Issue 34

DECEMBER 2018 | ISSUE 34

“IT’S A METAPHOR” T H E R O L E O F R E L I G I O S I TY I N M E N TA L H E A LT H

NURSES PRESCRIBING A R E V I E W O F S TA K E H O L D E R P E R S P E CT I V E S

FROM PATIENT TO PERSON-CENTERED CARE I N T E RV I E W W I T H D R. M I C H A E L A P KO N, C E O O F S I C K K I D S H O S P I TA L

WWW.MEDUCATOR.ORG

1

M E D U CATO R

|

D E C E M B E R 2018

table of contents

Welcome to Issue 34 of The Meducator! The field of health sciences is subject to cycles of iterative renewal. Discovery does not occur through isolated strokes of genius; rather, we build upon past knowledge to tell a story of health and disease. This idea is exemplified by Ruby Zheng’s cover design. The raven represents both death and wisdom. In this instance, the avian specimen —nameless, opened-up, and pinned— imparts knowledge on those who have the privilege of learning from its intricate anatomy. We hope you will explore this issue with a mindset of gratitude to all the people and animals that have advanced the literature from a cellular to a population level —elevating societal health and wellbeing.

The articles of Issue 34 celebrate exciting student-driven innovations, initiatives, and evidence explorations. Hanzhuang Zhu advances our methodological understanding of early-life research studies through a qualitative investigation of infant recruitment in non-invasive experiments.

Medical student and McMaster University alumnus Paul Lee illuminates the intersectional role of religiosity on mental health and wellbeing. Arbaaz Patel examines the frightening evidence-based progression of bacterial antibiotic resistance and extends a call to arms for preventive care. Lastly, Dr. Mike Apkon, President and CEO of SickKids hospital in Toronto, reflects on what it means to be an effective leader in an interview conducted by student contributor Romi Lifshitz.

In this issue, we are delighted to introduce an undergraduate nursing section of The Meducator in partnership with the McMaster School of Nursing. These articles, which highlight the complexities of social and human dimensions in patient-centered healthcare, complement the biomedical dimension of The Meducator. Janet Hélène kicks off our inaugural nursing section with an investigation into the historical and present-day role of nurses in healthcare.

Daniel Kim examines the impact of the recent proposal to allow nurses to prescribe medications in Ontario. In our new Case Report article format, Wendy Fu —inspired by a first-hand patient care experience— re-evaluates the use of restraints on uncooperative patients.

Sincerely,

M E D U CATO R

Advancements and improvements in the health sciences require collaboration between research teams, healthcare providers, policymakers, and the patients they aim to benefit. Similarly, this issue of The Meducator showcases the work of many. In particular, we would like to extend a special thank you to members of our executive team which includes Kevin, Sheila, Matilda, Bob, Adrian, Edward, Parnika, and Daniel; we are immensely grateful for your dedication and passion for building communities within The Meducator. Most importantly, we would like to thank you, our reader.

There is much to be explored. Let your wings take flight.

introduction

INTRODUCTION ISSUE 34

dear reader,

|

OWEN DAN LUO

D E C E M B E R 2018

EVA LIU

Bachelor of Health Sciences (Honours) Class of 2020

Bachelor of Health Sciences (Honours) Class of 2019

2

ELIMINATION OF TB

New York, September 2018 Political leaders and tuberculosis (TB) experts met for the first UN High-Level Meeting on TB to reaffirm declarations to diagnose and treat 40 million people by 2022, and provide 30 million with preventative treatment. The aim is to end TB globally by 2030. However, with fewer than 20 heads of state present, and a funding gap of $3.5 billion per year, it remains to be seen whether the declarations will be actualized.1

BAN OF CHLORPYRIFOS United States, August 2018

The U.S. Environmental Protection Agency was ordered by the Court of Appeals to "revoke allowable limits" of chlorpyrifos, a harmful pesticide linked to neurological disorders in children.

Chlorpyrifos was identified as a human health risk in 2015 due to its actions in inhibiting acetylcholinesterase, an enzyme essential for neurological signaling pathways. In light of the recent court order, lobbyists are hopeful for a full ban on the use of this harmful insecticide in the very near future.2

WRITTEN BY

MATTHEW LYNN & JAMES YU

ARTIST ANQI WU

LASSA FEVER CRISIS Nigeria, April 2018

Lassa fever is a viral hemorrhagic fever that has seen 413 confirmed cases in the first quarter of 2018, resulting in 114 deaths in 21 West African states. A national Emergency Operations Center was activated by the Nigeria Center for Disease Control to coordinate preventative efforts with the World Health Organization. Although the incidence of Lassa fever has declined, the infection of 27 health workers with the virus highlights the need to strengthen control practices in emergency health care settings.3

TEENAGE DRINKING England, September 2018

The World Health Organization reports that youth consumption of alcohol has decreased across Europe, with the largest decline in England. Nearly 10% of deaths in Europe are attributed to alcohol. The proportion of teenage boys in England who drank weekly dropped from 50% in 2002 to just 10% in 2014.

Putative reasons for this drop include changes in cultural norms, household income, and preventative approaches.4

GLOBAL WARMING

South Korea, October 2018 The Intergovernmental Panel on Climate Change reports that limiting the average global temperature increase to 1.5°C would require carbon dioxide emissions to fall by 45% by 2030 and reach net zero by 2050. While reaching this goal will be difficult, keeping global warming at 1.5°C instead of 2°C would save $38.5 trillion in associated damages by the end of the century.5

ROTAVIRUS VACCINE India, January 2018

CHOLERA OUTBREAK

Yemen, October 2016 - Current Cholera has plagued Yemen since an outbreak in October 2016, following a war that erupted in March 2015. Damaged health, sanitation, and water infrastructure has led to a lack of clean water for over 14.5 million people, over 1 million cholera cases, and 2 000 deaths —the most in modern history.7

India-based pharmaceutical company, Bharat Biotech, received prequalification from the World Health Organization for its Rotavac vaccine. Rotavac protects against rotavirus, which is the main cause of diarrheal death in children, leading to approximately 80 000 deaths per year in India alone.

Rotavac's low cost of 1 USD per dose allows humanitarian organizations to vaccinate a greater number of people, reducing the incidence of rotavirus, particularly in low-income countries.6

EDITED BY

PARNIKA GODKHINDI & NADIN ABBAS

References can be found at www.meducator.org

MEDBULLETIN PARKINSON’S

GENE REPAIR

ANI TA S HA H

N AD IN AB B AS

Parkinson’s disease (PD) affects 1 in 500 Canadians, a significant statistic considering the severe deterioration in quality of life induced by the disease. 1,2 PD is the result of the progressive death of dopaminergic neurons in the brain, often due to the abnormal aggregation of proteins forming Lewy bodies. 3 These Lewy bodies are formed as a result of multiple protein interactions, primarily α-synuclein, influencing the microenvironment of the cell. 4,5 Ultimately, the affliction leads to impaired control of movement with symptoms including tremors, rigidity, and disrupted balance. 1

β-thalassemia is a recessive blood disorder characterized by a reduction in the synthesis of β-globin which can subsequently give rise to severe anemia. 1 The annual global incidence of individuals symptomatic for a form of β-thalassemia is 1 in 100,000. 1 Presently, the only available treatment focused on increasing β-globin is allogeneic bone marrow transplantation. This therapy, requiring donor stem cells, is heavily limited by the stringent criteria of human leukocyte antigen compatibility. 3

M E D U CATO R

|

D E C E M B E R 2018

medbulletin

TEARS AS A DIAGNOSTIC TOOL FOR PARKINSON’S DISEASE

Although the pathophysiology underlying PD is thoroughly researched, there remains no clinically utilized method of diagnosis beyond mere observation of symptoms as the disease progresses. 1 Findings from a study conducted at the University of Southern California may represent a potential change to this, with researchers identifying tears as a reliable and non-invasive screening tool for PD. 3 To arrive at this conclusion, researchers compared the oligomeric form of α-synuclein in the tear samples of those with and without PD. 4 Their results showed significantly higher levels of α-synuclein in the tears of those with PD when measured against those without the disease. 4 Given that symptoms of PD can be absent for years following the onset of the disease, a biomarker in tears could be useful in making an early diagnosis. However, further research is required to determine the efficacy of this biomarker, primarily in determining its sensitivity and specificity. 5 Such findings would represent a significant advancement in PD management, facilitating advanced coordination of living arrangements and services required for those experiencing symptoms. It would also allow for the employment of practices that delay the onset of symptoms.

1.

2.

3.

4.

5.

6.

7.

5

UCB. Parkinson’s Disease. [Internet]. 2017 [Accessed 2018 Sep 11]. Available from: https://www. ucb-canada.ca/en/Patients/Conditions/Parkinson-s-Disease.

Menon B, Nayar R, Kumar S, Cherkil S, Venkatachalam A, Surendran K et al. Parkinson’s disease, depression, and quality-of-life. Indian J Psychol Med. 2015;37(2):144. Available from: doi:10.4103/02537176.155611.

Paddock C. Could Your Tears Help to Diagnose Parkinson’s?. [Internet]. 2018 [Accessed 2018 Sep 11].

Available from: https://www.medicalnewstoday.com/articles/321015.php.

Spillantini MG, Schmidt ML, Lee VM, Trojanowski JQ, Jakes R, Goedert M. α-Synuclein in Lewy bodies.

Nature. 1997;388(6645):839. Available from: doi:10.1038/42166.

Pollanen MS, Dickson DW, Bergeron C. Pathology and biology of the Lewy body. J Neuropathol Exp Neurol. 1993;52(3):183-91. Available from: doi: 10.1097/00005072-199305000-00001.

Feigenbaum D, Lew M, Janga S, Shah MK, Mack W, Okamoto C, et al. Tear proteins as possible biomarkers for Parkinson’s disease. Neurology. 2018;90(15 S3.006). Available from: http://n.neurology.org/ content/90/15_Supplement/S3.006/tab-article-info [Accessed 2018 Sep 11].

American Association of Neurology. Shedding a Tear May Help Diagnose Parkinson’s Disease. [Internet].

2018 [Accessed 2018 Sep 11]. Available from: https://www.aan.com/PressRoom/Home/PressRelease/1623.

β-THALASSEMIA: A NEW ROAD TO A CURE

Research by Liang and colleagues has led to the development of an alternative approach to treating β-thalassemia. 3 The specific pathogenic variant considered by these scientists is a single nucleotide polymorphism (A>G) at position 28, cited as being one of the three most prevalent mutations causing β-thalassemia in Chinese and Southeast Asian populations. 3 The researchers employed a base editor system, BE3, to repair point mutations in heterozygous embryos. 3 This base editor system allowed for high editing efficiency in correcting the point mutation. The mechanism of this edit was initiated by binding to a target nucleotide C, and catalyzing its deamination and conversion to a U. 4 The resultant U:G mismatch is detected and transformed by cellular DNA repair machinery to a T:A base pair, thereby producing a C>T or G>A substitution in the desired DNA sequence. 4 Of the 48 embryos that underwent base editing, 11 were repaired, of which 8 were restored to the wild-type state with both mutant alleles corrected. 3 While this data illustrates the potential of such technology to repair causative mutations in β-thalassemia and other genetic diseases, future investigation is needed to optimize the precision with which BE3 can be made to repair disease mutations. For instance, the authors note that the specificity of the base editor system must be examined more comprehensively using genomewide specificity assays to profile BE3 off-target effects. 2

1.

2.

3.

4.

Galanello R, Origa R. Beta-thalassemia. Orphanet J Rare Dis. 2010;5(1):11. Available from: doi:10.1186/1750-1172-5-11.

Leukemia Foundation. Allogeneic stem cell transplants [Internet]. 2018 [Accessed 2018 Oct 22]. Available from: https://www.leukaemia.org.au/disease-information/transplants/allogeneic-transplants/ Liang P, Ding C, Huang J, Sun H, Xie X, Xu Y, et al. Correction of β-thalassemia mutant by base editor in human embryos. Protein Cell. 2017; 8(11):1-12. Available from: doi:10.1007/s13238-017-0475-6.

Garibyan L, Avashia N. Research techniques made simple: Polymerase Chain Reaction(PCR). J Invest Dermatol. 2013;133(3):e6. Available from: doi:10.1038/jid.2013.1.

TOURETTE

UNCOVERING THE CONNECTION BETWEEN GENES AND SYMPTOMS

ROSEHIP NEURON DISCOVERING LIMITATIONS IN CURRENT NEUROLOGICAL RESEARCH AAR O N WEN

Tourette Syndrome (TS) is a common behavioural and neurological disorder characterized by involuntary phonic and motor tics, onsetting primarily between early childhood to adolescence. 1 One common problem facing TS diagnosis is the comorbidity of the syndrome, where similar symptoms are shared amongst different diseases. Comorbidity is prevalent in those affected, with approximately 85% of individuals experiencing additional neuropsychiatric disorders. 1 Common comorbidities include: attention-deficit/hyperactivity disorder, obsessive-compulsive disorder, and autism spectrum disorders. 1,2,3 As a result, TS is considered a model neuropsychiatric disorder and discovery of its etiology may present findings applicable to other psychiatric disorders. 3

In 2013, Barack Obama announced the federal BRAIN initiative in partnership with the National Institute of Health. 1 The goal was simple: identify every type of cell found in the brains of mice, monkeys, and humans. Amongst the 100 billion neurons in the human brain, 60 types had been identified and categorized to date. 2 In August of 2018, scientists identified yet another type of neuron with perplexing features. Researchers at the Allen Institute of Brain Science and University of Szeged have discovered a new neuron that is present in humans, but not rodents. The rosehip neuron, named after its striking resemblance to a rose and its petals, inhibits neuronal functioning through the repression of other neurons. 3 Although these neurons are few in number, their strategic locations have made scientists hypothesize that they function in regulating the complex circuitry that comes with human consciousness. 4

Although there is an association between environmental factors and a greater risk of developing TS, it is primarily a genetic disorder. In fact, Davis and colleagues estimated that heritability for TS is 58%, making it one of the most heritable complex neuropsychiatric disorders. 3,4 Past studies have suggested that dysregulated development and/or the maintenance of parallel cortico-striatal-thalamo-cortical circuits are the main cause of TS and its comorbidities. Despite this lead, identification of TS susceptibility genes has proven to be difficult, with minimal consensus across studies. 3

2.

3.

4.

5.

Thenganatt MA, Jankovic, J. Recent advancements in understanding and managing tourette syndrome. F1000Research. 2016;5:1-10. Available from: doi:10.12688/f1000research.7424.1.

Robertson MM. The gilles de la tourette syndrome: The current status. Arch Dis Child Educ Pract Ed. 2012; 97(5):166-175. Available from: doi:10.1136/archdischild-2011-300585.

Huang AY, Yu D, Davis LK, Sul JH, Tsetsos F, Ramensky V, et al. Rare copy number variants in NRXN1 and CNTN6 increase risk for Tourette syndrome. Neuron. 2017;94(6):1101-11. Available from: doi:10.1016/j.neuron.2017.06.010.

Davis LK, Yu D, Keenan CL, Gamazon ER, Konkashbaev AI, Derks EM, et al. Partitioning the heritability of Tourette syndrome and obsessive compulsive disorder reveals differences in genetic architecture.

PLOS Gene. 2013; 9(10). Available from: doi:10.1371/journal.pgen.1003864.

Thapar A, Cooper M. Copy number variation: What it is and what has it told us about child psychiatric disorders?. J Am Acad Child Adolesc Psychiatry. 2013; 52(8): 772-4. Available from: doi:10.1016/j. jaac.2013.05.013.

