MMJ Final 6 14x9 21

Foreword by Professor Tony Freemont
If it is statistically significant does it

make it clinically important
?
Treatment options for patients with

primary myelofibrosis
Abstracts of the 7th Scalpel
Undergraduate Surgical Conference
LAUNCH
NOVEMBER 2016
MANCHESTERMEDICALJOURNAL COM
.
Manchester Medical Journal, 2016 The Authors 2016

Editor in Chief: Professor Tony Freemont
Student Editors: Harriet Van Den Tooren (Lead), Tadhg Blunt, Catherine Donnelly, James Keitley and Hannah McKay
Associate Editors: Dr Joshua Burke, Dr Sadhia Khan, Dr Jack Samways and Dr Rachael Morley
Journal founders: Dr Joshua Burke, Dr Adam Mitchell and Dr Sadhia Khan
Published by Manchester University Press, The University of Manchester Library and the Manchester Medical School
Pilot edition printed November 2016
All featured articles are Open Access and published under the conditions of the Creative Commons Attribution-NonCommercial
licence https://creativecommons.org/licenses/by-nc/4.0/
CONTENTS
Foreword
Inspirational doctors, back pain and the MMJ - Tony Freemont
Editorials
Gene discovery for rare diseases - Miriam J Smith
Critical appraisal skills, tomorrow's doctors and the Manchester
Medical Journal - Joshua Burke, Sadhia Khan, Adam Mitchell
If it is statistically significant does it make it clinically
important? - Simon Beecroft
Original research
Transition at Emerge: evaluating transition practice and
elucidating ethnic differences - Adam Kuhivchak
Audits
Readmissions at Royal Oldham Hospital AMU - Samuel W G
Hogg
Cardiovascular disease risk assessment in psoriasis patients Vera Nakata
Case reports
Treatment options for patients with primary myelofibrosis Andrew Swali, Montaser Haj
Abstracts
Post-surgical complication rates of elective excision of
pilondial sinus disease and the need of post-operative
appointments - Ardit Begaj
Use of augmented reality in surgery - Rathaven Gunaratnarajah,
Parthvi Vanalia
Intraoperative glycaemic control - Dillon Horth
A 3D in vitro co-culture to model peripheral nerve
remyelination after injury - Benjamin Kadler
Bunions, feet and battling nerve damage: is the sentinel vein
a reliable landmark to locate the dorsomedial cutaneous
nerve of the hallux? - Jennifer Lindsay
Cosmetic surgery: a curse or a blessing? - Amir P Salahi
Indications for dual-mobility hip replacements - Jennifer
Rossiter, Anthony Helm
Local excision of early rectal cancers by transanal endoscopic
microsurgery (TEM) - Hon L Wu
The use of routine CT imaging to assess sarcopenia in patients
undergoing chemo-radiotherapy for rectal cancer - Sean Young
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Manchester Medical Journal (2016)
FOREWORD
Inspirational doctors, back pain

and the MMJ
Were I ever to be asked who were my medicine heroes, three names
would immediately come to mind.
Ibn al-Nais (121388), against all Galenic teaching, described the circulation of blood through the lungs 400 years before Harvey wrote his De
Motu Cordis; he was the author of 110 volumes of medical texts and based
his studies on human dissection.
John of Ardern (130792) was arguably the irst English surgeon, and
certainly one of the irst surgeons to develop cures (his most renowned
for istula-in-ano).
Barry Marshall (1951date) is Professor of Microbiology at the
University of Western Australia, and won the Nobel Prize for Medicine
in 2005 for discovering the link between Helicobacter pylori and gastritis;
on the way, testing Kochs postulate on himself and proving his detractors
wrong.
There have been many other great doctors over the centuries, but surely
none who could be held to have questioned established practice, contemporary thinking and cultural taboos by the application of pure clinical
scientiic research in the way these three have.
Nowadays everyone is searching for the evidence base of diagnostics
and patient management, and we would be shocked were our students not
to understand the importance of evidence in developing medicine.
But whilst many of us practise evidence-based medicine, few are privileged to be permitted to develop that evidence base. A privilege it most
certainly is, but it is also hard work. I have studied the pathology of discogenic back pain and the biology of the intervertebral disc for 30 years.
Only after that time and working as part of a fabulous team including
Professor Judith Hoyland, a gifted molecular pathologist, and Professor
Brian Saunders, a radical innovator in nanobiomaterial chemical engineering, have we been able to come up with a new evidence-based treatment
for patients with chronic back pain. This has been facilitated by working
in a far-sighted university and with clinical colleagues who recognise the
limitations of their existing practice.
The route into clinical research has never been more structured, with
funding for academic posts at foundation-, early-, mid- and late-career
1
Manchester Medical Journal, 2016 The Authors.
http://dx.doi.org/10.7227/MMJ.0001
This is an Open Access article published under the conditions of the Creative Commons Attribution-NonCommercial licence
https://creativecommons.org/licenses/by-nc/4.0/
Tony Freemont
level being made available through the National Institute for Health
Research, universities, research councils and research charities. Even so,
entering into and lourishing in a research career is not easy, and that is
why there is a real shortage of clinical researchers in the UK. However,
after 35 years as a clinician scientist I would recommend trying the intellectual freedom, the chance to meet great minds and the opportunity to
make a diference to patients lives.
So, supposing you are now thinking that research, as part of a wider
clinical career, might be for you. How should you proceed? Well two big
questions are asked by those considering a medical research career:
How do I discover if I like the rigour of clinical research?
How do I get into medical research?
Firstly, if you are reading this then you have started. You have enquired,
and an enquiring even overtly questioning mind is a prerequisite. But
you need a little (!!) more than that.
You need to build your CV. There are few other medical schools that
allow students the opportunities Manchester does to investigate research
on their course and through sponsoring extracurricular societies. Take
those opportunities; undertake an intercalating degree, and meet and
nurture a relationship with the great clinical researchers in Manchester
in your chosen area of medicine. Take every opportunity to do research,
write it up, present it at meetings and meet more like-minded people.
You have to do the leg work, but there is loads of advice out there. What
everyone worth listening to will tell you is to build your CV, prove that
you are interested, publish and present your indings and listen to, and
learn from, criticism.
It is impossible to think of a better way to cut your research teeth than
by submitting to the MMJ. You wont be successful all, or even most,
of the time, but the feedback from peers and more senior colleagues will
guide your future research and make you a better thinker and researcher.
The only advice I can add is be lucky, and remember the aphorism,
The harder I work, the luckier I get. Or, to translate to the here and now:
support the MMJ and it will support you.
Tony Freemont
University of Manchester
2
EDITORIAL
Gene discovery for rare diseases

M. J. Smith
Centre for Genomic Medicine, University of Manchester
miriam.smith@manchester.ac.uk
Within Europe, a disease is classiied as rare if it afects fewer than 1 in

2,000 people. Currently there are between 5,000 and 8,000 known rare
diseases, while further novel syndromes are reported every month. There
is wide variation in the numbers of people afected by each condition, with
some conditions only known to afect a single family or person. However,
while each of these disorders is individually rare, overall, rare disorders
afect more than 5% of the population worldwide,(1,2) thus representing a
signiicant medical problem. Few drug therapies exist for these diseases
and investment in drug development by pharmaceutical companies for a
rare disease is often not seen as economical, which leads to diiculties in
providing suitable treatment options.
Rare genetic disorders can be caused by mutation of a single gene or
multiple genes, or by large chromosomal rearrangements. Early diagnosis
and treatment of these disorders, many of which are present at birth, can
be a critical part of their successful clinical management. However, the
genetic causes and deinitive diagnostic criteria of a large number of these
disorders are still unknown, making them unfamiliar to most clinicians.
In addition, there can be signiicant clinical variability within a disease
phenotype. In some cases this has resulted in genetically distinct disorders
with overlapping clinical symptoms being erroneously grouped together.
In other cases, variations in the presentation of a single disorder may
result in subdivision of syndromes that are in fact a single entity. This
means that obtaining a correct diagnosis is challenging and time-consuming, which exacerbates the problem of providing efective clinical management for afected individuals. Genetic characterisation of these disorders
can be important for unequivocal diagnosis, and there is a pressing need
for further research to identify the underlying genetic causes of uncharacterised rare diseases to inform patient care.
The large number of known rare disorders, together with the small
number of people afected by each condition, often means that there is
little research into their underlying causes. Traditionally, identiication
of pathogenic mutations has been achieved through the use of a variety
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M. J. Smith
of techniques, including chromosome mapping, Sanger sequencing and

copy number analysis. More recently there has been a rapid increase in the
number of whole-exome sequencing investigations, which has helped to
accelerate the rate of identiication of novel pathogenic mutations for rare
diseases. As the cost of whole-genome sequencing decreases, it is becoming the new standard in gene discovery. This technology has the potential
to enhance mutation discovery further, as it has the capacity to cover up
to 100% of the genome sequence rather than the 12% obtained by exome
sequencing,(3) thus allowing identiication of mutations in non-proteincoding regulatory regions of the genome, and provides more comprehensive copy number information.
While whole-genome sequencing generates a large amount of genetic
data, it also brings new challenges in data interpretation. There are
increasing numbers of rare polymorphisms appearing on public online
databases, obtained from large cohorts of anonymised individuals, either
with a particular type of disease, or with no known disease. This can cause
confusion when deciding whether a variant is clinically signiicant, particularly when trying to distinguish pathogenic low-penetrance variants
from rare non-pathogenic polymorphisms without comprehensive clinical
information. New programs and algorithms are being created to interpret
copy number data, as well as non-exonic variants, and to make the data
analysis pipeline more user friendly.
High-throughput sequencing eforts will enhance our ability to ind
the underlying causative variants of rare diseases and to delineate genotypephenotype correlations, but collaboration is required to achieve this.
This includes pooling of DNA samples from many institutions to increase
the power of these studies, along with rapid high-throughput sequencing
of those samples and large-scale bioinformatic data interpretation. One
large-scale project aimed at identifying the causes of uncharacterised rare
diseases is the 100,000 Genomes Project (http://www.genomicsengland.
co.uk/the-100000-genomes-project/). Manchester is one of 11 sites across
the country involved in the pilot study. The project has the overarching
aim of integrating genomic data into the healthcare system to inform
future clinical management decisions. An initial push for gene discovery
will subsequently be translated into routine genomic diagnosis to allow
faster, more accurate, diagnosis and improved medical care.
Identiication of pathogenic mutations in genes that are involved in the
same pathways as other known disease genes allows for the repurposing
of existing drugs to expedite provision of efective drug therapies. This,
in turn, will reduce the costs of developing medication for rare-disease
patients. For diseases caused by mutations in genes without a known function, targeted drugs will take longer to develop, but their initial identiication will provide the basis for future research to characterise them and to
delineate the mechanism of pathogenicity so that novel drugs can be devel-
4
oped. In the meantime, clinicians need to be made aware of the collective

prevalence of rare diseases and the importance of medical genetic research
to improve future healthcare for these patients.
1 Kaplan W, Wirtz VJ, Mantel-Teeuwisse A, Stolk P, Duthey B, Laing

R. Priority medicines for Europe and the World 2013 update [Internet].
Geneva: World Health Organization; 2013 [cited 2016 May 23].
Available from: www.who.int/medicines/areas/priority_medicines/
MasterDocJune28_FINAL_Web.pdf.
2 European Organisation for Rare Diseases (EURORDIS). Rare diseases:
understanding this public health priority [Internet]. Paris: EURORDIS;
2005 Nov [cited 2016 May 23]. Available from: http://www.eurordis.org/
sites/default/iles/publications/princeps_document-EN.pdf.
3 International Human Genome Sequencing Consortium. Finishing
the euchromatic sequence of the human genome. Nature. 2004
Oct;431:93145.
Gene discovery for rare diseases
References
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6
EDITORIAL
Critical appraisal skills, tomorrows

doctors and the Manchester
Medical Journal
J. Burke,1 S. Khan,2 A. Mitchell3
1
Manchester Medical Journal founder and Associate Editor; Academic Foundation

Doctor, Barts and the Royal London Hospitals
joshburke@doctors.org.uk
2
Manchester Medical Journal founder and Associate Editor; Foundation Doctor, East
Midlands
3
Manchester Medical Journal founder and level 2 reviewer; Foundation Doctor,
London North West Healthcare NHS Trust
Evidence-based medicine (EBM) provides the foundation for gold standard healthcare worldwide, encouraging the use of high-quality clinical
research to optimise patient care. Since the conception of EBM, research
output has increased exponentially, as has the number of published articles. In 2012, it was estimated that around 28,000 active peer-reviewed
journals in circulation collectively published around 1.8 million articles
per annum.(1) The increasing number of published articles can dilute the
quality of research that contributes towards EBM, posing a challenge
for the healthcare professional trying to keep up to date; journal clubs
have therefore emerged as a useful tool. They have been utilised from as
early as the nineteenth century by Sir William Osler for the purpose and
distribution of periodicals to which he could ill aford to subscribe as an
individual.(2)
More recently the use of social media has revolutionised the journal club
platform,(3,4) but there have been no direct comparative studies between
pedagogical, lecture and group-based journal clubs and those which are
based on the internet. There has been a rise in both free open-access
medical education (FOAM) and open-access (OA) journals. The origins
of both could be argued to come from the Hippocratic oath,(5) which
states: and to teach them this art if they desire to learn it without fee
and covenant.(6) Unfortunately, the critical analysis of research is not necessarily seen as a priority for all medical undergraduates or junior doctors.
As the student doctor reaches for the safe environment of a peer-favoured
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J. Burke, S. Khan, A. Mitchell
textbook to reach his or her primary target of passing exams,(7,8) the junior
doctor may utilise online point-of-care tools (e.g. UpToDate, BMJ Best
Practice, DynaMed) which have become popular in recent years,(9,10) but
with standards for evaluating these tools yet to be fully established.(11) For
both demographics the demands foster a diicult environment in which to
pursue academic interest.(12)
In 1996, the Royal College of Physicians and Surgeons of Canada produced a framework that proposed six pillars of the medical expert.(13) One
of these pillars was the medical scholar, which necessitated the ability to
critically analyse medical literature. It seems reasonable to suggest that
a newly qualiied foundation doctor should have a basic understanding
of how to interpret and digest medical literature. It could be argued that
the motivation to do so is on the decline; however, with the rise of big
data and increasing literature there is a growing necessity to diferentiate good-quality research to ensure excellent clinical care is continually
provided. A number of attempts have been made to assist clinicians in
the development of their critical-appraisal skills, but training currently
varies widely at an undergraduate and postgraduate level.(1416) The latest
Cochrane review suggested that low-intensity critical-appraisal teaching
interventions may result in modest gains despite most studies failing to
blind the outcome assessment.(17) In parallel with difering medical school
curriculums and varied basic surgical teaching, the Royal College of
Surgeons of England has recently published a new national undergraduate
curriculum.(18) Perhaps a national academic undergraduate curriculum
would aid medical students in developing critical-appraisal skills.
Conceivably in an attempt to ill this void, a number of undergraduate
medical journals have been established, many of which utilise undergraduate medical students as reviewers and promote active participation
in critical appraisal. One undergraduate medical journal also involves
consultants or specialist reviewers in its process.(19) However, there exists
a niche for a journal with both high-quality output and formal teaching.
This year has seen the launch of the Manchester Medical Journal
(MMJ), which has the primary aim to promote an environment where all
levels of the academic ladder can learn from critical appraisal. Ofering
the opportunity to publish during a students undergraduate years allows
the journal to facilitate, guide and develop interest and skills in academic
writing. This is the irst student-led open-access journal to utilise an
original blinded peer-review system. PRISM (Peer Review Integrated
Student Model) is a novel platform for undergraduates and junior doctors
to receive timely feedback on both writing and critiquing papers. It is
expected that reviewers will gain experience in critical appraisal and
consolidate this through the feedback loops with academic trainees and
specialists.(20) To uphold reviewer status, participants are required to
attend regular audited critical-appraisal workshops, abide by the journals
8
References
1 Ware M, Mabe M. The STM Report; an overview of scientiic and
scholarly journal publishing [Internet]. The Hague: International
Association of Scientiic, Technical and Medical Publishers; 2012 [cited
2015 Oct 18]. Available from http://www.stm-assoc.org/2012_12_11_
STM_Report_2012.pdf.
2 Linzer M, DeLong ER, Hupart KH. A comparison of two formats for
teaching critical reading skills in a medical journal club. J Med Educ.
1987 Aug;62(8):6902.
3 Sherbino J, Joshi N, Lin M. 2015 JGME-ALiEM Hot Topics in Medical
Education Online Journal Club: an analysis of a virtual discussion about
resident teachers. J Grad Med Educ. 2015 Sep;7(3):43744.
4 Roberts MJ, Perera M, Lawrentschuk N, Romanic D, Papa N, Bolton D.
Globalization of continuing professional development by journal clubs
via microblogging: a systematic review. J Med Internet Res [Internet].
2015 [cited 2015 Oct 18]; 17(4):e103. Available from http://www.ncbi.nlm.
nih.gov/pmc/articles/PMC4424319/.
5 Nickson CP. From Hippocrates to Osler to FOAM [Internet].
Lifeinthefastlane.com; 200716 [updated 2016 May 24; cited
2016 Aug 1]. Available from: http://lifeinthefastlane.com/
from-hippocrates-to-osler-to-foam/.
6 Edelstein L. The Hippocratic oath: text, translation and interpretation.
Baltimore: Johns Hopkins University Press; 1943.
7 Mcloughlin CS. Characteristics of students failing medical education.
Med Educ Online [Internet]. 2009 [cited 2015 Oct 18]; 14. Available from:
http://www.med-ed-online.org/pdf/L0000029.pdf.
Critical appraisal skills, tomorrows doctors and the Mancheter Medical Journal
critical-appraisal guidance and relect on feedback of their critiques from

