Research Report 2015-18 by Canadian Memorial Chiropractic College

Research Report 2015–18 A selection of published research by CMCC faculty Featured articles include: 7

The Biological Basis of Degenerative Disc Disease: Proteomic and Biomechanical Analysis of the Canine Intervertebral Disc

Erwin WM, DeSouza L, Funabashi M, Kawchuk G, Karim MZ, Kim S1, Mädler S, Matta A, Wang X, Mehrkens KA

38 Changes in Manipulation Peak Force Modulation and Time to Peak Thrust Among First-Year Chiropractic Students Following a 12-Week Detraining Period

Starmer DJ, Guist BP, Tuff TR, Warren SC, Williams MG

50 Clinical Practice Guidelines for the Noninvasive Management of Low Back Pain: A Systematic Review by the Ontario Protocol for Trafﬁc Injury Management (OPTIMa) Collaboration

Wong JJ, Côté P, Sutton DA, Randhawa K, Yu H, Varatharajan S, Goldgrub R, Nordin M, Gross DP, Shearer HM, Carroll LJ, Stern PJ, Ameis A, Southerst D, Mior S, Stupar M, Varatharajan T, Taylor-Vaisey A

64 Prescription Dispensing Patterns Before and After a Workers’ Compensation Claim: An Historical Cohort Study of Workers With Low Back Pain Injuries in British Columbia Carnide N, Hogg-Johnson S, Furlan AD, Côté P, Koehoorn M

Our Mission An academic institution recognized for creating leaders in spinal health

Our Vision Deliver world class chiropractic education, research and patient care

CMCC is dedicated to pursuing innovation in education, research and patient care. In this way, the institution effectively prepares its students to become tomorrowâ&#x20AC;&#x2122;s leaders in spinal health. CMCCâ&#x20AC;&#x2122;s achievements in these academic years demonstrate the success of this approach in paving the way toward increased collaboration with other health care professions, and helping to define the profession within the changing Canadian health care landscape.

CMCC Research Report 2015–18 A selection of published research by CMCC faculty 4

Welcome

The Biological Basis of Degenerative Disc Disease: Proteomic and Biomechanical Analysis of the Canine Intervertebral Disc Erwin WM, DeSouza L, Funabashi M, Kawchuk G, Karim MZ, Kim S, Mädler S, Matta A, Wang X, Mehrkens KA

20 Effect of Interactive Neurostimulation Therapy on Inflammatory Response in Patients With Chronic and Recurrent Mechanical Neck Pain Teodorczyk-Injeyan JA, Triano JJ, McGregor M, Woodhouse L, Injeyan HS 21 Differential Displacement of Soft Tissue Layers From Manual Therapy Loading Engell S, Triano JJ, Fox JR, Langevin HM, Elisa E.Konofagou EE 22 Patient-Induced Reaction Forces and Moments Are Influenced by Variations in Spinal Manipulative Technique D’Angelo K, Triano JJ, Kawchuk GN, Howarth SJ 23 Molecular Therapy for Degenerative Disc Disease: Clues from Secretome Analysis of the Notochordal Cell-Rich Nucleus Pulposus Matta A, Karim MZ, Isenman DE, Erwin WM 24 Procedure Selection and Patient Positioning Influence Spine Kinematics During HighVelocity, Low-Amplitude Spinal Manipulation Applied to the Low Back Bell S, D’Angelo K, Kawchuk GN, Triano JJ, Howarth SJ 25 TENS-like Stimulation Downregulates Inflammatory Cytokines in a PC-12 Cell Line Sovak G, Budgell B 26 Elevated Production of Nociceptive CC Chemokines and sE-Selectin in Patients With Low Back Pain and the Effects of Spinal Manipulation: A Nonrandomized Clinical Trial Teodorczyk-Injeyan JA, McGregor M, Triano JJ, Injeyan SH 27 A Randomized Pragmatic Clinical Trial of Chiropractic Care for Headaches With and Without a Self-Acupressure Pillow Vernon H, Borody C, Harris G, Muir B, Goldin J, Dinulos M 28 Effectiveness of Acupuncture Therapies to Manage Musculoskeletal Disorders of the Extremities: A Systematic Review Cox J, Varatharajan S, Côté P, OPTIMa Collaboration 29 Effect of Two Consecutive Spinal Manipulations in a Single Session on Myofascial Pain Pressure Sensitivity: A Randomized Controlled Trial Laframboise MA, Vernon H, Srbely J 30 Are Manual Therapies, Passive Physical Modalities, or Acupuncture Effective for the Management of Patients with WhiplashAssociated Disorders or Neck Pain and Associated Disorders? Wong JJ, Shearer HM, Mior S, Jacobs C, Côté P, Randhawa K, Yu H, Southerst D, Varatharajan S, Sutton D, van der Velde G, Carroll LJ, Ameis A, Ammendolia C, Brison R10, Nordin M11, Stupar M1, Taylor-Vaisey A

31 Risk of Carotid Stroke after Chiropractic Care: A Population-Based Case-Crossover Study Cassidy JD, Boyle E, Côté P, Hogg-Johnson S, Bondy SJ, Haldeman S 32 The Effect of Phase of Menstrual Cycle on Joint Mobility in the Cervical Spine and Extremities in Nulliparous Women: A Cross-Sectional Study Weis CA, Grondin D, Vernon H 33 Ultrasound Assessment of Abdominal Muscle Thickness in Women With and Without Low Back Pain During Pregnancy Weis CA, Nash J, Triano JJ, Barrett J 34 Validity and Reliability of Clinical Prediction Rules Used to Screen for Cervical Spine Injury in Alert Low-Risk Patients with Blunt Trauma to the Neck: Part 2. A Systematic Review From the Cervical Assessment and Diagnosis Research Evaluation (CADRE) Collaboration Moser N, Lemeunier N, Southerst D, Shearer H, Murnaghan K, Sutton D, Côté P 35 Association of Venous Leg Ulcers With Ankle Range of Motion in People Attending Chiropractic Mobile Clinics in the Dominican Republic Tavares PA, Landsman V, Gomez N, Ferreiras A, Lopez RA 36 Tool to Assess Causality of Direct and Indirect Adverse Events Associated with Therapeutic Interventions Zorzela L, Mior S, Boon H, Gross A, Yager J, Carter R, et al. 37 Chiropractic Spinal Manipulation and the Risk for Acute Lumbar Disc Herniation: A Belief Elicitation Study Hincapié CA, Cassidy JD, Côté P, Rampersaud YR, Jadad AR, Tomlinson GA 38 Changes in Manipulation Peak Force Modulation and Time to Peak Thrust Among First-Year Chiropractic Students Following a 12-Week Detraining Period Starmer DJ, Guist BP, Tuff TR, Warren SC, Williams MG 45 No Difference in Learning Retention in Manikin-Based Simulation Based on Role Giuliano D, McGregor, M 46 Description of the case mix experienced by chiropractic students during a clinical internship Puhl AA, Reinhart CJ, Injeyan SH, Tibbles A 47 Concussion Knowledge Among Sport Chiropractic Fellows from the Royal College of Chiropractic Sports Sciences (Canada) Kazemi M, Bogumil ME, Vora K 48 The Effectiveness of Exercise on Recovery and Clinical Outcomes in Patients with Soft Tissue Injuries of the Hip, Thigh, or Knee: A Systematic Review by the Ontario Protocol for Traffic Injury Management (OPTIMa) Collaboration Brown CK, Southerst D, Côté P, Shearer HM, Randhawa K, Wong JJ, Yu H, Varatharajan S, Sutton D, Stern PJ, D’Angelo K, Dion S, Cox J, Goldgrub R, Stupar M, Carroll LJ, Taylor-Vaisey A 49 Exercise as a Vital Sign: A Preliminary Pilot Study in A Chiropractic Setting Howitt S, Simpson K, Suderman D, Mercer A, Rutherford S, deGraauw C

50 Clinical Practice Guidelines for the Noninvasive Management of Low Back Pain: A Systematic Review by the Ontario Protocol for Trafﬁc Injury Management (OPTIMa) Collaboration Wong JJ, Côté P, Sutton DA, Randhawa K, Yu H, Varatharajan S, Goldgrub R, Nordin M, Gross DP, Shearer HM, Carroll LJ, Stern PJ, Ameis A, Southerst D, Mior S, Stupar M, Varatharajan T, Taylor-Vaisey A 64 Prescription Dispensing Patterns Before and After a Workers’ Compensation Claim: An Historical Cohort Study of Workers With Low Back Pain Injuries in British Columbia Carnide N, Hogg-Johnson S, Furlan AD, Côté P, Koehoorn M 78 Patients’ Experiences with Vehicle Collision to Inform the Development of Clinical Practice Guidelines: A Narrative Inquiry Lindsay GM, Mior SA, Côté P, Carroll LJ, Shearer HM 79 Attitudes Toward Chiropractic: A Survey of Canadian Obstetricians Weis CA, Stuber K, Barrett J, Greco A, Kipershlak A, Glenn T, Desjardins R, Nash J, Busse J 79 Building Multidisciplinary Health Workforce Capacity to Support the Implementation of Integrated, People-Centred Models of Care for Fusculoskeletal Health. Chehade MJ, Gill TK, Kopansky-Giles D, Schuwirth L, Karnon J, McLiesh P, Alleyne J, Woolf AD 80 Exploring Approaches to Patient Safety: The Case of Spinal Manipulation Therapy Rozmovits L, Mior S, Boon H 81 Core and Complementary Chiropractic: Lowering Barriers to Patient Utilization of Services Triano JJ, McGregor M 82 Who will have Sustainable Employment After a Back Injury? The Development of a Clinical Prediction Model in a Cohort of Injured Workers Shearer HM, Côté P, Boyle E, Hayden JA, Frank J, Johnson WG 83 Spinal Manipulative Therapy and Other Conservative Treatments for Low Back Pain: A Guideline from the Canadian Chiropractic Guideline Initiative Bussières AE, Stewart G, Al-Zoubi F, Decina P, Descarreaux M, Haskett D, Hincapié C, Pagé I, Passmore S, Srbely J, Stupar M, Weisberg J, Ornelas J 84 The Global Spine Care Initiative: a Summary of the Global Burden of Low Back and Neck Pain Studies Hurwitz EL, Randhawa K, Yu H, Côté P, Haldeman S 85 Conference Proceedings 2015 – 2016 Academic Year 88 Conference Proceedings 2016 – 2017 Academic Year 90 Conference Proceedings: 2017-2018 Academic Year

CMCC Research Report 2015–2018

Welcome CMCC has long been home to a tradition of scholarship and the pursuit of discovery and innovation through research and pioneering graduate work amongst chiropractic programs worldwide. CMCC is dedicated to leading the scientific exploration and validation of the basic and clinical concepts related to manipulation. Our scientists, clinicians, educators and graduate students recognize that their responsibility is to probe, question, challenge and build upon the best available evidence to expand our understanding of the body and our ability to positively impact patients’ lives. We believe that it is critical to the chiropractic profession that the premier research on spinal manipulation and the chiropractic adjustment be the product of chiropractic institutions, our talented researchers and our adjunct faculty holding research positions in various universities.

Dr. David Wickes President

Our commitment to excellence in Research, Scholarship and Innovation is a key pillar in our 2017-2021 Strategic Plan and renews our dedication to evidence and knowledge sharing. This plan establishes a solid framework for growth and development and is a means to reinforce our vision to create leaders in spinal care.

Dr. Christine Bradaric-Baus Vice President, Academic

Dr. Samuel Howarth Director, Human Performance Research and McMorland Family Research Chair in Mechanobiology

It is our pleasure to provide you with the 2015-18 Research Report – a report that speaks to the sophistication and diversity of research that has emerged from the dedicated, hard work of CMCC’s educators and scientists. It contains a selection of abstracts and four feature articles from CMCC’s academic community published over the 2015-2016, 20162017, and 2017-2018 academic years. It is the culmination of efforts from scientists and collaborators in CMCC’s five research streams, defined in CMCC’s Strategic Plan as the core elements of chiropractic: 1. Biological basis of musculoskeletal injury and manual therapies 2. Clinical and health services research 3. Education in healthcare 4. Health and wellness 5. Knowledge translation and health policy

Dr. Brian Budgell Director, Life Sciences Research

Dr. Silvano Mior Director, Research Partnerships and Health Policy

CMCC researchers have received funding from national and international granting agencies, provincial government agencies and professional and private organizations, and donors. The program continues to evolve and most recently with the retirement of several prolific research faculty, CMCC has been privileged to be able to add new, enthusiastic scientists to ensure that together we sustain CMCC’s position as a worldwide leader in musckuloskeletal research in our profession.

A selection of published research by CMCC faculty

Reflecting on these past years of research, there is clear recognition of how the work in each of our research streams is connected and integrated across several if not all of these areas. We can now see how they serve to move forward the knowledge and understanding of chiropractic education and patient care and contribute to knowledge in interprofessional education and collaboration.

As research continues to evolve, CMCC is committed to maximizing the integration of its key research processes to empower knowledge translation between research domains and within clinical care. Please enjoy this sample of our scientistsâ&#x20AC;&#x2122; recent work as we look together toward the future.

The generous contributions from CMCC members and donors, as well as our funding agencies have provided critical support to CMCCâ&#x20AC;&#x2122;s research efforts. The successful campaign establishing the endowed McMorland Family Research Chair is a testament to the support we receive from our graduates, colleagues and strategic partners. Grantsmanship continues to yield strong returns and research productivity remains high.

Research Activity Publications and Presentations

80 70 60 50 40 30 20 10 0 2012-13

2013-14

2014-15 Publications

2015-16

2016-17

2017-18

Presentations

CMCC Research Report 2015–2018

CMCC Research Report 2015–18 Grant Submissions by Funder 4% Corporate

29% Federal Government

8% Provincial Government 58% Foundation

Grant Success

9 8 7 6 5 4 3 2 1 0 2012-13

2013-14

2014-15 Declined

2015-16 Awarded

2016-17

2017-18

A selection of published research by CMCC faculty

Biological Basis of Musculoskeletal Injury and Manual Therapies

The Biological Basis of Degenerative Disc Disease: Proteomic and Biomechanical Analysis of the Canine Intervertebral Disc Erwin WM1,2,3 , DeSouza L 4, Funabashi M5 , Kawchuk G3,5 , Karim MZ1, Kim S1, Mädler S 4, Matta A1, Wang X1, Mehrkens KA6 1 6

Toronto Western Research Institute, 2University of Toronto , 3Canadian Memorial Chiropractic College, 4York University, 5University of Alberta, University of Basel

Abstract Introduction: In the present study, we sought to quantify and contrast the secretome and biomechanical properties of the nonchondrodystrophic (NCD) and chondrodystrophic (CD) canine intervertebral disc (IVD) nucleus pulposus (NP). Methods: We used iTRAQ proteomic methods to quantify the secretome of both CD and NCD NP. Differential levels of proteins detected were further verified using immunohistochemistry, Western blotting, and proteoglycan extraction in order to evaluate the integrity of the small leucine-rich proteoglycans (SLRPs) decorin and biglycan. Additionally, we used robotic biomechanical testing to evaluate the biomechanical properties of spinal motion segments from both CD and NCD canines. Results: We detected differential levels of decorin, biglycan, and fibronectin, as well as of other important extracellular matrix (ECM)-related proteins, such as fibromodulin and HAPLN1 in the IVD NP obtained from CD canines compared with NCD canines. The core proteins of the vital SLRPs decorin and biglycan were fragmented in CD NP but were intact in the NP of the NCD animals. CD and NCD vertebral motion segments demonstrated significant differences, with the CD segments having less stiffness and a more varied range of motion. Conclusion: The CD NP recapitulates key elements of human degenerative disc disease. Our data suggest that at least some of the compromised biomechanical properties of the degenerative disc arise from fibrocartilaginous metaplasia of the NP secondary to fragmentation of SLRP core proteins and associated degenerative changes affecting the ECM. This study demonstrates that the degenerative changes that naturally occur within the CD NP make this animal a valuable animal model with which to study IVD degeneration and potential biological therapeutics.

Introduction Degenerative disc disease (DDD) affects the cellular and extracellular compartments of the entire intervertebral disc (IVD), often leading to associated pain and disability. The specific compartments of the disc affected by degenerative changes include the inner nucleus pulposus (NP), the annulus fibrosus (AF), the transition zone interposed between the NP and AF, and the vertebral end plates (VEPs). All of these components, in addition to vital extracellular matrix (ECM) molecules within the IVD NP, such as proteoglycans, contribute to the function of the IVD as a hydrophilic, multiaxial, viscoelastic, and flexible joint between vertebrae [1–3]. Within the IVD NP ECM, the small leucine-rich proteo-glycans (SLRPs) are involved with fibrillogenesis and interact and bind growth factors dependent upon the integrity of their core proteins and functioning glycosaminoglycan (GAG) side chains [4]. The non-degenerative NP, with its high water content, has biomechanical characteristics that are more fluidlike than those of the more fibrous, degenerative NP (with inferior hydrophilic properties), which behaves more like a solid [5]. However, with increasing degeneration, there is fragmentation of the SLRP core proteins, leading to a loss of ECM homeostasis, water content, and further biochemical and biomechanical compromise [6]. With progressive degeneration, although the overall collagen content remains relatively stable, there is a shift in the expression of collagen type II to collagen type I within the nucleus [4, 7–9]. This shift in the secretion of collagen, along with degradation of other ECM proteins within the NP, may contribute to aberrant biomechanical properties, pain, reflexive muscular spasm, and disability. In an effort to mimic human DDD, non-physiologic perturbations intended to create IVD degeneration, such as needle puncture, have been developed in animals such as the rat, mouse, rabbit, pig, sheep, and canine. However, there are tremendous differences in the morphologies and cellular phenotypes of the IVDs of many animal models that bear varying resemblance to the human condition. However, two subspecies of canine differentially develop DDD in the absence of any external stimulus. Specifically, the chondrodystrophic (CD) canine (e.g.,

CMCC Research Report 2015–2018

beagle or dachshund) develops DDD early and profoundly by the age of 1 year [10]. This is in stark contrast to the nonchondrodystrophic (NCD) animal, which does not develop DDD until much later in life, if at all [10–13]. Zhou et al. proposed that the histological, radiological, and biochemical changes within the CD animal resemble the pathology of human DDD [14, 15]. Notably, DDD is diagnosed and treated both medically and surgically the same in dogs as in humans [14]. The gross pathological and biochemical characteristics (including matrix metalloproteinase [MMP] activity and GAG content) are similar in canine and human IVD NP, such that the hallmarks of DDD at different stages (both dogs and humans) include chondroid cell clusters, disorganization of the AF, and increasing appearance of clefts and cracks of increasing severity [14]. These histological characteristics are supported by magnetic resonance imaging (MRI) scans showing striking similarities between the appearance of DDD in the different stages of degeneration in humans and dogs [14]. However, despite these imaging comparisons and assessment of GAG content, most comparisons are qualitative in nature, and the degenerative phenotype often ascribed to the CD IVD NP has not been quantified. In the present study, we used high-throughput quantitative proteomic analysis to compare the secretome of the CD canine (beagle) IVD NP (similar to the human disc)with that of the NCD (mongrel) canine subspecies, which is analogous to the IVD of a healthy, young human. We validated our proteomic investigation using Western blot analysis and immunohistochemical assays for both NCD and CD canines. After proteoglycan extraction, we characterized the integrity of the core proteins of the SLRPs decorin and biglycan obtained from the IVD NP of these animals. Finally, we quantified and compared the bio-mechanical properties of spinal motion segments obtained from both subspecies using robotic biomechanical testing.

Methods Sample Collection of NCD and CD Intervertebral Disc Nucleus Pulposus All procedures involving the sacrifice of the NCD and CD dogs and tissue handling were carried out in accordance with established animal use protocols at the University Health Network, University of Toronto, ON, Canada, and in compliance with the regulations of the Canadian Council on Animal Care. We removed the T5-L6 spinal motion segments immediately after the animals were sacrificed, and then we placed all the specimens on ice. All canines used for the study were between 20 and 24 months of age and equally divided by sex. For biomechanical studies, the L4-L5 motion segment was recovered in its entirety, cleared of all soft tissues including ligaments, labeled, and immediately stored at −80 °C. For proteomic and biochemical analyses, we performed a wide laminectomy on the remainder of the spine using a Stryker saw (Stryker, Kalamazoo, MI, USA) followed by clearing of all soft tissues. After the posterior elements were removed, the spine was washed with Clidox (Pharmacal Research Laboratories, Waterbury, CT, USA)

and Betadine (Purdue Products, Stamford, CT, USA) and cooled on ice. Thereafter the discs were incised immediately adjacent to the inferior end plate with a number 10-blade, and the NP was removed in its entirety as per our established methods [16, 17]. The NP was placed into warmed physiological phosphatebuffered saline (PBS; 0.1 M, pH 7.4), rinsed, and then divided for isobaric tags for relative and absolute quantitation (iTRAQ) or immunohistochemical analysis. We were meticulous in the selection of the IVD NP used for these experiments, such that all NCD discs used were of the jellylike, mucoid, translucent appearance and all CD discs appeared fibrocartilaginous and pulpy, consistent with the degenerative phenotype widely used to describe this animal. For histological preparation, the removed IVD NP was fixed in 10 % formalin, placed in appropriately labeled cassettes, and processed using 10 % neutral buffered formalin, ascending grades of ethanol, two changes of the clearing agent xylol, and infiltrated with three changes of molten paraffin (Paraplast) for 12 h. After processing, the samples were placed into an automated embedding unit, and one sample at a time was moved from its cassette into a metal mold, appropriately oriented, filled with molten paraffin, and cooled on a cold plate and then sent for analysis. Sample Processing and iTRAQ Labeling The NP was obtained in its entirety from the IVD of CD (CD1– CD4; beagle) and NCD (NCD1–NCD4; mongrel) canines immediately after the dogs were killed as per our established methods [16]. The IVD NP thus obtained was washed three times in 1 ml of cold PBS (0.1 M, pH 7.2) and homogenized in 0.5 ml of PBS with a protease inhibitor cocktail (Sigma-Aldrich, St. Louis, MO, USA). Next, the mixture was centrifuged at 15,000×g for 20 minutes, and the supernatant was collected. The total protein concentration was determined using a Bradford-type colorimetric assay as described elsewhere [18]. For each set, clarified tissue lysates were individually denatured, alkylated, digested with trypsin, and labeled with iTRAQ labels (SCIEX, Concord, ON, Canada). The sets were grouped as follows:

•

Set 1: iTRAQ label 114: mongrel, M1; iTRAQ label 115: mongrel, M2; iTRAQ label 116: M3; iTRAQ 117: reference sample Set 2: iTRAQ label 114: mongrel, M4; iTRAQ label 115: beagle, B1; iTRAQ label 116: reference sample; iTRAQ label 117: beagle, B2 Set 3: iTRAQ label 114: beagle, B3; iTRAQ label 115: reference sample; iTRAQ label 116: beagle, B4

The reference sample consisted of equal amounts of total protein from each of the eight samples used in this study, thereby providing a global reference that was common to all three sets. We randomized the labeling of the reference sample in each set to prevent any inadvertent introduction of labeling bias. We then pooled the labeled samples to form three 4-plex iTRAQ sets.

Erwin et al

Mass Spectrometry and Data Analysis Each iTRAQ set was processed by two-dimensional liquid chromatography–tandem mass spectrometry analysis as described earlier [18]. Briefly, the samples were separated offline using strong cation exchange (SCX) chromatography and fractionated into 30 SCX fractions. Each of these SCX fractions was then dried and redissolved in a minimal volume (20–30 μl) of 0.1 % formic acid. The redissolved fractions were injected into a reversed-phase (RP) trap column, where they were de-salted before being eluted into an analytical nano liquid chromatography (LC) RP column (75-μminternal diameter (i.d.) × 150 mm). Elution and separation on the nano LC column were effected using a binary gradient of water and acetonitrile with 0.1 % formic acid at a 200 nl/min flow rate. Eluting peptides were analyzed on a 5600 Triple time-of-flight instrument (SCIEX) in information-dependent acquisition mode. Each set was analyzed a minimum of two times, and the resulting MS data were then analyzed using the ProteinPilot software (v4.0) package from SCIEX using a mammalian database. A false discovery rate (FDR) was calculated to provide a measure of confidence in the proteins reported. To minimize redundancy between proteins reported in the three individual iTRAQ sets and to ensure consistency of reported iso-forms from one set to the next, the results of the three sets were aligned using a Microsoft Excel-based (Microsoft, Redmond, WA, USA) protein alignment template as described elsewhere [19]. We first generated a master list of all the proteins identified in this study by performing a search of the combined data from all three iTRAQ sets and duplicate runs using ProteinPilot. Relative quantification of proteins, which was simultaneously performed using ProteinPilot, was based on the areas of the iTRAQ signature ion peaks. Only peptides not shared with other reported proteins (or group) contribute to the overall ratios reported for the protein. The overall protein ratios reported represent a weighted average of the ratios of the contributing unique peptides, where the weighting factor is determined by the percentage error of the individual peptide ratios. Further, the reported ratios were normalized using a factor, termed the applied bias, that is calculated based on the assumption that the majority of the proteins being compared between the samples in a set are expressed at similar levels. Western Blot Analysis As further validation of the iTRAQ data, we chose to probe the same NP homogenate supernatants from which we generated samples for iTRAQ for the level of proteins secreted, as determined in our proteomic experiments. Equal amounts of tissue homogenates from one representative sample each of NCD and CD NP that was used for iTRAQ analysis and immunohistochemistry were subjected to Western blot analysis and probed for the levels of secreted fibromodulin, biglycan, and hyaluronan and proteoglycan link protein 1 (HAPLN1) as additional verification of our iTRAQ results. Briefly, 50 μg of total protein obtained from IVDs were resolved on SDS-PAGE

A selection of published research by CMCC faculty

gels. Proteins were then electrotransferred onto polyvinylidene difluoride membranes (Bio-Rad Laboratories, Hercules, CA, USA). After blocking with 5 % non-fat powdered milk in Trisbuffered saline (TBS; 0.1 M, pH 7.4), blots were incubated with either rabbit polyclonal antibody against fibromodulin (1:1000, catalog number sc-33772; Santa Cruz Biotechnology, Santa Cruz, CA, USA), goat polyclonal antibody against biglycan (1:1000, catalog number sc-27936; Santa Cruz Biotechnology), and goat polyclonal antibody against HAPLN1 (1:1000, catalog number sc-46826; Santa Cruz Biotechnology) at 4 °C overnight. We used protein lysates obtained from canine articular cartilage as positive controls. Membranes were incubated with the corresponding secondary antibody, horseradish peroxidase (HRP)-conjugated rabbit/goat anti-immunoglobulin G (antiIgG; Bio-Rad Laboratories) diluted 1:10,000 in 1 % bovine serum albumin (BSA) for 2 h at room temperature. After each step, blots were washed three times with TBS with Tween 20 (0.1 %). Protein bands were detected by the enhanced chemiluminescence method (GE Healthcare Bio-Sciences, Pittsburgh, PA, USA) on Kodak Hyperfilm (Amersham; GE Healthcare, Little Chalfont, UK). Histology and Immunohistochemistry To validate the cellular morphology and characteristics of the discs obtained from both NCD and CD animals, we stained representative sections of the discs using hematoxylin and eosin and Safranin O. We performed immunohistochemical analysis for fibromodulin, HAPLN1, biglycan, decorin, and aggrecan using independent sets of paraffin-embedded sections of IVD NP from the same animals used for iTRAQ analysis. In brief, the sections were deparaffinized in xylene, hydrated in gradient alcohol, and pretreated in a microwave oven for 10 minutes at maximum power in Trisethylenediaminetetraacetic acid (EDTA) buffer (0.01 M, pH 9.0, 0.05 % Tween-20) for antigen retrieval. The sections were incubated with hydrogen peroxide (0.3 % vol/vol) in PBS (0.1 M, pH 7.2) for 15 minutes to quench the endogenous peroxidase activity, followed by blocking with 5 % BSA to preclude non-specific binding. Thereafter the slides were incubated with fibromodulin, HAPLN1, biglycan, decorin, and aggrecan antibodies for 16 h at 4 °C. The primary antibody was detected using the streptavidin–biotin complex with the Dako LSAB+ kit (Dako Cytomation, Glostrup, Denmark) and diaminobenzidine as the chromogen. All procedures were carried out at room temperature unless otherwise specified. The slides were washed three times after every step using PBS containing 0.025 % Triton X-100, and finally the sections were counterstained with Mayer’s hematoxylin and mounted with DPX mountant (distrene, plasticizer, and xylene). We replaced the primary antibody with isotype-specific non-immune goat/rabbit IgG for negative controls, and all sections were evaluated by light microscopic examination. Proteoglycan Extraction and SLRP Assay As described above, entire NPs were removed from five spinal segments of each of three CD and NCD donor animals, all of

