Midlands Medicine October 2016 Volume 28 Issue 2 by netinspire

MIDLANDS MEDICINE OCTOBER 2016

VOLUME 28 - ISSUE No 2

EDITORâ&#x20AC;&#x2122;S NOTES

REGULATING REPRODUCTION

IN OUT, SHAKE IT ALL ABOUT

RECOGNISING AND SUPPORTING STUDENTS IN DIFFICULTY

ABSTRACTS OF WORK PRESENTED AT THE HEALTHCARE RESEARCH IN STAFFORDSHIRE CONFERENCE

CASE REPORT: ACUTE GRANULOMATOUS TUBULO-INTERSITITAL NEPHRITIS SECONDARY TO IPILIMUMAB TREATMENT FOR MALIGNANT MELANOMA

NEWS

REGIONAL UPDATE IN MEDICINE

101

GETTING TO KNOW: KEVIN GREAVES

103

TEN QUESTIONS ON DIABETES MELLITUS

104

INTERESTING IMAGES

106

TEN ANSWERS AND EXPLANATIONS

Midlands Medicine is the journal of the North Staffordshire Medical Institute, whose purpose is to promote postgraduate medical education and research. The journal was first published in 1969 as the North Staffordshire Medical Institute Journal.

COVER IMAGE

A x100 micrograph showing a kidney biopsy depicting a granulomatous tubuo-interstitial nephritis (see case report).

Midlands Medicine

MIDLANDS MEDICINE

CONTENTS

EDITOR

Dr D de Takats

ASSISTANT EDITOR Mr C Bolger

EDITORIAL BOARD Mr D Gough Dr I Smith K Stevenson Mr D Griffiths Helen Inwood Dr B Davies Professor R Chambers Clive Gibson Professor Bob McKinley Tracy Hall

EDITORIAL ASSISTANT Spencer Smith

THE NORTH STAFFORDSHIRE MEDICAL INSTITUTE President: Mr B Carnes Chairman: Professor S O'Brien Honorary Secretary: Mr J Kocierz Honorary Treasurer: Mr M Barnish

Please forward any contributions for consideration by the Midlands Medicine Editorial Board to the Editor c/o Spencer Smith, Editorial assistant. By email: spencer@nsconferencecentre.co.uk Or by post: North Staffs Medical Institute, Hartshill Road, Hartshill, Stoke-on-Trent ST4 7NY Views expressed are solely those of the author(s) and do not reflect the views of the Midlands Medical Journal. All material herein copyright reserved, Midlands Medicine Â©2016.

Volume 28, No 2, October 2016

EDITOR'S NOTES Once again, I suspect, this issue of Midlands Medicine finds its way onto your mat somewhat late. But I hope you’ll agree that the wait has been worth it. Much of what has been included has only become available for publication during the month of October and the concentrated timelines do mean that getting really upto-date material into the journal becomes a little selfdefeating in delaying publication: I hope you will not mind, but instead relish the broad depth and range of content contained within the covers.

The North Staffordshire Medical institute has as one of its founding tenets the support of medical research, particularly locally in Staffordshire. We were delighted to host a conference: Healthcare in Staffordshire; Strengthening Partnerships Research Conference earlier this month and I am delighted to be able to bring you the submitted abstracts in this issue of the journal; they display and admirable range of interest and innovation, please do look through and be encouraged regarding the current state and the We start this edition with a heartfelt ethical piece future of medical research in our local area. exploring a really difficult area of assisted conception and the appropriate handling of embryos in those very From science of the experimental sort we move to what difficult situations where the parties to the process fall can be learnt from clinical observation by presenting into dispute. As it states below, the views expressed a case report of a rare side effect of a biological antitherein are those of the author and not of Midlands cancer agent. Some of the lessons are likely to be Medicine or the NSMI. This allows Dr Crews the space generalisable. to develop his argument. Quite where you feel you stand as you start and where you find yourself at the We continue several rich veins in reportage with end, I don’t know, but some appreciation of how blunt news, developments and updates, including getting to an instrument the law can be and just how difficult know how Kevin greaves’ role as a physiotherapist is and emotive human wants and feelings can be will evolving as his career progresses. In his account many very likely visit you if you read this paper. a paradigm (shift) might be seen. Much has happened since May. Indeed May has happened to us and Cameron has withdrawn for us. Jeremy Hunt has stayed resolutely put and resolutely unbending in his desire to impose new terms and conditions of service on the junior doctors still willing to work for the NHS. Enough from me here as Ian Thornflesh will take up the reins of this and the other hot socio-political topic of the season in his editorial piece.

Once again I find myself indebted to Oluseyi Ogunmekan for the quiz, specifically themed this time on diabetes mellitus. The range and amount of content of the material that appears in this journal is very largely a matter of what is submitted. There remains the possibility of a paucity of contributions and a consequent ‘slim’ edition of the journal at any point. Also, editions are harder to produce on time if contributions hoping to catch an edition are late. As Editor, I would like to encourage you to consider Midlands Medicine as a suitable vehicle for the dissemination of your interesting case, your QIP or your point of view.

After reproductive ethics and the socio-political aspects of NHS staffing we move on to continue our study of the vital pastoral responsibility there is towards students and others in our midst with Carol Gray’s article on recognising and supporting students with difficulties. Anyone who works with students, particularly medical students, should read this article. Until next time, Happy Reading!

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REGULATING REPRODUCTION William Crews, Junior Doctor I continue to discuss the ethical problems outlined in this case and argue that there were some crucial The Courts in Evans v Johnston were wrong to protect ethical wrongdoings, such as: his rights not to reproduce over her right to reproduce • Ruling by the Human Fertilisation and using the embryo to which they both contributed. Embryology Authority (HFEA) fails to recognise unique circumstances (such as Evans’ INTRODUCTION circumstances). SUMMARY THESIS

Natallie Evans, in October 2000, was diagnosed with • Ruling by the HFE Authority fails to outline multiple pre-cancerous tumours in both her ovaries, alternative plans of action in recognition of unique which had to be immediately removed. As surgery circumstances (i.e. alternative options apart from would result in absolute infertility, Evans agreed to freezing fertilized embryos). harvest some eggs which would be fertilized in-vitro • A significant lack of guidance and insufficient [IVF] with donated sperm from her partner, Howard time given to both Evans and Johnston during Johnston, to be stored for future use. This would be the process of consent, which is not congruent Evans’ only hope of having a genetically related child.1 with the sheer importance of the decision to be In May 2002, the relationship broke down and Johnston made along with the lifelong implications of that later requested that their embryos be destroyed. The decision. clinic subsequently informed Evans and Johnston that it was under an obligation to destroy the embryos. Although I believe there has been no breach of the law in this case, ethically there have been significant Evans began proceedings for an injunction to stop failures which should have been identified and acted the destruction of the embryos, which failed in both upon by thoroughly reviewing the legislation of the the High Court and Court of Appeal. Leave to appeal HFE Authority and the procedures which were in to the House of Lords was also been denied. Evans practice at the time. decided to take the United Kingdom to the European Court of Human Rights (ECHR), where judges further decided there had been no breach of her Rights, under articles 2, 8 or 14.3,4 This case creates several interesting ethico-legal considerations which I discuss in this paper. Initially, I will consider some of the legal aspects and argue that the Courts were right to find that; • An embryo has no rights to life (thus, no violation of Article 2 of the ECHR) • Johnston’s withdrawal of consent was not unlawful • Allowing him the right to veto fatherhood was not discrimination on the basis of sex or infertility (thus, no violation of Article 14) • A fair balance had been struck between the interests of Evans and Johnston in this case (thus, no violation of Article 8) Volume 28, No 2, October 2016

DISCUSSION In the Case of Evans v The United Kingdom, the Courts ruled that the frozen embryos had no right to life.5 Several viewpoints that argue against the Courts’ ruling surround the issue of potentiality. For example, the fact that frozen embryos are not yet implanted or lack any of the properties that afford them the title of being a ‘person’ is irrelevant, as they have the potential to develop these properties and “if an embryo has the potential to be a person with 'the right to life', the right to life should apply”.6 This argument seems to ignore the issue that there is no guarantee that any given embryo, whether created naturally or via IVF will continue to survive its long developmental journey - “approximately 30% of (naturally) conceived pregnancies will progress to live birth”7 and the failure rate of IVF stands at 68% for women at the optimum age.8 There seems little reason to give an embryo rights that it will have at a later stage, as it is likely never to reach that stage. 45

Supporting potentiality further raises the question of how far back these rights should be extended. In my opinion, if society upheld the potentiality theory, it would be totally irrational to also ignore the potential that sperm and ova have to develop. However, to respond to this, would result in the ban of all contraception in order to protect the rights of the sex cells, which is completely unfeasible in modern society.

use all their power to ensure Evans was granted the right to found a family in accordance with Article 12, as this was Evans’ last chance to have a genetically related child.

Nevertheless, empathising does not necessarily mean the Courts should have done everything in their power to ensure Evans’ needs were met, as to do this would be unrealistic, just as it would be unrealistic to give money to every needy beggar that one comes In response to the lack of a European consensus on an across, or give all one’s income to charity. If the Courts accepted definition of the beginning of life, the Grand were to stop the destruction of the fertilized embryos Chamber in the case of Evans, ruled that, “under following Johnston’s withdrawal of consent, the Courts English law...an embryo does not have independent would be acting upon Evans’ positive rights to found rights or interests and cannot claim...a right to life a family but at the same time acting against Johnston’s under Article 2. There had not, accordingly, been a negative rights not to found a family. breach of that provision.”9 Ultimately, positive and negative rights cannot coexist, since they are polar opposites.12 For the Courts to stop the destruction of the embryos would be against Schedule 3 of the 1990 HFE Act13, which outlines the issues regarding variation of withdrawal of consent and the Courts would have been defaulting on their Duty to act fairly in respect to Johnston - stripping him of his entitlement to veto legal fatherhood of any child resulting from the implantation of an embryo, made from use of his gametes. Furthermore, to disallow a male veto in this situation would, not only be against the Courts’ duty to act fairly, as Johnston was not acting unlawfully by withdrawing his consent, but would also be against that duty to act fairly in respect Secondly, it seems implausible that a non-implanted to gender (in accordance with Article 14). To disallow frozen embryo which cannot develop any further the destruction of the embryos would be classed as without implantation occurs be afforded the same direct sex discrimination against Johnston. rights as an already implanted embryo. (An embryo develops into a foetus at six weeks gestation.11) As Consider a different situation, where a male was previously mentioned, if the point that the developing involved in a serious road traffic collision, resulting cells have a right to life errs nearer to the last date of in serious damage to his reproductive organs and a legal abortion, the right to life can only rationally be substantial probability of the loss of his capacity to afforded to foetuses (and not to embryos or zygotes), procreate in the imminent future. In this situation, as six weeks gestation is closer to zero than it is to similarly to the Evans case, the option of IVF would be offered to the patient and his female partner. They twenty-four. both consent and fertilized embryos are created using Undoubtedly, it is part of society’s innate moral all the donated eggs and sperm. The male patient code that we sympathise with those in less fortunate undergoes surgery and loses all reproductive capacity, circumstances as ourselves, such as Evans, and it is the patient’s relationship with his female partner in accordance with these morals that we would give also breaks down and she withdraws her consent money to a needy beggar, or undertake fundraising to the donation of her eggs. In this case, the female events for charity, for example. Based on these partner would be in the realms of the law, considering principles, it would appear that the Courts ought Schedule 3 of the HFE Act and the fertilized embryos sympathise with this particularly ‘difficult’ case and would be destroyed. I agree with the Courts’ decision in this case that destroying the embryos was not in violation of the embryos’ right to life under Article 2, as embryos have no right to life. Furthermore, the potentiality viewpoint is irrational - although there is no scientifically proven time which an embryo or foetus should be afforded the ‘right to life’, the Abortion Act (1967)10 states an abortion must be carried out before twenty four weeks of pregnancy. It seems fair to assume that if UK Law allows termination of a pregnancy up to twenty four weeks, the point at which we afford the developing cells a right to life would err nearer to twenty four weeks than zero weeks gestation.

Midlands Medicine

This fictitious scenario, nevertheless realistic and possible, draws various parallels with the Evans case. In the fictitious case, if the female party has the right to withdraw consent, then Johnston also has this right in the Evans case without any discrimination on the basis of gender and without violation of Article 14. My argument that no gender discrimination has occurred is further highlighted by the ECHR Grand Chamber decision that when concerning the birth of a child, parallels cannot be drawn between a male and a female as the roles they play are totally different and therefore women require different treatment.14 I am in agreement that, when considering the act of giving birth, the female party has spent up to nine months’ gestation developing an intimate bond sharing her body with the unborn foetus, therefore the female has established a different role to that of the male. However, when considering the case of Evans, the fact that the embryos had not been implanted rebukes the argument of different roles – Evans and Johnston have equal roles, as the only action they have both undertook is the donation of their respective sex cells. No special bond between mother and embryo has developed which can differentiate Evans and Johnston’s individual circumstances. Although my overall argument does support the Courts’ decision in the case of Evans, another key factor of the discussion lies with the question of whether the legal framework of the IVF procedure is fundamentally flawed. It is arguable that the HFE Act policy does not take into account special circumstances, as absolute infertility, in the case of Evans, whereby Johnston’s withdrawal of consent ultimately led to the loss of her right to found a family under Article 12. For example, one may view the legal framework, especially that of the variation and withdrawal of consent under Schedule 3 of the HFE Act as justified when considering a couple undergoing IVF due to difficulties of natural conception with respect to either or both parties if this was not their last chance for a genetically related child. If the relationship broke down, either party may either undergo further IVF with a future partner or explore the possibility of using donor sperm or eggs (i.e.– they would still have future chances to parent a genetically related child). There appears to be a massive disparity between depriving a woman to have a genetically related child at any one point in time and depriving a woman to ever have a genetically related child. Volume 28, No 2, October 2016

Nevertheless, a contractual agreement was signed which stipulated the male and female’s equal rights to the embryos and the freedom to withdraw consent at any time. I consider analogies with other contractual agreements, when signing a rental agreement for a property, whereby the contract stipulates a thirty-six month minimum lease, for example. This stipulation may seem unreasonable, as how can anybody predict what circumstances one will find themselves in, ten, twenty or thirty months in the future. The contract does not take into account special circumstances, for example, an unforeseen job offer in the future, which involves moving to a different location. However, if one is not in agreement with the contractual stipulations, then consent should not be given or discussions around renegotiation of the contract should take place. I am aware it is unfeasible to draw comparisons with a woman’s right to found a family and signing a rental agreement, however, the basic principles still complement each other – if one does not agree with the terms and conditions of a contract, one has an autonomous right to decline consent to the agreement and/or renegotiate the stipulated obligations. When considering the ethical implications of the case, the HFE Act appears not to offer satisfactory support to individuals with special circumstances and may have defaulted on their ethical duty to Evans, for example, why was Evans not offered further options, such as the option to freeze unfertilized eggs? Similarly to my analogy of a future job offer implicating the contractual stipulations of a property rental, Evans would not have been able to predict that her relationship with Johnston would breakdown, however, situations like this are always a possibility. When considering somebody’s last chance, I advocate that it seems ethically appropriate to offer further options in the event that they are later needed. The option of sperm freezing for men (before surgery on a male with testicular cancer, for example) has been commonplace clinical practice for many years.15 It only seems ‘fair’ that Evans be offered the option, in order for her to have the option to fertilize these eggs at a later date with either the sperm from a future partner or donor sperm. In the event of this happening, withdrawal of Johnston’s consent would not have stripped Evans of her last chance to have a genetically related child. 47

Although there seems no ethical barrier to egg freezing (ultimately, it is ethically comparable with sperm freezing), the formation of ice crystals in the liquid within the egg can damage its structure, rendering it unusable.16 Therefore, the survival rates of fertilized eggs are much higher. At the point in time of Evans decision to freeze frozen embryos, egg storage was at an early, experimental stage and had not yet resulted in a single successful pregnancy in the UK.17 From my point of view, any potential survival rate of unfertilized eggs in storage is better than not having the option to freeze unfertilized eggs at all. However, “If Ms Evans had pushed … for egg storage that she would have been refused” based on the fact that to request such a procedure, as unfertilized egg storage alongside fertilized egg storage would raise a question of why Evans would want both options when she is in a stable relationship with Johnston.17

of unfertilised eggs may not have had sound clinical evidence, however, the risk of harm was no more than the alternative method of freezing fertilised embryos, if that failed for whatever reason.