more senior reviewers.
Recently the UK Secretary of State for Health concluded that a doctors
role in diagnosis would be obsolete in two decades.(21) It was suggested
that technological systems could replace the art of diagnosis in governing
patient care. This notion provides a challenging environment to educate
healthcare professionals, not only in the process of critical appraisal but
also its value in delivering EBM. Further work is needed to identify the
optimum platform for the teaching of critical appraisal; the MMJ provides
one such platform that, if successful in its aim, could be considered as a
model for others looking to promote skills in academia amongst students.
We are extremely proud to present the irst pilot issue of the MMJ
and would like to thank our collaborators: Manchester University Press,
which leads internationally on open-access journals; Manchester Medical
School for its ongoing support and guidance; and our undergraduate editorial board, whom we congratulate for this achievement.
9
J. Burke, S. Khan, A. Mitchell
8 Folb BL, Wessel CB, Czechowski LJ. Clinical and academic use
of electronic and print books: the Health Sciences Library System
e-book study at the University of Pittsburgh. J Med Libr Assoc. 2011
Jul;99(3):21828.
9 Younger P. Internet-based information-seeking behaviour amongst
doctors and nurses: a short review of the literature. Health Info Libr J.
2010 Mar;27(1):210.
10 Ketchum AM, Saleh AA, Jeong K. Type of evidence behind point-of-care
clinical information products: a bibliometric analysis. J Med Internet
Res [Internet]. 2011 [cited 2015 Oct 18]; 13(1):e21. Available from: http://
www.jmir.org/2011/1/e21.
11 Shurtz S, Foster MJ. Developing and using a rubric for evaluating
evidence-based medicine point-of-care tools. J Med Libr Assoc. 2011
Jul;99(3):24754.
12 Goldacre M, Stear S, Richards R, Sidebottom E. Junior doctors views
about careers in academic medicine. Med Educ. 1999 May;33(5):31826.
13 Frank, JR. The CanMEDS 2005 physician competency framework.
Ottawa: Royal College of Physicians and Surgeons of Canada; 2005.
14 Oxman AD, Sackett DL, Guyatt GH. 1993. Users guides to the medical
literature: I. How to get started. JAMA. 1993 Nov 3;270(17):209395.
15 Greenhalgh T. How to read a paper: getting your bearings (deciding what
the paper is about). BMJ. 1997 Jul 26;315(7102):2436.
16 Milne R, Donald A, Chambers L. Piloting short workshops on the
critical appraisal of reviews. Health Trends. 199596;27(4):1203.
17 Horsley T, Hyde C, Santesso N, Parkes J, Milne R, Stewart R. Teaching
critical appraisal skills in healthcare settings. Cochrane Database Syst
Rev. 2011 Nov 9; (11):CD001270.
18 Royal College of Surgeons England. National undergraduate curriculum
in surgery [Internet]. RCSENG Professional Standards and Regulation;
2015 [cited 2015 Oct 18]. Available from: http://www.rcseng.ac.uk/
publications/docs/national-undergraduate-curriculum-in-surgery.
19 Scottish Universities Medical Journal. Review process [Internet].
University of Dundee; n.d. [cited 2015 Oct 18]. Available from: http://
sumj.dundee.ac.uk/index.php?id=review-process.
20 Burke J, Mitchell A, Khan S. PRISM (Peer Review Integrated Student
Model). Unpublished.
21 Matthews-King A. 2015. GPs diagnostic skills could be obsolete within
20 years, says Hunt. PULSE [Internet]. 2015 Oct 6 [cited 2015 Oct 18].
Available from: http://www.pulsetoday.co.uk/political/political-news/
gps-diagnostic-skills-could-be-obsolete-within-20-years-time-sayshunt/20030142.fullarticle.
10
EDITORIAL
If it is statistically signiicant does

it make it clinically important?
S. Beecroft
Manchester Medical School, University of Manchester
simon.beecroft@student.manchester.ac.uk
In answering any question it is irst imperative to deine the key terms contained therein. The question that forms the title of this essay refers to two
key concepts in the application of evidence to the practice of medicine: statistical signiicance and clinical importance. This essay considers the link
between these two notions in the context of research consisting of clinical
trials evaluating interventions in healthcare.
Of the two, statistical signiicance appears to be the more straightforward to deine, as there is currently a broad consensus on the calculation
of statistical signiicance, although the most common deinition does
have its detractors. The prevailing method of identifying statistical signiicance in hypothesis testing is the use of the p value.(1) The p value represents the probability of obtaining results as extreme as those observed
if the null hypothesis were true. In this system, statistical signiicance is
achieved when the p value is below an (arbitrary) deined signiicance
level, typically set at 0.05 in medical research. It is occasionally argued
that p values should be incorporated into a Bayesian calculus which
includes prior probability(2) in order to better represent the continually evolving nature of scientiic knowledge, but this is not yet common
practice.
In the medical literature the terms clinical importance,(3) clinical relevance(4) and clinical signiicance(5) appear to be used interchangeably, and
the inconsistent terminology seems to be associated with confusion in the
deinition of the concept. This is unfortunate as the diferent terms could
be better used to circumscribe some distinct concepts. Clinical signiicance
could be best used in a narrow sense to describe whether an identiied
efect size achieves the smallest efect of clinical interest. This could free
up clinical importance to cover a more expansive set of issues related to the
application of research indings to medical practice. In this instance, clinical importance would refer to the uptake of the intervention in real-world
clinical practice. Thus the redeined concept of clinical importance should
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S. Beecroft
encompass clinical signiicance in the narrow sense described above, along

with processes which afect the translation of knowledge from research to
practice. In addition to adding clarity, having the broader term available
could help align the lexicon of medical research with a more practical and
patient-centred approach.
The process of deining the key terms enables an exploration of
the process of generating clinically important research as deined here.
Firstly, the reported statistically signiicant result must truly be statistically signiicant; there must have been no error in generating the result.
Secondly, the statistically signiicant result must achieve the smallest
efect of clinical interest, which must be deined appropriately. Finally, the
intervention must be adopted and practised efectively by clinicians and
patients. Running this gauntlet successfully is far from guaranteed for any
research project, and as a result there are a multitude of situations in which
reported statistical signiicance does not equate to clinical signiicance or
importance. The many stages involved in the translation of research into
clinical practice each have their own capacity for error which could reduce
or nullify the clinical importance of the indings. Error may be introduced
in the identiication of the research question, the design and conduct of the
study, the presentation of the results, the statistical analysis of the results,
and the communication and application of the research indings. The following are brief elaborations of some of the key problems encountered at
each stage, and this is necessarily not an exhaustive list but should serve
to highlight some important pitfalls that can sever the connection between
statistical signiicance and clinical importance.
Research question
There are a number of ways in which research can be poorly conceived
that mean no matter how signiicant the results they are unlikely to be
clinically important. Producing redundant work or work that does not
address patient concerns or investigate outcomes important to patients is a
recipe for wasted time and money. Ensuring that a statistically signiicant
result would be useful to practising clinicians at the very least means ensuring one is not duplicating work that has already been done (except in the
context of replication trials). Sadly, the process of undertaking a systematic review to identify the state of existing knowledge before embarking on
a new research project is not universal.(6) Work that is genuinely new may
also have limited clinical applicability if it fails to focus on what matters to
patients.(7,8) There have been a number of initiatives aimed at improving
patient involvement in setting research agendas, but progress is slow. Both
of these errors end up efectively producing research of extremely limited
clinical value; unfortunately the reward structure for medical research
continues to incentivise this kind of work.
12
Study design and conduct

Statistical signiicance/clinical importance
In spite of decades of collective experience of designing and conducting clinical trials, the medical research community continues to produce
research that is methodologically lawed. A raft of issues in the design and
conduct of medical research can lead to type I error, which is to reject the
null hypothesis when it is true. A brief exposition of commonly encountered problems at this stage includes insuiciently powered studies, studies
that do not appreciate the prior probability of detecting an efect and
studies that investigate too many outcomes.(9) These are problems that
should be identiied by clinicians trained in critical appraisal of literature.
However, constant vigilance on behalf of those involved in front-line care
is not a particularly robust system for weeding out lawed research, and
much research that is unable to demonstrate the relationships it reports
may well be translated into changes in clinical practice.
Statistical analysis
The phenomenon of p-hacking has received increasing scrutiny in recent
years as meta-research indings have begun to suggest that there is widespread inappropriate data manipulation occurring in scientiic research.(10)
There are a number of ways in which data may be treated to increase the
likelihood of generating a statistically signiicant result. These methods
include using interim analyses during data collection; post hoc selection of
primary outcome measures; and modiications of the treatment of outliers,
subgroup analyses, and inclusion and exclusion criteria.(11) These methods
may be subtle and can be diicult to identify during critical appraisal of
research papers, thus leading to unchallenged claims of statistical signiicance that are unfounded. Unfortunately, even when such discrepancies
in research are identiied there are a number of barriers to correcting the
scientiic record,(12) not least editors inability or unwillingness to appreciate the presence of inappropriate treatment of data in research published
in their journals.(13)
Communicating research findings
If clinicians are unable to access research indings then it is impossible for
the insights to be implemented in clinical practice. The issue of knowledge
translation(14) has been explored by researchers in medical education,
and there are a number of barriers identiied to closing the implementation gap. These challenges include the polar opposite issues of restricted
access to information and information overload. Many medical journals
require a paid subscription or apply a per article charge which is generally prohibitively expensive for those without institutional access. Whilst
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S. Beecroft
open-access journals have become more successful recently, there is still

a massive wodge of medical knowledge that is stuck on the other side of
a paywall for many clinicians around the world.(15) On the other hand,
the sheer volume of research being produced is a problem for practising
clinicians who wish to provide the best care for their patients. When the
amount of time required to read all relevant journals exceeds the number
of waking hours in the day(16) this is clearly an issue pertinent to the uptake
of new interventions. It appears as though continuing medical education
will remain a piecemeal afair for the foreseeable future; a situation which
is not conducive to maximising the clinical importance of the medical
research that is conducted.
It seems valid in the context of assessing the clinical importance of statistically signiicant results to understand their relative contribution to the
sum of knowledge. The totality of evidence available via a literature review
is not generated as by a pure, disinterested process. The complex interplay
of a number of diferent motivations on behalf of researchers, institutions,
commercial interests and publishers(17) means that results that do not
achieve statistical signiicance are less likely to be published than those
that do.(18) This publication bias signiicantly afects the context in which
new research indings are assessed. The interpretation of new research
does not occur in isolation; it is incorporated into existing knowledge,
whether formally in the setting of systematic review and meta-analysis, or
informally through amalgamation with healthcare professionals existing
decision-making heuristics. Although tools exist to identify publication
bias,(19) the preponderance of statistically signiicant indings in medical
research afects the quality of this process and limits the utility of the
research base as a whole.
Application of research findings
Even with clinicians who are up to date with the literature, there can be
many more barriers to implementation of interventions in clinical practice.
Clinicians own motivation and/or willingness to modify their current
practice are paramount in this regard. Resistance to the adoption of new
interventions is dependent on the environment, personality, identity and
cognitive architecture of those expected to implement it, which deine their
assessment of commitment to and capacity for the intervention.(20) Once
the clinician has agreed to the change of practice, other issues come to the
fore. Amongst others, access to the new intervention and any necessary
training required to implement it, the cost-efectiveness of the intervention
compared with existing therapeutic strategies, and local governance and
funding arrangements will signiicantly impact on ability to modify practice.(21) Once these issues have been ironed out, the stage is inally set for
the clinical use of the intervention. The inal hurdle is patient acceptance
14
Conclusion
In conclusion, the simple answer to the question of whether statistical
signiicance invariably means clinical importance is an emphatic no.
Statistically signiicant results may be clinically important but the association is by no means certain; as the old proverb has it, Theres many a slip
twixt cup and lip. The decoupling of statistical signiicance and clinical
importance is important not only when attempting to ensure a robust
evidence base to be drawn upon when clinicians provide care and make
shared decisions with patients, but also to protect those who participate in
medical research as subjects. If the clinical importance of research indings
is undermined, then the risk:beneit calculus for clinical trial participants
is changed and any harm sufered by participants becomes objectively less
justiiable. It is therefore incumbent on those engaged in medical research
and practice to be aware of these issues and to do all that is reasonably
practical to mitigate them.
of or adherence to the intervention, which can be inluenced by a number

of diferent factors. Some factors relevant to the researcher planning to
investigate an intervention they wish to become clinically important are
regimen complexity, economic and structural factors, patient-related
factors, and pattern of healthcare delivery.(22) If the proposed intervention is overly onerous for patients or they are unable to access the service
appropriately or cope with practical aspects of receiving the intervention,
then its clinical importance will be manifestly reduced.
References
1 Sterne JAC, Smith GD. Sifting the evidence: whats wrong with
signiicance tests? Br Med J. 2001 Jan 27;322(7280):22631.
2 Goodman SN. Of p-values and Bayes: a modest proposal. Epidemiology.
2001 May;12(3):2957.
3 Mon-Son-Hing M, Laupacis A, ORourke K, Molnar FJ, Mahon J,
Chan KBY, et al. Determination of the clinical importance of study
results: a review. J Gen Intern Med. 2002 Jun;17(6):46976.
4 Bhardwaj SS, Camacho F, Derrow A, Fleischer AB, Feldmann SR.
Statistical signiicance and clinical relevance: the importance of power in
clinical trials in dermatology. Arch Dermatol. 2004 Dec;140(12):15203.
5 Sedgwick P. Clinical signiicance versus statistical signiicance. Br Med J
[Internet]. 2014 [cited 2016 Feb 5]; 348:g2130. doi: 10.1136/bmj.g2130.
6 Chalmers I, Glasziou P. Avoidable waste in the production and reporting
of research evidence. Lancet. 2009 Jul 4;374(9683):869.
7 Perel P, Miranda JJ, Ortiz Z, Casas JP. Relation between the global
burden of disease and randomized clinical trials conducted in Latin
15
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13
14
15
16
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America published in the ive leading medical journals. PloS ONE

[Internet]. 2008 [cited 2016 Feb 5]; 3(2):e1696. doi: 10.1371/journal.
pone.0001696.
Crowe S, Fenton M, Hall M, Cowan K, Chalmers I. Patients, clinicians
and the research communities priorities for treatment research: there is
an important mismatch. Res Involv Engagem. 2015 Jun 25;1(1):110.
Ioannidis JPA. Why most published research indings are false. PloS
Med. 2005 Aug 30;2(8):696701.
Gadbury GL, Allison DB. Inappropriate iddling with statistical analyses
to obtain a desirable p-value: tests to detect its presence in published
literature. PloS One [Internet]. 2012 [cited 2016 Feb 5]; 7(10):e46363.
doi:10.1371/journal.pone.0046363.
Head ML, Holman L, Lanfear R, Kahn AT, Jennions MD. The extent
and consequences of p-hacking in science. PloS Biol [Internet]. 2015 [cited
2016 Feb 5]; 13(3):e1002106. doi:10.1371/journal.pbio.1002106.
Allison DB, Brown AW, George BJ, Kaiser KA. Reproducibility: a
tragedy of errors. Nature. 2016 Feb 4;530(7588):279.
Slade E, Drysdale H, Goldacre B, COMPare Team. Discrepancies
between prespeciied and reported outcomes. Ann Intern Med [Epub
ahead of print]. 2015 [cited 2016 Feb 5]; 164(5):374. doi: 10.7326/L15-0614.
Graham ID, Logan J, Harrison MB, Straus SE, Tetroe J, Caswell W, et
al. Lost in knowledge translation: time for a map? J Contin Educ Health
Prof. 2006 Winter;26(1):1324.
Zachariah R, Ford N, Maher D, Bissell K, Van den Bergh R, van den
Boogaard W, et al. Is operational research delivering the goods? The
journey to success in low-income countries. Lancet Infect Dis. 2012
May;12(5):41521.
Alper BS, Hand JA, Elliott SG, Kinkade S, Hauan MJ, Onion DK, et
al. How much efort is needed to keep up with the literature relevant for
primary care? J Med Libr Assoc. 2004 Oct;92(4):42937.
Dickersin K. Publication bias: recognizing the problem, understanding
its origins and scope, and preventing harm. In: Rothstein HR, Sutton
AJ, Borenstein M, editors. Publication bias in meta-analysis: prevention,
assessment and adjustments. Chichester: John Wiley & Sons; 2005.
p.1133.
Hopewell S, Loudon K, Clarke MJ, Oxman AD, Dickersin K.
Publication bias in clinical trials due to statistical signiicance or direction
of trial results. Cochrane Database Syst Rev [Internet]. 2009 [cited 2016
Feb 5]; 1:MR000006. doi: 10.1002/14651858.MR000006.pub3.
Peters JL, Sutton AJ, Jones DR, Abrams KR, Rushton L. Comparison
of two methods to detect publication bias in meta-analysis. JAMA. 2006
Feb 8;295(6):67680.
Laws RA, Kemp LA, Harris MF, Davies GP, Williams AM, EamesBrown R. An exploration of how clinician attitudes and beliefs inluence
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the implementation of lifestyle risk factor management in primary

healthcare: a grounded theory study. Implement Sci. 2009 Oct 13;4:66.
21 Durlak JA, DuPre EP. Implementation matters: a review of research
on the inluence of implementation on program outcomes and the
factors afecting implementation. Am J Community Psychol. 2008
Jun;41(34):32750.
22 Sabat E. Adherence to long-term therapies: evidence for action. Geneva:
World Health Organization; 2003.
17
18
RESEARCH ARTICLE
Transition at Emerge: evaluating

transition practice and elucidating
ethnic differences
A. Kuhivchak
adam.kuhivchak@gmail.com
Abstract
Background Transition between child and adult services is a notoriously
dificult area of mental health provision. This service evaluation was designed
to determine the standard of transition practice, as well as analysing any
differences in transition between ethnicities at Emerge, a service for 1617 year
olds in Manchester Child and Adolescent Mental Health Services (CAMHS).
Methods This study utilised 68 randomly selected sets of case notes of
cases closed to Emerge. The data was collected manually from these case
notes using a data-collection tool and analysed using Microsoft Excel.
Results Of the seven cases in the sample that transitioned to adult services,
none experienced an optimal transition as deined by the TRACK study.(1)
Only seven of the total cases were from a black and minority ethnic (BME)
background, so elucidating any ethnic differences in transition was not possible.
Conclusion The results showed that transition practice at Emerge did
not meet the standard of practice, prompting a recommendation for better
liaison between CAMHS and Adult Mental Health Services (AMHS). Access to
Emerge for ethnic minorities was shown to be limited, although the study failed
to reveal ethic differences in transition owing to its small sample size.
Aims of the study

