Table Of ContentDownloaded for Anonymous User (n/a) at Rutgers University - NERL from ClinicalKey.com by Elsevier on March 19, 2019.
For personal use only. No other uses without permission. Copyright ©2019. Elsevier Inc. All rights reserved.
A Companion to Specialist Surgical Practice
Series Editors
O. James Garden
Simon Paterson-Brown
CORE TOPICS IN GENERAL
AND EMERGENCY SURGERY
SIXTH EDITION
Edited by
Simon Paterson-Brown
MBBS MPhil MS FRCS(Ed) FRCS(Engl) FCS(HK) FFST(RCSEd)
Honorary Clinical Senior Lecturer, Clinical Surgery,
The University of Edinburgh; Consultant General and
Upper Gastrointestinal Surgeon, Royal Infirmary of Edinburgh,
Edinburgh, UK
Hugh M. Paterson
BMedSci MBChB MD FRCS(Ed)
Clinical Senior Lecturer Coloproctology,
The University of Edinburgh; Honorary Consultant
Colorectal Surgeon, Western General Hospital, Edinburgh, UK
For additional online content visit ExpertConsult.com
Edinburgh London New York Oxford Philadelphia St Louis Sydney 2019
Downloaded for Anonymous User (n/a) at Rutgers University - NERL from ClinicalKey.com by Elsevier on March 19, 2019.
For personal use only. No other uses without permission. Copyright ©2019. Elsevier Inc. All rights reserved.
© 2019, Elsevier Limited. All rights reserved.
First edition 1997
Second edition 2001
Third edition 2005
Fourth edition 2009
Fifth edition 2014
Sixth edition 2019
No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical,
including photocopying, recording, or any information storage and retrieval system, without permission in writing from
the publisher. Details on how to seek permission, further information about the Publisher’s permissions policies and our
arrangements with organizations such as the Copyright Clearance Center and the Copyright Licensing Agency, can be
found at our website: www.elsevier.com/permissions.
This book and the individual contributions contained in it are protected under copyright by the Publisher (other than as
may be noted herein).
Notice
Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any
information, methods, compounds or experiments described herein. Because of rapid advances in the medical sciences,
in particular, independent verification of diagnoses and drug dosages should be made. To the fullest extent of the law,
no responsibility is assumed by Elsevier, authors, editors or contributors for any injury and/or damage to persons
or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods,
products, instructions, or ideas contained in the material herein.
ISBN: 978-0-7020-7247-5
Printed in China
Last digit is the print number: 9 8 7 6 5 4 3 2 1
Content Strategist: Laurence Hunter
Content Development Specialist: Lynn Watt
Project Manager: Umarani Natarajan
Design: Miles Hitchen
Illustration Manager: Nichole Beard
Illustrator: MPS North America LLC
Downloaded for Anonymous User (n/a) at Rutgers University - NERL from ClinicalKey.com by Elsevier on March 19, 2019.
For personal use only. No other uses without permission. Copyright ©2019. Elsevier Inc. All rights reserved.
Series Editors’ preface
The Companion to Specialist Surgical Practice series We have recognised in this Sixth Edition that
has now come of age. This Sixth Edition takes the new blood is required to maintain the vitality of
series to a different level since it was first published content. We are indebted to the volume editors, and
in 1997. The intention from the outset was to ensure contributors, who have stood down since the last
that we could support the educational needs of those edition and welcome the new leadership on several
in the later years of specialist surgical training and volumes. The contents have been comprehensively
of consultant surgeons in independent practice who updated by our contributors and editorial team. We
wished for contemporary, evidence-based information remain grateful for the support and encouragement
on the subspecialist areas relevant to their general of Laurence Hunter and Lynn Watt at Elsevier.
surgical practice. Although there still seems to be a We trust that our original vision of delivering
role for larger reference surgical textbooks, and having an up-to-date affordable text has been met and
contributed to many of these, we appreciate that it is that readers, whether in training or independent
difficult for them to keep pace with changing surgical practice, will find this Sixth Edition an invaluable
practice. resource.
