, costing and promoting implementation of a new model of hospital service delivery based on appropriately trained doctors providing patients with the highest quality service, using available resources as equitably, efficiently and effectively as possible”.10

Recently, however, almost reneging on their stance for the past five years, the HSE has announced that it is to make “significant changes to its organisational structure”, reflecting the need to bring decision-making closer to where the service is delivered. The report recommended re-orientation, thereby introducing a “consultant-provided” service as opposed to the existing “consultant-led” system.10 This would result in a reduction of NCHDs’ working hours and attain the goal of complying with the EWTD. This re-orientation would require both the re-organisation of the hospital, and a review of medical education and training, while being sensitive to industrial relations issues. Somewhat unbelievably, the cost of such extensive restructuring was never considered.3 Unfortunately, implementation of these proposals has been marred by controversy and industrial relations difficulties. It is further complicated by the fact that these recommendations were made at a time of relative economic prosperity. Consultant-provided care necessitates significant changes in existing consultant work practices. These include increased availability, longer working hours, shared consultant management and facilitating efficient treatment with shorter in-patient stays. The negotiation of an acceptable contract for all parties has been lengthy, with an agreement on a revised Common Contract only being accepted in June 2008. In addition, despite many consultants adapting to the new regulations, the HSE has been reluctant to honour its own commitments.6 These commitments concern both remuneration and identifying issues that continue to hinder optimum implementation of the new contract. While the Minister for Health and Children, Mary Harney TD, has categorically stated that the contract should be, and will be, honoured, this remains to be seen. As previously mentioned, the “consultant-provided” service was initially proposed to combat the “excessively long working hours” of the majority of NCHDs. It was also considered to be the only solution that would simultaneously address the need “to improve patient care, reform medical education and training, and support the continued provision of safe, high quality, acute hospital care”.10 While this may be a worthwhile endeavour, failure to acknowledge

the very different roles of consultants and NCHDS, particularly interns, means that the reality has been very different. Negotiations for a new NCHD contract reached an abrupt halt following the announcement in November 2008 that NCHDs would bear the brunt of further and immediate cutbacks beyond those already implemented earlier that year. While additional cuts are inevitable in the current economic climate, NCHDs would bear nearly 50% of the HSE’s proposed cost-saving measures across the health system.6 These cuts included curtailment of allowances and training grants, along with significant reductions in payments for overtime and on-call, which represented up to a 40% decrease in potential income.6 Not only did this conflict with their contractual terms and conditions, it also interfered with the development of their careers in medicine. Reducing the working hours of junior doctors, without increasing their numbers in the hospitals, ultimately impacts the quality of care these junior doctors are capable of providing. This is not only in terms of hours dedicated to patient care and hospital duties but, equally, in training hours necessary to improve clinical knowledge and skill.

The HSE’s lack of partnership and willingness to harness the experience and expertise that is found at the front line has been detrimental. The response from NCHDs was unanimous. A ballot conducted by the Irish Medical Organisation (IMO) in favour of industrial action passed with 99% support. Legal action for breach of contract was taken against the HSE to the High Court in April 2009. A new agreement stipulated that all NCHD terms and conditions of employment were to be honoured and remunerated in full by the HSE with immediate effect. This agreement also provided a platform for negotiations about implementation of the EWTD, during which terms and conditions of existing contracts were not to be altered by the HSE.11 Members of the IMO voted in favour of the Labour Court’s recommendations on the implementation of the EWTD in June 2009.12 The next phase of discussions took place in September with the aim of reaching an agreement in time to implement a new contract by 2010.The IMO’s NCHD committee has reiterated that “all new working arrangements must prioritise patient safety, training for NCHDs, and health and safety issues”. Junior doctors, however, remain wary, considering the HSE’s attitude towards the value of other healthcare professionals.