To elucidate any ethnic or demographic diferences in service use with
particular focus on transition
To look at the practice of transition at Emerge compared against established standard of a good transition.
19
A. Kuhivchak
As Emerge is a specialist service that deals with young people in the 1617
age range, transition is a key process. Many young people are close to
adulthood when they are referred and may well turn 18 in the care of
Emerge, possibly requiring referral to adult services. One of the main aims
of this service evaluation is to look at transition practice at Emerge. Singh
et al. propose in the TRACK study, a major study looking at transition
between Child and Adolescent Mental Health Services (CAMHS) and
Adult Mental Health Services (AMHS), that there are four major criteria
for an optimal transition:
(a) information transfer (information continuity): evidence that a
referral letter, summary of CAMHS care, or CAMHS case notes
were transferred to AMHS along with a contemporaneous risk
assessment
(b) period of parallel care (relational continuity): a period of joint
working between CAMHS and AMHS during transition
(c) transition planning (cross-boundary and team continuity): at least one
meeting involving the service user and/or carer and a key professional
from both CAMHS and AMHS prior to transfer of care
(d) continuity of care (long-term continuity) either engaged with AMHS
3 months post-transition or appropriately discharged by AMHS following transition.(2)
It is against these criteria that transition at Emerge is compared.
This evaluation also aims to look at the demographics of the Emerge
caseload. With a particular focus on ethnicity, this evaluation aims to
bring to light any link between the background of a young person and
their likelihood to transition.
Methods
This service evaluation was begun after informing the trust audit department on 21 January 2014. Data was collected from all the closed case notes
in storage at Emerge between 27 and 28 January 2014; notes were collected
at random from closed cases in storage at Emerge. Any notes that did
not contain information on more than three of the speciied criteria were
not included, as this was insuicient for analysis; in total information for
68cases was collected. A data-collection tool was used to collect the data.
The data was compiled in a document in Microsoft Excel.
For each case the following were collected: gender, age at referral,
ethnic group, referrer, priority, reason for referral, service referred on to,
reason for case closure, outcome of case and attendance statistics. Missing
data was supplemented if possible using the CORC (Child Outcomes
Research Consortium) database. For those cases referred to adult services,
20
Results
The total number of cases in the sample was 68. Females numbered 47
(69%) and males 21 (31%). White British was the most commonly recorded
ethnic group with 44 cases (64.7%); in 17 (25%) cases the ethnicity was not
recorded. There were 7 (10.3%) cases in which black or ethnic minority
was recorded: 2 black Somali, 2 British/Pakistani dual heritage, 1 white
Romanian, 1 Arabic and 1 Pakistani (see Table 1).
The median number of ofered sessions attended was 3, the most attended
was 37 and the least 0. The higher median value for number of sessions
listed as did not attend (DNA) than could not attend (CNA) suggests
patients were more likely to not attend a session than for the session to be
cancelled ahead of time by the patient or his or her practitioner. Of patients
referred to Emerge, 20.6% never attended a single session (see Table 2).
The most common referral route was from a GP practice, in 32 (47.1%)
of cases, followed by another trust, 8 (11.8%), a school or pastoral care in
7 cases (10.3%), and from Connexions, Youth Ofending Service (YOS) or
A & E, all noted in 5 cases (7.4%). More detail on referral route is shown
in Table 3.
Transition at Emerge: evaluating practice
information about whether they had transferred to adult services was

sought by phone call to Single Point of Access on 23 January 2014.
The case notes were used to ind evidence of transfer of information
between CAMHS and AMHS, a period of parallel care and a joint planning meeting. Owing to there being a relatively small amount of data, it
was analysed manually, with the use of some of the graph- and table-building tools in Microsoft Excel. No statistical tests were used; the analysis
looks purely at frequencies, medians, modes, means and ranges.
Table 1: Ethnicity vs gender of cases in the study sample.

White British
BME
Not recorded
Total
Male
Female
Total
10
4
7
21
34
3
10
47
44
7
17
68
BME: black and minority ethnic.
Table 2: Mean, median and range for numbers of sessions attended, not attended
and cancelled.
Attended
CNA
DNA
Mean
Median
Range
5.19
1.06
1.8
3
0
1
037
013
09
CNA = could not attend; DNA = did not attend.
21
Table 3: Frequency of recorded referrer and ethnicity.
A. Kuhivchak
Referrer
Number of cases
White British/ethnicity
not recorded
A&E
GP
Connexions
Other trust
School/pastoral care
Self referral
Youth Ofending
Service
Other
Total
5
28
5
8
7
3
4
1
61
Total
Black and minority

ethnic
1
1
5
32
5
8
7
4
5
1
7
2
68
The most common reason, in 24 (35.3%) cases, for a case being closed
was at the mutual consent of the patient and/or his or her family and
their practitioner. Never having attended a session ofered by Emerge, or
disengaging with the service after attending at least one appointment, was
the next most likely reason, attributable in 14 (20.6%) cases. In 7 (10.3%)
instances, cases were closed when the patient turned 18 and were recorded
as not being transferred to AMHS, and 5 (7.4%) patients were recorded as
being transferred when they turned 18 (see Figure 1).
After initially collecting data from CORC, seven cases were found
in which the recorded case outcome was turned 18, not transferred to
AMHS. However, on examining the case notes, it was found that in two
of these cases a referral to AMHS had in fact been made. This discrepancy is probably due to administrative error, but it should be taken into
account when looking at the graph in Figure 1.
After correcting for the errors on CORC, of the 12 cases in which the
patient had turned 18, 7 were referred to adult services, 1 of which was
from an ethnic minority background. A total of 5 were not referred on to
AMHS. Of those 5 not referred, 3 were not considered for transition to
AMHS and 2 declined onward referral.
Of those that were referred, all case notes showed evidence of transfer
of information between CAMHS and AMHS. None indicated a period of
parallel care. There was no evidence of joint planning meetings involving
CAMHS and AMHS practitioners. Over three months after their discharge from CAMHS, ive cases were still open to AMHS (see Table 4).
Discussion
Of the cases in the study sample where ethnicity was recorded, 12% were
from a non-white ethnic minority, a igure three times lower than the
22
30
25
Frequency
15
10
0
Closed at
paent's
request
Closed by
mutual
consent
Disengaged
Turned 18
not
transferred
Turned 18
transferred
Other
Never
aended
Reason case closed
20
Figure 1: Bar chart showing reason for case closed and frequency.
Table 4: For all cases referred to AMHS, criteria for optimal transition as deined
by TRACK study.(1)
Criterion
Yes
No
Transfer of
information
Parallel care
Joint planning
Continuity of
care
7
0
0
7
0
7
5
2
general population. Mental health problems in children and young people

do not vary much in prevalence between ethnicities, with the exception of
the Indian population, where the prevalence is signiicantly higher.(4) It is
therefore worrying that the proportion of ethnic minorities in the sample
is so much lower than in the population. This could be because of variation in having such a small sample, but the diference is very large and
more likely represents a gap in access between the white and non-white
population. This is the type of gap that initiatives such as the Delivering
Racial Equality in Mental Healthcare initiative are aimed at reducing on
a national level; the results of this survey show that there is still a large
divide in access at Emerge.
The data shows how big an issue attendance is for Emerge, with a
ifth of patients referred to the service never even attending an opening
appointment, and a further ifth disengaging with the service after at
least one appointment. Patients failing to attend sessions without cancelling beforehand waste practitioners time and drain the resources of the
service. However, for a service that deals with mentally ill teenagers, these
problems come with the territory. Emerge already ofers appointments at
23
A. Kuhivchak
locations around the city, even visiting patients in their homes to try to
deliver the help patients need. Although patients disengaging is worrying
if they have an ongoing need, if patients do not want to engage with the
service that is their prerogative. An audit of cases at Emerge, looking at
whether young people who disengage have been ofered a full and appropriate service before their cases being closed, would ensure that Emerge is
doing all that it can to meet the needs of young people.
Of the seven cases studied that transferred to AMHS, none experienced
an optimal transition. The transfer of information was the strongest
aspect of transition practice, with detailed referral information sent to
AMHS through speciied referral channels. Also, positively, ive of the
patients were still in adult services when this was checked; this is a demonstration of the fact that transfer can happen quite successfully without
a good transition. However, worryingly, in one case that was closed and
apparently referred on, it appeared adult services had never received a
referral at all.
Whilst there was evidence in some cases of planning meetings for
transition involving CAMHS practitioners, there was no evidence of
joint working between AMHS and CAMHS practitioners to hand over
a patient. This echoes other studies into transition between CAMHS and
AMHS that show although joint working is often speciied in transition
protocols, in reality it does not happen owing to a lack of time, poor communication and misunderstanding of opposite services.(2) For practitioners at Emerge, time is of the essence; there is often very little time between
a referral being made and a referral to adult services being considered. The
poor attendance of patients increases this time pressure to try to implement joint work with AMHS. Whilst diiculties clearly exist in making
joint planning meetings part of standard practice, improvement in this
area needs to be made to provide good transition experiences to patients.
A dearth of joint working is also shown by the lack of periods of parallel care. A patient referred to AMHS is unlikely to be ofered an appointment in the near future; so often by the time they have attended their irst
appointment with AMHS, their case has been closed by CAMHS. The
worry is that if patients were to then miss their irst adult appointment,
they may well fall into the gap between services if they are not re-referred.
The age limits of transition boundaries could be lexible, allowing for the
period of parallel care that is essential in the transition process.
Conclusions and recommendations
Transition practice is suboptimal at Emerge. Although transition practice
is followed broadly and transfer into adult services is usually successful,
improvements could be made to make the process smoother for the young
people involved. The creation of new posts for speciic transition workers
24
or liaison oicers seems unrealistic, given the stretched resources within

mental health services, but is a possibility that has been suggested elsewhere.(3) Alternatively, better lines of communication and liaison could
be opened up between people already working at Emerge and in AMHS.
Practitioners could be given the speciic task of organising a regular
meeting with a worker within AMHS to discuss cases approaching the
transition stage, to decide whether they are suitable for transition and to
plan for the process if so.
A checklist for a good standard of transition practice agreed by Emerge
could be created and inserted into the notes at the close of a case. This
would aid good practice, as well as audit of transition practice in the
future. This checklist could demand a joint planning meeting, evidence of
a referral and risk assessment, and a follow-up of patients transitioned to
ensure they are still receiving the care they require.
Attempts to engage with ethnic minorities in Manchester should also be
made or increased. Creating links with the community, through religious
groups, third-sector organisations or any group concerned with improving
services for ethnic minorities, could help improve mutual understanding
and possibly provide new routes for referral. Providing new training for
staf may be necessary to create a more culturally sensitive service, so that
ethnic minorities enjoy a good standard of service with Emerge.
The major limitation of this study is in the sample size. The small
proportion of ethnic minorities within the already small sample made
it redundant to look at variations in transition practice between ethnic
groups. Although the study highlighted a problem with access for ethnic
minorities, it failed to look at the way they use the service and are transferred from it. A larger, perhaps longitudinal, study would be required to
do this. The problems inherent in a small sample also apply to the examination of those cases that did transition; as there were so few of them it
makes it diicult to draw solid conclusions about transition practice at
Emerge. Future audits that focus purely on those cases that have transitioned would shed more light. This study is also subject to a signiicant
amount of error, as the data was compiled and analysed manually. The
use of CORC to collect some of the data may also have introduced some
bias, as this data is known to be inaccurate in places, which in itself is a
possible target for audit.
References
1 Singh SP, Paul M, Ford T, Kramer T, Weaver T. Transitions of care
from Child and Adolescent Mental Health Services to Adult Mental
Health Services (TRACK Study): a study of protocols in Greater
London. BMC Health Serv Res [Internet]. 2008 Jun 23; 8:135. doi:
10.1186/1472-6963-8-135.
25
A. Kuhivchak
2 Singh SP, Paul M, Ford T, Kramer T, Weaver T, McLaren S, et al.

Process, outcome and experience of transition from child to adult mental
healthcare: multiperspective study. Br J Psychiatry [Internet]. 2010 Sep
30; 197(4):305. doi: 10.1192/bjp.bp.109.075135.
3 Lamb C, Murphy M. The divide between child and adult mental health
services: points for debate. Br J Psychiatry [Internet]. 2013 Jan 3;
202(s54):s41. doi: 10.1192/bjp.bp.112.119206.
4 Green H. Mental health of children and young people in Great Britain.
Oice for National Statistics; 2004.
26
AUDIT
Readmissions at Royal Oldham

