Pain Management Yearbook 2017 9781536136944

Table of contents :
Cover......Page 1
Copyright......Page 8
Contents......Page 9
Introduction......Page 15
Abstract......Page 17
Introduction......Page 18
Why psychosocial oncology is important......Page 19
References......Page 20
Section one: Psychosocial and ethical issues along the cancer care continuum......Page 21
Abstract......Page 23
Discussion......Page 24
Conclusion......Page 27
References......Page 28
Abstract......Page 29
Methods......Page 30
Therapies treating side-effects......Page 31
Discussion......Page 36
Acknowledgments......Page 37
References......Page 38
Abstract......Page 41
Methods......Page 42
Results......Page 43
Psychological interventions......Page 44
Psycho-educational interventions......Page 46
Discussion......Page 47
References......Page 48
Abstract......Page 51
Introduction......Page 52
Methods......Page 54
Characteristics of included studies......Page 55
Thematic synthesis......Page 56
Presence of refractory physical symptoms......Page 57
Alternative interventions......Page 58
Discussion......Page 59
Conflict of interest......Page 60
References......Page 61
Abstract......Page 63
Methods......Page 64
Participation and leadership role in multidisciplinary follow-up service......Page 65
Assist with return to school......Page 67
Discussion......Page 68
References......Page 69
Abstract......Page 71
Introduction......Page 72
Methods......Page 73
Results......Page 74
Discussion......Page 78
Acknowledgments......Page 80
References......Page 81
Abstract......Page 83
Structure and function of PFACs......Page 84
Methods......Page 85
PFAC organization......Page 86
PFAC goals......Page 87
PFAC accomplishments and obstacles......Page 88
Discussion......Page 89
Acknowledgments......Page 90
References......Page 91
Abstract......Page 93
Methods......Page 94
Results......Page 95
Factors contributing to depression......Page 96
Discussion......Page 101
References......Page 104
Abstract......Page 107
Introduction......Page 108
Results......Page 109
Comparing other hospitalization-related factors based on resuscitative status......Page 111
Discussion......Page 117
References......Page 118
Abstract......Page 121
Methods......Page 122
Results......Page 123
Communication skills......Page 124
Oncologist burnout......Page 128
Discussion......Page 129
References......Page 130
Abstract......Page 133
Introduction......Page 134
Methods......Page 135
Conceptualizing ICDs as medical devices versus biological transplants......Page 136
Autonomy, informed consent, and advance directives......Page 137
Withdrawal of ICDs versus euthanasia......Page 138
Conclusion......Page 139
References......Page 140
Abstract......Page 143
Methods......Page 144
Results......Page 148
Inadequacy of support services......Page 149
Inadequacy of home locations and sizes......Page 150
Discussion......Page 151
References......Page 152
Abstract......Page 155
Methods......Page 156
Expert interviews......Page 157
Expert interviews......Page 158
Unique aspects of children’s grief......Page 159
Recommended practices for helping bereaved children......Page 160
Discussion......Page 162
Conclusion......Page 163
References......Page 164
Section two: Pain and palliative care......Page 167
Abstract......Page 169
Methods......Page 170
Results......Page 171
Discussion......Page 172
Appendix 1......Page 173
References......Page 175
Abstract......Page 177
Introduction......Page 178
Methods......Page 180
Results......Page 181
Future studies......Page 184
References......Page 185
Abstract......Page 187
Intervention......Page 188
Treatments and professional support......Page 189
Analysis......Page 190
Pain problems......Page 191
Quality of life, mood and function......Page 192
Brief pain inventory......Page 193
Health care use......Page 194
Social participation, employment support and activities post-discharge......Page 196
Discussion......Page 197
Weaknesses and strengths......Page 199
References......Page 200
Abstract......Page 203
Case report......Page 204
Discussion......Page 205
References......Page 206
Abstract......Page 209
Case report......Page 210
Discussion......Page 212
References......Page 213
Abstract......Page 215
Case report......Page 216
Discussion......Page 218
References......Page 219
Abstract......Page 221
Case report......Page 222
Discussion......Page 224
References......Page 225
Introduction......Page 227
Case report......Page 228
References......Page 230
Introduction......Page 233
Case report......Page 234
Discussion......Page 237
References......Page 238
Abstract......Page 239
Case report......Page 240
Discussion......Page 244
References......Page 245
Abstract......Page 247
Case report......Page 248
Discussion......Page 250
References......Page 251
Section three: Biomarkers in oncology......Page 253
Abstract......Page 255
Introduction......Page 256
Methods......Page 257
Breast cancer......Page 258
Lung cancer......Page 271
Hepatobiliary carcinoma......Page 272
Myeloproliferative neoplasms......Page 273
Other neoplastic sites......Page 274
Discussion......Page 275
References......Page 277
Abstract......Page 281
Introduction......Page 282
Ineligibility Criteria......Page 283
Results......Page 284
Cancer cachexia......Page 294
Symptom burden and quality of life......Page 295
Discussion......Page 296
References......Page 298
Abstract......Page 301
Introduction......Page 302
Data extraction......Page 303
µ-Opioid Receptor (OPRM)......Page 304
Catechol-O-methyltransferase (COMT)......Page 310
β-Arrestin 1 and 2 (ARRB1 & ARRB2)......Page 311
Signal transducer and activation of transcription 6 (STAT6)......Page 312
Discussion......Page 313
References......Page 316
Abstract......Page 319
Introduction......Page 320
Methods......Page 321
Study eligibility......Page 322
Colorectal cancer (CRC)......Page 327
Lung cancer......Page 328
Discussion......Page 329
References......Page 331
Abstract......Page 333
Introduction......Page 334
Data extraction......Page 335
Results......Page 336
Discussion......Page 339
References......Page 341
Abstract......Page 343
Methods......Page 344
Toxicities in breast cancer patients......Page 345
Pneumonitis and esophagitis in NSCLC patients......Page 348
Discussion......Page 349
References......Page 351
Abstract......Page 353
Introduction......Page 354
Data extraction......Page 355
Results......Page 356
Discussion......Page 364
References......Page 365
Abstract......Page 369
Introduction......Page 370
Methods......Page 371
Results......Page 372
Discussion......Page 379
References......Page 380
Abstract......Page 383
Introduction......Page 384
Data extraction......Page 385
Results......Page 386
Discussion......Page 392
References......Page 393
Section four: Medical cannabis......Page 397
Abstract......Page 399
Introduction......Page 400
Baseline......Page 401
Patient conditions......Page 402
Patient symptoms......Page 404
Discussion......Page 405
Conclusion......Page 406
References......Page 407
Abstract......Page 409
Methods......Page 410
Results......Page 414
Discussion......Page 416
References......Page 417
Abstract......Page 419
Introduction......Page 420
Baseline......Page 421
Statistical analysis......Page 422
Pain and ability to cope with pain......Page 424
Improvements in symptoms......Page 425
Improvement in quality of life (QOL)......Page 426
Discussion......Page 428
Conclusion......Page 429
References......Page 430
Abstract......Page 431
Survey design......Page 432
Follow-up......Page 433
Pain and ability to cope with pain......Page 434
Improvements in symptoms......Page 436
Improvement in quality of life (QOL)......Page 438
Discussion......Page 440
References......Page 443
Abstract......Page 445
Introduction......Page 446
Methods......Page 447
Data analysis......Page 448
Improvements in conditions, symptoms, and QOL items......Page 450
Improvements in pain as a symptom at 4 months and 10 months......Page 451
Discussion......Page 453
Acknowledgment......Page 454
References......Page 455
Abstract......Page 457
Introduction......Page 458
Survey design......Page 459
Follow-up......Page 460
Pain and ability to cope with pain......Page 461
Improvement in medical conditions......Page 463
Improvements in quality of life (QOL)......Page 464
Improvement in symptoms......Page 465
Discussion......Page 467
Conclusion......Page 468
References......Page 469
Abstract......Page 471
Introduction......Page 472
Data collection......Page 473
Medical cannabis use......Page 474
Improvement in PTSD-related symptoms and pain......Page 476
Impact of PTSD on social and family life......Page 477
Discussion......Page 478
References......Page 480
Abstract......Page 483
Introduction......Page 484
Data collection......Page 485
Previous treatment prevalence and effectiveness......Page 486
Improvement in alcohol and tobacco use......Page 488
Discussion......Page 489
References......Page 490
Abstract......Page 493
Introduction......Page 494
Baseline......Page 495
Improvement of PTSD and its common symptoms......Page 496
Preferred varieties for relief of PTSD......Page 497
Usage of medical cannabis......Page 498
Discussion......Page 500
References......Page 501
Section five: Acknowledgments......Page 503
About the editor......Page 505
Service and academic activities......Page 507
International collaborations......Page 508
Contact......Page 509
About the book series “Disability studies”......Page 511
Contact......Page 512
Section six: Index......Page 513
Index......Page 515
Blank Page......Page 2

Citation preview

DISABILITY STUDIES

PAIN MANAGEMENT YEARBOOK 2017

No part of this digital document may be reproduced, stored in a retrieval system or transmitted in any form or by any means. The publisher has taken reasonable care in the preparation of this digital document, but makes no expressed or implied warranty of any kind and assumes no responsibility for any errors or omissions. No liability is assumed for incidental or consequential damages in connection with or arising out of information contained herein. This digital document is sold with the clear understanding that the publisher is not engaged in rendering legal, medical or any other professional services.

DISABILITY STUDIES Joav Merrick - Series Editor – NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT, MINISTRY OF SOCIAL AFFAIRS, JERUSALEM

Pain Management Yearbook 2017 Joav Merrick (Editors) 2018. ISBN: 978-1-53613-693-7 (Hardcover) 2018. ISBN: 978-1-53613-694-4 (e-book) Quality of Life and Intellectual Disability: Knowledge Application to other Social and Educational Challenges Roy I. Brown and Rhonda M. Faragher (Editors) 2014. ISBN: 978-1-62948-264-4 (Hardcover) 2018. ISBN: 978-1-53613-063-8 (Softcover) 2014. ISBN: 978-1-62948-272-9 (e-book) Parkinson’s Disease: Awareness among Young Adults Ronald Chow, Jaclyn Viehweger, Michael Borean, Drew Hollenberg, and Joav Merrick (Editors) 2017. ISBN: 978-1-53612-745-4 (Hardcover) 2018. ISBN: 978-1-53612-745-4 (Softcover) 2017. ISBN: 978-1-53612-746-1 (e-book) Human Development: Equipping Minds with Cognitive Development Carol T. Brown and Joav Merrick 2018. ISBN: 978-1-53613-053-9 (Softcover) 2018. ISBN: 978-1-53613-054-6 (e-book) Autism Spectrum Disorder: Awareness among Young Adults Ronald Chow, Jaclyn Viehweger, Joav Merrick (Editors) 2017. ISBN: 978-1-53612-730-0 (Hardcover) 2017. ISBN: 978-1-53612-731-7 (e-book)

Virtual Reality: Recent Advances in Virtual Rehabilitation System Design Wendy Powell, Albert “Skip” Rizzo, Paul M. Sharkey and Joav Merrick 2017. ISBN: 978-1-53612-040-0 (Softcover) 2017. ISBN: 978-1-53612-061-5 (e-book) Child Abuse: Children with Disabilities Vincent J Palusci, Dena Nazer, Donald E Greydanus and Joav Merrick 2017. ISBN: 978-1-53612-035-6 (Hardcover) 2017. ISBN: 978-1-53612-056-1 (e-book) Rehabilitation: Innovations and Challenges in the Use of Virtual Reality Technologies Wendy Powell, Albert “Skip” Rizzo, Paul M. Sharkey and Joav Merrick, (Editors) 2017. ISBN: 978-1-53612-080-6 (Hardcover) 2017. ISBN: 978-1-53612-099-8 (e-book) Virtual Reality: Recent Advances for Health and Wellbeing Wendy Powell, Paul M Sharkey and Albert “Skip” Rizzo 2017. ISBN: 978-1-53612-454-5 (Softcover) 2017. ISBN: 978-1-53612-455-2 (e-book) Pediatric Pain: Current Aspects Hatim A. Omar, Dilip R. Patel, Donald E. Greydanus, and Joav Merrick (Editors) 2016. ISBN: 978-1-63485-505-1 (Hardcover) 2016. ISBN: 978-1-63485-537-2 (e-book)