Additionally, rosehip neurons are a type of inhibitory neuron for which several highly selective markers have been implicated as risk factors for neuropsychiatric disorders. 5 A better understanding of this neuron and its connection to the overlying neuronal circuitry may lead to the development of more promising treatments against human neurological pathologies.

1.

2.

3.

4.

5.

National Institutes of Health. What is the National Brain Initiative? [Internet]. 2018 [Accessed 2018 Sep 12]. Available from: https://www.braininitiative.nih.gov/ Houzel S. The human brain in numbers: A linearly scaled-up primate brain. Front Hum Neurosci.

2009;3:31. Available from: doi:10.3389/neuro.09.031.2009 Eyal G, Verhoog M, Testa-Silva G, Deitcher Y, Lodder J, Benavides-Piccione R, et al. Unique membrane properties and enhanced signal processing in human neocortical neurons. eLife. 2016;5:e16553.

Available from: doi:10.7554/eLife.16553 Boldog E, Bakken TE, Hodge RD, Novotny M, Aevermann BD, Baka J, et al. Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type. Nat Neurosci.

2018;21(9):1185-95. Available from: doi:10.1038/s41593-018-0205-2.

Hamilton J. What makes a human brain unique? A newly discovered neuron may be a clue [Internet]. 2018 [Accessed 2018 Sep 9]. Available from: https://www.npr.org/sections/healthshots/2018/08/27/642255886/a-new-discovery-may-explain-what-makes-the-human-brainunique.

| D E C E M B E R 2018

1.

While further research is being conducted to examine the specific role of rosehip neurons, lead researchers Ed Lein and Gabor Tamas are concerned with the implications of this discovery. Lein stated, “[Rosehip neurons] throw some doubt on the ability to use [murine models] to study certain elements of human function and disease.� 5 However, researchers are unsure if rosehip neurons are truly unique to humans. Hence, more research is needed to evaluate the use of animal systems as models for human disease.

M E D U CATO R

In an analysis of genotypes with potential influence on comorbidity, both copy number variations (CNVs) and gene deletions in specific gene loci were found to increase the risk of TS. Genetic and CNV analysis conducted by Huang and colleagues identified two individual, genome-wide, significant loci: CNTN6 duplications and NRXN1 deletions. These genetic variations substantially increased TS risk and were found in approximately 1% of TS patients in the study. 3 In analyzing the genetic etiology of TS, new treatments may be developed for this disorder. Given its many comorbidities, this research also has the potential to improve our understanding of other neuropsychiatric syndromes.

medbulletin

DANIE L R AYNE R

6

7

1.

2.

3.

4.

5.

6.

7.

8.

9.

10.

11.

12.

Fatoye F, Gebrye T, Svenson LW. Real-word incidence and prevalence of systemic lupus erythematosus in Alberta, Canada. Rheumatol Int. 2018;38(9):1721-26. Available from: doi:10.1007/s00296-018-4091-4.

Rahman A, Isenberg D. Systemic lupus erythematosus. N Engl J Med. 2008;358(9):929–39. Available from: doi:10.1056/ NEJMra071297.

Casciola-Rosen LA, Anhalt G, Rosen A. Autoantigens targeted in systemic lupus erythematosus are clustered in two populations of surface structures on apoptotic keratinocytes. J Exp Med. 1994;179(4):1317–30. Available from: doi:10.1084/jem.179.4.1317.

Cutolo M, Sulli A, Seriolo B, Accardo S, Masi AT. Estrogens, the immune response and autoimmunity. Clin Exp Rheumatol.

1995;13:217–26. Available from: https://www.ncbi.nlm.nih.gov/pubmed/7656468 [Accessed 2018 Nov 6].

Silva MT. Secondary necrosis: The natural outcome of the complete apoptotic program. FEBS Lett. 2010;584(22):4491-9. Available from: doi:10.1016/j.febslet.2010.10.046.

Biermann MH, Veissi S, Maueröder C, Chaurio R, Berens C, Herrmann M, et al. The role of dead cell clearance in the etiology and pathogenesis of systemic lupus erythematosus: Dendritic cells as potential targets. Expert Rev Clin Immunol. 2014;10(9):1151-64.

Available from: doi:10.1586/1744666X.2014.944162.

Muñoz LE, Lauber K, Schiller M, Manfredi AA, Herrmann M. The role of defective clearance of apoptotic cells in systemic autoimmunity. Nat Rev Rheumatol. 2010;6(5):280. Available from: doi:10.1038/nrrheum.2010.46.

Tsokos GC, Lo MS, Reis PC, Sullivan KE. New insights into the immunopathogenesis of systemic lupus erythematosus. Nat Rev Rheumatol. 2016;12(12):716. Available from: doi:10.1038/nrrheum.2016.186.

Theofilopoulos AN, Kono DH, Beutler B, Baccala R. Intracellular nucleic acid sensors and autoimmunity. J Interferon Cytokine Res. 2011;31(12): 867–86. Available from: doi:10.1089/jir.2011.0092.

Radic M, Marion T, Monestier M. Nucleosomes are exposed at the cell surface in apoptosis. J Immunol. 2004;172(11):6692–700.

Available from: doi:10.4049/jimmunol.172.11.6692.

Buyon JP, Clancy RM. Maternal autoantibodies and congenital heart block: Mediators, markers, and therapeutic approach. Semin Arthritis Rheum. 2003;33(3):140–54. Available from: doi:10.1016/j.semarthrit.2003.09.002.

Ravirajan CT, Rahman MA, Papadaki L, Griffiths MH, Kalsi J, Martin ACR, et al. Genetic, structural and functional properties of an IgG DNA-binding monoclonal antibody from a lupus patient with nephritis. Eur J Immunol. 1998;28(1):339–50. Available from: doi:10.1002/(SICI)1521-4141.

13.

14.

15.

16.

17.

18.

19.

20.

21.

22.

23.

24.

Coffman RL, Lebman DA, Rothman P. Mechanism and regulation of immunoglobulin isotype switching. Adv Immunol. 1993;54:229– 70. Available from: doi:10.1016/S0065-2776(08)60536-2.

Biesecker G, Katz S, Koffler D. Renal localization of the membrane attack complex in systemic lupus erythematosus nephritis. J Exp Med. 1981;154(6):1779–94. Available from: doi:10.1084/jem.154.6.1779.

Noris M, Remuzzi G. Overview of complement activation and regulation. Semin Nephrol. 2013;33(6):479-92. Available from: doi:10.1016/j.semnephrol.2013.08.001.

Mahajan A, Herrmann M, Muñoz LE. Clearance deficiency and cell death pathways: A model for the pathogenesis of SLE. Front Immunol. 2016;7:35. Available from: doi:10.3389/fimmu.2016.0003.

Lintner KE, Wu YL, Yang Y, Spencer CH, Hauptmann G, Hebert LA, et al. Early components of the complement classical activation pathway in human systemic autoimmune diseases. Front Immunol. 2016;7:36. Available from: doi:10.3389/fimmu.2016.00036.

Ehrenstein MR, Cook HT, Neuberger MS. Deficiency in serum immunoglobulin (Ig) M predisposes to development of IgG autoantibodies. J Exp Med. 2000;191(7):1253-8. Available from: doi:10.1084/jem.191.7.1253.

Boes M, Schmidt T, Linkemann K, Beaudette BC, Marshak-Rothstein A, Chen J. Accelerated development of IgG autoantibodies and autoimmune disease in the absence of secreted IgM. Proc Natl Acad Sci USA. 2000;97(3):1184-9. Available from: doi:10.1073/ pnas.97.3.1184.

Jiang C, Foley J, Clayton N, Kissling G, Jokinen M, Herbert R, Diaz M. Abrogation of lupus nephritis in activation-induced deaminasedeficient MRL/lpr mice. J Immunol. 2007;178(11):7422-31. Available from: doi:10.4049/jimmunol.178.11.7422.

Lee YH, Choi SJ, Ji JD, Song GG. Overall and cause-specific mortality in systemic lupus erythematosus: An updated meta-analysis.

Lupus. 2016;25(7):727-34. Available from: doi:10.1177/0961203315627202.

Nieves CE, Izmirly PM. Mortality in systemic lupus erythematosus: An updated review. Curr Rheumatol Rep. 2016;18(4):21. Available from: doi:10.1007/s11926-016-0571-2.

Bengtsson AA, Rönnblom L. Systemic lupus erythematosus: Still a challenge for physicians. J Intern Med. 2017;281(1):52-64.

Available from: doi:10.1111/joim.12529.

Larsen JL, Hall EO, Jacobsen S, Birkelund R. Being in a standstill-of-life: Women’s experience of being diagnosed with systemic lupus erythematosus: A hermeneutic-phenomenological study. Scand J Caring Sci. 2018;32(2):654-62. Available from: doi:10.1111/ scs.12491.

8

NEUROABSTRACTS MANF, ER STRESS, AND THE PATHOPHYSIOLOGY OF PARKINSON’S DISEASE KHALED NAWAR1, ASHLEY BERNARDO2, SUMITHA SIVA3, RAM MISHRA2

Department of Biology, McMaster University Department of Psychiatry and Behavioural Neurosciences, McMaster University 3 Department of Biochemistry, McMaster University

1

table of contents neuroabstracts

2

Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a critical protein that promotes the survival of midbrain dopaminergic neurons and has therefore been implicated in the pathophysiology of Parkinson’s disease.

MANF mainly localizes in the ER and plays a major role in maintaining ER homeostasis, specifically by stopping the unfolded protein response (UPR) during ER stress and preventing the cell from undergoing apoptosis. Lentiviralmediated shRNA MANF knockdown in the substantia nigra of male Sprague Dawley rats led to the development of motor deficits and the manifestation of Parkinson’s-like symptoms, as shown via the beam transversal test, fixedspeed rotarod test, and the assessment of local asymmetry through the cylinder test. The binding immunoglobulin

protein (BiP), activating transcription factor 4 (ATF4), and transcription factor C/EBP homologous protein (CHOP) play a major role during ER stress and the UPR, and are used as ER stress and apoptosis markers. PCR quantification of ER stress through the analysis of BiP, ATF4, and CHOP mRNA showed elevated ER stress levels and apoptosis following MANF knockdown. The increased levels of ER stress and apoptosis led to the death of midbrain dopaminergic neurons and suggest that MANF is involved in the pathophysiology of Parkinson’s disease.

Acknowledgments: Special thanks to the members of the Mishra lab for their effort and their constant support. This research was supported by CIHR and NSERC.

DO THE BENEFITS OF RETRIEVAL PRACTICE REMAIN UNDER STRESS? OMER BAIG1, SEBASTIAN SCIARRA2, JOSEPH KIM2

Department of Biology and Psychology, Neuroscience & Behaviour, McMaster University Department of Psychology, Neuroscience & Behaviour, McMaster University

1

M E D U CATO R

|

D E C E M B E R 2018

2

99

The testing effect demonstrates that long-term memory is better encoded when the learning period is devoted to retrieving rather than restudying information. Recent research regarding this effect has found that encoding information through restudying leaves subsequent retrieval vulnerable to stress, whereas studying information by practicing retrieval protects later retrieval from stress.

The current study seeks to replicate these findings using ecologically valid materials, while investigating whether protection against stress, developed by practicing retrieval, remains after completing a more difficult task. This experiment employed a 2x2 between-participant design. On the first day, participants learned a prose passage by either

repeatedly restudying the passage (SSSS) or by practicing retrieval following an initial study session (SRRR). They returned two days later to complete either the Trier Social Stress Test or a control analogue. Afterwards, they recalled the passage and subsequently completed a set of multiplechoice questions. The results displayed an inoculation against stress for participants retrieving for the final free recall, but stress was observed to affect participants when answering the multiple-choice questions. Stress impairments were seen on the multiple-choice questions regardless of learning strategy, suggesting a dependency of the testing effect on automatization.

EDITED BY DANIEL DIATLOV & ALBERT STANCESCU

EFFECTS OF EARLY LIFE STRESS ARE ATTENUATED BY EXPOSURE TO L. RHAMNOSUS INDIKA SOMIR1 & PAUL FORSYTHE1,2,3

The Brain Body Institute, St. Joseph’s Healthcare, Charlton Campus Firestone Institute for Respiratory Health, McMaster University 3 Department of Medicine, McMaster University

1

2

anxiety-like behaviour and splenocytes were isolated to assess alterations in immune responses. ELS was observed to be associated with behavioural changes, decreased stressinduced corticosterone release, and increased inflammation.

The results demonstrate that the ELS-associated symptoms of anxiety-like behaviour and stress-induced corticosterone release were diminished in the JB-1 treatment group.

EXAMINING THE EFFICACY OF GOAL MANAGEMENT TRAINING AS A COGNITIVE REMEDIATION APPROACH IN A SAMPLE OF INDIVIDUALS WITH MAJOR DEPRESSIVE DISORDER

neuroabstracts introduction

Alterations in gut microbiota can affect the development of the immune and nervous systems. In particular, microbebased interventions may attenuate the detrimental effects of early life stress (ELS), such as immune and neurodevelopmental disorders. This study assessed the impact of ELS on anxiety-like behaviour and immune function, and determined the potential therapeutic effects of Lactobacillus rhamnosus ( JB-1). BALB/c mice were exposed to a limited nesting paradigm. Stressed mice were either given JB-1 dissolved in their drinking water or water alone. Behavioural tests were conducted to measure

MARIA NICULA1, JENNA BOYD1,2, MARGARET MCKINNON1,2,3

Department of Psychology, Neuroscience & Behaviour, McMaster University Mood Disorders Research Unit, St. Joseph’s Healthcare Hamilton 3 Department of Psychiatry and Behavioural Neurosciences, McMaster University

1

2

received this intervention and a waitlist control (WLC) sample on their self-reported measures of cognitive difficulty, functional outcomes, and clinical symptoms of depression and anxiety. We hypothesized that, in comparison to the WLC group, the GMT group would subjectively report improvements on these domains after treatment. Our results indicate that the GMT group reported a significant decline in their cognitive difficulties, with improved social functioning and fewer symptoms of depression and anxiety.

These findings suggest that GMT is a useful tool for rehabilitating cognitive function in the MDD population.

M E D U CATO R | A P R I L 2015 M E D U CATO R | D E C E M B E R 2018

Cognitive impairment is a central component of major depressive disorder (MDD). These deficits are shown to persist after euthymia and are associated with poor functional outcomes and diminished treatment effectiveness.

Cognitive remediation therapies (CRTs) have the potential to re-establish cognitive functioning in the MDD population because these approaches have been effective in populations that suffer similar deficits. In the present study, we tested the efficacy of a successful CRT program called Goal Management Training (GMT), which employs takehome strategies targeted at improving executive functioning skills. We investigated the differences between a sample that

Acknowledgments: Research supported by the J.P. Bickell Foundation, as well as the Mood Disorders Research Unit and Mood Disorders Program at St. Joseph’s Healthcare Hamilton.