Hospital AMU
S. W. G. Hogg
samuel.hogg@student.manchester.ac.uk
Abstract
Background This paper contributes to the developing body of literature that
explores the theme of hospital readmissions. Interest in this area has grown
since a policy of non-payment for 30-day readmissions was introduced by the
Department of Health. This has moved hospitals to seek out ways of reducing
their readmission rates.
Aim The goal of this study was to investigate the drivers of readmissions at
the Royal Oldham Hospital of the Pennine Acute Trust, by identifying patterns
existing within a sample of readmitted patients.
Methodology A random sample of 55 patients readmitted to the Acute
Medical Unit (AMU) within 30 days of a previous discharge during December
2013 was used. Factors frequently implicated in readmissions were selected
as variables for analysis.
Results The indings were largely concurrent with previous observations
that old age, male gender, previous hospital admissions and existing comorbid conditions increase the risk of readmission. The indings were
consistent with reports that diagnoses at the times of admission and
readmission are typically different, and that common causes of readmission
are infection and complications relating to co-morbid conditions.
Conclusion This study forms solid foundations upon which more expansive
auditing can take place, and speciic recommendations are made for the
reduction of readmission rates on AMU.
27
S. W. G. Hogg
Introduction
In 2011 the Department of Health introduced legislation which means
that hospitals do not get paid for patients acutely readmitted within 30
days of their previous discharge. This applies to all readmissions for which
the index admission was elective, and 25% of readmissions following an
emergency admission.(1) Readmissions relating to mental health, maternity, children under four years and cancer were excluded on the basis that
in these cases readmission is often considered a necessary part of care.(2)
Beyond these exceptions, it is felt that readmissions following both elective
and emergency admissions should largely be preventable, and high 30-day
readmission rates are seen as indicative of inefective patient management
and inadequate quality of care.(3)
The policy launched on a background of increasing readmission rates:
from 8.4% in 20001 to 11.63% in 201011.(4) According to healthcare
data provider CHKS, hospital admissions occurring within 30 days of a
previous discharge provided hospital trusts with an income of 2.2 billion in
200910. Based on these igures, the 2011 changes to readmissions policy
equate to an annual income deicit for hospitals of 790 million.(2) The
inancial incentives of reducing 30-day readmissions are therefore clear.
The story is similar in the US, where, since 2012, inancial penalties are
applied to underperforming hospitals.(5) Consequently, interest in readmissions has grown, with literature exploring three themes: (1) investigations into whether readmission rates are a good measure of quality of
care, (2) studies of interventions which might reduce readmissions, and (3)
attempts to identify factors that drive readmissions.(6) This paper falls into
the last of these categories.
The list of factors that potentially contribute to readmissions is
long and complex.(2) This may be relected in the varying readmission
rates of diferent hospitals and trusts.(7) Although igures like these
are undoubtedly inluenced by factors outside of trust control, such
as community backup and population demographics, there is growing
evidence that the key determinants of readmissions may originate from
within. For instance, Dharmarajan et al.(8) studied readmissions of
patients in the US with an index admission diagnosis of heart failure,
acute myocardial infarction or pneumonia. The authors report that
the spectrum of diagnoses at readmission is consistent across hospitals with high, average and low readmissions. That is, the distribution of readmission diagnoses does not vary between hospitals but the
absolute rate of readmission does. This indicates that readmissions performance may not be related to disease- and treatment-speciic factors,
but to institution-wide policies and practices, along with demographic
factors such as socioeconomic status afecting the general health of the
population.
28
Readmissions at Royal Oldham Hospital AMU
Most relevant are those practices that inluence the standard of inpatient care, the transition from inpatient to outpatient, and community
care at discharge. It is probable that patients experiencing optimal levels
of inpatient care and a smooth, well-coordinated discharge into outpatient or community care, are less likely to be readmitted within 30 days
than those who do not. As such, readmissions could be considered as a
marker of hospital performance in these areas. The contexts of readmissions are equally important. The method or route of index admission
and the latency between discharge and readmission may be particularly
signiicant. A high proportion of readmissions following elective admission periods could well be a consequence of substandard inpatient care
and discharge procedure, and likewise short intervals between the time
of discharge and readmission. This is especially true if a patient rebounds
within seven days. It has been stated that in these circumstances, poor
medical management and insuicient discharge support and medication
reconciliation are frequently implicated.(3) This is also the period in which
iatrogenic causes and hospital-acquired infection are likely to be present.
This would imply that the hospital is often more culpable when the turnaround between discharge and readmission is quick. It is therefore quite
alarming that nearly 50% of readmissions in the NHS occur within seven
days.(3,7)
Avoiding unnecessary readmissions relies on understanding which
patients are likely to be readmitted. Donz et al.(9) report that potentially
avoidable readmissions are commonly related to complications associated
with seven co-morbid conditions: diabetes, chronic heart failure, atrial
ibrillation, ischaemic heart disease, neoplasm, chronic obstructive pulmonary disease (COPD) and chronic kidney disease. Patients with these
co-morbid conditions are therefore a high-risk group. The most frequent
causes of readmission in this study were infection, care of neoplasm and
heart failure. Signiicantly, diagnoses at irst admission and readmission
were typically diferent, suggesting that readmissions are as likely to relate
to a patients co-morbidities as they are to the cause of index admission.(7)
Katikireddi and Cloud(10) have produced a comprehensive list of patient
characteristics commonly associated with readmission. These red lags
are summarised in Table 1. The authors argue that through assessing
patients for these criteria early in their admission period, it is possible to
tailor their care, and make appropriate discharge planning, greatly reducing risk of readmission.
Aims and standards
The aim of this project was to contribute to an ongoing review of
readmissions within the Pennine Acute Trust. Currently, the trust
readmission rate is 8.61%, higher than the average of 8.20% in its peer
29
Table 1: Red lag warnings for patients at high risk of readmission.
S. W. G. Hogg
Medical factors
Coronary artery
disease
Advanced and
disseminated
malignancy
Chronic renal
failure
Chronic obstructive
pulmonary disease
Diabetes
Heart failure
Dysphagia
3+ chronic diseases
Psychosocial
factors
Use of medical
resources
Patient
characteristics
Poor self-rated
general health
Moderate to severe
functional disability
6+ visits to GP
within 1 year
At least 1 hospital
admission within
1year
Aged 80+
Male
Living alone
group.(7) Based on the 200910 readmissions data, the potential annual

loss of income resulting from readmissions is 9.4 million. This represents3.4% of total income, which can be compared to a national igure
of 3.0%.(3)
The Pennine Acute Trust operates from four sites. This audit aims to
examine readmissions at one of these: Royal Oldham Hospital. Owing to
time limitations, only readmissions to the Acute Medical Unit (AMU) at
this hospital within one calendar month were included for analysis. The
goal of this project was not to assess performance of the unit in comparison with other hospitals, but to identify patterns within the readmission
data, providing insight into the types of patient most likely to be readmitted and the ways in which the hospital may be contributing to readmissions. This may then inform future audit loops and ultimately begin the
process of reducing readmissions.
Methodology
This was a retrospective study of patients readmitted to AMU within
30 days of their last hospital discharge. Data from patients for whom
the date of readmission took place within the month of December 2013
was included. A sample of 55 patients meeting these inclusion criteria
was arbitrarily selected. Demographic details for all patients admitted to
AMU in the same time frame were attained for comparison. The relevant
data was received in Excel iles from the Divisional Information Manager,
or accessed through the ALS/Healthview system on the Pennine Acute
Trust intranet.
30
The following variables were selected for further analysis:

age
gender
number of previous hospital admissions within a year
type of residence inhabited by patient
method of index admission
admission diagnosis
readmission diagnosis
existing chronic co-morbidities
latency between discharge and readmission.
Results and analysis

Age and gender
Of 55 readmitted patients, 31 (56.4%) were male and 24 (43.6%) were
female. In contrast, of 1,078 patients admitted to AMU in the same
period, 510 (47.3%) were male and 568 (52.7%) were female. The age
distributions of these patients are presented in Table 2. The mean age of
readmitted patients was 68.4 years (range 1693). The 70+ age group had
the highest proportion of readmitted patients, followed by the 6069 and
4049 age groups. The relative risk of readmission was highest in the 017
and 4049 age groups, however.
Previous hospital admissions

Of readmitted patients, in the previous year 40 (72.7%) had been admitted to hospital at least once, 12 (21.8%) had been admitted at least three
times and 5 (9.1%) had been admitted at least ive times.
Residential source of readmissions
The types of residence inhabited by patients in our sample are outlined in
Table 3.
Table 2: Age distribution of patients admitted to AMU in December 2013 and
patients readmitted to AMU in December 2013.
Admitted patients
Relative risk of
readmission
Readmitted patients
Age
Frequency
Age
Frequency
017
1829
3039
4049
5059
6069
70+
15
66
80
105
144
157
511
1.4
6.1
7.4
9.7
13.4
14.6
47.4
017
1829
3039
4049
5059
6069
70+
1
2
1
7
4
9
31
1.8
3.6
1.8
12.7
7.3
16.4
56.4
1.31
0.59
0.24
1.31
0.54
1.12
1.19
31
S. W. G. Hogg
Table 3: The distribution of patients according their residential inhabitancy.

Residence
Frequency
Own home
Retirement home
Care home
Nursing home
47
3
3
2
85.5
5.5
5.5
3.6
Table 4: The distribution of patients by admission method.

Admission method
Frequency
A&E
Elective planned
GP or locum GP
Emergency other
38
8
1
8
69.1
14.6
1.8
14.6
Method of index admission

The relative distributions of patients according the route of their index
admission are outlined in Table 4. In total, 14.6% of patients were readmitted following an elective admission.
Primary diagnoses at index admission and readmission
There was a great range of diagnoses at admission and readmission.
Infection was the most common diagnosis at admission (n = 15 (27.3%)).
The most common type of infection was pneumonia (n = 4 (7.3%)). The
most common cause of readmission was also infection. In total, 22 (40%)
patients were readmitted with infection, including eight (14.5%) cases of
pneumonia, and three unspeciied lower respiratory tract infections. In
total, 20 (36.4%) patients were readmitted with the same problem that they
were originally admitted with.
Co-morbid conditions
Of 55 readmitted patients, 51 (92.7%) had at least one chronic condition.
These co-morbidities can be grouped based on the body systems they
afect. The percentage of patients with a co-morbid condition afecting
each body system is illustrated in Figure 1. A total of 34 (61.8%) patients
were readmitted with a potential complication of their co-morbidity.
Figure 1 also illustrates the relative numbers of patients for whom
readmission was related to a co-morbidity afecting these diferent
systems.
Of readmitted patients, 31 (56.4%) had at least one of the seven chronic
co-morbid conditions identiied by Donz.(9) The relative numbers of
patients with each co-morbidity are illustrated in Figure 2. All readmitted
patients with a co-morbid condition of the immune system were readmitted with a possible complication of that condition.
32
50
Readmied paents with a co-morbid condion
40
35
% of paents
30
25
20
15
10
5
ta
ry
en
un
v
e
In
te
gu
m
Im
cu
lo
s
M
us
Di
ge
s
le
ta
l
ke
oc
rin
e
En
d
sir
at
or
y
Re
p
ita
l
Ur
og
en
em
st
sy
us
rv
o
Ne
Ca
rd
io
va
s
sy cul
st ar
em
Readmied paents for whom readmission may have

related to possible complicaon of co-morbid
condion
45
Body system aected by co-morbid condion
Figure 1: The percentage of patients with a co-morbid condition according to the

body system that co-morbid condition affects.
Latency between discharge and readmission

The mean time between discharge and readmission was 12 days (+/ 9.1,
median = 12, range = 29). There were 21 (38.2%) patients readmitted
within 7 days of discharge. Of these, 10 had the same diagnosis as at
admission and 9 were readmitted with an infection. The distribution of
readmissions according to the time period between discharge and readmission is illustrated in Figure 3.
Discussion and potential future work
The characteristics of readmitted patients in this report were generally
consistent with risk groups acknowledged in the literature review.(10) When
compared with the sample of all patients admitted to AMU, the sample of
patients readmitted to AMU in the same time frame contained a higher
proportion of males, patients with at least one previous hospital admission within a year, and patients in the older age groups. These characteristics could therefore be used as markers for identifying and red lagging
potential readmission candidates. Interestingly, however, the relative risk
of readmission was highest in the 017 and 4049 age groups. The small
sample may well account for the high relative risk in the 017 age group,
33
S. W. G. Hogg
25
20
% of paents
15
10
Diabetes
Heart Failure
Atrial
Fibrillaon
Ischaemic
Heart Disease
Co-morbid
condion
Neoplasm
COPD
Chronic
Kidney
Disease
Figure 2: The percentage of readmitted patients with speciic co-morbid conditions.
but the high relative risk in the 4049 group is more likely to be signiicant.
This is diicult to reconcile with previous reports, and any future work
should seek to ascertain whether the pattern is repeated at Oldham or elsewhere, and analyse possible causes. Interestingly, our results also indicate
low readmissions from care and nursing homes. This could be the result
of advance care planning, which may also be an efective tool for reducing
readmissions.
Over 92% of our sample had at least one co-morbid condition. These
were most frequently cardiovascular or neurological. The most common
cardiovascular co-morbid conditions were ischaemic heart disease, atrial
ibrillation and heart failure, whilst dementia accounted for the majority
of neurological co-morbidities. This is perhaps unsurprising given the age
distribution of the sample. The single most common co-morbid condition
was ischaemic heart disease. All co-morbidities identiied by Donz(9) featured heavily in our sample. In concordance with that study, over 61% of
patients in our study were readmitted with diagnoses that are potentially
34
Number of pa
ents
0
0
7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29
Time period between discharge and readmission (days)
Figure 3: The distribution of readmitted patients according to the time between

discharge and readmission.
related to their co-morbidities. Where readmissions were deemed likely to

be related to a co-morbid condition, those afecting the cardiovascular and
gastrointestinal systems were most frequently implicated. Liver pathologies were particularly prominent in our sample. This suggests that liver
and gastroenterology specialist input at AMU may beneit from a review.
Our results tie in with previous reports that only a minority of primary
diagnoses at admission and readmission are the same, and that patients
are more often readmitted with a complication of a co-morbid condition than recurrence of the condition they were originally admitted with.
However, 10 patients with seven-day readmissions did have the same
diagnosis at admission and readmission. Worryingly, this implies that the
patients problem was not adequately managed during their initialadmission, indicating poor patient care. It is equally concerning that 40% of
patients were readmitted due to infection. The nine patients readmitted
with infection within seven days are of particular interest, as in these cases
there is an increased likelihood that the infection was acquired in hospital.
35
S. W. G. Hogg
The possibility that readmissions result from hospital-acquired infection

therefore requires further investigation. Given that pneumonia was the
most common infection, investment in resources for the specialist respiratory multidisciplinary team (MDT) might be cost-efective.
The distribution of readmissions over time is bimodal, peaking in the
irst few days and at around two weeks. These peaks may represent a
breakdown in the provision of seamless community support. This requires
further investigation. The percentage of patients readmitted within seven
days was 38%; less than the 50% seen across the NHS.(3,7) This is a positive outcome for the Pennine Acute Trust, as it has been suggested that
readmissions occurring within seven days often result from hospital
care issues or issues relating to discharge.(3) Likewise, that only 14% of
readmissions followed an elective admission is a positive sign. A goal of
future work should be to see whether these patterns repeat over longer
durations and hospital-wide. Extension of our study over a period of 12
months could form the basis for a larger prospective audit, and produce
more robust conclusions for the trust. The limitations of our study could
be overcome with greater access to case notes, and details of support provisions made in the community.
Limitations
The desirable goal of this audit would be to deinitively identify the causes
of readmission and state conclusively whether readmissions had been
preventable. However, the causes of readmission are often complex and
multifactorial. Precise causality is therefore diicult to establish. In addition, there were limitations with the electronic system used. Missing letters
and vague or incomplete notes made it diicult to build a complete picture
of the sequence of events and standard of patient care. A signiicant limitation is the small sample size, which leaves a degree of uncertainty about
patterns identiied in terms of their capacity to represent AMU over an
extended time period.
Conclusions
The methodological diiculties experienced highlight a need for auditing
in order to address the diiculties of data collection and interpretation
for hospital readmissions. This has signiicant inancial implications for
the future. Our indings concur with observations already proposed by
researchers in the US and UK about the types of patient most likely to be
readmitted. A tool for identifying these high-risk candidates for readmission could therefore be an efective means by which to reduce readmissions.
The study also highlights local observations at Oldham and identiies
the need for speciic issues to be addressed. For example, the study suggests a need to review speciality service provision within AMU, especially
36
gastroenterology and respiratory. In addition, diabetes and cardiopulmonary hospitalcommunity interface may have solutions to ofer in
reducing hospital readmissions. However, the low number of nursing- and
care-home readmissions indicates that advance care planning is efective
and should therefore be continued as a development for reducing hospital readmissions. Infection is an ongoing source of readmission. Whilst
infection-prevention measures have yielded lower incidence, this study
highlights a continuing need for improvement in the long term. In addition, it suggests a need for primary and secondary care interaction and
engagement, which may bring in new solutions such as community IV
antibiotic therapy. A prospective audit using our template over a period
of 12 months could provide the trust with a more reliable understanding of hospital readmissions and enable more speciic recommendations
for reducing them. Expansion of the database to include readmissions
to other sites within the Pennine Trust would also help to produce more
robust conclusions for the trust.
Acknowledgements
With thanks to Dr Venkat Sridharan, Consultant in Elderly Medicine
at the Royal Oldham Hospital, who was my supervisor throughout this
project.
References
1 Department of Health. A simple guide to payment by results, gateway
reference 18135. London: Department of Health; 2011.
2 NHS Confederation, Foundation Trust Network. The impact of nonpayment for acute readmissions. Brieing [Internet]. 2011 [cited 2014
Jan 20]; 211:110. Available from: http://www.chks.co.uk/useriles/
iles/The%20impact%20of%20non-payment%20for%20acute%20
readmissions%20FINAL%20FOR%20WEB.pdf.
3 Sg2Healthcare intelligence. Sg2 Service Kit: reducing 30 day emergency
readmissions [Internet]. London: Sg2 Healthcare intelligence; 2011
[cited 2014 Jan 20]. Available from: http://www.hsj.co.uk/Journals/2/
Files/2011/6/15/Sg2_Service%20Kit_Reducing%2030-Day%20
Readmissions.pdf.
4 Department of Health. Research and analysis: emergency readmissions
data. London: Department of Health; 2013.
5 American College of Emergency Physicians. Medicares hospital
readmission reduction programme FAQ [Internet]. 2015 [cited 2014
Feb 10]. Available from: https://www.acep.org/Physician-Resources/
Practice-Resources/Administration/Financial-Issues-/-Reimbursement/
Medicare-s-Hospital-Readmission-Reduction-Program-FAQ/.
37
S. W. G. Hogg
6 Drozda JP. Readmission rates. BMJ. 2013;347:f7478.