Recent Advances on Using Virtual Reality Technologies for Rehabilitation Paul M. Sharkey and Joav Merrick (Editors) 2016. ISBN: 978-1-63484-027-9 (Hardcover) 2015. ISBN: 978-1-63484-028-6 (e-book) Technology, Rehabilitation and Empowerment of People with Special Needs Lena Pareto, Paul M Sharkey and Joav Merrick (Editors) 2015. ISBN: 978-1-63482-713-3 (Hardcover) 2015. ISBN: 978-1-63482-737-9 (e-book) Virtual Reality: Rehabilitation in Motor, Cognitive and Sensorial Disorders Paul M. Sharkey and Joav Merrick (Editors) 2014. ISBN: 978-1-63321-773-7 (Hardcover) 2014. ISBN: 978-1-63321-787-4 (e-book)

Pain: International Research in Pain Management Joav Merrick, Patricia Schofield and Mohammed Morad (Editors) 2013. ISBN: 978-1-62948-423-5 (Hardcover) 2013. ISBN: 978-1-62948-435-8 (e-book) Disability and Chronic Disease Joav Merrick, Shoshana Aspler and Mohammed Morad (Editors) 2013. ISBN: 978-1-62948-288-0 (Hardcover) 2013. ISBN: 978-1-62948-307-8 (e-book) Down Syndrome and Dementia. A Comprehensive and Historical Review Vee P. Prasher 2012. ISBN: 978-1-62081-263-1 (Hardcover) 2012. ISBN: 978-1-62081-271-6 (e-book)

Virtual Reality: People with Special Needs Paul M. Sharkey and Joav Merrick (Editors) 2014. ISBN: 978-1-63321-729-4 (Hardcover) 2014. ISBN: 978-1-63321-734-8 (e-book)

Rett Syndrome: Therapeutic Interventions Meir Lotan and Joav Merrick (Editors) 2011. ISBN: 978-1-61728-614-8 (Hardcover) 2011. ISBN: 978-1-61728-080-1 (Softcover) 2011. ISBN: 978-1-61761-131-5 (e-book)

Intellectual Disability: Some Current Issues Joav Merrick, Donald E Greydanus and Dilip R. Patel (Editors) 2014. ISBN: 978-1-63321-855-0 (Hardcover) 2014. ISBN: 978-1-63321-867-3 (e-book)

Pain Management Yearbook 2010 Joav Merrick (Editor) 2011. ISBN: 978-1-61209-972-9 (Hardcover) 2011. ISBN: 978-1-62808-255-5 (e-book)

From One Century to the Next: A History of Wrentham State School and the Institutional Model in Massachusetts Ingrid Grenon 2014. ISBN: 978-1-63117-711-8 (Hardcover) 2014. ISBN: 978-1-63483-805-4 (Softcover) 2014. ISBN: 978-1-63117-712-5 (e-book) Pain and the Elderly Joav Merrick and Mimi M.Y. Tse 2013. ISBN: 978-1-62948-468-6 (Hardcover) 2013. ISBN: 978-1-62948-475-4 (e-book)

Pain Management Yearbook 2009 Joav Merrick (Editor) 2011. ISBN: 978-1-61209-666-7 (Hardcover) 2011. ISBN: 978-1-62081-774-2 (e-book) Pain. Brain Stimulation in the Treatment of Pain Helena Knotkova, Ricardo Cruciani and Joav Merrick (Editors) 2011. ISBN: 978-1-60876-690-1 (Hardcover) 2011. ISBN: 978-1-61470-495-9 (e-book)

Neural Plasticity in Chronic Pain Helena Knotkova, Ricardo A. Cruciani and Joav Merrick (Editors) 2011. ISBN: 978-1-61324-657-3 (Hardcover) 2011. ISBN: 978-1-62417-407-0 (e-book) Disability from a Humanistic Perspective: Towards a Better Quality of Life Shunit Reiter 2011. ISBN: 978-1-60456-412-9 (Hardcover) 2011. ISBN: 978-1-63117-654-8 (e-book)

Cancer in Children and Adults with Intellectual Disabilities: Current Research Aspects Daniel Satgé and Joav Merrick (Editors) 2011. ISBN: 978-1-61761-856-7 (Hardcover) 2011. ISBN: 978-1-61122-187-9 (e-book) Contemporary Issues in Intellectual Disabilities V. P. Prasher 2010. ISBN: 978-1-61668-023-7 (Hardcover) 2010. ISBN: 978-1-61209-292-8 (e-book)

DISABILITY STUDIES

PAIN MANAGEMENT YEARBOOK 2017

JOAV MERRICK EDITOR

Copyright © 2018 by Nova Science Publishers, Inc.

All rights reserved. No part of this book may be reproduced, stored in a retrieval system or transmitted in any form or by any means: electronic, electrostatic, magnetic, tape, mechanical photocopying, recording or otherwise without the written permission of the Publisher. We have partnered with Copyright Clearance Center to make it easy for you to obtain permissions to reuse content from this publication. Simply navigate to this publication’s page on Nova’s website and locate the “Get Permission” button below the title description. This button is linked directly to the title’s permission page on copyright.com. Alternatively, you can visit copyright.com and search by title, ISBN, or ISSN. For further questions about using the service on copyright.com, please contact: Copyright Clearance Center Phone: +1-(978) 750-8400 Fax: +1-(978) 750-4470 E-mail: [email protected]. NOTICE TO THE READER The Publisher has taken reasonable care in the preparation of this book, but makes no expressed or implied warranty of any kind and assumes no responsibility for any errors or omissions. No liability is assumed for incidental or consequential damages in connection with or arising out of information contained in this book. The Publisher shall not be liable for any special, consequential, or exemplary damages resulting, in whole or in part, from the readers’ use of, or reliance upon, this material. Any parts of this book based on government reports are so indicated and copyright is claimed for those parts to the extent applicable to compilations of such works. Independent verification should be sought for any data, advice or recommendations contained in this book. In addition, no responsibility is assumed by the publisher for any injury and/or damage to persons or property arising from any methods, products, instructions, ideas or otherwise contained in this publication. This publication is designed to provide accurate and authoritative information with regard to the subject matter covered herein. It is sold with the clear understanding that the Publisher is not engaged in rendering legal or any other professional services. If legal or any other expert assistance is required, the services of a competent person should be sought. FROM A DECLARATION OF PARTICIPANTS JOINTLY ADOPTED BY A COMMITTEE OF THE AMERICAN BAR ASSOCIATION AND A COMMITTEE OF PUBLISHERS. Additional color graphics may be available in the e-book version of this book.

Library of Congress Cataloging-in-Publication Data ISBN: H%RRN ISSN: 2163-7504

Published by Nova Science Publishers, Inc. † New York

CONTENTS Introduction Chapter 1

1 Complexity in psychosocial oncology Blair Henry, Arnav Agarwal, Edward Chow and Joav Merrick

3

Section one: Psychosocial and ethical issues along the cancer care continuum

7

Chapter 2

Finding a home (somewhere) for medical aid in dying Kathryn Morrison

9

Chapter 3

The use of vitamins, minerals, herbal supplements, and other dietary supplements as complementary and alternative therapies in cancer care: A literature review Nicholas Lao, Madeleine Lao, Michael Lam, Arnav Agarwal, Edward Chow and Blair Henry

Chapter 4

Chapter 5

Chapter 6

Chapter 7

A scoping review of psychosocial interventions for informal caregivers of palliative cancer patients Leone L Sutanto, Fiona M Ying, Arnav Agarwal, Michael Lam, Edward Chow and Blair Henry Clinicians’ views on palliative sedation for existential suffering: A systematic review and thematic synthesis of qualitative studies Michael Lam, Helen R Lam, Arnav Agarwal, Ronald Chow, Selina Chow, Edward Chow, Christina De Longhi and Blair Henry The role of social work in the long-term care of childhood cancer survivors: A literature review Helen R Lam, Michael Lam, Arnav Agarwal, Ronald Chow, Selina Chow, Edward Chow, Reena Besa and Blair Henry Cultural and religious considerations in cancer care: Where do desires for life-sustaining care and miracles come from? Eva Bain, Michael Puopolo, Arnav Agarwal, Michael Lam, Edward Chow and Blair Henry

15

27

37

49

57

viii Chapter 8

Chapter 9

Chapter 10

Chapter 11

Chapter 12

Chapter 13

Chapter 14

Contents A qualitative review of patient and Family Advisory Councils in cancer care Shangjun (Collier) Jiang, Bo A Wan, Michael Lam, Arnav Agarwal, Edward Chow and Blair Henry Factors and correlates of depression in advanced cancer patients: A scoping review Michael Puopolo, Eva Bain, Arnav Agarwal, Michael Lam, Edward Chow and Blair Henry A review on the impact of “do-not-resuscitate” orders on mortality and quality of care Bo Angela Wan, Collier Jiang, Arnav Agarwal, Michael Lam, Edward Chow and Blair Henry The impact of breaking bad news on oncologist burnout and how communication skills can help: A scoping review Stephanie Cheon, Wayne Fu, Arnav Agarwal, Edward Chow and Blair Henry Deactivating implantable cardioverter-defibrillators (ICDs) in cancer patients: A scoping review of ethical considerations Adrianne Lebner and Maxwell J Smith Barriers to home death for Canadian cancer patients: A literature review Michael Lam, Helen R Lam, Arnav Agarwal, Henry Lam, Ronald Chow, Selina Chow, Stephanie Chan, Pearl Zaki and Edward Chow Best practices in children’s bereavement: A qualitative analysis of needs and services Molly Gao and Marissa Slaven

Section two: Pain and palliative care Chapter 15

Improving sublingual fentanyl (Abstral) prescribing, administration and titration in an in-patient specialist palliative care unit in Scotland Alison Thompson, Marnie Ferguson, Elinor Brabin, Katharine Thompson, Shirley Kelly and Rosie Conway

Chapter 16

Oska pulse: A new method of pain management Kathy Davis

Chapter 17

A clinical evaluation of a community-based rehabilitation and social intervention programme for patients with chronic pain with associated multi-morbidity Ellen Wright, Roxaneh Zarnegar, Ingrid Hermansen and David McGavin

69

79

93

107

119

129

141 153

155

163

173

Contents Chapter 18

A bone scan alone may not be enough for the diagnosis of bone metastases Shannon Goodall, Ronald Chow, Leigha Rowbottom, Rachel McDonald, Monique Christakis, Carlo DeAngelis, Flay Charbonneau and Edward Chow

Chapter 19

Disseminated fungal infection mimicking malignancy Mary J Tao, Rachel McDonald, Linda Probyn, Leigha Rowbottom, Michael Poon, Stephanie Chan and Edward Chow

Chapter 20

The improvement of bone metastases on bone scans following palliative radiotherapy: A case report Pearl Zaki, Stephanie Chan, Linda Probyn, Bo A Wan, Matthew Hwang, Angela Turner, Mary J Tao and Edward Chow

Chapter 21

Chapter 22

Chapter 23

Chapter 24

Chapter 25

Reactivation of tuberculosis of the left hip masquerading as bone metastasis: A case report Adam Bobrowski, Rachel McDonald, Stephanie Chan, Linda Probyn, Leigha Rowbottom, Pearl Zaki, Bo Angela Wan, Mary Jiayi Tao and Edward Chow The rare presentation of lytic bone metastases in prostate cancer patients Matthew Hwang, Stephanie Chan, Pearl Zaki, Linda Probyn, Bo Angela Wan, Mary Jiayi Tao and Edward Chow Cervical spine surgery for complicated spinal metastases secondary to breast cancer: A case report Pearl Zaki, Michael Ford, Stephanie Chan, Linda Probyn, Justin Lee, Bo Angela Wan, Matthew Hwang, Angela Turner, Mary Jiayi Tao and Edward Chow Diffuse-type tenosynovial giant cell tumor of the posterior C1 arch: A case report Linda Probyn, Julia Keith, Brendan C Dickson, Catherine Lang, Nicholas Phan, Soliman Hany and Richard I Aviv Pelvic insufficiency fracture mimicking bone metastasis: A case report Yusuf Ahmed, Chris Dey, Stephanie Chan, Bo Angela Wan, Arnav Agarwal, Marko Popovic, Leila Malek and Edward Chow