CMCC Research Report 2015–2018

which had the same gross morphological appearance and were within the same age range as the donors of our iTRAQ samples. Proteoglycans were then extracted using GuHCl according to the method described by Melrose et al. [6, 20]. NCD and CD NP were diced, weighed (approximately 0.4 g wet weight), and extracted with 10 volumes of 4 M GuHCl 100 mM acetate buffer (pH 5.8 containing 20 mM EDTA, 100 mM 6-amino hexanoicacid, 25m Mbenzamidine) for 40 hat 4°C with constant end-over-end mixing. The tissue residue was removed by centrifugation, and the supernatant was concentrated by ultrafiltration (Amicon Ultra-15, 15 ml, 3000 kDa, catalog number UFC900308; EMD Millipore, Billerica, MA, USA), dialyzed against three changes of deionized cold water using a D-Tube Dialyzer Maxi (MWXO 3.5 kDa, catalog number 71508-3; EMD Millipore) with a fourth overnight dialysis. The dialyzed extracts were then freeze-dried. The freeze-dried proteoglycans thus extracted were dissolved in 2.1 ml of digestion buffer (0.1 M Tris, 0.03 M acetate, pH 6.5) overnight at 4 °C with constant shaking, and the protein content of the dissolved extracts was calculated using a Bradford assay. Briefly, 500 μg of protein from NCD and CD samples were digested with 1.0 U of chondroitinase ABC (C3667; SigmaAldrich) and 0.05 U of keratinase (G6920; Sigma-Aldrich) overnight at 37 °C. Next, 30 μgof total protein obtained from the extracted proteoglycans (digested and undigested) were mixed with SDS loading buffer and dithiothreitol, electrophoresed, and visualized by Western blotting as described above. For the decorin and biglycan Western blot primary antibodies, we used a rabbit polyclonal antibody against decorin (1:200, cata-log number NBP1-57923; Novus Biologicals, Littleton, CO, USA) and a goat polyclonal antibody against biglycan (1:200, catalog number sc-27936; Santa Cruz Biotechnology). The secondary antibodies were both HRP conjugates. We used a goat antirabbit IgG (heavy and light chains, catalog number (170-6515; Bio-Rad Laboratories) and a rabbit anti-goat IgG (heavy and light chains, catalog number#A24452; Life Technologies, Carlsbad, CA, USA), both used at 1:10,000 dilution. Biomechanical Testing We harvested the L4-L5 lumbar motion segments from CD and NCD animals within 1–4 h after they were sacrificed. These segments were removed from the spines from which the IVDs were subjected to both iTRAQ analysis and Western blot analysis. CD and NCD canines (n=6 samples each) were age-matched (20–24 months) and had average weights of 10 kg and 14 kg, respectively. Following lumbar segment harvesting, the muscle tissues, intertransverse ligaments, and supra- and interspinous ligaments were carefully dissected, leaving the posterior joints and the IVD intact. All segments were kept frozen at −20 °C until testing. The IVD dimensions of each specimen were measured, and the cross-sectional areas were calculated. Before testing, the lumbar segments were thawed at room temperature, and pilot holes were then drilled into each VEP. Each hole accommodated two anchor screws (#3 × 25.3 mm) in the superior L4 end plate and one screw (#8 × 43 mm) in the inferior L5 end plate, perpendicular to the middisc

plane. Dental stone (Modern Materials; Heraeus Kulzer, South Bend, IN, USA) was prepared according to the manufacturer’s recommendations and used to cement the segments within 3.5-inch–diameter plastic pots. The two vertebra composing the motion segments (inclusive of the intervening IVD) were seated within opposing pots using a standardized template, and cement was added to the pot until two-thirds of the vertebral body height was covered, leaving the IVD exposed (Fig. 1). Each segment was kept hydrated with gauze soaked in isotonic saline and covered in plastic wrap during tissue preparation, potting, and testing. The pot containing the caudal vertebra (L5) was fixed to a stationary crossbeam, and the pot containing the cephalad vertebra (L4) was fixed to a six-axis load cell (AMTI MC3A-100, Advanced Mechanical Technology, Watertown, MA, USA), which in turn was attached rigidly to the parallel robot (Parallel Robotic Systems, Hampton, NH, USA). This robot is composed of a rigid platform suspended by six rigid struts of fixed length. Each strut was attached to an electromechanical motor that travels about a circular track to alter the position and/or orientation of the robot platform and thus the potted motion segment. Custom computer software (National Instruments, Austin, TX, USA) was employed to control robot position and orientation. The resolution of the robot is a function of the motor performance (0.05 mm with a repeatability of 0.025 mm; Mikrolar, Hampton, NH, USA), which translates into a linear resolution of less than 1 μmandan angular resolution of approximately 0.001 degree [20]. The methodology used for biomechanical testing involved a standardized procedure according to an established testing protocol [21, 22]. Specimens were tested using an unconstrained force control system that permitted the application of a desired load in a specific axis of motion without any constraints on the segment’s motion behavior, regardless of the specimen condition (e.g., intact, injured) [23]. Specifically, we employed our software to position the specimen in a neutral pose (e.g., loads and moments in all directions were minimized), after which a bending moment about all three axes of movement (i.e., flexion and extension, lateral bending, and axial rotation) (Fig. 1c) was applied until the moment obtained from the load cell reached a maximum predetermined value. When the maximum moment was reached in the positive direction, the direction of rotation was reversed to provide a corresponding negative moment. Based on preliminary tests conducted in three additional CD specimens (not included in this study), maximum moments of newton meters were predetermined for flexion and extension, ±3 Nm for lateral bending, and ±4.5 Nm for axial rotation [24, 25]. The robot’s displacement during specimen rotation was recorded directly through a software query via the robot. This query and collection of specimen moment and load data occurred at 200 Hz. Five moment cycles around each Cartesian axis were performed at 0.1/s. The first two cycles were applied to precondition the specimens and load deformation data from the last three cycles used in the statistical analysis [26, 27]. The specimens’ moment and rotation data were plotted, and specific point displacements were obtained at the neutral position, the midpoint of the

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ascending moment, the peak moment, and the midpoint of the descending moment for both positive and negative rotations. Statistical Analysis Before statistical analysis, the biomechanical data were normalized to the cross-sectional area of the IVDs to account for any differences in the sizes of the respective IVDs. We used the Shapiro–Wilk normality test to verify the normal distribution of data obtained from biomechanical testing, and numeric data were represented as the mean ± standard deviation. We compared normalized displacement mean values between the CD and NCD groups using an independent t test, with p < 0.05 considered statistically significant. The proteomic data are presented as weighted averages of the ratios of the relevant peptides (ratio calculated with respect to the reference standard) as described, and the data were normalized using the applied bias with β-actin as a normalizing factor. All proteins and peptides were statistically analyzed within the iTRAQ analysis software platform (ProteinPilot) after having achieved a 95 % confidence interval and 1 % global FDR cutoff plus up- or downregulation with respect to the reference pool of at least 0.5 of greater than 2.0-fold. The proteins and peptides identified by iTRAQ and their expression ratios are therefore not directly comparable to each other. a

NCD or CD cases that were greater than twofold relative to the reference pool for further investigation. Following these criteria, our data analysis revealed 13 upregulated protein levels in CD (beagles) with respect to the reference pool and compared with the expression ratio of these proteins in the NCD animals. Interestingly, we observed dramatic differences between the secretion of a number of proteins critical for the function of the ECM in the IVD and cartilage. These included decorin, fibronectin, cartilage oligomeric matrix protein, cartilage intermediate layer protein, HAPLN1, biglycan, isoform B of proteoglycan 4, fibromodulin, and aggrecan core protein (Table 1). Verification of Differential Expression of Proteins in Nucleus Pulposus (CD vs. NCD Animals) We determined the secretion of fibromodulin, HAPLN1, and biglycan in NCD and CD NP homenates using Western blot analysis with total protein extracted from articular cartilage as a control (see Methods section). We observed increased levels of fibromodulin, biglycan, and HAPLN1 in CD canines compared with NCD canines (Fig. 2). However, we were unable to determine the expression of β-actin or glyceraldehyde 3-phosphate dehydrogenase, used as loading controls in the Western blot experiments, because we used the same IVD NP

Fig. 1 Robotic biomechanical setup for intervertebral disc (IVD) motion segments. a and b Potted IVD motion segment mounted upon the robotic platform. c The rotational axis x, y and z reflect the three dimensions of movement afforded by biomechanical testing

Results Identification of Differentially Secreted Proteins in Nucleus Pulposus of NCD vs. CD Canines Using a 95 % confidence interval and a cutoff of 1 % global FDR, we identified 377 proteins in our comparative proteomic analysis of proteins secreted within the NP of the two respective canine species (please see Additional file 1 Table S1). We expressed the levels of all proteins in each of the individual samples as ratios relative to the level of secretion of the same protein in the reference sample. The use of a common reference sample in all three sets therefore permitted direct comparisons of protein expression ratios across the different sets. We selected proteins showing consistent differential secretion in either the

homogenate samples for these Western blot experiments as we did for the iTRAQ experiments. These homogenates were not extracts of total protein but consisted of supernatants obtained from NP homogenates in PBS (as outlined above) and therefore contained insufficient β-actin such as would be obtained using a total protein lysate sample (as was done with the articular cartilage controls). We maintained strict controls over protein quantification (Bradford assays in quadruplicate) and scrupulously loaded the same total protein for each Western blot experiment. We repeated each experiment at least three

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times to confirm the protein expression in CD canines compared with NCD canines. The results of these analyses were consistent with the iTRAQ data. Histological and Immunohistochemical Analysis of Intervertebral Discs (CD vs. NCD Canines) We used Safranin-O staining to evaluate proteoglycan content and distribution throughout the IVD NP and immunohistochemical methods to verify the differential expression of the proteins identified in our iTRAQ analysis (decorin, biglycan, fibromodulin, HAPLN1, and aggrecan) in IVDs obtained from beagles and mongrels (n=3 each). Representative images are shown in Fig. 3. All samples revealed the same overall morphology without exception. Safranin-O staining revealed a dramatic difference in appearance, with the CD

NP demonstrating intense staining throughout the ECM and abundant clusters of chondrocyte-like cells. The NCD NP, however, revealed abundant physaliferous appearing cells with positive Safranin-O staining at the intercellular spaces. The salient differences between the two canine subspecies was the abundant cell-free and intense Safranin-O staining within the ECM of the CD NP. The NCD NP contained a highly cellular NP with intense Safranin-O staining in the smaller intercellular space, and there were no chondrocyte like clusters as seen in the CD IVD NP (Fig. 3). For all ECM proteins, the NCD canine IVD NP had a cobweb appearance with intense staining for all proteins located at the areas tightly between the cells. Immunostaining with decorin revealed diffuse intercellular staining. Much of the areas that were devoid of staining for any of the antibodies were contained within the large NP cells with

Table 1 iTRAQ analysis of differential nucleus pulposus homogenate protein expression in NCD and CD dogs

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a physaliferous appearance. This observation is in contrast to the abundant staining of these proteins in every CD NP sample. Decorin, biglycan, and HAPLN1 revealed intense staining within the ECM of the CD samples, with abundant clusters of small numbers of cells present within the NP (Fig. 3). Immunostaining for fibromodulin and aggrecan in the CD NP was less intense than for the other three proteins; however, the ECM staining was still more intense than that seen in the NCD NP (Fig. 3). Furthermore, the CD NP stained for aggrecan revealed intense pericellular immunostaining diffusely through the ECM that was much less cellular than the NCD NP. The overall appearance of the CD NP bore a strong resemblance to a fibrocartilaginous phenotype that was distinctly different from the NCD canine NP. SLRP Expression in Intervertebral Disc Nucleus Pulposus We hypothesized that the CD IVD NP represents a naturally occurring degenerative phenotype. Therefore, we extracted proteoglycans from NCD and CD canine NP to ascertain whether the core proteins in selected SLRP species were fragmented, as has been reported to occur in degenerative human discs [4, 20]. Interestingly, we observed multiple bands demonstrating fragmentation of the core proteins of decorin (30, 25, 20, 17, and 15 kDa) and biglycan (37, 28, and 25 kDa) in the CD samples, whereas the NCD samples were completely intact (Fig. 4). There was no evidence of non-specific binding of the antibodies in any samples, and these fragmentation bands visualized on the Western blots were entirely in keeping with what has been reported in human degenerative discs [4]. Biomechanical Robotic Testing and Analysis The average IVD cross-sectional areas were 2.45 cm2 for the CD specimens and 3.10 cm2 for the NCD specimens. The averaged moment–rotation curve of CD and NCD specimens for flexion and extension and axial rotation movements are depicted in Fig. 5a and b, respectively. Differences observed between moment–rotation curves are indicative of greater stiffness during flexion and extension and axial rotational loading in the NCD motion segments compared with CD motion segments. Specifically, angular displacements in flexion and extension and axial rotation were significantly reduced (p < 0.05) in NCD specimens at the midpoint of both ascending and descending moments as well as at the peak moment (Table 2). There was no statistically significant difference between the neutral position displacements (p > 0.05).

Discussion In the present study, we used quantitative proteomic analysis, immunohistochemistry, Western blot analysis, and robotic biomechanical analysis to demonstrate salient molecular and biomechanical differences between the notochordal cell-rich (NCD) and notochordal cell-deficient (CD) IVD NP. In particular, supernatants developed from mechanically disrupted CD NP yielded far greater amounts of ECM products than NCD NP samples did. Furthermore, consistent with prior reports concerning degenerative human discs, we detected

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fragmentation of the core proteins of the vital SLRPs decorin and biglycan. However, within the NP of the NCD animal (just as is the case with healthy IVD NP), the core proteins of these same SLRPs were intact and we did not detect any nonspecific binding in any samples. We also demonstrate that the notochordal cell-rich NCD IVD is stiffer and less variable than the CD IVD NP, which has reduced stiffness and more variable motion characteristics.

(i) Fibromodulin

(ii) Biglycan (iii) HAPLN1

67 kDa

45 kDa

43 kDa

Fig. 2 Western blots for fibromodulin, biglycan, and hyaluronan and proteoglycan link protein 1 (HAPLN1) expression in non-chondrodystrophic (NCD) and chondrodystrophic (CD) canine nucleus pulposus (NP) homogenates. Lane (i) depicts the expression of these proteins in articular cartilage used as a control. Lanes (ii) and (iii) represent the expression of these proteins in intervertebral disc NP homogenates for CD (beagle) and NCD (mongrel) samples. It is clear that there is strong expression in both articular cartilage and CD samples for all three proteins. However, in the NCD samples, fibromodulin and HAPLN1 are undetectable, and the expression of biglycan is markedly reduced

The SLRP family of proteins, including decorin, biglycan, and fibromodulin, is of considerable importance in the function and homeostatic regulation of the NP as well as articular cartilage. SLRPs facilitate interaction with fibrillar collagens, regulate fibrillogenesis and sequester growth factors such as epithelial growth factor and transforming growth factor (TGF)-β, in addition to their interaction with the cytokine tumor necrosis factor-α [20]. Intact SLRP GAG side chains interact with ECM proteins and facilitate fibril– fibril interaction, cellular proliferation, matrix adhesion, the modulation of cell growth, and the protection of the GAG side chains from proteolysis [4]. In this regard, decorin in particular performs a vital function with respect to its interaction with TGF-β, where decorin-TGF-β binding serves to provide a tissue reservoir of this ubiquitous growth factor that is essential for ECM homeostasis [28]. Decorin is reported to regulate collagen fibrillogenesis and matrix maintenance via interaction with fibronectin and thrombospondin, and its expression increases in cartilaginous tissues with increased degeneration [28]. TGF-β is released into the ECM upon cleavage and fragmentation of the decorin core protein, and unbound TGF-β in turn leads to increased MMP-13 expression, downstream inflammation, and accelerated degeneration of the ECM that are inextricably linked with degenerative disease [6, 20].

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Fig. 3 Comparative immunohistochemical analysis of non-chondrodystrophic (NCD) and chondrodystrophic (CD) canine nucleus pulposus (NP) expression and distribution of decorin, biglycan, fibromodulin, hyaluronan and proteoglycan link protein 1 (HAPLN1), and aggrecan. For all extracellular matrix (ECM) proteins, the NCD canine intervertebral disc NP reveals a cobweb appearance, demonstrating intense staining for all proteins located in the areas tightly between the cells. Immunostaining with decorin reveals diffuse intercellular staining with negative immunostaining within the large, physaliferous-appearing notochordal cells. This presentation is in contrast to the abundant staining of these proteins in every CD NP sample. Decorin, biglycan, and HAPLN1 reveal intense staining within the ECM, with abundant clusters of small numbers of cells present within the NP. Although the ECM staining is less intense than that for the other three proteins, fibromodulin and aggrecan immunostaining is present. Furthermore, the CD NP stained for aggrecan reveals intense pericellular immunostaining diffusely throughout the ECM that is much less cellular than the NCD NP staining. Safranin-O staining shows quite intense ECM staining in the CD NP, whereas the NCD sample demonstrates intense intercellular staining without large, acellular ECM areas rich in proteoglycan staining. The overall appearance of the CD NP bears a strong resemblance to a fibrocartilaginous phenotype that is distinctly different from the NCD canine NP

(a)

(b)

Fig. 4 Western blots depicting the expression of decorin and biglycan after proteoglycan extraction from non-chondrodystrophic (NCD) and chondrodystrophic (CD) canine intervertebral disc (IVD) nucleus pulposus (NP). For each Western blot, lane (a) is undigested (U) proteoglycan extract from NCD (mongrel) and lane (c) is from CD (beagle) canine NP. Lanes (b) and (d) depict the detection of the specific small leucine-rich proteoglycan (SLRP) indicated above after digestion (D) with chondroitinase ABC and keratinase in NCD canine (lane b) and CD canine (lane d). a The decorin core protein is visualized appropriately at the 43 kDa molecular weight after digestion (lane b), with a clear, single band found from NCD NP extracts. NP extracts from CD canines (lane d) reveal fragmentation of decorin with multiple lower molecular weight bands visualizedat 30, 25–20, and 17–15 kDa. b The biglycan core protein provides a clear, single band at the 45 kDa molecular weight in the NCD NP extract; however, the CD NP extract reveals multiple fragments of the core protein visualized at 37–35, 28, and 25 kDa

Capello et al. [29] reported that NP cells obtained from CD and NCD canines assemble and process proteoglycans (aggrecan in particular) very differently, in large part owing to the phenotype of the cell (small, chondrocyte-like, or large notochordal). In the Capello et al. study, NCD discs that contained predominantly

large notochordal cells (>99 %) were found to synthesize and distribute low molecular weight proteoglycan aggregates into the intercellular phase at a much faster (threefold) rate than did the small NP cells obtained from CD discs, allowing the aggregates to be formed farther from the cell surface. However,

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the CD NP-derived small chondrocyte-like cells synthesized high molecular weight proteoglycans that were rapidly assembled as high molecular weight aggregates within both the pericellular and intercellular compartments, a phenomenon considered to impose a tendency for reduced matrix remodeling and repair capacity. We observed that the NCD NP is highly cellular (predominantly physaliferous-appearing notochordal cells) with a cobweb appearing ECM tightly held between the cells. In contrast, the CD animals contain many small clusters of cells with intense pericellular staining for aggrecan, decorin, biglycan, and fibromodulin surrounding the cells, as well as large patches of diffusely stained ECM with a distinctly fibrocartilaginous appearance. The IVD NP of CD animals has been characterized as degenerating prematurely compared with NCD animals, and possible genetic reasons for this advanced aging and degeneration have been hypothesized [14, 30]. Furthermore, on the basis of gross pathology, histology, and MMP activity, it has been demonstrated that DDD is a common occurrence in dogs just as it is in humans, with the CD dogs experiencing these changes much earlier in life [14]. The GAG content within the NP of CD dogs is less than that found within NCD dogs, a

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is notochordal cell–deficient and susceptible to degenerative change [12]. A number of published studies have begun to shed some light on possible genetic susceptibility that could contribute to the development of DDD in some people (such as vitamin D receptor, collagen type XI, and others); however, this area of investigation remains to be elucidated [33–35]. The alternative hypothesis is that the CD IVD, having lost its developmentally notable notochordal cell population, has assumed a fibrocartilaginous phenotype (cartilage like cells) with much more secreted matrix, and therefore the differences we have detected reflect accelerated turnover within the more fibrocartilaginous IVD NP. This alternative hypothesis actually supports an important observation: that the fibrocartilaginous IVD NP inclusive of fragmented SLRPs and labile ECM molecules that are not tightly bound within the matrix in fact actually epitomize the degenerative NP phenotype. We strongly feel that our data dovetail with those reported by Brown et al., who demonstrated the same fragmented SLRP core proteins in degenerative human NP that we detected within the CD IVD NP [4]. Furthermore, if this fibrocartilaginous phenotype were healthy, it would not explain the fragmentation of the SLRPs or the impaired biomechanics compared with the NCD animal.

Fig. 5 Averaged moment–rotation curves during (a) flexion and extension and (b) axial rotation movements for non-chondrodystrophic (NCD; red) and chondrodystrophic (CD; white) specimens. Differences observed between moment–rotation curves are indicative of greater stiffness during flexion and extension and axial rotation loading in the NCD motion segments compared with CD motion segments

finding consistent with the premature degeneration that occurs within this subspecies, just as are MRI classifications that are strikingly similar to those in humans, strongly supporting the role of the canine as a model of human DDD [14]. The relatively high ratio of ECM proteins in CD NP samples, fragmentation of decorin and biglycan, and sparse clusters of cells in the CD samples suggest that, akin to the degenerative human IVD NP, the CD IVD NP represents a naturally occurring degenerative phenotype in contrast to the non-degenerative NCD NP [4]. Further support for this hypothesis is that not all humans develop DDD as opposed to aging, suggesting an underlying genetic switch or series of switches that may predispose some people to DDD [31, 32] The CD canine may represent a similar genetically predetermined subset of animals that, like humans,

To test our hypothesis that the notochordal cell–rich IVD NP confers more optimal biomechanical properties upon the NP, in this study we measured the moment-rotation response of CD and NCD specimens during the application of a 1 Nm bending moment around the flexion and extension and 4.5 Nm around the rotational axis. The unconstrained force control testing procedure allowed the application of loads about a specific axis at the same time as minimizing the loads in the other axes of movement. The biomechanical results of the current study showed a statistically significant difference between the displacements of CD and NCD spines during flexion and extension and axial rotation movements. The flexion and extension and axial rotation parameters of the CD and NCD IVDs in our study indicate that the more degenerative and

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Table 2 Analysis of angular displacements during the application of 1 Nm moment in flexion and extension and axial rotation motions Movement Flexion

Extension

Right axial rotation

Left axial rotation

CD canines Zero crossing displacement

0.01° (±0.02)

NCD canines 0.01° (±0.03)

p value 0.850

95 % CI −0.003, 0.024

Halfway from zero to peak displacement

1.16° (±0.39)

0.73° (±0.16)

0.000

0.584, 0.876

Peak displacement

2.29° (±0.79)

1.44° (±0.33)

0.000

1.150, 1.735

Halfway from peak to zero displacement

1.15° (±0.39)

0.72° (±0.16)

0.000

0.573, 0.866

Zero crossing displacement

0.00° (±0.00)

0.753

−0.001, 0.002

Halfway from zero to peak displacement

−0.82° (±0.28)

−0.44° (±0.19)

0.000

−0.554,−0.220

Peak displacement

−1.61° (±0.53)

−0.86° (±0.38)

0.000

−1.063,−0.434

Halfway from peak to zero displacement

−0.78° (±0.27)

−0.43° (±0.20)

0.000

−0.514,−0.185

Zero crossing displacement

0.00° (±0.01)

0.00° (±0.03)

0.358

−0.002, 0.001

Halfway from zero to peak displacement

0.55° (±0.25)

0.37° (±0.17)

0.016

0.036, 0.334

Peak displacement

1.10° (±0.50)

0.73° (±0.35)

0.017

0.071, 0.663

Halfway from peak to zero displacement

0.55° (±0.25)

0.36° (±0.17)

0.017

0.035, 0.331

Zero crossing displacement

0.00° (±0.01)

0.00° (±0.00)

0.492

−0.001, 0.001

Halfway from zero to peak displacement

−0.60° (±0.20)

−0.38° (±0.24)

0.007

−0.374,−0.066

Peak displacement

−1.20° (±0.41)

−0.73° (±0.48)

0.003

−0.778,−0.172

Halfway from peak to zero displacement

−0.56° (±0.21)

−0.34° (±0.22)

0.005

−0.366,−0.069

CD chondrodystrophic,CI confidence interval,NCD Non-chondrodystrophic Statistically significant differences between the NCD and CD motion segments in both flexion and extension and axial rotation motions are observed, indicating that the CD motion segments incur greater displacement (decreased stiffness) than the NCD motion segments p < 0.05 was considered significant

fibrocartilaginous CD IVD incurs greater displacement than does the NCD IVD, which is highly notochordal, highly hydrated, and non-degenerative. Our observations using this canine model are in agreement with the study by Iatridis et al. [5], who observed that the increase in solidlike behavior of degenerative human IVDs (compared with the more fluidlike IVD NP of youthful, non-degenerative discs) and their concomitant decreased hydrostatic pressurization reduced energy dissipation within the discs examined. Some limitations when interpreting our present bio-mechanical results are noteworthy. For example, it is possible that there could be minor differences in anatomy, morphology, and biochemistry between specimens involved in this study. However, previous studies have described similar macroscopic morphological, histological, and biochemical changes in IVD degeneration in CD and NCD dogs [14, 36]. Additionally, a decrease in proteoglycan content in the NP has been considered a governing factor affecting the dynamic viscoelastic properties of the entire disc [37]. Importantly, the results of this study involved the analysis of movements with data normalized to the IVDs’ cross-sectional area, accounting for differences in IVD sizes. Therefore, despite the potential differences between CD and NCD spines and IVDs in this study, these are likely to not significantly impact our results.