7 Robbins D. Analysis of emergency readmissions. Pennine Acute Trust;
2013.
8 Dharmarajan K, Hsieh AF, Lin Z, Bueno H, Ross JS, Horwitz LI, et
al. Hospital readmission performance and patterns of readmission:
retrospective cohort study of Medicare admissions. BMJ. 2013;347:f6571.
9 Donz J, Lipsitz S, Bates DW, Schnipper JL. Causes and patterns of
readmissions in patients with common comorbidities: retrospective
cohort study. BMJ. 2013;347:f7171.
10 Katikireddi SV, Cloud GC. Planning a patients discharge from hospital.
BMJ. 2008;337:a2694.
38
AUDIT
Cardiovascular disease risk

assessment in psoriasis patients
V. Nakata
vera.nakata@student.manchester.ac.uk
Abstract
Background Psoriasis is a signiicant health problem that affects 2.2% of
the UK population. Recent evidence also suggests an association between
psoriasis and an increased risk of cardiovascular disease (CVD). As such, the
National Institute for Health and Care Excellence (NICE) guidelines have made
recommendations pertaining to cardiovascular risk management in psoriasis
patients.
Aims An audit was conducted on a single general practice to evaluate how
well the practice was managing the CVD risk of its psoriasis patients on repeat
prescription.
Methods A search was conducted on the practices computer database to
identify all patients who are coded as suffering from psoriasis. Prescription
records were then reviewed to ascertain whether the patient was currently on
repeat prescription for psoriasis treatment. Patient records were then used to
determine the severity of these patients psoriasis, and whether their CVD risks
were calculated and managed appropriately.
Results A total of 32 patients on repeat prescription for psoriasis were
identiied. The practice performed moderately well, with 87.5% of its adult
severe psoriasis patients, 73.9% of its psoriasis patients aged 4074 years
and 100% of its psoriasis patients with a 10-year CVD risk 20% being
adequately managed as per NICE guidelines.
Conclusion This audit highlighted to the practices clinicians that psoriasis
patients require more CVD risk monitoring to achieve ideal 100% standards.
Appointments were arranged for patients whose CVD risk had not been
adequately assessed. Plan to re-audit in 12 months, and at least every ive
years thereafter.
39
V. Nakata
Introduction
Psoriasis is a signiicant clinical condition as it afects approximately 2.2%
of the UK population,(1) and is associated with considerable reduction in
health-related quality of life.(2) In addition, recent studies have indicated
that psoriasis patients are at increased risk of cardiovascular disease
(CVD).(35) This has been attributed to the similarities in T helper (Th)-celldriven inlammation, as well as the increases in pro-inlammatory cytokines,
which underlie both psoriasis and atherosclerosis.(6) These associations, if
proven true, possess great implications for the management of psoriasis.
Firstly, the recognition and treatment of modiiable CVD risk factors in
patients with psoriasis may help reduce associated cardiovascular morbidity and mortality. Equally, the efective management of co-morbidities may
also alleviate psoriasis, and thus maximise therapeutic outcomes.
According to the 2012 National Institute for Health and Care Excellence
(NICE) clinical guidance for psoriasis,(7) adults with severe psoriasis
(deined as requiring treatment with phototherapy, systemic agents or
hospital admission) of any type should be ofered cardiovascular risk
assessment at presentation using a validated risk-estimation tool. Further
assessment of cardiovascular risk should be ofered every ive years, or
more frequently if required. In addition, risk factors for cardiovascular
co-morbidities should be discussed with people who have any type of
psoriasis.(7)
However, a recent survey conducted by Parsi et al.(8) found that 45%
of primary care physicians and cardiologists were unaware of the link
between psoriasis and CVD, and that psoriasis patients were not routinely
screened for their cardiovascular risk factors. While this survey was conducted on American physicians, it is probable that in the UK psoriasis
patients are not being adequately screened for cardiovascular risk as per
guidelines. This situation may be compounded by the fact that the management of psoriasis is not included in the Quality Outcomes Framework
(QOF),(9) which rewards general practices in the UK according to how
well they care for patients with certain diseases, and may thus result in the
neglect of cardiovascular risk assessment in psoriasis patients.
Hence, an audit was conducted in a single general practice to evaluate
whether adults with severe psoriasis are being adequately assessed for their
cardiovascular risk using a validated risk-estimation tool. In view of the
fact that the recommendation only speciied patients with severe psoriasis,
the audit will also review whether cardiovascular risk assessments are
being carried out in the mild/moderate psoriasis patient population as per
guidelines for the primary and secondary prevention of CVD.(10)
The standards the practice should meet are as stated by the National
Audit Support Guide, which are typically 100% adherence to the guidelines,
with or without certain exceptions.(11,12)
40
Table 1: NICE criteria and standards for CVD risk assessment in psoriasis
patients.
Standard
Percentage of adults with severe psoriasis of

any type who are ofered a cardiovascular risk
assessment at presentation using a validated
risk-assessment tool. Further assessments of
cardiovascular risk are ofered at least every ive
years(11)
There is a systematic strategy in place to identify
people aged 4074 years who are likely to be at
high risk of CVD(12)
Percentage of people with a 20% or greater
10-year risk of developing CVD who have
statin therapy as part of the primary prevention
management strategy(12)
100%
No exceptions
100%
No exceptions
100%
Exceptions:
People who have potential drug
interactions or contraindications
People who decide, after an informed
discussion with their clinician about
risks and beneits, not to start statin
therapy
CVD risk assessment in psoriasis patients
Criterion
The criteria and standards for the audit are summarised in Table 1.
Thus, the aim of this audit is to give an objective evaluation of how the
practice is doing in terms of managing the cardiovascular risk of its psoriasis patients. The audit also expects to identify some patients whose cardiovascular risk has not been adequately assessed. These patients would then
be highlighted to the practice, so that their CVD risk can be appropriately
managed.
Consequently, recognition that psoriasis could be an independent cardiovascular risk factor may help to decrease cardiovascular co-morbidities
amongst the psoriasis population, and thus improve patients overall
quality of life. There will also be signiicant economic beneit to the NHS,
as it has been found that psoriasis patients with co-morbidities such as
hyperlipidaemia utilised healthcare services more frequently and incurred
greater healthcare costs than patients with psoriasis alone.(13)
Methods
A search was irst conducted on the practices computer system to identify
all the registered patients who are coded as sufering from psoriasis. This
came back with 189 patients. Prescription records were then manually
reviewed to ascertain whether the patient was currently on repeat prescription for psoriasis treatment. It was found that there were 32 patients
who are coded on the system as having psoriasis and are currently being
prescribed psoriasis medications on a repeat basis.
Medical records and clinic letters of the 32 patients were then analysed
to extract the following details:
41
V. Nakata
age
diagnosis
severity of psoriasis*
psoriasis medications on repeat prescription
alcohol intake and status
smoking intake and status
total cholesterol level
high-density lipoprotein (HDL) level
body mass index (BMI)
blood pressure
diabetes status
10-year CVD risk (based on the Joint British Societies Cardiovascular
Risk Prediction Chart(14))
date 10-year CVD risk was assessed
whether currently on statin therapy.
*
Severe psoriasis being deined by NICE(7) as requiring treatment with

phototherapy, systemic agents or hospital admission.
Trivial: <1 unit/day; light: 12 units/day; moderate: 36 units/day; heavy: 79

units/day.
Never smoked; light: 19 cigarettes/day; moderate: 1019 cigarettes/day; heavy:

2039 cigarettes/day.
Figure 1: Flow chart of how patients to be included in the audit were identiied.
Lastly, the average 10-year CVD risk for psoriasis patients currently on
repeat prescription and that for non-psoriasis patients were calculated
using the practice computer system, for the comparison of cardiovascular
risk between these patient groups.
Results
According to the NICE guidelines, severe psoriasis is deined as that
which requires treatment with phototherapy, systemic agents or hospital
admission.(7) Thus, of the 32 psoriasis patients on repeat psoriasis prescription, 8 patients met the criteria of having severe psoriasis. Of these
8 patients, it was found that 7 had been assessed using a validated risk42
estimation tool (Joint British Societies Cardiovascular Risk Prediction

Chart) within the last ive years, whereas 1 patient had not been assessed
(patient 4,095).
Of the sample group of 32 patients, 23 were aged 4074 years, and
should thus be systematically screened to determine whether they are at
high risk of CVD. However, of these 23 patients, there were 6 patients
whose cardiovascular risk had not been assessed (patients 548, 879, 4,095,
6,319, 9,825, 12,372).
Also, of the 23 patients aged 4074 years, there are 2 patients with a
10-year CVD risk greater than or equal to 20% (patients 1,308, 9,671).
However, neither of these patients is currently on statin therapy for
primary prevention of CVD. Upon review of their computerised records,
it was shown that both patients 1,308 and 9,671 had declined statin
therapy after an informed discussion with the doctors at the practice, on
21 January 2014 and 25 October 2012 respectively.
The practices performance in relation to the criteria are thus summarised in Table 2.
Table 2: Summary of practices audit performance.
Criterion
Standard
Practice
performance
Percentage of adults with severe

psoriasis of any type who are
ofered a cardiovascular risk
assessment at presentation using
a validated risk-assessment
tool. Further assessments of
cardiovascular risk are ofered at
least every ive years(11)
There is a systematic strategy in
place to identify people aged 4074
years who are likely to be at high
risk of CVD(12)
Percentage of people with a 20% or
greater 10-year risk of developing
CVD who have statin therapy as
part of the primary prevention
management strategy(12)
100%
87.5%
(7 out of 8
patients)
100%
100%
Exceptions:
People who have potential drug
interactions or contraindications
People who decide, after an
informed discussion with their
clinician about risks and beneits,
not to start statin therapy
73.9%
(17 out of 23
patients)
100%
exception
(2 out of 2
patients)
Further details of the audit data can be found in the Appendix.

The average 10-year CVD risk of the non-psoriasis patients currently
registered with the practice, mild/moderate psoriasis patients on repeat
prescription and severe psoriasis patients on repeat prescription was found
to be 10.48%, 13.04% and 10.08% respectively.
43
V. Nakata
Discussion
The aim of this audit was to evaluate how well the practice is managing
the cardiovascular risk of its psoriasis patients, in accordance with NICE
guidelines. In view of the evidence supporting the notion of a directly proportional relationship between the severity of psoriasis and the increase in
cardiovascular risk,(15,16) the average cardiovascular risk of non-psoriasis
patients, mild/moderate psoriasis patients and severe psoriasis patients
was also investigated.
Results from the audit showed that the practice only managed to
adequately assess the cardiovascular risk in 87.5% of its adult patients
with severe psoriasis, whereas only 73.9% of its psoriasis patients aged
4074 years were identiied and assessed for high risk of CVD. However,
it should be noted that the practice has met the 100% standard in managing its psoriasis patients with a 20% or greater 10-year CVD risk with
statin therapy, with the therapy being ofered and declined by the patients
informed decision.
Another interesting inding from this audit was that while current
literature proposes a doseefect relationship, whereby cardiovascular
risk increases with the severity of psoriasis, this was not observed in the
practices population of psoriasis patients on repeat prescription. It was
found that non-psoriasis patients had a cardiovascular risk of 10.48%,
mild/moderate psoriasis patients on repeat prescription had an increased
cardiovascular risk of 13.04%, but severe psoriasis patients on repeat prescription had a decreased cardiovascular risk of 10.08%. The inconsistency
between the results obtained from this audit and the existing literature
could be attributed to three main reasons.
Firstly, based on the methodology, only eight severe psoriasis patients
on repeat prescription were identiied for this audit. Hence, the average
cardiovascular risk calculated from this small sample group is inconclusive. Furthermore, owing to time constraints, the medical records of psoriasis patients not on repeat prescription were not reviewed. This meant
there could potentially be psoriasis patients who receive systemic treatment directly from secondary care, but are not on the practices repeat
prescription register, who were not identiied. Exclusion of this patient
group could have negatively afected the indings.
Secondly, while the psoriasis area and severity index (PASI) is considered the gold standard for assessing the severity of psoriasis,(17) this audit
assessed severity based on the treatment that the patient is on. In PASI,
severity of psoriasis is dependent on the redness, induration, scaling and
area of body surface involved. PASI scores range from 0 (no disease) to
72 (maximal disease), with severe psoriasis being deined as a PASI score
greater than 20.(18) On the other hand, this audit followed the NICE deinition of severe psoriasis as requiring treatment with phototherapy, systemic
44
agents or hospital admission.(7) Thus, based on this deinition, the eight

patients who are classiied as having severe psoriasis are those who are on
systemic therapy. Most importantly, seven out of these eight patients are
on methotrexate. Methotrexate, which has anti-inlammatory properties,
has recently been shown to reduce the risk of CVD in patients with chronic
inlammation.(19) As such, the prevalent use of methotrexate in the small
sample group of severe psoriasis patients may have contributed to the
decreased cardiovascular risk of 10.08%.
Thirdly, it should be noted that while traditional cardiovascular risk
factors(20) such as age, gender and diabetes were recorded for the sample
group, these were not adjusted for when calculating the average cardiovascular risk for the patients. As such, traditional cardiovascular risk factors
may have been more prevalent in the mild/moderate psoriasis patient
group, which could explain the higher cardiovascular risk observed as
compared with the severe psoriasis patient group.
As such, taking into account the aforementioned reasons, the average
10-year CVD risk calculated for the non-psoriasis patients, mild/moderate
psoriasis patients and severe psoriasis patients should be used for reference only, and does not invalidate the doseefect relationship observed
by other major studies.
Conclusion
There has been increasing evidence to support an association between psoriasis and cardiovascular morbidity. Additionally, there appears to be a
directly proportional relationship between the severity of psoriasis and the
increase in CVD risk. While results are not yet conclusive, and more rigorous research is required to ascertain the link between psoriasis and CVD,
it remains prudent to actively assess the CVD risk in psoriasis patients.
Results of the audit have shown that the practice has performed moderately well in managing the CVD risk of its psoriasis patients. While this
inding is encouraging, the practice could aim to achieve the ideal 100%
standard. This could be accomplished by raising awareness amongst the
practices GPs about the association between psoriasis and increased CVD
risk, as well as ensuring that GPs are actively assessing the CVD risk in
psoriasis patients through regular re-auditing of the topic.
Acknowledgements
Dr A. Buckley provided assistance and supervision of the audit process.
This work was part of a Manchester Medical School student project. Any
indings, conclusions or recommendations expressed in this material are
those of the author and do not necessarily relect those of the Manchester
Medical School.
45
V. Nakata
References
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Management of Psoriasis and Associated ComorbidiTy (IMPACT)
project team. Global epidemiology of psoriasis: a systematic review of
incidence and prevalence. J Invest Dermatol. 2013 Feb;133(2):37785.
2 Rapp SR, Feldman SR, Exum ML, Fleischer AB Jr, Reboussin DM.
Psoriasis causes as much disability as other major medical diseases. J Am
Acad Dermatol. 1999 Sep;41(3 Pt 1):4017.
3 Prodanovich S, Kirsner RS, Kravetz JD, Ma F, Martinez L, Federman
DG. Association of psoriasis with coronary artery, cerebrovascular,
and peripheral vascular diseases and mortality. Arch Dermatol. 2009
Jun;145(6):7003.
4 Ahlehof O, Gislason GH, Charlot M, Jorgensen CH, Lindhardsen
J, Olesen JB, et al. Psoriasis is associated with clinically signiicant
cardiovascular risk: a Danish nationwide cohort study. J Intern Med.
2011 Aug;270(2):14757.
5 Lin HW, Wang KH, Lin HC, Lin HC. Increased risk of acute myocardial
infarction in patients with psoriasis: a 5-year population-based study in
Taiwan. J Am Acad Dermatol. 2011 Mar;64(3):495501.
6 Sph F. Inlammation in atherosclerosis and psoriasis: common
pathogenic mechanisms and the potential for an integrated treatment
approach. Br J Dermatol. 2008;159(s2):1017.
7 National Institute for Health and Care Excellence (NICE). Psoriasis:
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Manchester: NICE; 2012 [cited 2014 Feb 1]. Available from: http://www.
nice.org.uk/nicemedia/live/13938/61190/61190.pdf.
8 Parsi KK, Brezinski EA, Lin TC, Li CS, Armstrong AW. Are patients
with psoriasis being screened for cardiovascular risk factors? A study of
screening practices and awareness among primary care physicians and
cardiologists. J Am Acad Dermatol. 2012 Sep;67(3):35762.
9 NICE. Quality and outcomes framework: NICE menu of indicators
[Internet]. London and Manchester: NICE; 2013 [cited 2014 Feb 1].
Available from: http://www.nice.org.uk/aboutnice/qof/indicators.jsp.
10 Cooper A, Nherera L, Calvert N, OFlynn N, Turnbull N, Robson J,
et al. Clinical guidelines and evidence review for lipid modiication:
cardiovascular risk assessment and the primary and secondary
prevention of cardiovascular disease. London: National Collaborating
Centre for Primary Care and Royal College of General Practitioners;
2008.
11 NICE. Psoriasis: clinical audit tool non-specialist services, CG153
[Internet]. London and Manchester: NICE; 2013 [cited 2014 Feb 1].
Available from: http://guidance.nice.org.uk/CG153/ClinicalAudit/
NonSpecialistServices/doc/English.
46
12 NICE. Lipid modiication: audit support [Internet]. London and

Manchester: NICE; 2013 [cited 2014 Feb 1]. Available from: http://
guidance.nice.org.uk/CG67/AuditSupport/doc/English.
13 Kimball AB, Guerin A, Tsaneva M, Yu AP, Wu EQ, Gupta SR, et
al. Economic burden of comorbidities in patients with psoriasis is
substantial. J Eur Acad Dermatol Venereol. 2011 Feb;25(2):15763.
14 British Cardiac Society, British Hypertension Society, Diabetes UK,
HEART UK, Primary Care Cardiovascular Society, Stroke
Association. JBS 2: Joint British Societies guidelines on prevention of
cardiovascular disease in clinical practice. Heart. 2005 Dec;91(Suppl
5):v152.
15 Horreau C, Pouplard C, Brenaut E, Barnetche T, Misery L, Cribier B,
et al. Cardiovascular morbidity and mortality in psoriasis and psoriatic
arthritis: a systematic literature review. J Eur Acad Dermatol Venereol.
2013 Aug;27(Suppl 3):1229.
16 Xu T, Zhang YH. Association of psoriasis with stroke and myocardial
infarction: meta-analysis of cohort studies. Br J Dermatol. 2012
Dec;167(6):134550.
17 Spuls PI, Lecluse LL, Poulsen ML, Bos JD, Stern RS, Nijsten T.
How good are clinical severity and outcome measures for psoriasis?:
quantitative evaluation in a systematic review. J Invest Dermatol. 2010
Apr;130(4):93343.
18 Mrowietz U, Kragballe K, Nast A, Reich K. Strategies for improving
the quality of care in psoriasis with the use of treatment goals: a report
on an implementation meeting. J Eur Acad Dermatol Venereol. 2011
May;25(Suppl 3):113.
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Nov 1;108(9):136270.
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Robinson J, et al. 2013 ACC/AHA guideline on the assessment of
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Am Coll Cardiol [Internet]. 2014 Jul 1; 63(25_PA). doi: 10.1016/j.
jacc.2013.11.005.
47
Appendix
V. Nakata
Psoriasis patients and CVD risk