Section three: Biomarkers in oncology Chapter 26

Genetic variants and biological markers of cancer-related pain sensitivity Rachel McDonald, Adam Bobrowski, Matthew Choi, Stephanie Chan, Pearl Zaki, Bo Angela Wan, Anthony Furfari, Leigha Rowbottom, Henry Lam, Ronald Chow, George Charames, Azar Azad, Edward Chow and Carlo DeAngelis

ix

189

195

201

207

213

219

225

233

239 241

x Chapter 27

Chapter 28

Chapter 29

Contents Biomarkers relating to cancer-related symptom burden and quality of life Leigha Rowbottom, Stephanie Chan, Bo Angela Wan, Pearl Zaki, Matthew Choi, Anthony Furfari, Rachel McDonald, Carlo DeAngelis, Azar Azad, Ronald Chow, Henry Lam, Edward Chow and George S Charames Biomarkers and predictors of efficacy of analgesics in the management of cancer pain Adam Bobrowski, Arnav Agarwal, Leigha Rowbottom, Rachel McDonald, Anthony Furfari, Stephanie Chan, Pearl Zaki, Bo Angela Wan, Henry Lam, Azar Azad, Ronald Chow, Edward Chow, George S Charames and Carlo DeAngelis Biomarkers and predictors of the chemopreventative capacity of non-steroidal anti-inflammatory drugs (NSAIDs) Adam Bobrowski, Arnav Agarwal, Anthony Furfari, Rachel McDonald, Leigha Rowbottom, Stephanie Chan, Pearl Zaki, Bo Angela Wan, Henry Lam, Azar Azad, Ronald Chow, George S Charames, Edward Chow and Carlo DeAngelis

267

287

305

Chapter 30

Biomarkers of radiation response Matthew Choi, Leigha Rowbottom, Rachel McDonald, Anthony Furfari, Stephanie Chan, Bo Angela Wan, Pearl Zaki, Azar Azad, Ronald Chow, Carlo DeAngelis, Henry Lam, Edward Chow and George S Charames

319

Chapter 31

Biomarkers of susceptibility to radiation-related toxicities Anthony Furfari, Stephanie Chan, Pearl Zaki, Bo Angela Wan, Leigha Rowbottom, Rachel McDonald, Azar Azad, Ronald Chow, Carlo DeAngelis, Michael Lam, Henry Lam, Edward Chow and George S Charames

329

Chapter 32

Common inflammatory biomarkers of cancer prognosis Bo Angela Wan, Michael Lam, Anthony Furfari, Rachel McDonald, Leigha Rowbottom, Stephanie Chan, Pearl Zaki, Carlo DeAngelis, Ronald Chow, George S Charames, Henry Lam, Edward Chow |and Azar Azad

339

Chapter 33

Biological biomarkers of cancer prognosis Bo Angela Wan, Michael Lam, Anthony Furfari, Rachel McDonald, Leigha Rowbottom, Stephanie Chan, Pearl Zaki, Carlo DeAngelis, Ronald Chow, George Charames, Henry Lam, Edward Chow and Azar Azad

355

Contents Chapter 34

Genetic biomarkers of cancer prognosis Bo Angela Wan, Michael Lam, Anthony Furfari, Leigha Rowbottom, Rachel McDonald, Stephanie Chan, Pearl Zaki, Carlo DeAngelis, Azar Azad, Ronald Chow, Henry Lam, Edward Chow and George S Charames

xi 369

Section four: Medical cannabis

383

Chapter 35

Patient characteristics from a medical cannabis provider Bo Angela Wan, Alexia Blake, Stephanie Chan, Amiti Wolt, Pearl Zaki, Liying Zhang, Marissa Slaven, Erynn Shaw, Carlo DeAngelis, Henry Lam, Vithusha Ganesh, Leila Malek, Edward Chow and Shannon O’Hearn

385

Chapter 36

Symptom clusters in patient-reported outcomes of medical cannabis patients Nicholas Lao, Vithusha Ganesh, Liying Zhang, Leah Drost, Bo Angela Wan, Alexia Blake, Stephanie Chan, Amiti Wolt, Pearl Zaki, Marissa Slaven, Erynn Shaw, Carlo DeAngelis, Henry Lam, Leila Malek, Edward Chow and Shannon O’Hearn

Chapter 37

The use of medical cannabis in cancer patients Pearl Zaki, Alexia Blake, Amiti Wolt, Stephanie Chan, Liying Zhang, Angela Wan, Henry Lam, Carlo DeAngelis, Marissa Slaven, Erynn Shaw, Vithusha Ganesh, Leila Malek, Edward Chow and Shannon O’Hearn

Chapter 38

The use of medical cannabis in common medical conditions excluding cancer Pearl Zaki, Vithusha Ganesh, Shannon O’Hearn, Amiti Wolt, Stephanie Chan, Liying Zhang, Henry Lam, Bo Angela Wan, Marissa Slaven, Erynn Shaw, Carlo DeAngelis, Leila Malek, Edward Chow and Alexia Blake

Chapter 39

Chapter 40

Efficacy of different varieties of medical cannabis in relieving symptoms Bo Angela Wan, Patrick Diaz, Alexia Blake, Stephanie Chan, Amiti Wolt, Pearl Zaki, Liying Zhang, Marissa Slaven, Erynn Shaw, Carlo DeAngelis, Henry Lam, Vithusha Ganesh, Leila Malek, Edward Chow and Shannon O’Hearn Medical cannabis use for patients with post-traumatic stress disorder (PTSD) Stephanie Chan, Alexia Blake, Amiti Wolt, Bo Angela Wan, Pearl Zaki, Liying Zhang, Henry Lam, Marissa Slaven, Erynn Shaw, Carlo DeAngelis, Vithusha Ganesh, Leila Malek, Edward Chow and Shannon O’Hearn

395

405

417

431

443

xii Chapter 41

Chapter 42

Chapter 43

Contents Medical cannabis use in military and police veterans diagnosed with post-traumatic stress disorder (PTSD) Paul A Smith, Stephanie Chan, Alexia Blake, Amiti Wolt, Liying Zhang, Bo Angela Wan, Pearl Zaki, Henry Lam, Carlo DeAngelis, Marissa Slaven, Erynn Shaw, Vithusha Ganesh, Leila Malek, Edward Chow and Shannon O’Hearn The effect of medical cannabis on alcohol and tobacco use in veterans with post-traumatic stress disorder (PTSD) Shicheng Jin, Bo Angela Wan, Stephanie Chan, Paul A Smith, Alexia Blake, Amiti Wolt, Liying Zhang, Henry Lam, Carlo DeAngelis, Marissa Slaven, Erynn Shaw, Vithusha Ganesh, Pearl Zaki, Leah Drost, Nicholas Lao, Leila Malek, Edward Chow and Shannon O’Hearn Efficacy of different varieties of medical cannabis in relieving symptoms in post-traumatic stress disorder (PTSD) patients Leah Drost, Bo Angela Wan, Alexia Blake, Stephanie Chan, Amiti Wolt, Vithusha Ganesh, Liying Zhang, Marissa Slaven, Erynn Shaw, Carlo DeAngelis, Henry Lam, Pearl Zaki, Leila Malek, Edward Chow and Shannon O’Hearn

457

469

479

Section five: Acknowledgments

489

Chapter 44

About the editor

491

Chapter 45

About the National Institute of Child Health and Human Development in Israel

493

About the book series “Disability studies”

497

Chapter 46

Section six: Index

499

Index

501

INTRODUCTION

In: Pain Management Yearbook 2017 Editor: Joav Merrick

ISBN: 978-1-53613-693-7 © 2018 Nova Science Publishers, Inc.

Chapter 1

COMPLEXITY IN PSYCHOSOCIAL ONCOLOGY Blair Henry, DBioethics1,*, Arnav Agarwal1, MD, Edward Chow1, MBBS and Joav Merrick2-6, MD, MMedSc, DMSc 1

Rapid Response Radiotherapy Program, Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada, 2 National Institute of Child Health and Human Development, Jerusalem, Israel, 3 Office of the Medical Director, Health Services, Division for Intellectual and Developmental Disabilities, Ministry of Social Affairs and Social Services, Jerusalem, Israel, 4 Division of Pediatrics, Hadassah Hebrew University Medical Center, Mt Scopus Campus, Jerusalem, Israel, 5 Kentucky Children’s Hospital, University of Kentucky School of Medicine, Lexington, Kentucky, United States and 6 Center for Healthy Development, School of Public Health, Georgia State University, Atlanta, Georgia, US

ABSTRACT Initially the stigma and fear associated with just the word "cancer" and its automatic association with death and dying made it an unspeakable experience for many patients, families and health care providers dealing with the disease. People were left alone to deal with the illness and it took until the mid to late 1970s that the use of the term psychooncology emerged. Though psychosocial oncology is being described as a distinct discipline- clinicians involved in cancer care need to rely and work closely with the members of the psychosocial team to provide whole person care in a complex disease such as cancer. Promulgation of the idea that body, mind and spirit are to be considered *

Correspondence: Mr Blair Henry, Ethicist, Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Toronto, ON Canada. E-mail: [email protected].

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Blair Henry, Arnav Agarwal, Edward Chow et al. as distinct and separate entities can only do a disservice to any attempt we make at providing health care.

INTRODUCTION Cancer care spans the continuum of health-care issues from primary prevention through longterm survival and end-of-life care. The Canadian Cancer Society estimated 196,900 cases of new cancer and 78,000 deaths from cancer in Canada in 2015 (1). The physical symptoms of cancer are complex and daunting, wherein even the basic treatment of the underlying disease can result in physical pain and discomfort. These symptoms are often addressed with medical treatment, such as the inclusion of palliative care earlier in the disease trajectory (2). However, it is the conjoined and often associated emotional impact of the disease that can be equally challenging for care providers, patients, family and friends alike, to deal with. Initially the stigma and fear associated with just the word "cancer" and its automatic association with death and dying made it an unspeakable experience for many patients, families and health care providers dealing with the disease. People were left alone to deal with the illness and it took until the mid to late 1970s that the use of the term psychooncology even emerged (2). As a disease and field of scholarship – the provision of cancer care is becoming increasingly complex, requiring a multi-disciplinary cadre of specialist in all aspects of holistic care to provide quality care (3). The undeniable link between the psychological and physiological elements to cancer treatment and survival are being looked into and researched through the field of psychoneuroimmunology- however component of holistic care, illustrated in figure 1, acknowledge the equal importance of mind, body and spirit as part of the care needs for patients and caregiver that forms the basis of an integrated approach to psychosocial oncology (3).

Figure 1. Integrated psychosocial oncology care.

Complexity in psychosocial oncology

5

WHY PSYCHOSOCIAL ONCOLOGY IS IMPORTANT A significant proportion of cancer patients will suffer some form of social, emotional and psychological distress and challenges as a result of the disease and its treatment. Unattended, psychosocial issues can leave patients and families ill-equipped to cope and manage their cancer diagnosis and treatment, particularly if they are unfamiliar with the variety of supports and resources available to them. Recent research into the psychosocial experience faced by patients identified the following significant themes experienced across a wide range of cancers: diminished sense of well-being, perceived role changes in intimate relationships, heightened awareness of limited time, a new order of priorities, taking things as they come and development of trust in health professionals. These themes indicate relevant areas of patients' well-being, which might be addressed through effective psychosocial support services (4). We know that when psychosocial care is properly integrated into clinical care, it has direct impact on a patient’s quality of life. In fact, new standards of quality cancer care, based on the 2007 Institute of Medicine of the National Academies of Sciences’ provided evidenced-based support strategies to provide good care for the whole patient; mandating that psychosocial aspects must be integrated into routine cancer care. Suggesting that patients should be screened at their initial visit for psychosocial needs and survivors should have a treatment plan that includes attention to possible increased anxiety on completing treatment, development of posttraumatic stress symptoms, and mixed anxiety and depressive symptoms (5). Table 1. Multiple factors along the cancer care continuum Body Type of cancer Type of treatment Age

Mind Developmental age Mental health Life stage

Gender

Grief/Bereavement

Sexuality Culture Language

Health literacy Illness understanding Survivorship or preparation for death

Stage of illness Goals of care Research/Treatment

Spirit Religious beliefs Spiritual beliefs Belief in alternative and complementary medicine Quality of life Hope

Relational Family Caregivers Age of children

Socio-economic factors Insurance Trust in health care Community supports Access to palliative care Heredity concerns

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CANCER CARE COMPLEXITY We know that cancer affects the whole family and not just the patient (6) and that patient/family centered care is needed to effectively provide whole level care. Table 1 outlines a very preliminary listing of multiple factors that need to be considered along the cancer care continuum. An artificial separation of physical care from other holistic components will not affectively address the complex and changing needs. The need for multidisciplinary rounds and comprehensive tumor rounds illustrate the evolving complexity and care needs that extend well beyond the limits of just the doctor-patient relationship.