Another ethical question that arises in this case surrounds the validity of consent provided by Evans and Johnston to use their respective gametes for fertilizing embryos. Evans and Johnston had approximately ninety minutes to consent to the procedure following the discussion that her ovaries would be removed, ultimately leaving her infertile.17 This raises the question of whether Evans and Johnston were in the correct mental state and had the time to fully understand the information that was given to them, in order to provide valid consent. It is common knowledge to health care professionals that “in cases of severe anxiety…such as when hearing bad news…a patient’s information processing may be totally I must question the completely irrational nature of this impaired.”19 Furthermore, the HFE Authority’s Code statement, in respect to who has the right to refuse a of Practice states that, “centres should allow people procedure, providing the agent involved is competent seeking treatment, people considering donation and to make a well informed decision about an ethically those seeking storage sufficient time to reflect on their and clinically acceptable procedure, of which the decision, before obtaining written consent…”20 agent can finance? Surely any refusal of this procedure would be breaching both Article 8 and Article 12? I It appears totally unreasonable that Evans and understand that clinically, at the point in time that Johnston were given such a short time to make such Evans found herself in this situation, determining the serious decisions with so many future implications. safety of frozen unfertilized eggs required more clinical There appeared to be no time for quiet reflection, trials, however, even if the procedure of freezing eggs away from the clinical setting or for either party to was deemed unsafe, who would it be harming? As have counselling alone, in which doubts about the already discussed, an embryo has no right to life, as stability of their relationship might have been raised. it is simply a frozen entity, so it certainly would not This not only seems to break the HFE Authority’s be harming a frozen egg. The only agents it would be Code of Practice, but also does not appear to comply harming would be Evans and Johnston in respect to with the HFE Act, that the individual seeking their mental, social and spiritual wellbeing if the eggs infertility treatment services “must be given a suitable did not survive. However this risk of harm to Evans opportunity to receive proper counselling.”21 If these and Johnston is no more or less than if the procedure options were offered to Evans or Johnston, it may have of freezing embryos did not succeed for whatever become apparent that Johnston did not in fact want to reason and as Evans would have both the frozen eggs give consent to the donation of his sperm and Evans and frozen embryos, she would have further chances could have made alternative arrangements – to have of having a genetically related child at some point in her gametes fertilized by donor sperm, for example. the future. Despite these apparent insufficiencies, I argue that For example, in the case of paediatric healthcare, regardless of the timeframe in which Evans had to many illnesses, especially rare paediatric conditions, make the decision, this was her final chance to have are treated with drugs that are unlicensed for the a genetically related child. As freezing fertilized eggs paediatric population.18 Nevertheless, the risk of harm was her only option, Evans would have consented to the children taking these drugs is minimal, as the regardless of whether Johnston consented or not, as drugs have been tested through clinical trials on the there was always the option of donor sperm. Therefore adult population. Similarly to the Evans case, freezing the limited time in which she, alone, was given to 48

Midlands Medicine

provide her consent, actually seems irrelevant, as she would still have consented even if the particular situation had complied with both the HFE Authority’s Code of Practice and the HFE Act in respect to time and counselling. However, it does seem that Johnston’s consent may not be valid. The fact that his initial consent was later withdrawn indicates that he was potentially rushed into making a decision and his overwhelming empathy for the situation Evans found herself in clouded his judgement. However, presuming Johnston declined consent initially and Evans had used a donor to fertilize her gametes, there would still be a possibility, albeit reduced, that the donor would withdraw his consent at any time until ‘use’ of the embryos.22 Therefore, even if donor sperm was used, Evans might still have found herself in the same position. CONCLUSION This case raises interesting ethico-legal issues, however it seems clear to me that there has been no legal wrongdoing and I support the decisions of the various Courts that there had been no breach of Convention rights. Despite this, the fact that Evans has no further chances of giving birth to a genetically related child undoubtedly generates a large amount of public sympathy. However, it is totally unfeasible to expect a Court of law to base its decisions entirely on morals and how much empathy they feel towards each particular case. The law is in place to avoid bias of key issues and to ensure that society is subjected to the same rules and regulations regardless of race, religion, social class, personal beliefs etc. Without this absolutist stance, there would be countless ‘exceptions to the rule’ which would lead to an unbalanced, confusing and inconsistent approach within the Courts.

of healthcare professionals, by not offering Evans the opportunity to freeze unfertilized eggs. Healthcare professionals are bound by a duty to provide all necessary information to the patients and although at the time the option of freezing unfertilised eggs had a limited evidence base, the fact that this was Evans last chance to have a genetically related child requires special consideration and I argue she should have been offered further options to ensure that her probability of founding a family, under Article 12 of the ECHR was maximised. Furthermore, the validity of Johnston’s consent in this situation must be questioned. However, even if he had declined and Evans had used donor sperm, there is no way that Evans could categorically predict that the donor she chose would not withdraw consent and it still remains that this was Evans’ last chance. I continue to argue that the fundamental flaw ultimately falls upon the fact that Evans was denied the right for alternative procedures, such as the freezing of unfertilized eggs, as she would still have more than one chance in the event that something went wrong the first time round (ie – the withdrawal of consent of the sperm donor, whether that donor was Johnston or another agent).

REFERENCES 1

ECHR. Case of Evans v The United Kingdom Application Number 6339/05, paragraph 8

2 ECHR. Case of Evans v The United Kingdom Application Number 6339/05, paragraphs 12&13 3

Smajdor A Deciding the fate of disputed embryos:ethical issues in the case of Natallie Evans Journal of Experimental & Clinical Assisted Reproduction (2007) Vol 4 p2 doi:10.1186/1743-1050-4-2

If the Courts were to agree to Evans’ demands not to destroy the embryos they would be supporting her positive rights, but at the same time, disregarding Johnston’s negative rights to veto fatherhood. As there has been no legal wrongdoing, the Courts had to adopt a fair and sensible approach which balances ECHR (1950) www.echr.coe.int/Documents the competing interests of both Evans and Johnston. 4 /Convention_ENG.pdf Nonetheless, the case of Evans is unique, and when Case of Evans v The United Kingdom considering the ethical issues, I strongly believe that 5 Application Number 6339/05 there has been a major breach in the ethical duties Volume 28, No 2, October 2016

6 Poplawski N & Gillett G 16 Egg-freezing technique 'is safe' (2008) www. Ethics & Embryos news.bbc.co.uk/1/hi/health/7458415.stm Journal of Medical Ethics (1991) Vol 17 pp62 69 doi:10.1136/jme.17.2.62 17 Sheldon S Evans v Amicus Health Care: Revealing Cracks 7 Macklon NS, Geraedts JP and Fauser BC in the “Twin Pillars”?’ Conception to ongoing pregnancy: the `black Child & Family Law Quarterly (2004) Vol 16 box' of early pregnancy loss Human Reproduction Update (2002)Vol 8 pp437-52 pp333-343 doi:10.1093/humupd/8.4.333 18 Choonara I, Longworth A, Nunn A and 8 HFEA statistics available at: www.hfea.gov.uk/ Turner S ivf-success-rates.html Unlicensed and off label drug use in paediatric wards: prospective study BMJ (1998) 9 ECHR. Case of Evans v The United Kingdom Vol 316 pp343-5 doi:http://dx.doi Application Number 6339/05, paragraph 54 org/10.1136 bmj.316.7128.343 10 The Abortion Act (1967) 19 Department of Nursing Education and Research City of Hope National Medical Center(2005). ‘Textbook of Palliative Nursing’ 12 Landauer J and Rowlands J (2001) OUP, p.70 ; 0199748160, 9780199748167 Importance of Philosophy ‘Positive Rights’ 11 Pregnancy Timeline www.news.bbc.co.uk/1/ hi/health/4121411.stm

13 Human Fertilisation and Embryology Act (1990) 14

ECHR. Case of Evans v The United Kingdom Application Number 6339/05, paragraph 20

HFE Act (1990) Paragraph 7.4

HFE Act (1990) Schedule 3, para 3(1)

HFE Act (1990) Schedule 3, para 6(3)

15 Dillon K and Fiester A (2012) Human Reproduction. Sperm and oocyte cryopreservation: comprehensive consent and ADDRESS FOR CORRESPONDENCE the protection of patient autonomy william.crews@nhs.net doi: 10.1093/humrep/des290

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IN OUT, SHAKE IT ALL ABOUT Ian Thornflesh, Commentator That title applies equally to two things in the air this autumn. One is the Junior Doctors’ dispute with their employers (or NHS employers, or the government or personally with Jeremy Hunt). The other is Brexit. Both are likely to change our NHS. NOT IMPOSING By failing to be deposed in the cabinet reshuffle following David Cameron’s resignation and Theresa May’s accession, Jeremy Hunt has become one of the longest serving Health Ministers since the Second World War. This has, no doubt, strengthened his hand and given him confidence. On the other side there has been renewal. Last time this journal went to press junior doctors were on strike and there was no end in sight to the bitter dispute. Then a deal was agreed and this was put to a vote over the Summer. Following the rejection of the deal he reached with Jeremy Hunt in a ballot of junior doctors, and medical students in their last two years of study, an electorate of about 37,000, by 58% to 42%, the then chair of the BMA Junior Doctors’ Committee (JDC), Johann Malawana, stepped down. Ellen McCourt, an Emergency Medicine trainee in Yorkshire and Humber, was unanimously elected to replace him.1 She immediately announced a series of signicant strikes designed to dent the smooth running of the NHS by causing actual disruption and thereby political consternation. But in the end they haven’t materialised. It seems that despite the junior doctors’ appetite for a fight expressed in their clear rejection of the agreed deal their support behind the scenes and their own true appetite may have waned. Perhaps there is also the sense that the public is no longer quite as with them as they seemed to be before. There were mutterings and murmurings about patient safety before the first due strike. Perceiving something about the support was not quite the same, the JDC called off the strike. Since much of the argument had been about too little notice, too little time to prepare cover and contingency arrangements, calling off the first strike allowed the junior doctors to appear responsible and magnanimous. Somehow the calling off of the first set of strike days has elided in the whole series of strikes being put in abeyance. So we find ourselves in a pretty strange place where there is a series of planned strikes that will not take place and a clear programme from the government to introduce (definitely not ‘impose’) the new junior doctors' contract that was agreed with the previous incarnation of the JDC but dismissed by a

Volume 28, No 2, October 2016

vote of the membership. The BMA’s current, extremely limp, alternative angle of attack is to suggest that letters be written to Chief Executives stating that “The BMA does not accept the new contract … and we continue to call for the imposition of the contract by Employers to stop while further negotiations take place…” Inaction at this time will allow the insidious and pervasive introduction of the contract and before you know it it will be fait accompli. Interesting times. HARD BREXIT Since the last issue of Midlands Medicine the United Kingdom of Great Britain and Northern Ireland (UK) has voted in a referendum to leave the European Union (EU) by a majority of 52% to 48%. As things currently stand, the government has changed, all talk of trying the referendum again has more or less been buried, and the now talk is of how to manage Brexit. Probably a majority of healthcare workers will have voted to remain, but like the Scots, they are now having to live with the democratically arrived at decision to leave. Because leaving the EU was deemed uncontemplatable by the government, no actual strategy for leaving has been developed. We have therefore been cast into the complex mix of certainty that England will leave the EU (I say England since there now exists an albeit remote possibility that Scotland will depart the UK and try to join the EU as an independent nation) but uncertainty about how and when. But we do now know that we are likely to start the Brexit process formally by triggering Article 50 of the Lisbon treaty in the Spring of 2017. That there are possible implications for the workings of the NHS is a given, though quite what the consequences might be are not clear. The Royal College of Physicians, among others, have begun to consider what areas might be affected.2 To start with: NHS funding, and not necessarily in a good way. The NHS is publically funded from a portion of tax receipts which are themselves a proportion of GDP. If GDP rises, the actual amount of money available for the NHS rises. But the signs are not necessarily good for the economy despite likely short term boosts due to the effective devaluation of sterling causing a drop in a cost of our exports and a rise in tourist spending to come next Summer because after that the cost of our imports will feed through to our daily costs both of directly imported products and raw materials, raising our manufacturing costs, and losing

us the pricing advantage that sterling devaluation might have temporarily brought us. Predictions by Remainers, though likely unreliable in their details, are likely to contain at least a grain of truth, in which case Brexit seems unlikely to mean more money for the NHS: ironic since there was an implication that Brexit would liberate EU membership fees to be diverted to the NHS. EU nationals make a significant contribution to staffing the NHS in doctors, nurses and allied health professionals. Over 10% of our NHS doctors are from the EU.2 This is made possible both due to the single market principles covering the free movement of goods, services and people, and mutual qualification recognition. If we cannot find a way to mitigate our exit from the single market and our obsession with exerting control over our borders then there is certainly an implication that we may struggle to staff our hospitals. It is at this point that we start to see the ingredients of an even more understaffed (specifically under-doctored) NHS coming together: if the implementation of an unpopular Junior Doctors’ contract chases off a good number of our home grown doctors whilst a quagmire of new bureaucracy and an unwelcoming attitude mean we cannot so easily plug the gaps with overseas doctors, then we are potentially going to be stretched quite thinly covering the increasing NHS workload. Just as well, then, that we’ll be in a position to ditch the EWTD! Wider-reaching consequences of these changes in our relationship with Europe and the wider world may

occur in the fields of academia and medical research. If we become perceived as a less open, less welcoming and less engaged society, academics may be less attracted to come here. Throw in the exchange rate considerations and they might be rightly put off even considering the UK as a suitable place to push on with a medical research academic career. And there is another consideration: grant funding. The EU is a significant sponsor of scientific, including biomedical, research; as we slip our EU bonds, that funding stream is going to dry up. Less research, less development, fewer bright minds means that we risk slipping from one of the word’s great innovating nations to a consumer of other people’s products - more than is already the case. Brexit, it seems, we are stuck with, so we need to get on and make a success of it. Better start by fixing that Junior Doctors’ contract to make it attractive for our trainees to stay here.

REFERENCES 1 www.bma.org.uk/news/2016/july/bma-junior- doctors-committee-elects-new-chair

2 Dacre J, Charlesworth A, Merkel B, Goddard A and Pritchard S What happens next? The consequences of Brexit Commentary (RCPL) October 2016 Issue 5 pp13-5

Midlands Medicine

RECOGNISING AND SUPPORTING STUDENTS WITH DIFFICULTIES Carol Gray, Director of Professional Development and Welfare Keele University Medical School INTRODUCTION

of this both emotionally and in practical terms can be immense. This happens to a cross section of students, both graduates with older parents but also undergraduates from communities where a strong sense of family duty exists. Parents may be very unaware of the impact of their demands after all, their son or daughter is not at work, is â&#x20AC;&#x2DC;only a studentâ&#x20AC;&#x2122; and so must be able to spare the time to help out. The massive workload of the medical course may not be clear to them.

This article continues the series on Mentoring, Appraisal and Support. In the first article we heard about the value of mentoring in general and specifically the role of the Professional Development Tutor in supporting undergraduate medical students. In this article we will discuss what types of difficulties are commonly experienced in our student body and how this manifests. Although this is based in the main on our undergraduate experience, many of the issues that arise with our junior postgraduate colleagues There seems to be a significant rise in mental illness (especially if these have not been identified before amongst medical students and indeed in medical staff. qualification) do mirror these. Some of the strategies This has been so evident that the GMC has issued that are used to help students are also outlined. guidance to medical schools about this.1 There has been much research that suggests that 20% of medical staff THE DIFFICULTIES OUR STUDENTS EXPERIENCE suffer from mental ill health but it is acknowledged that disclosure is still a significant issue due to the fear of Not surprisingly, our students are as vulnerable as any stigmatisation. The GMC guidance talks about stress, other young person to all of the difficulties that life mild to moderate problems and serious ill health can offer. They have difficulties with their families, and acknowledges the topics of eating disorders and be it parents or siblings, and their own relationships, substance abuse separately. It is our experience that with friends or partners, can cause problems. They the prevalence of severe mental illness is unchanged can have physical and mental health issues, or may amongst our students and probably occurs in less have a recognised disability. Money is often very than 1%. However, the reporting of stress or anxiety tight. Some struggle with the course academically, and mild-to-moderate depression is frequent and we despite having high A level grades or a good degree. feel there is evidence of more students with eating This is familiar territory to anyone already dealing disorders. Consequently, much of our work revolves closely with students, however, it may be of value around helping our student body understand that to pick out a few areas that seem to be more recent such things are commonplace, manageable and no bar phenomena and perhaps may surprise those of us to practising as a doctor. who were medical students a long time ago. A small but significant proportion of our students are acting as carers for a member of their family. This can vary between having to offer almost constant emotional support to a parent, to living at home and providing hands on care. In extreme circumstances this can lead to a student being phoned repeatedly during the day (one of the perils of mobile phone technology) or needing to go home either daily or every weekend to cook, clean, nurse, etc. The burden Volume 28, No 2, October 2016

A third, new, phenomenon is the risk posed to our students by the use of social media. Students are at risk both from their personal use of media (e.g. posting intimate or offensive material without considering the consequences) and from social media as a channel for bullying, harassment or, in extreme cases, stalking. Protecting students from making these types of mistakes and supporting them when they are suffering at the hands of other users has become a much more significant task over the last few years. 53

GETTING TO KNOW ABOUT DIFFICULTIES

SUPPORT OFFERED

In an ideal world, students self-declare difficulties and seek to get some help as soon as they are aware of their problems. Some illnesses will be disclosed on the Admissions form and then the student will be assessed by Occupational Health as part of the admissions process. Some chronic health problems, including mental health problems, may be considered a disability under the Equality Act (usually if the condition has lasted over a year and interferes with everyday living activities). Students may then register directly with the Disability Service of the central university who then notify the School Disability Link Officer. Students may disclose to friends about some difficulties and may then be encouraged by their friends to access the School Student Support Service as a starting point for making the School aware. It is not unusual for students to attend the service to report their concerns about a friend and to get advice.

There is a very considerable range of support for students and doctors with difficulties. Discussion of the full range is beyond the remit of this article. Some of the support offered by the School of Medicine and by Keele University will be covered. It is worth commenting that the support offered at Keele is open to postgraduate as well as undergraduate students. Many qualified doctors will be registered for postgraduate studies and may overlook the fact that this may be a way to access help for ongoing troubles, which they might feel is preferable to accessing support offered by their Trust or the Professional Support Unit of Health Education West Midlands.