10 3

VIEWPOINTS

Ethics of paediatric Medical Assistance in Dying ANGELA DONG1 , AARON WEN 2

EDITED BY MATTHEW LYNN & JAMES YU

Bachelor of Health Sciences (Honours) Class of 2020, McMaster University 2 Bachelor of Health Sciences (Honours) Class of 2022, McMaster University 1

INTRODUCTION

viewpoints

Medical assistance in dying (MAID) —formerly known as euthanasia— is sought after by terminally ill individuals to relieve their pain and suffering. In the 2015 Carter vs Canada ruling, the Canadian Parliament invalidated prohibitions on MAID in the Canadian Charter of Rights and Freedoms. Although adult MAID is now permitted, MAID for minors is still up for debate.1 Over the past few years, the discussion of MAID has become increasingly prevalent amongst children and teens. In a Canadian Paediatric Surveillance Program survey of 1050 paediatricians, 118 indicated that over the course of one year, they had “[MAID] discussions with over 419 patients.”2 These results have the potential to alter current MAID laws and reform the arguments between an individual’s right to autonomy and society’s responsibility to protect the most vulnerable. To date, only two countries allow MAID for minors: the Netherlands and Belgium.

This Viewpoints piece will provide two opposing opinions on the legalization of paediatric MAID in congruence with the enacted MAID laws within Canada.

FOR PAEDIATRIC MAID

M E D U CATO R

| D E C E M B E R 2018

“Do not go gentle into that good night,” we used to say on the subject of dying. However, death comes for us all in the end, and in recent times, dialogue has shifted towards leaving with dignity into the great beyond.3 Current methods of end-of-life care for minors center around palliative care, where opioids are prescribed in increasing dosages to relieve pain and counteract long-term tolerance.

However, providing increasing doses of opioids may still end in death, just like other widespread passive measures of letting the patient die, such as “pulling the plug” or stopping treatment. Opponents of MAID argue that palliative care’s existence should preclude the use of MAID as it achieves the same effect passively, something presumably more moral than an active decision. However, from a utilitarian point of view, both seek the same result of relieving pain and causing death, and are therefore equivalently moral. One could even argue that palliative care —the terminally ill languishing for weeks, minds addled with opioids, while the family waits with bated breath for the tragic, unpredictably-timed conclusion— is less 1.

2.

3.

4.

5.

6.

11

humane as it prolongs the suffering of everyone involved. One must also remember that patients are often those who have lost almost all control of their lives —to deny them one more opportunity for autonomy would be against their best interests psychologically.4 Upon establishing the necessity of MAID even in the age of palliative care, the line in the sand between MAID and paediatric MAID, autonomy, must be addressed. For mature minors and incompetent minors seeking MAID, one current legal caveat unjustifiably limits their access to relief: the arbitrariness of the age limit. In the Netherlands, only mature minors aged 12 to 18 or infants under 1 year old (Groningen Protocol) are eligible.5 Such strict age limits fail to consider vast differences in maturity uncorrelated with biological age and undermine case-based evaluation, an approach more thoroughly considerate of complex situational factors. Opponents of paediatric MAID argue that minors should not be trusted with such decisions, citing immaturity. However, due to the highly unique medical histories of MAID-requesting youth, no one else can understand the impact of the disease on their life as much as they do. One can even argue that they grasp the gravitas of their choice moreso than adult patients, as many paediatric patients with lifelong conditions have grown used to confronting their mortality, while adult patients often face shocking lifestyle changes overnight, potentially skewing their perspective.5 In the case of incompetent minors where parental determination comes into play, there is a societal right for parents to raise offspring as they see fit. Compared to hours of doctors’ visits, a parent’s experience with their child extends into months and years. Not only do they know the full story and what their child might want, but there is also a higher likelihood of compatible values between parent and child than child and doctor —they are the primary caregivers.6 In cases of terminally-ill neonates, parents will be toiling long after intensive care discharge, an oftentimes fruitless and life-altering endeavour especially deleterious to disadvantaged parents.

Some may say that parental determination opens the door to abuse. However, safety measures exist to prevent policy abuse such as strict regulations and evaluations on eligibility after opting-in, and intervention by courts and physicians if ulterior motives are suspected.3 Similarly, if opponents cite systemic abuse incentives —such as claiming that corporate hospitals will pressure for MAID to cut costs— there is no telling that this does not currently exist on a more opaque level. To

Health Canada. Medical assistance in dying [Internet]. 2018 [Accessed 2018 Oct 26]. Available from: https://www.canada.ca/en/health-canada/services/medical-assistance-dying.html.

Baum K. Children, teens, parents asking Canadian pediatricians about assisted dying [Internet]. 2018 [Accessed 2018 Oct 26]. Available from: https://www.theglobeandmail.com/news/national/pediatricians-acrosscanada-report-fielding-questions-on-assisted-dying-survey/article36723278/.

Davies D. Medical assistance in dying: A paediatric perspective. Paediatr Child Health. 2018;23(2):125-130. Available from: doi:10.1093/pch/pxx181 Wakefield D, Bayly J, Selman L, Firth A, Higginson I, Murtagh F. Patient empowerment, what does it mean for adults in the advanced stages of a life-limiting illness: A systematic review using critical interpretive synthesis.

Palliat Med. 2018;32(8):1288-1304. Available from: doi:10.1177/0269216318783919.

Brouwer M, Kaczor C, Battin M, Maeckelberghe E, Lantos J, Verhagen E. Should pediatric euthanasia be legalized?. Pediatrics. 2018;141(2):e20171343. Available from: doi:10.1542/peds.2017-1343 Bovens L. Child euthanasia: Should we just not talk about it?. J Med Ethics. 2015;41(8):630-634. Available from: doi:10.1136/medethics-2014-10232

address this political issue, the solution is not to stand by and force patients to suffer longer as collateral damage. Instead, we should push for legislation that protect the rights of patient and prevent them from making decisions based on economic needs.

This solution benefits more than just the MAID movement.

Death comes for us all, regardless of age or background. Legalizing MAID for minors would destigmatize the taboo around end-of-life options for terminal patients, which allows for more preparedness for end-of-life.4 As with all medical decisions, one does not have to take it —MAID will simply be another device in the toolkit for minors and parents as they grapple with the complex tribulations of terminal illness.

AGAINST PAEDIATRIC MAID

question the minor’s ability to make sound judgments in complex situations, free from the influence of authority figures in their life such as physicians and parents.12 In fact, some medical experts have termed the concerning proposal in the Netherlands to offer MAID to severely disabled newborns as “non-voluntary active euthanasia” to illustrate how the practice severely undermines patient autonomy.9 Hence, there are many logistical difficulties in ARTIST ensuring that children making deciPERI REN sions about MAID are fully informed, able to appreciate the complex consequences and benefits of treatment choices, and act free of impulse or coercion.

14.

| D E C E M B E R 2018

11.

12.

13.

Ogden R. The right to die: A policy proposal for euthanasia and aid in dying. Can Public Policy. 1994;20(1):1. Available from: doi:10.2307/3551832.

Government of Canada. Medical Assistance in Dying [Internet]. 2018 [Accessed 2018 Nov 2]. Available from: https://www.canada.ca/en/health-canada/services/medical-assistance-dying.html.

Siegal A, Sisti D, Caplan A. Pediatric euthanasia in Belgium. JAMA. 2014;311(19):1963-4. Available from: doi:10.1001/jama.2014.4257.

Johnson, S., Blum, R. and Giedd, J. Adolescent maturity and the brain: The promise and pitfalls of neuroscience research in adolescent health policy. J Adolesec Health, 2009; 45(3): 216-221. Available from: doi:10.1016/j. jadohealth.2009.05.016 Sowell ER, Thompson PM, Holmes CJ, Jernigan TL, Toga AW. In vivo evidence for post-adolescent brain maturation in frontal and striatal regions. Nat Neurosci. 1999;2(10):859. Available from: doi:10.1038/13154.

Weinberger DR, Elvevag B, Giedd JN. The Adolescent Brain: A work in progress. Washington, D.C.: 1001 Property Solutions; 2005.

Zeng Y, Wang C, Ward K, Hume A. Complementary and alternative medicine in hospice and palliative care: A systematic review. J Pain Symptom Manage. 2018; 56(5): 781-794. Available from: doi:10.1016/j.jpainsymman.2018.07.016.

Fine S, Stone L. In absence of federal law, assisted dying enters era of uncertainty [Internet]. 2018 [Accessed 2018 Nov 7]. Available from: https://www.theglobeandmail.com/news/national/leading-constitutional-expertsays-assisted-dying-law-unconstitutional/article30283048/

M E D U CATO R

7.

8.

9.

10.

viewpoints

Since the 1990s, society has become increasingly liberal in its attitude on the individual’s “right to die.”7 Despite this shift in opinion, the discussion on the ethics and logistics of institutional MAID has been slow and uncertain. The current laws in Canada only grant MAID to individuals aged 18 or older, citing their abilities to make informed healthcare decisions.8 Proponents of paediatric MAID argue that the exclusion of minors is not only unethical but also unconstitutional, as the Charter of Rights and Freedoms states that all individuals have the right to “life, liberty, and security of the person.”8 Hence, there has been a call for the Canadian government to extend Although children may not be able to grasp the complexities MAID to paediatric populations. However, given the inherent inherent to end-of-life decisions in their entirety, the negative complexity in assessing and obtaining informed consent from experiences of physical pain can be understood at all developminors, the proponents fail to appreciate the full scope of the mental stages, making pain management a viable alternative.9 issue and consequently fail to provide convincing safeguards to Current studies surrounding palliative care have identified protect this vulnerable population from impulse and coercion. techniques that significantly improve the quality of life of patients with a variety of intractable symptoms through pain alleOne of the most prevalent issues that emerges in paediatric viation.13 Although palliative care methods are not perfect and MAID is the maturity of patients involved, which determines research is ongoing, it is preferable to the extreme option of their ability to provide informed consent. Even though the par- MAID while still addressing the needs of the child. ent is allowed to provide informed consent on behalf of the incapable child for most medical decisions, for a decision as When adult MAID legislation was introduced in Canada, it irreversible as MAID, it is paramount that the autonomy of received criticism for being overly vague —providing poor defithe child is safeguarded and respected throughout the decision- nitions of terminal illness and intractable pain.14 In a paediatric making process. Current MAID laws strive to respect auton- context, this establishes an environment of uncertainty for chilomy by requiring that the patient understands the available dren and families in which the standard practices of care would alternatives —such as palliative care and aggressive pain man- vary drastically between healthcare providers and legal instituagement— and the consequences of choosing MAID. However, tions within and between Canadian provinces. there are some key differences between paediatric and adult terminal patients that complicate the issue of informed consent in Current evidence presents clear obstacles to paediatric MAID the former. For adults, their decision for choosing MAID over including difficulties in ascertaining informed consent, inadalternatives such as palliative care may include fear of losing equate legal infrastructure to address the complex concerns personal integrity and burdening their family —reasons that around paediatric MAID, and the availability of other end-ofchildren may not fully understand.9 Over the past decade, a life care options. Thus, we believe the legalization of paediatric preponderance of neuroimaging research has indicated that ad- euthanasia could lead to deleterious consequences as it is far too olescence is a period of continued brain growth and change.10 ethically dangerous and legislatively premature. Further invesThe frontal lobe —the region associated with conscience, high- tigation into alternatives must thus be prioritized. Death may er-level thinking, and decision making— does not mature un- come for us all at the end but not today. ■ til late adolescence.11 These physiological differences call into

12

ARTIST SUFFIA MALIK

RESEARCH INSIGHT

Developing effective recruitment strategies for young infants

Hanzhuang Zhu1 , Natalie Wagner 2 , Ranil Sonnadara 3 Arts and Science Program, McMaster University Department of Psychology, Neuroscience & Behaviour, McMaster University Department of Surgery, McMaster University Correspondence: wagnernk@mcmaster.ca 1 2 3

ABSTRACT The purpose of this study was to explore researchers’ perspectives on the challenges and strategies associated with recruiting infants for non-invasive experiments. Nine researchers participated in semi-structured interviews. The interviews were analyzed using a grounded theory approach. Access was cited as a major challenge to recruitment. Successful strategies involved forming positive relationships with participants, hospitals, and community partners. Those who agreed to participate were often of high socioeconomic status or had a connection to McMaster University. Interviewed researchers believed that collaborating with colleagues, communicating directly with new mothers, and establishing partnerships with individuals in related professional fields were all effective in facilitating infant recruitment. As recruiting infants for non-invasive studies remains challenging, this study aims to assist researchers in finding successful strategies.

INTRODUCTION Assessment of these approaches in vulnerable population recruitment has yielded mixed results, potentially due to major differences across the various vulnerable populations themselves.12 For infant populations, the literature more consistently reports that interpersonal contact and relationship building are effective strategies.12 However, obtaining permission from parents on behalf of very young infants can be particularly challenging, due to the overwhelming nature of childbirth and the unpredictable schedule of newborn children and their parents.9 To date, most research on infant recruitment has concentrated on ethically complex procedures involving invasive methodology or randomized controlled trials; however, little is known about recruiting infants for non-invasive studies.15

M E D U CATO R | D E C E M B E R 2018

Vulnerable populations are social groups who demonstrate a comparatively greater susceptibility to adverse health outcomes.7 This definition includes groups such as ethnic minorities, the economically disadvantaged, the elderly, and individuals with serious physical and mental health conditions.8 Infants are also considered a vulnerable population because they have The present study aimed to explore the perspectives of researchers developmental and cognitive limitations, and are incapable of involved with non-invasive and observational infant studies. giving informed consent.9 Since their participation in research The primary objectives were to identify perceived recruitment studies requires consent through a parent or another authorized challenges, effective recruitment strategies, observations of substitute decision maker, recruiting infants into research demographic trends among participants, and how these factors studies is strategically and ethically complex.6,10 Establishing compared to recruitment for more invasive infant studies. a trusting relationship between the participant, any substitute METHODS decision makers, and the researcher is thus crucial.11 As a result, the impersonal nature of conventional recruitment strategies, Participants for the present study included researchers affiliated such as mass advertisement via flyers and media postings, are with McMaster University who conducted non-invasive generally ineffective.6 behavioural studies involving infants. Study subjects were identified from research descriptions on their websites. Some Recruitment strategies targeting vulnerable populations participants also referred colleagues who met the inclusion typically emphasize direct communication between researchers criteria. An email was sent to all participants inviting them to and potential participants, which can occur through in-person participate in a brief 20- to 30-minute interview at a time and presentations at relevant community outreach locations. These place of their choosing. This email also included information interactions are followed up with face-to-face discussions, phone and consent forms. A total of nine researchers were recruited: calls, and written correspondence.12 Partnering with community one principal investigator, one graduate student, two research leaders and service providers has been shown to be effective coordinators, and five recruitment coordinators. in building rapport with members of vulnerable populations.13 For example, church personnel, medical professionals, and Prior to the interview, the consent form was reviewed and organization managers are in positions of trust and can act as participants were given the opportunity to ask questions. A semigatekeepers to recruitment.11 Finally, “snowball recruitment� structured interview guide was used in the interview. Participants through referrals from previous participants also establishes were prompted to discuss personal experiences regarding infant a trusted point of contact between the researcher and other recruitment challenges, effective and ineffective recruitment potential participants.14 strategies, and demographic trends of consenting parents. All

research insight

Studies exploring the early stages of life have facilitated greater understanding of typical psychological and physical development.1-3 This enhanced understanding has improved newborn screening techniques and has been influential in developing better postnatal care practices.4,5 Yet, despite the social and scientific benefits of infant research, recruiting newborns into research studies remains extremely difficult due to their status as a vulnerable population.6

participants also consented to be recorded. Recordings were later

14

transcribed verbatim and analyzed using NVivo software.