CONCLUSION Though psychosocial oncology is being described as a distinct discipline- clinicians involved in cancer care need to rely and work closely with the members of the psychosocial team to provide whole person care in a complex disease such as cancer. Promulgation of the idea that body, mind and spirit are to be considered as distinct and separate entities can only do a disservice to any attempt we make at providing health care.

REFERENCES [1]

[2] [3] [4]

[5]

[6]

Canadian Cancer Society. Canadian Cancer Statistics 2015: Special Topic: Predictions of the future burden of cancer in Canada, May 2015. URL: http://www.cancer.ca/en/cancer-information/cancer101/canadian-cancer -statistics-publication/?region=on Holland JC. History of psycho-oncology: overcoming attitudinal and conceptual barriers. Psychosom Med 2002;64(2):206-21. Canadian Association of Psychosocial Oncology. Why is psychosocial oncology important? URL: http://www.capo.ca/patient-family-resources/what-is-psychosocial-oncol ogy/ Aldaz BE, Treharne GJ, Knight RG, Conner TS, Perez D. 'It gets into your head as well as your body': The experiences of patients with cancer during oncology treatment with curative intent. J Health Psychol 2016 Oct 5. pii: 1359105316671185. [Epub ahead of print] Holland J, Weiss T. The new standard of quality cancer care: integrating the psychosocial aspects in routine cancer from diagnosis through survivorship. Cancer J 2008;14(6):425-8. doi: 10.1097/ PPO.0b013e31818d8934. Blanchard CG, Albrecht TL, Ruckdeschel JC. The crisis of cancer: psychological impact on family caregivers. Oncology (Williston Park) 1997;11(2):189-94,196, 201-2.

SECTION ONE: PSYCHOSOCIAL AND ETHICAL ISSUES ALONG THE CANCER CARE CONTINUUM

In: Pain Management Yearbook 2017 Editor: Joav Merrick

ISBN: 978-1-53613-693-7 © 2018 Nova Science Publishers, Inc.

Chapter 2

FINDING A HOME (SOMEWHERE) FOR MEDICAL AID IN DYING Kathryn Morrison*, MA Department of Philosophy, University of Waterloo, Waterloo, Ontario, Canada

ABSTRACT Recent alterations to the criminal code following the passing of Bill C-14 have made Medical Aid in Dying (MAID) legal in Canada. With the new legislation in place, institutional questions arise concerning how MAID should be provided within the health care system. Alternatively, what are the limitations of conscientious objection to MAID? Palliative Care Units (PCUs) are in dire need of the answers to these questions, as they face contrary obligations towards patients requesting MAID. MAID seems to contradict some of the principle values of palliative care, while palliative care patients are also in a condition where they more likely to be eligible for MAID. Yet, examining some of these value contradictions more closely, there are more commonalities between MAID and palliative care than it would first seem. As a result, if PCUs conscientiously object to MAID as departments, then they are neglecting to fulfill their responsibility to honor their own missions and values. These commonalities in value between MAID and palliative care have clinical implications, as many of the patients who would prefer palliative care are also patients who would consider pursuing MAID concurrently. Three cases where patients could request both MAID and palliative care are outlined. They reveal a risk that a departmental conscientious objection to MAID in the PCU comes at the expense of patients receiving necessary palliative care.

Keywords: medical assistance in dying, palliative care, moral responsibility

*

Correspondence: Ms Kathryn Morrison, Department of Philosophy, University of Waterloo, 200 University Avenue West, Waterloo, Ontario N2L 3G1, Canada. E-mail: [email protected].

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INTRODUCTION Is it morally justifiable for palliative care units (PCU) as organizations to conscientiously object to providing medical aid in dying (MAID)? Sentiments in PCUs on MAID are divided, as they face contradictory obligations with regard to MAID. A worry of providing MAID in the PCU is that it conflicts with the missions and values of palliative care. In fact, MAID seems so contradictory to the purpose of palliative care that the Hospice Palliative Care of Ontario (HPCO) portrays requests for MAID as a failure of the health care system underutilizing and insufficiently delivering palliative services (1). Yet palliative care is an end-of-life service. As such, the PCU provides care to many of the people who would be expected to make a MAID request – intolerably suffering patients who have a naturally foreseeable death. While some patients are likely to request MAID in the community or as part of a freestanding hospice care program, patients requesting MAID within the hospital may not have access to care in the PCU. It would be inappropriate to abandon the patients who seek palliative care options on the basis of a MAID request. There has been little legal and political guidance on whether PCUs can collectively conscientiously object to MAID. Following Carter v Canada (2015), where the Supreme Court of Canada decided that MAID is constitutional, concerns arose in the medical community about physicians’ rights to conscientiously object, on an individual, and institutional basis (2). Modifications to the criminal code in light of the Carter decision, outlined in Bill C-14, guarantees the right of health care professionals to conscientiously object, with a proviso that effective referral is initiated to transfer care of patients to other health care providers who can meet their needs (3). Additionally, in Ontario, the Ministry of Health announced that hospitals may conscientiously object as institutions (4). Yet it does not speculate on the limitations of this right. If both individuals and institutions as a whole are able to conscientiously object, where does this leave health care departments? Rather than examining the legal limitations of the PCU’s right to conscientious objection, I will approach this issue morally by considering whether MAID and palliative care indeed have contrary missions and values that would justify conscientious objection. What I find is that MAID is highly compatible with palliative care values of avoiding hastening death, respecting autonomy, and encouraging compassion for suffering. As a result palliative care bears some responsibility to honor MAID requests, such that conscientious objections from PCUs fail to fulfill their own missions and values. Clinically, this responsibility to palliative care missions and values affects end-of-life patients, who are likely to pursue MAID and palliative care concurrently.

DISCUSSION Internationally, federally, and provincially it seems as though, insofar as MAID intentionally causes the death of the patient, it cannot be part of palliative care. The World Health Organization (WHO), and the HPCO define palliative care as an “approach that improves the quality of life of patients and their families facing the problem[s] associated with life threatening illness[es]” (5). Among the intentions listed by the WHO, palliative care is to neither hasten nor postpone death (5). HPCO similarly claims that quality hospice palliative

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care neither hastens death nor prolongs life (1), a claim echoed at the federal level by the Canadian department of justice (6). Naturally, this value directly conflicts with one of the primary goals of MAID, to intentionally end the patient’s life. As a result, palliative care organizations such as the HPCO explicitly distinguish euthanasia and physician assisted dying as not being part of the practice of palliative care (1). Clinically this interpretation of MAID is true; the treatments are meant to hasten the death of the patient. Yet it ignores the legal, social, and political factors which justify MAID as a charter right. In Carter v Canada, the Supreme Court ruled that access to MAID is protected by our section seven charter right to “life liberty and security of the person” (2). This is because, through gathering testimony from end of life patients, the Supreme Court discovered that denying MAID to patients encourages them to take their lives in anticipation of their further decline. After all, at the point where these patients would pursue MAID, they would be incapable of taking their lives on their own (2). MAID invokes the right to life by protecting patients from taking their lives prematurely, instead allowing them to end their lives when their condition is intolerable. To the extent that it does hasten death, MAID does so minimally. Since Bill C-14 outlines a reasonably foreseeable natural death as one of the eligibility requirements, patients who qualify for MAID are likely to die whether they pursue MAID or not. Additionally, hastening death through MAID does not conflict with palliative care anymore than other end-of-life practices. In Carter v. Canada, MAID is likened to treatments that intentionally hasten death and are ethically acceptable: palliative sedation and the withholding or withdrawal of lifesaving or life-sustaining medical treatment (2). Consequentially, this resemblance could also mean that there is no ethical distinction between palliative care and MAID. For instance, the trial judge of the British Columbia Supreme Court referred to as Smith J. argues that, ethically, if the outcome is likely to be death there is little distinguishing MAID from end-of-life practices (2). Palliative care units regularly reconcile their mission not to hasten death with end-of-life practices which allow for a hastened death to occur. There is no reason to think MAID should be treated any differently. There could be an important difference between these other end of life treatments and MAID which reveals a difference in priorities between palliative care values, and those which motivate MAID. Palliative care “deploys nurses, doctors, and social workers to help people with a fatal illness have the fullest possible life right now... focusing on objectives like freedom from pain and discomfort, or maintaining mental awareness for as long as possible, or getting out with family once and a while” (7). In contrast, the first priority of MAID is to end the patient’s life. As a treatment which prioritizes the death of the patient, possibly the most grievous and irreversible harm, MAID has no place being part of palliative care. Yet quality of life is influenced by more factors than harm avoidance, many of which motivate access to both MAID and palliative care. When patients could pursue aggressive treatment options which are more likely to cure them, what justifies their choice to pursue palliative care is that they have a right to dignity, which allows patients to decide what they value in their care. “People have concerns besides simply prolonging their lives and avoiding suffering” (7). For instance, patients surveyed in the US prioritized “being with family, having the touch of others, being mentally aware, and not becoming a burden to others” (7). Deciding what the patient values in their care is likewise an important value of MAID. Outlined in Bill C-14, the Parliament of Canada recognizes the autonomy of persons (3): allowing patients to have control over the time and manner of their death. Gloria Taylor, an

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appellant in Carter v. Canada (2015), recognizes the importance of autonomy in upholding a good quality of life when she explains that, as her condition progressed, she wanted independence and control over how she died (2). She did not want to “live in a bedridden state, stripped of dignity and independence…[or an] ugly death” (2). In Canada, “numerous polls indicate that a majority of Canadians believe medical aid in dying should be an option” (6). As Dr. Francine Lemire executive director and chief executive officer of the College of Family Physicians Canada, claims “we have a responsibility as health care providers... as decision makers and advisors, to listen to the public” (6). Additionally pain management, one of the primary missions of palliative care according to the WHO, is also a principle motivator of MAID. After all, patients request MAID in order to end “suffering that is intolerable to the individual in the circumstances of his or her condition” (2). While, at face value, it may seem as though MAID has no place in palliative care, it is in fact compatible with the missions and values of palliative care in many ways. With these compatibilities, it is problematic for PCUs to conscientiously object to providing MAID, because it involves objecting to some of the fundamental values which drive palliative care. By extension, for the PCU to ignore these compatibilities is to ignore their responsibilities to patients. Data collected in Oregon over a ten-year period reveals that this commonality between palliative care values and the values that drive MAID translates clinically, as patients often want to pursue palliative care and MAID concurrently. Oregon has a health care system and population which most closely resembles our own, yet it has one key difference. There, only physician assisted suicide (PAS), where the patient self-administers a lethal dose of medication is legal. Over 85 per cent of patients in Oregon who completed an assisted suicide treatment have been in a hospice (8), with the percentage of patients electing assisted suicide who were already enrolled in a hospice increasing in recent years (8). While these cases are typically completed in the community, and therefore avoid the complications arising in our PCUs, it reveals interesting values on behalf of patients. For most patients, palliative care and MAID are not treatments one chooses between, but treatments which are taken together (8). As part of end-of-life care, MAID is “a measure of last resort within palliative care, not… an alternative to it” (8). Consider three clinical scenarios where a patient may make a MAID request, and concurrently require treatment from the PCU. One scenario is where a patient’s condition is so severe that they require palliative services up between the point where they make a MAID request, and the treatment is completed. At minimum, this may occur during the ten clear day waiting period; a required time period beginning the day after a patient makes a request for MAID which allows for reflection and coordination. The patient may require longer than ten days to arrange their preferred conditions of their death – including both personal and clinical factors. Alternatively, some patients may initiate a MAID request, but may opt instead for palliative care as their circumstances change. Consider a patient who experiences grievous and irremediable suffering that they find intolerable. Yet the patient’s natural death is not reasonably foreseeable since the patient has an implanted device which supports heart function, and on which they are completely reliant. They are therefore ineligible for the treatment but they have thought about the process for many years. If the patient’s device were to be turned off, they could be eligible for a MAID treatment. Yet the prospect is risky. It is possible that, upon withdrawing the implanted device, their heart rate could return to a