Patients The wide-ranging incomes of citizens, coupled with a multitude of public, private and combined health plans and entitlements, makes it difficult to ensure equitable and fair access to healthcare. During the years of economic growth, Irish citizens benefited from many subsidised schemes. For example, the medical card scheme gave holders access to a range of health services free of charge. In 2001, this scheme was extended to include all those over the age of 70

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RCSIsmjstaff feature regardless of financial status. A similar scheme was introduced offering free GP consultations to GP Visit Card holders. Under the Drugs Payment Scheme as of January 2009, non-Medical Card holders and families are only required to pay a maximum of €100 per calendar month for prescription medicines, while the balance is reimbursed by the Government. Attempts were made to reduce waiting lists by introducing the National Treatment Purchase Fund (NTPF) in 2002. Under this programme, any adult waiting one year or more (or any child waiting six months or more) for treatment can have that treatment in a private facility or abroad at the expense of the Fund.3

Under the Drugs Payment Scheme as of January 2009, non-medical card holders and families are only required to pay a maximum of €100 per calendar month for prescription medicines, while the balance is reimbursed by the Government. However, there are serious concerns about the equality of healthcare provision in Ireland and its accessibility for the non-cardholding Irish

taxpayer. A survey conducted by the Central Statistics Office in 2008 showed an increase of 9.1% in the previous year in doctors’ fees and a similar increase in the cost of other medical services.13 An independent nationwide survey conducted in 2007 also showed that over half the population (55%) had put off, and over one-third (36%) had delayed, routine medical check-ups because of the cost.13 Furthermore, research on the utilisation of GP services showed that those with medical cards, despite controlling for a range of socio-economic variables, have an average of 1.6 more visits each year compared to those with similar characteristics and no medical card.3 Of more concern is that this research was conducted before the 2008 budget, a budget that increased upfront accident and emergency and outpatient fees, as well as a 10% increase in inpatient admission charges.14 The budget also called for a review of the eligibility criteria for medical cards and removal of the automatic entitlement at age 70, a move that caused an outspoken public rebuke. With increasing unemployment and economic deterioration, the physical and mental health of our population is certainly under pressure. While prevention may be the best medicine, the rising cost of healthcare in these difficult economic times will make households less likely to spend money on preventive health, which can seem like an intangible expense.

References 1. Murphy AE. The ‘Celtic Tiger’ – An Analysis of Ireland’s Economic Growth Performance. Cited April 2000. Available from: http://www.eui.eu/RSCAS/WP-Texts/00_16.pdf. 2. McArdle P. A Private Sector Perspective on the Celtic Tiger Experience. Cited October 2005. Available from: http://www.ulsterbank.com/content/group/economy/ri_indi cators/downloads/articles/Article_5.pdf. 3. Wiley MM. The Irish health system: developments in strategy, structure, funding and delivery since 1980. Health Econ 2005; 14: S169-S186. 4. Department of Health and Children. Quality and Fairness: A Health System for You, Health Strategy. Dublin: The Stationery Office, Dublin. Cited November 2001. Available from: http://www.healthreform.ie/ publications/reports.html. 5. Department of Health and Children. Commission on Financial Management and Control Systems in the Health Service. The Stationery Office, Dublin. Cited June 2003. Available from: http://www.healthreform.ie/publications/reports.html. 6. Irish Medical Organisation. Leadership with Responsibility – Annual General Meeting. Cited April 2009. Available from: http://www.imo.ie/Documents/IMO%20AGM%20Report%2 02009.pdf.

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7. Dickson S. Safe Practice Equals Safe Care, 90 years of experience – Presidential address to Annual Delegate Conference of the Irish Nurses Organisation. Cited May 2009. Available from: http:// www.ino.ie/DesktopModules/articles/Documents/Presidential%20S peech%20-%206-5-09.pdf. 8. Health Service Executive. National Service Plan 2009. Cited November 2008. Available from: http://www.hse.ie/eng/Publications /corporate/HSE_National_Service_Plan_2009.html. 9. O’Regan E. HSE back to Health Boards. The Irish Independent, Sept 16, 2009. 10. Irish Medical Organisation. Press Release: IMO and HSE negotiate High Court settlement. Cited April 2009. Available from: http://www.imo.ie/IMOPage_2_13.aspx?ID=2266&No=0. 11. Irish Medical Organisation. Press Release: NCHDs vote on Labour Court proposals on the implementation of the EWTD. Cited June 2009. Available from: http://www.imo.ie/IMOPage_ 2_13.aspx ?ID=2290&No=0. 12. Hodgson L. The health of a nation. Cited May 9, 2009. Available from: http://www.hermitageclinic.ie/newsAndEvents /releases/healthcare.pdf. 13. Citizen’s Information. Budget 2008. Cited April 8. Available from: http://www.citizensinformation.ie/categories/money-andtax/budget-2008#rates.