Conclusions The CD canine NP represents a naturally occurring degenerative phenotype that shares many features of the degenerative human disc, notably fragmented SLRPs such as decorin and biglycan, the expression of which likely potentiates further ECM degradation and degeneration of the IVD. Our data suggest that the compromised bio-mechanical properties of the degenerative disc arise at least in part from fibrocartilaginous metaplasia of the NP secondary to fragmentation of these SLRP core proteins and the associated loss of ECM homeostasis. These observations add quantitative proteomic and biomechanical data that support the use of the dog as an optimal model with which to study human DDD and the evaluation of potential biologic therapeutics [14]. This study demonstrates that the degenerative changes that naturally occur within the CD NP make this animal a valuable animal model with which to study IVD degeneration and potential biologic therapeutics.

Additional File Additional file 1: Table S1. Complete data set for iTRAQ analysis of differential NP homogenate protein expression (NCD and CD animals). This table presents the accession number and names of all proteins detected within the NP homogenates of the two subspecies of canine.(PDF 151 kb)

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Abbreviations AF: Annulus fibrosus; BSA: Bovine serum albumin; CD: Chondrodystrophic; CI: Confidence interval; COMP: Cartilage oligomeric matrix protein; DDD: Degenerative disc disease; ECM: Extracellular matrix; EDTA: Ethylenediaminetetraacetic acid; FDR: False discovery rate; GAG: Glycosaminoglycan; HAPLN1: Hyaluronan and proteoglycan link protein 1; HRP: Horseradish peroxidase; IgG: Immunoglobulin G; iTRAQ: Isobaric tags for relative and absolute quantitation; IVD: Intervertebral disc; LC: Liquid chromatography; MMP: Matrix metalloproteinase; MRI: Magnetic resonance imaging; MS: Mass spectrometry; NCD: Non-chondrodystrophic; NP: Nucleus pulposus; PBS: Phosphate-buffered saline; RP: Reversed phase; SCX: Strong cation exchange; SLRP: Small leucine-rich proteoglycan; TBS: Tris-buffered saline; TGF-β: Transforming growth factor beta; VEP: Vertebral end plate.

Competing Interests The authors declare that they have no competing interests.

Authors’ Contributions WME conceived the study and experimental design and supervised and performed tissue harvest and proteomic sample preparation. WME also supervised the preparation of the manuscript, the manuscript revisions, and journal communication and provided overall supervision. LD designed and performed iTRAQ proteomic analysis and also interpreted data and prepared the manuscript with respect to the proteomic data, including manuscript revisions. MF and GK designed and performed biomechanics experiments concerning the CD and NCD spinal motion segments. MF and GK also interpreted the robotic biomechanics data and wrote the biomechanics sections of the manuscript, including manuscript revisions. MZK assisted with NCD and CD tissue harvest and performed all aspects of IVD proteoglycan extraction from NCD and CD IVD NP samples, dialyzing of the extracted proteoglycans and Western blotting experiments to visualize CD and NCD SLRPs as sourced from the CD and NCD IVD NP. MZK also assisted with proteomic sample preparation, data interpretation and manuscript preparation. SK assisted with tissue harvest, tissue cataloguing, iTRAQ sample preparation and proofreading of the manuscript.

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SM assisted LD with proteomic sample analysis, data interpretation and manuscript preparation. AM assisted with proteomic data interpretation, performed immunohistochemical analysis of the canine IVD NP and assisted with manuscript preparation and revision. KAM assisted with CD and NCD tissue harvest and manuscript preparation, manuscript revision and proofreading. XW assisted with NCD and CD tissue harvest, performed all Western blotting experiments for articular cartilage expression of SLRPs and assisted with immunohistochemical analysis of CD and NCD canine IVD NP. All authors read and approved the final manuscript.

Acknowledgements The authors gratefully acknowledge Drs. Jon Hare and Cheryl Niemuller for technical assistance with the CD animals.

Author Details Toronto Western Research Institute, Toronto Western Hospital, Toronto, ON M5T 2S8, Canada. 2Divisions of Neurological and Orthopaedic Surgery, University of Toronto, Toronto, ON, Canada. 3Canadian Memorial Chiropractic College, North York, ON, Canada. 4Department of Chemistry, York University, Toronto, ON, Canada. 5Department of Physical Therapy, University of Alberta, 8205 114 Street, 2-50 Corbett Hall, Edmonton, AB T6G 2G4, Canada. 6Spinal Surgery, University of Basel, Basel, Switzerland. Received: 29 May 2015 Accepted: 30 July 2015 Published online: 05 September 2015

References 1. Cole TK, Burkhardt D, Frost L, Ghosh P. The proteoglycans of the canine intervertebral disc. Biochim Biophys Acta. 1985;839:127–38. 2. Ghosh P. The biology of the intervertebral disc, vol. 2. Boca Raton, FL: CRC Press; 1988. 3. Ghosh P, Taylor TKF, Braund KG. The variation of the glycosaminoglycans of the canine intervertebral disc with ageing. I. Chondrodystrophoid breed. Gerontology. 1977;23:87–98. 4. Brown S, Melrose J, Caterson B, Roughley P, Eisenstein SM, Roberts S. A comparative evaluation of the small leucinerich proteoglycans of pathological human intervertebral discs. Eur Spine J. 2012;21:S154–9. 5. Iatridis JC, Setton LA, Weidenbaum M, Mow VC. Alterations in the mechanical behavior of the human lumbar nucleus pulposus with degeneration and aging. J Orthop Res. 1997;15:318–22. 6. Melrose J, Smith SM, Fuller ES, Young AA, Roughley PJ, Dart A, et al. Biglycan and fibromodulin fragmentation correlates with temporal and spatial annular remodelling in experimentally injured ovine intervertebral discs. Eur Spine J. 2007;16:2193–205. 7. Eyre DR, Matsui Y, Wu JJ. Collagen polymorphisms of the intervertebral disc. Biochem Soc Trans. 2002;30:844–8.

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8. Feng H, Danfelter M, Strömqvist B, Heinegård D. Extracellular matrix in disc degeneration. J Bone Joint Surg Am. 2006;88:25–9. 9. Antoniou J, Steffen T, Nelson F, Winterbottom N, Hollander AP, Poole RA, et al. The human lumbar intervertebral disc: evidence for changes in the biosynthesis and denaturation of the extracellular matrix with growth, maturation, ageing, and degeneration. J Clin Invest. 1996;98:996–1003. 10. Hansen HJ. A pathologic-anatomical study on disc degeneration in dogs, with special reference to the socalled enchondrosis intervertebralis. Acta Orthop Scand Suppl. 1952;11:1–117. 11. Braund KG, Ghosh P, Taylor TK, Larsen LH. Morphological studies of the canine intervertebral disc: the assignment of the beagle to the achondroplastic classification. Res Vet Sci. 1975;19:167–72. 12. Aguiar DJ, Johnson SL, Oegema TR. Notochordal cells interact with nucleus pulposus cells: regulation of proteoglycan synthesis. Exp Cell Res.1999;246:129–37. 13. Allison CC. The intervertebral disc syndrome of the dog. Can J Comp Med Vet Sci. 1961;25:179–83. 14. Bergknut N, Rutges JPHJ, Kranenburg HJC, Smolders LA, Hagman R, Smidt HJ, et al. The dog as an animal model for intervertebral disc degeneration? Spine. 2012;37:351–8. 15. Zhao CQ, Wang LM, Jiang LS, Dai LY. The cell biology of intervertebral disc aging and degeneration. Ageing Res Rev. 2007;6:247–61. 16. Erwin WM, Islam D, Inman RD, Fehlings M, Tsui FW. Notochordal cells protect nucleus pulposus cells from degradation and apoptosis: implications for the mechanisms of intervertebral disc degeneration. Arthritis Res Ther. 2011;13:R215. 17. Erwin WM, Islam D, Eftekhar E, Inman RD, Karim M, Fehlings MG. Intervertebral disc-derived stem cells: implications for regenerative medicine and repair. Spine. 2013;38:211–6. 18. DeSouza LV, Siu KW. Mass spectrometry-based quantification. Clin Biochem. 2013;46:421–31. 19. DeSouza LV, Grigull J, Ghanny S, Dubé V, Romaschin AD, Colgan TJ, et al. Endometrial carcinoma biomarker discovery and verification using differentially tagged clinical samples with multidimensional liquid chromatography and tandem mass spectrometry. Mol Cell Proteomics. 2007;6:1170–82. 20. Melrose J, Fuller ES, Roughley P, Smith MM, Kerr B, Hughes CE, et al. Fragmentation of decorin, biglycan, lumican and keratocan is elevated in degenerate human meniscus, knee and hip articular cartilages compared with age-matched macroscopically normal and control tissues. Arthritis Res Ther. 2008;10:R79. 21. Kawchuk GN, Carrasco A, Beecher G, Goertzen D, Prasad N. Identification of spinal tissues loaded by manual therapy: a robot-based serial dissection technique applied in porcine motion segments. Spine. 2010;35:1983–90.

22. Goertzen DJ, Kawchuk GN. A novel application of velocitybased force control for use in robotic biomechanical testing. J Biomech. 2009;42:366–9. 23. Goel VK, Wilder DG, Pope MH, Edwards WT. Biomechanical testing of the spine: load-controlled versus displacementcontrolled analysis. Spine.1995;20:2354–7. 24. Meij BP, Suwankong N, Van der Veen AJ, Hazewinkel HA. Biomechanical flexion–extension forces in normal canine lumbosacral cadaver specimens before and after dorsal laminectomy-discectomy and pedicle screw-rod fixation. Vet Surg. 2007;36:742–51. 25. Zimmerman MC, Vuono-Hawkins M, Parsons JR, Carter FM, Gutteling E, Lee CK, et al. The mechanical properties of the canine lumbar disc and motion segment. Spine. 1992;17:213–20. 26. Hediger KU, Ferguson SJ, Gedet P, Busato A, Forterre F, Isler S, et al. Biomechanical analysis of torsion and shear forces in lumbar and lumbosacral spine segments of nonchondrodystrophic dogs. Vet Surg. 2009;38:874–80. 27. Vizcaíno Revés N, Bürki A, Ferguson S, Geissbühler U, Stahl C, Forterre F. Influence of partial lateral corpectomy with and without hemilaminectomy on canine thoracolumbar stability: a biomechanical study. Vet Surg. 2012;41:228–34. 28. Monfort J, Tardif G, Reboul P, Mineau F, Roughley P, Pelletier JP, et al. Degradation of small leucine-rich repeat proteoglycans by matrix metalloprotease-13: identification of a new biglycan cleavage site. Arthritis Res Ther. 2006;8:R26. 29. Cappello R, Bird JLE, Pfeiffer D, Bayliss MT, Dudhia J. Notochordal cell produce and assemble extracellular matrix in a distinct manner, which may be responsible for the maintenance of healthy nucleus pulposus. Spine. 2006;31:873–83. 30. Ghosh P, Taylor TKF, Braund KG, Larsen LH. A comparative chemical and histochemical study of the chondrodystrophoid and nonchondrodystrophoid canine intervertebral disc. Vet Pathol. 1976;13:414–27. 31. Rajasekaran S, Babu JN, Arun R, Armstrong BR, Shetty AP, Murugan S.A study of diffusion in human lumbar discs: a serial magnetic resonance imaging study documenting the influence of the endplate on diffusion in normal and degenerate discs. Spine. 2004;29:2654–67. 32. Rajasekaran S, Venkatadass K, Naresh Babu J, Ganesh K, Shetty P. Pharmacological enhancement of disc diffusion and differentiation of healthy, ageing and degenerated discs: results from in-vivo serial post-contrast MRI studies in 365 human lumbar discs. Eur Spine J. 2008;17:626–43. 33. Williams FMK, Bansal AT, van Meurs JB, Bell JT, Meulenbelt I, Suri P, et al. Novel genetic variants associated with lumbar disc degeneration in northern Europeans: a meta-analysis of 4600 subjects. Ann Rheum Dis. 2013;72:1141–8. 34. Erwin WM, Fehlings MG. Intervertebral disc degeneration: genes hold the key. World Neurosurg. 2013;80:e131–3.

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35. Kalb S, Martirosyan NL, Kalani MY, Broc GG, Theodore N. Genetics of the degenerated intervertebral disc. World Neurosurg. 2012;77:491–501. 36. Smolders LA, Kingma I, Bergknut N, van der Veen AJ, Dhert WJ, Hazewinkel HA, et al. Biomechanical assessment of the effects of decompressive surgery in non-chondrodystrophic and chondrodystrophic canine multisegmented lumbar spines. Eur Spine J. 2012;21:1692–9. 37. Inoue N, Espinoza Orías AA. Biomechanics of intervertebral disk degeneration. Orthop Clin North Am. 2011;42:487–99.

Originally published in Arthritis Research & Therapy (2015) 17:240 . This is an Open Access article under license to Biomed Central and is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/). Access Online: https://doi.org/10.1186/s13075-015-0733-z

CMCC Research Report 2015–2018

Biological Basis of Musculoskeletal Injury and Manual Therapies

Effect of Interactive Neurostimulation Therapy on Inflammatory Response in Patients With Chronic and Recurrent Mechanical Neck Pain Teodorczyk-Injeyan JA1, Triano JJ1, McGregor M1, Woodhouse L 2, Injeyan HS1 Canadian Memorial Chiropractic College, 2University of Alberta

Abstract Objective: The purpose of this study is to evaluate the effect of treatment with a novel noninvasive interactive neurostimulation device (InterX5000) on the production of inflammatory biomarkers in chronic and recurrent mechanical neck pain (NP) syndrome. Methods: This study represents pilot biological data from a randomized controlled clinical trial. Twenty-five NP patients and 14 asymptomatic subjects included for baseline comparison only completed the study. The patients received 6 InterX5000 or placebo treatments within 2 weeks, and pretreatment and post-treatment blood samples were collected for in vitro determination of biomarker production. Whole blood cell cultures were activated by lipopolysaccharide or by the combination of lipopolysaccharide and phytohemagglutinin for 24 to 48 hours. The levels of tumor necrosis factor α (TNFα) and its soluble type II receptor (sTNFR II), interleukin (IL) 1, IL-1 receptor antagonist (IL-1RA), IL-6, IL-10, and monocyte chemotactic protein (CCL2/MCP-1) were determined by specific immunoassays.

Results: Compared with asymptomatic subjects, baseline production levels of all proinflammatory mediators (TNFα, IL-1β, IL-6, and CCL2/MCP-1) were significantly augmented or trended higher (P = .000-.008) in patients with NP. Of the anti-inflammatory markers, only IL-1RA was significantly elevated (P = .004). The increase in IL-10 and tumor necrosis factor receptor II levels did not reach statistical significance. Neither InterX5000 nor placebo therapy had any significant effect on the production of the inflammatory mediators over the study period. Conclusion: This investigation determined that inflammatory cytokine pathways are activated in NP patients but found no evidence that a short course of InterX5000 treatment normalized the production of inflammatory biomarkers.

Originally published in the Manipulative and Physiological Therapeutics, 2015 Oct;38(8):545-54. Reproduced with permission from Elsevier. Access Online: https://doi.org/10.1016/j.jmpt.2015.08.006, Epub 2015 Oct 4.

A selection of published research by CMCC faculty

Differential Displacement of Soft Tissue Layers From Manual Therapy Loading Engell S1, Triano JJ1,2 , Fox JR3, Langevin HM3,4, Konofagou EE5 McMaster University, 2Canadian Memorial Chiropractic College, 3University of Vermont, 4Harvard Medical School and Brigham and Womenâ&#x20AC;&#x2122;s Hospital, Columbia University

1 5

Abstract Background: Understanding the biomechanics of spinal manipulative therapy requires knowing how loads are transmitted to deeper structures. This investigation monitored displacement at sequential depths in thoracic paraspinal tissues parallel with surface load directions. Methods: Participants were prone and a typical preload maneuver was applied to thoracic tissues. Ultrasound speckle tracking synchronously monitored displacement and shear deformation of tissue layers in a region of interest adjacent to load application to a depth of 4 cm. Cumulative and shearing displacements along with myoelectric activity were quantitatively estimated adjacent to loading site. Findings: The cephalocaudal cumulative displacement in layers parallel to the surface were, in order of depth, 1.27 (SD = 0.03), 1.18 (SD = 0.02), and 1.06 (SD = 0.01) mm (P < 0.000), respectively.

Interpretation: Surface loading of the torso in combined posteroanterior and caudocephalic directions result in both displacement of tissues anteriorly and in shearing between tissue layers in the plane of the tissues strata to depths that could plausibly affect spinal tissues. Displacements of tissues more likely arise passively, consistent with load transmitted by the retinacula cutis and epimuscular force pathways. Displacements are similar in magnitude to those known to evoke biologically relevant responses in both animal and human studies.

Originally published in Clinical Biomechanics, 2016 Feb 23;33:66-72. [Epub ahead of print]. Reproduced with permission from Elsevier. Access Online: https://doi.org/10.1016/j.clinbiomech.2016.02.011

The superficial/intermediate shear was 2.1 Âą 2.3% whereas the intermediate/deep shear was 4.4% (SE = 3.7, P = 0.014). Correlation of tissue layers was stronger with application site displacement at the surface (0.87 < r < 0.89) than with muscle activation (0.65 < r < 0.67).

CMCC Research Report 2015–2018

Patient-Induced Reaction Forces and Moments Are Influenced by Variations in Spinal Manipulative Technique D’Angelo K1, Triano JJ1, Kawchuk GN1,2, Howarth SJ1 Canadian Memorial Chiropractic College, 2University of Alberta

Abstract Study Design: An in vivo biomechanical study. Objective: The aim of the present study was to quantify and compare the reaction loads for two spinal manipulation therapy (SMT) procedures commonly used for low back pain using a biomechanical computer model. Summary of Background Data: Contemporary computer-driven rigid linked-segment models (LSMs) have made it feasible to analyze low back kinetics and kinematics during various activities including SMT procedures. Currently, a comprehensive biomechanical model analyzing actual differences in loading effects between different SMT procedures is lacking. Methods: Twenty-four healthy/asymptomatic participants received a total of six SMT applications, representing all combinations of two similar SMT procedures within three patient hip flexion angles. All contact forces, patient torso kinematics, and inertial properties were entered into a dynamic three-dimensional LSM to calculate lumbar reaction forces and moments. Peak net applied force along with the maximums, minimums, and ranges for each component of the three-dimensional reaction force and moment vectors during each SMT procedure was analyzed

Results: One specific SMT technique (lumbar spinous pull) produced greater maximum anterior-posterior reaction force and both lateral bending and axial twisting reaction moments compared to the other technique (lumbar push procedure [all P ≤ 0.034]). SMT trials without hip flexion had lower maximum mediallateral reaction force and range compared to those with 45 and 90 degrees of hip flexion (all P ≤ 0.041). There were no interactions between procedure and hip angle for any of the dependent measurements. Conclusion: The technique used to apply SMT and the participant’s initial hip orientation induced significantly different actions on the low back. These findings and future research can improve patient outcomes and safety by informing clinicians on how to best use SMT given specific types of low back pain.

Originally published in Spine, 2016 Jun 6. [Epub ahead of print]. Reproduced with permission of Wolters Kluwer Health, Inc. Access Online: https://DOI: 10.1097/BRS.0000000000001725

A selection of published research by CMCC faculty

Molecular Therapy for Degenerative Disc Disease: Clues from Secretome Analysis of the Notochordal Cell-Rich Nucleus Pulposus Matta A1, Karim MZ1, Isenman DE2, Erwin WM1,2,3 1

Toronto Western Hospital,2University of Toronto, 3Canadian Memorial Chiropractic College

Abstract Degenerative disc disease (DDD) is associated with spinal pain often leading to long-term disability. However, the nonchondrodystrophic canine intervertebral disc is protected from the development of DDD, ostensibly due to its retention of notochordal cells (NC) in the nucleus pulposus (NP). In this study, we hypothesized that secretome analysis of the NC-rich NP will lead to the identification of key proteins that delay the onset of DDD. Using mass-spectrometry, we identified 303 proteins including components of TGFβ- and Wnt-signaling, anti-angiogeneic factors and proteins that inhibit axonal ingrowth in the bioactive fractions of serum free, notochordal cell derived conditioned medium (NCCM). Ingenuity Pathway Analysis revealed TGFβ1 and CTGF as major hubs in protein interaction networks. In vitrotreatment with TGFβ1 and CTGF promoted the synthesis of healthy extra-cellular matrix proteins, increased cell proliferation and reduced cell death in human degenerative disc NP cells. A single intra-discal injection of recombinant TGFβ1 and CTGF proteins in a pre-clinical rat-tail disc injury model restored the NC and stem cell rich NP. In conclusion, we demonstrate the potential of TGFβ1 and CTGF to mitigate the progression of disc degeneration and the potential use of these molecules in a molecular therapy to treat the degenerative disc.

Originally published in Science Reports, 2017; 7: 45623, Published online 2017 Mar 30. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. Access Online: https://doi.org/10.1038/srep45623

CMCC Research Report 2015–2018

Procedure Selection and Patient Positioning Influence Spine Kinematics During High-Velocity, Low-Amplitude Spinal Manipulation Applied to the Low Back Bell S1, D’Angelo K1, Kawchuk GN1,2, Triano JJ1, Howarth SJ1 Canadian Memorial Chiropractic College, 2University of Alberta

Abstract Objectives: This investigation compared indirect 3-dimensional angular kinematics (position, velocity, and acceleration) of the lumbar spine for 2 different high-velocity, low-amplitude (HVLA) spinal manipulation procedures (lumbar spinous pull or push), and altered initial patient lower limb posture. Methods: Twenty-four participants underwent 6 HVLA procedures directed toward the presumed L4 vertebra, reflecting each combination of 2 variants of a spinal manipulation application technique (spinous pull and push) and 3 initial hip flexion angles (0°, 45°, and 90°) applied using a right lateral recumbent patient position. All contact forces and moments between the patient and the external environment, as well as 3-dimensional kinematics of the patient’s pelvis and thorax, were recorded. Lumbar spine angular positions, velocities, and accelerations were analyzed within the preload and impulse stages of each HVLA trial. Results: Lumbar spine left axial rotation was greater for the pull HVLA. The pull HVLA also generated a greater maximum (leftward) and lower minimum (rightward) axial rotation velocity and deceleration and greater leftward and rightward lateral bend velocities, acceleration, and deceleration components. Not flexing the hip produced the greatest amount of extension, as well as the lowest axial rotation and maximum axial rotation acceleration during the impulse.

Conclusions: This investigation provides basic kinematic information for clinicians to understand the similarities and differences between 2 HVLA side-lying manipulations in the lumbar spine. Use of these findings and novel technology can drive future research initiatives that can both affect clinical decision making and influence teaching environments surrounding spinal manipulative therapy skill acquisition.

Originally published in the Journal of Manipulative and Physiological Therapeutics, 2017 Mar - Apr;40(3):147-155. Epub 2017 Feb 10. Reproduced with permission from Elsevier. Access Online: https:// 10.1097/BRS.0000000000001725

A selection of published research by CMCC faculty

TENS-like Stimulation Downregulates Inflammatory Cytokines in a PC-12 Cell Line Sovak G, Budgell B Canadian Memorial Chiropractic College

Abstract Objectives: The purpose of this study was to evaluate the effects of transcutaneous electrical nerve stimulation (TENS)-like stimulation on the expression of the proinflammatory cytokines tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), and IL-6 in PC-12 cells, which are commonly used as neuronal cell models. Methods: Nerve growth factor-differentiated PC-12 cells were exposed to electrical stimulation for 15 minutes at 1 mA, 200 μs, and 100 Hz. Cell lysate from stimulated and control cells was assayed for TNF-α, IL-1β, and IL-6. In 6 trials, cells were preincubated with the L-type ion channel blocker nicardipine. Cultured cells were also incubated with Alexa Fluor 488 and visualized by fluorescence microscopy to determine the nuclear vs cytoplasmic distribution of the p65 sub-unit of NF-κB RESULTS: Compared with control (unstimulated) cells, the stimulated cells had a downregulation of the assayed cytokines. However, preincubation with the L-type ion channel blocker nicardipine blocked this effect of stimulation. Additionally, it was noted that TENS-like stimulation promoted a relative sequestration of the p65 subunit of NF-κB in the cytoplasm vs the nucleus.

Conclusions: It appears that in this cell line and with these stimulation parameters, TENS-like stimulation attenuated the expression of the assayed proinflammatory cytokines, in part by promoting the relative sequestration of the p65 subunit of NF-κB in the cytoplasm, and that voltage-dependent calcium channels have a role in the cascade of events initiated by the TENS-like stimulation.manipulative therapy skill acquisition.

Originally published in the Journal of Manipulative and Physiological Therapeutics, 2017 Jul - Aug;40(6):381-386. Reproduced with permission from Elsevier. Access Online: https://doi.org/10.1016/j.jmpt.2017.03.008

CMCC Research Report 2015â&#x20AC;&#x201C;2018

Elevated Production of Nociceptive CC Chemokines and sE-Selectin in Patients With Low Back Pain and the Effects of Spinal Manipulation: A Nonrandomized Clinical Trial Teodorczyk-Injeyan JA, McGregor M, Triano JJ, Injeyan SH Canadian Memorial Chiropractic College

Abstract Background: The involvement of inflammatory components in the pathophysiology of low back pain (LBP) is poorly understood. It has been suggested that spinal manipulative therapy (SMT) may exert anti-inflammatory effects. Purpose: The purpose of this study was to determine the involvement of inflammation-associated chemokines (CC series) in the pathogenesis of nonspecific LBP and to evaluate the effect of SMT on that process. Methods: Patients presenting with nonradicular, nonspecific LBP (minimum pain score 3 on 10-point visual analog scale) were recruited according to stringent inclusion criteria. They were evaluated for appropriateness to treat using a high velocity low amplitude manipulative thrust in the lumbar-lumbosacral region. Blood samples were obtained at baseline and following the administration of a series of 6 high velocity low amplitude manipulative thrusts on alternate days over the period of 2 weeks. The in vitro levels of CC chemokine ligands (CCL2, CCL3, and CCL4) production and plasma levels of an inflammatory biomarker, soluble E-selectin (sE-selectin), were determined at baseline and at the termination of treatments 2 weeks later.

Results: Compared with asymptomatic controls baseline production of all chemokines was significantly elevated in acute (P=0.004 to <0.0001), and that of CCL2 and CCL4 in chronic LBP patients (P<0.0001). Furthermore, CCL4 production was significantly higher (P<0.0001) in the acute versus chronic LBP group. sEselectin levels were significantly higher (P=0.003) in chronic but not in acute LBP patients. Following SMT, patient-reported outcomes showed significant (P<0.0001) improvements in visual analog scale and Oswestry Disability Index scores. This was accompanied by a significant decline in CCL3 production (P<0.0001) in both groups of patients. Change scores for CCL4 production differed significantly (P<0.0001) only for the acute LBP cohort, and no effect on the production of CCL2 or plasma sE-selectin levels was noted in either group. Conclusions: The production of chemotactic cytokines is significantly and protractedly elevated in LBP patients. Changes in chemokine production levels, which might be related to SMT, differ in the acute and chronic LBP patient cohorts.