M E D U CATO R

|

D E C E M B E R 2018

research insight

RESULTS AND DISCUSSION

15

Gaining access to the infant population When asked about the most challenging aspect of recruiting infants, the majority of researchers described difficulties related to obtaining contact with new mothers. Hospital settings were frequently cited as being effective for accessing the infant population, but competition for time and attention with other researchers and hospital staff at maternity wards presented difficulties.

Researchers were aware that parents approached in these hospital settings may be in emotional shock due to the recent experience of childbirth, and may thus find it difficult to actively listen to their project descriptions. Furthermore, there was significant variability in parental interest and scientific background during the consent process. As a result, researchers and coordinators often had to develop a basic explanation of their study, and tailor their explanations to the specific knowledge level of each individual. However, as coordinators often have a small window of opportunity to engage with parents, deciding how much detail to provide without knowledge of the person can be extremely challenging. Moreover, even after obtaining contact information from an interested parent, it can still be very difficult to bring infants into the laboratory to complete an experiment. Only a small proportion of parents who enroll their infants in research studies book a data collection session, and of those who do, less than half attend the session.

Strong relationships are essential When asked about useful recruitment strategies, all researchers cited some aspect of forming positive interpersonal connections with the participating parent and general community.

As previously mentioned, the most common method of obtaining access to infant participants was to work in collaboration with healthcare providers and recruit from hospital settings. The endorsement of healthcare professionals was often noted as an important factor contributing to recruitment success. In addition to clinical care settings, many researchers reported success approaching prospective participants in recreational or social contexts, such as at yoga sessions, birthing classes, and teddy bear picnics for new mothers, due to their interpersonal nature.

This phenomenon was particularly true for rural areas. One researcher who was recruiting infants across multiple cities speculated that tight-knit community networks often found in less urbanized locations played a role in enhancing recruitment.

Many researchers noted that having a prepared pamphlet for prospective participants was useful in ensuring they were communicating the right amount of information and providing an opportunity for parents to privately consider the decision. However, one researcher mentioned that hiring a public relations company to create promotional materials was a comparably ineffective strategy. This finding is supported by previous research on infant recruitment for more invasive procedures, which demonstrated that parents responded better to face-to-face contact with researchers, rather than flyers and other print advertisements.11

Other issues elucidated by researchers included the unreliability of contact information provided Beyond the initial recruitment process, the by parents, which often changed by the time researchers also emphasized the importance infants were at an appropriate age for recruitment of having flexible availabilities for parents (generally 6 months to several years later). The with infants. Ensuring a positive experience process of connecting with parents who had for parents throughout the experimental previously given consent to be contacted over the sessions was frequently mentioned as being an phone was frequently compared to telemarketing. effective way to recruit new participants, as it Many recruiters found it challenging to would influence word-of-mouth recruitment quickly but precisely explain their research and from previous participants. Furthermore, simultaneously retain prospective participants’ many researchers noticed that individuals engagement in the conversation. The ability to who had completed a study previously communicate information quickly and effectively were more likely to participate in another. was difficult to teach to new recruiters, but vital to establishing a good first impression with Finally, the researchers identified that a the parent. These concerns demonstrated that collaborative patient database, compiled by accessing participants was difficult at all stages multiple laboratories at McMaster University of the recruitment process. Having the means to facilitate recruitment from regional hospital to gather contact information did not always maternity wards, was especially useful for guarantee successful recruitment of the infant identifying potential participants. One researcher into the laboratory. briefly mentioned the potential benefits of

expanding the database to encompass more laboratories and research projects. This expansion would benefit non-invasive infant research by distributing the burden of recruitment among more research groups, and by taking further advantage of the parental tendency to enroll in additional studies as they become more comfortable with researchers and the research experience.

Demographic trends in those who consent When asked to reflect on demographic trends among parents who enrolled their infant in a behavioural study, almost all researchers established that their participants had diverse backgrounds. Most mentioned that the majority of their participants seemed to be of high socioeconomic status and have more extensive educational backgrounds. However, studies offering paid compensation also attracted many participants of low socioeconomic status. Middleclass families were consistently perceived to be the most difficult to recruit.

LIMITATIONS This study only involved researchers from McMaster University due to time constraints associated with an undergraduate thesis project; thus, the findings may neither be generalizable to other institutions nor represent all recruitment strategies. Furthermore, as the researchers who participated were not required to list the studies they were currently working on, it is possible that some studies may have been over or underrepresented.

1.

2.

3.

4.

5.

6.

7.

CONCLUSIONS 8.

This study explored researchers’ perspectives on the challenges associated with infant recruitment, effective and ineffective recruitment strategies, and perceived demographic characteristics among consenting parents. While additional research is needed to better understand why parents may be opting out of studies, researchers should use these findings to inform their recruitment practices.

REVIEWED BY DR. VICKIE GALEA

Dr. Galea is an Associate Professor at McMaster University with a primary appointment in the School of Rehabilitation Science. She is on the graduate faculty of the Rehabilitation Science, Human Biodynamics, and Neuroscience (MINDS) programs. Her primary research focus is on the modeling of generalized movements in full-term and premature infants.

9.

10.

11.

12.

13.

14.

15.

16.

Shultz S, Vouloumanos A, Bennett RH, Pelphrey K. Neural specialization for speech in the first months of life. Dev Sci. 2014;17(5):766-74.

Available from: doi:10.1111/desc.12151.

Maurer D, Werker JF. Perceptual narrowing during infancy: A comparison of language and faces.

Dev Psychobiol. 2014;56(2):154-78. Available from: doi:10.1002/dev.21177.

Trainor LJ, Cirelli L. Rhythm and interpersonal synchrony in early social development. Ann N Y Acad Sci. 2015;1337(1):45-52. Available from: doi:10.1111/nyas.12649.

Prechtl HFR. Qualitative changes of spontaneous movements in fetus and preterm infant are a marker of neurological dysfunction. Early Hum Dev. 1990;23(3):151-8. Available from: doi:10.1016/0378-3782(90)90011-7.

Guyer C, Huber R, Fontijn J, Bucher H, Nicolai H, Werner H, et al. Cycled light exposure reduces fussing and crying in very preterm infants.

Pediatr. 2012;130(1):e145-51. Available from: doi:10.1542/peds.2011-2671.

Knox CA, Burkhart PV. Issues related to children participating in clinical research. Pediatr Nurs. 2007;22(4):310-8. Available from: doi:10.1016/j.pedn.2007.02.004.

Flaskerud JH, Winslow BJ. Conceptualizing vulnerable populations health-related research. Nurs Res. 1998;47(2):69-78.

Available from: https://www.ncbi.nlm.nih.gov/ pubmed/9536190 [Accessed 2018 Oct 23].

American Journal of Managed Care. Vulnerable populations: Who are they? [Internet]. 2006 [Accessed 2018 Nov]. Available from: http:// www.ajmc.com/.

Sutton LB, Erlen JA, Glad JM, Siminoff LA. Recruiting vulnerable populations for research: Revisiting the ethical issues. J Prof Nurs. 2003;19(2):106-12. Available from: doi:10.1053/jpnu.2003.16.

Dibartolo MC, McCrone S. Recruitment of rural community-dwelling older adults: Barriers, challenges, and strategies. Aging Ment Health.

2003;7(2):75-82. Available from: doi:10.1080/ 1360786031000072295.

UyBico SJ, Pavel S, Gross CP. Recruiting vulnerable populations into research: A systematic review of recruitment interventions. J Gen Intern Med. 2007;22(6):852-63. Available from: doi:10.1007/s11606-007-0126-3.

Patel MX, Doku V, Tennakoon L. Challenges in recruitment of research participants. Adv Psychiatr Treat. 2003;9(3):229-38. Available from: doi:10.1192/apt.9.3.229.

Sadler GR, Lee HC, Lim RS, Fullerton J. Recruitment of hard to reach population subgroups via adaptations of the snowball sampling strategy. Nurs Health Sci. 2010;12(3):36974. Available from: doi:10.1111/j.14422018.2010.00541.x.

Pike NA, Pemberton V, Allen K, Jacobs JP, Hsu DT, Lewis AB, et al. Challenges and successes of recruitment in the “angiotensin-converting enzyme inhibition in infants with single ventricle trial” of the Pediatric Heart Network. Cardiol Young. 2013;23(2):248-57. Available from: doi:10.1017/S1047951112000832.

Daniels LA, Wilson JL, Mallan KM, Mihrshashi S, Perry R, Nicholson J, et al. Recruiting and engaging new mothers in nutrition research studies: Lessons from the Australian NOURISH randomised controlled trial. Int J Behav Nutr Phys Act. 2012;9(1):129. Available from: doi:10.1186/1479-5868-9-129.

Charmaz K. Constructing grounded theory: A practical guide through qualitative research.

London: SAGE; 2006. 224 p.

research insight

Many researchers also specified that families with postsecondary graduates and professionals in health-related or child care-related fields were more likely to be interested in participating in research. These findings support the observation that parents are more willing to consent to studies when they feel a personal connection with the research topic.11 However, this tendency may result in sampling bias and reduce the generalizability of infant studies to the entire population. Limitations in external validity are of

major concern when creating new developmental measures for testing infants.

EDITED BY NADIN ABBAS & PARNIKA GODKHINDI

M E D U CATO R | D E C E M B E R 2018

16

A RT I S T ESRA RAKAB

CRITICAL REVIEW

Carbapenem-resistant Enterobacteriaceae: Resistance mechanisms and alternative strategies

ARBAAZ PATEL

Bachelor of Health Sciences (Honours) Class of 2019, McMaster University Correspondence: patela11@mcmaster.ca

INTRODUCTION

β-Lactam antibiotics β-lactam antibiotics are a class of antibiotics that can be categorized into four structural subdivisions: penams, cephems, monobactams, and carbapenems, the last of which is considered the most potent form.3 The potency of carbapenems is attributed to their distinctive molecular configuration, consisting of a pyrroline ring fused to a β-lactam.4 This configuration provides the antibiotic class with stability against a broad spectrum of β-lactamases in addition to reduced susceptibility to resistance elements, such as degradation and inactivation.4 Most β-lactam antibiotics function by interfering with the transpeptidation step of peptidoglycan biosynthesis.5 Peptidoglycan is the principle component of the cell wall in nearly all bacteria and serves as the stress-bearing layer and cell shape determinant. The efficacy of β-lactam antibiotics is attributed to the fact that they structurally mimic specific precursor peptides involved in peptidoglycan cross-linking. This property allows β-lactam antibiotics to irreversibly bind the transpeptidase domain of penicillin-binding proteins (PBP), preventing the cross-linking of peptidoglycan.6 The structural integrity of the bacterial cell wall is thus compromised, leading to cell death.5,6 Among other β-lactam antibiotics, carbapenems, once considered a last resort antibiotic, are now being rendered impotent by emerging strains of CREs.7 The mechanisms of resistance are becoming increasingly diverse and difficult to circumvent as they are adapted to specific selective pressures, such as drug-mediated removal.6,8

| D E C E M B E R 2018

CREs: Mechanisms of resistance, carbapenemase classes Selective pressures that threaten the survival of bacterial species initiate evolutionary mechanisms which drive the development of antibiotic resistance.9 Such evolutionary mechanisms include horizontal gene transfer (HGT), which allows for the acquisition of external DNA, and genetic mutations.9 Typically, bacteria acquire resistance genes through three HGT mechanisms: transformation (the process of spontaneous DNA uptake), transduction (the process of DNA transfer between a bacteriophageinfected bacterium and an uninfected bacterium),

M E D U CATO R

The introduction of antibiotics has contributed to the vast eradication of infectious organisms. Since then, the boundaries of antibiotic properties have been manipulated to counter emerging infections and introduce novel bactericidal mechanisms.

Penicillin and streptomycin work via bacterial cell wall synthesis inhibition and protein synthesis inhibition, respectively.1 These are early examples of mechanisms among the enormous repertoire of antibiotics at our disposal.1 Despite the antimicrobial evolution, targeting specific bacteria is becoming increasingly arduous due to a co-evolutionary arms race: the rise of antibiotic resistance. In recent years, the emergence of a specific group of Gram-negative bacteria, carbapenem-resistant Enterobacteriaceae (CRE), symbolizes the necessity of alternative modes of eradication. These bacteria are resistant to carbapenems, which are considered the most potent group of β-lactam antibiotics. Thus, CREs represent an intricate and significant problem in the clinical setting.2 The following review will comment on the mechanisms of β-lactam antibiotics and resistance in CREs, with the aim of contextualizing the importance of optimized prevention and detection strategies.

REVIEW FINDINGS

critical review

ABSTRACT Carbapenem-resistant Enterobacteriaceae (CRE) are the alarming outcome of an ongoing biological arms-race between humans and infectious bacteria.

Once considered a last resort class of antibiotics, carbapenems are now effectively evaded by CREs through porin downregulation and efflux pump upregulation mechanisms. Together, these bacterial systems work to reduce the toxicity of carbapenems by preventing their entrance into the cell. More important is the production of diverse classes of carbapenemases, enzymes which effectively inactivate carbapenems by hydrolyzing the β-lactam ring of β-lactam antibiotics. The various mechanisms of these carbapenemases compound the problem of infection treatment to a point where drugs are not being developed fast enough to counter the rapid evolution of resistance.

In the face of this antibiotic crisis, it is important to focus attention on prevention and detection strategies in addition to treatment techniques.

18

1.

2.

3.

4.

5.

6.

7.

8.

critical review

9.

10.

11.

12.

13.

14.

15.

16.

M E D U CATO R

| D E C E M B E R 2018

17.

19

Zaffiri L, Gardner J, Toledo-Pereyra LH. History of antibiotics. From salvarsan to cephalosporins. J Invest Surg.

2012;25(2):67-77. Available from: doi:10.3109/08941939.2012.6640 99.

Iovleva A, Doi Y. Carbapenem-resistant Enterobacteriaceae. Clin Lab Med. 2017;37(2):303-15. Available from: doi: 10.1016/j.cll.2017.01.005.

Holten KB, Onusko EM. Appropriate prescribing of oral beta-lactam antibiotics.

Am Fam Physician. 2000;62(3):611-20.

Available from: https://www.aafp.org/ afp/2000/0801/p611.html [Accessed 2018 Nov 14].

Meletis G. Carbapenem resistance: Overview of the problem and future perspectives. Ther Adv Infect Dis. 2016;3(1):15-21.

Available from: doi:10.1177/2049936115621709.

Sauvage E, Terrak M. Glycosyltransferases and transpeptidases/penicillin-binding proteins: Valuable targets for new antibacterials. Antibiotics. 2016;5(1):12.

Available from: doi:10.3390/ antibiotics5010012.

Nordmann P, Dortet L, Poirel L. Carbapenem resistance in Enterobacteriaceae: here is the storm!.

Trends Mol Med. 2012;18(5):26372. Available from: doi:10.1016/j. molmed.2012.03.003.

McKenna M. The last resort. Nature.

2013;499(7459):394. Available from: doi:10.1038/499394a.

Blair JM, Webber MA, Baylay AJ, Ogbolu DO, Piddock LJ. Molecular mechanisms of antibiotic resistance. Nat Rev Microbiol.

2015;13(1):42-51. Available from: doi:10.1038/nrmicro3380.

Munita JM, Arias CA. Mechanisms of antibiotic resistance. Microbiol Spectr.

2016;4(2):481-511. Available from: doi:10.1128/microbiolspec.

Thomas CM, Nielsen KM. Mechanisms of, and barriers to, horizontal gene transfer between bacteria. Nat Rev Microbiol.

2005;3(9):711-21. Available from: doi:10.1038/nrmicro1234.