RCSIsmjelective PAUL SINGH DHILLON describes a unique experience in Africa.

LIBERIAN HEARTT:

post-conflict emergency medicine “The love of liberty brought us here” The motto of the Republic of Liberia is in stark contrast to the lack of liberty that the Liberian people experience today. However, after decades of tumultuous politics and civil war, a modicum of peace and stability has entered the daylight hours of the West African nation. Liberia is a unique country, the only country that was not cut up and shorn along arbitrary lines of latitude and longitude by colonial powers during the scramble for Africa. This fact has not, however, protected Liberia from the civil unrest that has become so common among post-colonial African states. Liberia was created by freed American slaves during the 1800s. This connection to America is visible throughout the country, including the naming of the major hospital in Monrovia, The John F. Kennedy Medical Center. For my last elective in medical school, through a fortuitous series of connections I was linked up with the HEARTT (Health Education And Relief Through Teaching) programme in Liberia. The HEARTT programme’s mission is to “educate and assist local healthcare providers in the development and/or improvement of a healthcare system and infrastructure”, and their vision is to have a “world where there are fully functioning healthcare systems in all communities, including the communities of underdeveloped countries”. Due to issues with medical indemnity I was unable to complete a full elective and was restricted to an observership; this situation may change in the future.

After decades of tumultuous politics and civil war, a modicum of peace and stability has entered the daylight hours of [this] West African nation. Arrival I arrived over land from the border with Sierra Leone in an old station wagon that broke down a number of times only to be fixed with some plastic and wires that were sacrificed from other areas in the vehicle. The road quality was not great but the abandoned and bullet-scarred vehicles dotting the roadside were a sombre reminder of previous conflicts. For this observership I was shadowing a doctor from Brown University (Providence, Rhode Island, USA) who was completing her Fellowship in International Emergency Medicine, and during my week in Liberia I was based mainly in the Emergency Department. The Emergency Department was nothing like any other I had seen in terms of supplies and structure. It was rudimentary and the Americans that were working in the hospital on an aid mission brought all of their equipment with them, right down to cannulas and alcohol swabs. I had to make numerous trips to the supplies closet, which was always kept locked, to get supplies, as anything left around would probably disappear.

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RCSIsmjelective

Far left: The weapon of choice in Liberia is the machete. Above: The Emergency Department was rudimentary and foreign staff had to bring all of their equipment with them. Left: I arrived over land from the border with Sierra Leone in an old station wagon that broke down a number of times.

Extraordinary circumstances

A worthy elective

There is still a high level of mob violence in Liberia and the weapon of choice is the machete. I had never seen machete wounds before and they are quite graphic. One patient had both his Achilles tendons cut and was unable to walk, and another had a massive incision across his back from a machete attack. Patients of all ages were treated in the emergency room and there were quite a few interesting religious–psychiatric presentations, which I had never witnessed before, but which are apparently common in Liberia. One patient was actually discharged to church after her family members and pastor attended to her in the emergency room and the healing olive oil that was placed in her mouth and ears did not seem to work.

Life outside the hospital–hotel axis is limited in Liberia. There is still the active threat of violence and even the United Nations staff have a 10.00pm curfew. In terms of cheap accommodation, there really wasn’t any at the time I was there and the hotel at US$100 a night was the only option. Hopefully, with time and stability this will change, and more people will be able to enjoy meeting the people of Liberia and enjoying the beautiful beaches and sunsets without worrying about personal safety.

[The Emergency Department] was rudimentary and the Americans that were working in the hospital on an aid mission brought all of their equipment with them, right down to cannulas and alcohol swabs.