This Sixth Edition continues to keep abreast of the
increasing specialisation in general surgery. The rise
O. James Garden, CBE, BSc, MBChB, MD, FRCS
of minimal access surgery and therapy, and the desire
(Glas), FRCS(Ed), FRCP(Ed), FRACS(Hon), FRCSC
of some subspecialities, such as breast and vascular
(Hon), FACS(Hon), FCSHK(Hon), FRCSI(Hon),
surgery, to separate away from 'general surgery' may
FRCS(Engl)(Hon), FRSE
have proved challenging in some countries. However,
Regius Professor of Clinical Surgery, Clinical
they also underline the importance for all surgeons of
Surgery, The University of Edinburgh and Honorary
being aware of current developments in their surgical
Consultant Surgeon, Royal Infirmary of Edinburgh,
field. This series as a consequence continues to place
Edinburgh, UK
emphasis on the need for surgeons to deliver a high-
quality emergency surgical practice. The importance
of evidence-based practice remains throughout, Simon Paterson-Brown, MBBS, MPhil, MS,
and authors have provided recommendations and FRCS(Ed), FRCS(Engl), FCSHK, FFST(RCSEd)
highlighted key resources within each chapter. The Honorary Clinical Senior Lecturer, Clinical Surgery,
ebook version of the textbook has also enabled The University of Edinburgh and Consultant
improved access to the reference abstracts and links General and Upper Gastrointestinal Surgeon, Royal
to video content relevant to many of the chapters. Infirmary of Edinburgh, Edinburgh, UK
v
Downloaded for Anonymous User (n/a) at Rutgers University - NERL from ClinicalKey.com by Elsevier on March 19, 2019.
For personal use only. No other uses without permission. Copyright ©2019. Elsevier Inc. All rights reserved.
Editors’ preface
While surgical subspecialisation within the speciality ‘specialist’. In such cases the reader will be referred
of ‘General Surgery’ remains central to the delivery to the relevant specialist volume of this series.
of overall general surgical care, there is an increasing
realisation that the core topics of general surgery,
including emergency surgery, are a fundamental
Acknowledgements
part of this practice. This requires the general
surgeon to see and treat undifferentiated referrals
We are both grateful to our long-suffering wives
and conditions outwith their normal everyday
and families for their ongoing support and
elective and emergency ‘specialist’ practice.
understanding in the time taken for us to complete
This volume of the Sixth Edition of the Companion
the Sixth Edition of this volume of Core Topics in
to Specialist Surgical Practice series provides the
General and Emergency Surgery for the Companion
background information on these key areas of
to Specialist Surgical Practice series. The success of
general surgery for all practising general surgeons
this volume, as for previous editions, very much
in both the elective and emergency situation. It
lies in the quality of the chapters written by our co-
has been divided into two main sections: the first
authors and we are extremely grateful to all of them
includes the core topics relevant to all general
for the hard work that has gone into writing, or
surgeons and the second, those related to the care
re-writing, each chapter. The additional workload
of emergency patients. As with previous editions
required in the timely delivery of concise, well-
of the Companion series, this volume should be
referenced and up-to-date chapters for a book such
considered as complementary to the other more
as this, by busy practising surgeons, should never be
specialist volumes, while still encompassing all
underestimated. We would also like to recognise the
those emergency areas that remain within the remit
help and support of Elsevier, and particularly Lynn
of the general surgeon.
Watt, in the production of this volume.
In everyday practice there remains a group of
We would also would like to acknowledge and
emergency patients who, having been resuscitated
offer grateful thanks for the input of all previous
and a diagnosis reached, might be better served
editions’ contributors, without whom this new
by referral to a colleague or unit with the relevant
edition would not have been possible.
subspecialist interest. This volume discusses those
conditions that the general surgeon might be Simon Paterson-Brown
expected to deal with and, where appropriate, Hugh M. Paterson
identifies those that might be better managed by a Edinburgh
vii
Downloaded for Anonymous User (n/a) at Rutgers University - NERL from ClinicalKey.com by Elsevier on March 19, 2019.
For personal use only. No other uses without permission. Copyright ©2019. Elsevier Inc. All rights reserved.
Evidence-based practice in surgery
Critical appraisal for developing evidence-based preferences, local facilities, local audit results or
practice can be obtained from a number of sources, available resources.
the most reliable being randomised controlled c. A recommendation made where there is no
clinical trials, systematic literature reviews, meta-
adequate evidence as to the most effective
analyses and observational studies. For practical
practice, although there may be reasons for
purposes three grades of evidence can be used,
making a recommendation in order to minimise
analogous to the levels of ‘proof’ required in a court
of law: cost or reduce the chance of error through a
locally agreed protocol.