Patient
code
Age
(years) Diagnosis
429*
61
Psoriatic
arthropathy
441
29
548
42
614*
64
879
59
897
64
1,308
70
Psoriasis
NOS,
psoriasis
and similar
disorders
Psoriasis
NOS
Psoriatic
arthropathy,
psoriasis
and similar
disorders
Psoriasis
NOS
Psoriasis
NOS
Psoriasis
NOS
2,370*
47
Psoriatic
arthropathy
2,782*
39
Psoriasis
NOS
4,034
54
Psoriatic
arthropathy,
psoriasis
NOS
Psoriasis
medication on
repeat
JBS
Date CVD
10-year risk was
CVD risk recorded
Methotrexate 2.5
mg, sulfasalazine
500 mg
Exorex lotion,
Doublebase gel
3.23
Dermol 200
shower emollient
Methotrexate 2.5
mg, Diprobase
cream, Dermol
500 lotion
Not
Not
None
recorded recorded
10.51
8
None
November
2013
Dovobet gel
Not
Not
recorded recorded
10.5
23 April
2013
33.69
8 October
2013
Lotiderm cream,
Dovobet gel
Lotriderm cream,
calcipotriol
0.005%/
betamethasone
dipropionate
0.05%,
Dermol cream,
Doublebase gel
Methotrexate 2.5
mg, prednisolone
5 mg
Methotrexate 2.5
mg
Calcipotriol
0.005%/
betamethasone
dipropionate
0.05% ointment,
paracetamol 500
mg
27 August None
2013
Not
Not
recorded recorded
16.7
6.57
2.95
Statin
therapy
None
None
None
None
5
Atorvastatin
November
2013
6
None
February
2012
16
None
October
2013
48
Patient
code
Age
(years) Diagnosis
Psoriasis
NOS
4,675
65
6,319
54
Psoriasis
NOS
Psoriasis
NOS
6,899
55
Psoriasis
NOS
6,946*
63
Psoriatic
arthropathy
6,961
57
Psoriasis
NOS
8,002
80
H/O
psoriasis
8,840
74
Psoriasis
unspeciied
JBS
Date CVD
10-year risk was
CVD risk recorded
Hydromol
Not
Not
Bath&Shower
recorded recorded
emollient,
tacrolimus
0.1% ointment,
Hydromol
ointment,
Doublebase
gel, Dermax
Therapeutic 0.5%
shampoo, coconut
oil compound
ointment,
Dovobet gel,
Diprosalic
0.05%/3%
ointment
Diprobase cream 10.75
6 June
2013
Dermax
Not
Not
Therapeutic
recorded recorded
0.5% shampoo,
hydrocortisone 1%
cream
Dermax
7.48
22
Therapeutic 0.5%
October
shampoo, Aveeno
2013
body wash,
Aveeno lotion,
Aveeno cream
Methotrexate 2.5 13.99
7 January
mg, fFolic acid
2014
5 mg
QV gentle wash,
8.15
30
calcipotriol
December
0.005%/
2013
betamethasone
dipropionate,
Emollin
aerosol spray,
hydroxyzine 25
mg tablets
Cetraben
43.59
9 January
emollient cream
2014
Sebco ointment
15.56
Statin
therapy
None
Simvastatin
4,095* 50
Psoriasis
medication on
repeat
None
None
Atorvastatin
Simvastatin
Pravastatin
16
Simvastatin
September
2013
49
V. Nakata
Patient
code
Age
(years) Diagnosis
9,089
52
Psoriasis
NOS, H/O
psoriasis
9,671
70
Psoriasis
NOS
9,717
24
9,825
47
9,856
35
Psoriasis
NOS
Psoriasis
NOS, H/O
psoriasis
Psoriasis
NOS
10,163* 83
10,734
60
10,853* 58
11,081 25
11,609
36
12,257
44
12,372 40
Psoriasis
medication on
repeat
JBS
Date CVD
10-year risk was
CVD risk recorded
Statin
therapy
Calcipotriol
0.005%/
bethamethasone
dipropionate
0.05% ointment
Betacap 0.1%
scalp application
9.13
None
Epaderm cream
Calcitriol 3 mg/g
ointment
Calcipotriol
0.005%/
betamethasone
dipropionate
0.05% ointment
Psoriatic
Methotrexate
arthropathy, 2.5 mg, folic acid
H/O
5 mg
psoriasis
Guttate
Betamethasone
psoriasis,
valerate 0.1%
psoriasis
scalp application,
NOS
Capsal
Therapeutic
shampoo
Psoriasis
Methotrexate 2.5
NOS
mg, E45 emollient
bath oil, Dermol
cream, Dovobet
gel
H/O
Balneum 84.75%
psoriasis
bath oil, Epaderm
ointment
Psoriasis
Calcipotriol
NOS
0.005%/
betamethasone
dipropionate
0.05% ointment
Psoriatic
Paracetamol 500
arthropathy, mg, amitriptyline
psoriasis
10 mg
NOS
Psoriasis
Dovonex 50
NOS
mg/g ointment,
Dovobet ointment
22 May
2012
27.37
5
None
September
2012
Not
Not
None
recorded recorded
19
Not
None
recorded
Not
Not
recorded recorded
None
6.93
20
January
2014
None
3.82
3
Simvastatin
September
2013
12.64
9
None
December
2013
Not
Not
recorded recorded
None
4.24
14
None
December
2011
4.22
22
None
December
2011
Not
Not
recorded recorded
None
50
Age
(years) Diagnosis
12,415
38
Pustular
psoriasis
12,764
43
Psoriasis
NOS
Psoriasis
medication on
repeat
JBS
Date CVD
10-year risk was
CVD risk recorded
Balneum Plus
bath oil, Epaderm
ointment
Diprosalic
0.05%/2% scalp
application
3.18
5.07
Statin
therapy
5
None
September
2012
8 March
None
2013
H/O = history of; NOS = not otherwise speciied.

*Severe psoriasis patients deined as requiring treatment with phototherapy, systemic agents or hospital
admission.
Psoriasis patients aged 4074 years whose CVD risk has yet to be adequately assessed.
Psoriasis patients with a 20% or greater 10-year risk of developing CVD.
Psoriasis patients and lifestyle risk factors (alcohol and smoking)

Patient
code
Age
Alcohol (units/
week)
Alcohol intake
status*
Smoking
(cigarettes/day)
Smoking
status
429
61
Trivial
441**
548**
614
29
42
64
Not recorded
Not recorded
8
Light
Not recorded
Light
10
10
0
879**
59
14
Light
897
64
Not recorded
Moderate
Never
smoked
Moderate
Light
Ex-light
smoker
Ex-light
smoker
Ex-heavy
smoker
Moderate
1,308
70
Not recorded
Moderate
20
47
10
Light
2,782
4,034
39
54
1
7
Trivial
Trivial
7
0
4,095,**
4,675
50
65
15
1
Heavy
Trivial
15
0
6,319**
54
Not recorded
Not recorded
6,899
55
Not recorded
(alcohol
dependence
syndrome)
9
Moderate
6,946
63
Not recorded
Light
6961
57
Teetotaller
8002
80
Teetotaller
8,840
74
Trivial
2,370
Patient
code
Never
smoked
Light
Ex-heavy
smoker
Light
Never
smoked
Heavy
Ex-light
smoker
Ex-moderate
smoker
Never
smoked
Ex-light
smoker
Light
51
V. Nakata
Patient
code
Age
Alcohol (units/
week)
Alcohol intake
status*
Smoking
(cigarettes/day)
Smoking
status
9,089
52
12
Not recorded
9,671
70
14
Not recorded
9,717**
24
Not recorded
Not recorded
9,825
9,856**
10,163
47
35
83
4
10
0
Light
Not recorded
Teetotaller
1
10
0
10,734
60
Trivial
10,853
58
20
Moderate
11,081**
25
18
Not recorded
11,609
36
Not recorded
Not recorded
12,257
44
Not recorded
12,372**
40
Not recorded
Light
12,415
12,764
38
43
Not recorded
1
Light
Trivial
10
0
Ex-moderate
smoker
Never
smoked
Never
smoked
Light
Moderate
Never
smoked
Never
smoked
Never
smoked
Never
smoked
Never
smoked
Ex-heavy
smoker
Never
smoked
Moderate
Ex-heavy
smoker
*Alcohol intake status teetotaller; trivial: <1 unit/day; light: 12 units/day; moderate: 36 units/day;
heavy: 79 units/day.
Smoking status never smoked; light: 19 cigarettes/day; moderate: 1019 cigarettess/day; heavy: 2039
cigarettes/day).
Severe psoriasis patients deined as requiring treatment with phototherapy, systemic agents or hospital
admission.
**Psoriasis patients aged 4074 years whose CVD risk has yet to be adequately assessed.
Psoriasis patients lipid levels, BMI, blood pressure and diabetes status
Patient
code
Age
Cholesterol HDL
(mmol/L)
(mmol/L) BMI
Blood
pressure Blood pressure
(mm Hg) status
429*
61
5.5
2.5
26.8
118/72
Normal
No
441
29
Not
recorded
Not
recorded
25.62
110/60
Normal
No
548
42
Not
recorded
Not
recorded
31.43
112/70
Normal
No
614*
64
6.2
1.7
33.76
144/88
No
Essential
hypertension on
medication (ramipril,
amlodipine)
879
59
4.8
Not
recorded
21.1
125/79
Normal
Diabetes
No
52
Patient
code
Age
Cholesterol HDL
(mmol/L)
(mmol/L) BMI
Blood
pressure Blood pressure
(mm Hg) status
897
64
6.1
1.7
38
122/84
No
Essential
hypertension on
medication (lisinopril)
1,308
70
5.6
1.6
29.05
148/80
Raised
No
2,370*
47
3.8
0.7
30.69
128/80
Normal
Type 2
2,782*
39
5.8
1.1
29.7
110/80
Normal
No
4,034
54
5.5
1.8
29.86
110/60
Normal
No
4,095* 50
5.1
Not
recorded
21.83
128/86
Normal
No
Diabetes
65
5.7
1.5
31.9
126/80
Normal
No
6,319
54
6.5
0.9
26.42
120/70
Normal
No
6,899
55
1.4
37.45
120/60
Normal
No
6,946*
63
3.5
1.6
24.73
130/60
Normal
Type 2
6,961
57
3.5
1.9
68.4
136/74
Borderline raised
Type 2
8,002
80
3.9
1.1
28.62
130/75
Type 2
Essential
hypertension on
medication (ramipril)
8,840
74
3.6
1.2
31.48
132/71
Raised diastolic
9,089
52
6.1
1.1
27.97
120/68
Normal
No
9,671
70
5.5
1.5
27.29
132/75
Raised diastolic
No
9,717
24
Not
recorded
Not
recorded
27.59
130/80
Normal
No
No
9,825
47
3.9
0.9
29.75
118/70
Normal
No
9,856
35
Not
recorded
Not
recorded
28.5
115/85
Normal
No
10,163* 83
2.1
20.03
122/50
Essential hypertension No
on medication
(lisinopril, atenolol,
bendrolumethiazide)
10,734
4.7
1.9
25.89
110/60
No
Essential
hypertension on
medication (lisinopril)
60
10,853* 58
5.8
26.57
144/80
Borderline raised
No
11,081 25
Not
recorded
Not
recorded
42.83
143/78
Raised
No
11,609
36
6.3
1.2
35.81
120/70
Normal
Diabetes
insipidus
12,257
44
132/76
6.3
1.3
34.58
Normal
No
12,372 40
Not
recorded
Not
recorded
Not
Not
recorded recorded
Not recorded
No
12,415
38
5.9
1.4
Not
132/84
recorded
Normal
No
12,764
43
5.3
1.1
27.41
Normal
No
118/62
4,675
*Severe psoriasis patients deined as requiring treatment with phototherapy, systemic agents or hospital
admission.
Psoriasis patients aged 4074 years whose CVD risk has yet to be adequately assessed.
53
54
CASE REPORT
Treatment options for patients with

primary myeloibrosis
A. B. Swali,1 M. Haj2
1

andrew.swali@student.manchester.ac.uk
2
Stockport NHS Foundation Trust
Abstract
Background Primary myeloibrosis (PMF) is a myeloproliferative disorder
resulting in progressive bone marrow ibrosis. In some PMF patients, a
mutation in the gene coding for janus-associated kinase 2 (JAK2) results in cell
proliferation and evasion of apoptosis. PMF typically occurs in older patients,
and is associated with poor prognosis and low survival, with death occurring
secondary to cardiovascular disease.(1) Investigations include full blood counts,
blood ilm analysis, and bone marrow aspiration and trephine. Treatment is
largely palliative; the single curative intervention of stem-cell transplant being
available only to low-risk younger patients. Potential supportive treatments
include the use of JAK2 inhibitors.
Method This case report studies a patient who was diagnosed with PMF at
the age of 60.
Results The patients condition remained stable for up to 11 years before
her symptoms deteriorated and her treatment was altered. The report focuses
on current and upcoming treatments including JAK inhibitors, and evaluates
their possible future implications for the management of patients with PMF.(2,3)
Conclusion Breakthroughs in the understanding of the underlying PMF
molecular mechanisms have led to improved treatments. There is a future role
for JAK2 inhibitors in the management of palliative care. Ruxolitinib, which
is now available for use in clinical practice, may alter treatment and improve
quality of life for those living with PMF.
55
A. B. Swali, M. Haj
Introduction
The aims of this article are to gain an understanding of myeloibrosis
(MF), including the pathophysiology, clinical presentation, investigations, and diagnostic and prognostic features. More speciically, it looks at
current treatment options and future developments which could alter the
disease course. In addition, through this case report, we aim to analyse the
management of a patient with longstanding primary myeloibrosis (PMF)
and to discuss currently available and emerging treatment options.
The current guidelines for the diagnosis and management of MF,
published by the British Journal of Haematology in 2012, were used as
the benchmark for current practice in this area. The management of the
patient in our case report was compared to the standards laid out within
these guidelines, and a subsequent review of the literature aimed to identify any advances in therapy since their publication.
Points raised in the discussion focus on the reasons for denial of speciic
treatments to the patient. It looks at future therapies and how they may be
adapted for elderly patients (the majority of PMF patients) who currently
are unsuitable for a number of treatment options. The only curative treatment is currently only suitable for younger patients, with strict controls on
eligibility. A number of journals touch on advances in research into not
only the understanding of the science behind myeloibrosis, but the combination of diferent therapies to achieve desired therapeutic goals.
Case presentation
In June 1998 a 60-year-old Caucasian woman was referred to the haematology department with thrombocytopenia and a suspected possible MF.
At presentation to the haematology clinic, the patient had been bruising
easily for the last four months; there was no history of bone pain, abdominal pain, night sweats or bleeding. The patients past medical history
included hypothyroidism and asthma. She was a non-smoker and drank
two units of alcohol a week. Her medication at the time included clomipramine, thyroxine, hormone replacement therapy and beclomethasone.
On examination the patient had petechiae over her shins, two small
bruises on her sternum and right arm, and some generalised itching.
There was no palpable lymphadenopathy, cardiovascular and respiratory systems were unremarkable, and abdominal examination revealed a
marked splenomegaly, with the tip extending 3 cm below the umbilicus,
and slight hepatomegaly.
A full blood count showed haemoglobin (Hb) 110 g/L, white blood cell
count (WBCC) 4.1 109/L and platelets 57 109/L. A peripheral blood ilm
demonstrated increased reticulin with ine collagenisation; features consistent
with an underlying MF. A bone marrow biopsy resulted in a dry tap and a
56
Treatment for primary myeloibrosis patients
trephine analysis showed marrow spaces which contained a marked increase