I would recommend Liberia as an elective location for anyone who would like to see how an attempt at rebuilding a healthcare system in an English-speaking post-conflict area is progressing. There are still many NGOs active in the area; however, safety-wise it is not the most stable environment. It is a great chance to see how stability is brought to an area but also to become acutely aware of the social, political, and monetary challenges that hinder the rebuilding of healthcare systems post conflict and in lowresource settings.

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One patient had both his Achilles tendons cut and was unable to walk, and another had a massive incision across his back from a machete attack.


RCSIsmjelective REACHING OUT TO

rural communities

ASHLEY FREEMAN, DENA EL SAYED and MEGAN DEVLIN describe their elective in South Africa. Imagine yourself, a young medical student, in rural South Africa. You are on a weekend trip to visit the remote Drakensberg National Park with your seasoned tour guide, a native of South Africa. While you are enjoying the exquisite mountain views, your guide begins to experience chest pains. Frightened by the prospect of a heart attack, he looks to you for comfort and a plan. You are two hours from the nearest hospital. This is a true story of our experience while on an elective in South Africa. An ambulance was able to transport our guide to the nearest rural hospital. The lone junior doctor offered what little help he could, apologising for the lack of an ECG and laboratory facilities. Due to the urgent nature of the presentation, we were left with no other option but to hook up our guide’s IV fluids to the inside of our rental car and drive him back to the city where he could undergo more thorough investigation. While our guide survived the ordeal, the incident was a shocking introduction to the sparse healthcare provided to the people of rural South Africa.

A makeshift ambulance in Kwazulu-Natal.

Working in a relatively well equipped tertiary care centre, we observed the unique burdens of a population plagued by HIV/AIDS and tuberculosis. Rural crisis In April 2009, we travelled to Pietermaritzburg, within the province of Kwazulu-Natal (KZN), to undertake a three-week elective at Grey’s Hospital. Working in a relatively well equipped tertiary care centre, we observed the unique burdens of a population plagued by HIV/AIDS and tuberculosis. One doctor described “the dubious distinction of being consultant-in-charge

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RCSIsmjelective

Far left: Dr Caldwell preparing for an Outreach visit. Left: Dena El-Sayed with a paediatric patient.

of the first female inpatient diagnosed with AIDS in Pietermartizburg�. Unfortunately, within three years, 70% of the occupants of that ward would have HIV/AIDS. This is also now the case in public hospital medical wards throughout the province. However, we were also troubled by the stark differences we had witnessed between urban and rural care. It was evident that the difficulties of rural healthcare go beyond a high disease prevalence and lack of funding. The severe physician shortage in South Africa is creating huge gaps in the system. We found that rural medical staff were very much isolated by a lack of consultant guidance.

A lucky break Rather serendipitously we met two veteran consultants in internal medicine, Dr RI Caldwell and Dr Jim Muller. They introduced us to their own project, the Red Cross Outreach Programme, which was established to alleviate some of the problems we witnessed on our tour. Funded in part by the province of KZN and the Red Cross Air Mercy Service, the Outreach Programme is responsible for 20 district hospitals serving a population of three million people. These two heroic men are working with the Outreach Programme to ensure that consultant advice is made available to rural centres despite physician shortage. The goal of the Outreach Programme is to bridge the gap in knowledge and care that exists between tertiary and district hospitals, and to foster an environment of continuing medical education. This is accomplished by ensuring that each district hospital gets a monthly visit from a consultant in each major discipline.

The Outreach Programme is responsible for 20 district hospitals serving a population of three million people.

airfield outside of town where we boarded a small propeller plane that would take us to a rural hospital. Each visit was structured, with consultations on difficult or puzzling medical cases, clinical teaching rounds and formal tutorials for medical staff. The consultants even provided their own personal contact details so that they could be contacted in emergencies. Prior to this outreach programme, the teams were isolated with little or no opportunity for continued learning or consultation on challenging cases. We discovered that many of the staff live on the grounds of the hospital, and are completely dedicated to patient care. The staff were extremely grateful for these visits and described their relief to know that they had support. In rural South Africa, a junior doctor may have to wait weeks for advice, while a junior doctor in Ireland can take comfort in the fact that there is always a senior physician to consult in the case of uncertainty.