1. Beyond all reasonable doubt. Such evidence
is likely to have arisen from high-quality
randomised controlled trials, systematic reviews Evidence where a conclusion can be reached
or high-quality synthesised evidence such as ‘beyond all reasonable doubt’ and therefore
decision analysis, cost-effectiveness analysis or where a strong recommendation can be given.
This will normally be based on evidence levels:
large observational datasets. The studies need
• Ia. Meta-analysis of randomised controlled trials
to be directly applicable to the population of
• Ib. Evidence from at least one randomised
concern and have clear results. The grade is controlled trial
analogous to burden of proof within a criminal • IIa. Evidence from at least one controlled study
court and may be thought of as corresponding without randomisation
• IIb. Evidence from at least one other type of quasi-
to the usual standard of ‘proof’ within the
experimental study.
medical literature (i.e. P <0.05).
2. On the balance of probabilities. In many cases
a high-quality review of literature may fail to
Evidence where a conclusion might be reached
reach firm conclusions due to conflicting or
‘on the balance of probabilities’ and where there
inconclusive results, trials of poor methodological
may be other factors involved which influence the
quality or the lack of evidence in the population recommendation given. This will normally be based
to which the guidelines apply. In such cases on less conclusive evidence than that represented
it may still be possible to make a statement by the double tick icons:
• III. Evidence from non-experimental descriptive
as to the best treatment on the ‘balance of
studies, such as comparative studies and case–
probabilities’. This is analogous to the decision in
control studies
a civil court where all the available evidence will • IV. Evidence from expert committee reports or
be weighed up and the verdict will depend upon opinions or clinical experience of respected
the balance of probabilities. authorities, or both.
3. Not proven. Insufficient evidence upon which to
base a decision, or contradictory evidence. Evidence that is associated with either a strong
recommendation or expert opinion is highlighted in
Depending on the information available, three
the text in panels such as those shown above, and is
grades of recommendation can be used:
distinguished by either a double or single tick icon,
a. Strong recommendation, which should be respectively. The references associated with double-
followed unless there are compelling reasons to tick evidence are listed as Key References at the
end of each chapter, along with a short summary of
act otherwise.
the paper's conclusions where applicable. The full
b. A recommendation based on evidence of
reference list for each chapter is available in the ebook.
effectiveness, but where there may be other
The reader is referred to Chapter 1, ‘Evaluation
factors to take into account in decision- of surgical evidence’ in the volume Core Topics in
making, for example the user of the guidelines General and Emergency Surgery of this series, for a
may be expected to take into account patient more detailed description of this topic.
ix
Downloaded for Anonymous User (n/a) at Rutgers University - NERL from ClinicalKey.com by Elsevier on March 19, 2019.
For personal use only. No other uses without permission. Copyright ©2019. Elsevier Inc. All rights reserved.