Dever LA, Dermody TS. Mechanisms of bacterial resistance to antibiotics.

Arch Intern Med. 1991;151(5):88695. Available from: doi:10.1001/ archinte.1991.00400050040010.

Papp-Wallace KM, Endimiani A, Taracila MA, Bonomo RA. Carbapenems: Past, present, and future. Antimicrob Agents Chemother.

2011;55(11):4943-60.

Available from: doi:10.1128/AAC.0029611.

Fernández L, Hancock RE. Adaptive and mutational resistance: Role of porins and efflux pumps in drug resistance.

Clin Microbiol Rev. 2012;25(4):66181. Available from: doi:10.1128/ CMR.00043-12.

Eser F. Carbapenem-resistant Enterobacteriaceae. Med J Islamic World Acad Sci. 2017;25(1):6-11. Available from: doi:10.5505/ias.2017.15045.

Waxman DJ, Strominger JL. Penicillinbinding proteins and the mechanism of action of beta-lactam antibiotics. Annu Rev Biochem. 1983;52(1):825-69.

Available from: doi:10.1146/annurev. bi.52.070183.004141.

Livermore DM, Woodford N. Carbapenemases: A problem in waiting?.

Curr Opin Microbiol. 2000;3(5):489-95.

Available from: doi:10.1016/S13695274(00)00128-4.

Naas T, Dortet L, Iorga BI. Structural and functional aspects of class A carbapenemases. Curr Drug Targets.

2016;17(9):1006-28. Available from: doi:10.2174/138945011766616031 0144501.

and conjugation (the pili-mediated transfer of DNA between adjacent bacteria).10 The incorporation of external DNA into the bacterial genome or plasmid may provide resistance to bacteria that did not previously possess it. In contrast, most genetic mutations result in antibiotic target site modification, upregulated efflux mechanisms, downregulated influx pathways, and metabolic pathway alterations.9 For most bacteria that have acquired resistance through either genetic mutations or HGT, the major mechanistic pathways remain: enzymatic inactivation or degradation of the antibiotic, alteration of the antibiotic target, and modification of membrane permeability.11 In CREs, carbapenem efficacy is either drastically reduced or rendered completely ineffective through three main modes of resistance: efflux pump upregulation, decreased outer membrane permeability via porin downregulation, and carbapenemase production.6 Efflux pumps redistribute a successfully penetrated antibiotic back into the extracellular environment.12 In contrast, porins increase permeability; thus, through porin expression downregulation, CREs can effectively prevent antibiotics from penetrating their cellular envelopes.13 Finally, carbapenemases provide CREs with the strongest mode of resistance. These are specific and unique classes of β-lactamases —enzymes which hydrolyze β-lactams— that selectively target and inactivate carbapenems.14 The general mechanism of most β-lactamase enzymes involves the hydrolysis of the β-lactam ring. Without the β-lactam ring, β-lactam antibiotics are unable to bind to PBP and disrupt cross-linking between peptidoglycan polymers.15 As a result, bacteria continue to thrive unaffected in their environment.

Mechanistic variations between different classes of carbapenemases pose a challenge in targeting them.16 These carbapenemases are classified as either serine-carbapenemases (classes A, C, D) or metallo-β-lactamases (class B). In general, class C is considered to have weak activity for carbapenems, rendering its clinical significance uncertain. 6 Class A serine carbapenemases utilize

Ser70 in their active sites to facilitate the hydrolysis of β-lactam rings.17 Previous research suggests that this mechanism proceeds in two steps: acylation and deacylation.17 In the acylation step, Ser70 of the carbapenemase acts as a nucleophile and attacks the amide bond of the β-lactam.

This interaction creates an acyl-enzyme complex, where Ser70 remains covalently modified by the drug. The deacylation step begins with the activation of a deacylating water molecule by conserved glutamate and tyrosine residues. The deacylating water subsequently hydrolyzes the acyl-enzyme complex and releases the inactivated open-ring form of the β-lactam and the free enzyme.17 The intricacy of class A carbapenemases is increased by structural variations between their different forms.

For instance, class A carbapenemase SME1 exhibits shorter positional distances between Ser70 and Glu166 compared to other variants, facilitating more effective hydrolysis.18 This phenomenon depicts the level of complexity that exists within specific classes in addition to inter-class variation.

Class D carbapenemases facilitate ring hydrolysis similar to class A in that both utilize acylation and deacylation steps.19 In both, the acylation steps involve a catalytic serine residue to produce an acylenzyme intermediate. In contrast to class A, the deacylation step involves the use of a carboxylated lysine residue to activate a deacylating water molecule, rather than by glutamate and tyrosine.19 Similar to class A, class D also has intra-class variation within its diverse group of enzymes. For instance, the Oxa 24/40 variant consists of a hydrophobic bridge which facilitates easier carbapenem active site hydroxyethyl group entry.19 Class B metallo-β-lactamases contain a Zn2+ ion cofactor(s) in their active site, necessary for β-lactam ring hydrolysis.12 Class B1 and B3 enzymes contain two such Zn2+ ions, whereas class B2 enzymes contain only one.12 Previous studies have indicated that the binding of another Zn2+ ion on class B2 enzymes would instead decrease their activity.12,20 These enzymes use different mechanistic pathways compared to those from class A and D because their catalytic activity does not

involve the hydroxyl group of a serine residue.

Instead, the Zn2+ ion cofactor(s) activates a water molecule, which serves directly as the catalytic nucleophile to attack the β-lactam ring. Several other amino acids, along with Zn2+ ions and an additional water molecule, participate in various stabilizing interactions to complete ring hydrolysis.12

further investigation, including phenotypic methods such as the Modified Hodge Test and the Carbapenem Inactivation Method, as well as genotypic methods such as Metagenome Sequencing and Conventional Polymerase Chain Reactions.2 Such measures should be implemented in a timely fashion in order to inform clinical decisions.

The implications of these findings suggest that the co-evolution of bacterial resistance is becoming increasingly complex; alternative strategies which do not introduce significant selective pressures may be required. The implementation of such strategies may improve patient outcomes and overall public health.

CONCLUSION

FUTURE DIRECTIONS

REVIEWED BY DR. DAVID SYNCHANTHA Dr. David Sychantha is a postdoctoral fellow in Dr. Wright’s lab at McMaster University. He is interested in the structure, mechanism, and inhibition of bacterial enzymes. Currently, he is working on the discovery and characterization of inhibitors of metallo-β-lactamases and bacterial cell wall biosynthesis.

19.

20.

21.

22.

23.

1.

Jeon JH, Lee JH, Lee JJ, Park KS, Karim AM, Lee CR, et al. Structural basis for carbapenem-hydrolyzing mechanisms of carbapenemases conferring antibiotic resistance. Int J Mol Sci. 2015;16(5):965492. Available from: doi:10.3390/ ijms16059654.

Toth M, Smith CA, Antunes NT, Stewart NK, Maltz L, Vakulenko SB. The role of conserved surface hydrophobic residues in the carbapenemase activity of the class D β-lactamases. Acta Crystallogr D Struct Biol. 2017;73(8):692701. Available from: doi:10.1107/ S2059798317008671.

Bebrone C, Anne C, De Vriendt K, Devreese B, Rossolini GM, Van Beeumen J, et al. Dramatic broadening of the substrate profile of the Aeromonas hydrophila CphA metallo-β-lactamase by site-directed mutagenesis. J Biol Chem.

2005;280(31):28195-202. Available from: doi:10.1074/jbc.M414052200.

Kong L, Vijayakrishnan B, Kowarik M, Park J, Zakharova AN, Neiwert L, et al. An antibacterial vaccination strategy based on a glycoconjugate containing the core lipopolysaccharide tetrasaccharide Hep2Kdo2. Nat Chem. 2016;8(3):242-9. Available from: doi:10.1038/nchem.2432.

Galloway WR, Hodgkinson JT, Bowden SD, Welch M, Spring DR. Quorum sensing in Gram-negative bacteria: Smallmolecule modulation of AHL and AI-2 quorum sensing pathways. Chem Rev. 2010;111(1):28-67. Available from: doi:10.1021/cr100109t.

Alanis AJ. Resistance to antibiotics: Are we in the post-antibiotic era?. Arch Med Res. 2005;36(6):697-705. Available from: doi:10.1016/j.arcmed.2005.06.009.

critical review

EDITED BY MILENA CIOANA & SABA MANZOOR

M E D U CATO R | D E C E M B E R 2018

Current antibiotic treatments are becoming increasingly diverse in order to target different bacterial functions. Further research is also being conducted on quorum-sensing methods and anti-bacterial vaccines to combat the emerging antibiotic resistance crisis.21,22 This evolutionary arms race may, however, be a losing battle if prevention and detection strategies are not optimized.

The diversity of CRE resistance pathways, in tandem with complicated variations in carbapenemase mechanisms, represents the near loss of an extremely potent antibiotic that was once considered a last resort in the clinical setting. It is of greater concern that the rate of resistance evolution is outpacing the development of new drugs, as more complex and lengthy research needs to be performed to target evolved mechanisms.7 Therefore, it is paramount to consider preventative and screening measures for CREs.7 Implementing proper hygiene practices and limiting antibiotics to only required usage remain crucial.7 Clinicians should be wary of prescribing antibiotics as unnecessary usage increases selective pressures and facilitates resistance development.23 Several studies have found that antibiotics are over-prescribed in hospital settings, with some identifying 50% of antibiotic prescriptions as being inappropriate.24,25 The apt and accurate detection of CREs is also critical in informing clinical decisions involving antibiotics. Numerous measurement methods are available for

Antibiotic resistance is a growing worldwide threat with catastrophic health implications.

The problem also brings with it complicated social and economic ramifications which necessitate immediate attention. By 2050, it is estimated that drug resistance will result in 10 million global deaths per year, with 315 000 of those being in North America alone, and a loss of over 100 trillion CAD from the global GDP.26,27 In the face of this global and rapid biological arms race, it is important to consider strategies beyond treatment techniques, such as those of prevention and screening, and work towards a more sustainable global solution.

18.

20

CRITICAL REVIEW

A RT I S T MICHELLE CHEN

“It’s a metaphor”: The role of religiosity in mental health

PAUL MUNIL LEE

Bachelor of Health Sciences (Honours) Class of 2018, McMaster University Correspondence: p.munil.lee@gmail.com

ABSTRACT Religion plays a significant role in the lives of many, and its impact on mental health cannot be underplayed. An individual’s religiosity can be measured by their involvement with institutions and behaviours associated with their religion, their attitudes and ideologies of religious faith, as well as their devotion to faith and God. All three aspects of religiosity play some role in the individual’s mental health, although each has different psychological, biological, and behavioural effects. Profound positive effects on mental health have been found for religious attitudes, while negative or no effects have been found for religious behaviours. These findings can have important clinical implications.

partakes in the institutions and behaviours of religion, 2) believes in the ideologies of religious faith, and 3) devotes oneself to faith and God.4 Mental health is a more multifaceted concept to define. Even the World Health Organization addresses the concept in broad strokes by describing it as a state of self-realization, resilience against stress, and the ability to contribute to the community.6 Negative indicators of mental health, such as psychological distress (e.g. depression or anxiety) and substance addiction, are often cited alongside positive indicators such as life satisfaction and motivation.4,7,8 Broadly speaking, mental health outcomes can be categorized into psychological, behavioural, and biological outcomes.

EMPIRICAL FINDINGS

INTRODUCTION AND HISTORY

M E D U CATO R | D E C E M B E R 2018

Proper operationalizations of both “religion”and “mental health” are incredibly important in this discussion.4,5 The framework outlined by Hackney and Sanders helps to organize concepts under the overarching term Two competing theories have been used to explain the of religion.4 By their account, the term ‘religiosity’ positive and negative effects of religiosity on mental defines the extent to which an individual or group: 1) health. The first is the theory of terror management,

critical review

Religion plays a major role in civilizations across the world, defining many aspects of individuality, culture, social organizations, institutions, and politics. Unsurprisingly, responses to its influence on mental health have been contentious. In the field of psychology, some prominent figures such as Sigmund Freud have considered adherence to religious practice to be a sign of neurosis —dangerous to the individual psyche and the greater community.1 Other psychologists have argued that adherence to religion can lead to a healthier mentality that is more hopeful and optimistic.1 The prevailing stance is that religious belief in and of itself is not indicative of an individual’s mental health or well-being. This has not always been the case. In the third edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM), published in 1980, no clear diagnostic lines were drawn between zealous religious belief and delusion or mental disorder. Later versions of the DSM clarified that distortions were a result of underlying mental health conditions, shifting away from pathologizing religiosity itself.2,3 This shift was accompanied by a greater focus on the concept of spirituality, which refers more broadly to the quality of the individual that is attuned to self-flourishing, something that can be independent of any formal institution.2

Psychological Outcomes Significant effect sizes have been found for religiosity on psychological distress, life satisfaction, and selfactualization.4 A meta-analysis of 35 studies found that overall scores of religiosity were positively correlated with scores in life satisfaction and selfactualization (r=0.12 [0.11–0.13], p<0.0001; r=0.24 [0.21–0.26], p<0.0001), and inversely related with psychological distress (r=0.02 [0.01–0.03], p<0.0001; reverse-coded). However, these results represent overall effect sizes; individual aspects of religion had varying associations with these three outcomes. For instance, greater involvement with the institutions of religion predicted significantly higher psychological distress. Participating in religious practices and organizations was negatively associated with the individual’s psychological adjustment and mental health, which may be due to incompatibility between external institutions and individual needs or desires.

By contrast, high levels of personal devotion —the aspect of religion connected most closely with religious attitude and emotional attachment— most strongly predicted high self-actualization. One of the main limitations of this meta-analysis, however, was the heterogeneity in definitions of religiosity and mental health in the included studies. The authors judiciously categorized the studies’ outcomes into the previous categories, but different results could have been obtained had these categories been operationalized differently. Nevertheless, this meta-analysis was conducted in the context of other previous systematic reviews and meta-analyses, and operationalizations were done appropriately and systematically.

22

1.

Levin J. Religion and mental health: Theory and research. Int J Appl Psychoanal. 2010;7(2): 102-115. Available from: doi:10.1002/aps.240.

2.

Turner RL, Lukoff D, Barnhouse R, Lu F. Religious or spiritual problem: A culturally sensitive diagnostic category in the DSM-IV. J Nerv Ment Dis. 1995;183(7): 435-44. Available from: doi:10.1097/00005053-19950700000003.

3.

Post S. DSM-III-R and religion. Soc Sci Med. 1992;35(1): 81-90. Available from: doi:10.1016/0277-9536(92)901216.

4.

Hackney C, Sanders G. Religiosity and mental health: A meta-analysis of recent studies. J Sci Study Relig.

2003;42(1): 43-55. Available from: doi:10.1111/1468-5906.t01-100160.

5.

Wong Y, Rew L, Slaikeu K. A systematic review of recent research on adolescent religiosity/spirituality and mental health. Issues Ment Health Nurs.

2006;27(2): 161-83. Available from: doi:10.1080/01612840500436941.

6.

World Health Organization. Mental health: A state of well-being [Internet]. 2014 [Accessed 2018 Nov 6]. Available from: http://www.who.int/features/factfiles/ mental_health/en/.

7.

Baetz M, Toews J. Clinical implications of research on religion, spirituality, and mental health. Can J Psychiatry.

2009;54(5): 292-301. Available from: doi:10.1177/070674370905400503.

M E D U CATO R

| D E C E M B E R 2018

critical review

8.