The goal of the Outreach Programme is to bridge the gap in knowledge and care that exists between tertiary and district hospitals, and to foster an environment of continuing medical education. The Outreach Programme is a novel approach that succeeds in making specialist advice available to rural medical staff. We feel privileged to have participated in such dedicated efforts to enhance healthcare for a neglected population. Given the opportunity, we recommend that other RCSI students experience the Outreach Programme by applying for the elective through the University of KZN.

Acknowledgements We accompanied Dr Caldwell and Dr Muller on several Outreach trips throughout the elective. Our days began at dawn at an

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We would like to thank Dr RI Caldwell, Dr Jim Muller and the University of Kwa-Zulu Natal for this opportunity.


RCSIsmjstaff picks Highlighting the latest developments in medicine With a massive volume of medical research released every year, it is often difficult to keep abreast of the latest developments influencing clinical practice. Here, RCSIsmj staff members present their picks of some of the most influential papers of the last year to give an insight into the new and changing face of medicine. Pre-eclampsia and the risk of end-stage renal disease

Aspirin use and survival after diagnosis of colorectal cancer

Vikse BE, Irgens LM, Leivestad T et al. N Engl J Med 2008; 359 (8): 8009. Chosen by: Kristl Vidya Dorschner

Chan AT, Ogino S, Fuchs CS. JAMA 2009; 302 (6): 649-58. Chosen by: Rowena Almeida

Abstract The authors linked data on all births in Norway since 1967 with data from the Norwegian Renal Registry, which contains data on all patients receiving a diagnosis of end-stage renal disease (ESRD) since 1980, to assess the association between pre-eclampsia/toxaemia (PET) in one or more pregnancies and the subsequent development of ESRD. The relative risk of developing ESRD increased with each pregnancy. Although the absolute risk of ESRD in women who have had preeclampsia is low, pre-eclampsia is a marker for an increased risk of subsequent ESRD.

Comments Pre-eclampsia affects 3-14% of all pregnancies world-wide and carries a 65% risk of recurrence in subsequent pregnancies. Development of PET carries morbidity and mortality risks for mothers during pregnancy and delivery, but little is known about the long-term effects of the disease post partum. This study indicates that there may be a risk of developing ESRD later in life, and women who suffered from PET, particularly in multiple pregnancies, may benefit from regular life-long blood pressure surveillance.

Dabigatran versus warfarin in patients with atrial fibrillation Connolly SJ, Ezekowitz MD, Yusuf S et al. N Engl J Med 2009; 361 (12): 1139-51. Chosen by: James Young

Abstract Dabigatran is an oral thrombin inhibitor with twice-daily dosing – no INR monitoring is required. This trial randomised 18,113 patients with atrial fibrillation to receive dabigatran 150mg BD, 110mg BD or warfarin. Both doses were shown not to be inferior to warfarin in preventing the primary endpoint of the trial: stroke or systemic embolism. The 110mg dose was also associated with fewer haemorrhagic complications. Problems with elevated liver enzymes, which plagued the previous thrombin inhibitor ximelagatran, do not appear to be any more frequent than those associated with warfarin.

Comment The quest for an effective oral anticoagulant to replace warfarin continues and this drug could change the face of anticoagulation as we know it.

Abstract A prospective cohort study suggests that regular aspirin use after the diagnosis of colorectal cancer is associated with lower risk of colorectal cancer-specific and overall mortality, especially among individuals with tumours that over-express COX-2. The study found fewer cancer-related deaths among regular aspirin users versus non-aspirin users. The researchers indicate that aspirin conferred similar benefits regardless of stage of disease at diagnosis or receipt of standard adjuvant chemotherapy.

Comment Aspirin was known to reduce the risk of colorectal neoplasia in randomised controlled trials, and inhibited growth and metastases in animal models. Now there is evidence for the influence of aspirin on survival after colorectal cancer diagnosis. These findings may encourage tailored treatment to specific patients using COX-2 as a predictive biomarker, and may lead to aspirin as standard adjuvant therapy in the management of colorectal cancer. It also provides cancer patients with a way to help themselves through lifestyle changes.