in reticulin with ine collagenisation, in keeping with PMF. The majority of
cells examined showed a translocation between the short arms of chromosomes 2 and 6 and an extra copy of chromosome 8, which is commonly found
in myeloid disorders. Megakaryocytes were recognised with a few white cell
precursors, although no deinite evidence of malignancy was present.
The patient was initially treated with folic acid and iron tablets to maintain normal erythropoiesis.
The patient had good prognostic factors for her MF, there was no overt
bleeding, and over the following years she has remained relatively well;
however, her Hb and platelets remained low and her splenomegaly progressed. By 2009 the patient had been haematologically stable for 11 years
with no constitutional symptoms; she was discussed in a multidisciplinary
team (MDT) meeting where a decision for active monitoring was made.
In 2010, owing to worsening anaemia, the patient underwent extensive
investigation, and a JAK2 V617F mutation was detected. The patient
had received some blood transfusions and was taking tranexamic acid
and prednisolone owing to platelet deiciency, which level had dropped to
2040 109/L. A CT scan revealed a small pericardial efusion, some lung
consolidation, and difuse sclerosis of the bones with multiple well-deined
lytic areas; the patients renal function was also declining (creatinine = 145
mol/L, urea = 17 mmol/L, by 2011 estimated glomerular iltration rate =
36 ml/min/1.73 m2). An endoscopy showed a hiatus hernia, multiple ulcers
and telangiectasia, and she was started on lansoprazole. In 2011 the patient
was started on furosemide, ramipril, candesartan and spironolactone for
symptoms of early heart failure. A further CT scan was performed owing
to the deteriorating renal function that revealed three lesions in the spleen;
these were discussed at a radiological MDT. The decision was taken not
to biopsy the lesions because of the signiicant risk of bleeding. In October
2011 a chromosome analysis showed evidence of clonal evolution, with an
unbalanced translocation between the long arms of chromosomes 1 and
11 resulting in trisomy 1q; this is a common inding in myeloproliferative
neoplasia and is associated with disease transformation. The patient was
referred for a trial involving a new JAK2 inhibitor in 2012, but was unfortunately ineligible owing to her decreased platelet count and thrombocytopenia being one of the possible side efects of the treatment. In 2013 the
patient had been given immunoglobulin, Octagam and hydrocortisone for
her MF, and is continuing with blood transfusions.
Myelofibrosis
MF is a myeloproliferative disorder; this term refers to disorders
which involve clonal increase of the blood-forming cells in the bone
marrow. Other myeloproliferative disorders include polycythaemia rubra
57
A. B. Swali, M. Haj
vera (PRV) and essential thrombocytopenia (ET). These disorders can be

transitional and can evolve into one another over time. In PMF, ibrosis
of the bone marrow occurs progressively and is secondary to hyperplasia
of abnormal megakaryocytes. Fibroblasts are thought to be stimulated by
cytokines and growth factors secreted by platelets and megakaryocytes.
Anaemia may occur, resulting in extramedullary haemopoiesis in the
spleen and liver, causing splenomegaly. Some patients may develop osteosclerosis.(2) MF usually ensues after 50 years of age but sometimes presents
in children; it may later transform to acute leukaemia.(3)
Clinical features
Patients with MF can sufer from thrombocytosis or thrombocytopenia,
leukocytosis or leukopenia, and ongoing anaemia.(3) There are manifestations of constitutional symptoms such as low-grade temperature, night
sweats and cachexia.(4) Hepatomegaly due to extramedullary haemopoiesis results in symptoms such as pain, abdominal distension, early satiety,
diarrhoea, dyspnoea, portal hypertension and splenic infarction.(4,5)
Janus-associated kinase 2
A mutation (Val617Phe) in JAK2 (a tyrosine kinase in the cytoplasm of
the bone marrow and blood) is present in nearly every patient with PRV,
and half the patients with ET and MF. JAK2 transduces signals from
various cytokines and growth factors that are involved in myeloid growth.
Many haemopoietic growth factor receptors interact with a protein
kinase. The cytoplasmic domains of the receptors move closer with growth
factor binding. Concurrently the two JAK2 kinases are phosphorylated by
each other and become activated. When mutation occurs it afects an area
of the pseudo-kinase domain which negatively controls JAK2. The V617F
mutation results in activation of the JAK molecules without the presence
of a growth factor.(2,6)
As JAK2 is activated, this results in cell survival and proliferation via
three diferent paths. These include the phosphoinositide 3-kinase (PI3K)
path with Akt (also known as protein kinase B), the signal transducer
and activator of transcription (STAT) factors, and the activation of Ras
leading to activation of mitogen-activated protein kinases (MAPK) and
extracellular-signal-regulated kinases (ERK). The outcome is a collection
of proteins that result in cell proliferation and survival.(2,6)
Investigations and diagnosis
Blood ilms usually demonstrate the presence of myelocytes and normoblasts denoting a leukoerythroblastic reaction appearing as teardrop
58
Treatment
Elderly patients with PMF tend to be treated conservatively. If they have
no symptoms or low risk factors for further development of the disease,
careful observation is adequate.(6)
The most widely used agent for haemopoiesis and splenomegaly is
hydroxycarbamide. Approximately 45% of patients respond within 810
weeks; cytopenias can develop at certain doses. Other drugs such as lowdose melphalan, interferon-alpha (IFN-), cladribine, and immunomodulatory drugs such as low-dose thalidomide when used in combination
with prednisolone have produced weaker responses, often with myelosuppressive side efects. For treatment of splenomegaly, initially hydroxycarbamide should be used. If the patient sufers from cytopenias, then
thalidomide and prednisolone should be used simultaneously. Medical
therapies are the preferred treatment for splenomegaly; however, the use
of splenectomy is also well established. It should only be carried out in
patients with speciic factors such as hypercatabolic symptoms, splenic
infarction, refractory haemolysis, portal hypertension and symptomatic
splenomegaly, and not before the patient has been assessed for hepatic,
renal, cardiac, metabolic and haemostatic risks. Other risks include
hepatic enlargement due to extramedullary haemopoiesis, and thrombocytosis leading to an elevated thrombotic risk; hence the requirement for
normalisation of platelet counts pre- and post-splenectomy. Cytoreductive
therapy post-surgery includes hydroxycarbamide and cladribine as a palliative option. Patients who are inappropriate for surgery with symptoms
of splenomegaly and a platelet count of more than 50 109/L may gain
some relief and a relative decrease in their spleen size. Reduction in size
is temporary and severe cytopenia can be a side efect requiring platelet
transfusion. Therefore, radiotherapy is not an alternative for patients who
are eligible for surgery.(4)
poikilocytes. Because of ibrosis, a bone marrow aspiration typically

results in a dry tap; trephine biopsies reveal atypical megakaryocytes
which proliferate and show cytoplasmic and nuclear abnormalities
these are seen with collagen ibrosis and/or reticulin.(3,7) Investigations
should include screening for JAK2 V617F mutations. If patients lack
this, a BCR-ABL1 genetic abnormality rearrangement should be sought
if trephine biopsy shows uncharacteristic features and is representative of
chronic myeloid leukaemia.(3) Diagnosis is based on a mixture of clinical
and histopathology indings, using the World Health Organizations 2008
principles.(5,8) Proven PMF is based on meeting all three major criteria and
also two minor criteria from the WHOs primary myeloibrosis diagnostic
principles.(6) The combination of the major and minor criteria helps rule
out other disorders such as ET.(5)
59
A. B. Swali, M. Haj
Blood transfusions are recommended for the treatment of anaemia in

PMF. This is the standard therapy; however, patients must be assessed
individually. Chronic use of blood transfusions may lead to the patient
developing iron overload; fortunately this does not afect patient survival
and there is no indication to use chelation therapy. Erythropoietin (EPO)
is limited to PMF patients with low endogenous EPO levels (below 125
/l). Androgens have various results in anaemic patients. Danazol is the
irst line androgen therapy for PMF patients receiving blood transfusions
for anaemia; it has additional roles in recovering platelet numbers and
spleen size reduction. Side efects include hepatic tumours, deranged liver
function tests (LFTs), increased libido, luid retention and hirsutism. Thus
it is recommended that LFTs are reviewed regularly and liver ultrasound
scans (USS) are carried out every 612 months to exclude hepatic disease
for patients receiving danazol. Prostate cancer screening should also be
carried out on male patients.(4)
Fatigue, weakness, night sweats, bone pain, abdominal pain, weight
loss, pruritus and cachexia represent the main constitutional symptoms
of PMF. Increased pro-inlammatory cytokines and splenomegaly cause
these incapacitating symptoms in advanced stages of the disease and
according to Scherber et al., as cited by Reilly et al.(4) quality of life
for PMF patients is similar to that of patients sufering from metastatic
cancer. There is no evidence of beneit from conventional agents for the
treatment of constitutional symptoms in PMF. Randomised clinical trials
(Harrison et al. in 2012, Verstovsek et al. in 2012) have demonstrated possible beneit of JAK inhibitors on these symptoms.(4)
In order to control thrombocytosis; leukocytosis; and symptoms such as
bone pains, night sweats, fatigue and weight loss which are associated with
hypercatabolism and splenomegaly, myelosuppressive therapy is indicated. First-line medication for hyperproliferation includes hydroxycarbamide. Anagrelide, although linked with an increase in reticulin which is an
important prognostic parameter associated with a worse life expectancy,
can be used with caution with appropriate reviews of MF in patients. In
early stages of the disease IFN- should only be used in patients with proliferative features as it has been shown to slow the disease and even show
regression of the ibrosis.(4,9)
Allogeneic haemopoietic stem cell transplantation (allo-HSCT) has
a potentially curative efect with regression in bone marrow ibrosis.
However the reports have been non-comparative. The toxicity associated
with the standard doses limits its availability to young patients, excluding
the bulk of patients with PMF. Reduced intensity conditioning (RIC) is
now widely available to elderly patients, in whom it broadens the applicability of allo-HSCT, it is based on eradicating neoplastic cells through the
graft-vs-tumour efect.(4,6) Patients are only able to undergo bone marrow
transplantation if they have manageable co-morbidities, have a human
60
JAK2 inhibitors
Present management options for PMF, which include androgens, thalidomide, transfusions and myelosuppressive medications, do not alter
the course of the disease. Discovery of JAK2 mutations in approximately
half of PMF patients has led to new research.(10) JAK inhibitors are one
of a few potential treatments that are being currently examined. They are
concerned with improving the symptoms of PMF and spleen enlargement
and have shown consistent responses. Patients who are not eligible for
bone marrow transplants and have not beneited from hydroxycarbamide treatment should be recommended for JAK inhibitor randomised
controlled trials.(4) Currently they are not available for clinical use, but
JAK inhibitors may be suitable as irst-line treatment for patients with
constitutional symptoms and splenomegaly.(4,10) The JAK2 trials which
have been described show active control of constitutional symptoms and
splenomegaly in patients resistant to hydroxycarbamide and alternative
management options. Unfortunately they were less successful in improving anaemia. JAK2 inhibitors including CYT387, AZD1480, SB1518 and
LY2784544 were not able to encourage any remission of PMF or eliminate
the mutated JAK2 clone. Responses were not dependent on the JAK2
mutational status, meaning that it was not clear whether their beneits
were due to inhibition of JAK2 in neoplastic cells or from a global downregulation of the proinlammatory cytokinase signalling.(6)
Ruxolitinib is a powerful JAK1 and JAK2 inhibitor that is approved for
the management of high-risk and intermediate myeloibrosis.(11) It selectively inhibits JAK2 V617F-driven Ba/F3 cell proliferation. This results
in reduced activation of STAT factors by reduced phosphorylation of
JAK2. In 2012, Harrison et al.(12) evaluated the eicacy of ruxolitinib when
compared with the best available therapy, which included commercially
available monotherapies or combination therapies such as antineoplastic
agents (hydroxyurea) and glucocorticoids. Using MRI or CT they found
that 28% of the patients on ruxolitinib had a 35% spleen volume reduction,
leukocyte antigen (HLA)-matched donor, and are well enough for the procedure. Patients who should be considered for myeloablative (MA) alloHSCT include those under the age of 45 with an international prognostic
scoring system (IPSS) of intermediate 2 or higher, and who are having
blood transfusions and/or have adverse cytogenetic irregularities. Similar
patients over the age of 45 should be considered for RIC allo-HSCT.
Bone marrow transplantation should take place before the patient has had
20units of blood transfusions. Plasma levels are used to estimate dosing of
oral busulfan; IV busulfan can be given provided dosage is estimated using
plasma levels. Increased risk of relapse may be seen in patients who have
undergone splenectomies prior to transplant.(4)
61
A. B. Swali, M. Haj
compared with 0% in patients on the best available therapy. By just

under a year, the mean palpable spleen length had decreased by 56% in the
ruxolitinib patients but with the best available therapy it had increased
by 4%. Patients taking ruxolitinib also had improved symptoms and
quality-of-life scores. However, side efects included thrombocytopenia
and anaemia; these were treated by postponing treatment, dose reduction
or blood transfusion. Studies so far have shown that continuous therapy
with ruxolitinib can improve quality of life, reduce splenomegaly and
PMF symptoms, and improve overall survival; however it does not reduce
the rate of transformation to leukaemia and is not curative.(5,11,12)
Future treatments
Other than allo-HSCT, management is palliative.(12) However there are
possible future treatments being investigated to improve the quality of
management for patients with PMF. Improved eicacy against JAK2
V617F can be achieved by either reducing the JAK2 V617F allelic burden,
or by inactivating the components of the signal transduction paths. Four
types of treatment are being investigated; these include PIM kinase inhibitors, MEK inhibitors, histone deacetylase inhibitors (HDACis)/heatshock protein 90 (Hsp90) inhibitors and PI3K/mTOR inhibitors.(5)
PMF patients have increased histone deacetylase (HDAC) expression.
The acetylation status of histones and other proteins is modulated by
HDACis; this has efects such as cell-cycle and growth arrest, and inhibition of angiogenesis, cellular diferentiation, apoptosis and immune surveillance. Consistent use of panobinostat, a pan-HDACi, has been shown
in some cases to eliminate leukoerythroblastic blood features, resolve
splenomegaly, improve anaemia, reduce symptoms, and feature regression
of bone marrow ibrosis. Future studies will evaluate panobinostat and
ruxolitinib used simultaneously to treat MF patients.(5)
STAT and JAK2 are client proteins (also referred to as substrate proteins) for Hsp90, an ATP-dependent, dimeric molecular chaperone. Hsp90
stabilises these and folds them into their active coniguration. Hsp90
inhibitors bind to the N-terminal ATP-binding domain of Hsp90 and
inhibit this, resulting in proteasome-mediated degradation of the client
protein in myeloproliferative neoplasm (MPN) cells.(6)
PI3K/mTOR is involved in signalling for the cell proliferation and
growth pathway involved in malignancies, including MF. DEZ235 is a dual
PI3K/mTOR inhibitor that can cause MPN cells to undergo apoptosis.(5)
Prognosis
Treatment of PMF such as allogeneic stem-cell transplantation (allo-SCT)
depends on the patients prognosis. The IPSS is based on age, leukocyte
62
Discussion
count, circulating blasts, Hb concentration and constitutional symptoms;

it is used to classify patients with PMF into diferent risk groups. It has
been modiied recently to the dynamic IPSS (DIPSS) so that it can be used
at any time during the course of the disease, and also the DIPSS plus, with
the additional parameters of transfusion dependence, platelet count and
unfavourable karyotype. It is recommended that the DIPSS plus be used
when contemplating the use of allo-SCT.(4)
PMF has the worst prognosis of the MPNs; patients are classiied into
diferent risk groups which determine their survival. The median survival
from diagnosis is approximately six years, with mortality occurring secondary to cardiovascular disease.(1,6)
When PMF transforms to leukaemia, most patients survive for less than
a year, with many dying within six months. Curative allo-SCT is the only
treatment that could lead to the long-term remission of chronic leukaemia,
but it is diicult to achieve.(4)
The patient studied is signiicant for a number of reasons. She had been
managed conservatively for a number of years without the need for PMF medication. Her anaemia was controlled on folic acid and iron tablets for 12 years
before any further deterioration, perhaps because she was diagnosed before
such guidelines were recommended. In 2010 she was given blood transfusions
when her anaemia became signiicant. She sufered from chronic thrombocytopenia and was eventually started on tranexamic acid and prednisolone.
Later in the disease the patients symptoms included massive splenomegaly but she did not receive any treatment such as hydroxycarbamide; this
was probably owing to her signiicant thrombocytopenia. Additionally,
the patients advanced age meant that she would not have been eligible for
allo-SCT therapy. This is unfortunate as it is still the only management
available with the potential to cure as long as there is no signiicant risk of
mortality or morbidity. In the future as treatments are reined and dosage
reduced, new transplant methods will simultaneously use JAK2 inhibition; this will allow PMF patients of increased age to become eligible for
this type of management.(5)
In 2012 the patient was referred for a ruxolitinib trial. The patient was
regrettably denied, as two of the major side efects were anaemia and
thrombocytopenia. This was unfortunate, as some of the recent reports
concerning ruxolitinib have stated that they were able to manage the issues
of anaemia and thrombocytopenia by briely interrupting the therapy,
reducing the doses, or simply discontinuing the treatment. Patients treated
with ruxolitinib were able to continue with blood transfusions if needed.(12)
Recent studies have led to the development of newer, highly speciic JAK
inhibitors, which reduce undesirable efects such as cytopenia.(13)
63
A. B. Swali, M. Haj
The use of azacitidine in transformed MPN has shown promising