23

Kasen S, Wickramaratne P, Gameroff M, Weissman M. Religiosity and resilience in persons at high risk for major depression. Psychol Med. 2013;42(3): 509-19. Available from: doi:10.1017/ S0033291711001516.

9.

Greenberg J, Simon L, Pyszcnski T, Solomon S. A terror management theory of social behavior: The psychological functions of self-esteem and cultural worldviews. Adv Exp Soc Psychol. 1991;24: 93-160. Available from: doi:10.1016/ S0065-2601(08)60328-7.

10.

Deci E, Ryan R. Intrinsic Motivation and Self-Determination in Human Behavior.

New York: Plenum Press; 1985.

11.

Dezutter J, Soenens B, Hutsebaut D. Religiosity and mental health: A further exploration of the relative importance of religious behaviors vs. religious attitudes. Pers Individ Dif. 2006;40(4): 807-18. Available from: doi:10.1016/j. paid.2005.08.014.

12.

McCullough M, Willoughby B. Religion, self-regulation, and self-control: Associations, explanations, and implications. Psychol Bull. 2009;135(1): 69-93. Available from: doi:10.1037/a0014213.

13.

Seeman T, Dubin L, Seeman M. Religiosity/Spirituality and health: A critical review of the evidence for biological pathways. Am Psychol. 2003;58(1): 5363. Available from: doi:10.1037/0003066X.58.1.53.

14.

Boyer P. Religious thought and behaviour as by-products of brain function.

Trends Cogn Sci. 2003;7(3): 119-24.

Available from: doi:10.1016/S13646613(03)00031-7.

15.

Kapogiannis D, Barbey A, Su M, Zamboni G, Krueger F, Grafman J. Cognitive and neural foundations of religious belief. Proc Natl Acad Sci U S A. 2009;106(12): 4876-4881. Available from: doi:10.1073/pnas.0811717106.

16.

Harris K, Edlund M, Larson S. Religious involvement and the use of mental health care. Health Serv Res. 2006;41(2): 395-410. Available from: doi:10.1111/ j.1475-6773.2006.00500.x.

which describes the protective effects of adhering to a ‘shared cultural worldview’ and how it can provide a sense of security and greater meaning to the individual.9 However, this theory contrasts with some of the authors’ findings, primarily that partaking in religious institutions was positively associated with psychological distress.

The theory of self-determination presents an alternative perspective.10 This theory supports the finding that personal devotion or investment in religion —so long as it is accompanied by healthy internalization of values, beliefs, and motivation— can provide benefits to an individual’s self-esteem, selfdetermination, and mental health.

The theory of self-determination is in line with another study that investigated the differential effects of religious behaviour and religious attitude on the mental health of an individual. This study administered a questionnaire to 472 participants to assess their religious involvement, religious orientation, and social-cognitive approaches to religion.11 It was found that the two domains involving the attitudinal aspects of religion —religious orientation and socialcognitive approaches to religion— were significantly and positively correlated to outcomes of well-being. However, religious involvement, which is primarily associated with the behavioural aspects of religion, was not at all associated with psychological well-being.

Behavioural and Biological Outcomes Despite the evidence suggesting a

negative correlation between religious behaviour and psychological well-being, religious involvement can promote healthy behaviours such as tobacco and alcohol avoidance, as well as reduce antisocial behaviours.1 Furthermore, because religion can be a means of establishing community, social, and emotional supports, it can promote healthy behaviours that are not directly religious. Notably, some of the psychological outcomes, such as those of self-actualization and selfmotivation, can also be found in nonreligious and non-spiritual people. These outcomes may be results of improved self-control and self-regulation, and not religious belief specifically.12 More recent research tries to connect behaviour with neurobiology, often with the motive of finding new methods of therapy. Unfortunately, literature that assesses correlates of religiosity and neural structure and function is scant. Very little is known about the exact neural foundations of religiosity, and past research has focused primarily on unusual religious experiences resulting from abnormalities in limbic and temporal areas of the brain.14,15 It is unwise to generalize these findings to all religious thought, given that they are likely exceptions to the vast majority of religious thoughts and experiences, which are not pathological.

One recent fMRI study examined particular regions of the brain that were activated when patients thought about certain religious statements.15 The findings showed that statements reflecting God’s perceived emotion activated areas involved in higherorder emotional regulation, while statements regarding ‘God’s love’ activated an area involved in positive emotional states and suppression of sadness.The authors suggested

health care. Furthermore, a negative relationship was found between the perceived importance of religious beliefs and use of outpatient mental health care. The data suggest that religious behaviours provide a greater facilitative effect in the usage of mental health services than religious attitude. This finding demonstrates that although religion need not be at the core of mental health care, religious institutions and organizations can provide the scaffolding for mental health care service delivery. This sort of mental health service would be most helpful for patients who are already involved with a religion, or who have a desire to become involved.

CLINICAL IMPLICATIONS

CONCLUSION

In their paper, Baetz and Toews highlight how current research on religion, spirituality, and mental health can inform clinical practice.7 They discuss practical means of incorporating ‘psychospiritual interventions’ into patient treatment by referring to common spiritual issues such as forgiveness, gratitude, and altruism.

These concepts are common in most major religions and for a good reason: researchers have discovered that “positive acts and emotions have a profound effect on health,” which is a theory central to positive psychology.7

Involvement with religious practices and institutions can help facilitate mental well-being, although it is more so the individual’s orientation toward self-determination and flourishing that has the greater positive impact. To some, religious doctrines and practices act as symbols or metaphors that help them grapple with the difficulties of life. This does not downplay the significance of religious institutions and frameworks; further research may be able to identify the core therapeutic aspects of religion that can be translated to other forms of mental health therapy.

Data from the 2001–2003 National Surveys on Drug Use and Health were used to identify subgroups with moderate and serious mental or emotional distress.16 This outcome was related to frequency of religious service attendance and strength and influence of religious belief.

Evidence was found of a positive relationship between religious service attendance and use of outpatient mental

critical review

that activation of this positive emotion area may explain the inverse relationship between positive conceptualizations of God and the incidence of depressive symptoms. However, it is unclear if those thoughts exclusively result in activation of positive emotion areas, or if any thought associated with positive emotion, such as one of a loved one or family member, activates such areas. Regardless, it is evident that religious or spiritual attitudes may orient the individual towards better mental health outcomes. More research needs to be done to ascertain the exclusive effects of religiosity on neural functioning.

REVIEWED BY DR. DEBBIE NIFAKIS

| D E C E M B E R 2018

EDITED BY JESSICA CHEE & ANITA SHAH

M E D U CATO R

Dr. Debbie Nifakis is an Associate Director for Counselling and an Associate Clinical Professor in the Department of Psychiatry and Behavioural Neurosciences at McMaster University. She has received the Alan Blizzard Award for Teaching in Higher Education, President’s Award of Excellence in Teaching, and Distinguished Service Award for Teaching from Niagara University.

24

INTERVIEW SPOTLIGHT

DR. MIK E A P KO N AN INTERVIEW WITH THE CEO OF SICKKIDS

FROM PATIENT TO PERSON-CENTERED CARE ROMI LIFSHITZ Bachelor of Arts and Science, Class of 2021, McMaster University

As a successful healthcare leader, innovator, and catalyst for change, Dr. Michael Apkon, MD, PhD, MBA, has led three of the largest academic medical institutions in North America. This fall, Dr. Apkon —the President and CEO of The Hospital for Sick Children in Toronto since 2014— was appointed as the President and CEO of Tufts Medical Center and Floating Hospital for Children in Boston. In addition to his administrative role, Dr. Apkon holds the position of Physician Executive and Professor of Pediatrics at the University of Toronto. Prior to his role at SickKids, Dr. Apkon was the Chief Medical Officer for the Children’s Hospital of Philadelphia and the Executive Director of Yale-New Haven Children’s Hospital.



A LOT O F T H E S T U D E N T S AT M C M A S T E R M I G H T B E W O N D E R I N G, “ W H AT D O E S A C E O D O?” I see the CEO role as what I would call a “sense-maker.”

They help the executive team and people within the organization make sense of what is happening in the world around them to be able to align and direct their energy to have a bigger impact than anyone could have —where the sum is more than its parts, if you will. A CEO also plays a similar role in helping the public, government, and any other external stakeholders understand the organization, and engage in public discourse to determine how, given what society needs from us, an organization like SickKids can be successful.



WHAT WOULD BE A TYPICAL DAY IN THE LIFE OF A SICKKIDS CEO?

That’s a great question! I think every day is a different set of challenges or activities. I would say that a lot of the work is focused on what we’re doing inside the hospital —series of meetings, either one-on-one or with large

groups, to both set direction and monitor progress towards the objectives that we all commit to. Sometimes it’s problemsolving, sometimes it’s just listening to understand how things are working and where we can do things differently.

Another big part of the job is working with external stakeholders; for example, participating in committees with other hospitals connected to the university, or partners across the healthcare system, to see how we can collaborate to create a more seamless experience for children and their families, and create a more efficient healthcare system together.

Then, there is a small part of my job that is still seeing patients, as I continue having a small number of patients that I care for here at SickKids. There are a number of physician-CEOs that continue to be actively involved in patient care, but that’s not true of every CEO.

 SO, YOU WERE A PHYSICIAN, A RESEARCHER, AND, NOW, ALSO A CEO. WHAT DROVE YOU TO THE POSITION OF CEO?



DO YOU THINK THAT THE TECHNICAL SKILLS FROM BEING A PHYSICIAN AND RESEARCHER ARE NECESSARY TO BE A CEO?

I personally feel that healthcare workers have two responsibilities. One is to do the very best that they can with the way healthcare or medicine is practiced today. The other is to make the system better for the future. Thus, learning the terms of quality improvement, thinking about the policy space and how society makes the decision of whether we pay for drug A or drug B is very important.



SO WHERE DO YOU SEE HEALTHCARE ADVANCING WITHIN THE NEXT FEW YEARS?

At the highest level, I see healthcare transforming [away] from a focus on episodes of care. In other words, going from people shifting [between] emergency departments to the operating room for a surgery and later to a doctor’s visit, towards care as a more continuous process. Data will be driven from a person’s minute-to-minute existence —from wearables to smartphones. That feeds a system that engages multiple caregivers to be able to work together to extend the [length] and quality of life.

If I think about a place like SickKids, historically, we would have focused on how well a surgery went: did the child survive a really complex surgery? Now, we really are focused on how [we can] help children have the most functional and happiest and most productive childhood possible, and how [we] help them become productive, engaged adults that live up to their fullest potential. Getting there requires a different way of thinking about the way all the different healthcare caregivers work together, and how we use information and coordinate the work that we do with each other, to better understand what’s happening with people minute-to-minute, if necessary.

That’s the biggest transformation that I think we will see.

| D E C E M B E R 2018

I’d say what has been helpful more so than being a physician is being a caregiver. I do think that experience gives you a deeper understanding of patients and what people go through during the experience of injury, illness, and recovery. That influences the way I make decisions, at least, around how we operate, what we invest in, [and] how we appropriate funds for our budgets.

I don’t know what the gap areas are in terms of typical medical disciplines because I’m not sure that healthcare will be organized according to the typical medical disciplines when you look at five or ten years from now. What’s interesting is to think about where medicine is going with respect to precision medicine and genomics, and how those concepts weave across different specialties. Fields like regenerative medicine and immunotherapeutics are areas that will touch many disease categories, many different “-ologies” (cardiology, endocrinology, gastroenterology, etc.). I think that each of those create a new opportunity for students to advance the field and create a role for themselves in medicine going forward.

M E D U CATO R

I think the skills of a physician or a scientist are not necessary, but I do think they have been valuable. I would say that as a scientist, your understanding of the world is only as good as the hypothesis that you have, and the mental model that you have, until somebody is able to disprove that. I think that creates a certain open-mindedness […] that’s quite helpful for an executive. Certainly, [when] leading a research enterprise like SickKids, having at least an understanding of what scientists do has been very helpful as well.

THERE ARE A LOT OF STUDENTS WHO ARE INTERESTED IN HEALTHCARE, WHETHER IT BE IN HEALTH POLICY, HEALTH INNOVATION, BIOMEDICAL ENGINEERING, OR OTHER FIELDS. WHAT DO YOU THINK ARE THE BIGGEST GAP AREAS IN WHICH STUDENTS SHOULD FOCUS ON?

interview spotlight

I found as a physician that there were aspects of the environment that I worked in that were frustrating —either programs that I felt we should have that didn’t exist, or opportunities to improve quality that I didn’t feel were addressed quickly enough. So, I began to get involved in quality improvement and found that I liked the teamwork [and] having a positive effect on many more kids than I could care for by myself, as a physician. In some ways, the CEO role is an opportunity to do that in the highest level within the organization, and to ensure that all parts of the organization are following a path towards greater impact and greater value for the children and families that we serve.



26

M E D U CATO R

|

D E C E M B E R 2018

interview spotlight table of contents

[This change] will be powered, in my view, by a number of other transformations. One is around precision medicine — going from treating syndromes, for example the syndrome of cystic fibrosis, to treating very specific genetic causes of cystic fibrosis, many of which need different kinds of treatment. We will also go through a transformation where doctors, nurses, and other caregivers individualize decisions based on what they’ve last seen, what their knowledge base has to be, and how they’re thinking that day [about] using artificial intelligence and machine learning to guide people in making the best decisions possible.

27

I also think that we’ll see a transformation driven by people having more information in their own hands about their health status, about the state of the medical literature, and about [the] best evidence-based approaches to certain treatments. If you think about how people navigate their travel, their dining, and pretty much any sphere, they [want] to have a lot more information at their fingertips and [...] control over their life. And, as we talk about patient-centred care, I think that people-centred care is going to be the next frontier. It will be less about how hospitals want to care for people and how hospitals conceptualize themselves. It’s going to be more driven by what people need from us and the choices that they make to go to one organization or another to get what they need.



WHAT WOULD YOU WANT MEDICINE TO LOOK LIKE IN 25 YEARS?

It’s really hard to imagine what medicine will look like in 25 years. Here [are] a couple of predictions: I do think that we will have to work in a much more seamless way, where we will integrate a lot of more varied information into clinical decision-making. We will know a lot more about how a person spends their time, what they eat, and what the environmental influences are on their healthcare.

We’ll know a lot more about their genetic makeup and the way they have developed as people. They will be able to use information technology to much more finely tune the treatment we will give them. We will also have much better tools to coordinate the care across [not only] many different disciplines of doctors, but also between doctors [and other healthcare professionals].

In 25 years, it will be the patient driving how those interactions happen with high expectations about a seamless hand-off between caregivers. [This will be] a much more integrated and coordinated approach, the impact of which will not be measured by any one episode, but by what that person’s life becomes under the care of the system.

We are a very fragmented healthcare system [that is] moving towards consolidation. I think in 25 years, we may be fragmented again, but with other tools to create the connective tissue between all the different pieces. But, I think we’ve got to be prepared for a time where hospitals don’t have the importance that they [currently] have in the healthcare system, where most care happens at home [and] the individual is really the driver of what they get...



WHAT IS YOUR NEW ROLE GOING TO BE AND WHAT WOULD BE YOUR FIRST CHALLENGE TO SOLVE?

I’ll be the President and CEO at the Tufts Medical Centre in Boston, which is affiliated with Tufts University. It’s also the academic medical centre within a multi-hospital system. I think one of the challenges will be working on a strategy that will allow the medical centre to add value to that integrated system, and also to be able to have the best advantage of the system in furthering the academic mission.