Toward clinical therapies utilising haematopoietic cells derived from human pluripotent cells Kaufman DS. Blood 2009; blood-2009-03-191304v1 [epub ahead of print]. Chosen by: Amrita Roy

Abstract The author conducts a review of the literature to date regarding the use of human embryonic stem cells and induced pluripotent stem cells in haematopoietic cell-based therapies. Kaufman outlines the current obstacles in bringing this technique from bench to bedside, while stressing that these concerns can and should be dealt with so that areas such as transfusion therapies and immune therapies can benefit.

Comment Using stem cells to create human blood is a huge step forward in transfusion therapies, as it could benefit patients of any blood group. It is also promising as there could be a limitless supply of type O-negative ‘universal donor’ red blood cells. While the research is promising, the risk of uncontrolled cell growth must be thoroughly examined. Should this be clinically viable, it benefits the patient immensely, and also has potential to be used in military medicine

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RCSIsmjabstract Molecular interactions of Staphylococcus aureus-induced osteomyelitis McDonagh P1, Widaa A2,3, Claro T2, O’Brien FJ3, Kerrigan S2 1RCSI medical student 2Molecular and Cellular Therapeutics, RCSI 3Department of Anatomy, RCSI

Background

Results

Staphylococcus aureus is a commensal gram-positive organism of the skin and mucous membranes but may become pathogenic in the right circumstance. As a pathogen, S. aureus represents the most common cause of osteomyelitis and localised bone destruction. S. aureus binds to the osteoblast, is internalised and then inhibits osteoblast proliferation, leading to weakening of the bone.1 Previous reports demonstrate that internalisation is mediated by S. aureus cell wall protein FnbpA binding to the osteoblast.2 This paper investigates if S. aureus FnbpA plays a role in inhibiting osteoblast proliferation.

In the absence of S. aureus, osteoblasts exponentially proliferated over 24 hours and 48 hours. Addition of S. aureus strain SH1000 ablated proliferation at both 24 hours and 48 hours (0% growth at both time points, p<0.01, n=3). Furthermore, deletion of FnbpA from S. aureus SH1000 failed to recover proliferation after 24 hours or 48 hours (0% growth, p<0.05, n=3).

Methods S. aureus strain SH1000 and a mutant lacking expression of FnbpA were grown to the exponential phase of growth for four hours in brain heart infusion broth. Bacteria fixed in formaldehyde were allowed to adhere to cell culture plates. Mouse osteoblast cells (2x105 cells/well) were added at 0 hour. Following a proliferation time of 24 and 48 hours, osteoblasts were removed and counted using a haemocytometer. The experiment was repeated three times with three wells allocated to each strain and the control. Statistical analysis was carried out using paired student t-tests.

References 1. Tucker KA, Reilly SS, Leslie CS, Hudson MC. Intracellular Staphylococcus aureus induces apoptosis in mouse osteoblasts. FEMS Microbiology Lett 2000; 186: 151-6.

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Conclusion When S. aureus enters bone it binds viable osteoblasts, is internalised and then inhibits proliferation. Binding and internalisation is mediated by S. aureus protein FnbpA. Deletion of FnbpA from parent strain S. aureus SH1000 failed to recover the proliferation, which suggests that another protein expressed on S. aureus is responsible for preventing osteoblast proliferation. We therefore propose that S. aureus binding to osteoblasts is a multifactorial event involving several protein-protein interactions. Understanding the molecular mechanisms of osteomyelitis will aid in the development of novel treatments for this disease. This work was kindly supported by a grant from the Royal College of Surgeons in Ireland Charitable Infirmary Charitable Trust.

2. Sinha B, François PP, Nüße O, Foti M, Hartford OM, Vaudaux P et al. Fibronectin-binding protein acts as Staphylococcus aureus invasion via fibronectin bridging to integrin 5β1. Cellular Microbiology 1999; 1 (2): 101-17.