Students may disclose difficulties to staff members that they come across in the course of their studies, particularly if they perceive them to be supportive or are in a support-giving role. Obvious choices are their Professional Development Tutor, Problem Based Learning tutor or in later years an Educational Supervisor. However, all staff can be, and often are, approached including skills tutors, lab technicians or administrative staff. Consequently, those staff need to know who to approach for advice about these disclosures and at Keele they are encouraged to go to any member of the student support team. Students who do not disclose are, of course, the greatest challenge. This is often due to fear of the consequences, but may be due to lack of insight. In many students, however, their personal difficulties lead to problems on the course. These may be academic but are also often manifested in subtle behavioural changes. These may include poor timekeeping or attendance, disengagement with the course, poor participation in group work, etc. These latter manifestations are commonly regarded as markers of poor professionalism but often are due to underlying difficulties. This is the main reason that the School looks for these patterns and is keen to be informed of apparently minor matters. If these are persistent over time, it may mean that the student needs help and support. It may be that this allows the student to accept that their problems do have an effect on their career and need to be addressed. 54

Family matters can be very difficult to discuss and there can be a sense of betraying the family causing the stress. To be torn between family and career is a fundamental issue and is one of balance, a balance that we all seek in our lives. Sympathetic support is the key in this situation and it is important that the individual reaches their own conclusions about this. Some with this difficulty may access the confidential School Student Support Service. This may serve the purpose of helping the student face up to the issue (and on occasions being reminded of the consequences if they do not resolve the situation, especially if they are failing exams). It is also a safe place to think and test out possible solutions. Some will prefer to be seen by a counsellor, available free of charge at the University. In this instance there will be much less guidance as to the solution - the individual will need to reach the answer themselves. Either way, this takes time and patience to resolve; the School service can see an individual as much as they feel necessary to achieve this. The perceived stigma of mental health is a barrier to accessing help but much is available when the individual acknowledges they do need support. The first recommendation is to see their general practitioner as they will be the bedrock of the required care. Keele University has acknowledged the increasing issue of student mental health and there is a mental health team of experienced health professionals who have excellent links to the local services. They offer a superb service and can intervene immediately in times of crisis. The University has a Critical Incident Support mechanism available in working hours and Nightline ensures that there is almost always someone to talk Midlands Medicine

to in emergencies. If there are very serious problems with either physical or mental health in students, leave of absence can be granted using the Health and Conduct Committee procedures and with the support of Occupational Health. In our experience, the vast majority of our students with any level of mental health issues can (and do) successfully complete the course. The key is recognising that help is needed and accessing this.

staff not to divulge the whereabouts of a student, accessing the support of ASK (the Student Union advice service which has good legal expertise) to involving the police. For the individual, knowing that the School is “on their side” can be important and may be all the intervention that is required.

The use of social media is so commonplace now that it is perhaps inevitable that increasingly it is a source of difficulties either caused by unwise postings or from being the victim of harassment. The Medical School has had guidance in place for some years on the use of social media, and organisations such as the BMA and the GMC have issued this as well. Whilst recognising the value of these media, most advice can be paraphrased as “don’t post anything you wouldn’t want a patient/your granny/the boss to see”. This advice is given to students in their first week. Even so, we receive reports of a variety of unwise postings (frequently from other students) that range from mildly unadvisable to the altogether more serious. Often a gentle reminder of the advice suffices but more serious action has had to be taken on occasions. Mobile phones, emails and social media sites can also lead to students being harassed in a variety of ways. This ranges from family members who call too frequently through to ex-partners who are issuing threats via social media. Support in these situations is dependent on the problem but can include instructing

Dr Carol Gray Director of Professional Development and Welfare Keele University School of Medicine Keele University STAFFORDSHIRE ST5 5BG

Volume 28, No 2, October 2016

ADDRESS FOR CORRESPONDENCE

c.a.m.gray@keele.ac.uk REFERENCES 1

General Medical Council, 2013. Supporting medical students with mental health conditions. London: GMC

FURTHER INFORMATION www.keele.ac.uk/student-ser vices-director y/ bycategory/healthandwellbeing www.keele.ac.uk/medicine/studentsupportservices

ABSTRACTS OF WORK PRESENTED AT THE HEALTHCARE RESEARCH IN STAFFORDSHIRE CONFERENCEFUNCTIONAL RECOVERY AFTER STROKE SELF-MANAGEMENT SUPPORT FOR PEOPLE AFFECTED BY MULTIPLE SCLEROSIS: STUDY PROTOCOL Badrieh Alabbad , Helena Priest , Clive Hawkins , Susan M Hunter 1

1, 3, 4

Insitute for Science and Technology in Medicine; School of Psychology; School of Health and 4 Rehabilitation; Institute of Applied Clinical Sciences (IACS) – Keele University Contact: s.m.hunter@keele.ac.uk

BACKGROUND Self-management programs help patients manage symptoms of long-term conditions, such as Multiple Sclerosis (MS), and contain utilization of health-care resources; people with multiple sclerosis (PwMS) manage day-today effects of MS, but the optimum level and type of support to self-manage is unknown. This study aims to develop a ‘best-practice’ model of self-management for PwMS based on: evidence from literature; views, experiences and perceptions of PwMS and health professionals with self-management experience. METHOD Following systematic review of literature, three studies will be undertaken: 1: Field study. Purpose: explore self-management support for PwMS in three contrasting service settings: a) NHS hospital-based; b) NHS community-based; c) charity registered community-based. A separate group interview with each healthcare team will explore underpinning philosophy, practice, and content of services provided to support self-management for PwMS. Specific components of each service will be observed to gain further insights. Thematic and content analysis will be undertaken to identify individual and common approaches to delivering self-management support for PwMS. 2: Individual interviews with PwMS. Purpose: explore experiences, expectations and perceptions of PwMS in self-managing MS. Individual semi-structured interviews will be conducted with 12 PwMS from the three services in study 1; purposive sampling will ensure that both progressive and remitting types of MS are represented. Thematic analysis will be undertaken to identify individual and common experiences and expectations of self-management support. 3: Consensus study. Purpose: develop a ‘best practice’ model of self-management support for PwMS based on literature, and data from studies 1 and 2. Following synthesis of data, a model of perceived best-practice of selfmanagement of MS will be drafted. Six health professionals and six PwMS, all with experience of self-management, will discuss and agree content of a ‘best-practice’ model for use in a future trial. 56

Midlands Medicine

PREDICTION OF ARM FUNCTIONAL RECOVERY AFTER STROKE 1

Ahmad AL-Shallawi , Dimitra Blana , Anand Pandyan

1, 2

Institute for Science and Technology in Medicine, Keele University, UK; School of Health and Rehabilitation, Keele University, UK Contact: a.n.s.al-shallawi@keele.ac.uk

Loss of arm function after stroke is common and this can severely affect a person’s life. Predicting arm recovery after stroke can be very beneficial; it can help with planning the rehabilitation of the stroke patient. The study’s aim is to predict which patients recover arm function in the late stages after stroke based on the measurements taken immediately after a stroke. For this study arm function will be measured using the Action Research Arm test (ARAT). A sample of secondary anonymised data was adopted from a previous study reported by Church et al., (2006). The data represent a sample of measurements of upper limb functional ability of patients in stroke over three time points (within a week of a stroke, 4-weeks and 12-weeks after stroke). The first step was to identify a cut-off point that was indicative of recovery potential at 12 weeks after stroke. This was done using a hierarchical clustering method. A logistic regression model was then used to estimate the probability of patient recovering or not using commonly used clinical measures (NIHSS score, Frenchay Arm Test (FAT) and Motricity Index (MI)). The ARAT cut-off point to differentiate function vs. no function was 7 out of 57. The logistic regression model demonstrated that the NIHSS and FAT were significantly able to classify probability of recovery [sensitivity = 0.90; specificity = 0.93; p value = 0.01]. Although the model developed appears to be good, more work is needed as the errors associated with the model we have developed are unlikely to be clinically acceptable. REFERENCES Church, C. et al., 2006. Randomized controlled trial to evaluate the effect of surface neuromuscular electrical stimulation to the shoulder after acute stroke. Stroke, 37(12), pp.2995–3001.

Volume 28, No 2, October 2016

SENSORY STIMULATION OF THE FOOT AND ANKLE EARLY POST-STROKE: A FEASIBILITY STUDY (MOTASTIM â&#x20AC;&#x201C;FOOT) Alison Aries 1,2 Istitute for Science and Technology in Medicine, Keele University

School of Health and Rehabilitation, Keele University Contact: a.m.aries@keele.ac.uk

INTRODUCTION Stroke affects 15 million people in the world and approximately 150,000 people in the United Kingdom annually. Walking is a priority for many stroke survivors. Sensory stimulation/retraining to the lower limb post-stroke is a part of routine clinical practice, however, insufficient information is currently available to either support or refute this practice. The importance of sensory input to influence motor function is now widely agreed upon in order to perform voluntary activity with good coordination and control. Increasing the ability to feel may, therefore, help a stroke survivor to balance and walk. Three types of rehabilitation strategies have been proposed to facilitate successful goal attainment: priming, which prepares the sensorimotor system for motor function; augmenting techniques, to enhance the sensory input during activity; and task specific practice. Protocols for Mobilization and Tactile Stimulation (to prime the sensory system), wearing textured insoles (to augment) and task specific walking training will be developed and explored in the MoTaStimFoot feasibility study. METHODS A mixed-methods design is being undertaken, involving a randomized, single blinded trial and qualitative methods (diaries and focus groups) [Figure 1]. CONCLUSION At the present time there is insufficient evidence available to enable informed decisions to be made regarding the place for sensory stimulation/re-education to the lower limb post stroke in clinical practice; the MoTaStim-Foot feasibility study is an important step towards evidence-based rehabilitation post-stroke. ACKNOWLEDGEMENTS This study is being undertaken as part of a National Institute for Health Research (NIHR) Clinical Academic Fellowship. Norwich Clinical Trials Unit (NCTU) are also supporting the trial. The author would like to thank her supervisory team and NCTU for all their support and the NIHR for this opportunity.

Midlands Medicine

BASELINE

QUANTITATIVE STUDY

Mobilization and Tactile Stimulation (MTS) Group: Up to 60 mins MTS plus 30 mins of Task Specific Gait Training (TSGT), 20 sessions within 6 weeks.

Clinical measurements*

RANDOMISATION (immediately post baseline clinical measurements)

Textured Insoles (TI) Group: TIs plus 30 mins of Task Specific Gait Training (TSGT), 20 sessions within 6 weeks

Acute blood flow studies* before and after one treatment SELECTIVE CLINICAL OUTCOMES after 5,10 & 15 interventions: • Pressure under feet • Ankle ROM d/flexion / p/flexion • Sensory threshold testing

OUTCOME Clinical outcomes*, within 7 days of completing the 20 sessions

FOLLOW UP

* Please note blood flow studies are supplementary, and subject to availability of therapist and equipment.

Clinical outcomes*, within one calendar month (±7 days) after the completion of the intervention

-------------------------------------------------------------------QUALITATIVE STUDY Daily Diary record kept throughout intervention and follow-up (n=34)

Focus group lasting up to 90 mins with 6-8 participants

Figure 1: Overview: Sensory stimulation of the foot and ankle post stroke: A feasibility study (MoTaStim-Foot)

Volume 28, No 2, October 2016

BEHAVIOURAL ANALYSIS OF GROUP-BASED WEIGHT MANAGEMENT INTERVENTIONS 1

Sonia Begum , Dr Rachel Povey , Dr Christopher Gidlow , Dr Naomi Ellis , 1

Dr Lynne Duval , Victoria Riley 1

Faculty of Health Sciences, Staffordshire University Contact: sonia.begum@research.staffs.ac.uk

The Healthier You: NHS Diabetes Prevention Programme (DPP) is an evidence-based behaviour change programme, that has been currently developed and launched in the UK to prevent the at-risk population from developing Type 2 Diabetes, which in itself has major health, financial and economic implications. Weight management (WM) programmes will be key components in DPP services as one of the core goals of the DPP is weight loss. The aims of this research is to understand the range of different factors that affect uptake of these programmes, and factors which will impact retention levels. The behavioural analysis involved classifying programme characteristics linked with uptake and retention from the relevant, identified quantitative studies, and identifying Behaviour Change Techniques (BCTs) that are present in group-based WM programmes with high and low retention. Preliminary findings include: improving health was the main reason why participants attended WM interventions, whereas denial of being overweight was the main reason for non- participation. The incompatibility of the intervention with participantsâ&#x20AC;&#x2122; lives, was the main barrier during intervention, social support was the key reason why participants decided to continue to attend and most studies stated the need for ongoing support for participants after the intervention had finished. This research will help inform practice and contribute towards developing and improving the DPP by providing recommendations for specific techniques to maximise uptake and retention.

Midlands Medicine

A CLINICALLY APPLICABLE NON-INVASIVE METHOD TO ASSESS THE MECHANICAL PROPERTIES OF HUMAN HEEL PAD Sara Behforootan1, Panagiotis Chatzistergos1, Nachiappan Chockalingam1 and Roozbeh Naemi1 1

Faculty of Health Sciences, Staffordshire University, Stoke-on-Trent, UK Contact: Sara.behforootan@research.staffs.ac.uk

Introduction: There is an increasing awareness that pathological conditions such as diabetes or heel pain affect the biomechanical properties of the soft tissues of the sole of the foot. Changes in the mechanical properties of planar soft tissue can make it more vulnerable to trauma. However the exact cause and the implications of altered tissue properties are not yet understood. To address this question there is a need for non-invasive methods to quantitatively assess the mechanical properties of plantar soft tissue in the clinic. Aim: To develop a clinically applicable non-invasive method to assess the mechanical properties of human heel pad. Method: An ultrasound indentation device was manufactured for the non-invasive mechanical testing of the heel pad. Moreover an automated algorithm was developed to design subject-specific models of the heel pad based on the results of the indentation tests and to inverse engineer their mechanical (visco-hyperelastic) properties. This method was used for 5 volunteers and its accuracy was assessed against actual lab based measurements. More specifically, two validation tests were performed: a) for the first test the virtual heel pad models were utilised to simulate compression under controlled conditions and to predict reaction force for known values of deformation b) for the second test, the models were used to simulate walking and the predicted plantar pressures were compared to in vivo measured values. Results: The average difference between the numerically against the in vivo measured values was 4.72% for the reaction forces and was 3% peak plantar pressure. Conclusions: The validation showed that the method is reliable and accurate enough to assess the mechanical properties of the plantar soft tissue. The technique presented here was developed for the heel pad, however with minimal modifications it can also be used for other areas of the foot or for other musculoskeletal structures.

Volume 28, No 2, October 2016

INVESTIGATION OF THE MECHANICAL PROPERTIES IN OF PRETERM PREMATURE RUPTURE OF MEMBRANE (PPROM) 1

1, 2

Sudeshna Bhunia , Shaughn Oâ&#x20AC;&#x2122;Brien , Pensee Wu , Ying Yang 1

Institute for Science and Technology in Medicine, School of Medicine, Keele University, UK 2

University Hospital of North Midlands NHS Trust, Stoke-on-Trent, ST4 6QG Contact: s.bhunia1@keele.ac.uk

Preterm premature rupture of membranes (PPROM) (â&#x2030;¤ 34 weeks) is a leading cause of premature birth. Despite of advances in research, improvements in perinatal care and high quality treatment strategies, preterm birth remains a major concern worldwide as the greatest contributor of perinatal and neonatal mortality and morbidity. The underlying mechanism of PPROM remains to be elucidated. The human fetal membrane consists of amnion and chorion membrane. The cellular structure of them and the proteins synthesized by these cells maintain the mechanical integrity of the fetal membrane. We hypothesized that there may be weak region in fetal membranes which trigger the premature rupture and biochemical factors interact and interplay toward tissue damage. The aim of this project is to explore the new mechanical assessment protocol involved in PPROM, and to develop a better technique which may lead to improved diagnostic kits and potential prevention of PPROMs. Fetal membranes were collected from full term and preterm deliveries following PPROM and mechanical testing was conducted by using the ball indentation technique. Biochemical testing was performed on these membranes to study MMP-9 & 13 expression levels, alongside progesterone and apoptosis biomarkers by immunostaining. Optical coherence tomography was used for recording the tissue thickness and microstructure. Our study has confirmed that ball indentation technique is a convenient, flexible and bio mimic protocol tool for mechanical assessment. Membranes from ruptured areas of preterm membrane were mechanically weaker than their corresponding areas in full term. Preterm tissues were thicker. Expressions of MMP-9 & 13 were higher in preterm than full term membranes. Also variations were found between amnion and chorion. These findings are useful for better understanding of PPROM etiology.