COMMUNITY SPACE WHAT IS NURSING & WHAT IS A NURSE? AUTHOR: JANET HÉLÈNE REVIEWED BY DR. RUTH CHEN

ACCELERATED NURSING CLASS OF 2019, MCMASTER UNIVERSITY CORRESPONDENCE: JANET.ZANIN@GMAIL.COM

Welcome to a new section of The Meducator, published in collaboration with the School of Nursing. This is a new feature in The Meducator, but nursing certainly isn’t a novel addition to the health sciences. So, where did we come from, and where are we going?

Most people believe that the history of nursing began with Florence Nightingale. In reality, she was a part of the relatively recent formalization of a long history of informal roles spanning many cultures. As early as the seventh century, both Islamic and Christian orders established informal roles of providing services to, and advocating for, the marginalized and weak in society.1,2,3 Prior to that, oral tradition established common archetypal figures, such as the ‘healer’ or ‘witch’, who provide pseudo-mystical care in psychosocial, physical, and spiritual domains.4

1.

2.

7.

8.

9.

10.

11.

12.

13.

Fissel ME. Introduction: Women, health, and healing in early modern Europe. Bull Hist Med. 2008;82(1): 1-17. Available from: doi:10.1353/bhm.2008.0024.

Rassool GH. The crescent and Islam: Healing, nursing and the spiritual dimension. Some considerations towards an understanding of the Islamic perspectives on caring. J Adv Nurs. 2000;32(6):1476-1484. Available from: doi:10.1046/j.1365-2648.2000.01614.x.

Nelson S, Gordon S. The rhetoric of rupture: Nursing as a practice with a history? Nurs Outlook. 2004; 52(5): 255-261. Available from: doi:10.1016/j.outlook.2004.08.001.

Ehrenreich B, English D. Witches, midwives, & nurses: A history of women healers. 2nd ed. New York: The Feminist Press at CUNY; 2010 McDonald L. Florence Nightingale and the early origins of evidence-based nursing. Evid Based Nurs. 2001;4(3): 68-69. Available from: doi:10.1136/ebn.4.3.68.

Whittock M, Leonard L. Stepping outside the stereotype: A pilot study of the motivations and experiences of males in the nursing profession. J Nurs Manag. 2003;11(4): 242-249. Available from: doi:10.1046/j.13652834.2003.00379.x.

Draper C, Louw G. What is medicine and what is a doctor? Medical students’ perceptions and expectations of their academic and professional career. Med Teach. 2007;29(5): 100-107. Available from: doi:10.1080/01421590701481359.

Daly WM, Carnwell R. Nursing roles and levels of practice: A framework for differentiating between elementary, specialist and advancing nursing practice. J Clin Nurs. 2003;12(2):158-167. Available from: doi:10.1046/ j.1365-2702.2003.00690.x.

El-Jardali F, Lavis JN. Issue brief: Addressing the integration of nurse practitioners in primary healthcare settings in Canada. McMaster Faculty of Health Sciences. 2011.

Martin-Misener R, Donald F, Kilpatrick K, Bryant-Lukosius D, Rayner J, Landry V et al. Benchmarking for nurse practitioner patient panel size and comparative analysis of nurse practitioner pay scales: Update of a scoping review. McMaster Faculty of Health Sciences. 2015.

College of Nurses of Ontario. Entry to practice competencies for registered nurses [Internet]. 2014 Available from: https://www.cno.org/globalassets/docs/reg/41037_entrytopracitic_final.pdf. [Accessed 2018 Sept 20].

Maier CB, Aiken LH. Task shifting from physicians to nurses in primary care in 39 countries: a cross-country comparative study. Eur J Public Health. 2016;26(6): 927-934. Available from: doi:10.1093/eurpub/ckw098.

Verma S, Paterson M, Medves J. Core competencies for health care professionals: What medicine, nursing, occupational therapy, and physiotherapy share. J Allied Health. 2006;35(2):109-115. Available from: http:// europepmc.org/abstract/MED/16848375 [Accessed 2018 Sept 20].

| D E C E M B E R 2018

3.

4.

5.

6.

EDITED BY SARAH ASHBURY & KEVIN ZHAO

M E D U CATO R

While the root of nursing has often been associated with women —even the Latin origin of the word nutrire means to suckle— this profession is not solely associated with feminine characteristics. In fact, the rise of male nurses has paralleled the rise of female physicians since the 1970s, with the number of men qualified as registered nurses having tripled in the past 40 years.6 However, nursing has not often had the social prestige that is attached to other health professions. An unclear definition of the nursing profession, complicated by the various roles in which nurses are employed, may contribute to this phenomenon.7,8 Nonetheless, nurses play an integral role in the interprofessional health care team. They work alongside surgeons in the operating room, radiographers in diagnostic imaging, physiotherapists in rehabilitation, social workers in family services, epidemiologists in public health, and midwives in labour and delivery. Nurses practise autonomously in areas all over the world; advanced practice nurses are the primary health care providers for approximately one million Canadians.9,10 The possibilities of the nursing profession are almost limitless.

community space

The formalization of nursing as a secular profession did begin with Florence Nightingale, and many picture her as “The Lady with the Lamp,” dedicated to the care of wounded soldiers.5 However, the development of nursing as a profession extends far beyond this traditional picture. Nightingale’s longest-lasting contributions to the nursing profession are those of evidence-based research. Deeply affected by the high mortality she witnessed during the Crimean War, Nightingale pressed to investigate the causes. Her findings, which linked soldier mortality with poor sanitation, inspired a recommendation for disease and mortality records which would allow problems to be identified and resolved more promptly.5 This research became one of the most successful knowledge translation campaigns ARTIST KARISHMA MEHTA on sanitation of the 19th century, establishing Nightingale as a pioneer who advanced the nursing profession.5 She demonstrated that nurses could not only promote physical, psychosocial, and spiritual health, but also apply empirical, scientific methods to induce individual and societal change.

28

Restraint use in an acute setting: A nursing student’s perspective WENDY FU Accelerated Nursing, Class of 2019, McMaster University Correspondence: fuwt@mcmaster.ca 1.

2.

3.

4.

5.

6.

7.

| M E D U CATO R

ARTIST LAURA NGUYEN

29

I stood at the foot of the stretcher and I watched a team of police officers, nurses, and security staff fighting to detain an agitated young woman.

She was brought into the emergency department due to abnormal behaviour and substance abuse.

As the team tried to restrain her, she began to flail, kick, and spit at anyone within arm’s reach.

After she had been secured to the stretcher, she threatened us by promising that she would remember our names, find our homes, and kill our families. Five milligrams of Haldol and two milligrams of Ativan later, she was heavily sedated.

For the next four hours, she remained secured in a five-point restraint as we monitored her vital signs and circulation.

the minimal restraint approach, the least coercive interventions should have been considered first.3 Currently, evidence strongly suggests that verbal de-escalation can be effective and should be attempted before employing any form of coercive control intervention.3 In fact, coercive control interventions, such as involuntary medication and mechanical restraints, have been demonstrated to escalate aggression.7 The team failed to choose the least restrictive option when there was an opportunity to do so. Rather than simply calming the patient, she was sedated and physically restrained with the five-point restraint for four hours. Alternatives such as soft-tie restraints were not considered.

The use of mechanical, physical, and chemical restraints to control patients has always carried ethical controversy.1 Chemical restraints are typically psychoactive medications, while physical and mechanical restraints are designed to limit a client’s mobility.2 The major consequences of restraint use in an acute setting include psychological distress, physical injury, and damage to therapeutic relationships between patients and staff.3 In Ontario, legislations such as the Mental Health Act, the Patient Restraint Minimization Act, and the Health Care Consent Act have guided the development of multiple initiatives supporting the use of minimal restraint.4,5,6 With this approach, all alternative measures available to control a patient should be exhausted before resorting to restraints.3 If restraint is deemed necessary, the least restrictive method should be implemented.3

Individuals who are more likely to receive control interventions in a hospital setting include those who have a substance addiction, a mental health diagnosis, and/or a history of abuse.7 Evidence suggests that patients are less likely to attend prescribed follow-up mental health treatments after being physically or mechanically restrained.8 Given the cyclic nature of this issue, we should be asking ourselves: does the short-term benefit of using control interventions outweigh the long-term costs?

As a student nurse, it can feel uncomfortable to challenge the decisions made by experienced healthcare professionals. However, it is imperative to advocate for the conservative use of restraints on behalf of patients who cannot do so themselves. As the paradigm continues to shift away from the traditional practice of routine restraint use, advocating in favour of a minimal restraint approach should be a responsibility shared by every healthcare professional.3

In this situation, the use of multiple restraints was effective in protecting the patient and staff from harm. However, there is a need to evaluate REVIEWED BY DR. LYNN MARTIN whether these control interDr. Martin is a full-time teaching professor in the McMaster University School of Nursing. Her research ventions were necessary interests include topics in nursing education for care, or simply resuch as faculty development, clinical teaching, flexive and convenient. skill development, and video assessment/virtual simulation.

In keeping with

D E C E M B E R 2018

case study

8.

Colaizzi J. Seclusion & restraint: A historical perspective. J Psychosoc Nurs Ment Health Serv. 2005;43(2):31-7. Available from: doi:10.3928/02793695-20050201-07.

College of Nurses of Ontario. Practice standard: Restraints. College of Nurses Ontario. 2017.

Knox DK, Holloman GH. Use and avoidance of seclusion and restraint: consensus statement of the American association for emergency psychiatry project BETA seclusion and restraint workgroup. West J Emerg Med. 2012;13(1):3540. Available from: doi:10.5811/ westjem.2011.9.6867.

Government of Ontario. Mental health act.

Government of Ontario. 2001.

Government of Ontario. Patient restraint minimization act. Government of Ontario. 2001.

Government of Ontario. Health care consent act.

Government of Ontario. 1996.

Canadian Institute for Health Information.

Restraint use and other control interventions for mental health inpatients in Ontario [Internet].

ON: CIHI; 2011. Available from: https://secure. cihi.ca/free_products/Restraint_Use_and_ Other_Control_I nterventions_AIB_EN.pdf [Accessed 2018 Oct 22].

Currier GW, Walsh P, Lawrence D. Physical restraints in the emergency department and attendance at subsequent outpatient psychiatric treatment. J Psychiat Pract. 2011;16(6):38593. Available from: doi:10.1097/01. pra.0000407961.42228.75.

EDITED BY PARNIKA GODKHINDI & NADIN ABBAS

M E D U CATO R

|

APRIL

2015

2

ABSTRACT DANIEL KIM Accelerated Nursing Class of 2019, McMaster University Correspondence: kimd57@ mcmaster.ca

Since the advent of legal non-medical prescribing in 1992, the number of non-medical prescribers, especially nurses, has been rapidly increasing. Although pending legislative development, Ontario has followed suit by legally permitting nurses to prescribe for non-complex conditions such as immunizations, contraception, and travel medicine. Enacted in response to criticisms on the quality of primary care and accessibility of necessary medical interventions in Ontario, non-medical prescribing is hoped to increase clinical effectiveness, quality of care, and job satisfaction for nurses, physicians, and allied health professionals. However, legitimate concerns have been raised about the safety of nurse prescribing and its impact on the coordination of care between nurses and physicians.

M E D U CATO R

|

D E C E M B E R 2018

critical review

INTRODUCTION

31

According to the World Health Organization (WHO), maximizing the roles of existing healthcare workers is critical for the modernization of healthcare.1 This means the historical constraints and traditions within healthcare must be re-evaluated. One example of this is expanding the practice of legal prescribing to non-doctor healthcare professionals.

In May 2017, the Ontario government officially permitted registered nurses (RNs) to “prescribe medications and communicate a diagnosis for the purpose of prescribing.” The College of Nurses of Ontario (CNO) has been tasked with implementing the regulatory framework that will make this possible, with a focus on the expanded scope of practice and setting the necessary requirements for nurse prescribers.2 The CNO plans to take a phased approach, allowing nurse prescribers to initially prescribe for non-complex conditions (e.g. immunizations, contraception, wound care) in community settings. Upon further evaluation, the CNO will consider the inclusion of prescribing for more complex conditions (e.g. chronic conditions, infections) in secondary and tertiary care.

The Registered Nurses’ Association of Ontario called for this change in 2012 amidst growing concerns about timely access to medications, especially amongst vulnerable populations.3 The Commonwealth Fund found that Canada consistently scores lower in timely access to healthcare and primary care compared to other OECD countries.4 In 2017, the median wait time for medically necessary treatment

in Canada was a record high of 21.2 weeks, a 128% increase from 9.3 weeks in 1993.5 The CNO plans to publish the new regulations and by-laws by December 2018. Once enacted, Ontario will become the first province in Canada where RNs can prescribe.2 However, Canada is not the first country to make this change, as there are currently nine countries that provide RNs with prescribing privileges.6 As a result, there exists an established body of literature that has investigated the impacts of nurse prescribing. This critical review will explore what is currently known about the safety and clinical outcomes associated with nurse prescribing. Moreover, the perspectives of various stakeholders including patients, nurses, and physicians will also be explored.

PATIENT SAFETY AND OUTCOMES Prescribing is a highly complex decisionmaking process requiring extensive knowledge and technical judgement.6 The WHO defines rational prescribing as, “patients receiving medications appropriate for their clinical needs, in doses that meet their own individual requirements, for an adequate period of time, and at the lowest cost to them and their community.”7 The most dominant criticism for nurses prescribing is whether nurses can accomplish this safely and effectively.

In a multi-center study conducted in Ireland, two independent expert reviewers evaluated the prescribing records of 25 nurse prescribers to assess their clinical decision-making.8 They found that the medications prescribed were

PATIENTS’ PERSPECTIVES

2.

3.

4.

5.

6.

7.

8.

9.

10.

11.

12.

13.

14.

15.

16.

17.

18.

World Health Organization. World report on knowledge for better health: Strengthening health systems. Geneva: World Health Organization; 2004.

College Nurses of Ontario. RN prescribing: What happened, what’s next? [Internet]. 2017 [Accessed 2018 Sept 23].

Available from: http://www.cno.org/en/ learn-about-standards-guidelines/magazines-newsletters/the-standard/September-2017/rn-prescribing-update/ Registered Nurses’ Association of Ontario. Independent RN prescribing [Internet].

2014 [Accessed 2018 Oct 20]. Available from: https://rnao.ca/policy/political-action/independent-rn-prescribing Marchildon GP, Hutchison B. Primary care in Ontario, Canada: New proposals after 15 years of reform. Health Policy.

2016;120(7): 732-8. Available from: doi:10.1016/j.healthpol.2016.04.010.

Fraser Institute. Waiting your turn: Wait times for health care in Canada, 2017 Report [Internet]. 2017 [Accessed 2018 Sept 23]. Available from: https:// www.fraserinstitute.org/studies/waitingyour-turn-wait-times-for-health-care-incanada-2017 Cope LC, Abuzour AS, Tully MP. Nonmedical prescribing: Where are we now? Ther Adv Drug Saf. 2016;7(4): 165-72. Available from: doi:10.1177/2042098616 646726.

World Health Organization. Promoting rational use of medicines. New Delhi: WHO Regional Office for South-East Asia; 2011.

Naughton C, Drennan J, Hyde A, Allen D, O’boyle K, Felle P et al. An evaluation of the appropriateness and safety of nurse and midwife prescribing in Ireland. J Adv Nurs. 2013;69(7): 1478-88. Available from: doi:10.1111/jan.12004.