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minimal yet sustainable rate – worsening their suffering, and leaving them still unable to meet the criteria for MAID. Such a patient is likely better off in the PCU where they have better access to palliative sedation. A case which begins as a MAID request could at any time become a purely palliative case. Patients may also be initiating a MAID request not as a means to end their lives immediately, but as a contingency. This way, if their condition worsens to a point they can no longer bare, they can have some control over when and how they die. Such patients may prefer palliative care treatments to MAID treatments. They may request MAID without the intention of ever having to complete the treatment. In fact, they may never complete the treatment that they requested. In Oregon, “the number of patients who request assisted death is quite small and the number who follow through with it is even smaller” (8). There, where there is a requirement for a six month waiting period between a request for MAID and the completion of the treatment, patients who have elected assisted suicide have lived well beyond that deadline before using the prescribed medication (8). In each of these cases, a unit-wide conscientious objection to MAID could result in patients having to be transferred out of palliative care at the time that their request arises: a course of action that is unacceptable for most patients in end-of-life care. Unit-wide conscientious objection could additionally effect who would be eligible for palliative care, as patients may be refused transfer to the PCU. This course of action is irresponsible and negligent for two main reasons. Firstly, in each of these cases patients are in conditions which require, or are likely to require, palliative treatments. It is unfair to leverage an essential service for end-of-life patients on the condition that patients will not pursue MAID. Secondly, in two of the three aforementioned scenarios, there is no certainty that the patient will ever complete their MAID treatment simply because they made a request. As a result, denying palliative care to patients is not done on the basis of conscientious objection to MAID, but a conscientious objection to the possibility that they could pursue a MAID treatment. This reasoning is insufficient to justify denying patients essential care.

CONCLUSION In summary, the commonalities between the values motivating both MAID and palliative care reveal that a departmental conscientious objection on behalf of the PCU would be inappropriate. For the PCU to object to MAID would be, on some level to object to palliative care itself. Further, because of these commonalities in value, many of the patients who believe in palliative care values are likely to pursue both palliative care and MAID. In fact three common clinical scenarios can arise where a patient requires both MAID and palliative care treatments: the patient is either in need of palliative care during the waiting period between making a formal request and completion of the treatment, requires palliative care in case they lose eligibility for MAID, or is planning to use MAID as a contingency and primarily wishes to pursue palliative care. The patient in each scenario has a need for palliative care and a legitimate reason for transfer. Why should one’s objections to MAID treatments be prioritized above one’s duty to palliative care patients? Allowing MAID to be offered in the PCU is an important step to furthering our responsibility of compassion towards patients, and to uphold the autonomy and longevity of

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patients. To close, consider how embracing these values could improve both the quality and user-ship of the PCU. Based on data from Oregon the passage of the Oregon Death with Dignity Act in 1994, it is likely that the use of hospice facilities and the quality of hospice care will rise (8). Accessibility to MAID could also help advance palliative care services, so that fewer MAID treatments are necessary. Until patients in end-of-life care have the option to access MAID, we will not fully understand the limitations of palliative care (8). By understanding these limitations, we could have a tangible understanding of how palliative care might grow and advance.

CONFLICT OF INTEREST The authors have no relevant conflicts of interest to disclose.

ACKNOWLEDGMENTS None.

REFERENCES [1] [2] [3]

[4]

[5] [6]

[7] [8]

Hospital Palliative Care Ontario. About hospice palliative care. URL: http://www.hpco.ca/who-weare/ about-hospice-palliative-care/. Supreme Court of Canada. Carter v. Canada (Attorney General). SCC 2015:19-31. Department of Justice. Legislative background: Medical assistance in dying (Bill C-14, as assented to on June 17, 2016). Government of Canada 2016. URL: http:// www.justice.gc.ca/eng/rp-pr/otherautre/adra-amsr/. Ministry of Health and Long Term Care and the Ministry of the Attorney General. Medical assistance in dying: update stakeholder presentation. Government of Ontario 2016. URL: https://www.oha.com/Current Issues/LegalProfessional/Documents/MAID%20-%20 June%206%20%20stakeholder%20presentation%20-%20FINAL.PDF. World Health Organization. WHO definition of palliative care, 2016. URL: http://www.who.int/cancer/palliative/definition/en/. Department of Justice. Part IV – End-of-life care in Canada. Consultations on physician-assisted dying - Summary of results and key findings, 2015. Government of Canada 2015. URL: http://www.justice.gc.ca/eng/rp-pr/other-autre/pad-amm/p9.html. Gawande A. Letting go: What should medicine do when it can’t save your life? New Yorker 2010. URL: http:// www.newyorker.com/magazine/2010/08/02/letting-go-2. Sumner W. Assisted death: a study in ethics and law. Toronto, ON: Oxford University Press, 2011.

Submitted: July 03, 2016. Revised: July 26, 2016. Accepted: August 07, 2016.

In: Pain Management Yearbook 2017 Editor: Joav Merrick

ISBN: 978-1-53613-693-7 © 2018 Nova Science Publishers, Inc.

Chapter 3

THE USE OF VITAMINS, MINERALS, HERBAL SUPPLEMENTS, AND OTHER DIETARY SUPPLEMENTS AS COMPLEMENTARY AND ALTERNATIVE THERAPIES IN CANCER CARE: A LITERATURE REVIEW Nicholas Lao, BMSc(C), Madeleine Lao, BSc(C), Michael Lam, BMSc(C), Arnav Agarwal, MD(C), Edward Chow, MBBS and Blair Henry*, DBioethics Rapid Response Radiotherapy Program, Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada

ABSTRACT Complementary and alternative medicines have become increasingly popular among cancer patients over the past 45 to 55 years. Among the various types of complementary and alternative therapies, vitamins, minerals, and supplements appear to be most commonly used. This literature review aims to identify evidence related to the efficacy and safety of vitamins, minerals, herbal supplements, and any other dietary supplements (VMHD) as complementary and alternative therapies in the treatment of cancer. Methods: A literature search was conducted using Ovid MEDLINE, Embase, and Cochrane Central databases to identify any trials assessing the efficacy and safety of VMHD over the past 5 years. Results: Twenty studies were included in this review. Included studies investigated the use of VMHD as treatments for traditional medicine side effects, or as potential treatments for cancer. Goshajinkigan was reported to significantly reduce peripheral neurotoxicity in two independent studies. However, outcomes for other VHMD therapies were not reported across multiple studies, making comparison of findings challenging. Conclusions: Limited evidence supporting VHMD therapies for disease management and remedying the side-effects of traditional treatments *

Correspondence: Blair Henry, D.Bioethics, The Ethics Centre, Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Toronto ON, Canada. E-mail: [email protected].

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Nicholas Lao, Madeleine Lao, Michael Lam et al. is available from the past five years. Comparisons using recent trial evidence are challenging due to limited cases where multiple studies evaluate the same VHMD therapies for the same outcomes, and quality of evidence is limited by small sample sizes and drawbacks in study design. Future syntheses may benefit from inclusion of other study designs and peer-reviewed literature published prior to the year 2011.

Keywords: complementary, alternative, vitamins, minerals, herbal supplements, dietary supplements

INTRODUCTION The National Center for Complementary and Integrative Health defines an alternative medicine or therapy as “a non-mainstream practice used in place of conventional medicine,” while, a complementary medicine or therapy is defined as “a non-mainstream practice used together with conventional medicine” (1). Typical complementary health approaches among adults in the United States include natural products (herbs, vitamins, minerals, and probiotics), mind and body practices (yoga, chiropractic and osteopathic manipulation, meditation, massage therapy, acupuncture, relaxation techniques, tai chi, healing touch, hypnotherapy, movement therapies and qi gong), and other approaches including traditional Chinese medicine, homeopathy, naturopathy, ayurvedic medicine, and traditional healers (1). Some forms of alternative medicine, such as traditional Chinese medicine, date back over 3,000 years ago. Despite this, it was in the 1960s and 1970s that complementary and alternative medicine (CAM) first rose in visibility and availability (2-4). Since then, the use of CAM for diseases and disorders, including cancer, has increased significantly. A recent systematic review and meta-analysis of articles from 15 countries found the average proportion of cancer patients using CAM in the 1970s and 1980s to be 25% (5). This proportion increased significantly to 49% for investigations completed after the year 2000 (5). Among types of complementary and alternative therapies, vitamins, minerals, and supplements seem to be most commonly used among cancer patients (6, 7). The 2007 National Health Interview Survey conducted in the United States found that among 1,785 respondents, vitamin/mineral supplementation were used by nearly 77% (7). The purpose of this literature review is to discuss the efficacy and safety of vitamins, minerals, herbal supplements, and any other dietary supplements (VMHD) as complementary and alternative therapies in the treatment of cancer.

METHODS A literature search was conducted using Ovid MEDLINE (2011 – August Week 31 2016), Embase (2011 – 2016 Week 31) and Cochrane Central (2011 – 2016 Week 31) databases. Search terms included: “vitamins,” “minerals,” “supplements,” “herbs,” “cancer or neoplasm,” “integrative therapy,” “alternative therapy” and “complementary therapy.”

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Eligibility criteria Articles were considered eligible if they: a) involved an experimental study design; b) involved a cancer patient population; and c) evaluated the effectiveness of orally-ingested VMHD therapies on cancer symptom outcomes. Other study designs, studies examining other patient populations, and studies evaluating VMHD therapies administered through other routes were excluded.

Selection process, data abstraction and analysis Titles and abstracts from the literature search were screened for eligibility by a single reviewer. Potentially eligible titles and abstracts were retrieved as full-text articles and screened using the same a priori eligibility criteria by the reviewer. Data extraction was subsequently completed by the reviewer for studies deemed eligible for inclusion, and checked for accuracy by a second reviewer, with discrepancies resolved via discussion. Results were subsequently summarized qualitatively.

RESULTS One hundred and eighteen articles were identified by the literature search using the three electronic databases. Following the removal of duplicates, titles and abstract screening yielded 40 potentially eligible hits, of which 20 were finally deemed eligible following fulltext review (see Figure 1). Of the 20 eligible studies, 15 evaluated herbal supplements (8-22), 4 evaluated dietary supplements (23-26), 2 evaluated vitamins (8, 27), and two evaluated minerals (in combination with herbal supplements) (13, 14) (see Table 1). Four enrolled patients from the United States of America (9, 10, 18, 23), 4 from Japan (8, 17, 20, 21), 3 from Iran (24-26), 2 from China (15, 22), 2 from Taiwan (12, 16) 1 from Egypt (14), 1 from Germany (27), 1 from India (13), 1 from Israel (19), and 1 from Malaysia (11).

Therapies treating side-effects Two independent studies investigated the efficacy of Goshajinkigan (GJG), a traditional Japanese medicine, in treating chemotherapy-induced neurotoxicity and found promising results. Abe and colleagues compared GJG with Mecobalamin (vitamin B12) as treatments for peripheral neurotoxicity associated with docetaxel in breast cancer patients (8). It was found that there were significantly fewer incidences of neurotoxicity (p < 0.01) in patients given GJG compared to vitamin B12. In a study by Nishioka and colleagues, colorectal patients received the FOLFOX6 chemotherapy treatment regimen and received GJG or no therapy (17). Those given GJG experienced significantly less grade 3 peripheral neuropathy than those in the control group given placebo (p < 0.01). No significant differences were found between the two treatment arms in number of adverse events or tumor response to the

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FOLFOX regimen (17). Another study by El-Ghiaty and colleagues examined the ability of cystone to reduce cisplatin-induced nephrotoxicity (14). Clearance and serum creatinine was found to be significantly better in those receiving cystone compared to baseline (p < 0.05), indicating some potential protective effects of cystone with regard to nephrotoxicity (14). Rostock and colleagues also investigated the efficacy of vitamin B1/B6 in treating chemotherapy-induced peripheral neuropathy, but found no significant difference across any assessment measures when compared to placebo (27). Records identified through database searching (n = 118 in total); MEDLINE (n = 23), Embase (n = 9), Cochrane Central (n = 86).