Midlands Medicine

BIOIMPEDANCE TO MAINTAIN RENAL OUTPUT: THE BISTRO TRIAL 1,2

1,3

Simon J Davies , Ivonne Solis-Trapala , Louise Phillips-Darby , Nancy Fernandes da Silva , Katie Stanley , 4 and Julius Sim on behalf of the BISTRO Study Group 1

Institute for Applied Clinical Sciences, Guy Hilton Research Centre, Thornburrow Drive, Hartshill, Stokeon- Trent, Staffordshire, ST4 7QB, UK;

University Hospitals of North Midlands, Royal Stoke University Hospital, Newcastle Road, Stoke-on-Trent, ST4 6QG, UK; 3

Keele CTU, Keele University, Staffordshire, ST5 5BG, UK;

Keele University, Arthritis Res UK Primary Care Centre, Institute Primary Care & Health Sciences, Keele ST5 5BG, Staffordshire, England. Contact: n.fernandesdasilva@keele.ac.uk

BACKGROUND Most patients who develop kidney failure choose unit-based haemodialysis treatment. One of the main functions of dialysis is to control the amount of fluid in the body. Too much fluid can lead to raised blood pressure that damages the heart and increases the risk of stroke, and may cause fluid to collect in the lungs leading to breathing difficulties. Too little fluid causes dehydration, cramps and low blood pressure on dialysis and more rapid or complete loss of any remaining kidney function. Bioimpedance is a simple, bedside measurement giving information about body composition, in particular how much excess fluid is present. Clinicians can use this to guide how much fluid should be removed from the body in conjunction with the normal clinical assessment of the amount of fluid in the body, but it is not known if this results in better decisions and outcomes for patients. AIMS To test whether taking regular measurements with a bioimpedance device, which gives information about body composition, improves outcomes for people who have newly started haemodialysis treatment for kidney failure. In particular, the study aims to see if this helps patients maintain their remaining kidney function, as this is associated with improved survival, fewer symptoms of kidney failure, fewer side effects of dialysis treatment and a better quality of life including confidence in managing their health, and cost benefit analysis. STUDY People starting haemodialysis as an outpatient who still have some remaining kidney function will be invited to participate in a clinical trial that compares current best practice with the same but additionally guided by regular bioimpedance measurements. The study will randomise 516 patients from 30 dialysis units across the UK and will start in 2017 for 2 years. WORD COUNT: 286 words ACKNOWLEDGEMENTS BISTRO is funded by the National Institute for Health Research's Health Technology Assessment Programme.

Volume 28, No 2, October 2016

“WHEN YOU’RE IN YOUR 80S IT’S A BIT DIFFICULT TO START…YOU CAN’T TEACH AN OLD DOG NEW TRICKS”: EXPLORING THE INFLUENCE OF SELF-DIRECTED AGEING STEREOTYPE ON HEALTH BEHAVIOUR 1

Dr Amy Burton , Dr Sarah Dean , Weyinmi Demeyin 1

Psychology, Sport and Exercise, Staffordshire University Contact: amy.burton@staffs.ac.uk

Stereotype Embodiment Theory proposes that, as we age, we internalise stereotypes about old age (Levy, 2009). Blaming old age for illness and decline in abilities, and holding the belief that ‘to be old is to be ill’ is associated with poorer memory, attention and physical health (Levy, 2003) and doing fewer health promoting activities (Beyer, Wolff, Warner, Schüz, & Wurm, 2015; Stewart, Chipperfield, Perry, & Weiner, 2012). For example, despite the benefits, we found that older people with sight loss use negative ageing stereotypes to justify decisions not to be physically active (‘Young adults, rather than 70 or 80 year olds [...] they are the ones that really need all of the exercise and can actually do it’) (Burton, Clancy & Cowap, under review). Our research aims to explore the impact of self-directed ageing stereotype on health. Currently, we are systematically identifying and evaluating existing measures of this concept and have found 25 different measures. Our exploration has highlighted that most research has been conducted outside of the UK and, as evidence suggests that ageing stereotypes vary across cultures (Hung, Kempen, & Dr Vries, 2010; Yun & Lachman, 2006), we believe there is a need to explore ageing stereotypes in a UK context. Therefore, if we are unable to identify a suitable measure, the next stage of our work will involve the creation of a UKspecific questionnaire to measure self-directed ageing stereotype. Once this is developed we intend to use the questionnaire to explore the relationship between self- directed ageing stereotype and a range of health behaviours. We believe that improved knowledge about the contribution of self-directed ageing stereotype to health and health behaviour in a UK context can contribute to recommendations for the design and targeting of NHS and public health interventions to improve the health of older adults.

Midlands Medicine

REFERENCES Burton, Clancy & Cowap (Under Review). Exploring the facilitators and barriers to physical activity in older people with sight loss. Beyer, A.-K., Wolff, J. K., Warner, L. M., Schüz, B., & Wurm, S. (2015). The role of physical activity in the relationship between self-perceptions of ageing and self-rated health in older adults. Psychology & Health, 30(6), 671–85. Hung, L.-I., Kempen, G. I. J. M., & Dr Vries, N. K. (2010). Cross-cultural comparison between academic and lay views of healthy ageing: a literature review. Ageing and Society, 30(08), 1373–1391. Levy, B. R. (2003). Mind matters: cognitive and physical effects of aging self-stereotypes. The Journals of Gerontology. Series B, Psychological Sciences and Social Sciences, 58(4), P203–11. Levy, B. R. (2009). Stereotype Embodiment: A Psychosocial Approach to Aging. Current Directions in Psychological Science, 18(6), 332–336. Stewart, T. L., Chipperfield, J. G., Perry, R. P., & Weiner, B. (2012). Attributing illness to “old age:” consequences of a self-directed stereotype for health and mortality. Psychology & Health, 27(8), 881–97. Yun, R. J., & Lachman, M. E. (2006). Perceptions of aging in two cultures: Korean and American views on old age. Journal of Cross-Cultural Gerontology, 21(1-2), 55–70.

Volume 28, No 2, October 2016

UNDERSTANDING THE ROLE OF PSYCHOSOCIAL FACTORS IN THE EXPERIENCE OF SUICIDALITY BY PEOPLE WITH BIPOLAR DISORDER DIAGNOSES Robert C. Dempsey1

Staffordshire Centre for Psychological Research, Staffordshire University Contact: robert.dempsey@staffs.ac.uk

Bipolar Disorder is a recurrent mental health condition associated with the experience of severe manic and depressive mood episodes. Approximately 19-20% of people with a bipolar disorder diagnosis die by suicide and the experience of suicidal thoughts, feelings and behaviours is common for people with bipolar diagnoses. However, there has been limited research understanding the experiences of suicidality and the psychosocial mechanisms which confer a risk of suicide in bipolar populations. Understanding how and why some people with bipolar disorder experience high levels of suicidality is important for developing appropriate psychological therapies by identifying those factors which can be changed through therapy (e.g. negative thoughts about the self and/or the social environment). This poster will provide an overview of collaborative research between Staffordshire, Manchester and Lancaster Universities investigating the role of psychological and social factors in the experience of suicidal thoughts, feelings and behaviours by people with diagnoses of bipolar disorder. Our work to date has included a review of the existing research investigating the role of psychological factors in the experience of suicidality by people with bipolar disorder (Owen et al., under review). We have also conducted a series of interviews with people with bipolar disorder to understand which psychological and social factors worsen or reduce suicidal feelings (Owen et al., 2015; in press). The results of the literature review and the qualitative studies have informed an online study which is investigating the role of psychosocial factors, including psychological resilience, feelings of defeat and entrapment, social support, mood symptoms and thinking style, on the experience of suicidal thoughts, feelings and behaviours over a four-month time period. A summary of our findings to date will be presented at the conference. REFERENCES Owen, R., Gooding, P., Dempsey, R., & Jones, S. (2015). A qualitative investigation into the relationships between social factors and suicidal thoughts and acts experienced by people with a Bipolar Disorder diagnosis. Journal of Affective Disorders, 176, 133-140. Owen, R., Gooding, P. A., Dempsey, R. C., & Jones, S. H. (Under Review). A systematic review of the role of psychological and social factors in the suicidal thoughts, feelings and attempts of people with Bipolar Disorder. Owen, R., Gooding, P., Dempsey, R., & Jones, S. (in press). The Experience of Participation in Suicide Research from the Perspective of Individuals with Bipolar Disorder. Journal of Nervous & Mental Disease.

Midlands Medicine

RANDOMIZED CONTROLLED TRIAL ELECTRICAL VAGAL NERVE STIMULATION PREVENTS THE DEVELOPMENT OF ACID INDUCED GULLET PAIN 1, 2, 3

AD Farmer *, G Amersinghe , C Brock , A Drewes , AM Drewes , D Sifrim , Q Aziz 1 Department of Gastroenterology, University Hospitals of North Midlands, Stoke on Trent, UK

Wingate Institute of Neurogastroenterology, Barts and the London School of Medicine, London, UK 3Mech-Sense, University of Aalborg, Aalborg, Denmark Contact: Adam.farmer@uhnm.nhs.uk

INTRODUCTION Accumulating evidence suggests that the vagus nerve exerts a painkilling in the viscera. Visceral pain hypersensitivity is a key pathophysiological facet of a number of common disorders such as gastro-esophageal reflux disease and irritable bowel syndrome. We have previously demonstrated that physiologically increasing vagal tone, with deep breathing, prevents the development of acid induced esophageal pain hypersensitivity. AIMS To determine whether electrical stimulation of the auricular branch of the vagus nerve influences the development of hypersensitivity in a validated model of acid induced esophageal pain. DESIGN Prospective randomised placebo controlled crossover trial. METHODS Prior to, and following, a 30-minute distal oesophageal infusion of 0.15M hydrochloric acid, pain thresholds to electrical stimulation were determined in the proximal non-acid exposed oesophagus in 15 healthy subjects (11 male, mean age 30 years, range 21-42). Validated sympathetic (cardiac sympathetic index) and vagal (cardiac vagal tone) parameters were measured at baseline and continuously thereafter. Subjects were randomized in a blinded crossover design to receive either transcutaneous auricular electrical vagal nerve stimulation (VNS) (pulse width: 250 μs, 25 Hz, cycle: 30s on, 30 s off), or sham stimulation, during acid infusion. RESULTS VNS increased cardiac vagal tone (31.6% ± 58.7 vs. -9.6 ± 20.6, p=0.02) in comparison to sham stimulation. VNS did not influence cardiac sympathetic index (-5.8% ± 41.7 vs. 17.7 ± 84, p=0.35). Mixed effects linear regression, controlling for age and gender, demonstrated that VNS prevented the development of acidinduced esophageal hypersensitivity in comparison to sham stimulation (coefficient 15.4mA /unit time (95% confidence interval 8.8 to 22.2), p=0.001), [Figure 1] CONCLUSIONS The development of oesophageal hyperalgesia is prevented by electrically stimulating the auricular branch of the vagus nerve. Further work is warranted in patient groups. Volume 28, No 2, October 2016

ACKNOWLEDGEMENTS Funded by the Pain Relief Foundation.

Figure 1 â&#x20AC;&#x201C; Percentage change in pain thresholds following a 30 distal esophageal acid infusion.

Midlands Medicine

ULTRASOUND IMAGING IN MUSCULOSKELETAL SYSTEM ANALYSIS AT GLANCE Shaima I. Jabbar1, Charles R. Day2, Edward K. Chadwick1

1Institute for Science and Technology in Medicine, Keele University; 2School of Computing and Mathematics, Keele University, UK Contact: s.i.jabbar@keele.ac.uk Ultrasound Imaging (UI) is considered a popular and user-friendly imaging modality because it is free from ionizing radiation and magnetic fields, portable, relatively low-cost and non-invasive. Ultrasound has been in use in medical applications for more than 70 years, and has several applications in musculoskeletal system analysis. PAST We can consider four decades of development: in the first two decades, researchers concentrated on observation of musculoskeletal diseases such as hip and shoulder dislocation. A ‘comparison decade’ is a convenient term to describe the third decade (2000’s) because in this period researchers tried to show differences and similarities between ultrasound and other ways of taking measurements such as Electromyography and Magnetic Resonance Imaging. The fourth decade is the ‘motion analysis’ decade: researchers were interested in estimating tendon excursion and the analysis of mechanical properties of tendon and muscle. PRESENT Panoramic imaging has added a new evolution to ultrasound imaging because it significantly expands the field of view. It is possible to see a whole tendon or muscle from origin to the insertion with this method. In addition, sono-elastography has emerged as a development of ultrasound imaging to measure mechanical properties of tendon tissue. For example, changes in tendon mechanical properties change can be demonstrated on UI ultrasound in vitro. FUTURE AND CHALLENGES One of the key areas for ultrasound imaging research is increasing the quality of the image. Advanced methods for removing noise, and enhancing image contrast using digital image processing tools are active areas. Automatic extraction of key information from Musculoskeletal Ultrasound Images will be a major advance. Such key information might describe the shape of musculoskeletal system components such as tendon length and muscle volume. This would make personalised models of the musculoskeletal system for clinical decision making a real possibility. Finally, creating three dimensional ultrasound reconstructions from two dimensional images is another challenge in musculoskeletal ultrasound imaging with great potential benefits.

Volume 28, No 2, October 2016

ULTRASOUND IMAGING IN MUSCULOSKELETAL SYSTEM ANALYSIS AT GLANCE Shaima I. Jabbar1, Charles R. Day2, Edward K. Chadwick1

Midlands Medicine

THERAPISTS’ PERCEPTIONS OF IMPLEMENTING CONSTRAINT INDUCED MOVEMENT THERAPY: THE ENABLERS AND BARRIERS 1,2

Kathryn Jarvis , Nicola Edelstyn , Gaynor Reid , Susan M Hunter

1,3,4

Research Institute for Social Sciences, Keele University; Directorate of Occupational Therapy, 3 4 University of Liverpool; School of Health and Rehabilitation, and Institute for Applied Clinical Sciences (IACS), Keele University Contact: s.m.hunter@keele.ac.uk BACKGROUND: Constraint Induced Movement Therapy (CIMT) is an approach to stroke rehabilitation involving a constraint applied to the non-paretic upper limb, for up to 90% of waking hours, plus intensive task- specific training for the paretic upper limb for up to 7 hours/day for 10-14 days. Whilst evidence suggests that CIMT is effective in reducing disability after stroke, therapists are not implementing evidence-based CIMT protocols. Reasons for this are unclear. This study aimed address the following research questions: • Which evidence-based CIMT protocols do therapists perceive could be provided within a UK stroke service? • What are therapists’ perceived enablers and barriers to implementing the identified CIMT protocols? METHOD: With ethical approval, a group of eight occupational therapists and physiotherapists experienced in stroke rehabilitation participated in a focus group discussion, which was audio-taped and transcribed verbatim. Data were analysed by two independent researchers using an inductive thematic analysis. Emergent themes were discussed and differences agreed through consensus. Themes were organised to answer the research questions. Reflexive documentation recorded all decisions and provided an audit trail. MAIN FINDINGS: Six themes were identified from the data: CIMT intervention; personal characteristics; setting and support; ethical considerations; education and training; practicalities. Protocols with shorter intensity of daily training time and shorter constraint times were perceived to be more feasible; the overall length (duration) of the protocol was considered to be less important. A wide range of enablers and barriers spanning all six themes were identified, including importance of informal support for stroke survivors, and staff training. CONCLUSION: Therapists made decisions about feasibility of CIMT based on their current service constraints. Evidencebased protocols that required changes to service structure or additional funding were not seen as feasible for stroke service users. If CIMT is to be implemented successfully, enablers and barriers identified in this study should be addressed.

Volume 28, No 2, October 2016

STUDY OF IMMUNOLOGICAL AND GENETIC FACTORS AFFECTING MULTIPLE SCLEROSIS 1, 2, 3

Dr Seema Kalra 1

1, 2

, Dr SJ Curnow , Professor CP Hawkins

& MS Research Group

University Hospitals of North Midlands NHS Trust; Institute for Science and Technology in Medicine, 3 Keele University; University of Birmingham Contact: s.kalra@keele.ac.uk

Multiple Sclerosis (MS) is an immune disease that affects the brain. Our immune cells attack our own brain tissue. Genetic factors affect the risk of developing MS and also affect the behaviour of the immune cells. Around 100,000 people in the UK have MS. Over the last decade there has been much advancement in fields of immunology and genetics that could be applied to understand MS. We are conducting this study for 3 years to bring together patientsâ&#x20AC;&#x2122; symptoms, immunological changes and measures from brain scans to build our understanding of the factors that affect the progression of multiple sclerosis. We have found that auto-aggressive T cells (Th17, Th1) increase and regulatory T cells show a drop in MS. Our group has also identified an increase in novel type of auto-aggressive T cell (Th17/Th1). We are now studying characteristics of this cell in detail. We plan to follow these patients over the coming years. In the next phase of the study we plan to bring together the genetic information to see how this affects the MS over time. This information would help us identify the factors that would lead to severe MS versus mild MS, which in turn, would let us choose the right type of treatment for patients in future. Our long-term aim is to be able to define the factors that would slow down and halt the progress of the disease. ACKNOWLEDGEMENTS We thank North Staffordshire Medical Institute for their generous grant and support towards this project. We are indebted to our patients for their kind support and belief - Together we will beat MS.