RCSIsmjawards Upjohn Medal in Molecular Medicine 2009 Cancer stem cells – the key to carcinogenesis? Sheryl Ramdass

Carcinogenesis is the process where normal cells are transformed into malignant cells. The classic genetic model describes the sequential accumulation of mutations in oncogenes and tumour suppressor genes as responsible for tumour development.1 The cancer stem cell hypothesis adds another layer of complexity in the process of malignant transformation. It postulates that malignant tumours are initiated and maintained by a single abnormal population of adult stem cells, called cancer stem cells (CSCs). Studies supporting the CSC theory are based largely on xenotransplantation of a specific subpopulation of cells into immunodeficient mice. CSCs were first discovered in acute myeloid leukaemia cells and this study provided an impetus for similar experiments involving solid tumours. To date, the existence of CSCs has been shown in carcinomas of the brain, lung, prostate, testis, ovary, stomach, colon, skin, liver, and pancreas.2-6 Further

supporting evidence arises from observing the striking parallels that exist between normal stem cells and cancer cells, including the capacity for self-renewal, active telomerase expression, activation of anti-apoptotic pathways and the ability to migrate and metastasise.7,8 However, despite this persuasive evidence, the theory does not go unopposed as critics have highlighted a number of theoretical and methodological points that question the validity of the CSC hypothesis. For example, they argue that xenograft experiments do not adequately model the interaction between tumour cells and the tumour microenvironment that occurs in humans. Hence, although the CSC theory provides an attractive explanation of carcinogenesis, the current limitations that exist must be resolved before the hypothesis can be fully accepted. If proven, however, it will have profound implications for cancer prevention, diagnosis, and treatment.

References 1. Vermeulen L, Sprick MR, Kemper K, Stassi G, Medema JP. Cancer stem cells – old concepts, new insights. Cell Death and Differentiation 2008; 15 (6): 947-58. 2. Kim CF, Jackson EL, Woolfenden AE, Lawrence S, Babar I, Vogel S et al. Identification of bronchioalveolar stem cells in normal lung and lung cancer. Cell 2005; 121: 811-3. 3. Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, Hide T et al. Identification of human brain tumour initiating cells. Nature 2004; 19: 396-401.

4. Al-Hajj M, Clarke MF. Self-renewal and solid tumour stem cells. Oncogene 2004; 23: 7274-82. 5. Woodward WA, Chen MS, Behbod F, Rosen JM. On mammary stem cells. Cell Science 2005; 118: 3585-94. 6. Moore KA, Lemischka IR. Stem cells and their niches. Science 2006; 311: 1880-5. 7. Reya T, Morrison SJ, Clarke MF, Weissman IL. Stem cells, cancer, and cancer stem cells. Nature 2001; 414: 105-11. 8. Wicha MS, Liu S, Dontu G. Cancer stem cells: an old idea – a paradigm shift.Cancer Research 2006; 66 (4): 1883-90.

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RCSIsmjawards Kane Medal Neuroprotection in acute stroke: future or fantasy? Amrita Roy Stroke is a devastating health concern in the modern world, resulting in compromised quality of life, long-term disability and, at times, death. It also has a heavy impact on the public sector by straining already limited healthcare resources. At present, recombinant tissue plasminogen activator (rtPA) is the only approved medical treatment for stroke. Due to the limitations of rtPA, other therapeutic options have been actively explored, such as neuroprotective drugs. Neuroprotective drugs attempt to salvage the ischaemic penumbra, the potentially salvageable tissue surrounding the ischaemic core, thereby reducing sequelae and improving prognosis.1,2 Unfortunately, consistent failures in both pre-clinical and clinical trials have dampened the enthusiasm for neuroprotection research. The unsuccessful SAINT-II trial has left many researchers with serious doubts. However, while the past has been bleak, there is optimism in the future of neuroprotective research. Post-hoc analysis into failed trials has shown considerable room for improvement in trial design, such as using animal models closer in neuro-morphology to humans,3 accounting for co-morbidities,3 implementing realistic window to treatment times,4 and re-evaluating biologically relevant endpoints and outcome measures.5 With this in mind, the STAIR committee plans to discuss the necessary changes needed to increase the validity and precision of future pre-clinical and clinical trials. In addition to improving trial design, alternative approaches to neuroprotective research also show potential. Rogaliewski et al stress that the complexities of the ischaemic cascade make it unlikely that single mechanism approaches will have a substantial impact on stroke outcome.6 Instead,

combination therapy matching drugs with different neuroprotective mechanisms may have synergistic effects. For example, new studies have demonstrated the effectiveness of using improved shivering management and endovascular cooling technology.7 Alternative neuroprotective treatments, including albumin and magnesium therapy, may also play a role in the future.8 In light of the potential for improved trial design and the encouraging results from multi-modal stroke management, there may yet be room for new research in neuroprotective agents.