Originally published in the Clinical Journal of Pain, 2018 Jan;34(1):68-75, Published online 2017 Dec 6. Reproduced with permission from Wolters Kluwer Health, Inc. Access Online: https://doi: 10.1097/AJP.0000000000000507

A selection of published research by CMCC faculty

Clinical and Health Services Research

A Randomized Pragmatic Clinical Trial of Chiropractic Care for Headaches With and Without a Self-Acupressure Pillow Vernon H, Borody C, Harris G, Muir B, Goldin J, Dinulos M Canadian Memorial Chiropractic College

Abstract Objective: The purpose of this study was to determine if the addition of a self-acupressure pillow (SAP) to typical chiropractic treatment results in significantly greater improvement in tension-type and cervicogenic headache sufferers. Methods: A pragmatic randomized clinical trial was conducted in a chiropractic college teaching clinic. Thirty-four subjects, including tension-type and cervicogenic headache sufferers, 21 to 60 years of age, male or female, completed the study. Group A (n = 15) received typical chiropractic care only (manual therapy and exercises), and group B (n = 19) received typical chiropractic care with daily home use of the SAP. The intervention period was 4 weeks. The main outcome measure was headache frequency. Satisfaction and relief scores were obtained from subjects in the SAP group. Analysis of variance was used to analyze the intergroup comparisons.

Conclusion: This study suggests that chiropractic care may reduce frequency of headaches in patients with chronic tension-type and cervicogenic headache. The use of a self-acupressure pillow (Dr Zaxx device) may help those with headache and headache pain relief as well as producing moderately high satisfaction with use.

Originally published in the Journal of Manipulative and Physiological Therapeutics, 2015 Nov-Dec;38(9):637-43. Epub 2015 Nov 6. Reproduced with permission from Elsevier. Access Online: https://doi.org/10.1016/j.jmpt.2015.10.002

Results: Owing to failure of randomization to produce group equivalence on weekly headache frequency, analysis of covariance was performed showing a trend (P = .07) favoring the chiropracticonly group; however, this was not statistically significant. Group A obtained a 46% reduction of weekly headache frequency (t = 3.1, P = .002; d= 1.22). The number of subjects in group A achieving a reduction in headaches greater than 40% was 71%, while for group B, this was 28%. The mean benefit score (0-3) in group B of the use of the SAP was 1.2 (.86). The mean satisfaction rating of users of the SAP was 10.4 (2.7) out of 15 (63%).

CMCC Research Report 2015–2018

Effectiveness of Acupuncture Therapies to Manage Musculoskeletal Disorders of the Extremities: A Systematic Review Cox J1, Varatharajan S 1,2,3 , Côté P1,2, OPTIMa Collaboration4 Canadian Memorial Chiropractic College, 2UOIT-CMCC Centre for the Study of Disability Prevention and Rehabilitation, University of Ontario Institute of Technology and Canadian Memorial Chiropractic College, 3University of Ontario Institute of Technology, 4The Ontario Protocol for Traffic Injury Management (OPTIMa) Collaboration

Abstract Objective: To assess the effectiveness and safety of acupuncture therapies for musculoskeletal disorders of the extremities. Methods: We searched MEDLINE, Embase, CINAHL, PsycINFO, and Cochrane Central Register of Controlled Trials from 1990 to 2015 for randomized controlled trials, cohort studies, and casecontrol studies. Eligible studies were appraised with Scottish Intercollegiate Guidelines Network criteria. A best-evidence synthesis was performed to synthesize results from included studies with a low risk of bias. A sensitivity analysis was conducted to determine the impact of excluding studies with a high risk of bias. Results: The search revealed 5180 articles; 15 were included (10 with a low risk of bias, 5 with a high risk of bias). The studies with a low risk of bias suggested that (1) traditional needle acupuncture was superior to oral steroids (1 RCT, n = 77) and may be superior to vitamin B1/B6 supplements (1 RCT, n = 64) for carpal tunnel syndrome (CTS), and was superior to exercise for Achilles tendinopathy (1 RCT, n = 64). Traditional needle acupuncture did not provide important benefit over placebo for upper extremity pain (1 RCT, n = 128), or no intervention for patellofemoral pain (1 RCT, n = 75), and was inconclusive for shoulder pain (2 RCTs, n = 849), suggesting no important benefit; (2) electroacupuncture may be superior to placebo for shoulder injuries (1 RCT, n = 130) and may not be superior to night splinting for persistent CTS (1 RCT, n = 78); and (3) dry needling may be superior to placebo for plantar fasciitis (1 RCT, n = 84). Sensitivity analysis suggests that including studies with a high risk of bias might have impacted the evidence synthesis in support of managing shoulder pain with traditional needle acupuncture, and that would suggest traditional needle acupuncture may be effective for lateral epicondylitis and piriformis syndrome.

Conclusion: Evidence for the effectiveness of acupuncture for musculoskeletal disorders of the extremities was inconsistent. Traditional needle acupuncture may be beneficial for CTS and Achilles tendinopathy, but not for nonspecific upper extremity pain and patellofemoral syndrome. Electroacupuncture may be effective for shoulder injuries and may show similar effectiveness to that of night wrist splinting for CTS. The effectiveness of dry needling for plantar fasciitis is equivocal

Originally published in the Journal of Orthopaedic & Sports Physical Therapy, 2016;46:409-429. Reproduced with permission from Cox J, Varatharajan S, Côté P, OPTIMa Collaboration. Access Online: https://doi.org/10.2519/jospt.2016.6270

A selection of published research by CMCC faculty

Effect of Two Consecutive Spinal Manipulations in a Single Session on Myofascial Pain Pressure Sensitivity: A Randomized Controlled Trial Laframboise MA, Vernon H, Srbely J Canadian Memorial Chiropractic College

Abstract Objective: To investigate the summative effect of two consecutive spinal manipulative therapy (SMT) interventions within the same session on the pain pressure sensitivity of neurosegmentally linked myofascial tissues. Methods: 26 participants were recruited and assessed for the presence of a clinically identifiable myofascial trigger point in the right infraspinatus muscle. Participants were randomly assigned to test or control group. Test group received two consecutive real cervical SMT interventions to C5-C6 segment while controls received one real SMT followed by one validated sham SMT intervention to C5-C6 segment. Participants received the two consecutive SMT interventions 30 minutes apart. Pain pressure threshold (PPT) readings were recorded at pre-SMT1 and 5, 10, 15, 20 and 25 minutes post-SMT1 and post-SMT2. PPT readings were normalized to pre-SMT1 values and averaged.

Results: Repeated measures ANOVA demonstrated a significant main effect of SMT intervention [F(1,24)=8.60, p<0.05] but not group [F(1.24)=0.01] (p=0.91). Post-hoc comparisons demonstrated a statistically significant (p<0.05) increase in SMT2 versus SMT1 (18%) in the test group but not in controls (4%) (p=0.82). Conclusion: Two consecutive SMT interventions evoke significant decreases in mechanical pressure sensitivity (increased PPT) within neurosegmentally linked myofascial tissues. The antinociceptive effects of SMT may be summative and governed by a doseresponse relationship in myofascial tissues.

Originally published in the Journal of the Canadian Chiropractic Association, 2016 Jun;60(2):137-45. Reproduced with permission.

CMCC Research Report 2015–2018

Are Manual Therapies, Passive Physical Modalities, or Acupuncture Effective for the Management of Patients with Whiplash-Associated Disorders or Neck Pain and Associated Disorders? An Update of the Bone and Joint Decade Task Force on Neck Pain and Its Associated Disorders by the OPTIMa collaboration Wong JJ1, Shearer HM1, Mior S2, Jacobs C 2, Côté P1,2,3, Randhawa K1, Yu H1,4, Southerst D4, Varatharajan S1,2, Sutton D1, van der Velde G5,6,7, Carroll LJ8, Ameis A9, Ammendolia C 6,7, Brison R10, Nordin M11, Stupar M1, Taylor-Vaisey A1 UOIT-CMCC Centre for the Study of Disability Prevention and Rehabilitation, University of Ontario Institute of Technology and Canadian Memorial Chiropractic College, 2Canadian Memorial Chiropractic College, 3University of Ontario Institute of Technology (UOIT). 4Mount Sinai Hospital, 5Toronto Health Economics and Technology Assessment (THETA) Collaborative, 6Institute for Work and Health, 7University of Toronto, 8University of Alberta, 9 University of Montreal, 10Queens University, 11New York University 1

Abstract Background Context: In 2008, the Bone and Joint Decade 2000-2010 Task Force on Neck Pain and Its Associated Disorders (Neck Pain Task Force) found limited evidence on the effectiveness of manual therapies, passive physical modalities, or acupuncture for the management of whiplash-associated disorders (WAD) or neck pain and associated disorders (NAD). Purpose: This review aimed to update the findings of the Neck Pain Task Force, which examined the effectiveness of manual therapies, passive physical modalities, and acupuncture for the management of WAD or NAD. Study Design/ Setting: This is a systematic review and best evidence synthesis. Sample: The sample includes randomized controlled trials, cohort studies, and case-control studies comparing manual therapies, passive physical modalities, or acupuncture with other interventions, placebo or sham, or no intervention. Outcome Measures: The outcome measures were self-rated or functional recovery, pain intensity, health-related quality of life, psychological outcomes, or adverse events.

Methods: We systematically searched five databases from 2000 to 2014. Random pairs of independent reviewers critically appraised eligible studies using the Scottish Intercollegiate Guidelines Network criteria. Studies with a low risk of bias were stratified by the intervention’s stage of development (exploratory vs. evaluation) and synthesized following best evidence synthesis principles. Funding was provided by the Ministry of Finance. Results: We screened 8,551 citations, and 38 studies were relevant and 22 had a low risk of bias. Evidence from seven exploratory studies suggests that (1) for recent but not persistent NAD grades I-II, thoracic manipulation offers short-term benefits; (2) for persistent NAD grades I-II, technical parameters of cervical mobilization (eg, direction or site of manual contact) do not impact outcomes, whereas one session of cervical manipulation is similar to Kinesio Taping; and (3) for NAD grades I-II, strain-counterstrain treatment is no better than placebo. Evidence from 15 evaluation studies suggests that (1) for recent NAD grades I-II, cervical and thoracic manipulation provides no additional benefit to high-dose supervised exercises, and Swedish or clinical massage adds benefit to self-care advice; (2) for persistent NAD grades I-II, home-based cupping massage has similar outcomes to home-based muscle relaxation, lowlevel laser therapy (LLLT) does not offer benefits, Western acupuncture provides similar outcomes to non-penetrating placebo electroacupuncture, and needle acupuncture provides similar outcomes to sham-penetrating acupuncture; (3) for WAD grades I-II, needle electroacupuncture offers similar outcomes as simulated electroacupuncture; and (4) for recent NAD grades III, a semi-rigid cervical collar with rest and graded strengthening exercises lead to similar outcomes, and LLLT does not offer benefits

A selection of published research by CMCC faculty

Conclusions: Our review adds new evidence to the Neck Pain Task Force and suggests that mobilization, manipulation, and clinical massage are effective interventions for the management of neck pain. It also suggests that electroacupuncture, strain-counterstrain, relaxation massage, and some passive physical modalities (heat, cold, diathermy, hydrotherapy, and ultrasound) are not effective and should not be used to manage neck pain.

Originally published in The Spine Journal, 2016 Dec;16(12):1598-1630. Epub 2015 Dec 17. Reproduced with permission from Elsevier. Access Online: https://doi.org/10.1016/j.spinee.2015.08.024

Risk of Carotid Stroke after Chiropractic Care: A Population-Based Case-Crossover Study Cassidy JD1,2, Boyle E1,2, CĂ´tĂŠ P 2,3, Hogg-Johnson S 2,4 , Bondy SJ4, Haldeman S5 University of Southern Denmark, 2University of Toronto, 3University of Ontario Institute of Technology and UOIT-CMCC Centre for Disability Prevention and Rehabilitation, 4Institute for Work and Health, 5University of California 1

Abstract Background: Chiropractic manipulation is a popular treatment for neck pain and headache, but may increase the risk of cervical artery dissection and stroke. Patients with carotid artery dissection can present with neck pain and/or headache before experiencing a stroke. These are common symptoms seen by both chiropractors and primary care physicians (PCPs). We aimed to assess the risk of carotid artery stroke after chiropractic care by comparing association between chiropractic and PCP visits and subsequent stroke. Methods: A population-based, case-crossover study was undertaken in Ontario, Canada. All incident cases of carotid artery stroke admitted to hospitals over a 9-year period were identified. Cases served as their own controls. Exposures to chiropractic and PCP services were determined from health billing records.

Conclusion: We found no excess risk of carotid artery stroke after chiropractic care. Associations between chiropractic and PCP visits and stroke were similar and likely due to patients with early dissection-related symptoms seeking care prior to developing their strokes.

Originally published in the Journal of Stroke and Cerebrovascular Diseases, 2017 Apr;26(4):842-850. Epub 2016 Nov 21. Reproduced with permission from Elsevier. Access Online: https://doi.org/10.1016/j.jstrokecerebrovasdis.2016.10.031

Results: We compared 15,523 cases to 62,092 control periods using exposure windows of 1, 3, 7, and 14 days prior to the stroke. Positive associations were found for both chiropractic and PCP visits and subsequent stroke in patients less than 45 years of age. These associations tended to increase when analyses were limited to visits for neck pain and headache-related diagnoses. There was no significant difference between chiropractic and PCP risk estimates. We found no association between chiropractic visits and stroke in those 45 years of age or older.

CMCC Research Report 2015â&#x20AC;&#x201C;2018

The Effect of Phase of Menstrual Cycle on Joint Mobility in the Cervical Spine and Extremities in Nulliparous Women: A Cross-Sectional Study Weis CA, Grondin D, Vernon H Canadian Memorial Chiropractic College

Abstract Objective: The purpose of this study was to investigate the range of motion (ROM) of various joints in women throughout the menstrual cycle to determine whether there would be a difference in the ROM between the luteal and follicular phases during extension at the fifth metacarpophalangeal joint and bilateral rotation of the cervical spine in young adult nulliparous women. Methods: Sixteen nulliparous women of childbearing age (mean age, 26 years) were recruited from the academic institution where the study was being performed. Participants were randomized into and tested during either the luteal or follicular phases of the menstrual cycle. In the following month, participants were tested in the opposite phases of the menstrual cycle. All testing was performed by a doctor of chiropractic. Differences in ROM were measured in single joint movements (fifth digit hyperextension) and in multijoint movements (bilateral cervical rotation) using an electromagnetic sensor system.

Results: No significant effects of phase were found on peak ROM of the fifth digit or during cervical spine rotation (left, right, or bilaterally), irrespective of trial. Conclusion: There is no difference in ROM of the cervical spine or the fifth metacarpophalangeal joint, regardless of the phase of menses, suggesting there is likely no hormonal influence on these structures during the follicular or luteal phases.

Originally published in the Journal of Manipulative and Physiological Therapeutics, 2016 Jul-Aug;39(6):393-400. Epub 2016 Jun 23. Reproduced with permission from Elsevier Access Online: https://doi.org/10.2519/jospt.2016.6270

A selection of published research by CMCC faculty

Ultrasound Assessment of Abdominal Muscle Thickness in Women With and Without Low Back Pain During Pregnancy Weis CA1, Nash J2, Triano JJ1, Barrett J3 Canadian Memorial Chiropractic College, 2McMaster University, 3Sunnybrook Health Sciences Centre

Abstract Objective: The aim of this preliminary study was to determine the differences in abdominal musculature thickness, within 1 month of delivery, in women who experienced back pain during pregnancy compared with those who did not. Methods: B-mode ultrasound imaging was used to measure abdominal muscle thickness on 76 postpartum participants who participated in a larger study; 47 women experienced back pain during pregnancy, and 29 did not. Participant data were stratified by group, and primary comparisons were based on these grouping across the abdominal muscles, including rectus abdominis (upper and lower fibers), external oblique, internal oblique, and transversus abdominis. Means and standard deviations were also used to set parameters for future studies.

Conclusion: The results of this study showed no variation in abdominal muscle thickness in women who had back pain during pregnancy and those who did not.

Originally published in the Journal of Manipulative and Physiological Therapeutics, 2017 May;40(4):230-235. Epub 2017 Apr 12. Reproduced with permission from Elsevier. Access Online: https://doi.org/10.1016/j.jmpt.2017.02.002

Results: In the present study, there was no difference in any abdominal muscle thickness between groups. Women with low back pain were significantly shorter (165.19 Âą 6.64 cm) than women who did not have back pain during pregnancy (169.38 Âą 7.58 cm). All other demographics, such as age, weight, and date tested postpartum, were not significantly different between groups.

CMCC Research Report 2015–2018

Validity and Reliability of Clinical Prediction Rules Used to Screen for Cervical Spine Injury in Alert Low-Risk Patients with Blunt Trauma to the Neck: Part 2. A Systematic Review From the Cervical Assessment and Diagnosis Research Evaluation (CADRE) Collaboration Moser N1, Lemeunier N2,3, Southerst D4, Shearer H1,3, Murnaghan K1, Sutton D3, Côté P1,3,5 Canadian Memorial Chiropractic College , 2Institut Franco-Européen de Chiropraxie, 3University of Ontario Institute of Technology (UOIT), UOIT-CMCC Centre for the Study of Disability Prevention and Rehabilitation, 4NYU Hospital for Joint Diseases, 5University of Ontario Institute of Technology 1

Abstract Purpose: To update findings of the 2000-2010 Bone and Joint Decade Task Force on Neck Pain and its Associated Disorders (Neck Pain Task Force) on the validity and reliability of clinical prediction rules used to screen for cervical spine injury in alert low-risk adult patients with blunt trauma to the neck. Methods: We searched four databases from 2005 to 2015. Pairs of independent reviewers critically appraised eligible studies using the modified QUADAS-2 and QAREL criteria. We synthesized low risk of bias studies following best evidence synthesis principles. Results: We screened 679 citations; five had a low risk of bias and were included in our synthesis. The sensitivity of the Canadian C-spinerule ranged from 0.90 to 1.00 with negative predictive values ranging from 99 to 100%. Inter-rater reliability of the Canadian C-spine rule varied from k = 0.60 between nurses and physicians to k = 0.93 among paramedics. The inter-rater reliability of the Nexus Low-Risk Criteria was k = 0.53 between resident physicians and faculty physicians.

Conclusion: Our review adds new evidence to the Neck Pain Task Force and supports the use of clinical prediction rules in emergency care settings to screen for cervical spine injury in alert low-risk adult patients with blunt trauma to the neck. The Canadian C-spine rule consistently demonstrated excellent sensitivity and negative predictive values. Our review, however, suggests that the reproducibility of the clinical predictions rules varies depending on the examiners level of training and experience.

Originally published in the European Spine Journal, Jun;27(6):1219-1233. Epub 2017 Sep 22. Reproduced with permission from Springer Nature. Access Online: https://doi: 10.1007/s00586-017-5301-6

A selection of published research by CMCC faculty

Association of Venous Leg Ulcers With Ankle Range of Motion in People Attending Chiropractic Mobile Clinics in the Dominican Republic Tavares PA1, Landsman V2,3, Gomez N4, Ferreiras A5, Lopez RA 4 Canadian Memorial Chiropractic College, 2Institute for Work and Health, 3Private Practice, Dominican Republic, 4Fundacion Sol Naciente

Abstract Objective: The goal of the study was to determine if there was an association between chronic venous disorders (CVDs), particularly venous leg ulcers, and ankle range of motion (ROM) in the Dominican Republic.

Conclusion: A significant decrease was observed in ankle ROM for participants with active and healed leg venous ulcers compared with those without ulcers. There appeared to be an association between venous leg ulcers and ankle ROM in this sample.

Methods: Chronic venous disorders were classified using the clinical manifestations portion (C) of the CEAP (clinical manifestations, etiology, anatomy, pathophysiology) method. The legs of participants attending mobile chiropractic clinics in rural, low-income areas in the Dominican Republic were assessed for clinical signs of CVD and venous ulcers. Ankle ROM was then measured, and photographs of the legs were taken. The 6 clinical stages of CVD were divided into 3 groups: normal legs (normal), no ulcer CVD, and ulcer CVD (healed and active). Multiple linear regression of ankle ROM against CVD grouping was used to test the association.

Originally published in the Journal of Chiropractic Medicine J Chiropr Med. 2017;16(4):263-70. Reproduced with permission from Elsevier. Access Online: https://doi.org/10.1016/j.jcm.2017.08.004

Results: Eight of the 837 patients for whom CVD classification was obtained had venous ulcers (healed or active) on at least 1 leg. About 30% relative reduction in ROM (ankle dorsiflexion plus plantar flexion) was observed between the ulcer group and the normal group. Regression analysis comparing legs with ulcers to healthy legs (normal), adjusted for age, gender, indicator for obesity, and previous legtrauma, revealed a significant decrease of approximately 14° (P = .0007) in ankle ROM. Age was also found to be strongly significant in the regression analysis, 1 year of aging was associated with a decrease of 0.16° (P < .0001) in ankle ROM (approximately 1.6° in 10 years).

CMCC Research Report 2015â&#x20AC;&#x201C;2018

Tool to Assess Causality of Direct and Indirect Adverse Events Associated with Therapeutic Interventions Zorzela L1, Mior S2, Boon H3, Gross A 4, Yager J1, Carter R1, et al. University of Alberta, 2Canadian Memorial Chiropractic College, 3University of Toronto, 4McMaster University

Abstract Objective: To develop and test a tool to assess the causality of direct and indirect adverse events associated with therapeutic interventions. The intervention was one or more drugs and/ or natural health products, a device, or practice (professional delivering the intervention).

Results: The tool was used in assessment of eight serious adverse events. Each event was independently evaluated by two assessors. The algorithm facilitated assessment of a serious direct or indirect harm. Assessors agreed in the final score on seven of eight cases (weighted kappa coefficient of 0.75).

Methods: Through the assessment of causality of adverse events, we can learn about factors contributing to the harm and consider what modification may prevent its reoccurrence. Existing scales (WHO-UMC, Naranjo and Horn) were adapted to develop a tool (algorithm and table) to evaluate cases of serious harmful events reported through a national surveillance study. We also incorporated a novel approach that assesses indirect harm (caused by the delay in diagnosis/treatment) and the health provider delivering the intervention (practice). The tool was tested, revised and then implemented to assess all reported cases of serious events resulting from use of complementary therapies. The use of complementary therapies was the trigger to report the event. Each case was evaluated by two assessors, out of a panel of five, representing different health care professionals.

Conclusion: A tool to support the assessment of causality of adverse events was developed and tested. We propose a novel method to assess direct and indirect harms related to product(s), device(s), practice or a combination of the previous. Further research will probably help evaluate this approach across different settings and interventions.

Originally published in Current Medical Research and Opinion, 2018 Mar;34(3):407-414, Epub 2017 Oct 24. Reproduced with permission from Taylor & Francis Group. Access Online: https://doi.org/10.1080/03007995.2017.1383891

A selection of published research by CMCC faculty

Chiropractic Spinal Manipulation and the Risk for Acute Lumbar Disc Herniation: A Belief Elicitation Study Hincapié CA1,2,, Cassidy JD2, Côté P3,4,5 , Rampersaud YR6, Jadad AR2,7, Tomlinson GA7 St. Michael’s Hospital, 2University of Toronto, 3Canadian Memorial Chiropractic College, 4University of Ontario Institute of Technology, UOIT-CMCC Centre for Disability Prevention and Rehabilitation, 6Toronto Western Hospital, 7University Health Network

1 5

Abstract Purpose: Chiropractic spinal manipulation treatment (SMT) is common for back pain and has been reported to increase the risk for lumbar disc herniation (LDH), but there is no high quality evidence about this. In the absence of good evidence, clinicians can have knowledge and beliefs about the risk. Our purpose was to determine clinicians’ beliefs regarding the risk for acute LDH associated with chiropractic SMT. Methods: Using a belief elicitation design, 47 clinicians (16 chiropractors, 15 family physicians and 16 spine surgeons) that treat patients with back pain from primary and tertiary care practices were interviewed. Participants’ elicited incidence estimates of acute LDH among a hypothetical group of patients with acute low back pain treated with and without chiropractic SMT, were used to derive the probability distribution for the relative risk (RR) for acute LDH associated with chiropractic SMT.

Conclusion: Clinicians’ beliefs about the risk for acute LDH associated with chiropractic SMT varied systematically across professions, in spite of a lack of scientific evidence to inform these beliefs. These probability distributions can serve as prior probabilities in future Bayesian analyses of this relationship.

Originally published in the European Spine Journal, 2018 Jul;27(7):1517-1525. Epub 2017 Sep 18. Reproduced with permission from Springer Nature. Access Online: https://doi.org/10.1007/s00586-017-5295-0

Results: Chiropractors expressed the most optimistic belief (median RR 0.56; IQR 0.39-1.03); family physicians expressed a neutral belief (median RR 0.97; IQR 0.64-1.21); and spine surgeons expressed a slightly more pessimistic belief (median RR 1.07; IQR 0.95-1.29). Clinicians with the most optimistic views believed that chiropractic SMT reduces the incidence of acute LDH by about 60% (median RR 0.42; IQR 0.29-0.53). Those with the most pessimistic views believed that chiropractic SMT increases the incidence of acute LDH by about 30% (median RR 1.29; IQR 1.11-1.59).