Midlands Medicine

BODY MASS INDEX AND OUTCOMES AFTER PERCUTANEOUS CORONARY INTERVENTIONS: DOES THE OBESITY PARADOX EXIST IN PCI? Chun Shing Kwok*, Eric W Holroyd, Alex Sirker, Evangelos Kontopantelis, Peter F Ludman, Mark A de Belder, Robert Butler, James Cotton, Azfar Zaman, Mamas A Mamas Corresponding author*: Chun Shing Kwok, Cardiology Registrar, Academic Clinical Fellow and Honorary Clinical Lecturer, Keele University, Stoke-on-Trent, UK. Tel: 017872671653. Contact: shingkwok@doctors.org.uk BACKGROUND Previous studies have identified more favorable outcomes following percutaneous coronary intervention (PCI) in obese patient compared to patients with normal body mass index (BMI) and this is known as the â&#x20AC;&#x2DC;obesity paradoxâ&#x20AC;&#x2122;. However, it has not been consistently observed across all published studies. We aimed to examine the relationship between BMI and clinical outcomes following PCI in a national United Kingdom cohort and determine the relevance of difference clinical presentations. METHODS We retrospectively analysed data from the British Cardiovascular Intervention Society database, which contained all records of PCI between 2005 in 2013 in England, which had data available on BMI. Clinical, demographic, procedural and outcome data were collected and used to generate multiple logistic regression models to determine the impact of different BMI groups on mortality at different time points and in-hospital major adverse cardiovascular events and major bleeding. RESULTS A total of 345,152 participants were included in the study. Compared to participants with normal BMI, obese participants had reduced risk of mortality at 30 days (adjusted OR 0.90 95%CI 0.82-0.98), 1 year (adjusted OR 0.73 95%CI 0.69-0.77) and 5 years (adjusted OR 0.88 95%CI 0.84-0.92). While major bleeding was also reduced in obese participants (adjusted OR 0.87 95%CI 0.81-0.93), there was no significant difference in major adverse cardiovascular events (adjusted OR 0.95 95%CI 0.89-1.02). A similar reduction in adverse outcomes for obese patients was observed for the subgroups of stable angina, unstable angina/NSTEMI and STEMI. CONCLUSIONS A paradox regarding the independent association of elevated BMI to reduce long and short-term mortality after PCI is evident in contemporary UK practice. This phenomenon is observed in both stable and acute setting and its causes remain uncertain and controversial. ACKNOWLEDGEMENTS We would like to thank the North Staffs Heart Committee for supporting our work.

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SLEEP DURATION AND MORTALITY AND ADVERSE CARDIOVASCULAR EVENTS: A SYSTEMATIC REVIEW AND META-ANALYSIS Chun Shing Kwok*, George Kuligowski, Matthew Gray, Alan Muhyaldeen, George Peat, Carolyn ChewGraham, Yoon K Loke, Mamas A Mamas Corresponding author*: Chun Shing Kwok, Cardiology Registrar, Academic Clinical Fellow and Honorary Clinical Lecturer, Keele University, Stoke-on-Trent, UK. Tel: 017872671653. Contact: shingkwok@doctors.org.uk BACKGROUND Cardiovascular disease is the leading cause of death in Europe and the United States. While not a traditional risk factor for cardiovascular disease, certain sleep duration has been shown in several studies to be associated with mortality and cardiovascular disease. We aimed to describe the association between sleep duration and mortality and cardiovascular disease. METHODS We conduced a systematic review and meta-analysis of cohort studies. We search MEDLINE and EMBASE for studies published between 1946 to 2015 for prospective cohort studies that evaluated sleep duration and their association with cardiovascular outcomes (coronary heart disease, stroke, cardiovascular disease) and death from all causes. Two independent reviewers extracted study design, participant characteristics, study results and performed the quality assessment. The most adjusted results were used for inverse variance weighted random effects meta-analysis to pool risk ratios. RESULTS 60 studies including 3,248,768 participants. We observed a U-shaped relationship between sleep duration and mortality and adverse cardiovascular outcomes. Compared to 7 to 8 hours of sleep, there was a higher risk of mortality for fewer hours of sleep (3 hours (RR 1.26 95%CI 1.08-1.46), 4 hours (RR 1.17 95%CI 1.081.28), 5 hours (RR 1.11 95%CI 1.08-1.15) and 6 hours (RR 1.07 95%CI 1.04-1.10)). Even high greater mortality was observed for 9, 10 and 11 hours of sleep compared to 7 to 8 hours (RR 1.26, 95%CI 1.21-1.31, RR 1.52 95%CI 1.38-1.68, RR 1.66 95%CI 1.23-2.24, respectively). Similar relationships were observed for cardiovascular disease mortality, coronary heart disease mortality, stroke mortality, cardiovascular disease, stroke and heart disease. CONCLUSIONS Divergence from the recommended 7 to 8 hours of sleep appears to associated with a higher risk of mortality and cardiovascular events. Longer duration of sleep shows a stronger relationship with adverse outcomes compared with shorter sleep durations.

Midlands Medicine

EXPLORING THE IMPACT OF FOOT AND ANKLE IMPAIRMENTS ON MOBILITY IN PEOPLE WITH STROKE 1

Cramp M , Lyddon A , Gorst T ,Freeman J , Paton J , Morrison S , Marsden J

Centre for Health and Clinical, Faculty of Health and Applied Science, University of the West of 2 3 England; School of Health and Bioscience, University of East London; School of Health Professions, 4 University of Plymouth; School of Health Sciences, University of Brighton Contact: a.lyddon@keele.ac.uk BACKGROUND Foot posture abnormalities have been reported in 30% of people with stroke[1] and are suggested to occur more frequently in people who walk indoors only[1]. Stroke survivors also report that foot and ankle impairments are problematic and impact on everyday function[2]. PURPOSE To compare foot and ankle sensori-motor function of people with stroke with controls and to examine foot and ankle impairments as predictors of mobility. METHODS This cross-sectional observational study involved 180 people with stroke, >3 months post onset and mobilising independently, recruited from NHS stroke services and support groups at two UK sites, and 46 age- and gender-matched controls. Foot and ankle impairments assessed included foot posture, muscle strength, ankle and hallux joint ROM, spasticity, sensation, foot pain, and dynamic foot loading. Mobility and balance assessments included fast paced timed 10m walk and timed up and go tests. Preliminary analysis compared the stroke and control groups and explored impairments predicting mobility after stroke. RESULTS The stroke group comprised of 107 [59%] males, 81 [45%] with right CVA, mean 38 [range 3-224] months post stroke and mean age of 67 [SD 11] years. The control group included 22 [48%] males, mean age of 66 [SD 12] years. Mean gait velocity was 1.09 (0.8) m.s-1 for stroke and 1.81 (0.36) m.s-1 for controls (t=-10.45, p<0.001); significant group differences were also observed for the presence of pain (_2= 5.104, p<0.025) and muscle strength (t=11.382, p<0.001). 11% of stroke patients demonstrated abnormal foot posture[3] on their most affected side and 22% showed inter-limb differences in foot types. Preliminary regression analysis indicated that muscle strength and ankle ROM impairments accounted for 47% of variance in walking velocity (p<0.001). CONCLUSION Foot and ankle sensori-motor function was impaired in stroke participants. Foot posture abnormalities Volume 28, No 2, October 2016

and asymmetry were lower than previously reported. The observed relationship between foot and ankle impairments and mobility warrants further analysis. ACKNOWLEDGEMENTS I would like to thank the whole FAiMiS project team, especially Dr Mary Cramp. REFERENCES Forghany S, Tyson S, Nester, C, et al. Foot posture after stroke: frequency, nature and clinical significance. Clin Rehabil 2011;25:1050â&#x20AC;&#x201C;5. Gorst T, Lyddon A, Marsden J, Paton J, Morrison S, Cramp M, Freeman J. Foot and ankle impairments affect balance and mobility in stroke (FAIMIS): the views and experiences of people with stroke. Disabil Rehabil 2015, 12:1-8. Redmond AC, Crane YZ, Menz HB. Normative values for the Foot Posture Index. J. Foot Ankle Res 2008, 1(1):6.

Midlands Medicine

OXYGEN SATURATION IN STROKE PATIENTS AT THE TIME OF ARRIVAL IN HOSPITAL 1

Maguire H , Barry A , Grocott J , Finney K , Abano N , Remegoso A , Butler A , Stevens S , Carpio R , 1 1, 2 Varquez R , Roffe C 1

Stroke Research in Stoke, University Hospital of North Midlands; Institute for Science & Technology in Medicine, Keele University Contact: Holly.Maguire@uhnm.nhs.uk

BACKGROUND Hypoxia is common, but frequently intermittent, in the first few days after stroke and associated with worse outcomes. UK Stroke guidelines suggest that oxygen should be given if the oxygen saturation falls below 95%. The aim of this survey is to determine how common hypoxia is very early after the stroke, immediately after presentation to accident and emergency. METHOD Baseline demographics and vital physiological parameters including oxygen saturation are recorded immediately after arrival for every patient who presents to the emergency services at the Royal Stoke University Hospital. These data were collected retrospectively for all patients with a confirmed diagnosis of acute stroke for this audit between 1st November 2015 and 31st March 2016. RESULTS Two hundred seventy-four sequential patients were included. The mean oxygen saturation on arrival was 96.9% (range 85-100%). Of these 244 (89%) had an oxygen saturation >95%, 28 (10 %) a saturation of 90-95%, and 2 (0.7%) a saturation below 90% (85 and 86% respectively). Four patients (1.5%) were treated with oxygen at the time of arrival. Their oxygen saturations were 92% on 2L/min, two with 93% on 4 L/min, 93%, and 95% on 4 L/min. Severe hypoxia (saturation less than 90% on air or <95% on oxygen) occurred in 6 (2%). CONCLUSION Very early after acute stroke, most patients have normal or high normal oxygen saturation. Severe hypoxia is very uncommon on arrival.

Volume 28, No 2, October 2016

SUPERVISED EXERCISE THERAPY IN PATIENTS WITH INTERMITTENT CLAUDICATION: DOES BMI AFFECT PATIENT OUTCOMES? 1

Michael McCluskey , Eve Scarle , Simon Fryer , Keeron Stone , Diane Crone . 1

School of Health and rehabilitation, Keele university

School of Sport & Exercise, University of Gloucestershire Contact: m.mccluskey@keele.ac.uk

BACKGROUND Intermittent Claudication (IC) a condition in which cramping pain in the leg is induced by exercise, typically caused by obstruction of the arteries. Exercise has been shown to be effective in reducing short-term pain and disability in general populations however, the influence of Body Mass Index (BMI) on patient outcomes has yet to be investigated. The aim of this study was to determine if Body Mass Index affects physical activity and Quality of Life (QoL) outcomes in adults with IC following SET. METHODOLOGY 39 patients with IC received 2 weekly SET sessions for 12 weeks. Each session included lower limb resistance and cardiovascular exercises. The group consisted of 15 ‘overweight’, 13 ‘obese’ and 8 ‘normal’ adults. Average daily steps and SF36 Questionnaire were assessed before and oncompletion of SET to assess physical activity levels and QoL respectively RESULTS The greatest improvement in activity levels was seen in those categorised as ‘overweight’; they gained a significant increase in the daily steps (average +2006 steps per day). A nonsignificant but meaningful meaningful increase in steps was seen for ‘Normal’ participants (average + 1687 steps per day). No improvement was noted in ‘obese’ adults (average 186 steps). QoL changes were greatest in ‘normal’ participants; they experienced significant increases in social functioning and general health elements of SF36 by 12.71% and 4.72% respectively. ‘Overweight’ individuals significantly increased in the physical functioning element of SF36. Obese participants did not experience improvements in elements of QoL measured by SF36 CONCLUSION This investigation indicates that BMI may have a significant bearing on the outcomes of physical activity levels and QoL in adults with IC following SET, with ‘normal’ and ‘overweight’ adults being more likely to gain improvements than obese adults. Weightloss management in addition to SET may be indicated for patients with obesity and IC; this warrants further investigation ACKNOWLEDGEMENTS The authors would like to thank Gloucestershire Hospitals NHS Foundation Trust for their financial and logistical support throughout this trial.

Midlands Medicine

QUANTIFYING COORDINATION PATTERNS OF THE MULTI-SEGMENT FOOT DURING GAIT 1

Robert Needham , Roozbeh Naemi , Nachiappan Chockalingam

Faculty of Health Sciences, Staffordshire University Contact: r.needham@staffs.ac.uk

INTRODUCTION A dynamical systems approach using vector coding (VC) and circular statistics provides non-linear techniques to quantify coordination and variability. The coupling angle (CA) is the outcome measure from the VC technique and refers to the vector orientation between two adjacent data points on an angle-angle diagram relative to the right horizontal. Based on the polar position (between 0-360) the CA can be assigned to a coordination pattern (Chang et al. 2008). The purpose of this study was to quantify rear-foot and fore-foot coordination during gait using a new coordination pattern classification recently developed (Needham et al. 2015), and to expand on the knowledge of multi-segment foot motion. METHODOLOGY Ten male participants with a mean age of 21.6 (±3.13) years, height of 180.9 (±8) cm and mass of 74.85 (±11.10) kg, with no history of musculoskeletal impairments participated in the study. Ethical Approval was sought and received from the University Research Ethics Committee. Participants were required to walk barefoot at a preferred walking speed. An 8 camera motion capture system (Vicon, Oxford, UK.) was used to collect kinematic data. The general protocols and VC calculations are reported elsewhere (Needham et al. 2014). RESULTS

Figure 1. Mean coupling angle for rear-foot/medial fore-foot coordination in the sagittal, frontal, and transverse plane during gait presented using the new illustration and coordination pattern classification

Volume 28, No 2, October 2016

DISCUSSION The new coordination pattern classification utilised in this study expanded on the work of Chang et al. (2008), and provided a detailed account of multi-segment foot kinematics during gait. This data will provide useful information to support clinical interventions and lead to informed footwear designs. REFERENCES Chang, R., Emmerik, R.V., & Hamill, J. (2008). Quantifying rearfoot-forefoot coordination in human walking. J. Biomech, 41(14), 3101-3105. Needham, R., Naemi, R., & Chockalingam, N. (2014). Quantifying lumbar-pelvis coordination during gait using a modified vector coding technique. J. Biomech, 47(5), 1020-1026. Needham, R.A. et al. (2015). A new coordination pattern classification to assess gait kinematics when utilising a modified vector coding technique. J. Biomech, 4812), 3506-3511.

Stephen Hawking

â&#x20AC;&#x153;

Look up at the stars and not down at your feet. Try to make sense of what you see, and wonder what makes the universe exist. Be curious.

Midlands Medicine

THORAX MOTION DURING GAIT: A COMPARISON BETWEEN TWO KINEMATIC MODELLING TECHNIQUES 1

Robert Needham , Panagiotis Chatzistergos , Nachiappan Chockalingam 1

Faculty of Health Sciences, Staffordshire University Contact: r.needham@staffs.ac.uk

INTRODUCTION Optoelectronic motion capture provides a non-invasive approach to measure dynamic movement of the spine. In clinical gait analysis, the conventional gait model considers the thorax as a rigid segment that represents movement of the entire trunk. To represent three-dimensional (3D) movement of the thorax markers are placed on the spinous processes and sternum. Markers on the superior and inferior aspect of the sternum can have practical concerns for assessment of female participants. An alternative approach is to use a 3D cluster that can be applied over a spinous process (Needham et al. 2015; Needham et al. 2016). The purpose of this preliminary study was to compare the kinematic data often reported within modelling techniques of the thorax. METHODOLOGY Eight male participants with a mean age of 20.9 (±2.11) years, height of 181.6 (±9.3) cm and mass of 77.55 (±9.13) kg, participated in the study. Ethical Approval was sought and granted by the institutional ethics committee. The conventional thorax model consisted of four markers attached to the thorax and sternum (IOR), Leardini et al. 2011). The Staffordshire Thorax Model (STM) denotes one 3D cluster attached over the spinous process of T1. The 3D cluster was built by a 3D printer using ABS thermoplastic material (Dimension bst 1200es, Stratasys, Germany). Participants walked barefoot at a preferred walking speed. An 18 camera motion capture system (Vicon, Oxford, UK.) collected kinematic data at 100 Hz. A data analysis technique proposed by Meldrum et al. (2014) was used to assess the differences between thorax models for the group and for each participant. RESULTS

Figure 1: Bland and Altman plots of thorax kinematic waveforms were created in the sagittal (a), frontal (b), and transverse plane (c). Mean waveforms of IOR and STM were plotted against their corresponding differences at each time point of the gait cycle (from right initial contact to right initial contact). Volume 28, No 2, October 2016

DISCUSSION Similar relative movements patterns were noted between the thorax models. Although greater relative ROM was highlighted for the STM in all three planes of movement in comparison to IOR thorax model, the 3D cluster technique is a suitable approach for assessing thorax movement during gait. REFERENCES Leardini, A., Biagi, F., Merlo, A., Belvedere, C., Benedetti, M.G. (2011). Multi-segment trunk kinematics during locomotion and elementary exercises. Clin Biomech, 26(6), 562-571 Meldrum, D., Shouldice, C., Conroy, R., Jones, K., Forward, M. (2014). Test-retest reliability of three dimensional gait analysis: including a novel approach to visualising agreement of gait cycle waveforms with Bland and Altman plots. Gait Posture, 39(1), 265-71. Needham, R.A., Naemi, R, Healy, A., & Chockalingam, N. (2015). Multi-segment kinematic model to assess three-dimensional movement of the spine and back during gait. Prosthetic Orthot Int, doi: 0309364615579319 Needham, R.A., Stebbins, J., Chockalingam, N. (2016). Three-dimensional kinematics of the lumbar spine during gait using marker-based systems: a systematic review. J Med Eng Technol, 40(4), 172-85.