Contributors
Iain D. Anderson, MBE, MD, FRCS(Eng, Edin, Timothy Forgan, BSc(Hons), MBBCh, MMed(Surg),
Glas), FRACS(Hon) FCS(SA), Cert Gastroenterology(SA)Surg
Consultant Surgeon, Intestinal Failure Unit, Salford Consultant Colorectal Surgeon, Tygerberg Academic
Royal NHS Foundation Trust, Salford, UK Hospital; Senior Lecturer, Surgery, Stellenbosch
University, Cape Town, Republic of South Africa
Robert Baigrie, BSc, MBChB, FRCS, MD
Adjunct Professor, Surgery, The University of Cape Sarah A. Goodbrand, MBChB, BMSc, MD,
Town and Groote Schuur Hospital, Cape Town, FRCS
Republic of South Africa Colorectal Department, Western General Hospital,
Edinburgh, UK
Ian Bailey, MBChB, MS, FRCS(GS)
Consultant Surgeon, Acute General Surgery, Ewen M. Harrison, MBChB, PhD, FRCS
University Hospital Southampton, Southampton, UK Consultant HPB Surgeon, Clinical Surgery,
Royal Infirmary of Edinburgh; Senior Lecturer,
Andrew C. de Beaux, FRCSEd, MD, MBChB Clinical Surgery, The University of Edinburgh,
Consultant General and Upper GI Surgeon, Edinburgh, UK
Department of General Surgery, Royal Infirmary of
Edinburgh; Honorary Senior Lecturer, The University
Steven D. Heys, BMedBiol, MBChB, MD, PhD,
of Edinburgh, Edinburgh, UK
FRCS(Eng), FRCS(Ed), FRCS(Glas), FHEA
Dean of the School of Medicine, Medical
Maurizio Cecconi, MD, FRCA
Sciences and Nutrition, University of Aberdeen;
Reader, Intensive Care Medicine, General Intensive
Honorary Consultant Surgeon, NHS Grampian,
Care Unit, St George’s University Hopsitals NHS
Aberdeen, UK
Foundation Trust, London, UK
Scott R. Kelley, MD, FACS, FASCRS
Saxon Connor, MBChB, FRACS
Assistant Professor of Surgery, Colon and Rectal
Consultant HPB Surgeon, Department of Surgery,
Surgery, Mayo Clinic, Rochester, MN, USA
Christchurch Hospital, Christchurch, New Zealand
Jacob C. Langer, MD
Dafydd A. Davies, MD, MPhil, FRCSC
Professor of Surgery, University of Toronto, Attending
Division Head, Division of Paediatric General and
Surgeon, Paediatric General and Thoracic Surgery,
Thoracic Surgery, Trauma Program Medical Director,
The Hospital for Sick Children, Toronto, Ontario,
IWK Health Centre; Paediatric Trauma Director,
Canada
Nova Scotia Trauma Program; Assistant Professor,
Dalhousie University, Nova Scotia, Canada
David W. Larson, MD, MBA
Chair, Colon and Rectal Surgery; Professor of
Chris Deans, MBChB(Hons), FRCS, MD
Surgery; Mayo Clinic, Rochester, MN, USA
Part-time Senior Lecturer, Clinical Surgery School
of Clinical Sciences, The University of Edinburgh;
Kristoffer Lassen, MD, PhD
Consultant General and Upper Gastrointestinal
Consultant Surgeon/Professor, Department of
Surgeon, Royal Infirmary of Edinburgh, Edinburgh, UK
Gastrointestinal Surgery/HPB-Section, Oslo
University Hospital at Rikshospitalet, Oslo
Thomas M. Drake, MBChB, BMedSci
Faculty of Medicine, University of Tromsø, Norway
Department of Clinical Surgery, The University of
Edinburgh, Edinburgh, UK
James Lau, MD
Jonathan C. Epstein, MA, MD, FRCS Professor of Surgery, The Chinese University of
Consultant Surgeon, Intestinal Failure Unit, Salford Hong Kong; Director, Endoscopy Centre, Prince of
Royal NHS Foundation Trust, Salford, UK Wales Hospital, Hong Kong, PR China
xi
Downloaded for Anonymous User (n/a) at Rutgers University - NERL from ClinicalKey.com by Elsevier on March 19, 2019.
For personal use only. No other uses without permission. Copyright ©2019. Elsevier Inc. All rights reserved.