Duplicates removed (n = 30) Records after duplicates removed (n = 88)

Records screened using title and abstract (n = 88)

Records screened in full after reading titles and abstracts (n = 40)

Records excluded (n = 48): Articles not related to cancer or vitamins, minerals, herbal supplements or dietary supplements

Full text articles excluded with reasons (n = 20): Only study protocol included (n = 7) Review articles (n = 6) Vitamin, mineral, dietary supplement or herbal supplement was not ingested (n = 2) More than one therapy was given in the treatment arm (n = 2) Retrospective analysis using secondary data (n = 2) Did not assess efficacy of therapy (n = 1)

Studies included in literature review (n = 20)

Figure 1. Identification of studies on vitamins, minerals, herbal supplements or dietary supplements as complementary or alternative therapies used in cancer patients.

Vitamin, minerals and more

19

Other studies have focused on chemotherapy-induced side effects and quality of life (QoL), and have discovered potential benefits for specific outcomes. Deshmukh and colleagues found the use of ayurvedic drugs MPP and MKD significantly increased patient Karnofsky Performance Status (KPS) (p < 0.0001) and decreased Eastern Cooperation Oncology Group (ECOG) scores (p = 0.0022) compared to placebo, when used for 6 months after treatment (13). Ryan and colleagues found significant reduction in average nausea (p = 0.013) and nausea at its worst (p = 0.003) when comparing ginger to control (18). However, no difference in QoL or vomiting symptoms were found (18). Some gastrointestinal adverse events were reported, including grade 2 heartburn, bruising/flushing and rashes (18). Yaal-Hahoshen and colleagues found significantly less severe anemia (p < 0.01), leukopenia (p < 0.03) and neutropenia (p < 0.04) in breast cancer patients treated with botanical compound mixture LCS101 (19). The use of oral Fructus bruceae oil for radiotherapy-induced side effects in esophageal cancer patients was assessed by Shan and colleagues (15). The rate of complete and partial remission was reported to be significantly higher in the treatment arm compared to the control group with no treatment (p < 0.05) (15). A significant improvement in KPS, nausea and vomiting, and radiation esophagitis and pneumonitis was also seen (p < 0.05 for all) (15). In addition to chemotherapy and radiotherapy, three studies investigated the use of herbal supplements on postoperative adverse effects and recovery. Yoshikawa and colleagues investigated the use of daikenchuto on gastrectomy and laparoscopic colectomy side effects and complications (20, 21). For those undergoing gastrectomy who were randomized to receive daikenchuto, the median time until first defecation and incidence of bowel movement disorder was significantly lower (p = 0.05 for both outcomes). No daikenchuto-related serious advese events occurred. For those undergoing laparoscopic colorectal resection who received daikenchuto, a significantly shorter time until first flatus was seen when compared to control (p = 0.02) (20, 21). Zhong and colleagues administered Jianpi Huayu, a mixture of herbal extracts, to patients after hepatectomy (22). Significant differences favoring the treatment arm were seen in length of stay (p = 0.034), postoperative alanine aminotransferase (ALT) levels (p = 0.042), disease recurrence, number of singular recurrent lesions, and disease-free survival and overall survival at 1, 3 and 5 years follow-up (22). Three studies assessed the efficacy of therapies on sleep and fatigue. Cruciani and colleagues found no significant difference between L-carnitine and placebo for the treatment of fatigue (23). Barton and colleagues did not provide data to support the efficacy of Valeriana officinalis on improving sleep, but an exploratory analysis found that use for fatigue may warrant further study (10). Biswal and colleagues found that the treatment arm given herbal supplement Withania somnifera produced significantly lower scores on the Piper’s Fatigue Scale (PFS), Schwartz’s Cancer Fatigue Scale (SCFS-6) and the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 quality of life questionnaire fatigue scale (p < 0.001, p = 0.003 and p < 0.001, respectively) (11). Lastly, Madhavi and colleagues investigated conjugated linoleic acid (CLA) supplementation as a therapy for improving nutritional status, and symptoms of eating problems and dietary intake in patients with rectal cancer (24). In those receiving CLA, a significant decrease was seen in appetite loss, nausea, diarrhea, pain, and significant increase in dietary intake (p5 points) in the RDAS score (15). These findings were further substantiated by latter studies by McLean and colleagues in 2013, where 50% of intervention group caregivers had clinically improved RDAS score, compared to 11% in control group (16). There were no significant changes in the improvement in RDAS score from T1 (immediately post-intervention) to T2 (3 month post-intervention) confers stability of the intervention effect (16) (see Table 1).

Psychological interventions One particular study examined the feasibility and efficacy of a telephone-based dyadic psychosocial intervention. In this, Badr and colleagues highlighted the feasibility of such interventions, and their results showed significant improvements in depression, anxiety and caregiver burden in the intervention group in comparison to usual medical care (17). In measuring the Patient Reported Outcomes Measurement Information System (PROMIS), the intervention group showed a mean decrease of 4.95 points in depression, 5.3 points in anxiety and 2.95 points in caregiver burden domains. For caregivers with high depression levels (n = 23), 2 of the 11 in the control group showed improvement (i.e., their T-score moved from >1SD to 4 years) were more likely to be depressed. Patients with metastases were 2.2 times more likely to be depressed, and patients with moderate or severe cognitive impairment were 3.61 times more likely to have depression, according to the GDS-15. The neuropsychological cluster (sleep problems, depression, and anxiety) was more common in patients under 70 (81% vs 77% for patients >70) and those with GI cancer (79% vs 70% for lung cancer patients). Depression significantly correlated with having a sleep disorder (71% of depressed patients also had a sleep disorder), as well as anxiety, drowsiness, dyspnea, and appetite (Spearman coefficients: 0.7, 0.2, 0.28, 0.25, 0.4).

n = 50 Age: 49.74

MDASI, HADS, FACT-pal, FACIT-sp ESAS

MDASI symptoms, and spiritual well-being

Depression was negatively correlated with spiritual well-being (regression of -0.862).

Gender, age, cancer location, all ESAS symptoms

Cancers of the CNS were most strongly correlated with depression (in a cluster of anxiety, depression, and wellbeing), followed by head/neck, gynecological, hematological, breast, lung, GI, and GU, in the stated order.

Hopelessness, Depression and Social Support with End of Life Turkish Cancer Patients

n = 1366 Age: 64.4

Author, Year (Country) Mako et al. 2009. (USA) (17) Mystakidou et al. 2006. (Greece) (19)

Cheung et al. 2011. (Canada) (6)

Hagelin et al. 2009. (Sweden) (16)

Article Title Spiritual pain among patients with advanced cancer in palliative care Psychological distress of patients with advanced cancer: influence and contribution of pain severity and pain interference Age and gender differences in symptom intensity and symptom clusters among patients with metastatic cancer Patterns of fatigue related to advanced disease and radiotherapy in patients with cancer—a comparative crosssectional study of fatigue intensity and characteristics

Sample Size & Mean Age n = 57 Age: 66.5

Test Used

Type of Factor

Significant Findings

Custom

Religiosity, spirituality, pain

n = 120 Age: 61.4

BPI, HADS

All categorical variables, age, mood, pain, sleep

Depression was significantly positively correlated with spiritual pain (regression of 0.43) and its intensity (regression of 0.5). Old age (regression of 0.205) and being female (HADS = 9.31 vs 7.21 for males) were positively correlated with more depressive symptoms.

n = 1358 Age: 64

ESAS

Age, gender

No significant difference was found in depressive scores across age or gender.

n = 228 CR-10. MFIFatigue, type of Depression was positively correlated with higher fatigue (PC patients), 20, HADS cancer in palliative care (HADS scores: mild = 6.5, n = 82 moderate = 5.7, and strong fatigue = 9.9) and in (outpatient radiotherapy (HADS scores: mild = 3.2, moderate = 4.3, radiotherapy strong fatigue = 7.7. In the radiotherapy clinic, lymph clinic patients) cancer (HADS = 8.3), followed by gynecologic cancer Age: 59 (HADS = 6.8), and urological cancer (HADS = 1.0). * Categorical variables: family status, gender, education, status, surgery, metastasis, chemotherapy, radiotherapy, opioids, and cancer location.

Table 2. Summary of findings regarding prevalence of depression between patients in palliative care and other care settings Author, Year (Country) Delgado-Guay et al. 2016. (USA) (22) Nipp et al. 2016. (USA) (8)

Article Title Characteristics and outcomes of patients with advanced cancer evaluated by a palliative care team at an emergency center. A retrospective study Age and gender moderate the impact of early palliative care in metastatic non-small cell lung cancer

Sample Size & Mean Age In-patients (IP): n = 200 Emergency care (EC): n = 200 Age: 56 n = 47 Age < 65 N = 60 Age > 65

Test Used ESAS

MSAS, PPS, HADS, EORTC QLC-C30 HADS, BHS, SAHD, FSSQ

Home care vs IP care

PHQ-9

Early palliative care vs standard care

CR-10. MFI20, HADS

Palliative care vs outpatient radiotherapy clinic

Peters et al. 2006. (Australia) (24)

Quality of life of cancer patients receiving inpatient and home-based palliative care

IP: n = 32 Home-care: n = 26 Age: 67

Kolva, et al. 2011. (USA) (23)

Anxiety in terminally ill cancer patients

Palliative care: n = 103 Life-prolonging care: n = 91 Age: 62.4

Pirl et al. 2012. (USA) (25)

Depression and survival in metastatic non– small-cell lung cancer: effects of early palliative care

Hagelin et al. 2009. (Sweden) (16)

Patterns of fatigue related to advanced disease and radiotherapy in patients with cancer—a comparative cross-sectional study of fatigue intensity and characteristics

Early palliative care: n = 77 Standard care: n = 74 Age: 64.4 Palliative care: n = 228 Outpatient radiotherapy clinic: n = 82

FACT-L, HADS, PHQ-9

Comparison Used EC patients versus IP receiving palliative care Palliative care vs standard care

Palliative care vs lifeprolonging care

Significant Findings 26% of EC patients compared to 20% of inpatients received antipsychotics (not significant). Young palliative care patients had significantly lower rates of depressive symptoms than young standard care patients (HADS = 4% vs 52.4%, PHQ-9 = 0% vs 28.6%). Male palliative care patients had significantly lower rates of depression than male standard care patients (HADS = 18.5% vs 60.9%, PHQ-9 = 3.8% vs 34.8%). IPs were significantly more likely to be depressed (HADS = 10.03 vs 6.69 for home care patients). Patients in palliative care on average had more severe depressive symptoms (elevated depression: palliative care = 21.4%, life-prolonging care = 4.4%; depression and anxiety: palliative care = 2%, life-prolonging care = 9.9%). Early palliative care patients had better improvements on average than those in standard care (42.9% vs 0%). Palliative care patients were much more likely to have more severe depressive symptoms than patients in the outpatient radiotherapy clinic (HADS: palliative care = 7.8. radiotherapy = 4.8).

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The differences in rates or severity of depression between different demographic factors were discussed in 10 out of the 19 studies in this review (6-8, 10, 12, 13, 18-21). Five of these studies found no significant correlation between depression and any demographic factors (6, 7, 10, 18, 20). With respect to age, 2 articles determined that younger patients were more likely to be depressed or have more severe depressive symptoms (19, 21) while two others determined the exact opposite (8, 13). The articles were less split on gender, with two articles concluding that females were more likely to be depressed (19, 21) and only one finding that males were more likely to be depressed (8). One study did not find any differences between age or gender groups, but did find that both married and/or Hispanic patients were less likely to experience depressive symptoms (12) (see Table 1). From the search, eight studies were found that did not discuss demographics or initial cancer site as factors of depression in advanced cancer patients, but did discuss other factors and correlates. Three studies concluded that patients in better spiritual health were less likely to be depressed or had less severe depressive symptoms (14, 15, 17). The presence of metastases were shown by two studies to be strongly correlated with depression (7, 20). One of these two studies also found that patients with cognitive impairment were also more likely to have depression (7), while the other found that patients in their first year of illness were more likely to be depressed (20). The only study to discuss the issue of patient control determined that patients with a lower perceived control over the cause of their illness and/or a higher perceived control of the course of illness generally had more severe depressive symptoms (18). In addition to these findings, it was also found that depression significantly correlated with having a sleep disorder (11) and strong fatigue (16) (see Table 1).