Midlands Medicine

MODIFICATION OF A VALIDATED PATIENT REPORTED EXPERIENCE MEASURE TOOL FOR RHEUMATOID ARTHRITIS FOR USE IN OTHER RHEUMATIC CONDITIONS: RESULTS OF A PILOT STUDY 1

Ailsa Bosworth , Maureen Cox , Anne O’Brien , Peter Jones , Ify Sargeant , Alison Elliott ,Marwan 7,8 Bukhari , on behalf of Commissioning for Quality in Rheumatoid Arthritis.

National Rheumatoid Arthritis Society, Maidenhead, Berkshire, United Kingdom; Rheumatology, 3 Nuffield Orthopaedic Centre, Oxford, United Kingdom; School of Health and Rehabilitation, Keele 4 University, Keele, United Kingdom; Health Service Research Unit, Keele University, Keele, United 5 6 Kingdom; ismedica ltd, Staffordshire, United Kingdom; Roche Products Ltd, Welwyn Garden City, 7 8 United Kingdom, Royal Lancaster Infirmary, Lancaster, United Kingdom; Clinical Sciences, University of Liverpool, Liverpool, United Kingdom. Contact: a.v.o’brien@keele.ac.uk BACKGROUND To date there have been no specific patient reported experience measures (PREMs) for rheumatology. A multi-disciplinary group¸ Commissioning for Quality in Rheumatoid Arthritis (RA) developed a PREM questionnaire for RA in 2012 confirming the PREM had good construct validity and is a valid instrument for measuring RA patient experience2. This PREM is being used nation-wide in the current Healthcare Quality Improvement Partnership (HQIP) National Clinical Audit of Rheumatoid and Early Inflammatory Arthritis3. METHODS The RA PREM was modified to capture the experience of patients with other rheumatic conditions using the same eight domains. Cronbach’s alpha4 measured construct validity; a value of at leat 0.7 being regarded as satisfactory. The modified PREM was then piloted and validated. RESULTS Twelve units volunteered to participate in the pilot. Patients (n=110) presented with a range of rheumatic conditions including: Sjögren's syndrome; fibromyalgia; systemic lupus erythematosus; gout; polymyalgia rheumatic; [adults with] juvenile idiopathic arthritis; chronic back pain; osteoarthritis; inflammatory polyarthritis; ankylosing spondylitis; psoriatic arthritis and scleroderma. The majority of patients had their condition ≥ 6 years; the median age was 60 years (IQR 18-84 years), 69.7% were female, 97% white. Cronbach’s alpha within the multi-question domains ranged from 0.76 to 0.91 and percentage agreement with the question on overall care ranging from 0.7 to 0.9. These results are consistent with those obtained for the RA-specific PREM (0.61 to 0.93) and (0.56, 0.81), respectively2. CONCLUSIONS The modified PREM was practical to administer, has good construct validity and is able to reliably capture the patient experience in rheumatic conditions other than RA. Some domains (e.g. needs and preferences/ emotional support) have higher agreement with overall patient experience. Both the RA and the modified PREMs provide valid and valuable tools for measuring and monitoring patient experience in rheumatology and aim to drive improvements in patient experience of care. Volume 28, No 2, October 2016

ACKNOWLEDGEMENTS With thanks to UK Rheumatology units participating in the survey who returned questionnaires for pooled analysis: Roche Products Ltd are supporting this project by providing project management, facilitation, medical writing support and printing costs. REFERENCES Bosworth A, et al. Rheumatology (2013);52 (suppl 1): i56-i94 (Abstract 93. Poster presentation) Bukhari M, et al. Arthritis Rheum (2013);65:S952 (Abstract 2239. Poster presentation) Healthcare Quality Improvement Partnership (HQIP) National clinical audit for rheumatoid and early inflammatory arthritis. Available at: http://www.rheumatology.org.uk/resources/audits/national_ra_audit/information_pack.aspx. Patient data collection form - follow up at 3 months (accessed March 2014) M. Bland & D. Altman (1997) Statistics notes: Cronbachâ&#x20AC;&#x2122;s alpha BMJ;314:572

Midlands Medicine

HOPES AND EXPECTATIONS FOR RECOVERY OF THE UPPER LIMB: A QUALITATIVE STUDY OF STROKE SURVIVORS’ EXPERIENCES 1,2

Judith Purton , Susan M Hunter 1

2,3,4

, Julius Sim

2,3,4

Faculty of Health Sciences, York St John University; Research Institute for Social Sciences, Keele University;

School of Health and Rehabilitation and Institute for Applied Clinical Sciences (IACS), Keele University Contact: s.m.hunter@keele.ac.uk

BACKGROUND Bilateral upper limb (UL) function is essential in many valued activities/life roles e.g. employment, leisure, creative arts, sport. Approximately 70% of stroke-survivors experience altered UL function and 40% experience persistent UL dysfunction. UL rehabilitation is challenging because of complex processes involved in controlling UL movement. The aim of this study was to explore stroke-survivors’ hopes and expectations for UL recovery during the first 18 months post-stroke. METHOD Design: a qualitative, phenomenological longitudinal study involving semi-structured interviews with strokesurvivors at two-, six-, twelve-, and eighteen months post-stroke. Adult participants were recruited from a stroke rehabilitation unit following stroke diagnosis of over two-month duration, with UL impairment and limited spontaneous use, and no significant dysphasia or cognitive difficulties that would prevent engagement in an interview. Thematic analysis of data was undertaken, with independent confirmation of analysis to ensure credibility and dependability. FINDINGS Thirteen participants completed the study. Four main themes were identified: priorities, hopes and ‘getting on with life’; experiences of therapy; lack of information/advice; personal responsibility for recovery. Participants’ hopes and expectations evolved over the 18 months, from focus on lower limb (LL) recovery to the UL, which became their priority. Nevertheless, therapy continued to focus on the LL rather than UL; community therapy was short-lived; and participants felt abandoned. The lack of advice on how to progress UL recovery was frustrating, and health professionals did not fully understand the impact of UL dysfunction on participants’’ lives. Stroke-survivors want to be active partners in their UL rehabilitation but need guidance and advice. CONCLUSIONS UL recovery is as important as mobility to stroke-survivors in the longer-term. Stroke rehabilitation should continue for longer in the community, and should acknowledge stroke-survivors’ desire to be active partners in UL rehabilitation. Timely access to information and advice about UL rehabilitation should be provided.

Volume 28, No 2, October 2016

MAPS-2 (METOCLOPRAMIDE AND SELECTIVE ORAL DECONTAMINATION FOR AVOIDING PENEUMONIA AFTER STROKE (MAPS-2) TRIAL 1

C Roffe , C Smith , M Gosney , T Nevatte , J Sim , H Maguire , B Helliwell , A Jeans , M Harrison , B 6 7 Bray , P Barton and A Warusevitane1

University Hospital of North Midlands NHS Trust, Stoke on Trent Salford Royal Foundation NHS 3 4 5 Trust, Salford Royal Berkshire NHS Foundation Trust, Reading Keele University, Keele Anglia Ruskin 6 7 University, Chelmsford Kings College London, London University of Birmingham, Birmingham Pneumonia is a common complication of stroke and is associated with high mortality, long length of stay and lower potential for functional recovery. Stroke patients who have swallowing problems are more likely to develop pneumonia than stroke patients with normal swallowing function. Patients who require nasogastric feeding are at highest risk of pneumonia. Two small pilot studies have shown that metoclopramide, an antiemetic, and selective oropharyngeal decontamination (SOD), each decrease pneumonia in stroke patients. 1160 patients will be recruited from 50 emergency departments and stroke wards across England. The criteria will be patients who are within 9 hours of having an acute stroke and are required to be fed by nasogastric tube. This study will use two methods in pneumonia prevention the first is a drug called metoclopramide, this drug is used widely across the NHS to prevent vomiting which can occur when patients are moved and turned and easily inhaled into the airways. The second method with use an antibiotic paste in the patientsâ&#x20AC;&#x2122; mouth to reduce the bacteria in their saliva. Both methods will be carried out for 21 days, metoclopramide 3 times a day and the paste 4 times a day or until the NG tube is removed. Patients will then be monitored daily for signs and symptoms of pneumonia. After 30 days the patients will be assessed to see how they are recovering neurologically, further follow up will be carried out at 90 days. All data collected looking at how patients are doing physically, how they are eating, where they are living and what their quality of life is like will be analysed to see if either treatment can prevent pneumonia and reduce the number of deaths in these patients. Alison Buttery, Clinical Studies Co-ordinator on behalf of MAPS-2 team. (01782) 671658 alison.buttery@uhnm.nhs.uk

Midlands Medicine

REDUCING THE RISK OF HARM BY IDENTIFYING A DAMAGED BLOOD VESSEL AS A CAUSE OF NECK PAIN IN A PHYSIOTHERAPY CLINIC 1

Dr Claire Stapleton , Sally Chatting

School of Health and Rehabilitation, Keele University c .stapleton@keele.ac.uk 2

Good Hope Hospital, Birmingham, UK

BACKGROUND Physiotherapists regularly treat patients with neck pain. Treatment options include the therapist applying a movement to one or two bones in the neck. In some people, these treatments are thought to briefly stress a blood vessel in the neck that supplies the brain with essential blood and oxygen. In healthy individuals the blood vessels can cope with this stress. However, in some instances the cause of neck pain is due to a damaged blood vessel which if exposed to further stress from therapeutic treatment could worsen, potentially resulting in a stroke. The challenge for Physiotherapists is to identify those patients at risk and refer on for immediate medical attention. The current guidelines to inform Physiotherapists about identifying patients with this condition are outdated. BRIEF METHODS This study will identify and review published reports of cervical artery dissection. Published literature was electronically searched by combining terms on the specific blood vessel (cervical artery), the type of damage to the blood vessel (dissection) and signs and symptoms. Nineteen articles were identified that reported 7,351 cases. MAIN FINDINGS Many signs and symptoms do overlap with those commonly associated with patients at risk of stroke however there were some exceptions. Patients with damage to a blood vessel in the neck were younger (36 Â48 yrs), and less likely to smoke or suffer from diabetes. In addition, head and neck pain, which are typically symptoms associated with conditions that Physiotherapists would treat, were often reported. Other signs and symptoms that were commonly reported included: high blood pressure, high cholesterol, migraines, recent infection and trivial head trauma. CONCLUSIONS These results highlight the need for updated advice and clinical guidelines for Physiotherapists providing treatment for patients with neck pain. Young patients without the typical risk factors associated with stroke may still be at risk.

Volume 28, No 2, October 2016

PREDICTING SPASTICITY AFTER STROKE BY A SIMPLE BLOOD TEST Wasif A , Pandyan A , Roach P1, Roffe C . 1

Institute for Science and Technology in Medicine, Keele University Contact: a.m.wasif@keele.ac.uk

Spasticity is one of the most common neurological dysfunctions observed following a stroke. It is a clinical condition that can manifest as inappropriate, involuntary muscle activity in people who have an injury to the nervous system (Pandyan et al., 2009). If left untreated it may lead to the development of contracture and pain. Early correct diagnosis of spasticity might be essential for optimum management. There are various scales routinely used to measure spasticity all of which are limited to measuring some features of spasticity, e.g. stiffness (The modified Ashworth scale). These scales usually detect stiffness at a later stage of spasticity, weeks after the development of muscle over-activity based on EMG measurements. Electromyography method can detect muscle over-activity at a very early stage however, it is not implemented in the routine clinical setting; therefore, there is a gap between the start of muscle over- activity and the detection of stiffness based on the current scales (Malhotra et al., 2009). The objective of this study is to identify potential blood molecules that can be used for early detection and diagnosis of post-stroke spasticity. In the eventual clinical setting, such biomarkers may also be used to augment the precision of clinical diagnosis, follow disease progression and help with drug development. REFERENCES Malhotra S, Pandyan A, Jones P and Hermens H. Spasticity, an impairment that is poorly defined and poorly measured. Clin Rehabil 2009; 23: 651-658 Pandyan A , Gregoric M, Barnes MP, Wood D, Van Wijck F, Burridge J, Hermens H, Johnson GR. Spasticity: clinical perceptions, neurological realities and meaningful measurement. Disability and rehabilitation 2005, 27 (1/2), 2-6

Midlands Medicine

HYPERTENSION – A NEW RISK FACTOR FOR VAGINAL WALL PROLAPSE IN WOMEN? 1

Institute for Science and Technology in Medicine, Keele University 2

University Hospital of North Midlands, UHNM, NHS Contact: h.k.weli@keele.ac.uk

Many women, as they get older, experience a downward descent of their vaginal wall called pelvic organ prolapse. Aptly described as “the silent epidemic” by Sherrie Palm, it is a very unpleasant condition affecting millions of women worldwide but with inconclusive understanding of how it happens. Common treatment strategies target the symptoms rather than a root cause leading to high rates of recurrence after previous treatment. Generally accepted risk factors do not consistently explain the presence of the disease in many sufferers. We aimed to study some aspects of the medical history of women with prolapse and the prolapsed tissues themselves to understand changes that made them different from normal tissues with the hope of finding new risk factors. Following ethical approval and informed consent, we obtained vaginal tissues from 65 women undergoing surgery for prolapse and other types of diseases for comparison. We administered questionnaires to the women to obtain information on known and potential risk factors, including hypertension. We observed the composition and structure of the tissues using chemical separation techniques and tissue staining methods, respectively. Prolapsed tissues had reduced muscle layer (figure 1) and higher amounts of sugar modifications of collagen (called glycation) linked with ageing and were more likely to have hypertension as comorbidity.

Figure 1: Muscle layer (red) staining in prolapsed and control tissues. Glycation was particularly higher in women with hypertension. Our findings associate hypertension with presence of the disease and glycation changes. Reduction in the muscle layer of prolapse tissues suggests loss of original elements of the tissue and potential weakening leading to prolapse. Hypertension has been previously associated with loss of blood supply and damage in other tissues and may be a new risk factor for prolapse. ACKNOWLEDGMENTS UHNM gynaecology theatre and surgical staff, UHNM charitable fund, Rivers State Sustainable Development Agency, Nigeria, Guy Hilton Research Centre Staff and students

Volume 28, No 2, October 2016

PRE-ECLAMPSIA QUADRUPLES THE RISK OF FUTURE HEART FAILURE: A SYSTEMATIC REVIEW AND META-ANALYSIS 1,2

4,5

Pensee Wu , Randula Haththotuwa , 1Chun Shing Kwok , Aswin3,7Babu , Rafail A Kotronias , Azfar 6 4,5 Zaman , Anthony A Fryer , Carolyn A Chew-Graham , Mamas A Mamas

Institute for Science and Technology in Medicine, Keele University, Stoke-on-Trent, Academic Obstetrics 3 and Gynaecology, Maternity Centre, Royal Stoke University Hospital, Stoke-on-Trent, Primary Care 4 and Health Sciences, Keele University, Stoke-on-Trent, Keele Cardiovascular Research Group, Keele 5 6 University, Stoke-on-Trent, The Heart Centre, Royal Stoke University Hospital, Stoke-on-Trent, Freemans Hospital and Institute of Cellular Medicine, Newcastle University, Newcastle-Upon-Tyne, 7 NIHR Collaboration for Leadership in Applied Health Research and Care (CLAHRC) West Midlands, Keele University, Stoke-on-Trent Contact: p.wu@keele.ac.uk

AIMS/HYPOTHESIS

Pre-eclampsia is a pregnancy specific disorder resulting in hypertension and multi-organ dysfunction. There is growing evidence that these effects persist after pregnancy. We aimed to systematically evaluate and quantify the evidence on the relationship between pre-eclampsia and the future risk of cardiovascular disease. METHODS

We studied the future risk of heart failure, coronary heart disease, composite cardiovascular disease, cardiac death, stroke and stroke death following pre-eclampsia. A systematic search of MEDLINE and EMBASE was performed to identify relevant studies. We used random effects meta-analysis to determine the risk of future cardiovascular diseases following pre-eclampsia. RESULTS

Twenty-two studies were identified with over 6.4 million women including >258,000 women with preeclampsia. Meta-analysis of studies that adjusted for potential confounders demonstrated that pre- eclampsia was independently associated with an increased risk of future heart failure (risk ratio (RR) 4.19, 95% CI 2.09, 8.38), coronary heart disease (RR 2.50, 95% CI 1.43, 4.37), composite cardiovascular disease death (RR 2.21, 95% CI 1.83, 2.66) and stroke (RR 1.81, 95% CI 1.29, 2.55). After adjusting for age or BMI, pre-eclampsia continued to be associated with an increased risk of future heart failure (RR 3.89, 95% CI 1.83, 8.26 or RR 3.16, 95% CI 1.41, 7.07, respectively). CONCLUSIONS/INTERPRETATION

Pre-eclampsia is independently associated with a four-fold increase in future incident heart failure and a two-fold increase risk in coronary heart disease and cardiac death. Our study highlights the importance of regular monitoring of cardiovascular risk factors in women who have had pre- eclampsia.