CMCC Research Report 2015–2018

Education in Health Care

Changes in Manipulation Peak Force Modulation and Time to Peak Thrust Among First-Year Chiropractic Students Following a 12-Week Detraining Period Starmer DJ1, Guist BP1, Tuff TR1, Warren SC1, Williams MG1,2 Canadian Memorial Chiropractic College, 2University of New Brunswick

Abstract Objective: The purpose of this study was to analyze differences in peak force modulation and time-to-peak thrust in posteriorto-anterior (PA) high-velocity-low-amplitude (HVLA) manipulations in first-year chiropractic students prior to and following a 12-week detraining period. Methods: Chiropractic students (n=125) performed 2 thrusts prior to and following a 12-week detraining period: total peak force targets were 400 and 600 N, on a force-sensing table using a PA hand contact of the participant’s choice (bilateral hypothenar, bilateral thenar, or cross bilateral). Force modulation was compared to defined target total peak force values of 600 and 400 N, and time-to-peak thrust was compared between data sets using 2-tailed paired t-tests. Results: Total peak force for the 600 N intensity varied by 124.11 + 65.77 N during the pre-test and 123.29 + 61.43 N during the post-test compared to the defined target of 600 N (P = .90); total peak force for the 400 N intensity varied by 44.91 + 34.67 N during the pre-test and 44.60 + 32.63 N during the post-test compared to the defined target of 400 N (P = .57). Time-to-peak thrust for the 400 N total peak force was 137.094 + 42.47 milliseconds during the pre-test and 125.385 + 37.46 milliseconds during the post-test (P = .0004); timeto-peak thrust for the 600 N total peak force was 136.835 + 40.48 milliseconds during the pre-test and 125.385 + 33.78 milliseconds during the post-test (P =.03). Conclusion: The results indicate no drop-off in the ability to modulate force for either thrust intensity, but did indicate a statistically significant change in time-to-peak thrust for the 400 N total peak force thrust intensity in first-year chiropractic students following a 12-week detraining period. (J Manipulative Physiol Ther 2016;39:311-317)

A chiropractic manipulation is a complex motor skill that involves a high velocity, low amplitude (HVLA) thrust targeted at specific joints and adjacent tissues in order to produce a therapeutic outcome. This skill involves a combination of applied speed, force, and motor control. Upon application, HVLA manipulations cause deformations of the joints and surrounding soft-tissues such that the boney articulations are briefly taken beyond the clinical end range of motion.1 In addition to increasing clinical range of motion, it is hypothesized that the manipulation elicits a reflex response in the surrounding musculature causing post-treatment relaxation. Hertzog et al measured EMG muscle activity following the application of a HVLA spinal manipulation in human subjects and found a brief increase in activity 200 to 400 milliseconds following manipulation indicating the presence of a muscle pindle reflex response.2 Hertzog subsequently measured resting muscle EMG activity in patients with spastic muscles and found that activity was significantly diminished following a HVLA spinal manipulation indicating muscle relaxation.1 In order to elicit this reflex response, the manipulation might need to be applied with sufficient speed such that time-to-peak force is less than 150 milliseconds.3 The magnitude of the applied force is also an important component of the chiropractic manipulation, with force modulation being an important and necessary aspect of HVLA manipulations. It is necessary that the practitioner accurately modulate total peak force depending on the physical characteristics of the patient.4–6 However, there is no clear understanding of the appropriate dosage as it relates to clinical outcomes for specific conditions. Animal studies have demonstrated that the variation of procedural components including preload, peak force, and applied force direction may result in different biomechanical, neurological, and metabolic responses.7–12 These responses have been shown in a limited number of human studies, but there is no direct clinical relation as of yet.13–15,4,16–18

Starmer et al

In chiropractic students, the acquisition of skill in performing a HVLA manipulation occurs throughout the four years of their required education. Although the exact targets are unclear, based on evidence informed faculty consensus, total peak force targets of 400 N, 600 N, and 800 N are being used within the curriculum and Force Sensing Table Technology™ (FSTT®) is being used to provide appropriate and timely feedback to the students. The institution where this research was conducted has a strict policy regarding the performance of HVLA manipulations without faculty supervision in accordance with jurisdictional rules and regulations:

“The policies of the Chiropractic Act and the Regulated Health Professionals Act (1991), and Canadian Memorial Chiropractic College (CMCC), and the Canadian Chiropractic Protective Association (CCPA) state that no person shall be adjusted by a student, on or off campus or at any facility or during any activity, at any time, without the supervision or direction of a member of the chiropractic profession who is a CMCC faculty member or a representative/designate of the institution and is a licensed chiropractor in the Province of Ontario and a member of the CCPA.”

During the academic year spanning from late August to the beginning of June, students receive 4 to 5 hours per week of scheduled class time to practice a range of chiropractic techniques including HVLA manipulations. The first year curriculum includes HVLA manipulations directed toward both the thoracic and lumbar spines, with cervical manipulations being taught during second year. Chiropractic students at CMCC have a unique opportunity to learn and practice HVLA manipulations using FSTT® allowing for instant feedback regarding target peak force.19 However, during the 12-week detraining period spanning from the beginning of June to late August students are unable to practice HVLA manipulation skills as the procedure is a Controlled Act under the relevant regulations that govern this act. This extended period without practice is comparable to a period of detraining and thus may negatively impact skill development. Mujika and Padilla have defined detraining as the “partial or complete loss of training-induced adaptations in response to an insufficient training stimulus.”16,20 Research on detraining has shown that older men will experience a loss of force production after only 4 weeks of detraining, however these individuals were also able to maintain some gains in neuromuscular performance.21 Additionally, Dai et al have shown that knee biomechanics are altered following a four-week post-season break, and speculate that decreased muscle strength may be due to a loss of motor control.20,22

A selection of published research by CMCC faculty

Similarly, chiropractic students may experience declines in proficiency of manipulation during a critical time in early skill development. Currently there is no literature that addresses whether manual therapy skills, including HVLA manipulations, are affected by periods of detraining. Therefore, it is necessary to examine the potential changes in proficiency of manipulation following a detraining period. The objective of this study was to determine whether there was a change in peak force modulation and time-to-peak force in first-year chiropractic students following a 12-week detraining period from practice and feedback. The usage of FSTT® as part of the chiropractic curriculum provides an ideal scenario for data collection of students’ performance prior to and following a 12-week detraining period, as they were already familiar with the technology being used. Results may indicate the need for an intervention designed to attenuate such changes.

Methods This investigative study consisted of pre-post measures, which took place in a force-sensing table (FST) lab at a chiropractic college, before and after a 12-week detraining period. Since this study involved human subjects, institutional ethics approval was obtained from the CMCC Research Ethics Board (1304X05). All data was collected at the Simulation Laboratory located at the Canadian Memorial Chiropractic College (CMCC) where the participants signed an approved informed consent form. Participants All subjects were first-year chiropractic students at the time of the preliminary data collection. These subjects were near the end of their first year at Chiropractic College and were taught several variations of a prone thoracic, double transverse process contact that is generally used to “correct apparent rotation dysfunction of either the posterior facets or the costotransverse joints.”23 At CMCC, the standard procedures taught within the chiropractic curriculum to treat thoracic spine pain include bilateral hypothenar, bilateral thenar, or cross-bilateral.24 Subjects were obtained using convenience sampling. A total of 167 subjects volunteered for initial data collection and 125 first-year chiropractic students volunteered for follow-up data collection. Data collection occurred during normal technique hours, and any students whom were unable to perform HVLA manipulations in technique class because of personal injuries that would make the execution of these procedures unsafe were excluded. All subjects were requested to attend two sets of data collection, in May 2013 and September 2013. No control group for this study was used as the participants served as their own comparison. Procedure Subjects were asked to perform thrusts with two (2) different total peak target forces: (1) 400 N total peak force and (2) 600 N total peak force on foam Human Analogue Mannequins™ (HAM®). Full details of the standardized protocol can be found

CMCC Research Report 2015–2018

elsewhere, as they are described by Triano et al (2015). In brief and as shown in Figure 1, subjects chose a standard maneuver for the treatment of thoracic spine pain (bilateral hypothenar, bilateral thenar, or cross-bilateral) and used this as their means of delivering both thrusts to customized foam Human Analogue Mannequins™ (HAM®). Thrusts were targeted at the level of T9 for consistency.

Data Analysis A total of 167 subjects volunteered for pre data collection and 125 for post data collection, giving a total of 125 of complete data sets. All data collected was usable, there were no missing or corrupt files in our data set. All data was collected using Force Sensing Table Technology™, which has previously been shown to have excellent reliability and validity.18

Fig 1. Student performing thrust on HAM® using FSTT®.

Equipment All data was collected on the Leander 900 Z Series treatment table (Leader Health Technologies Corporation, Port Orchard, Washington) with an imbedded AMTI force plat (Advanced Mechanical Technology Inc, Watertown, Mass). Peak force and time-to-peak force (thrust acceleration) was collected using Force-Sensing Table Technology™ (FSTT®). Previous research has demonstrated excellent reliability and validity of the FSTT® in measuring force loads during manipulations.3,25 Thrusts were performed directly on a customized foam Human Analogue Mannequin™ (HAM®) with both anatomical landmarks and foam that is consistent with observed soft tissue compliance.26,27 The HAM® was placed in a prone position over the force plate of the FSTT®. The mannequin and FSTT® are part of a high fidelity simulation laboratory at CMCC, which previous participants have reported as being an effective replication of real world experience.19,28,29 Measured data was collected by the investigative team using the AMTI Netforce computer software. Measurements The FST recorded both forces and moments, and has the elements necessary to allow for accurate estimation of the loads transmitted during the HVLA manipulation. The force-time profiles were recorded electronically using MatLab software. Each profile was manually digitized to define the boundaries or data analysis: preload, peak thrust, time-to-peak thrust. All digitization was done by a singular individual on the research team. To evaluate consistency, ICCs were calculated on a pairwise basis using preload, speed, peak, and duration.

Fig 2. Percentage from target (400 N intensity).

Each time profile was collected using MatLab software (MATLAB; MathWorks, Natick, MA) using a window of approximately 1 second to ensure the peak thrust force was captured. Data for each subject was manually digitized using MatLab software to determine the characteristic features of the force-time profile including preload, peak, speed, and duration.19 The data for the subjects was recorded and entered into a Microsoft Excel spreadsheet, where it could be analyzed. Once all data for each intensity of total peak force (400 and 600 N) was obtained for each subject, the raw scores were organized using a Microsoft Excel spreadsheet. These values were then analyzed using STATA software (v10.0) to obtain the mean scores, standard deviations, and confidence intervals. For both peak thrust and time-to-peak thrust, we used 2-tailed paired t tests comparing pre and post values for all force targets (400 and 600 N total peak force). The α values were corrected to .00625 using the Bonferroni method to account for chance error associated with conducting eight paired t tests. Data sets beyond three standard deviations from the group mean were considered outliers. Outliers were removed to determine if there was any change in statistical significance.26 All statistical evaluations were conducted using STATA software (v10.0) and supplemented by Microsoft Excel for ICCs.

Starmer et al

A selection of published research by CMCC faculty

Results Statistical analysis of the 125 complete data sets revealed that total peak force varied by 124.11 + 65.77 N during the pre-test and 123.29 + 61.43 N during the post-test for the 600 N intensity (P = .90); total peak force varied by 44.91 + 34.67 N during the pre-test and 44.60 + 32.63 N during the post-test compared to the defined target of 400 N (P = .57, Fig 2). Percentage distance from total peak force was 11.23% + 8.67% during the pre-test and 10.65% + 7.22% during the post-test for the 400 N total peak force (Table 1). Percentage distance from total peak force was 20.69% + 10.96% during the pre-test and 20.55% + 10.24% during the post-test for the 600 N total peak force (Fig 3). There was no statistically significant change for either peak force intensity.

practitioners, they have retained their skill acquisition for HVLA manipulation, a complex motor task, following a 12week detraining period. Currently there is no research that demonstrates how periods of detraining may affect the ability of chiropractors or other manual therapists to perform HVLA manipulations; however, other research has demonstrated that detraining occurs with regards to other complex motor tasks.

Time-to-peak thrust for the 400 N total peak force was 137.094 + 42.47 milliseconds during the pre-test and 125.385 + 37.46 milliseconds during the post-test (P = .0004); timeto-peak thrust for the 600 N total peak force was 136.835 + 40.48 milliseconds during the pre-test and 125.385 + 33.78 milliseconds during the post-test (P = .031). There was a statistically significant improvement for time-to-peak thrust for the 400 N total peak force, with the subjects improving by an average of 11.709 milliseconds after the 12-week detraining period. There was no statistically significant change in time-topeak thrust for the 600 N total peak force (Table 2).

Table 1. Distance from Target Peak Thrust Force Target Total Peak Force

Session

Mean (N)

400 N

Pre Post

600 N

Pre Post

44.91 (34.67) 42.60 (28.88) P = .5690 124.11 (65.77) 123.29 (61.43) P = .8994

Discussion Due to this being a foundational study, the results help to inform whether periods of detraining can impact the skill acquisition of HVLA manipulations in manual therapy students. The results from this study show that the first-year chiropractic students were able to retain their ability to modulate their force and time-to-peak thrust following a 12-week detraining period. Percentage distance from total peak force was 11.23% + 8.67% during the pre-test and 10.65% + 7.22% during the post-test for the 400 N total peak force. Percentage distance from total peak force was 20.69% + 10.96% during the pre-test and 20.55% + 10.24% during the post-test for the 600 N total peak force. Despite the fact that the subjects were not able to match the defined target for total peak force, no statistically significant changes were observed between the pre and post testing sessions for their ability to modulate force with either intensity (400 or 600 N). This is an important finding as it shows that although the students are not yet on par with expert field

Fig 3. Percentage from target (600 N intensity).

The subjects were able to maintain their time-to-peak thrust for the 600 N total peak force intensity and decrease their time-to-peak thrust for the 400 N total peak force intensity. For the 400 N total peak force the average time-to-peak thrust decreased by 11.709 milliseconds, which indicates an increase in speed during the HVLA manipulation. This improvement is a statistically significant finding (P = .004); however, it is unclear if this improvement is clinically significant. For the 600 N total peak force, the average time-to-peak decreased by 11.450 milliseconds. This improvement was not statistically significant (P = .03086); however, it may suggest a trend within our study. This may be a spurious finding, but more in depth analysis in future studies may be helpful. Further research is warranted to determine what level of improvement represents a clinically significant finding during a HVLA manipulation. It is possible that the students were able to master the performance of this complex motor task so there was no drop off in overall performance. This scenario would be possible if one considers the complexity of performing a HVLA manipulation as a technical skill, which one could become proficient at performing prior to being proficient at their ability to modulate their forces. Reznick et al demonstrated that surgeons who were able to practice complex procedures â&#x20AC;&#x153;learned and practiced on models and simulatorsâ&#x20AC;? were able to enhance their performance.4,30 This could be accomplished

CMCC Research Report 2015–2018

Table 2. Time-To-Peak Force Target Total Peak Force 400 N 600 N

Session Mean (milliseconds) Pre Post Post-Pre Pre Post Post-Pre

137.094 125.385 − 11.709 136.835 128.545 − 8.290

SD 42.47 37.46 36.16 40.48 33.78 41.92

P P = .0004 P = .03086

through “deliberate practice,” where the individual spends time trying to master a particular skill rather than an entire task. It is possible that the students were able to amass enough hours of “deliberate practice” at performing these manipulations to have become masterful at modulating their force, while not yet becoming entirely proficient in their performance. Research on detraining has shown that after 4 weeks of detraining, older men may experience a loss in force production but maintain gains in neuromuscular performance.21 These gains in neuromuscular performance could help to explain the ability of these students to maintain their levels of performance for both target peak force and time to peak thrust.

Limitations and Future Research One uncontrollable variable was that students could not be blinded and may have unintentionally altered the results. However, given that the students performed well overall we do not believe this is a concern. After discussions with a statistician, it was believed that outliers whom may have improved substantially after the detraining period could have done so due to regression towards the mean, therefore they were excluded from the overall data set. A major limitation to this study was that we did not control for possible practice during the detraining period, as it was assumed the students did not have access to practice their HVLA manipulation skills. Although spinal manipulation is a controlled act, it is possible the students could practice their HVLA manipulation skills during the detraining period; this could have been accomplished either by attending continuing education opportunities, or unethically practicing the procedure without supervision. The possibility of attending practice hours in the FST lab is low, as there is no scheduled time available to practice at the facility during the detraining period. Hall et al have demonstrated that high fidelity simulation can be effective at training emergency medicine residents, while Starmer et al have presented a case study that demonstrates how technical emergency skills have been carried over using high-fidelity manikins at a chiropractic college.1,26,31 Using one or more of these possible outlets, it is feasible that the students were able to practice HVLA manipulations during their time off. The students at this institution are uniquely trained in the performance of HVLA manipulations using FSTT®. It is possible that this prior exposure to technology-assisted knowledge-

of-results for force-time profiles makes the findings of our study limited. The usage of FSTT® is unique to the chiropractic curriculum at this institution, and makes the pedagogy of how HVLA manipulations are taught unlike others in manual therapy. Similarly, this study looks at one particular type of HVLA manipulations, those targeted at the thoracic spine. It is unclear if other types of HVLA manipulations, whether targeted at other areas of spine or at extremities, may be impacted by periods of detraining. Further research is needed to ascertain whether these findings are consistent across other types of HVLA manipulations, various chiropractic colleges, other manual therapy professions, and with experienced field practitioners. Another limitation of this study is that it did not measure the confidence of the students in performing their HVLA manipulations, but only the competence that they had in terms of modulating their applied total peak force. Although the results did not show any statistically significant changes for the ability to modulate force, it is possible that the students felt less confident following a 12-week detraining period. Incorporating exit interviews for this study could have helped to overcome these limitations and perhaps provided the authors with more data to help explain the observed findings. It is unclear what factors allowed the students to maintain their force modulation ability. Therefore, further research is recommended to ascertain whether these findings are consistent across other years, other institutions, and other professions.

Conclusion The results of this study illustrate that first-year chiropractic students are able to retain the ability to modulate their force following a 12-week period of detraining. The performance of first-year students when performing both 400 and 600 N total peak force was neither clinically nor statistically significant between the pre and post testing sessions. This study demonstrates that the first-year chiropractic students were able to maintain their force modulation ability following the 12-week detraining period, although the performance of the students varied from the target.

Funding Sources and Potential Conflicts of Interest No funding sources or conflicts of interest were reported for this study.

Starmer et al

Contributorship Information Concept development (provided idea for the research): D.J.S., B.P.G., T.R.T., S.C.W., M.G.R.W. Design (planned the methods to generate the results): D.J.S., B.P.G., T.R.T., S.C.W., M.G.R.W. Supervision (provided oversight, responsible for organization and implementation, writing of the manuscript): D.J.S., B.P.G., T.R.T., S.C.W., M.G.R.W. Data collection/processing (responsible for experiments, patient management, organization, or reporting data): B.P.G., T.R.T., S.C.W., M.G.R.W. Analysis/interpretation (responsible for statistical analysis, evaluation, and presentation of the results): B.P.G., T.R.T., S.C.W., M.G.R.W. Literature search (performed the literature search): B.P.G., T.R.T., S.C.W., M.G.R.W. Writing (responsible for writing a substantive part of the manuscript): B.P.G., T.R.T., S.C.W., M.G.R.W. Critical review (revised manuscript for intellectual content, this does not relate to spelling and grammar checking): D.J.S., B.P.G., T.R.T., S.C.W., M.G.R.W.

Acknowledgement We thank Dr. Dominic Giuliano, Dr. Jay Triano, and Steve Tran for all of their assistance and guidance on this project. They provided mentorship, investigator training, and assistance with data collection and analysis. Drs. Giuliano and Triano were instrumental during the experimental design, provided investigator training regarding the usage of the FSTTÂŽ, and assisted with data collection. Steve Tran provided assistance with the software and specific coding for MatLab, providing valuable insight into the usage of the FSTTÂŽ for our purposes. Practical Applications A group of 125 chiropractic students were able to maintain their ability to modulate force with both 400 and 600 N total peak force targets following a12-week detraining period.

Referances 1. Hall AK, Pickett W, Dagnone JD. Development and evaluation of a simulation-based resuscitation scenario assessment tool for emergency medicine residents. CJEM 2012;14:139-46. 2. Herzog W. The biomechanics of spinal manipulation. J Bodyw Mov Ther 2010;14:280-6. 3. Mujika I, Padilla S. Detraining: loss of training-induced physiological and performance adaptations: Part II Long term Insufficient training stimulus. Sports Med 2000;30:145-54. 4. Keller TS, Colloca CJ, Moore RJ, Gunzburg R, Harrison DD. Three-dimensional vertebral motions produced by mechanical force spinal manipulation. J Manipulative Physiol Ther 2006; 29:425-36.

A selection of published research by CMCC faculty

5. Marchand A. A proposed model with possible implications for safety and technique adaptations for chiropractic spinal manipulative therapy for infants and children. J Manipulative Physiol Ther 2015;38:713-26. 6. Triano J, Giuliano D, Kamga I, et al. Consistency and Malleability of Manipulation Performance in Experienced Clinicians. J Manipulative Physiol Ther 2015;38:407-15. 7. Cao DY, Reed WR, Long CR, Kawchuk GN, Pickar JG. Effects of thrust amplitude and duration of high-velocity, low-amplitude spinal manipulation on lumbar muscle spindle responses to vertebral position and movement. J Manipulative Physiol Ther 2013;36:68-77. 8. Pickar JG, Sung PS, Kang YM, Ge W. Response of lumbar paraspinal muscles spindles is greater to spinal manipulative loading compared with slower loading under length control. Spine J 2007;7:583-95. 9. Pickar JG, Wheeler JD. Response of muscle proprioceptors to spinal manipulative-like loads in the anesthetized cat. J Manipulative Physiol Ther 2001;24:2-11. 10. Reed WR, Long CR, Kawchuk GN, Pickar JG. Neural responses to the mechanical parameters of a high-velocity, low-amplitude spinal manipulation: effect of preload parameters. J Manipulative Physiol Ther 2014;37:68-78. 11. Reed WR, Cao DY, Long CR, Kawchuk GN, Pickar JG. Relationship between Biomechanical Characteristics of Spinal Manipulation and Neural Responses in an Animal model: Effect of linear control of thrust displacement versus force, thrust amplitude, thrust duration, and thrust rate. Evid Based Complement Alternat Med 2013;2013:492039. 12. Valliant M, Edgecomb T, Long CR, Pickar JG, Kawchuk GN. The effect of duration and amplitude of spinal manipulative therapy (SMT) on spinal stiffness. Man Ther 2012;17:577-83. 13. Cleland JA, Fritz JM, Kulag K, et al. Comparison of the effectiveness of three manual physical therapy techniques in a subgroup of patients with low back pain who satisfy a clinical prediction rule: a randomized clinical trial. Spine 2009;34:2720-9. 14. Colloca CJ, Keller TS, Gunzbug R. Biomechanical and neurophysiological responses to spinal manipulation in patients with lumbar radiculopathy. J Manipulative Physiol Ther 2004;27: 1-15. 15. Colloca CJ, Keller TS, Gunzburg R, Vandeputte K, Fuhr AW. Neurophysiologic response to intraopertiave lumbosacral spinal manipulation. J Manipulative Physiol Ther 2000;23:447-57. 16. Kelly TS, Colloca CJ, Moore RJ, Gunzburg R, Harrision DE. Increased multiaxial lumbar motion responses during multiple-impulse mechanical force manually assisted spinal manipulation. Chiropr Osteopat 2006;14:6. 17. Kelly TS, Colloca CJ, Gunzburg R. Neuromechanical characterization of in vivo lumbar spinal manipulation. Part 1. Vertebral motion. J Manipulative Physiol Ther 2003; 26:567-78.

CMCC Research Report 2015–2018

18. Nougarou F, Dugas C, Deslauries C, Page I, Decarreaux M. Physiological responses to spinal manipulation therapy: investigation of the relationship between electromyographic responses and peak force. J Manipulative Physiol Ther 2013;36: 557-63. 19. Triano J, Giuliano D, McGregor M, Howard L. Enhanced Learning of Manipulation Techniques using Force-Sensing Table Technology™ (FSTT®). Toronto: Higher Education Quality Council of Ontario; 2014. 20. Conway PJ, Hasler EM, Herzog W, Ladly K, Zhang Y. Forces required to cause cavitation during spinal manipulation of the thoracic spine. Clin Biomech 1993;8:210-4. 21. Kawchuk G, Herzog W. Biomechanical characterization (fingerprinting) of five novel methods of cervical spinal manipulation. J Manipulative Physiol Ther 1993;16:573-7. 22. Dai B, Sorensen C, Derrick T, Gillette J. The effects of postseason break on knee biomechanics and lower extremity EMG in a stop-jump task: implications for ACL injury. J Appl Biomech 2012;28:708-17. 23. Byfield D. Chiropractic Manipulative Skills. 2nd ed. St. Louis: Elsevier; 2005. 24. Bergman TF, Peterson DH. Chiropractic Technique Principles and Practice. 3rd ed. St. Louis: Elsevier; 2011. 25. Rogers C, Triano J. Biomechanical measure validation for spinal manipulation in clinical settings. J Manipulative Physiol Ther 2003;26:539-48. 26. Sackett DL. Bias in analytic research. J Chronic Dis 1979;32: 51-63. 27. Starmer D, Duqette S, Stainsby B, Giuliano A. Does soft tissue compliance of thoracic paraspinal musculature change based on body type. J Chiropr Educ 2015;27:80-3. 28. Giuliano DA, McGregor M. Assessment of a generalizable methodology to assess learning from manikin-based simulation technology. J Chiropr Educ 2014;28:16-20. 29. McGregor M, Giuliano D. Manikin-based clinical simulation in chiropractic education. J Chiropr Educ 2012;26:14-23. 30. Reznick R, MacRae H. Teaching surgical skills-changes in the wind. N Engl J Med 2006;355:2664-9. 31. Starmer DJ, Duquette SA, Guiliano D, et al. Observed improvements in an intern’s ability to initiate critical emergency skills in different cardiac arrest scenarios using high-fidelity simulation. J Chiropr Educ 2014;28:164-7.

Originally published in the Journal of Manipulative and Physiological Therapeutics, 2016 May;39(4):311-7. Epub 2016 Apr 6. Reproduced with permission from Elsevier. Access Online: https://doi.org/10.1016/j.jmpt.2016.02.010

A selection of published research by CMCC faculty

Education in Health Care

No Difference in Learning Retention in Manikin-Based Simulation Based on Role Giuliano D, McGregor, M Canadian Memorial Chiropractic College

Abstract Objective: We evaluated learning retention in interns exposed to simulation. It was hypothesized that learning would degrade after 6 months and there would be a difference in retention between interns who played a critical role versus those who did not. Methods: A total of 23 groups of 5 to 9 interns underwent a cardiac scenario twice during 1 simulation experience and again 6 months later. We captured 69 recordings (23 before debrief at baseline [PrDV], 23 after debrief at baseline [PoDV], and 23 at 6-month follow-up [FUV]). Students were assigned different roles, including the critical role of â&#x20AC;&#x153;doctorâ&#x20AC;? in a blinded, haphazard fashion. At 6-month follow-up, 12 interns who played the role of doctor initially were assigned that role again, while 11 interns who played noncritical roles initially were newly assigned to doctor. All videos of intern performance were scored independently and in a blinded fashion, by 3 judges using a 15item check list.

Results: Repeated-measures analysis of variance for interns completing all 3 time points indicated a significant difference between time points (F2,22 = 112, p = .00). Contrasts showed a statistically significant difference between PrDV and PoDV (p = .00), and PrDV and FUV (p = .00), but no difference between PoDV and FUV (p = .98). This was consistent with results including all data points. Checklist scores were more than double for PoDV recordings (16) and FUV (15), compared to PrDV recordings (6.6). Follow-up scores comparing old to new doctors showed no statistically significant difference (15.4 vs 15.2 respectively, t21 = 0.26, p = .80, d = .11). Conclusion: Learning retention was maintained regardless of role.

Originally published in the Journal of Chiropractic Education, 2016 Mar;30(1):20-4. Epub 2015 Sep 14. Reproduced with permission from the Association of Chiropractic Colleges. Access Online: https://doi.org/10.7899/JCE-15-1

CMCC Research Report 2015â&#x20AC;&#x201C;2018

Description of the Case Mix Experienced by Chiropractic Students During a Clinical Internship Puhl AA, Reinhart CJ, Injeyan SH, Tibbles A Canadian Memorial Chiropractic College

Abstract Objective: The primary objective of this study was to describe the case mix experienced by chiropractic students during their clinical internship at the Canadian Memorial Chiropractic College. Secondary objectives were to characterize teaching clinic patient populations, assess the similarity to previously published data for practicing chiropractors, and describe the treatment plans being recommended by interns. Methods: A prospective, observational study was conducted using a convenience sample of 24 chiropractic interns. Data were collected by interns using a standardized form that was completed for each new patient and each new complaint examined during the 1-year internship. Standardized forms included data regarding patient demographics, complaint characteristics, and treatment recommendations. Results: Data were included for 23 of 24 participating interns, who described 828 patients and a total of 948 unique complaint presentations. Overall, 60% of patients were female, 86% were 18 to 64 years old, and 23% were naive to chiropractic care. Of all presenting complaints, 93% were pain-based, 67% were chronic, 65% included spinal complaints, and 7% presented with red flags; individual internsâ&#x20AC;&#x2122; experiences were variable and are described. On average, treatment recommendations called for 9.4 visits and often included multimodal treatment approaches, most commonly soft-tissue therapies (91%), home-based active care (84%), and spine manipulation (70%).