Palliative care versus other care settings The other focus of this review was to examine the literature concerning the differences in depression rates between patients in palliative care and other care settings. Six articles were identified that discussed this difference (16, 8, 22-25). There was no consensus found on which care setting proved to be more beneficial in preventing or helping alleviate depressive symptoms based on these studies. Three studies concluded that patients in palliative care were significantly more likely to be depressed than their standard care counterparts (16, 23, 24). The other 2 studies found the opposite result, with palliative care patients showing a greater improvement in depressive symptoms than patients in non-palliative settings (8, 25). One of these studies did not find any significant difference in rates of depression in advanced cancer patients between care settings (22) (see Table 2).

DISCUSSION The purpose of this scoping review was to examine the current literature on depression in palliative cancer patients, with the goal of identifying any factors contributing to depression including any differences between depression rates of cancer patients based on care setting.

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This is a relevant issue, as major depressive disorder has been identified as the single most frequent problem in palliative care cancer patients (1). Therefore, by investigating any possible factors that may cause or correlate to depression, it may be possible to develop strategies improve patient quality of life. Multiples articles included in this study discussed the relationship between the initial cancer site in the palliative care patient and depression; however, there was little consensus found on this topic by this review. GI cancer was determined to be most strongly correlated to depression by two studies (13, 21), while blood/lymph cancer and cancers of the CNS were concluded to be the most by one study each (10, 16). Other research has shown that among general cancer patients, not just those in palliative care, stomach, pancreas, head/neck and lung cancers seem to be the most strongly correlated with depression (26). These findings appear to demonstrate that depression may be associated with cancers that have a more guarded prognosis (26). This idea also carries over into the findings of this review, in which it was found that patients with metastases were more likely to be depressed than patients without (7, 20), as the presence of metastases are a clear indicator of a poor prognosis (27). This may also be true for palliative cancer patients who have been ill for less than a year, as the disease may have moved quickly and therefore may be linked to a poor prognosis (20). With the exception of one study (11), the consensus seems to be that female palliative cancer patients are more likely to experience depressive symptoms than their male counterparts (19, 21). These findings regarding gender and depression are consistent with studies of elderly populations. A 2012 systematic review showed that women are far more likely to have a depressive disorder than men (28). The same review is also in line with this scoping review’s findings on cognitive impairment. Both in the healthy elderly and in palliative care cancer patients, cognitive impairment positively correlated with increased depressive symptoms (7). The findings of this review found conflicting evidence regarding the correlation between age and depression, with some studies concluding younger patients were more likely to be depressed (19, 21) and others reporting that older patients were more likely to be depressed (8, 13) in this advanced cancer patient population. This is an interesting finding, as a large, 60,000 person Norwegian study of the general population found that after controlling for multiple variables, there is a strong positive relationship between age and depression (29). Further research should be conducted in this area in order to reach a more definitive conclusion about how age influences the rates/severity of depression. One study in this review determined that ethnicity could influence rates of depression in palliative care cancer patients, stating that Hispanics were less likely to be depressed than other races (12). This same study also concluded that patients who were married were also less likely to be depressed than unmarried or divorced patients. These results are similar to other reported studies, including a large-scale American study that found both Hispanics and married people are indeed less likely to be depressed than Caucasian people and unmarried/divorced people respectively in a general population (30). The specific differences in ethnicity and the emotionally stabilizing aspects of marriage in palliative cancer patients would be worth exploring in future studies. Several studies included in this review discussed what effect spiritual well-being has on the mental health in palliative cancer care patients. They all concluded that depression is strongly correlated with spiritual distress in palliative cancer care (14, 15, 17). These results are in tune with studies of the general population, which have shown that those with a

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stronger spiritual background are less likely to have depressive symptoms (31). Specifically, a belief in a higher power and the power of prayer were most strongly associated with fewer depressive symptoms in the general population (31). In this review, it was found that both fatigue (16) and cognitive impairment (7) were positively correlated with depressive symptoms in palliative care cancer patients. This seems to be true for populations of patients with other illnesses as well. A study on how fatigue and depression are related in a population of multiple sclerosis patients determined that even after controlling for other variables, depression and fatigue were strongly associated with each other (32). A limitation of these studies and this review itself is that fatigue is difficult to define as a cause or symptom of depression, as it can be present both before and after a diagnosis. Therefore, only a correlation, not a causation, may be concluded. This may also be true for patients with a sleep disorder, as it could also be a cause or a symptom of the sleep disorder. This review as well as a study of the general population both determined that having a sleep disorder was positively correlated with being depressed (11, 33), neither determined whether the presence of a sleep disorder was a cause or a symptom of depression. Further research into this relationship may be beneficial to preventing and/or treating both disorders. The second major focus of this review was to discover what differences existed in rates of depression between palliative cancer care patients and cancer patients in other settings. From the literature search, it was found that 3 studies concluded that patients in palliative care were significantly more likely to be depressed than their standard care counterparts (16, 23, 24), while 2 found that patients in palliative care were more likely to be depressed than patients in other settings (8, 25). This lack of consensus on the subject is in line with another review discussing a similar scenario. It concludes that there is no significant difference between rates of depression in palliative cancer care patients, oncological patients, and hematological patients (4). Several factors could explain either result. The lack of control and greater sense of mortality possibly experienced by palliative care patients compared to patients living at home could explain why palliative care patients are more depressed (24). This is also seen in this review, in which one study found that a lower perceived control over the course of the illness is correlated strongly with depression in palliative care cancer patients (18). However, the finding that palliative patients on average are more accepting of their impending death than patients in other care settings may explain how palliative cancer patients experience fewer depressive symptoms (24). Further research into this area might be useful in creating guidelines on how to reduce the risk of depression in either setting. It is important to consider the findings of our scoping review with some limitations in mind. The use of several different assessment tools, many of them self–reported, to measure the severity of depressive symptoms in these patients makes generalizability of results between studies challenging. In a similar vein, self-reporting assessments can be more varied than a test performed by an independent professional third party due to personal bias (34). In addition to the limitations described above, we were unable to analyze certain correlates to/or factors of depression in significant depth. While this review is able to give a broad overview of the factors and correlates of depression, the broad range of topics addressed precluded detailed analysis of any specific correlate/factor.

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CONCLUSION Depression is a major concern for the quality of life of palliative care cancer patients and can possibly predict poor survival (5). Based on this review, having a worse prognosis, poor spiritual health, metastases, cognitive impairment, less control over the course of the illness, fatigue, sleep disorders, a longer illness and being female are positively correlated with having depression. The effects of age and the care setting are not as clear, with conflicting conclusions existing in the literature. It would be interesting to see future research conducted on how the physical and emotional stresses of cancer affects the rates/severity of depression, especially since the factors leading to depression in palliative cancer patients and the general population are generally the same. Further research should conduct in-depth analysis of these factors individually, which may be helpful in determining how to mitigate their effects if they are substantial and prevent depression in these patients. This may help facilities develop strategies to improve the quality of life for palliative patients with advanced cancer.

CONFLICT OF INTEREST The authors have no relevant conflicts of interest to disclose.

ACKNOWLEDGMENTS We thank the generous support of Bratty Family Fund, Michael and Karyn Goldstein Cancer Research Fund, Joey and Mary Furfari Cancer Research Fund, Pulenzas Cancer Research Fund, Joseph and Silvana Melara Cancer Research Fund, and Ofelia Cancer Research Fund.

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Nipp RD, Greer JA, El-Jawahri A, Traeger L, Gallagher ER, Park ER, et al. Age and gender moderate the impact of early palliative care in metastatic non-small cell lung cancer. Oncologist 2016;21(1):119–26. Visser MR, Smets EM. Fatigue, depression and quality of life in cancer patients: how are they related? Support Care Cancer 1998;6(2):101-8. Cheung WY, Le LW, Zimmerman C. Symptom clusters in patients with advanced cancers. Support Care Cancer 2009;17(9):1223-30. Delgado-Guay M, Yennurajalingam S, Parsons H, Palmer JL, Bruera, E. Association between selfreported sleep disturbance and other symptoms in patients with advanced cancer. J Pain Symptom Manage 2011; 41(5):819-27. Hui D, dos Santos R, Chisholm GB, Bruera E. Symptom expression in the last seven days of life among cancer patients admitted to acute palliative care units. J Pain Symptom Manage 2015;50(4):488-94. Jiménez A, Madero R, Alonso A, Martinez-Marin V, Vilches Y, Martinez B, et al. Symptom clusters in advanced cancer. J Pain Symptom Manage 2011; 42(1):24-31. Kandasamy A, Chaturvedi SK, Desai G. Spirituality, distress, depression, anxiety, and quality of life in patients with advanced cancer. Indian J Cancer 2011;48(1):55-9. Lee YP, Wu CH, Chiu TY, Chen CY, Morita T, Hung SH, et al. The relationship between pain management and psychospiritual distress in patients with advanced cancer following admission to a palliative care unit. BMC Palliat Care 2015;14:69. Lundh Hagelin C, Wengström Y, Fürst CJ. Patterns of fatigue related to advanced disease and radiotherapy in patients with cancer-a comparative cross-sectional study of fatigue intensity and characteristics. Support Care Cancer 2009;17(5):519-26. Mako C, Galek K, Poppito SR. Spiritual pain among patients with advanced cancer in palliative care. J Palliat Med 2006;9(5):1106-13. Mystakidou K, Tsilika E, Parpa E, Galanos A. The influence of sense of control and cognitive functioning in older cancer patients’ depression. Psychooncology 2015;24(3):311-7. Mystakidou K, Tsilika E, Parpa E, Katsouda E, Galanos A, Vlahos L. Psychological distress of patients with advanced cancer: influence and contribution of pain severity and pain interference. Cancer Nurs 2006; 29(5):400-5. Sahin ZA, Tan M, Polat, H. Hopelessness, depression and social support with end of life Turkish cancer patients. Asian Pac J Cancer Prev 2013;14(5):2823-8. Tai SY, Lee CY, Wu CY, Hsieh HY, Huang JJ, Huang CT, et al. Symptom severity of patients with advanced cancer in palliative care unit: longitudinal assessments of symptoms improvement. BMC Palliat Care 2016; 15:32. Delgado-Guay MO, Rodriguez-Nunez A, Shin SH, Chrisholm G, Williams J, Frisbee-Hume S, et al. Characteristics and outcomes of patients with advanced cancer evaluated by a palliative care team at an emergency canter. A retrospective study. Support Care Cancer 2016;24(5):2287-95. Kolva E, Rosenfeld B, Pessin H, Breitbart W, Brescia R. Anxiety in terminally ill cancer patients. J Pain Symptom Manage 2011;42(5):691-701. Peters L, Sellick K. Quality of life of cancer patients receiving inpatient and home-based palliative care. J Adv Nurs 2006;53(5):524-33. Pirl WF, Greer JA, Traeger L, Jackson V, Lennes IT, Gallagher ER, et al. Depression and survival in metastatic non–small-cell lung cancer: effects of early palliative care. J Clin Oncol 2012;30(12): 1310-15. Brintzenhofe-Szoc KM, Levin TT, Li Y, Kissane DW, Zabora JR. Mixed anxiety/depression symptoms in a large cancer cohort: prevalence by cancer type. Psychosomatics 2009;50(4):383-91. Yamashita H, Noguchi S, Murakami N, Kawamoto H, Watanabe S. Extracapsular invasion of lymph node metastasis is an indicator of distant metastasis and poor prognosis in patients with thyroid papillary carcinoma. Cancer 1997;80(12):2268-72. Luppa M, Sikorski C, Luck T, Ehreke L, Konnopka A, Wiese B, et al. Age-and gender-specific prevalence of depression in latest-life-systematic review and meta-analysis. J Affect Disord 2012;136:212-21.