Midlands Medicine

Volume 28, No 2, October 2016

CASE REPORT: ACUTE GRANULOMATOUS TUBULO-INTERSITITAL NEPHRITIS SECONDARY TO IPILIMUMAB TREATMENT FOR MALIGNANT MELANOMA Ronald Manorekang, FY2 in Renal Medicine, Monica Bowa-Nkhoma StR in Renal Medicine, Dominic de Takats and Daniela Farrugia, Consultant Nephrologists, all at UHNM progressed with evidence of pulmonary metastases. This was initially treated with bevacizumab, which We report the case of an 85-year-old man with had to be discontinued due to toxicity, and his metastatic melanoma, who developed acute Kidney treatment switched to ipilimumab. His past medical Injury (AKI) requiring haemodialysis, after being history included benign prostatic hypertrophy, atrial treated with ipilimumab. A kidney biopsy showed fibrillation, diverticulitis, dyspepsia and osteoarthritis. granulomatous interstitial nephritis. He was treated with prednisolone and his renal function recovered He developed an acute kidney injury, where his well enough for him to stop haemodialysis. With creatinine rose from normal levels to 540 Îźmol/L, these newer immunotherapies being used increasingly associated with a high eosinophil count between 9 9 in the management of cancer, we must be aware of the 0.68x10 to 0.85x10 /L. Blood cultures, urine cultures, possibility of immune-related adverse events (IRAE), immunology screen and virology screen were all negative. He had normal immunoglobulin levels and including acute kidney injury. an ultrasound of the urinary tract showed a simple BACKGROUND cyst in the lower pole of the left kidney and no signs of obstruction. There have been significant advances in the management of certain solid and haematological As the cause of his acute kidney injury was unclear, malignancies, with the development of immune a kidney biopsy was performed. Histology showed checkpoint inhibitors.1 These monoclonal antibodies, interstitial and tubular acute changes with normal such as ipilimumab, have been shown to be efficacious glomeruli. Furthermore, there were heavy diffused in melanoma, non-small cell lung cancer and renal mixed inflammatory infiltrates with numerous cell carcinoma.1 However, they have also been known eosinophils, mild fibrosis, and varying size of nonto cause immune-related adverse events in about necrotising granulomas in the interstitium (see Figure 60% of patients.2,3,4 Although rare, one of the IRAE is 1). Immunofluorescence of IgG, IgA, IgM, C3, and Acute Kidney Injury (AKI) of varying severity.5,6 We C1q also negative. In view of this a tissue diagnosis of report a case of a patient with metastatic melanoma, granulomatous acute tubulo-interstitial nephritis was who developed AKI and fever three weeks after then made. being treated with ipilimumab. We also present his clinical presentation, pathophysiological findings and management of this example of renal toxicity of ipilimumab. SUMMARY

CASE REPORT An 85-year-old man with known metastatic melanoma presented to the acute medical unit with fatigue, lethargy, and pyrexia, two weeks after he received his first cycle of ipilimumab. He had initially presented in 2011 with acrolentiginous melanoma on his right Figure 1: H & E stain x 400 micrograph shows disruption heel, which was excised. He required repeated of the normal renal architecture by a dense inflammatory resections of the area and, four years later, his disease cell infiltrate 92

Midlands Medicine

The differential diagnosis at this point included drug induced granulomatous interstitial nephritis, sarcoidosis and tuberculosis. The ZN stain and Groucott stain on the biopsy were negative. The patient’s calcium level was normal, there was no evidence of lymphadenopathy on examination. A chest radiograph showed congested lungs but no evidence of hilar lymphadenopathy. CT scan of the abdomen and pelvis showed small scattered mesenteric lymph nodes and slight hazy change around the pancreatic head but no obvious focal lesion was evident. In view of this a drug induced granulomatous interstitial nephritis was the most likely diagnosis. The patient’s drug history included tamsulosin, lansoprazole, digoxin, calcium-with-vitamin D3 and codeine, in addition to having recently received ipilimumab. A literature review showed cases of granulomatous tubulo-intersitital nephritis associated with proton pump inhibitors and ipilimumab.

In view of the temporal relationship between the patient receiving ipilimumab and developing acute kidney injury, the assumption was that the cause of the patient’s granulomatous acute tubulo-interstitial nephritis was the ipilimumab and not the proton pump inhibitor. The patient received three sessions of haemodialysis for his acute kidney injury, until the diagnosis was ascertained and more definitive treatment was started. The possible offending drug, ipilimumab, was stopped. He was started on prednisolone at 60mg daily, which was tapered down over three months. His renal function improved enough to come off dialysis, with creatinine levels halving four weeks after the start of prednisolone and his renal function eventually recovering to a baseline creatinine between 150 to 160 μmol/L six months after the acute insult (see Figure 2).

Figure 2: Change in serum creatinine after ipilimumab then steroid therapy DISCUSSION Cancer patients are vulnerable to renal impairment from a variety of conditions including risks posed by the tumour itself (e.g. multiple myeloma, renal cancer and obstruction by pelvic cancer), glomerulonephritis secondary to underlying malignancies (e.g. membranous nephropathy) tumour lysis syndrome, and nephrotoxicy secondary to anticancer chemotherapy. Nephrotoxicity secondary to chemotherapy can present in a number of ways such as thrombotic microangiopathy, tumour lysis syndrome, crystal nephropathy, nephrotic syndrome, tubulopathies and tubulo-intersitial nephritis.7 Volume 28, No 2, October 2016

Where there is uncertainty as to regards the cause of the renal impairment, a renal biopsy may be needed to make a more definitive diagnosis and direct treatment. Granulomatous interstitial nephritis (GIN) is a rare disease characterised by the presence of inflammatory infiltrates within the interstitium of the kidneys associated with the presence of granulomas.8 Causes of GIN include sarcoidosis, drugs, infections (especially tuberculosis, fungal and atypical bacteria), and other rare causes such as tubulo-intersitial nephritis with uveitis (TINU), Crohn’s disease, oxalosis and intravesicular injection of bacillus Calmette-Guerin (BCG). In around 10% of patients no obvious cause can be found.8-11 93

There have been reported cases in the literature of sarcoidosis complicating treatment with ipilimumab. In a systematic review of immune related side effects of ipilimumab of 234 patients, four patients had lung sarcoidosis, three cases of cutaneous and pulmonary sarcoidosis and one case of muscular sarcoidosis.3 In another systematic review and meta-analysis, six cases of sarcoidosis was reported mainly involving skin, lung and/or lymph nodes.4 In two cases with reported sarcoid related to ipilimumab, the angiotensin converting enzyme (ACE) levels were within reference ranges,12,13 while in another case the ACE level was raised.14 Our patient did not have any evidence or symptoms suggestive of extra-renal sarcoid. No case reports of tuberculosis (TB) in patients receiving ipilimumab were found. In our patient, there were no features in his history, and examination that suggested TB. Also, With tuberculosis the granulomas tend to be necrotizing or caesating11, unlike in our case.

[CTLA-4]. It works as an anti-cancer medication by inhibiting CTLA-4 thereby increasing the body’s anti-tumour immunity.15 These types of monoclonal antibodies are also referred to as Immune Checkpoint Inhibitors and have been shown to be very effective in treating melanoma and other malignancies.1 Immune-related adverse events are well recognised complications of monoclonal antibody treatment and these include colitis, hepatitis, dermatitis, endocrinopathies, eye, neuropathies and myopathies.2 There are a few reported cases of ipilimumab causing acute kidney injury. 6,16,17 It is important to be aware of this less common side effect, especially as these agents are increasingly being used in cancer treatment.

The incidence of AKI of any severity in patients on Immune Checkpoint Inhibitors is estimated to be about 2.2% and that of severe AKI is 0.6%.5 In most cases reported in literature, renal biopsies show granulomatous interstitial nephritis .6,17,18 Other pathological lesions reported include acute Drugs which are common culprits for granulomatous tubular necrosis6, lupus nephritis6,19,thrombotic interstitial nephritis fall in the common categories microangiopathy5,6,18 and minimal change disease.20 below: Two case series of acute kidney injury secondary to • Antibiotics (penicillin, cephalosporin, sulpha ipilimumab or check point inhibitors could be found. drugs, quinolones) The four biopsies in the case series by Izzedine et al • Non-steroidal anti-inflammatory drugs showed three with granulomatous tubulo-interstitial nephritis and one with membranous lupus nephritis.6 (ibuprofen, naproxen, diclofenac) In the case series by Cortazar et al, 12 of the 13 • Proton Pump Inhibitors (omeprazole, patients’ biopsies showed acute interstitial nephritis, lansoprazole) with three having granulomatous features and one with thrombotic microangiopathy. Four patients in • Other medications (allopurinol and this case series required renal replacement therapy anticonvulsants). similarly to the patient in this case report.5 The main pathophysiological mechanism of drug induced interstitial nephritis is thought to be an Withdrawal of the offending drug is usually enough immunologically induced hypersensitivity reaction.8 to treat mild renal impairment resulting from drug However, Cortazar et al have suggested the possibility induced interstitial nephritis. However, in severe of a different mechanism due to loss of tolerance cases, steroids are used to treat patients. In fact, other against endogenous antigens associated with immunosuppressive treatment such as mycophenolate 17 immunotherapy or indeed a reduction in tolerance to mofetil is added if steroids have had no effect. In drugs that are known to cause interstitial nephritis.5 Cortazar’s case series, nine of the 10 patients with This can occur within days of starting the offending interstitial nephritis treated with steroids had drug but can sometimes occur after several months complete or partial recovery of renal function. Our of exposure, with a range of 21 to 245 days seen in the patient received prednisolone, after discontinuing ipilimumab, and his renal function recovered well Cortazar et al case series.5 enough to get him off haemodialysis. Our patient had a drug induced granulomatous interstitial nephritis secondary to ipilimumab. This case report underscores the importance of today’s Ipilimumab is a human IgG1 monoclonal antibody physicians’ need to be aware of the potential adverse which targets cytotoxic T Lymphocyte Antigen 4 effects of newer anti-cancer treatments. 94

Midlands Medicine

3. Abdel-Wahab N, Shah M and SuarezAlmazor ME Adverse Events Associated with In this case report we present a patient who developed Immune Checkpoint Blockade in Patients with acute kidney injury from acute granulomatous Cancer: A Systematic Review of Case Reports tubulo-interstitital nephritis secondary to ipilimumab PLoS One [Internet]. 2016 [cited 2016 Oct treatment for metastatic malignant melanoma. 16];11(7):e0160221 The patient made a good renal recovery following Available from: http://www.ncbi.nlm.nih.gov/ withdrawal of the offending agent and treatment with pubmed/27472273 high dose steroids. CONCLUSION

Learning points • Beware of possible nephrotoxicities of new anti- 4. cancer treatment especially that of Immune Checkpoint Inhibitors. • A kidney biopsy may be needed to make the correct diagnosis and help to direct treatment appropriately. • Tubulo-interstitial nephritis is in the differential diagnosis of AKI. ACKNOWLEDGEMENTS We thank the patient for permission to tell his story. ADDRESS FOR CORRESPONDENCE Daniela Farrugia MD MRCP(UK) MMedSci Consultant Nephrologist The Kidney Unit Trent Building Royal Stoke University Hospital, UHNM Newcastle Road STOKE-on-TRENT ST4 6QG

REFERENCES

Hodi FS, O’Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB et al Improved Survival with Ipilimumab in Patients with Metastatic Melanoma N Engl J Med (2010) Vol 363pp711-23 Available from: http://www.nejm.org/doi/ abs/10.1056/NEJMoa1003466

Fecher LA, Agarwala SS, Hodi FS and Weber JS Ipilimumab and its toxicities: a multidisciplinary approach Oncologist (2013) Vol 18 pp733–43

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Bertrand A, Kostine M, Barnetche T, Truchetet M-E and Schaeverbeke T Immune related adverse events associated with anti-CTLA-4 antibodies: systematic review and meta-analysis BMC Med [Internet] 2015 Sep 4 [cited 2016 Oct 16];13:211 Available from: http://www.ncbi.nlm.nih.gov/ pubmed/26337719

5. Cortazar FB, Marrone KA, Troxell ML, Ralto KM, Hoenig MP, Brahmer JR et al. Clinicopathological features of acute kidney injury associated with immune checkpoint inhibitors Kidney Int (2016) Vol pp63847

Izzedine H, Gueutin V, Gharbi C, Mateus C, Robert C, Routier E et al Kidney injuries related to ipilimumab Invest New Drugs (2014) Vol 32 pp769-73

Małyszko J, Kozłowska K, Kozłowski L and Małyszko J Nephrotoxicity of anticancer treatment Nephrol Dial Transplant [Internet] 2016 Oct 5 [cited 2016 Oct 16];gfw338 Available from: http://ndt.oxfordjournals.org/ lookup/doi/10.1093/ndt/gfw338

8. Shah S, Carter-Monroe N and Atta MG Granulomatous interstitial nephritis Clin Kidney J (2015) Vol 8 pp516–23 Available from: http://www.ncbi.nlm.nih.gov/ pubmed/26413275 95

Robson MG, Banerjee D, Hopster D and Cairns 15. Peggs KS, Quezada SA, Korman AJ and Allison HS Seven cases of granulomatous interstitial JP nephritis in the absence of extrarenal sarcoid Nephrol Dial Transplant (2003) Vol 18 pp280-4 Principles and use of anti-CTLA4 antibody in human cancer immunotherapy

10. Joss N, Morris S, Young B and Geddes C Granulomatous interstitial nephritis Clin J Am Soc Nephrol (2007) Vol 2 pp22-30 11. Agrawal V, Kaul A, Prasad N, Sharma K and Agarwal V Etiological diagnosis of granulomatous tubulointerstitial nephritis in the tropics Clin Kidney J (2015) Vol 8 pp524–30 12. Berthod G, Lazor R, Letovanec I, Romano E, Noirez L, Mazza Stalder J et al. Pulmonary sarcoid-like granulomatosis induced by ipilimumab

Curr Opin Immunol (2006) Vol 18 pp206-13 16. Forde PM, Rock K, Wilson G and O’Byrne KJ Ipilimumab-induced immune-related failure - a case report

renal

Anticancer Res(2012) Vol 32 pp4607-8

17. Murakami N, Borges TJ, Yamashita M and Riella L V

Severe acute interstitial nephritis after combination immune-checkpoint inhibitor therapy for metastatic melanoma Clin Kidney J (2016) Vol 9 pp411-7

J Clin Oncol (2012) Vol 30 ppe156-9 Available from: http://www.ncbi.nlm.nih.gov/ 18. Thajudeen B, Madhrira M, Bracamonte E and pubmed/22547608 Cranmer LD Ipilimumab Granulomatous Interstitial Nephritis Am J Ther (2015) Vol 22 ppe84-7

13. Wilgenhof S, Morlion V, Seghers AC, Du Four S, Vanderlinden E, Hanon S et al Sarcoidosis in a patient with metastatic melanoma sequentially treated with anti-CTLA-4 monoclonal antibody 19. Fadel F, Karoui K El and Knebelmann B and selective BRAF inhibitor Anti-CTLA4 Antibody–Induced Lupus Nephritis Anticancer Res (2012) vol 32 pp1355-9 Available from: http://www.ncbi.nlm.nih.gov/ pubmed/22493370 14. Vogel W V, Guislain A, Kvistborg P, Schumacher TNM, Haanen JBAG and Blank CU Ipilimumab-induced sarcoidosis in a patient with metastatic melanoma undergoing complete remission J Clin Oncol (2012) J Vol 30 ppe710 Available from: http://www.ncbi.nlm.nih.gov/ pubmed/22124094

N Engl J Med (2009)Vol 361 pp211-2

20. Kidd JM, Gizaw AB, Perazella MA, Izzedine H, Thajudeen B, Madhrira M et al Ipilimumab-associated minimal-change disease Kidney Int (2016) Vol 89 p720 Available from: http://www.ncbi.nlm.nih.gov/ pubmed/26880464

Midlands Medicine

NEWS HEALTHCARE RESEARCH CONFERENCE & iACS LAUNCH On 12th October the NSMI played host to a research conference entitled Healthcare Research in Staffordshire; Strengthening Partnerships. Stakeholders included UHNM, Keele University and Staffordshire University. A key part of the day was the launch of a new institute, iACS (Institute of Applied Clinical Sciences). Its director, professor Simon Davies, explained its role in delivering clinical research for Keele and the complex overlapping and distinct roles of it and other units and institutes within sciences at Keele University. iACS hopes to effectively â&#x20AC;&#x153;tap into the vast potential clinical research resource that patients attending secondary care representâ&#x20AC;?. The day included plenary sessions with speakers representing all partners: Keele University, Staffordshire University and UHNM, and much of the ongoing clinical research in our area was showcased, some as oral presentations and a good number of posters too. Abstracts of these oral and poster presentations have been presented in the preceding pages. It can be appreciated what a great deal of useful, innovative and quality medical research is underway in the local area. The NSMI is proud to be associated with this research and to continue to play its active part in encouraging and funding local medical research. Though local in conception and leadership, some of the research undertaken or spawned locally is of global importance and reach and many involved should be justifiably proud of their achievements.

REGIONAL UPDATE IN MEDICINE On 17th October the Royal College of Physicians of London held its annual regional update meeting in Birmingham. Topics covered included genetics. Cardiovascular disease and pulmonary fibrosis. See report.

WADE LECTURE Phil Hammond, a funny doctor, gave the recent Wade lecture.

AWARDS Medical student prizes and research awards are being given out again this month. Details to follow in the next issue.