Latter S, Smith A, Blenkinsopp A, Nicholls P, Little P, Chapman S. Are nurse and pharmacist independent prescribers making clinically appropriate prescribing decisions? An analysis of consultations.

J Health Serv Res Policy. 2012;17(3): 149-56. Available from: doi:10.1258/ jhsrp.2012.011090.

Creedon R, O’Connell E, McCarthy G, Lehane B. An evaluation of nurse prescribing. Part 1: A literature review. Br J Nurs. 2009;18(21): 13227. Available from: doi:10.12968/ bjon.2009.18.21.45366.

Courtenay M, Carey N, Burke J. Independent extended and supplementary nurse prescribing practice in the UK: A national questionnaire survey. Int J Nurs Stud.

2007;44(7): 1093-101. Available from: doi:10.1016/j.ijnurstu.2006.04.005.

Dilles T, Vander Stichele RR, Van Bortel L, Elseviers MM. Nursing students’ pharmacological knowledge and calculation skills: Ready for practice? Nurse Educ Today. 2011;31(5): 499-505. Available from: doi:10.1016/j.nedt.2010.08.009.

Fletcher CE, Copeland LA, Lowery JC, Reeves PJ. Nurse practitioners as primary care providers within the VA. Mil Med. 2011;176(7): 791-7. Available from: doi:10.7205/MILMED-D-10-00329.

Houweling, ST, Kleefstra N, van Hateren KJ, Groenier KH, Meyboom-de Jong B, & Bilo HJ. Can diabetes management be safely transferred to practice nurses in a primary care setting? A randomised controlled trial. J Clin Nurs. 2011; 20(9-10):1264-72. Available from: doi: 10.1111/j.1365-2702.2010.03562.x.

Batbaatar E, Dorjdagva J, Luvsannyam A, Amenta P. Conceptualisation of patient satisfaction: A systematic narrative literature review. Perspect Public Health.

2015;135(5): 243-50. Available from: doi:10.1177/1757913915594196.

Courtenay M, Carey N, Stenner K, Lawton S, Peters J. Patients’ views of nurse prescribing: Effects on care, concordance and medicine taking. Br J Dermatol. 2011;164(2): 396-401.

Available from: doi:10.1111/j.13652133.2010.10119.x.

Brooks N, Otway C, Rashid C, Kilty E, Maggs C. The patient’s view: The benefits and limitations of nurse prescribing. Br J Community Nurs. 2001;6(7): 342-8. Available from: doi:10.12968/ bjcn.2001.6.7.7066.

Drennan J, Naughton C, Allen D, Hyde A, O’Boyle K, Felle P, et al. Patients’ level of satisfaction and self-reports of intention to comply following consultation with nurses and midwives with prescriptive authority: A cross-sectional

M E D U CATO R | A P R I L 2015 M E D U CATO R | D E C E M B E R 2018

Much of the current research supports the view that nurse prescribing leads to high patient satisfaction.10,14 As patient experience and satisfaction are critical indicators for quality of care, these measures are highly relevant and commonly used to inform health service improvements.15 According to patients, nurse prescribing received positive evaluations due to improved accessibility and efficiency of health services. Access to a nurse prescriber increases the number of appointments patients can make with a health professional. It is also associated with improved flexibility through telephone

Nurses have widely reported that being able to prescribe has improved their ability to provide care. In fact, some nurses have reported they already assist with prescribing on a regularly basis, and this change would simply formalize the process.22 Nurse prescribers have claimed this change has increased the amount of time they spend with patients and has allowed for more holistic care.23 Improved job satisfaction is also a commonly reported benefit of prescribing, with one study citing increased autonomy in areas of competency as a common reason.24,25 However, not all aspects of prescribing are associated with improved job satisfaction.

Nurses have reported that the increased

1.

critical review

clinically appropriate in 99% of all cases. Upon access and home visits.16 Nurse prescribers follow-up, only one adverse medication event can also offer the practicality of being assessed, was found. However, errors related to dosages, diagnosed, and prescribed in a single visit, drug-drug interactions, and drug-disease reducing the number of unnecessary referrals interactions were common.8 In addition, and consultations.17 another study with a similar design also found that experts widely considered nurse prescriber Patients have also reported differences in prescriptions as clinically appropriate but the consultation style of nurse prescribers had potential errors related to drug-disease compared to physicians, with nurse interactions and duration of therapy.9 Many prescribers being described as more of these errors were pharmacologically-related, approachable, attentive, and communicative.18 which validated a common concern that A study evaluating the effectiveness of nurse nurses may not possess the pharmacological prescriber-led dermatology clinics showed knowledge to safely prescribe.10 In response, that nurse prescribers adhere to high quality nurses voiced concerns that educational communication, information provision, and continuing professional development patient-centred care and consultation programs had glaring inadequacies related time, which are central aspects of effective to pharmacology.11 Inadequate knowledge in treatment.19,20 Patients interviewed after their pharmacology and medication competence clinic visit reported that nurse prescribers were also identified at the undergraduate showed greater interest in their concerns and level.12 It is crucial that educational involved them in the treatment decisionprograms at both the undergraduate and making process more frequently than professional level adequately prepare nurses physicians. They also reported having more to prescribe in order to ensure patient safety. time to discuss their treatment plans with a nurse prescriber compared to a physician.20 Another method of assessing patient safety Longer consultations allow for improved is evaluating clinical outcomes. Evidence information provision and patient education. that nurse prescribing will lead to similar For example, in an RCT comparing nurse or better outcomes compared to physician prescriber care to general practitioner (GP) prescribing is inconsistent. One randomized care, participants in the nurse prescriber control trial (RCT) assessing diabetic patients group reported receiving significantly treated by nurse prescribers versus physicians more information about their symptoms, found no differences in blood pressure or medication, lifestyle interventions, and were HbA1c levels, a measure of blood glucose, consulted about compliance more frequently.21 between the two groups.13 However, another These reported benefits were of particular RCT showed greater diabetes symptoms importance considering the increasing and quality of life deterioration under the burden of chronic disorders on the healthcare care of a nurse prescriber. Further studies, system, accompanied by the increasing especially large RCTs and longitudinal complexity and length of treatment plans. studies, are necessary to accurately assess the clinical outcomes of nurse prescribing.14 NURSES’ PERSPECTIVES

32 4

19.

20.

21.

22.

23.

24.

26.

27.

28.

29.

30.

31.

PHYSICIANS’ PERSPECTIVES

The Health Professions Regulatory Advisory Council (HRPAC) surveyed various stakeholders in Ontario, including physician associations, and found that only 52.4% of respondents agreed that having RNs prescribe would improve patient well-being. Among all health professions, physicians tended to be the most divided when it came to nurse prescribing.10

Important factors to successfully implement nurse prescribing at an organizational level include a highly committed and supportive team as well as a clear vision of how nurse prescribing can improve patient care.32 Policies alone are insufficient to ensure behavioural changes, and the successful translation of this new policy into action demands that both nurses and physicians examine their own values and biases.

CONCLUSION

Physicians voicing their approval of nurse prescribing state an improvement in quality of To improve access to care, nurses in Ontario care. Doctors have reported nurse prescribers have been legally permitted to prescribe can uniquely benefit patients because of their certain medications, which represents a step proficiency in relationship building.28 One forward in the current trend of expanding the reason for this is RNs tend to have prolonged responsibilities of healthcare professionals. and continuous contact with their patients, Although evidence suggests that nurses which could maximize patient autonomy.28 are capable of prescribing medications for Moreover, nurse prescribers have the potential various clinical conditions, the potential to directly improve the care physicians provide impact this will have on the number of by reducing physicians’ patient load and time medication errors is unclear. Moreover, spent on routine tasks, thus increasing time views from various stakeholders including patients, nurses, and physicians have been available for more complex cases.29 mixed. Many see benefits related to patient On the other hand, safety is a key concern and job satisfaction, but also recognize its that physicians have when considering nurse potential to complicate the delivery of health prescribing. Studies have shown that doctors services. As further research is conducted and were far more trusting of nurse prescribers if clinical guidelines become established, a more definitive picture of this change will emerge. ■ they had previously worked with them for a

M E D U CATO R

|

D E C E M B E R 2018

32.

workload and responsibility that comes with long time.22,28 However, this marginalizes new prescribing is associated with significant and inexperienced nurse prescribers who rely work-related stress and anxiety.25 Fear of on physicians for informal support and training. litigation, time constraints, pressure from Physicians have also raised concerns about role patients and physicians, continuous need clarity, professional boundaries, and the impact to update competencies, and an additional an additional prescriber will have on their documentation burden have all been described autonomy to lead care plans.22 Boundaries are as negative implications of prescribing.25,26 essential for maintaining professional identity This is especially important considering and power; therefore, blurred boundaries are the high prevalence of burnout that already a common source of conflict between nurses exists in nursing, which could result in and physicians.30 This is especially important poor quality of care and negative patient considering pre-existing nurse-physician outcomes.27 To ensure that the benefits tensions.31 Both nurses and physicians agree of nurse prescribing are sustainable, the that having an additional prescriber will additional challenges and stressors nurse complicate the coordination of care. Thus, prescribers will face must be addressed. improved communication between the two professions will be necessary.28

critical review

critical review

25.

survey. Int J Nurs Stud. 2011;48(7): 808-817. Available from: doi:10.1016/j. ijnurstu.2011.01.001.

Thompson L, McCabe R. The effect of clinician-patient alliance and communication on treatment adherence in mental health care: A systematic review. BMC Psychiatry. 2012;12(1): 87. Available from: doi:10.1186/1471-244X-12-87.

Courtenay M, Carey N, Stenner K, Lawton S, Peters J. Patients’ views of nurse prescribing: Effects on care, concordance and medicine taking. Br J Dermatol. 2011;164(2): 396-401.

Available from: doi:10.1111/j.13652133.2010.10119.x.

Allen JK, Himmelfarb CR, Szanton SL, Bone L, Hill MN, Levine DM. COACH trial: A randomized controlled trial of nurse practitioner/community health worker cardiovascular disease risk reduction in urban community health centers: Rationale and design. Contemp Clin Trials.

2011;32(3): 403-11. Available from: doi:10.1016/j.cct.2011.01.001.

Buckley P, Grime J, Blenkinsopp A. Inter and intra-professional perspectives on non-medical prescribing in an NHS trust.

Pharm J. 2006;277: 394. Available from: https://www.pharmaceutical-journal. com/libres/pdf/papers/pj_20060930_ prescribing.pdf [Accessed 2018 Sep 23] Nolan P, Bradley E. The role of the nurse prescriber: The views of mental health and non-mental health nurses. J Psychiatr Ment Health Nurs. 2007;14(3): 25866. Available from: doi:10.1111/j.13652850.2007.01072.x.

Creedon R, O’Connell E, McCarthy G, Lehane B. An evaluation of nurse prescribing. Part 2: A literature review. Br J Nurs.

2009;18(22):1398-402. Available from: doi:10.12968/bjon.2009.18.22.45570.

Cousins R, Donnell C. Nurse prescribing in general practice: A qualitative study of job satisfaction and work-related stress. J Fam Pract. 2011;29(2): 2237. Available from: doi:10.1093/fampra/ cmr077.

Kooienga S, Wilkinson J. RN prescribing: An expanded role for nursing. Nurs Forum. 2017;52(1): 3-11. Available from: doi:10.1111/nuf.12159.

Poghosyan L, Clarke SP, Finlayson M, Aiken LH. Nurse burnout and quality of care: Cross-national investigation in six countries. Res Nurs Health. 2010;33(4): 288-98. Available from: doi:10.1002/ nur.20383.

Courtenay M, Carey N. Nurse prescribing by children’s nurses: Views of doctors and clinical leads in one specialist children’s hospital. J Clin Nurs. 2009;18(18): 2668-75. Available from: doi:10.1111/ j.1365-2702.2009.02799.x.

Carey N, Stenner K, Courtenay M. Stakeholder views on the impact of nurse prescribing on dermatology services.

J Clin Nurs. 2010;19(3-4): 498-506.

Available from: doi:10.1111/j.13652702.2009.02874.x.

Abbott A. The system of professions: An essay on the division of expert labor.

United States: University of Chicago Press; 2014.

Walby S, Greenwell J. Medicine and nursing: Professions in a changing health service. Lancaster: Sage; 1994.

Patel MX, Robson D, Rance J, Ramirez NM, Memon TC, Bressington D, et al. Attitudes regarding mental health nurse prescribing among psychiatrists and nurses: A cross-sectional questionnaire study. Int J Nurs Stud. 2009;46(11): 1467-74. Available from: doi:10.1016/j. ijnurstu.2009.04.010.

REVIEWED BY DR. RUTH HANNON Dr. Hannon is a full-time teaching professor in the School of Nursing at McMaster University and a part-time Nurse Practioner (NP) in a Burlington Family Health Team.

She holds an MPA from Australia and completed her NP and DNP in Buffalo, NY. EDITED BY AARON WEN & ANGELA DONG

33 5

STAFF

VIDEO TEAM Managing Video Editor Adrian Marcuzzi

EDITORS-IN-CHIEF Owen Dan Luo Eva Liu

GRAPHICS & DESIGN Creative Directors Bob Yang Matilda Kim Anqi Wu Esra Rakab Wendy Zhang Ruby Zheng Kien Nagales

MEDUPROMO Director Daniel Diatlov Medupromoters Liz Jacob Natalie Palumbo Alisha Sharma Sherin Talebi Zahra Abdallah Angela Yang Stephanie Kay Milena Cioana

CONTACT US THROUGH EMAIL the.meducator@gmail.com

VISIT OUR WEBSITE FOR PAST ISSUES www.meducator.org

FOLLOW UPDATES ON FACEBOOK www.facebook.com/themeducator

FIND US ON YOUTUBE

www.youtube.com/user/MeducatorTV

INTERESTED IN WRITING FOR OUR NEXT ISSUE? Visit www.meducator.org/ submit-now

MEDUCOLLAB Directors Edward Cui Parnika Godkhindi

M E D U CATO R M E D U CATO R | D e c 2 0 1 4 | D E C E M B E R 2018

Graphic Designers Peri Ren Annisa Siu Laura Nguyen Suffia Malik Michelle Chen Karishma Mehta

Video Producers Albert Zhao Katherine Sliwowicz Khashayar Poorzargar Anson Lee Erin Lin Nina Vujovic

The Meducator, BHSc (Honours) Program Michael G. DeGroote Centre for Learning and Discovery Room 3308 Faculty of Health Sciences 1280 Main Street West Hamilton, Ontario L8N 3Z5

WE WOULD LIKE TO GIVE A THANK YOU TO OUR SPONSORS FOR THEIR GENEROUS SUPPORT

Bachelor of Health Sciences (Honours) Program

McMaster Student Union

Bachelor of Health Sciences Society

critical review contributors

EDITORIAL BOARD Managing Editors Sheila Yu Kevin Chen Editors Albert Stancescu Takhliq Amir Nadin Abbas Sarah Asbury Anita Shah Jessica Chee Kevin Zhao Angela Dong Saba Manzoor Jim Xie Daniel Rayner James Yu Matthew Lynn Milena Cioana Aaron Wen Daniel Diatlov Parnika Godkhindi Edward Cui

ADDRESS

Integrated Biomedical Engineering & Health Sciences Program

School of Nursing

Office of the President

34 6

INTERESTED IN WRITING FOR US? VISIT WWW.MEDUCATOR.ORG/SUBMIT-NOW