References 1. Yakovlev AG, Faden AI. Mechanisms of neural cell death: implications for development of neuroprotective treatment strategies. NeuroRx 2004; 1: 5-16. 2. Fisher M. The ischaemic penumbra: identification, evolution, and treatment concepts. Cerebrovasc Dis 2004; 17 (1): 1-6. 3. Hoyte L, Kaur J, Buchan AM. Lost in translation: taking neuroprotection from animal models to clinical trials. Exp Neurol 2004; 188: 200-4. 4. Grotta J. Neuroprotection is unlikely to be effective in humans using current trial design. Stroke 2002; 33: 306-7. 5. Duncan PW, Jorgensen HS, Wade DT. Outcome measures in acute stroke trials: a systematic review and some

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recommendations to improve practice. Stroke 2000; 31: 1429-38. 6. Rogaliewski A, Schneider A. Toward a multimodal neuroprotective treatment of stroke. Stroke 2006; 37: 1129-36. 7. Georgiadis D, Schwarz S, Kollmar R, Schwab S. Endovascular cooling for moderate hypothermia in patients with acute stroke: first results of a novel approach. Stroke 2001; 32: 2550-3. 8. Ginsberg MD, Palesh YY, Hill MD. The ALIAS (Albumin in Acute Stroke) Phase III randomised multi-centre clinical trial: design and progress report. Biochem Soc Trans 2006b; 34: 1323-6.


RCSIsmjawards Norman Rae Dissertation Medal Designing a national strategy aimed at preventing childhood obesity: a psychosocial approach Tristan Tham

Childhood obesity is a complex condition with a multi-factorial aetiology, which includes genetic, psychosocial and environmental factors1. Consequently, preventive measures must be equally diverse and address diet control, environment optimisation, and public education. Perhaps the greatest challenge will be the co-ordination of these efforts, as together they will be more effective than any one measure alone.2 The majority of the approaches for preventing obesity are based on modifying the behaviour of obese individuals. Cognitive biases, notably the attribution bias3 and the fundamental attribution error,4 focus the blame on the individuals, persuading the public and the

obese to see their condition as a consequence of personal flaws such as laziness or incompetence.5 These psychological stereotypes lead us to think that the only way to prevent obesity is to reform personal character. This is counter-productive because it undermines the multifactorial approach necessary for prevention. It is important to remember that children differ from adults in their maturity and therefore preventive measures should account for their stage of physical and intellectual development. It is also necessary to be mindful that preventing obesity is not entirely about physical health, and a more holistic approach with regard for the child’s psychological and social well-being is more appropriate and effective.

References 1. World Health Organisation. Obesity: Preventing and Managing the Global Epidemic (document on the Internet]). Geneva, 2000. Cited 2009. Available from: http://www.atividadefisica.pro.br/artigos/WHO%20obesity.pdf. 2. Epstein LH, Squires S. The Stoplight Diet for Children: an eightweek program for parents and children. New York: Little Brown & Co, 1988. 3. Crandall CS, Reser AH. Attributions and weight-based prejudice. In: Brownell KD, Puhl RM, Schwartz MB, Rudd L,

(eds.). Weight Bias: Nature, consequences, and remedies. New York: Guilford Press, 2005. 4. Ross L. The intuitive psychologist and his shortcomings: Distortions in the attribution process. In: Berkowitz L, (ed.). Advances in Experimental Social Psychology. New York: Academic Press; vol. 10: pp. 173-220. 5. Schartz MB, Vartanian LR, Nosek BA, Brownell KD. The influence of one’s own body weight on implicit and explicit antifat bias. Obesity 2006: 14: 440-7.

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RCSI editorsmj@rcsi.ie submissionssmj@rcsi.ie www.rcsismj.com.

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