Volume 28, No 2, October 2016

REGIONAL UPDATE IN MEDICINE Dominic de Takats, Editor, Midlands Medicine IBD in the elderly comprises those who have been diagnosed for some time and become old and those Professor Andrew Hattersley, University of Exeter diagnosed for the first time: 15% of cases diagnosed Medical School >60 years. UC may be more indolent. Crohn’s more likely to be colonic than in younger patients. Precision medicine is treatment based on some Polypharmacy means a greater interaction risk. precise knowledge about the genetic aspects of the pathophysiology in an individual. Most commonly 5-ASAs are first line Rx in UC but NOT in Crohn’s. currently practised in the context of cancer where Cortico-steroids are very good at inducing remission understanding the cancer mutation can direct but are poor at maintaining it. Of all steroids, therapy. There will be opportunities practise in in budesonide may be a better option. Mercaptopurine (but beware lymphoma risk); methotrexate many more diseases as sequencing becomes ever more is an option (but watch liver and renal function); available. Examples from diabetes mellitus including biologicals in the elderly: higher risks of infection, glucokinase mutations (stride 2014) in which malignancy and death ≥65 years than under 65 years. treatment is neither necessary nor effective. (HNF 1α Furthermore, these drugs may be less effective in the MODY Pearson et at Lancet 2003). In passing, the elderly. Surgery is still an option older patients and usefulness of probability modelling was discussed in might be a better choice in the relatively less co-morbid the context of distinguishing between Type 1 DM and for whom medical therapy is proving unsatisfactory in terms of side effects/lack of efficacy. MODY. (There’s an app [diabetes diagnostics]) THE DNA SEQUENCER WILL SEE YOU NOW

T1DM is very unlikely to be diagnosed before the age of 6 months, Gloyn et al NEJM 2004 Kir6.2 mutations Pearson et al NEJM so diabetics under 6 months should be offered a genetic diagnosis. Mr 33: 33 years, blood G 33 mmol/l, BMI 33 kg/m2 Theresa is a late presenting T1 GAD is very helpful in younger patients (under 20 years) but not very specific in those over 40 years

Small strokes, big problems; the ‘epidemic’ of cerebral small vessel disease by Hugh Markus, Small vessel disease. MR scanning has made appreciation much greater than was previously the case. Small perforating end arteries with no collateral circulation so loss of flow causes a lacunar infarct. More diffuse white matter damage is thought to largely be due to hypoperfusion. Churchill, Roosevelt and Stalin all had small vessel disease

Polygenic risk assessment retains a greater element of doubt than there is for the monogenic disorders. • Asymptomatic INFLAMMATORY BOWEL DISEASE IN THE ELDERLY: SENSE AND SENSIBILITY

• Stroke • Vascular dementia

Dr Jimmy K Limbdi, Consultant Gastroenterologist, • Parkinsonism Pennine Acute Hospitals NHS Trust • Depression Crohn’s and ulcerative colitis Lacunar infarcts as subcortical and may interrupt ECCO (European Crohn’s and colitis organisation) cortico-spinal tracts but since they are not in the cortex itself they don’t affect cognitive function: pure What elderly? What age? Biologically or motor stroke; pure sensory stroke; sensorimotor chronologically old? Over 60 years! stroke, clumsy hand-dystharthria syndrome; if one Broader differential including neoplasia and ischaemic limb only is affected then it is likely a cortical infarct. colitis 98

TOAST classification is better than the Oxford Midlands Medicine

Community Stroke project classification in these days of improved imaging.

Cardiac Arrest

Dysexecutive syndrome (planning and organisation: sophisticated review: MMSE is far too blunt an instrument to appreciate this level of disease). Start by taking a collateral history as the patient might be unaware, psychometric testing (BMET http://www. cambridgestroke.com/bmetcognitivetesting.php)

In cases of out-of-hospital ROSC (return of spontaneous circulation) Utstein ROSC: witnessed arrest, bystander CPR, first rhythm shockable and ROSC (http://circ. ahajournals.org/content/110/21/3385) is presumed to be cardiac in origin and should go directly to a cardiac centre in preference to the nearest hospital

Hypertension remains the key risk factor for stroke. (SPS3 trial)

Anti-platelets and related therapies:

Depression is over-represented in patients with small vessel disease correlating to ultrastructural white matter disease but it still responds to antidepressant treatments and successful treatment makes a big difference to quality of life. What to do with a report stating white matter damage in essentially asymptomatic patients? Address usual risk factors and screen for cognitive impairment first by the simple expedient of taking a collateral history, perhaps later apply BMET. ADVANCES IN THE MANAGEMENT OF CORONARY ARTERY DISEASE

Prasugrel, ticagrelor, cangrelor are in clinical use as are low molecular weight heparins and fondaparinux, and factor Xa inhibitors. We are still really in the era of learning how to use these drugs (Editor’s note: the big data studies led by Prof Mamas Mamas and supported by NSMI grants will log and interrogate the real world experience of using these treatments). Newer imaging methods for coronary arteries: intracoronary ultrasound scanning, intra-coronary near infrared scanning, PET CT scanning. These allow earlier assessment and more complex appreciation of CAD. What would you put in a poly pill?

Roby Rakhit, Consultant Interventional Cardiologist, ENABLING THE MEDICAL REGISTRAR Royal Free Hospital Dr Andrew Macleod, RCP West Midlands Regional • ACS Advisor • Arrest This is, in effect, a large scale and long term Quality • Anti-thrombotics improvement Project, starting with an audit documenting the current state of play through • Detection of vulnerable plaques e-questionnaires and focus group interviews. Heart attacks are not (quite) what they used to be: Consultant support is the key parameter in making specialty registrars feel safe and comfortable in their (a cardiac enzyme rise using new highly sensitive role. Generally support was thought to be good assays+ one or other of pain, ECG changes) and complaints of bullying at work was its absence. Unstable angina However, StRs do want mare feedback about patients they have seen. Some anxieties were expressed about NSTEACS roles where they overlap or interface with other professions such as senior nurses and physician STEMI associates. GRACE Global Registry of Acute Coronary Events (http://www.outcomes-umassmed.org/grace/acs_ The next step is a simple one: collating, publishing risk/acs_risk_content.html) and disseminating the report containing examples of Early rule out using high sensitivity troponins. High good practice. risk patients should have early (immediate) access to primary PCI. Best results are if PCI is delivered An open forum was held with national and local within 2 hours of admission to hospital. Direct access RCP officers. is preferable to via A&E. “Door-to-balloon time” “We find ourselves in a difficult position when it Radial approach is quicker and safer (Also in Mamas comes to speaking truth to power.” Mamas’) talk Jane Dacre, President of the RCPL Volume 28, No 2, October 2016

are related to connective tissue diseases and an appropriate auto-antibody screen is a worthwhile part of the diagnostic work-up, including Scl70 (antiPierpaolo Pellicori, Honorary Senior Lecturer in topoisomerase 1). Cardiology at Hull and York Medical School Idiopathic pulmonary fibrosis: a typical patient would This clearly is an area where our knowledge is not yet be an elderly male ex-smoker with clubbing and bimature. Often female, exertional dyspnoea, clinical basal inspiratory crackles. Progressive disease is the signs of heart failure and raised NTproBNP. New hallmark. Idiopathic is what is left un-understood guidance: when what can be explained has had a cause LVEF is a potentially a late consequence of heart attributed, so with each advance in understanding failure which has been developing slowly. We haven’t reduces those cases of PF which remain categorised as cryptogenic. Some turn out to be genetic (rarely really found great treatment for it yet. found from kindreds). Diagnosis of PF is on a CT scan HFpEF, HFmrEF, HfrEF (Heart failure with preserved (honeycombing, reticulation and traction change) but ejection fraction/mildly reduced/reduces) best appreciated on lung function tests, including gas https://w w w.ncbi.nlm.nih.gov/pmc/ar ticles/ transfer. HEART FAILURE WITH PRESERVED EJECTION FRACTION

PMC3211140/

Inflammatory ILD can be treated with steroids and NOVEL APPROACHES TO PULMONARY FIBROSIS immunosuppression but this doesn’t work in fibrotic disease. Effective disease modifying agents have Gisli Jenkins, Professor of experimental medicine at become available in recent years but good supportive the University of Nottingham and holistic care are still key in treating patients.

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Pirfenidone and nintedanib New biomarkers are being developed to allow the identification of those progressing more rapidly and who therefore potentially might better benefit from disease modifying.

There is nothing more vivifying than a hypothesis. Primo Levi, The Periodic Table, Nickel

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Idiopathic Pulmonary Fibrosis (IPF) and asbestosis and progressive pulmonary fibrosis are closely related. Sarcoidosis is different. In practice the more fibrotic conditions tend to be progressive whilst the more inflammatory ones appear more amenable to treatment. Many inflammatory lung diseases

Midlands Medicine

GETTING TO KNOW: KEVIN GREAVES DEVELOPING MY ROLE

THEN AND NOW My name is Kevin Greaves and I have been qualified as a physiotherapist since 2004. I specialised in cardiorespiratory care in 2005 following my junior rotations and have had experience working within the acute trust and primary care. I also worked for 12 months in a senior role on medicine at Wellington Hospital in New Zealand where I had the privilege of working on the medical wards and in the respiratory outpatient clinic. During this time I also had the honour of setting up and running a pulmonary rehabilitation programme. Since returning to the UK in 2007, I have worked in a clinical role as part of the specialist community respiratory team, working predominantly with patients diagnosed with Chronic Obstructive Pulmonary Disease (COPD) in a pulmonary rehabilitation setting. However, within this role I also support the nursing staff in the wider respiratory team in preventing acute hospital admissions and supporting early discharge from hospital. Within this role I am regulated by the Health and Care Professions Council (HCPC) and am able to work autonomously, assessing, diagnosing, treating and discharging patients. However up until recently I have been unable to provide a truly holistic service to the patient as there was no scope to prescribe or adjust medications necessary to their long term management. Volume 28, No 2, October 2016

I am moving on to encompass prescribing within my role. The ability to prescribe within my field of competence and confidence will complement the existing skillset and eliminate the frustration around completing the episode of care and reducing the reliance upon the availability of a doctor which can be problematic.1 It will also provide the opportunity to fully implement a person-centred approach that facilitates safe and effective medicine use through the optimisation of medication regimes that are essential when supporting the management of people who have a long term conditions, multi-morbidity and polypharmacy.2 The ability to prescribe offers potential benefits to the patient including improved access, improved patient safety and patient centred care.3 With this in mind the opportunity to extend my scope of practice has become available within the team, working in a more generic role alongside the specialist respiratory nurse specialists who are already nonmedical prescribers. As a part of this role I will be delivering respiratory clinics set in locations around Stoke-on-Trent providing better access for patients as suggested in Lord Darziâ&#x20AC;&#x2122;s report.4 Home visits will also be made to assist housebound patients which will allow me to provide medicines management support in the recovery phase following hospital discharge along with admission-avoidance input. This fits in with the local Trustâ&#x20AC;&#x2122;s aims of decreasing the amount of bed days for respiratory patients. Qualifying as a non-medical prescriber will allow me to work with greater autonomy in my role as a specialist respiratory physiotherapist, moving away from my traditional role and challenging professional roles, boundaries and hierarchies.5 Reduced dependence upon doctors and the provision of a more streamlined service for patients providing a complete episode of care are driving factors.6,7 However it will be important to continue to engage with medical staff and discuss medication choices.8 101

ADDRESS FOR CORRESPONDENCE Kevin Greaves Physiotherapist Community Respiratory Team Stoke Health Centre Honeywall Stoke on Trent ST4 7JB REFERENCES 1

Royal College of Physicians. (2005) Doctors in Society: Medical Professionalism in a Changing World. RCPL

High quality care for all: NHS next stage review final report Department of Health (2008)

Charles-Jones H, Latimer J and May C Transforming general practice: the redistribution of medical work in primary care Social Health Journal (2003) Vol 25 pp71-92

Wilhelmsson S and Foldevi M Exploring views on district nurses’ prescribing – a focus group study in primary health care Journal of Clinical Nursing (2003) Vol 12 pp643-50

2 National Institute for Health and Care 7 Gibson F, Khair K and Pike S Nurse Prescribing: Excellence. (2015) children’s nurses views Medicines Optimisation: the safe and effective Paediatric Nursing (2003) Vol 22 pp20-4 use of medicines to enable the best possible outcomes 8 Jones M and Jones A Prescribing new ways of 3 Royal College of Nursing. (2012). Nurse working Prescribing in the UK. London: RCN Mental Health Practice (2006) Vol 9 pp20-2

HG Wells

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Every time I see an adult on a bicycle, I no longer despair for the human race.

Midlands Medicine

TEN QUESTIONS ON DIABETES MELLITUS Oluseyi Ogunmekan, General Practitioner, Furlong Medical Centre, Stoke-on-Trent 1

Impaired fasting glucose is defined as a blood 6 level between 6.1 and 6.9 mmol/L (inclusive). True or False?

Patients with Impaired Fasting Glucose and Impaired Glucose Tolerance are at an increased risk of MICROVASCULAR complications such as retinopathy or nephropathy.

True or False?

Metformin should be discontinued if the eGFR falls below 30.

True or False?

Consider commencing patients for exenatide if on metformin and a sulfonylurea and BMI > 35kg/m2

True or False?

“Diabetic Jam” or “Diabetic ice-cream” is strongly recommended for patients with Type 2 Diabetes Mellitus.

True or False?

Volume 28, No 2, October 2016

Regarding the new units for measuring HBA1c, an HBA1c of 7% is equivalent to 53mmol/mol. True or False?

Microalbuminuria is a component of the metabolic syndrome.

True or False?

The value of HbA1c is affected by: (a) Haemoglobinopathies (b) Splenectomy (c) Iron deficiency anaemia (d) Acute blood loss (e) All of the above (f) None of the above

a. What does BM stand for? b. What does MODY stand for?

10 Which of the following is licensed with insulin?

(a) Gliclazide (b) Linagliptin (c) Metformin (d) Exenatide (e) All of the above (f) None of the above

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INTERESTING IMAGES

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Midlands Medicine

This elderly lady presented unwell due to oligo-anuric acute kidney injury. Many months earlier she had declined investigation of a left adnexal mass. In the first, coronal, CT image a left a hydro-ureter (yellow arrow) can be seen, capped by a shrunken non-functioning kidney. In the second, transverse, CT image a stone lodged in the vicinity of the pelvi-ureteric junction of the healthy right kidney is clearly identifiable as the cause of recent onset oligo-anuria and AKI. Non-contrast CT scanning was undertaken in view of her AKI. Another point to note on the first image is that black dot. It represents gas, thereby giving a diagnosis of emphysematous pyelonephritis. This is a true urological emergency and requires urgent intervention. The most practical specific next step is the insertion of a nephrostomy tube alongside the usual elements used to support a patient with severe sepsis: broad-spectrum antibiotics, intravenous fluids and inotropes. Sufficiently early de-obstruction in such cases as this one, as well as relieve the severity of the sepsis, will obviate the need for dialysis support; untreated, the combination of sepsis and AKI would inevitably prove fatal.

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TEN ANSWERS AND EXPLANATIONS 1 TRUE

7 TRUE

Impaired fasting glucose is defined as having a level between 6.1 and 6.9 mmol/L (inclusive).

Metabolic syndrome is a condition of abnormal glucose regulation (Impaired Fasting Glucose or Impaired Glucose Tolerance) associated with one or more risk factors for cerebrovascular disease. Remember:

2 FALSE Patients with Impaired Fasting Glucose and Impaired Glucose Tolerance are at increased risk of MACROVASCULAR complications such as cerebrovascular disease, Peripheral Vascular Disease or Ischaemic Heart Disease. It is because they are NOT at increased risk of MICROVASCULAR complications, that they do not require annual retinal or foot examinations. 3

Microalbuminuria Elevated Triglycerides And BP (Hypertension) Obesity Low HDL IFG / IGT (impaired glucose regulation) CVD risk factor

TRUE, sort of.

(e) All of the above, see the table: Metformin is advised to be stopped when the creati- 8 nine clearance is < 30mls / minute / 1.73m². Caution is advised when the eGFR falls below 45mls / min / Factors Increases HbA1c Decreased HbA1c 1.73m2. But careful use can continue to lower levels Deficiency of iron or Reticulocytosis of kidney function if backed up by ‘Sick Day rules’ vitamin B12 Chronic liver disease Erythropoiesis meaning that patients stop metformin if unwell. 4 TRUE However, exenatide may be considered in patients already on metformin and a Sulphonylurea if: “BMI < 35kglm2 and insulin is unacceptable because of occupational implications or weight loss would benefit other co-morbidities” (NICE Guidelines May 2009).

Glycation

Erythrocyte Destruction

Assays

Alcoholism Chronic renal failure

Aspirin Vitamin C

Splenectomy (increased RBC life span)

Splenomegaly (Decreased RBC life span)

Hyperbilirubinaemia Alcoholism

Hypertriglyceridaemia

5 FALSE These are often more expensive and not recommended.

b. MODY = Maturity onset diabetes of the young. Quaintly aged terminology for atypical, often monogenic, T2DM of early onset.

6 TRUE Remember the rule MINUS TWO MINUS TWO. So 7-2 = FIVE, 5-2= THREE. Thus 7% becomes 53 106

a. BM = Boehringer Mannheim

(e) All of the above Midlands Medicine

Thereâ&#x20AC;&#x2122;s more you can depict with red, purple, white, blue and an occasional splash of yellow than what you get with haematoxylin and eosin histology slides. This you can see above in the Gordon Mitchell Forsyth stained glass window which can be found in St Josephâ&#x20AC;&#x2122;s church in Burslem. For more information go to www.stjosephsburslem.org.uk. Volume 28, No 2, October 2016

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