Conclusion: The findings of this study suggest that patients presenting to CMCC teaching clinics are similar to those reported previously to attend private chiropractic clinics. While all participating interns encountered multiple complex clinical cases, very few had experience with pediatric populations. This study adds to the few that detail the characteristics of patients attending chiropractic teaching clinics; to our knowledge it is the first to describe average case loads of chiropractic interns.

Originally published in the Journal of Chiropractic Education, 2017 Oct;31(2):132-139. Epub 2017 Jun 28. Reproduced with permission from the Association of Chiropractic Colleges. Access Online: https://journalchiroed.com/doi/10.7899/JCE-16-00017

A selection of published research by CMCC faculty

Concussion Knowledge Among Sport Chiropractic Fellows from the Royal College of Chiropractic Sports Sciences (Canada) Kazemi M, Bogumil ME, Vora K Canadian Memorial Chiropractic College

Abstract Objectives: The objective of this study was to investigate the degree of knowledge that sports chiropractors have in regard to concussion diagnosis and management. Methods: A concussion knowledge survey was administered to Sport Chiropractic Fellows of the Royal College of Chiropractic SportsSciences - Canada (RCCSS(C)) (n=44) via SurveyMonkey.com. Results: Sports chiropractors scored statistically higher on the survey when compared to chiropractic residents (mean =5.57 vs. 5.25; t=2.12; p=0.04) and to fourth year chiropractic interns (mean = 5.57 vs 5.2; t=2.45; p=0.02). Additionally, with our modified scoring, the sports chiropractors scored 85.3%. A few knowledge gaps were identified in the sample population.

Conclusion: Sports chiropractors demonstrated the skills and knowledge to diagnose concussion and excel at identifying the definition and mechanism of concussion, but knowledge gaps regarding diagnosis and management of concussion were found in the sample population.

Originally published in the Journal of the Canadian Chiropractic Association. 2017 Dec;61(3):239-252. Reproduced with permission. Access Online: https://doi.org/10.1016/j.jmpt.2015.10.002

CMCC Research Report 2015–2018

Health and Wellness

The Effectiveness of Exercise on Recovery and Clinical Outcomes in Patients with Soft Tissue Injuries of the Hip, Thigh, or Knee: A Systematic Review by the Ontario Protocol for Traffic Injury Management (OPTIMa) Collaboration Brown CK1, Southerst D2, Côté P1,2,3,4, Shearer HM1,4, Randhawa K1, Wong JJ1,4, Yu H1,4, Varatharajan S1,4, Sutton D1,4, Stern PJ1, D’Angelo K1, Dion S1, Cox J1, Goldgrub R3, Stupar M1,4, Carroll LJ1,5, Taylor-Vaisey A 4 Canadian Memorial Chiropractic College, 2Mount Sinai Hospital, 3University of Ontario Institute of Technology, 4UOIT-CMCC Centre for the Study of Disability Prevention and Rehabilitation, University of Ontario Institute of Technology (UOIT) and Canadian Memorial Chiropractic College (CMCC), 5 University of Alberta 1

Abstract Objectives: The purpose of this systematic review was to determine the effectiveness of exercise for the management of soft tissue injuries of the hip, thigh, and knee. Methods: We conducted a systematic review and searched MEDLINE, EMBASE, PsycINFO, the Cochrane Central Register of Controlled Trials, and CINAHL Plus with Full Text from January 1, 1990, to April 8, 2015, for randomized controlled trials (RCTs), cohort studies, and case-control studies evaluating the effect of exercise on pain intensity, self-rated recovery, functional recovery, health-related quality of life, psychological outcomes, and adverse events. Random pairs of independent reviewers screened titles and abstracts and assessed risk of bias using the Scottish Intercollegiate Guidelines Network criteria. Best evidence synthesis methodology was used.

Results: We screened 9494 citations. Eight RCTs were critically appraised, and 3 had low risk of bias and were included in our synthesis. One RCT found statistically significant improvements in pain and function favoring clinic-based progressive combined exercises over a “wait and see” approach for patellofemoral pain syndrome. A second RCT suggests that supervised closed kinetic chain exercises may lead to greater symptom improvement than open chain exercises for patellofemoral pain syndrome. One RCT suggests that clinic-based group exercises may be more effective than multimodal physiotherapy in male athletes with persistent groin pain. Conclusion: We found limited high-quality evidence to support the use of exercise for the management of soft tissue injuries of the lower extremity. The evidence suggests that clinic-based exercise programs may benefit patients with patellofemoral pain syndrome and persistent groin pain. Further high-quality research is needed.

Originally published in the Journal of Manipulative and Physiological Therapeutics, 2016 Feb;39(2):110-20.e1. Reproduced with permission from Elsevier. Access Online: https://doi.org/10.1016/j.jmpt.2016.01.003

A selection of published research by CMCC faculty

Exercise as a Vital Sign: A Preliminary Pilot Study in a Chiropractic Setting Howitt S, Simpson K, Suderman D, Mercer A, Rutherford S, deGraauw C Canadian Memorial Chiropractic College

Abstract Background: The association between physical inactivity and noncommunicable disease risk has been well documented in recent literature. An exercise vital sign (EVS) is a measure that can routinely capture vital information about a patientâ&#x20AC;&#x2122;s physical activity behaviour. The objective of this study is to understand if (1) patient exercise minutes per week (EMPW) are being recorded by chiropractic interns, and (2) whether these patients are exceeding, meeting or falling short of the current recommendations provided by the Canadian Physical Activity Guidelines (CPAG). Methods: Electronic medical records obtained from two Canadian Memorial Chiropractic College (CMCC) teaching clinics for patients seen between August 01, 2015 and January 31, 2017 (N=273). EMPW, age, and gender were used to compare patient files relative to the CPAG.

Results: Overall, 86.4% of patient files had recorded data to the question of how many EMPW they perform. The majority (68.8%) of individuals appear to be meeting or exceeding the CPAG, leaving nearly one third (31.2%) of individuals failing to meet these guidelines. Conclusion: In this pilot study with two sports specialist clinicians an exercise vital sign had been integrated alongside traditional vital signs in order to identify issues of physical inactivity and improve opportunities for continued exercise counselling.

Originally published in the Journal of the Canadian Chiropractic Association, 2017 Dec;61(3):231-238. Reproduced with permission. Access Online: https://doi.org/10.1016/j.jmpt.2016.01.003

CMCC Research Report 2015–2018

Knowledge Translation and Health Policy

Clinical Practice Guidelines for the Noninvasive Management of Low Back Pain: A Systematic Review by the Ontario Protocol for Trafﬁc Injury Management (OPTIMa) Collaboration Wong JJ1,2, Côté P1,2,3, Sutton DA1,2, Randhawa K1,2, Yu H1,2, Varatharajan S1,2, Goldgrub R3, Nordin M4, Gross DP5, Shearer HM1,2, Carroll LJ5, Stern PJ2, Ameis A6, Southerst D1,7, Mior S1,2, Stupar M1, Varatharajan T1,8, Taylor-Vaisey A1 UOIT-CMCC Centre for the Study of Disability Prevention and Rehabilitation, University of Ontario Institute of Technology (UOIT) and Canadian Memorial Chiropractic College (CMCC), 2Canadian Memorial Chiropractic College, 3University of Ontario Institute of Technology, 4New York University, 5 University of Alberta, 6University of Montreal, 7Mount Sinai Hospital, Toronto, 8University of Saskatchewan 1

Abstract We conducted a systematic review of guidelines on the management of low back pain (LBP) to assess their methodological quality and guide care. We synthesized guidelines on the management of LBP published from 2005 to 2014 following best evidence synthesis principles. We searched MEDLINE, EMBASE, CINAHL, PsycINFO, Cochrane, DARE, National Health Services Economic Evaluation Database, Health Technology Assessment Database, Index to Chiropractic Literature and grey literature. Independent reviewers critically appraised eligible guidelines using AGREE II criteria. We screened 2504 citations; 13 guidelines were eligible for critical appraisal, and 10 had a low risk of bias. According to high-quality guidelines: (1) all patients with acute or chronic LBP should receive education, reassurance and instruction on self-management options; (2) patients with acute LBP should be encouraged to return to activity and may benefit from paracetamol, nonsteroidal anti-inflammatory drugs (NSAIDs), or spinal manipulation; (3) the management of chronic LBP may include exercise, paracetamol or NSAIDs, manual therapy, acupuncture, and multimodal rehabilitation (combined physical and psychological treatment); and (4) patients with lumbar disc herniation with radiculopathy may benefit from spinal manipulation. Ten guidelines were of high methodological quality, but updating and some methodological improvements are needed. Overall, most guidelines target nonspecific LBP and recommend education, staying active/exercise, manual therapy, and paracetamol or NSAIDs as first-line treatments. The recommendation to use paracetamol for acute LBP is challenged by recent evidence and needs to be revisited. Significance: Most high-quality guidelines recommend education, staying active/ exercise, manual therapy and paracetamol/NSAIDs as first-line treatments for LBP. Recommendation of paracetamol for acute LBP is challenged by recent evidence and needs updating.

Introduction More than 80% of people experience at least one episode of back pain during their lifetime (Cassidy et al., 1998; Walker, 2000). Back pain is a common source of disability, whether the pain is attributed to work, trafﬁc collisions, activities of daily living, or insidious onset (Cassidy et al., 1998, 2005; Hincapie et al., 2010). Back pain is costly, accounting for a considerable proportion of work absenteeism and lost productivity (Carey et al., 1995, 1996). Moreover, it is the most common reason for visiting a healthcare provider for musculoskeletal complaints (Cypress, 1983; Côté et al., 2001). Although multiple clinical interventions are available to treat back pain, current evidence suggests that their effects appear small and short term (Haldeman and Dagenais, 2008). Clinical practice guidelines are systematically developed statements that include recommendations intended to optimize patient care and improve patients’ health outcomes (Shekelle et al., 1999, 2012; Institute of Medicine Committee on Standards for Developing Trustworthy Clinical Practice Guidelines, 2011). Guidelines aim to reduce the gap between research and clinical practice and assist policy makers with decisions that impact the population (Whitworth, 2006; Alonso-Coello et al., 2010). However, concerns have been raised about the quality of many clinical practice guidelines (Ransohoff et al., 2013). Systematic reviews report that some guidelines have methodological limitations (Shaneyfelt et al., 1999; Graham et al., 2001; Hasenfeld and Shekelle, 2003; Alonso-Coello et al., 2010; Berrigan et al., 2011; Knai et al., 2012). Common ﬂaws include poor literature review methodology, limited involvement of stakeholders and unclear editorial independence (Alonso-Coello et al., 2010). Therefore, valid concerns exist about the potentially negative impact of biased guidelines on the care and health outcomes of patients (Delgado-Noguera et al., 2009; Shaneyfelt and Centor, 2009; Tricoci et al., 2009; Alonso-Coello et al., 2010).

Wong et al

Guidelines of poor methodological quality may lead clinicians to consider interventions that are ineffective, costly, or harmful. Low-quality guidelines may lead decision makers to invest in the implementation of ill-informed recommendations. Moreover, low-quality guidelines may reduce their adoption by clinicians and policy makers. Known barriers to the adoption of guidelines include lack of clarity of recommendation development, ambiguous recommendations, and inconsistent recommendations across guidelines (Côté et al., 2009). Finally, when combined with other barriers, such as lack of time, limited understanding of how guidelines are developed, and inadequate dissemination, it is easy to understand why the uptake of some clinical guidelines by clinicians has been disappointing (Côté et al., 2009; Bishop et al., 2015; Slade et al., 2015). Many clinical practice guidelines on the management of low back pain are available in the peer-reviewed literature. A systematic review of these guidelines found that the quality of their methodology was adequate but varied across guidelines (Dagenais et al., 2010). However, the literature search for this systematic review ended in 2009 (Dagenais et al., 2010), and many guidelines have been published or updated since (Cutforth et al., 2011; Livingston et al., 2011; Philippine Academy of Rehabilitation Medicine, 2011; Brosseau et al., 2012; Delitto et al., 2012; Kung et al., 2012; North American Spine Society, 2012; Scottish Intercollegiate Guidelines Network, 2013; Kreiner et al., 2014). An up-to-date systematic review of these guidelines is needed to assess their methodological quality and help guide appropriate management of low back pain. The purpose of this systematic review was to review clinical practice guidelines, programmes of care, and treatment protocols to identify effective conservative (noninvasive) interventions for the management of acute and chronic low back pain.

Methods Review Registration The protocol for our systematic review was registered on PROSPERO (CRD42015017762) and can be accessed at www.crd.york.ac.uk/PROSPERO/display_ record. asp?ID=CRD42015017762. Literature Search We developed the search strategy in consultation with a health sciences librarian. A second librarian reviewed the search strategy using the Peer Review of Electronic Search Strategies Checklist (Sampson et al., 2009). The search strategy combined terms relevant to low back pain and guidelines and included free-text words and subject headings speciﬁc to each database (Supporting Information Appendix S1). The following databases were searched from January 1, 2005, to April 30, 2014: MEDLINE, EMBASE, CINAHL, PsycINFO, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, Cochrane Central Register of Controlled Trials, National Health Services Economic Evaluation Database, Health

A selection of published research by CMCC faculty

Technology Assessment Database and the Index to Chiropractic Literature. Guidelines published prior to 2005 were considered outdated (Kung et al., 2012) and were captured in a previous systematic review of guidelines (Dagenais et al., 2010). We hand searched reference lists of relevant guidelines for supplemental documents relevant to the methodology of that guideline. We searched the grey literature using the following: National Guideline Clearinghouse (Agency for Healthcare Research and Quality), Canadian Medical Association Infobase, Guidelines International Network, PEDro, Trip Database, American College of Physicians Clinical Recommendations, Australian Government, National Health and Medical Research Council, Health Services/Technology Assessment Texts, Institute for Clinical Systems Improvement, National Institute for Health and Clinical Excellence (NICE) Guidance, NICE Pathways, New Zealand Guidelines Group, Scottish Intercollegiate Guidelines Network (SIGN), and World Health Organization guidelines approved by the Guidelines Review Committee. Study Selection We used the following inclusion criteria: (1) English language; (2) targeting adults and/or children with low back pain with or without radiculopathy; (3) guidelines, programmes of care, or treatment proto-cols; (4) including recommendations for therapeutic noninvasive management. We excluded guidelines that: (1) did not include treatment recommendations; (2) were a summary or copy of previous guidelines; (3) were developed solely on the basis of consensus opinion; (4) did not conduct a systematic literature search or critical appraisal of studies used to derive recommendations; and (5) only targeted invasive (e.g. injection, surgery) interventions. Title and Abstract Screening We used a two-stage (title/abstracts and full-text) screening process with random pairs of independent reviewers. Disagreements between pairs of reviewers were resolved by discussion. A third reviewer was used to resolve disagreements if consensus could not be reached. We contacted authors if additional information was necessary to determine eligibility. Critical Appraisal of Eligible Guidelines Randomly allocated pairs of independent reviewers appraised relevant guidelines using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument (Table 1; Brouwers et al., 2010). The AGREE II instrument is widely used to assess the development and reporting of guidelines. It consists of 23 items in six quality-related domains: scope and purpose, stakeholder involvement, rigour of development, clarity of presentation, applicability, and editorial independence of guidelines (Table 1). All reviewers were trained in critical appraisal of guidelines using the AGREE II instrument. Discussions were held between paired reviewers to reach

CMCC Research Report 2015–2018

consensus on: (1) individual AGREE II items; (2) overall guideline quality; (3) whether the guideline was high quality; and (4) whether modiﬁcations to the guideline would be needed for use in speciﬁc jurisdictions (e.g. updating literature, modifying the format of the guideline). We contacted authors if additional information was needed to complete the critical appraisal. Table 1 The AGREE II instrument (Brouwers et al., 2010). AGREE II domains and items Domain 1. Scope and purpose 1. The overall objective(s) of the guideline is (are) specifically described. 2. The health question(s) covered by the guideline is (are) specifically described. 3. The population (patients, public, etc.) to whom the guideline is meant to apply is specifically described. Domain 2. Stakeholder involvement 4. The guideline development group includes individuals from all the relevant professional groups. 5. The views and preferences of the target population (patients, public, etc.) have been sought. 6. The target users of the guideline are clearly defined. Domain 3. Rigour of development 7. Systematic methods were used to search for evidence. 8. The criteria for selecting the evidence are clearly described. 9. The strengths and limitations of the body of evidence are clearly described. 10. The methods for formulating the recommendations are clearly described. 11. The health benefits, side-effects, and risks have been considered in formulating the recommendations. 12. There is an explicit link between the recommendations and the supporting evidence. 13. The guideline has been externally reviewed by experts prior to its publication. 14. A procedure for updating the guideline is provided. Domain 4. Clarity of presentation 15. The recommendations are specific and unambiguous. 16. The different options for management of the condition or health issue are clearly presented. 17. Key recommendations are easily identifiable. Domain 5. Applicability 18. The guideline provides advice and/or tools on how the recommendations can be put into practice. 19. The guideline describes facilitators and barriers to its application. 20. The potential resource implications of applying the recommendations have been considered. 21. The guideline presents monitoring and/or auditing criteria. Domain 6. Editorial independence 22. The views of the funding body have not influenced the content of the guideline. 23. Competing interests of guideline development group members have been recorded and addressed. AGREE II, Appraisal of Guidelines for Research and Evaluation, Version II.

Guidelines with poorly conducted systematic literature searches (question 7 of AGREE II) or with inadequate methods to critically appraise the evidence (question 9 of AGREE II) were deemed to have fatal ﬂaws and were excluded from our synthesis. These criteria are described as fundamental steps to the development

of evidence-based guidelines (Ransohoff, 2013). Although not considered a fatal ﬂaw, we considered lack of editorial independence from the funding body (question 22 of AGREE II) an important limitation to the quality of the guideline. The absence of editorial independence would contribute to lower overall guideline quality, since this may suggest poor reporting and lack of transparency in guideline development (AlonsoCoello et al., 2010). Data Extraction One reviewer extracted data from high-quality guidelines and built evidence tables. A second reviewer checked the data that were extracted from each guideline by comparing the extracted data with the data reported in the guidelines. We did not extract data on the use of interventional (invasive, surgical) therapies. Data Synthesis We synthesized recommendations from high-quality guidelines using evidence tables. Recommendations from high-quality guidelines were synthesized by interventions and summarized according to whether an intervention is (1) recommended; (2) not recommended or (3) lacked evidence to support or refute its use. We considered an intervention to be ‘recommended’ if the high-quality guideline used the following terminology: ‘strongly recommended’, ‘recommended without any conditions required’, ‘should be used’, or ‘recommended for consideration’ [includes ‘offer’ or ‘consider’ (National Institute of Health and Care Excellence, 2014)]. We stratiﬁed recommendations by duration of low back pain (i.e., acute or chronic) and by the number of guidelines recommending the intervention (‘recommended by all guidelines’ or ‘recommended by most guidelines’, i.e., more than 50% of guidelines).

Results We screened 2504 titles and abstracts for eligibility (Fig. 1). Of those, 75 potentially relevant articles were assessed in fulltext screening and 61 were ineligible. Primary reasons for ineligibility during full-text screening were (1) no systematic search or critical appraisal methods (8/61); (2) ineligible study design (48/61); (3) ineligible interventions (4/61); and (4) ineligible population (1/61). We critically appraised 13 eligible guidelines (reported in 14 articles/publications) and needed to contact authors of five guidelines (3/5 responded) to obtain additional information to assess guideline quality (Airaksinen et al., 2006; Nielens et al., 2006; Livingston et al., 2011). We identified 10 high-quality guidelines (Airaksinen et al., 2006; Nielens et al., 2006; van Tulder et al., 2006; Chou et al., 2007; National Institute of Health and Care Excellence, 2009; Cutforth et al., 2011; Livingston et al., 2011; Delitto et al., 2012; North American Spine Society, 2012; Scottish Intercollegiate Guidelines Network, 2013; Kreiner et al., 2014). Inter-rater agreement for article screening was k = 0.66 (95% confidence intervals 0.51; 0.81). Percentage agreement for guideline admissibility during independent critical appraisal was 77%

Wong et al

(10/13). We reached consensus through discussion for the three guidelines where there was disagreement between reviewers’ independent appraisal review (Livingston et al., 2011; Philippine Academy of Rehabilitation Medicine, 2011; Brosseau et al., 2012).

A selection of published research by CMCC faculty

(5/10) (Airaksinen et al., 2006; Nielens et al., 2006; van Tulder et al., 2006; Chou et al., 2007; Livingston et al., 2011); (2) no description of the procedure to update the guideline (3/10) (Airaksinen et al., 2006; Nielens et al., 2006; van Tulder et al., 2006); or (3) no declaration of competing interests by the guideline development group (2/10) (Airaksinen et al., 2006; Livingston et al., 2011). Six guidelines were published more than 5 years ago and need to be updated (Airaksinen et al., 2006; Nielens et al., 2006; van Tulder et al., 2006; Chou et al., 2007, 2009; National Institute of Health and Care Excel-lence, 2009). The three low-quality guidelines had major limitations: (1) no clear selection criteria of the literature (2/3; Philippine Academy of Rehabilitation Medicine, 2011; Delitto et al., 2012); (2) no clear description of strengths and limitations of the literature (2/3; Brosseau et al., 2012; Delitto et al., 2012); (3) no clear description of the methods used to formulate recommendations (3/3; Philippine Academy of Rehabilitation Medicine, 2011; Brosseau et al., 2012; Delitto et al., 2012); (4) no description of side-effects and risks (2/3; Philippine Academy of Rehabilitation Medicine, 2011; Brosseau et al., 2012); (5) no description of editorial independence from funders (1/3; Delitto et al., 2012); and (6) no declaration of whether there were any competing interests by guideline development group (3/3; Philippine Academy of Rehabilitation Medicine, 2011; Brosseau et al., 2012; Delitto et al., 2012).

Fig 1 Flow diagram of the selection of guidelines on the management of low back pain.

Methodological Quality The methodological quality of the 13 relevant guidelines varied (Tables 2 and 3). Most guidelines did not adequately address guideline applicability, particularly facilitators and barriers, resource implication, and/or monitoring or auditing criteria upon implementation (8/13 guidelines; Airaksinen et al., 2006; Nielens et al., 2006; Chou et al., 2007, 2009; Livingston et al., 2011; Brosseau et al., 2012; Delitto et al., 2012; Kreiner et al., 2014). Similarly, most guidelines did not clearly indicate whether they sought the views or preferences of the target population (9/13 guidelines; Airaksinen et al., 2006; van Tulder et al., 2006; Chou et al., 2007, 2009; Cutforth et al., 2011; Livingston et al., 2011; Brosseau et al., 2012; Delitto et al., 2012; Kreiner et al., 2014). The 10 guidelines with high methodological quality met the following criteria: (1) systematic methods to search for evidence (10/10); (2) clearly described strengths and limitations of the evidence (10/10); (3) considered health beneﬁts, sideeffects and risks (10/10); (4) provided an explicit link between recommendations and supporting evidence (10/10); (5) clearly described methods for formulating recommendations (9/10); and (6) clearly described criteria for selecting evidence (7/10; Table 2). However, the high-quality guidelines had limitations, including (1) no description of an external review process

High-Quality Guidelines Nine of the 10 high-quality guidelines addressed nonspecific low back pain (Table S1 and Table 4). Of these, one guideline targeted acute low back pain (van Tulder et al., 2006), five targeted chronic low back pain (Airaksinen et al., 2006; Nielens et al., 2006; Chou et al., 2009; National Institute of Health and Care Excellence, 2009; Scottish Intercollegiate Guidelines Network, 2013), and three addressed both acute and chronic (Chou et al., 2007; Cutforth et al., 2011; Livingston et al., 2011). For chronic low back pain, one guideline commented on multimodal rehabilitation (combined physical and psychological interventions) only (i.e., no recommendations for any other noninvasive interventions; Chou et al., 2009). The remaining guideline targeted lumbar disc herniation with radiculopathy (Table S1 and Table 4; Kreiner et al., 2014). Acute Nonspecific Low Back Pain (Four High-Quality Guidelines) Interventions recommended by all guidelines: 1. Advice, reassurance, or education with evidence-based information on expected course of recovery and effective self-care options for pain manage-ment (van Tulder et al., 2006; Chou et al., 2007; Cutforth et al., 2011; Livingston et al., 2011). 2. Early return to activities, staying active, or avoiding prescribed bed rest (van Tulder et al., 2006; Chou et al., 2007; Cutforth et al., 2011; Livingston et al., 2011).