Contributors
B. James Mander, MBBS, BSc, FRCS, MS, Hugh M. Paterson, BMedSci, MBChB,
FRCS(Gen) MD, FRCS(Ed)
Consultant Colorectal Surgeon and Honorary Senior Clinical Senior Lecturer Coloproctology, The
Lecturer, Colorectal Unit, Western General Hospital, University of Edinburgh; Honorary Consultant
Edinburgh, UK Colorectal Surgeon, Western General Hospital,
Edinburgh, UK
Katherine McAndrew, MBChB
General Intensive Care Unit, St George's University Simon Paterson-Brown, MBBS, MPhil,
Hospitals NHS Foundation Trust, London, UK MS, FRCS(Ed), FRCS(Engl), FCS(HK),
FFST(RCSEd)
Craig McIlhenny, MBChB, FRCS(Urol), PGC, Honorary Clinical Senior Lecturer, Clinical Surgery,
Med, FFST(Ed) The University of Edinburgh; Consultant General and
Consultant Urological Surgeon, NHS Forth Valley, Upper Gastrointestinal Surgeon, Royal Infirmary of
Larbert, UK Edinburgh, Edinburgh, UK
Pradeep H. Navsaria, MBChB, MMed, FCS(SA), Andrew Rhodes, FCRP, FFICM,
FACS, Trauma Surgery FRCA, MD(res)
General Trauma Surgeon, Groote Schuur Hospital; Medical Director, Consultant in Anaesthesia and
Professor, University of Cape Town, Cape Town, Intensive Care Medicine, St George's University
Republic of South Africa Hospitals NHS Foundation Trust, London, UK
Valentin Neuhaus, MD, PD William G. Simpson, MBChB, FRCS
Trauma Centre, Groote Schuur Hospital, Cape Consultant Chemical Pathologist, Clinical
Town, Republic of South Africa; Department of Biochemistry, Aberdeen Royal Infirmary; Honorary
Trauma Surgery, University Hospital Zurich, Zurich, Senior Lecturer, School of Medicine, Aberdeen
Switzerland University, Aberdeen, UK
Andrew John Nicol, MBChB, FCS(SA), PhD Bruce R. Tulloh, MB, MS, FRACS, FRCS
Director of the Trauma Centre, Surgery, Groote Consultant General and Upper Gastrointestinal
Schuur Hospital; Professor Surgery, University of Surgeon, Royal Infirmary of Edinburgh and
Cape Town, Cape Town, Republic of South Africa Honorary Clinical Senior Lecturer, University of
Edinburgh, UK
Iain J. Nixon, MBChB, FRCS(ORL-HNS), PhD
ENT Consultant Surgeon, NHS Lothian; Honorary Diana A. Wu, MBChB
Clinical Senior Lecturer, The University of Edinburgh, Clinical Research Fellow, Transplant Unit, Royal
Edinburgh, UK Infirmary of Edinburgh, Clinical Surgery, The
University of Edinburgh, Edinburgh, UK
Gabriel C. Oniscu, MD, FRCS
Consultant Transplant Surgeon, Transplant Unit, Hon Chi Yip, MBChB
Royal Infirmary of Edinburgh; Honorary Clinical Resident Specialist, Department of Surgery, The
Senior Lecturer, Clinical Surgery, The University of Chinese University of Hong Kong, Hong Kong, PR
Edinburgh, Edinburgh, UK China
xii
Downloaded for Anonymous User (n/a) at Rutgers University - NERL from ClinicalKey.com by Elsevier on March 19, 2019.
For personal use only. No other uses without permission. Copyright ©2019. Elsevier Inc. All rights reserved.
1
Evaluation of surgical evidence
Thomas M. Drake
Ewen M. Harrison
Introduction to surgical
Australian surgeons found many believed their own
evidence clinical practice was superior to clinical guidelines;
that evidence-based surgery had an adverse effect
Evidence-based medicine is a recent innovation. on clinical decision-making; and that not using
It has only been over the past two centuries that evidence did not adversely affect patient care. Such
scientific methods have become the accepted means attitudes present a major barrier to the uptake
of establishing the most effective treatments and of evidence in surgery and require addressing if
tests. Nowhere in medicine has this transformation outcomes and patient care are to be the best they
been more vibrant than in surgical disciplines, where can be.2
numerous innovations have paved the way for the Thirdly, many operations have ancient origins,
treatments of today. This transformation, however, are performed for a given indication and lead to
has not been plain sailing. a resolution of the disease process, i.e. they are
The first person to coin the phrase ‘evidence- held to be effective. As such, there may be limited
based medicine’ was Dr David Eddy, who argued scientific evidence for these procedures as it would
that medical decision-making and policy should be seen as unethical to deny patients an effective
be supported by quantitative data.1 One of the and established treatment in the context of a
forefathers of evidence-based medicine in the UK, research study.
Archie Cochrane, strongly advocated the use of Finally, a lack of funding and interest in surgical
controlled experiments and randomisation methods research has led to research studies becoming
to reduce bias in research in order to arrive at the the exception rather than the norm. Currently
most reliable answer. The eponymous Cochrane it is unusual for a patient undergoing surgery
Collaboration began in 1993, in response to to be enrolled in a research study. When these
Cochrane’s call for better evidence to underpin different factors are considered in context, it is
medical decision-making. unsurprising that in 1998 surgical research was
The generation of high-quality evidence in compared to a ‘comic opera’ by the editor of The
surgery can be particularly difficult. The reasons Lancet.3
underpinning this are fourfold. Firstly, performing Over the past decade, considerable improvements
surgery is a complex intervention. There are many have been made. In a short space of time, several
variables to consider when designing research large initiatives have been launched by Royal
studies, including postoperative care, variation in Colleges and collaborations have led to new
surgical techniques and factoring in the natural surgery-specific research frameworks (e.g. the
learning curves required for surgeons to learn new IDEAL framework, see below) being introduced.
approaches or operative procedures. This is proving to be successful, with surgical
Secondly, there is evidence that surgeons themselves research increasingly being published in the world’s
are divided in their attitudes to research. A survey of largest medical journals.