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Michael Puopolo, Eva Bain, Arnav Agarwal et al. Stordal E, Mykletun A, Dahl AA. The association between age and depression in the general population: a multivariate examination. Acta Psychiatr Scand 2003; 107(2):132-41. Strine TW, Mokdad AH, Balluz LS, Gonzalez O, Crider R, Berry JT, et al. Depression and anxiety in the United States: findings from the 2006 Behavioral Risk Factor Surveillance System. Psychiatr Serv 2008;59(12):1383-90. Doolittle BR, Farrell M. The association between spirituality and depression in an urban clinic. Prim Care Companion J Clin Psychiatry 2004;6(3):114-8. Bakshi R, Shaikh ZA, Miletich RS, Czarnecki D, Dmochowski J, Henschel K, et al. Fatigue in multiple sclerosis and its relationship to depression and neurologic disability. Mult Scler 2000;6(3):181-5. Vandeputte M, de Weerd A. Sleep disorders and depressive feelings: a global survey with the Beck depression scale. Sleep Med 2003;4(4):343-5. Prince SA, Adamo KB, Hamel ME, Hardt J, Connor Gorber S, et al. A comparison of direct versus self-report measures for assessing physical activity in adults: a systematic review. Int J Behav Nutr Phys Act 2008;5:56.

Submitted: July 03, 2016. Revised: July 27, 2016. Accepted: August 11, 2016.

In: Pain Management Yearbook 2017 Editor: Joav Merrick

ISBN: 978-1-53613-693-7 © 2018 Nova Science Publishers, Inc.

Chapter 10

A REVIEW ON THE IMPACT OF “DO-NOT-RESUSCITATE” ORDERS ON MORTALITY AND QUALITY OF CARE Bo Angela Wan, MPhil, Collier Jiang, MD(C), Arnav Agarwal, MD(C), Michael Lam, BMSc(C), Edward Chow, MBBS and Blair Henry*, DBioethics Rapid Response Radiotherapy Program, Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada

ABSTRACT Do-not-resuscitate (DNR) orders inform staff to forgo resuscitation attempts in situations where cardiopulmonary resuscitation is unlikely to result in prolonging life or when patients have specifically requested it be withheld. As would be expected, the mortality rates for patients with DNR status is significantly higher than those without; however this may be due, in part, to differences in interpretations of goals of care beyond the mere provision of cardiopulmonary resuscitation when the heart stops. Objective: The objective of this scoping review is to summarize published studies that compare DNR status with regards to differences in mortality, non-resuscitative outcomes, and aspects of care. Methods: A literature search of MEDLINE, Embase, and CCTR databases was conducted to identify studies that compared mortality rates of patients with DNR status and patients with full code. Title and abstract screening and full-text screening was conducted to identify eligible studies, and data for relevant outcomes was extracted and compared across studies; both screening and data extraction were completed by paired reviewers. Results: Sixteen eligible studies were identified. All 16 studies reported a higher proportion of mortality in patients who had a DNR order, ranging from an increase of 7.3% to 72.1%. Ten studies included multivariate analysis, showing significant associations between DNR status and mortality, with odds ratios ranging from 2.07 to *

Correspondence: Blair Henry, D. Bioethics, The Ethics Centre, Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Toronto ON, Canada. E-mail: [email protected].

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Bo Angela Wan, Collier Jiang, Arnav Agarwal et al. 9.2. Eight out of 13 studies generally associated DNR status with worse non-mortality outcomes and lower quality of care. Conclusions: DNR status is associated with greater mortality across a wide variety of procedures and hospital settings. Differences in the treatment of patients with DNR status in areas beyond resuscitation may contribute to lower survival.

Keywords: DNR, do-not-resuscitate, mortality, survival, outcomes

INTRODUCTION Literature related to what has become known as the “do not resuscitate” (DNR) order was noted as early as 1976 and has since been the subject of much debate and controversy (1). Some have rightly noted that “few initials in medicine today evoke as much symbolism or controversy as the do-not-resuscitate (DNR) order” (1). Outside the hospital, cardiopulmonary resuscitation (CPR) has, and is still considered a public good, in that when a person is found in pulmonary and or cardiac arrest, a stranger is expected to initiate CPR, without consent. This societal allowance is predicated on the high value given to life and its preservation, such that CPR is the expected and preferred course of action to be undertaken during emergencies (2). However, in hospital settings, where time and more detailed investigations may be available, a patient's medical status and prognosis may call to question the utility of suggesting a resuscitation attempt. Additionally some patients, approaching the end of life, who may not want invasive attempts to prolong their life may ask or consent to a DNR as an expression of their autonomy. DNR orders are typically present in approximately 18-28% of hospitalized patients, a proportion that is generally increased in the elderly and in those with severe disease (1, 3). One of the concerns related to the DNR has been a lack of clarity and common understanding of what is or is not expected to be withheld or even provided during a medical crisis. DNR orders may constitute withholding interventions that range from chest compressions, defibrillation, artificial ventilation, cardiac medications, and even open chest heart massage (4). For hospitals using American Heart Association’s advanced cardiac life support algorithms, the interpretation of a DNR should mean that all of the above treatments should be considered as an integrated care package, wherein all interventions are withheld if CPR is to be withheld (5). In addition to a lack of clarity on what DNR actually means, it has also been suggested that the mere presence of a DNR order on a patient’s chart will affect the type of care being offered even beyond the provision of resuscitation. DNR status has been found to be an independent predictor of mortality (6). DNR status is associated with higher levels of comorbidities, more severe disease, and old age, suggesting that DNR status may serve as a surrogate indicator of overall health status. Patients with DNR status may justifiably have different attitudes towards receiving treatment, and prefer less invasive and less aggressive care given their overall health status. Unfortunately, it has been noted that DNR status itself is not always a reflection of the patient’s preferences in this aspect. In such cases, a patient’s DNR status may affect mortality because of unequal treatment by healthcare providers, leading to less intense treatments being offered (7).

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The objective of this scoping review is to explore how resuscitative status may impact mortality rates, and to draw a comparison across differences in treatment, quality of care and other non-mortality outcomes as a result of having a DNR order on a patient chart.

METHODS A systematic literature search limited to English-language publications was conducted in Ovid MEDLINE, Ovid EMBASE and CCTR databases, as of July 2016. We used the terms “DNR,” “do not resuscitate,” “no code,” “end of life,” “do not resuscitate order,” “DNR order,” “NTBR,” “not to be resuscitated,” “NFR,” “not for resuscitation,” “DNACPR,” “do not attempt CPR,” “no CPR,” “AND,” “allow natural death” combined with “outcome,” “survival,” and “epidemiology.” One member of the team (BW) manually removed duplicates and conference abstracts and limited studies to the last 10 years (2006 onwards). Two members of the team (BW, CJ) screened identified title and abstracts, and subsequently screened the full-texts of potentially eligible articles, based on the following inclusion criteria: (1) observational study design; (2) including patients with DNR status; and (3) comparing mortality rates between patients with DNR status and those without. Clinical trials and studies in paediatric patient populations were excluded. Discrepancies in screening were resolved by discussion or by a third adjudicator if necessary. For all included studies, the following information was extracted: study design, setting (including whether it was a single or multiple hospital, database source, and location), patient characteristics, years through which data was obtained, definition of DNR and time point it was evaluated for the study, and outcomes assessed. In addition, for each measurement of mortality, the number of patients with DNR status and without DNR status, with the associated mortality and statistical significance was recorded. Results of multivariate analyses with adjusted factors were also extracted if available, and displayed as odds ratio (OR) with a 95% confidence interval and p-value. Furthermore, results of non-mortality factors that reflected the quality of care or health outcomes after hospitalization of patients with and without DNR status was extracted and summarized. Data extraction was conducted by a pair of reviewers (BW, CJ), with discrepancies resolved by discussion with a third adjudicator involved if necessary.

RESULTS The literature search returned a total of 2,545 results (885 results from Ovid MEDLINE, 1375 results from Ovid Embase, and 285 results from CCTR). Following removal of 317 duplicates and 48 conference abstracts, 1,283 unique titles and abstracts were screened, identifying 20 potentially hits. Eighteen of 20 full-text articles were retrievable, of which two were excluded, one comparing differences in mortality for patients with and without DNR orders across different hospitals without providing patient sample size, and the second comparing mortality of medical-emergency-team-implemented DNR (MET-DNR) and non-MET DNR only. A total of 16 studies were finally deemed eligible for inclusion (6, 8–22) (see Figure 1).

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Bo Angela Wan, Collier Jiang, Arnav Agarwal et al.

Figure 1. Literature Search Results.

The 16 studies comprised a total of 23,710 patients with DNR status and 138943 patients without (6, 8–22). This included the study by Fernandez and colleagues, which evaluated the related concept of DNI rather than DNR (21). All studies were retrospective, using patient data collected between 1995 and 2013 (6, 8–22). Eleven studies were conducted across multiple hospitals (6 8–12, 16, 18–20, 22). Five studies were conducted in a single hospital setting (13–15, 17, 21). The most common reason for hospitalization was surgery (five studies) (6, 8, 12, 18, 19); other reasons include trauma (single study) (10), heart failure (two studies) (11, 20), out-of-hospital cardiac arrest (single study) (16), pneumonia (single study) (13), sepsis (single study) (15), stroke (single study) (22), intracerebral hemorrhage (two studies) (14, 17), traumatic brain injury (single study) (9), and non-invasive ventilation (single study) (21) (see Table 1). The study’s interpretation of the term “DNR” was included if explicitly stated in text. Differences in the definition of DNR order varied across studies, from withholding CPR only to withholding ventilation and cardio-active drugs as well. Moreover, studied assessed DNR status at different time points during hospitalization in order to generate the cohorts for comparison. This varied from assessing DNR at admission, to 24 hours, 48 hours, or 72 hours within admission, or within 30 days of surgery (see Table 1).

Do-not-resuscitate

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Comparing mortalities based on resuscitative status In all studies, mortality was greater in the DNR cohort, with significance reported to be p < 0.001 in all but one study by Dean and colleagues, for which significance was not reported (9). The greatest percentage difference between patients with DNR status and patients without was in 30-day mortality in patients with intracerebral haemorrhage (72.1%) (14). On the other hand, Saager and colleagues reported the smallest percentage difference (7.3%) for in-hospital mortality from major surgical procedures (19) (see Table 2). Measurements of mortality ranged in time periods from in-hospital (11 studies) (9–16, 19–21), 30-day (8 studies) (6, 8, 11, 13, 17, 18, 22), 60-day (single study) (15), 3-month (single study) (14), and 1 year (single study) (14), with six studies assessing multiple timeframes (11, 13–15, 20, 21). McAlister and colleagues independently assessed admission DNR and later DNR, reporting that later DNR is associated with higher mortality (11) (see Table 2). Nine studies contained a multivariate model of mortality, with odds ratios (OR) ranging from 2.07 for 30-day mortality following surgery to 9.2 for 6-month mortality following noninvasive ventilation, all indicating that DNR orders are significantly associated with greater mortality (6, 8, 10–12, 15, 17, 18, 21). Five of these studies propensity-matched DNR status patients with full code status patients (6, 10, 12, 18, 19) (see Table 2).

Comparing other hospitalization-related factors based on resuscitative status Differences in likelihood of being offered additional surgical interventions, secondary outcomes, complications, resource utilization, and length of stay were also examined between patients with DNR status versus patients without. Three out of five studies associated DNR status with complications (8, 12, 18), while two found similar complication rates among patients with and without DNR status (6, 19). The components of quality of care varied according to the patient population of the study, but contained factors that were relevant for the reason of hospitalization. Five studies assessed for differences in quality of care between patients with and without DNR status (11, 14, 15, 20, 22). Three studies found that patients with DNR status generally received less active care such as being less likely to be discharged with home support, less likely to be prescribed medications, less likely to have prophylactic treatments, and less likely to receive counselling or evaluations (11, 14, 20). Two found similar treatments between the two groups in terms of receiving invasive therapy or being discharged to a skilled nursing facility, or variable treatment depending on the specific aspect of care – for instance, patients with DNR status were less likely to be cared for by a stroke team, but were moved around less frequently (15, 22). The 2 studies that assessed interventions being offered both found that they were less likely to be given to patients with DNR status (9, 16). Three out of 4 studies also showed that patients with DNR status had longer length of hospitalization (11, 13, 14, 18). Overall, eight out of 13 studies showed that DNR status is generally associated with poor quality of care and increase the likelihood of complications (8, 9, 11, 12, 14, 16, 18, 23) (see Table 3).

Table 1. Characteristics of included studies Study

Study Design

Setting

Patient Characteristics

Years

DNR Functional Definition

Jawa et al. 2015 (10) Aziz et al. 2015 (8)

Retrospective

Trauma,