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3. Paracetamol (acetaminophen) or nonsteroidal antiinflammatory drugs (NSAIDs) if indicated (van Tulder et al., 2006; Chou et al., 2007; Cut-forth et al., 2011; Livingston et al., 2011), with advice and consideration of risks and warning symptoms and signs associated with these medications. Only one guideline specified the recommended type and dosage of NSAID use [i.e. Ibuprofen, up to 800 mg three times per day (maximum of 800 mg four times per day) or diclofenac, up to 50 mg three times per day](Cutforth et al., 2011). 4. Muscle relaxants (short course) alone or in addition to NSAIDs if an initial trial of paracetamol or NSAIDs failed to reduce pain on their own (van Tulder et al., 2006; Chou et al., 2007; Cutforth et al., 2011; Livingston et al., 2011), with advice and consideration of sedation risks associated with muscle relaxants (Chou et al., 2007; Livingston et al., 2011). Only one guideline specified the recommended type and dosage of muscle relaxant use (i.e. Cyclobenzaprine, 10–30 mg/day, with greatest benefit within 1 week, although up to 2 weeks may be justified) (Cutforth et al., 2011). 5. Spinal manipulation for those not improving with selfcare options (Chou et al., 2007; Livingston et al., 2011) or failing to return to normal activities (van Tulder et al., 2006; Cutforth et al., 2011). Interventions recommended by most guidelines: 1. Short-term use of opioids on rare occasions, to control refractory, severe pain (3/4 guidelines) (Chou et al., 2007; Cutforth et al., 2011; Livingston et al., 2011). However, long-term use of opioids may be associated with significant risks related to the potential for tolerance, addiction or abuse (Livingston et al., 2011). One guideline did not address opioids for acute low back pain (van Tulder et al., 2006). Chronic Nonspecific Low Back Pain (Eight High-Quality Guidelines) Interventions recommended by all guidelines: 1. Education including advice and information promoting self-management (Cutforth et al., 2011); evidence-based information on expected course and effective self-care options (Chou et al., 2007; Livingston et al., 2011); brief educational interventions for short-term improvement (Airaksinen et al., 2006); and advice to stay active or make an early return to activities as tolerated (Airaksinen et al., 2006; Nielens et al., 2006; Chou et al., 2007; National Institute of Health and Care Excellence, 2009; Cutforth et al., 2011; Livingston et al., 2011; Scottish Intercollegiate Guidelines Network, 2013). 2. Exercises (Nielens et al., 2006; Chou et al., 2007; Cutforth et al., 2011; Livingston et al., 2011; Scottish Intercollegiate Guidelines Network, 2013) including supervised exercises (Airaksinen et al., 2006; National Institute of Health and

Care Excellence, 2009) or yoga (Chou et al., 2007; Cutforth et al., 2011; Livingston et al., 2011). Three guidelines found insufficient evidence to make recommendations for or against any specific type of exercise (Airaksinen et al., 2006; Nielens et al., 2006; Scottish Intercollegiate Guidelines Network, 2013), but to instead consider patient preferences (Airaksinen et al., 2006). Recommended frequency/duration was a maximum of eight sessions over up to 12 weeks (National Institute of Health and Care Excel-lence, 2009). 3. Manual therapy, including spinal manipulation (Nielens et al., 2006; Chou et al., 2007; National Institute of Health and Care Excellence, 2009; Cutforth et al., 2011; Livingston et al., 2011) or mobilizations (Airaksinen et al., 2006; Nielens et al., 2006). Recommended treatment frequency/duration was a maximum of nine sessions over up to 12 weeks (National Institute of Health and Care Excellence, 2009). 4. Paracetamol or NSAIDs as therapeutic options while considering side-effects and patient preferences (Airaksinen et al., 2006; Nielens et al., 2006; Chou et al., 2007; National Institute of Health and Care Excellence, 2009; Cutforth et al., 2011; Livingston et al., 2011; Scottish Intercollegiate Guidelines Network, 2013). 5. Short-term use of opioids when paracetamol or NSAIDs provided insufficient pain relief (Airaksinen et al., 2006; Nielens et al., 2006; Chou et al., 2007; National Institute of Health and Care Excellence, 2009; Cutforth et al., 2011; Livingston et al., 2011; Scottish Intercollegiate Guidelines Network, 2013). However, it is important to take into account side-effects, risks, and patient preference (Chou et al., 2007; Livingston et al., 2009; Livingston et al., 2011; Nielens et al., 2006) and to continue only with regular reassessments and when there is evidence of ongoing pain relief (Scottish Intercollegiate Guidelines Network, 2013). 6. Multimodal rehabilitation that included physical and psychological interventions (e.g., cognitive/behavioural approaches and exercise) for patients with high levels of disability or significant distress (Airaksinen et al., 2006; Nielens et al., 2006; Chou et al., 2007, 2009; National Institute of Health and Care Excellence, 2009; Cutforth et al., 2011; Livingston et al., 2011; Scottish Intercollegiate Guidelines Network, 2013). Recommended treatment frequency/duration was around 100 h over a maximum of up to 8 weeks (National Institute of Health and Care Excellence, 2009). Interventions recommended by most guidelines: 1. Massage (Chou et al., 2007; Cutforth et al., 2011; Livingston et al., 2011; Nielens et al., 2006; Scottish Intercollegiate Guidelines Net-work, 2013); however, one guideline recommended against massage for chronic low back pain (Airaksinen et al., 2006). This difference is likely due to more recent evidence informing the newer guidelines’

Oregon Health Authority, 2011

GDG, Year

Oregon Health Authority, 2011

Alberta, 2012 (Cutforth et al., 2011) 5

(chronic) (Airaksinen et al., 2006)

COST B13 Working Group, 2006b

(acute) (van Tulder et al., 2006)

COST B13 Working Group, 2006a 1

North American Spine Society,

2012 (Kreiner et al., 2014)

NICE, 2009 (NICE, 2009)

(Livingston et al., 2011)

External review

(b) Items 13 –23

Guidelines Network, 2013)

SIGN, 2013 (Scottish Intercollegiate 7

Centre, 2006 (Nielens, 2006)

Belgian Health Care Knowledge

(Chou et al., 2007)

the American Pain Society, 2007

American College of Physicians and 6

(Chou et al., 2009)

Procedure for updating

American Pain Society, 2009

Alberta, 2012 (Cutforth et al., 2011) 7

(chronic) (Airaksinen et al., 2006)

COST B13 Working Group, 2006b

(acute) (van Tulder et al., 2006)

COST B13 Working Group, 2006a

North American Spine Society,

2012 (Kreiner et al., 2014)

NICE, 2009 (NICE, 2009)

GDG, Year

(Livingston et al., 2011)

Overall Health objectives questions

(a) Items 1–12

Specific and clear Options recommendations presented

Population

Views of target GDG population

Key Facilitators recommendations and barriers

Advice and tools

Resource implication

Monitoring and auditing criteria

Views of the funding body

Competing interests of GDG

Systematic Strengths Methods for Benefits, Link between Target search Selection and limitations formulating side-effects, recommendations users methods criteria of evidence recommendations risks and evidence

Table 2 AGREE II ratings a of high-quality guidelines: (a) Items 1–12 and (b) Items 13 – 23.

Wong et al A selection of published research by CMCC faculty

6 5

7 6 Guidelines Network, 2013)

SIGN, 2013 (Scottish Intercollegiate 5

Centre, 2006 (Nielens, 2006)

(Chou et al., 2007)

Belgian Health Care Knowledge

1 3 1 7 6 7

AGREE II, Appraisal of Guidelines for Research and Evaluation, Version II; GDG, Guideline Development Group; NICE, National Institute of Health and Care Excellence; SIGN, Scottish Intercollegiate Guidelines Network. a Each AGREE II item is rated on a 7-point scale, where 1 = strongly disagree or insufficient information provided and 7 = strongly agree. b Rating is based on current information available.

4 7

7 7

4 7 1

7 1 1 1 3 7 7 7

4 the American Pain Society, 2007

American College of Physicians and 2

GDG, Year

Specific and clear Options recommendations presented Procedure for updating External review (b) Items 13 –23

Table 2 (Continued)

Interventions not recommended by most guidelines: 1. Muscle relaxants (Chou et al., 2007; Cutforth et al., 2011; Livingston et al., 2011; Scottish Intercollegiate Guidelines Network, 2013); six guidelines made recommendations on the use of muscle relaxants (Airaksinen et al., 2006; Nielens et al., 2006; Chou et al., 2007; Cutforth et al., 2011; Livingston et al., 2011; Scottish Intercollegiate Guidelines Network, 2013). Of those, four recommended against its use (Chou et al., 2007; Cutforth et al., 2011; Livingston et al., 2011; Scottish Intercollegiate Guidelines Network, 2013) and two stated that muscle relaxants can be considered as an option for pain relief (Airaksinen et al., 2006; Nielens et al., 2006). Specifically, one guideline reported that the benefit of muscle relaxants could not be estimated due to low-quality evidence (Chou et al., 2007). Two guidelines reported that some muscle relaxants (cyclobenzaprine, benzodiazepines) may provide short-term pain relief, but cautioned against long-term use due to side-effects (drowsiness, dizziness, addiction, allergic side-effects, reversible reduction of liver function, gastrointestinal effects) (Airaksinen et al., 2006; Nielens et al., 2006). However, evidence on the effectiveness of muscle relaxants was conflicting (Nielens et al., 2006). One guideline did not address muscle relaxants (National Institute of Health and Care Excellence, 2009).

Key Facilitators recommendations and barriers

3. Antidepressants as an option for pain relief, but possible side-effects (drowsiness, anticholinergic effects) should be considered (Airaksinen et al., 2006; Chou et al., 2007; National Institute of Health and Care Excellence, 2009; Cutforth et al., 2011; Livingston et al., 2011). However, one guideline recommended that antidepressants should not be used for chronic low back pain (Scottish Intercollegiate Guidelines Network, 2013), while one guideline reported conﬂicting evidence on the effectiveness of antidepressants (Nielens et al., 2006).

et al., 2009)

Advice and tools

Resource implication

Monitoring and auditing criteria

Views of the funding body

2. Acupuncture (Nielens et al., 2006; Chou et al., 2007; National Institute of Health and Care Excellence, 2009; Cutforth et al., 2011; Livingston et al., 2011; Scottish Intercollegiate Guidelines Network, 2013); however, one guideline recommended against acupuncture (Airaksinen et al., 2006). Again, this difference is likely due to more recent evidence informing the newer guidelines’ recommendations (Chou et al., 2007; Cutforth et al., 2011; Livingston et al., 2009; Livingston et al., 2011; Nielens et al., 2006; Scottish Intercollegiate Guidelines Network, 2013). Recommended treatment frequency/duration was a maximum of 10 sessions over up to 12 weeks (National Institute of Health and Care Excellence, 2009).

American Pain Society, 2009 (Chou 4

Competing interests of GDG

recommendations (Nielens et al., 2006; Chou et al., 2007; National Institute of Health and Care Excellence, 2009; Cutforth et al., 2011; Livingston et al., 2011; Scottish Intercollegiate Guidelines Network, 2013).

CMCC Research Report 2015–2018

External review

2 6

Specific and clear Options recommendations presented

Procedure for updating

Views of target GDG population

Key Facilitators recommendations and barriers

Advice and tools

Resource implication

Monitoring and auditing criteria

Views of the funding body

Competing interests of GDG

Link Systematic Strengths and Methods for Benefits, between Selection limitations formulating side-effects, recommendations Target search users methods criteria of evidence recommendations risks and evidence

AGREE II, Appraisal of Guidelines for Research and Evaluation, Version II; GDG, Guideline Development Group. Each AGREE II item is rated on a 7-point scale, where 1 = strongly disagree or insufficient information provided and 7 = strongly agree.

Ottawa Panel, 2012 (Brosseau 2 et al., 2012) 5 American Physical Therapy Association, 2012 (Delitto et al., 2012) 1 Philippine Academy of Rehabilitation Medicine, 2011 (Philippine Academy of Rehabilitation Medicine, 2011)

GDG, Year

(b) Items 13 – 23

Population

Overall Health objectives questions

Ottawa Panel, 2012 (Brosseau 6 et al., 2012) 7 American Physical Therapy Association, 2012 (Delitto et al., 2012) 7 Philippine Academy of Rehabilitation Medicine, 2011 (Philippine Academy of Rehabilitation Medicine, 2011)

GDG, Year

(a) Items 1– 12

Table 3 AGREE II ratings a of low-quality guidelines: (a) Items 1 –12 and (b) Items 13 –23.

Wong et al A selection of published research by CMCC faculty

58 R R

Acute

Chronic

Acupuncture

or NSAID

modality

Rc (cautioned

2007 (Chou et al., 2007)

(>12 weeks)

Chronic

(>12 weeks) R

R R

evidence)

inconsistent

only based on

R (for laser

side-effects)

use due to

long-term

against

Rc (cautioned

Antidepressant

rehabilitation

Multimodal

NICE, National Institute of Health and Clinical Excellence; NSAID, non-steroidal anti-inflammatory drugs; SIGN, Scottish Intercollegiate Guidelines Network; R, recommended (includes interventions that are strongly recommended or recommended for consideration); RA, recommended against (includes interventions that should not be offered). a Recommendations that were not specific to the duration of low back pain were presumed to apply to both acute and chronic. b This guideline focused on the effectiveness of multimodal rehabilitation for chronic low back pain. c These guidelines recommended considering significant risks and possible side-effects.

Network, 2013)

Intercollegiate Guidelines

SIGN, 2013 (Scottish

(â&#x2030;¤12 weeks)

(Cutforth et al., 2011)

Chronic

subacute

Acute and

Excellence, 2012

Institute of Health

2011)

Chronic

2011 (Livingston et al.,

12 months)

Acute

Care Excellence, 2009)

Oregon Health Authority,

(6 weeks to

Chronic

Institute of Health and

NICE, 2009 (National

(Chou et al., 2009)

2009 b

American Pain Society,

Chronic

Physicians and the

American Pain Society,

Acute

(>12 weeks)

Chronic

American College of

2006 (Nielens, 2006)

Knowledge Centre,

Belgian Health Care

use due to

course)

(short

course)

Gabapentin

(short

long-term

therapy

Opioid

relaxant

Tulder et al., 2006)

Exercise

Acetaminophen

physical

Muscle

against

active

Manual

Passive

et al., 2006; van

Group, 2006 (Airaksinen

COST B13 Working

or reassurance

or staying

self-management

Low Back Pain

activities

education,

Guideline

Duration of

return to

Advice,

Early

Table 4 Recommended interventions from high-quality guidelines for the management of nonspecific low back pain a

CMCC Research Report 2015â&#x20AC;&#x201C;2018

Wong et al

2. Gabapentin (Airaksinen et al., 2006; Nielens et al., 2006; Cutforth et al., 2011; Scottish Inter-collegiate Guidelines Network, 2013); one guide-line found insufficient evidence to recommend for or against gabapentin for chronic low back pain (Chou et al., 2007). Two guidelines did not address gabapentin (National Institute of Health and Care Excellence, 2009; Livingston et al., 2011). Two guidelines recommended considering gabapentin for neuropathic pain (but not chronic low back pain) (Cutforth et al., 2011; Scottish Intercollegiate Guidelines Network, 2013). 3. Passive modalities (Airaksinen et al., 2006; Chou et al., 2007; Cutforth et al., 2009; Cutforth et al., 2011; Nielens et al., 2006), including transcutaneous electrical nerve stimulation (TENS), laser, interferential therapy or ultrasound (Airaksinen et al., 2006; Chou et al., 2007; Cutforth et al., 2009; Cutforth et al., 2011; Nielens et al., 2006). Two guidelines found insufficient evidence for or against laser (Chou et al., 2007; Cutforth et al., 2011) or interferential therapy (Chou et al., 2007). One guideline did not address passive modalities (Livingston et al., 2011). One guideline recommended that laser could be considered a treatment option based on inconsistent evidence (Scottish Intercollegiate Guidelines Net-work, 2013). Lumbar Disc Herniation with Radiculopathy (One High-Quality Guideline) One high-quality guideline made recommendations for the noninvasive management of lumbar disc herniation with radiculopathy (Kreiner et al., 2014). Five other high-quality guidelines (Airaksinen et al., 2006; van Tulder et al., 2006; Chou et al., 2007, 2009; Livingston et al., 2011) included low back pain with leg pain in their scope, but did not have specific recommendations for the noninvasive management of lumbar disc herniation with radiculopathy. Recommended interventions 1. Spinal manipulation may be an option for symptomatic relief (Kreiner et al., 2014). 2. A limited course of structured exercise for patients with mild to moderate symptoms. This option was based on the consensus opinion of the guideline development group (in the absence of reliable evidence; Kreiner et al., 2014). There was insufficient evidence to make a recommendation for or against the use of traction, ultra-sound, and low-level laser therapy (Kreiner et al., 2014).

Discussion We conducted a systematic review of clinical practice guidelines to identify effective conservative (noninvasive) interventions for the management of acute and chronic low back pain. Most recommended interventions provide time-limited and small

A selection of published research by CMCC faculty

benefits. Based on high-quality guidelines: (1) patients with low back pain should be provided with education and encouraged to stay active and return-to-activity as tolerated; and (2) the management of acute nonspecific low back pain includes spinal manipulation (when not improving with self-care or not returning to normal activities), paracetamol or NSAIDs as indicated. Based on high-quality guidelines, the management of chronic nonspecific low back pain includes the following: (1) paracetamol or NSAIDs (although the effectiveness of paracetamol is now being challenged by new evidence); (2) short-term use of opioids for relief of refractory, severe pain; (3) exercises; (4) manual therapy; (5) acupuncture, and (6) multimodal rehabilitation (combined physical and psychological treatment). Finally, the noninvasive management of lumbar disc herniation with radiculopathy may include spinal manipulation for symptomatic relief (Kreiner et al., 2014). Very few guidelines provided information on recommended dose and frequency of care. Our results agree with recommended interventions identified by a previous systematic review of guidelines on low back pain (Dagenais et al., 2010). We confirmed that most passive modalities (e.g. TENS, laser, ultrasound) are not recommended for managing chronic low back pain (Dagenais et al., 2010). In addition, we found one recent high-quality guideline on lumbar disc herniation with radiculopathy published in 2012 (North American Spine Society, 2012). However, the recommendation of paracetamol for acute low back pain is challenged by a recent high-quality randomized controlled trial, which found that paracetamol did not improve recovery time compared with placebo for acute low back pain (Williams et al., 2014). Previous systematic reviews found no evidence supporting paracetamol for low back pain (Davies et al., 2008; Machado et al., 2015). Moreover, some high-quality guidelines used evidence from other conditions (e.g., osteoarthritis) to inform recommended interventions [paracetamol (Chou et al., 2007; Cutforth et al., 2011; Livingston et al., 2011) or opioids (Deyo et al., 2015)] for acute low back pain. Therefore, it is possible that using evidence for the management of other conditions, even if clinically relevant, may lead to inadequate recommendations. Given the risk of adverse events, we should reconsider the universal endorsement of paracetamol for the management of low back pain (Williams et al., 2014; Machado et al., 2015). This emphasizes that guidelines must be updated every 5 years to ensure that the most up-todate evidence is used to inform clinical recommendations (Kung et al., 2012). We found that high-quality guidelines lacked details about the use of acupuncture for the management of low back pain (Nielens et al., 2006; Chou et al., 2007; National Institute of Health and Care Excellence, 2009; Cutforth et al., 2011; Livingston et al., 2011; Scottish Intercollegiate Guidelines Network, 2013). This is important because it is known that different

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acupuncture techniques have different levels of effectiveness (Furlan et al., 2005). Future guidelines should consider stratifying evidence by acupuncture technique and provide clear details about the parameters for acupuncture use in patients with low back pain. Clinical practice guidelines of low methodological quality are still being developed and published (Philippine Academy of Rehabilitation Medicine, 2011; Brosseau et al., 2012; Delitto et al., 2012). These guidelines typically fail to: (1) clearly outline selection criteria of the literature; (2) adequately describe strengths and limitations of the literature and (3) adequately describe the methods used to formulate recommendations (Ransohoff et al., 2013). Our review highlights that the next generation of high-quality guidelines must focus on applicability to specific populations and clear implementation strategies to promote adherence. Nine of 13 eligible guidelines did not adequately address the AGREE II applicability criteria. Recent evidence suggests that favourable health and economic outcomes could be achieved if evidence-informed decision making is used to manage low back pain (Kosloff et al., 2013). However, current clinical practice is ineffective in adhering to evidence-based guideline recommendations (Kosloff et al., 2013). Future guidelines need to integrate the views and preferences of the target population (patients, public) into guideline development. Nine of 13 eligible guidelines did not mention whether these views and preferences were sought (Airaksinen et al., 2006; van Tulder et al., 2006; Chou et al., 2007, 2009; Cutforth et al., 2011; Livingston et al., 2011; Brosseau et al., 2012; Delitto et al., 2012; Kreiner et al., 2014). Integrating patient preferences into the guideline development process: (1) improves uptake and real-world efficiency of recommended healthcare interventions;(2) enhances consumer empowerment, and (3) informs individual patient preferences in clinical decision making (Dirksen et al., 2013; Dirksen, 2014). The recommendations included in clinical practice guidelines typically involve the consensus of guideline expert panels who are asked to consider decision determinants, such as overall clinical benefit (effectiveness and safety), value for money (cost-effectiveness), consistency with expected societal and ethical values, and feasibility of adoption into the health system (Johnson et al., 2009). The scientific evidence serves as the foundation from which recommendations are built. Therefore, significant limitations are associated with recommendations solely developed using clinical opinions. Assembling, evaluation, and summarizing of evidence are fundamental aspects of guideline development, including a systematic review and assessment of the quality of evidence (Ransohoff et al., 2013). Recommendations based solely on opinion may be liable to biases and conflicts of interest or may not benefit patients (especially when patients’ views are not considered during guideline development).

Strengths and limitations Our review had strengths. The literature search was comprehensive, methodologically rigorous, and checked by a second librarian. We outlined detailed inclusion/exclusion criteria to identify relevant evidence-based guidelines. Pairs of independent, trained reviewers screened and critically appraised the literature. This review used a recommended critical appraisal instrument for evaluating guidelines to maintain high methodological rigour (Brouwers et al., 2010). Some guidelines lacked methodological details, and we made multiple attempts to contact authors so that our screening and critical appraisal was as accurate as possible. The main limitation was the restriction of guidelines published in English. Most guidelines are published in the language of the target users (e.g., Haute Autorité de Santé in France or El Instituto Aragones de Ciencas de la Salud in Spain) (El Instituto Aragones de Ciencas de la Salud, 2016; Haute Autorité de Santé, 2016). It is possible that excluding guidelines published in a language other than English may have biased our results. However, it is unclear whether recommendations that are not published in English would differ from those published in English. Finally, the external validity of our results may be limited to users from English-speaking jurisdictions. A second limitation concerns the definitions used to classify acute and chronic low back pain, which varied across guidelines. Four guidelines defined chronic low back pain as pain lasting more than 3 months (Airaksinen et al., 2006; Nielens et al., 2006; van Tulder et al., 2006; Cutforth et al., 2011). Three guidelines grouped recommendations for subacute and chronic low back pain into one category (Chou et al., 2007; National Institute of Health and Care Excellence, 2009; Livingston et al., 2011). Of those, two guidelines defined subacute/chronic low back pain as pain lasting more than 4 weeks (Chou et al., 2007; Livingston et al., 2011), and one guideline defined persistent low back pain as pain lasting more than 6 weeks (National Institute of Health and Care Excellence, 2009). Finally, two guidelines did not provide a clear definition of chronic low back pain (Chou et al., 2009; Scottish Intercollegiate Guidelines Net-work, 2013). The different classifications used to make recommendations for the management of low back pain complicate the evidence synthesis and may have led to the misclassification of recommendations.

Conclusions Most high-quality guidelines target the noninvasive management of nonspeciﬁc low back pain and recommend education, staying active/exercise, manual therapy, and paracetamol or NSAIDs as ﬁrstline treatments. However, the endorsement of paracetamol for acute low back pain is challenged by a recent high-quality randomized controlled trial and systematic review; therefore, guidelines need updating. Some high-quality guidelines used evidence from other conditions to inform recommendations, which can lead to inadequate recommendations. Most eligible guidelines poorly addressed the applicability and implementation of

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recommendations. Finally, guideline developers need to involve end users during guideline development.

Acknowledgements The authors acknowledge Carlo Ammendolia, J. David Cassidy, Gail Lindsay, John Stapleton, Leslie Verville, Michel Lacerte, Mike Paulden, Patrick Loisel, and Roger Salhany for their invaluable contributions to this review. The authors also thank Trish Johns-Wilson at the University of Ontario Institute of Technology for her review of the search strategy.

Author contributions All authors have made substantial contributions to all of the following: (1) the conception and design of the study, or acquisition of data, or analysis and interpretation of data; (2) drafting the article or revising it critically for important intellectual content; and (3) ﬁnal approval of the version to be submitted.

References 1. Airaksinen, O., Brox, J.I., Cedraschi, C., Hildebrandt, J., KlaberMoffett, J., Kovacs, F., Mannion, A.F., Reis, S., Staal, J.B., Ursin, H., Zanoli, G.; COST B13 Working Group on Guidelines for Chronic Low Back Pain. (2006). Chapter 4. European guidelines for the management of chronic nonspeciﬁc low back pain. Eur Spine J 15 (Suppl 2), S192–S300. 2. Alonso-Coello, P., Irfan, A., Sola, I., Gich, I., Delgado-Noguera, M., Rigau, D., Tort, S., Bonﬁll, X., Burgers, J., Schunemann, H. (2010). The quality of clinical practice guidelines over the last two decades: A systematic review of guideline appraisal studies. Qual Saf Health Care 19, e58. 3. Berrigan, L., Marshall, S., McCullagh, S., Velikonja, D., Bayley, M (2011). Quality of clinical practice guidelines for persons who have sustained mild traumatic brain injury. Brain Inj 25, 742–751. 4. Bishop, F.L., Dima, A.L., Ngui, J., Little, P., Moss-Morris, R., Foster, N.E., Lewith, G.T. (2015). “Lovely Pie in the Sky Plans”: A qualitative study of clinicians’ perspectives on guidelines for managing low back pain in primary care in England. Spine 40, 1842–1850. 5. Brosseau, L., Wells, G.A., Poitras, S., Tugwell, P., Casimiro, L., Novikov, M., Loew, L., Sredic, D., Clement, S., Gravelle, A., Kresic, D., Hua, K., Lakic, A., Ménard, G., Sabourin, S., Bolduc, M.A., Ratté, I., McEwan, J., Furlan, A.D., Gross, A., Dagenais, S., Dryden, T., Muckenheim, R., Côté, R., Paré, V., Rouhani, A., Léonard, G., Finestone, H.M., Laferriére, L., Haines-Wangda, A., Russell-Doreleyers, M., De Angelis, G., Cohoon, C. (2012). Ottawa panel evidence-based clinical practice guidelines on therapeutic massage for low back pain. J Bodyw Mov Ther 16, 424–455. 6. Brouwers, M.C., Kho, M.E., Browman, G.P., Burgers, J.S., Cluzeau, F., Feder, G., Fervers, B., Graham, I.D., Grimshaw, J., Hanna, S.E., Littlejohns, P., Makarski, J., Zitzelsberger, L. (2010). AGREE II: Advancing guideline development, reporting and evaluation in health care. CMAJ 182, E839–E842.

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7. Carey, T.S., Evans, A., Hadler, N., Kalsbeek, W., McLaughlin, C., Fryer, J. (1995). Care-seeking among individuals with chronic low back pain. Spine 20, 312–317. 8. Carey, T.S., Evans, A.T., Hadler, N.M., Lieberman, G., Kalsbeek, W.D. Jackman, A.M., Fryer, J.G., McNutt, R.A. (1996). Acute severe low back pain. A population-based study of prevalence and care-seeking. Spine 21, 339–344. 9. Cassidy, J.D., Carroll, L.J., Côté, P. (1998). The Saskatchewan health and back pain survey. The prevalence of low back pain and related disability in Saskatchewan adults. Spine 23, 1860–1866; discussion 1867. 10. Cassidy, J.D., Côté, P., Carroll, L.J., Kristman, V. (2005). Incidence and course of low back pain episodes in the general population. Spine 30, 2817–2823. 11. Chou, R., Qaseem, A., Snow, V., Casey, D., Cross, J.T., Shekelle, P., Owens, D.K., Clinical Efficacy Assessment Subcommittee of the American College of Physicians, American College of Physicians, and American Pain Society Low Back Pain Guidelines Panel (2007). Diagnosis and treatment of low back pain: A joint clinical practice guideline from the American College of Physicians and the American Pain Society. [Erratum appears in Ann Intern Med. 2008 Feb 5;148 (3):247-8; PMID: 18257154], [Summary for patients in Ann Intern Med. 2007 Oct 2;147(7):I45; PMID: 17909203]. Ann Intern Med 147, 478–491. 12. Chou, R., Loeser, J.D., Owens, D.K., Rosenquist, R.W., Atlas, S.J., Baisden, J., Carragee, E.J., Grabois, M., Murphy, D.R., Resnick, D.K., Stanos, S.P., Shaffer, W.O., Wall, E.M.; American Pain Society Low Back Pain Guideline Panel. (2009). Interventional therapies, surgery, and interdisciplinary rehabilitation for low back pain: An evidence-based clinical practice guideline from the American Pain Society. Spine 34, 1066–1077. 13. Côté, P., Cassidy, J.D., Carroll, L. (2001). The treatment of neck and low back pain: Who seeks care? Who goes where? Med Care 39, 956– 967. 14. Côté, A.M., Durand, M.J., Tousignant, M., Poitras, S. (2009). Physiotherapists and use of low back pain guidelines: A qualitative study of the barriers and facilitators. J Occup Rehabil 19, 94–105. 15. Cutforth, G., Peter, A., Taenzer, P. (2011). The Alberta health technology assessment (HTA) ambassador program: The development of a contextually relevant, multidisciplinary clinical practice guideline for non-specific low back pain: A review. Physiother Can 63, 278–286. 16. Cypress, B.K. (1983). Characteristics of physician visits for back symptoms: A national perspective. Am J Public Health 73, 389–395. 17. Dagenais, S., Tricco, A.C., Haldeman, S. (2010). Synthesis of recommendations for the assessment and management of low back pain from recent clinical practice guidelines. Spine J 10, 514–529 18. Davies, R.A., Maher, C.G., Hancock, M.J. (2008). A systematic review of paracetamol for non-specific low back pain. Eur Spine J 17, 1423– 1430.