results. In over half the cases reported there was a response resulting in
a median survival of eight months. This may be a possible treatment for
patients who have transformed PMF.(4)
Conclusion
In recent years, breakthroughs in the discovery of PMF molecular
mechanisms and pathogenesis have led to improved treatments and the
ongoing development of efective managements for the whole spectrum
of PMF patients.(5)
There is likely to be a role for JAK2 inhibitors in the management of
palliative care in patients with PMF regarding constitutional symptoms
and splenomegaly.(6)
PMF is a diicult myeloid malignancy to manage efectively; elderly
patients and co-morbid conditions limit the treatment options.
Ruxolitinib is now available for use in clinical practice; its future applications may alter this treatment pattern and greatly improve the quality
of life for those living with PMF.(5)
References
1 Polednak AP. Recent decline in the US death rate from
myeloproliferative neoplasms 19992006. Cancer Epidemiol [Internet].
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2 Hofbrand AV, Moss PAH, Pettit JE. Acute lymphoblastic leukaemia.
In: Hofbrand AV, editor. Essential haematology. 5th ed. Malden, MA:
Blackwell; 2006. p. 2309.
3 Hatton CSR, Hughes-Jones NC, Hay D, Keeling D. Bone marrow
transplantation. In: Ramasamy K, Mead A, Gatter K, editors. Haematology
lecture notes. 9th ed. Chichester: John Wiley & Sons; 2013. p. 1012.
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A, et al. Guideline for the diagnosis and management of myeloibrosis.
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Hofman R. Advances in myeloibrosis: a clinical case approach.
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myeloproliferative neoplasms: the 2008 World Health Organization
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Ivnyi JL, Mahunka M, Papp A, Kiss A, Telek B. Prognostic signiicance
of bone marrow reticulin ibres in idiopathic myeloibrosis: evaluation
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(Budap). 1994 Feb;26(2):7586.
Bacigalupo A, Soraru M, Dominietto A, Pozzi S, Geroldi S, Van Lint
MT, et al. Allogeneic hemopoietic SCT for patients with primary
myeloibrosis: a predictive transplant score based on transfusion
requirement, spleen size and donor type. Bone Marrow Transplant
[Internet]. 2010 [cited 2014 Feb 14]; 45(3):45863. Available from: http://
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65
66
ABSTRACT
Post-surgical complication rates of

elective excisionof pilonidal sinus
disease and the need of
post-operative appointments
Presentations from the 7th Scalpel Undergraduate
Surgical Conference, 24 October 2015
A. Begaj
ardit.begaj@student.manchester.ac.uk
Background Pilonidal sinus disease is a common disease of the natal cleft

with an incidence of 25/100,000 people in the UK. Males are most commonly
affected, compared to the females. It was reported to be caused from
ingrowing hair, leading to formation of an abscess and sinuses underneath
the skin. These sinuses discharge their contents in the skin surface by the aid
of skin pits. Surgery is the treatment of choice for chronic pilonidal disease;
however, literature has revealed high rates of postsurgical complications.
As a consequence, follow-up appointments are needed to monitor these
complications.
Aim To determine if a six-week post-surgery appointment is necessary and
beneicial for the patient.
Methods All the data from the patients that underwent elective excision
of pilonidal sinus by Mr Goscimski from 1 January 2012 to 30 November
2014 were screened to determine the attendance rate, complication rate and
healing time.
Results Out of 46 patients, 37 underwent excision and primary closure with
Karydakis lap, 6 patients underwent excision with Limberg lap and three
wounds were left open. Most complications (9/11 patients) were noticed
and treated by the colorectal nurse, and only 1 out of 11 was treated by the
surgeon during routine follow-up.
67
A. Begaj
Recommendations and conclusion A six-week follow-up with the surgeon

is not necessary, due to the low complication rate at that period; however a
two-week follow-up with the colorectal nurse has shown to be beneicial. The
outcomes of Mr Goscimskis practice in elective excision of pilonidal disease
have shown to be comparable to the literature, and therefore a safe practice.
68
ABSTRACT
Use of augmented reality in surgery

R. Gunaratnarajah, P. Vanalia
rathu@hotmail.co.uk
As technology improves, we are increasingly incorporating it into our daily

lives. This review aims to investigate the advantages and disadvantages of this
growing reliance on technology in the medical ield.
This paper will focus exclusively on augmented reality and how it can be
used innovatively to improve patient care and outcome in ophthalmology.
Performing ocular surgery is a very delicate process, and technology such
as Google Glass, Oculus Rift and Microsoft Hololens could open up so
opportunities in simplifying not only the surgeries themselves, but also
ophthalmic training. Surgeons around the world have trialled some of these
technologies in their operating theatres. This paper discusses whether
inclusion of these technologies in an ophthalmic setting offers any advantages.
We also investigate the learning curve associated with use, any potential risks
to the user and cost-effectiveness of these technologies.
69
70
ABSTRACT
Intraoperative glycaemic control

D. Horth
dillon.horth@student.manchester.ac.uk
Although there is strong evidence that supports the appropriate control of

intraoperative glycaemic levels, there is little literature we are aware of that
assesses how well perioperative physicians manage it.
This project describes an audit of intraoperative glycaemic control at Victoria
General Hospital in Victoria, British Columbia, Canada. There were 51surgical
patients included in the audit that took place over 19 days. The results showed
that 25.5% of patients included in the audit had a blood glucose level outside
the ideal range. Due to the association between poor glycaemic control and
increased morbidity and mortality, we found this percentage left considerable
room for improvement.
We make several recommendations, including the introduction of an
evidence-based protocol that guides anaesthetists when to measure and, if
clinically indicated, correct intraoperative glycaemic levels.
71
72
ABSTRACT
A 3D in vitro co-culture to model

peripheral nerve remyelination
after injury
B. Kadler
benjamin.kadler@student.manchester.ac.uk
Peripheral nerve injury is common, results in signiicant disability for patients

and imposes a heavy inancial burden on healthcare services. Recent research
identifying novel strategies to improve nerve regeneration is hindered by the
lack of a standardised model. This work soughttodevelop a versatile in vitro
construct to model remyelination after nerve injury.
Novel macroporous poly(-lysine) scaffolds with additional chemical groups
were characterised in a 3D Schwann cell culture model. Immunohistochemistry,
proliferation assays, LIVE/DEAD staining and scanning electron microscopy
(SEM) modalities were utilised in order to select the most promising scaffold.
A scaffold functionalised with IKVAV peptide was then used as a basis for
co-culture experiments utilising rat Schwann cells or adipose-derived stem
cells (ASCs) and neurons. Myelin formation was identiied on SEM and gene
expression quantiied using included real-time PCR.
We demonstrated that cultured Schwann cells and neurons maintain their
phenotype and morphology in this novel 3D scaffold. Compared to amine
scaffold variants, the IKVAV scaffold encouraged 2 times more cell viability
( p< 0.05 and 0.01) and 2.6 times higher proliferation ( p < 0.05). Schwann cells
and differentiated ASCs were seen to arrange linearly along neurites. Gene
expression of myelin basic protein, peripheral myelin protein and protein zero
were all upregulated in Schwann cell groups. Differentiated ASCs produced
more myelin-based gene expression than undifferentiated ASCs.
This study demonstrates that IKVAV poly(epsilon-lysine) is a promising
construct to model remyelination.
Furthermore, this high-throughput tool could be utilised for the study of
potential therapies for nerve injury.
73
74
ABSTRACT
Bunions, feet and battling nerve

damage: is thesentinel vein
a reliable landmark to locate
thedorsomedial cutaneous nerve
of the hallux?
J. Lindsay
jennifer.lindsay@student.manchester.ac.uk
Background Hallux valgus is a common condition in which the phalanges
of the hallux deviate laterally and the irst metatarsal deviates medially.
The deformity is attributed to the long-term wear of tightly itting footwear;
however, a genetic predisposition may contribute to developing the condition.
Surgical treatment of hallux valgus includes an osteotomy and rebalancing
of the soft tissues. The sensory branch of the dorsomedial cutaneous nerve
(DMCN) lies close to the surgical incision site and is at risk of iatrogenic
damage. Sensory nerve damage following the procedure has been reported in
up to 45% of patients.
Objectives A previous study described a transverse vessel, named the
sentinel vein, located immediately supericial to the DMCN. It was therefore
suggested that the sentinel vein could act as a landmark for the DMCN. The
objective of the current study was to recreate the work from this previous study
as far as possible, and determine if the sentinel vein is a reliable landmark for
the DMCN.
Methods Cadaveric specimens were carefully dissected to observe both the
appearance and position of the sentinel vein. Non-dimensional measurements
were then taken to report the anatomical location of the vein.
Results A preserved sentinel vein was observed in 18 out of 31 specimens.
In all cases the DMCN was found to either lie immediately deep to the overlying
75
J. Lindsay
sentinel vein or just distal at the point where the vein joined the plantar venous
network. Subjectively, the appearance and position of the vein was seen to
vary greatly between different specimens. Non-dimensional measurements
placed the sentinel vein at a mean of 30.17% of the total metatarsal
length. However intra- and inter-observer repeatability analysis of the results
suggested that the measurements may not be reliable in accurately describing
the location of the vein.
Conclusion The variation in appearance of the sentinel vein between the
specimens, along with the inability to reliably measure the position of the
vein, indicates that the sentinel vein may not be a reliable landmark for the
dorsomedial cutaneous nerve, and therefore the use of this structure as an
anatomical landmark should be cautioned.
76
ABSTRACT
Cosmetic surgery: a curse or a

blessing?
A. P. Salahi
amir.salahi@student.manchester.ac.uk
Aesthetic plastic surgery has always been a topic of controversy, but over
recent years public attitudes appear to be shifting in favour of cosmetic
surgery. Glamorisation by the media and advertising can account for this,
and have a predominant effect on how people view their body image.
With breast augmentation using prostheses being a highly sought-after
procedure, this report aims to delineate the preoperative and postoperative
psychology behind breast augmentation. Large numbers of studies have
reported high satisfaction rates in the short term; many women feel more
empowered, conident, and have a stronger positive body image evaluation.
Cosmetic surgery can thus be considered a blessing from this viewpoint.
However, the postoperative complications that may result can hinder these
positive psychological outcomes. Capsular contracture is the most common
complication, and can result in severe breast deformities. Patients living with
psychiatric conditions, including body dysmorphic disorder and personality
disorders, could psychologically be more vulnerable and affected by these
negative treatment results. In this sense, cosmetic surgery is a curse. Therefore,
psychotherapy (such as cognitive behavioural therapy) or pharmacotherapy
(such as selective serotonin reuptake inhibitors) would be a more appropriate
line of treatment for these patients.
77
78
ABSTRACT
Indications for dual-mobility hip

replacements
J. Rossiter1, A. T. Helm2
1

jennifer.rossiter@student.manchester.ac.uk
2
Lancashire Teaching Hospitals NHS Foundation Trust
This project was aiming to look at the indications for dual-mobility hip
replacements. Dual-mobility hip replacements are a type of total hip
replacement which aim to increase stability compared to standard total hip
replacement due to the large head size, increased range of motion, and, at
least theoretically, reduce wear due to lower frictional torque. Lancashire
Teaching Hospitals Trust began using dual-mobility hip replacements in 2013,
and this retrospective analysis looks at each of the 174 patients who received
one since then to discover why they were put in and how this relates to the
NICE guidelines for treating certain types of hip problems.
The results have shown that 102 were primary hip replacements for
displaced intracapsular fracture of the femur, 31 were revisions for instability
and 41 were for other indications, both primary and revision. Of the 174 dualmobility cups put in, 3 have dislocated, but all were reduced successfully
and have remained stable since. This gives the dual-mobility cups a current
revision rate of 0%, which is very successful in comparison to the average
revision rate for a standard (non-dual-mobility) total hip replacement.
79
80
ABSTRACT
Local excision of early rectal

cancers by transanal endoscopic
microsurgery (TEM)
H. L. Wu
hon.wu-2@student.manchester.ac.uk
Background Local excision of rectal cancers by Endoscopic Microsurgery

(TEM) has become accepted as a valid treatment modality for T1 rectal
carcinomas. Its singular use in carcinomas of stage T2 and above remains
controversial due to higher rates of local recurrence. The purpose of this
work was to evaluate the eficacy of TEM combined with radiotherapy as an
alternative to radical rectal resection in T2 rectal carcinomas.
Methods The records of twelve patients who underwent TEM for T2 rectal
carcinoma at the Royal Preston Hospital were reviewed. Their treatments and
outcomes were recorded.
Results Out of the twelve patients, six received radiotherapy and six did not
because they either elected for subsequent radical surgery (three patients)
or were unit for further treatment and underwent follow-up (three patients).
Median follow-up was 20 months. In the no-radiotherapy group, one patient
who underwent subsequent radical surgery had involved mesorectal lymph
nodes, and one patient undergoing follow-up without radical surgery developed
mesorectal nodal recurrence. In the radiotherapy group, all six patients underwent
follow-up with no recurrences to date. There was no 90-day surgical mortality.
Conclusion Whilst the numbers in the study were not suficient for valid
statistical comparison, the lack of tumour recurrences in the group receiving
radiotherapy does support the use of TEM with radiotherapy as a promising
alternative treatment modality for stage T2 rectal carcinoma, particularly
in patients who are at high risk for radical surgery, have a near complete
response to pre-op radiotherapy or are keen to avoid a permanent stoma.
81
82
ABSTRACT
The use of routine CT imaging

to assess sarcopeniain patients
undergoing chemo-radiotherapy for
rectal cancer
S. Young
sean.young@student.manchester.ac.uk
Background Long-course chemoradiotherapy (LCRT) followed by surgery

is utilised in patients with locally advanced rectal cancer, but associated with
reductions in physical activity, the effects of which are poorly characterised,
and increase postoperative complication rates and delay recovery. In previous
studies muscle area has been used to measure muscularity; this is the irst
study measuring muscle volume in addition to area.
Objectives We aimed to determine differences in muscularity between
demographic groups prior to LCRT, assess how LCRT affects muscularity and
determine if the technique to measure volume is replicable.
Methods Using routine CT images, muscle was differentiated using density
measurements, with volume and area calculated by Osirix. Volume was
measured 120 mm above the L5S1 intervertebral disc, and area at the L3
level. Intra- and inter-observer variability was assessed using six patients, with
two patients from each tertile.
Results 38 patients were assessed. Demographic factors affected
muscularity (area, volume) prior to therapy, including N stage ( p = 0.019,
p= 0.011), gender ( p = 0.0001, p = 0.0001) and age ( p = 0.002, p = 0.0001).
Assessment of pre- and post- LCRT scans showed treatment has no effect on
muscularity. The technique employed is replicable (concordance correlation
coeficient 0.98<).
83
S. Young
Conclusions There are signiicant differences in muscularity between

demographic groups prior to therapy, although LCRT was shown to have
no effect on muscularity. We also conirmed that the technique employed is
replicable and could be used to assess how muscularity impacts on surgical
outcomes.
84
85
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Foreword by Professor Tony Freemont

If it is statistically significant does it

Treatment options for patients with

Manchester Medical Journal, 2016 The Authors 2016

Manchester Medical Journal (2016)

Inspirational doctors, back pain

Gene discovery for rare diseases

Within Europe, a disease is classiied as rare if it afects fewer than 1 in

of techniques, including chromosome mapping, Sanger sequencing and

oped. In the meantime, clinicians need to be made aware of the collective

1 Kaplan W, Wirtz VJ, Mantel-Teeuwisse A, Stolk P, Duthey B, Laing

Gene discovery for rare diseases

Critical appraisal skills, tomorrows

Manchester Medical Journal founder and Associate Editor; Academic Foundation

J. Burke, S. Khan, A. Mitchell

critical-appraisal guidance and relect on feedback of their critiques from

J. Burke, S. Khan, A. Mitchell

If it is statistically signiicant does

encompass clinical signiicance in the narrow sense described above, along

Study design and conduct

open-access journals have become more successful recently, there is still

Statistical signiicance/clinical importance

of or adherence to the intervention, which can be inluenced by a number

America published in the ive leading medical journals. PloS ONE

Statistical signiicance/clinical importance

the implementation of lifestyle risk factor management in primary

Transition at Emerge: evaluating

Aims of the study

Transition at Emerge: evaluating practice

information about whether they had transferred to adult services was

Table 1: Ethnicity vs gender of cases in the study sample.

BME: black and minority ethnic.

CNA = could not attend; DNA = did not attend.

Table 3: Frequency of recorded referrer and ethnicity.

Black and minority

Reason case closed

Transition at Emerge: evaluating practice

general population. Mental health problems in children and young people

Transition at Emerge: evaluating practice

or liaison oicers seems unrealistic, given the stretched resources within

2 Singh SP, Paul M, Ford T, Kramer T, Weaver T, McLaren S, et al.

Readmissions at Royal Oldham

Readmissions at Royal Oldham Hospital AMU

Table 1: Red lag warnings for patients at high risk of readmission.

group.(7) Based on the 200910 readmissions data, the potential annual

The following variables were selected for further analysis:

Results and analysis

Readmissions at Royal Oldham Hospital AMU

Previous hospital admissions

Table 3: The distribution of patients according their residential inhabitancy.

Table 4: The distribution of patients by admission method.

Method of index admission

Readmissions at Royal Oldham Hospital AMU

Readmied paents for whom readmission may have

Body system aected by co-morbid condion

Figure 1: The percentage of patients with a co-morbid condition according to the

Latency between discharge and readmission

Figure 2: The percentage of readmitted patients with speciic co-morbid conditions.

Readmissions at Royal Oldham Hospital AMU

Figure 3: The distribution of readmitted patients according to the time between

related to their co-morbidities. Where readmissions were deemed likely to

The possibility that readmissions result from hospital-acquired infection

Readmissions at Royal Oldham Hospital AMU