1
Downloaded for Anonymous User (n/a) at Rutgers University - NERL from ClinicalKey.com by Elsevier on March 19, 2019.
For personal use only. No other uses without permission. Copyright ©2019. Elsevier Inc. All rights reserved.
Chapter 1
Changing the world with For example, we may study antibiotics in the
treatment of adults with acute appendicitis. In
evidence
this situation, antibiotics are used to reduce
complications of appendicitis and reduce the
In order for surgical research to change practice
necessity for surgical intervention. Using the PICOS
and influence patient care, it must address a new
approach:
question or an area of genuine clinical uncertainty.
The uncertainty as to which treatment is best • P – The population is adults with non-
is described as ‘clinical equipoise’. One of the
perforated acute appendicitis
key assumptions for the ethical conduct of any
• I – The intervention is antibiotics
interventional research is that equipoise exists,
• C – The comparison group is that of usual
that is, there must be genuine uncertainty as
to which treatment is best for a given patient clinical care (appendicectomy)
group. If clinical equipoise does not exist and it • O – The primary outcome is complication rate,
is definitively known that one treatment is better, defined using a validated grading system
it is unethical to knowingly expose patients to the • S – The study design is a randomised
inferior treatment.
controlled trial.
Any research study being evaluated should be read
in full, considering the following:
Study population or target
• Who is the patient population or target condition?
condition
• What was the intervention (for interventional
research, i.e. clinical trials) or exposure (for
A study population is a group of participants selected
observational research)?
from a general population on the basis of specific
• What was the comparison (or control group)?
characteristics. Having a clearly defined study
• How was the effect of the intervention
population is key to ensuring research is clinically
measured, and was it measured accurately? relevant and can answer a specific question. If a
• Are there any sources of bias or confounding target condition is used as the basis for selecting
present? a study population, validated diagnostic criteria
• What was the result? should be applied.
The basis for the inclusion of particular patients
• Is this study relevant to my clinical practice?
in a study should be systematic, to avoid bias. The
In this chapter we will discuss each point in further best way of ensuring a sample is both representative
detail. and free from selection bias is to approach every
eligible patient in a consecutive manner. This is
Formulating a clinical
often referred to as a consecutive sample.
question Specific study populations may have special
considerations that must be taken into account in
The first step in the design of a clinical research the study design. An example of this may be an older
study is to formulate a study hypothesis or question. age group, where visual or hearing impairment may
Understanding the constituent parts of a clinical present difficulties with particular data collection
hypothesis is key to evaluating the relevance and methods, e.g. telephone interviews.
quality of surgical research studies.
A simple, structured approach can be used to
Intervention or exposure
formulate clinical questions. This approach takes
into account several important aspects of a clinical
research study: The intervention is the main variable changed in
the treatment group. In observational research,
• ‘P’ – Population (those patients with the target patients and clinicians decide which treatment will
condition) be received. As no direct experimental intervention
• ‘I’ – Intervention or exposure (the intervention occurs, the variable is termed the ‘exposure’.
or exposure being studied) When considering an intervention for surgical
research, particular care must be given to delivering
• ‘C’ – Comparison (the control group that the
interventions in a standardised manner. Variation
intervention is being compared to)
in how a treatment may be delivered should
• ‘O’– Outcomes (what was the outcome of
be considered during the design process. For
interest and how was it measured) example, in a study of a new surgical technique
• ‘S’ – Study design (how the study was conducted). or approach, ensuring all patients receive a similar
2
Downloaded for Anonymous User (n/a) at Rutgers University - NERL from ClinicalKey.com by Elsevier on March 19, 2019.
For personal use only. No other uses without permission. Copyright ©2019. Elsevier Inc. All rights reserved.