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19. Delgado-Noguera, M., Tort, S., Bonfill, X., Gich, I., Alonso-Coello, P. (2009). Quality assessment of clinical practice guidelines for the prevention and treatment of childhood overweight and obesity. Eur J Pediatr 168, 789–799. 20. Delitto, A., George, S.Z., Van Dillen, L.R., Whitman, J.M., Sowa, G., Shekelle, P., Denninger, T.R., Godges, J.J. (2012). Low back pain: Clinical Practice Guidelines Linked to the International Classification of Functioning, Disability, and Health from the Orthopaedic Section of the American Physical Therapy Association. J Orthop Sports Phys Ther 42, A1–A57. 21. Deyo, R.A., Von Korff, M., Duhrkoop, D. (2015). Opioids for low backpain. BMJ 350, g6380. 22. Dirksen, C.D. (2014). The use of research evidence on patient preferences in health care decision-making: Issues, controversies and moving forward. Expert Rev Pharmacoecon Outcomes Res 14, 785–794. 23. Dirksen, C.D., Utens, C.M., Joore, M.A., van Barneveld, T.A., Boer, B., Dreesens, D.H., van Laarhoven, H., Smit, C., Stiggelbout, A.M., van der Weijden, T. (2013). Integrating evidence on patient preferences in healthcare policy decisions: Protocol of the patient-VIP study. Implement Sci 8, 64. 24. El Instituto Aragones de Ciencas de la Salud (2016). El Instituto Aragones de Ciencas de la Salud Guías de Práctica Clínica. 25. Furlan, A.D., van Tulder, M., Cherkin, D., Tsukayama, H., Lao, L., Koes, B., Berman, B. (2005). Acupuncture and dry-needling for low back pain: An updated systematic review within the framework of the Cochrane collaboration. Spine 30, 944–963. 26. Graham, I.D., Beardall, S., Carter, A.O., Glennie, J., Hebert, P.C., Tetroe, J.M., McAlister, F.A., Visentin, S., Anderson, G.M. (2001). What is the quality of drug therapy clinical practice guidelines in Canada? CMAJ 165, 157–163. 27. Haldeman, S., Dagenais, S. (2008). A supermarket approach to the evidence-informed management of chronic low back pain. Spine J 8, 1–7. 28. Hasenfeld, R.S., Shekelle, P.G. (2003). Is the methodological quality of guidelines declining in the US? Comparison of the quality of US Agency for Health Care Policy and Research (AHCPR) guidelines with those published subsequently. Qual Saf Health Care 12, 428–434. 29. Haute Autorité de Santé (2016). Haute Autorité de Santé Élaboration de recommandations de bonne pratique: Méthode recommandations pour la pratique clinique. 30. Hincapie, C.A., Cassidy, J.D., Côté, P., Carroll, L.J., Guzman, J. (2010). Whiplash injury is more than neck pain: A populationbased study of pain localization after traffic injury. J Occup Environ Med 52, 434–440. 31. Institute of Medicine Committee on Standards for Developing Trustworthy Clinical Practice Guidelines (2011). Clinical Practice Guidelines We Can Trust. R. Graham, M. Mancher, D. Miller Wolman, S. Greenfield, and E. Steinberg, eds (Washington, DC: National Academies Press (US)).

32. Johnson, A.P., Sikich, N.J., Evans, G., Evans, W., Giacomini, M., Glendining, M., Krahn, M., Levin, L., Oh, P., Perera, C. (2009). Health technology assessment: A comprehensive framework for evidence-based recommendations in Ontario. Int J Technol Assess Health Care 25, 141–150. 33. Knai, C., Brusamento, S., Legido-Quigley, H., Saliba, V., Panteli, D., Turk, E., Car, J., McKee, M., Busse, R. (2012). Systematic review of the methodological quality of clinical guideline development for the management of chronic disease in Europe. Health Policy 107, 157–167. 34. Kosloff, T.M., Elton, D., Shulman, S.A., Clarke, J.L., Skoufalos, A., Solis, A. (2013). Conservative spine care: Opportunities to improve the quality and value of care. Popul Health Manag 16, 390–396. 35. Kreiner, D.S., Hwang, S.W., Easa, J.E., Resnick, D.K., Baisden, J.L., Bess, S., Cho, C.H., DePalma, M.J., Dougherty, P. 2nd, Fernand, R., Ghiselli, G., Hanna, A.S., Lamer, T., Lisi, A.J., Mazanec, D.J., Meagher, R.J., Nucci, R.C., Patel, R.D., Sembrano, J.N., Sharma, A.K., Summers, J.T., Taleghani, C.K., Tontz, W.L. Jr, Toton, J.F. (2014). An evidence-based clinical guideline for the diagnosis and treatment of lumbar disc herniation with radiculopathy. Spine J 14, 180–191. 36. Kung, J., Miller, R.R., Mackowiak, P.A. (2012). Failure of clinical practice guidelines to meet Institute of Medicine standards: Two more decades of little, if any, progress. Arch Intern Med 172, 1628–1633. 37. Livingston, C., King, V., Little, A., Pettinari, C., Thielke, A., Gordon, C. (2011). Evidence-Based Clinical Guidelines Project. Evaluation and Management of Low Back Pain: A Clinical Practice Guideline Based on the Joint Practice Guideline of the American College of Physicians and the American Pain Society (Salem, Oregon: Office for Oregon Health Policy and Research). 38. Machado, G.C., Maher, C.G., Ferreira, P.H., Pinheiro, M.B., Lin, C.W., Day, R.O., McLachlan, A.J., Ferreira, M.L. (2015). Efficacy and safety of paracetamol for spinal pain and osteoarthritis: Systematic review and meta-analysis of randomised placebo controlled trials. BMJ 350, h1225. 39. National Institute of Health and Care Excellence (2009). Low back pain: early management of persistent non-specific low back pain. 40. National Institute of Health and Care Excellence (2014). NICE Guidance. 41. Nielens, H., Van Zundert, J., Mairiaux, P., Gailly, J., Van Den Hecke, H., Mazina, D., Camberlin, C., Bartholomeeusen, S., De Qauquier, K., Paulus, D., Ramaekers, D. (2006). Belgian Health Care Knowledge Centre. Chronic Low Back Pain (KCE Report). 42. North American Spine Society (2012). Evidence-Based Clinical Guidelines for Multidisciplinary Spine Care. Diagnosis and Treatment of Lumbar Disc Herniation With Radiculopathy (Rockville MD: Agency for Healthcare Research and Quality).

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43. Philippine Academy of Rehabilitation Medicine (2011). Low back pain management guideline. 44. Ransohoff, D.F., Pignone, M., Sox, H.C. (2013). How to decide whether a clinical practice guideline is trustworthy. JAMA 309, 139–140. 45. Sampson, M., McGowan, J., Cogo, E., Grimshaw, J., Moher, D., Lefebvre, C. (2009). An evidence-based practice guideline for the peer review of electronic search strategies. J Clin Epidemiol 62, 944–952. 46. Scottish Intercollegiate Guidelines Network (2013). Management of Chronic Pain. A National Clinical Guideline (Rockville MD: Agency for Healthcare Research and Quality). 47. Shaneyfelt, T.M., Centor, R.M. (2009). Reassessment of clinical practice guidelines: Go gently into that good night. JAMA 301, 868–869. 48. Shaneyfelt, T.M., Mayo-Smith, M.F., Rothwangl, J. (1999). Are guidelines following guidelines? The methodological quality of clinical practice guidelines in the peer-reviewed medical literature. JAMA 281, 1900–1905. 49. Shekelle, P.G., Woolf, S.H., Eccles, M., Grimshaw, J. (1999). Clinical guidelines: Developing guidelines. BMJ 318, 593–596. 50. Shekelle, P., Woolf, S., Grimshaw, J.M., Schunemann, H.J., Eccles, M.P. (2012). Developing clinical practice guidelines: Reviewing, reporting, and publishing guidelines; updating guidelines; and the emerging issues of enhancing guideline implementability and accounting for comorbid conditions in guideline development. Implement Sci 7, 62. 51. Slade, S.C., Kent, P., Patel, S., Bucknall, T., Buchbinder, R. (2015). Barriers to primary care clinician adherence to clinical guidelines for the management of low back pain: a systematic review and meta-synthesis of qualitative studies. Clin J Pain. 2015 Dec 24. [Epub ahead of print] 52. Tricoci, P., Allen, J.M., Kramer, J.M., Califf, R.M., Smith, S.C. Jr (2009). Scientific evidence underlying the ACC/AHA clinical practice guidelines. JAMA 301, 831–841. 53. van Tulder, M., Becker, A., Bekkering, T., Breen, A., del Real, M.T., Hutchinson, A., Koes, B., Laerum, E., Malmivaara, A., COST B Working Group on Guidelines for the Management of Acute Low Back Pain in Primary Care (2006). Chapter 3. European guidelines for the management of acute nonspecific low back pain in primary care. Eur Spine J 15 (Suppl 2), S169–S191. 54. Walker, B.F. (2000). The prevalence of low back pain: A systematic review of the literature from 1966 to 1998. J Spinal Disord 13, 205–217. 55. Whitworth, J.A. (2006). Best practices in use of research evidence to inform health decisions. Health Res Policy and Syst 4, 11. 56. Williams, C.M., Maher, C.G., Latimer, J., McLachlan, A.J., Hancock, M.J., Day, R.O., Lin, C.W. (2014). Efficacy of paracetamol for acute low-back pain: A double-blind, randomised controlled trial. Lancet 384, 1586–1596.

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Supporting Information Additional Supporting Information may be found online in the supporting information tab for this article: Appendix S1. MEDLINE search strategy on guidelines for the management of nonspeciﬁc low back pain. Table S1. Evidence table for high-quality guidelines. Originally published in the European Journal of Pain, 2017 Feb;21(2):201-216 Review. Reproduced with permission from John Wiley and Sons.

Access Online: https://doi.org/10.1002/ejp.931

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Knowledge Translation and Health Policy

Prescription Dispensing Patterns Before and After a Workers’ Compensation Claim: An Historical Cohort Study of Workers With Low Back Pain Injuries in British Columbia Carnide N1, Hogg-Johnson S1,2 , Furlan AD1,3, Côté P1,2,4 , Koehoorn M1,5 Institute for Work & Health, 2Canadian Memorial Chiropractic College, 3University of Toronto, 4University of Ontario Institute of Technology, University of British Columbia

1 5

Abstract Objective: Compare prescription dispensing before and after a workrelated low back injury. Methods: Descriptive analyses were used to describe opioid, nonsteroidal anti-inflammatory drug (NSAID), and skeletal muscle relaxant (SMR) dispensing 1 year pre- and post-injury among 97,124 workers in British Columbia with new workers’ compensation low back claims from 1998 to 2009. Results: Before injury, 19.7%, 21.2%, and 6.3% were dispensed opioids, NSAIDs, and SMRs, respectively, increasing to 39.0%, 50.2%, and 28.4% after. Median time to first post-injury prescription was less than a week. Dispensing was stable pre-injury, followed by a sharp increase within 8 weeks post-injury. Dispensing dropped thereafter, but remained elevated nearly a year post-injury, an increase attributable to less than 2% of claimants. Conclusion: These drug classes are commonly dispensed, particularly shortly after injury and dispensing is of short duration for most, though a small subgroup receives prolonged courses. Key Words: administrative data, cohort study, low back pain, opioids, prescription dispensing, workers’ compensation Low back pain (LBP) is one of the most prevalent physical health conditions to affect workers1–3 and is a leading cause of work disability.3–7 Pharmaceuticals are the mainstay of LBP medical management,8–10 with clinical guidelines typically recommending acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs) as first-line therapeutic options in the treatment of acute or subacute LBP.11 Along with NSAIDs, opioids and skeletal muscle relaxants (SMRs) are some of the most common drugs prescribed to treat LBP,8–10,12 though there is a lack of

high quality evidence demonstrating the effectiveness of any of these drug classes for LBP.13–16 Opioids are also associated with significant harms, including abuse, addiction, and overdose.17–21 Over the last decade, the use of opioids in workers’ compensation populations has been a major focus of research, with several studies documenting the high prevalence of opioid prescriptions following a work-related LBP injury.22–30 The majority of these studies, however, have been conducted in the United States (US) and have provided a limited characterization of prescription patterns. Comparatively, little is also known about prescription patterns of NSAIDs and SMRs after a workrelated LBP injury. Previous studies also used data of prescriptions reimbursed by the workers’ compensation system, thus not including prescriptions paid out-of-pocket or through private insurance. Two prior studies of workers’ compensation claimants in Canada found some evidence of incomplete opioid prescription capture by workers’ compensation data.26,31 The extent of exposure to opioids after injury may, therefore, have been underestimated. Pre-injury exposure to these medications is also unknown. Much concern has been raised regarding the early provision of opioids after injury.22,23,25–27,30 However, it is not clear whether claimants may have been receiving prescriptions prior to their injuries or before filing their claims. A report by the National Council on Compensation Insurance found approximately 80% of lost-time claims in the US had a lag between injury and claim reporting.32 It would not be surprising that some workers delay reporting, yet seek treatment before reaching a threshold where time off work is now required. This was the conclusion of one group of researchers who found a steady increase in the number of pre-claim health care contacts leading up to claim filing for a musculoskeletal disorder among health care workers.33 In a similar study of neck pain claimants, this pattern was not evident.34 These studies, however, both demonstrated that health care utilization after a claim remained elevated compared with before claim. To date, we are not aware of any study to compare pre- and post-injury prescription drug patterns among

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workers’ compensation LBP claimants in a similar manner. To address these knowledge gaps, we analyzed administrative data from a large population-based sample of workers’ compensation claimants with LBP injuries in British Columbia (BC), Canada. Our objectives were to describe and contrast prescription opioid, NSAID, and SMR dispensing patterns 1 year prior to a work-related low back injury through 1 year post-injury and to determine whether post-injury dispensing returns to pre-injury levels by 1 year after injury. Unlike previous studies, data on prescriptions were obtained from a provincewide prescription monitoring program, where all prescriptions dispensed in the community are required to be recorded, without restriction to those funded by workers’ compensation. This allowed us to comprehensively capture prescription dispensing in this population, both before the work-related injury, as well as after.

Methods Study Design and Setting We conducted an historical cohort study of workers’ compensation claimants in British Columbia (BC), Canada using linked administrative data. The source population included all employees working for employers insured through the provincial workers’ compensation board in BC and who filed a new short-term disability claim (ie, temporary wage loss due to missed work) for a LBP injury occurring between 1998 and 2009. Data from five databases capturing information on workers’ compensation claims (WorkSafeBC Claims and Firm Level Files), pharmacy dispensing (PharmaNet), outpatient health care (Medical Services Plan [MSP] Payment Information File), hospitalizations (Discharge Abstract Database [DAD]), and demographics (MSP Consolidation File)35–39 from 1996 through to 2010 were linked and delivered by Population Data BC.40,41 Population Data BC is a multi-university provincial population health data service containing longitudinal, person-specific, de-identified health data for British Columbia’s four and a half million residents for research purposes. WorkSafeBC is the provincial workers’ compensation system in BC. The agency oversees a publicly administered, no-fault single payer insurance system to compensate workers with work-related injuries and diseases for time missed from work, permanent disability, health care costs, rehabilitative services, and fatalities. Employers in BC are legally mandated to have WorkSafeBC coverage, with a few exceptions, such as the self-employed.42 During the study period from 2000 to 2009, 92.5% to 94.0% of the workforce were eligible for compensation coverage.43 PharmaNet is a province-wide, real-time system that captures detailed information for all prescription medications dispensed from community and hospital outpatient pharmacies in BC, regardless of payment source. Therefore, outpatient prescriptions paid out-of-pocket, through public or private insurance, through workers’ compensation benefits, or other

A selection of published research by CMCC faculty

means are all captured. Medical Services Plan (MSP) is the universal health insurance program in BC and covers approximately 96% of residents, excluding those covered by federal programs. MSP data consist of billing records for all medically required outpatient services provided by fee-for-service practitioners, including examinations and consultations and laboratory and diagnostic procedures. The Discharge Abstract Database (DAD) file contains diagnostic and intervention data for all hospital discharges (deaths, signouts, transfers) of acute care inpatients and day surgery patients from BC facilities. The MSP and DAD datasets were used in the creation of the cohort. Finally, the MSP Consolidation File includes basic demographic data on all individuals registered as eligible to receive health services in BC. WorkSafeBC, PharmaNet, and the British Columbia Ministry of Health approved access to and use of the data facilitated by Population Data BC in this analysis. The study was approved by the University of Toronto Health Sciences Research Ethics Board (protocol reference number 26885). Study Participants Linked data for workers who filed at least one new workers’ compensation short-term disability claim with WorkSafeBC for LBP between 1998 and 2009 were extracted and provided to the research team by Population Data BC. All claims for these workers dating back to 1991 were provided and claims were included if they met the following criteria: (1) claim was not a consolidated claim or linked to a consolidated claim. Claims may be consolidated for administrative reasons, such as when duplicate claims have been inadvertently created for the same worker and injury event. Consolidation may also occur if it is determined that a new claim is a compensable consequence of a previous injury for which a claim has been initiated.; (2) claimant was 18 years or older at injury; (3) claim was an accepted shortterm disability claim with at least 1 day of wage replacement benefits received in the first 8 weeks following injury date; (4) claim was for a nonspecific LBP disorder identified using four digit International Classification of Diseases, 9th Revision (ICD-9) codes 44 (see Table, Supplemental Digital Content 1, http://links.lww.com/JOM/A424 that provides the list of codes) occurring between January 1, 1998 and December 31, 2009; (5) claim had no LBP-related hospitalization or no serious LBP-related outpatient encounter within 5 days after injury, as identified using four digit ICD-9 and International Classification of Diseases, 10th Revision, Canada (ICD-10-CA) codes 45 (see Table, Supplemental Digital Content 2, http://links.lww.com/ JOM/A424 that provides the list of codes); (6) claimant was a BC resident and continuously registered as eligible to receive health services for at least 2 years before and 1 year after injury date; and (7) injury date was equal to or preceded claim registration date. Injury date was chosen to establish the inception point for entry into the cohort rather than registration date to best approximate clinical onset of the injury. In our data, 98% of claimants had injury dates that preceded claim registration date, with the mean (standard deviation) number of days between

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injury date and registration date being 6 (5.4) days (median of 5). After applying these criteria, some claimants had more than one eligible claim. From this pool of eligible claims, we selected one index claim per claimant as the earliest claim: (1) that had no other accepted claims (all types of claims, irrespective of diagnosis) in the year after injury; and (2) where the total benefits paid in the year after injury was greater than zero. If these conditions were not met by at least one claim, the claimant was excluded. Following selection of the index claim, one additional claimant-level exclusion was applied: claimants were excluded if they had at least one hospitalization and/or two outpatient health care billings for cancer (ICD-9 codes 140–209 and 235–239; ICD-10-CA codes C00-C97 and D37-D48) 2 years before through 1 year after injury. Study Variables Outcomes Detailed information for each prescription dispensed 1 year before and after the work-related LBP injury was obtained, including dispense date, active ingredient(s), quantity dispensed, days supply, dosage form, drug strength, and route of administration. Dispensing records from the following drug classes were retained for this study: opioids (American Hospital Formulary Service [AHFS] classification system codes, 46 28:08.08, 28:08.12), NSAIDs (28:08.04.08, 28:08.04.24, 28:08.04.92), and SMRs (12.20.04, 12.20.08, 12.20.12). All routes of administration were eligible with the exception of topical formulations. Oral formulations accounted for 99.4% of all opioid, 99.1% of all NSAID, and 99.7% of all SMR dispensing records. Over-the-counter medications were excluded as they are only infrequently entered into the PharmaNet system. A number of dispensing patterns for the three drug classes were constructed for the 1-year periods before and after the work-related LBP injury date and in 8-week periods pre- and post-injury. We chose 8-week increments as WorkSafeBC policy during the study period limited reimbursement of prescription opioids to the first 8 weeks after injury or surgery for most claims.47 Receipt of each drug class (yes/no) was estimated as the presence of at least one dispensing record for the specific drug class. A categorical variable describing the specific prescription combinations dispensed among claimants with at least one drug dispense was also created (ie, NSAIDs only, SMRs only, NSAIDS and SMRs, opioids only, opioids and NSAIDs, opioids and SMRs, all three drug classes). Dispensing of specific drugs within each drug class was estimated as individual dichotomous yes/no variables according to the active ingredient (eg, codeine, naproxen) among claimants with at least one dispensed prescription of a particular drug class. Number of dispensed prescriptions (1, 2, 3 to 4, more than or equal to 5) among claimants with at least one dispense was estimated for each drug class by counting the number of

unique dispensing records based on claimant and prescriber identification numbers, date of service, and active ingredient. Cumulative days supply dispensed for each drug class was calculated by summing the days supply across all prescriptions for a given class. When dispensing records for the same drug class overlapped in time, days were counted only once. Time since last dispensed prescription before injury was calculated as the number of days from date of injury to the date of the last dispensed prescription for a particular drug class within the year prior to injury date. Likewise, time to the first dispensed prescription after injury was calculated as the number of days between date of injury and date of the first dispensed prescription for a particular drug class within the year following injury. These two variables were derived only among those claimants who had at least one prescription dispensed for the particular drug class in the year before or the year after injury, respectively. A number of other variables were also derived among claimants receiving at least one opioid dispensed prescription. Two dichotomous variables describing receipt of at least one weak opioid (yes/no) and receipt of at least one strong opioid (yes/no) were constructed. Anileridine, codeine, meperidine, pentazocine, pro-poxyphene, and tramadol were considered to be weak opioids, while buprenorphine, butorphanol, fentanyl, hydromorphone, methadone, morphine, and oxycodone were considered strong.48–55 Variables denoting receipt of at least one short-acting opioid (yes/no) and receipt of at least one long-acting opioid (yes/no) were also constructed. In our data, codeine, hydromorphone, morphine, oxycodone, and tramadol were provided as both short- and long-acting formulations. Fentanyl and buprenorphine were available in the data as patches that are designed to release over a period of time, and were therefore considered long-acting. All other opioids were considered shortacting only (eg, meperidine, propoxyphene). To obtain the average daily morphine-equivalent dose (MED) for oral formulations, the daily dose for each day supplied with an opioid was first calculated as (drug strength × quantity dispensed)/days supply. A similar calculation for daily dose was conducted for transdermal formulations, incorporating the strength per hour delivered by each patch: (drug strength in microgram/hour × hours supplied)/days supply. A standardized daily dose was then calculated by multiplying the daily dose by previously published morphine-equivalent conversion ratios (see Table, Supplemental Digital Content 3, http://links.lww. com/JOM/A424 that provides the ratios).48–55 For transdermal formulations, the result was also divided by 1000 to convert from micrograms to milligrams. The average daily MED for each claimant was then calculated as the sum of the daily MED over the sum days supplied with opioids in a given time period. Opioids dispensed for parenteral, buccal, rectal, or nasal

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routes were not included in the calculation because the unit of measure in the dispensed quantity field was not clear. Opioids by these routes represented only 0.6% of all opioid dispensing records in the year before and after injury. In the calculation, we also included the daily dose of codeine in SMR combinations containing codeine. These dispensing records accounted for approximately 5.1% of all records used in the MED calculation in the 2 years around injury. Other Variables A number of other variables were constructed to describe the cohort, including sex, year of injury (in 2 year groups from 1998 to 2009), number of workers’ compensation claims in the 2 years before injury (0, 1, more than or equal to 2) and regional health authority. In BC, there are five regional health authorities (Fraser Health, Vancouver Coastal Health, Vancouver Island Health, Northern Health, and Interior Health), whose purpose is to govern, plan, and deliver health care services within their respective geographic areas.56 Year and month of birth were used to approximate age at injury date, grouped as 18 to 24, 25 to 34, 35 to 44, 45 to 54, and more than or equal to 55 years. Four-digit ICD-9 diagnosis code associated with the claim was re-categorized based on the first three digits: 722 (intervertebral disc disorders), 724 (other and unspecified disorders of back), 846 (sprains and strains of sacroiliac region), and 847 (sprains and strains of other and unspecified parts of back). Neighborhood income quintile was assigned to each claimant by Population Data BC analysts based on Census income data and claimant’s postal code at time of injury using Postal Code Conversion Fileþ (PCCFþ) software developed by Statistics Canada (Ottawa, Canada).57 Statistical Analyses Descriptive statistical methods were used to describe preto post-injury dispensing patterns, namely proportions for categorical variables and mean, standard deviation (SD), median, and interquartile range (IQR) for continuous variables. Ninety-five percent confidence intervals (95% CI) were also estimated around proportions and means. This was done overall, comparing 1 year pre-injury to 1 year period postinjury, as well as stratified into six 8-week periods before and after injury date. The data analysis was generated using SAS software Version 9.3. Copyright 2000–2010 SAS Institute Inc. SAS and all other SAS Institute Inc. product or service names are registered trademarks or trademarks of SAS Institute Inc., Cary, NC.

Results A total of 142,993 eligible work-related LBP claims linked to 113,434 claimants were included after applying the claimlevel inclusion criteria (Fig. 1). Choosing one index claim per claimant resulted in a total of 99,233 claimants each with one eligible index claim. A total of 2,109 claimants with a history of cancer related health care utilization were then excluded, resulting in a final cohort of 97,124 claimants.

A selection of published research by CMCC faculty

Sample Characteristics The cohort was comprised of 62.3% men (Table 1). Mean (SD) age at injury was 40.5 (11.2), with 30.8% between 35 and 44 years of age. A large proportion of claimants were located in the Fraser regional health authority (42.5%), the most densely populated health authority. Only 5.5% were in the Northern health authority region, with claimants fairly evenly distributed among the remaining three regions, representing the population distribution in the province. The vast majority of claimants had a diagnosis of sprain or strain (87%) and only 3% were diagnosed with an intervertebral disc disorder. Approximately, 33% had at least one previous workers’ compensation claim accepted by WorkSafeBC in the 2 years before injury. Comparing Prescription Dispensing Patterns 1 Year Pre-Injury to 1 Year Post-Injury The 1-year period prevalence of receiving at least one of the three drug classes doubled from 34.0% (95% CI 33.7% to 34.3%) pre-injury to 68.0% (95% CI 67.7% to 68.3%) post-injury (Table 2). Approximately one in five claimants received at least one opioid or NSAID in the year before injury. In the year after injury, 38.8%received opioids (95% CI 38.5% to 39.1%) and 50.2% received NSAIDs (95% CI 49.8% to 50.5%), representing a 98% and 138% relative increase from pre-injury, respectively. Although less commonly dispensed, the largest increase in prevalence was for SMRs: from 6.3% (95% CI 6.1% to 6.4%) pre-injury to 28.4% (95% CI 28.1% to 28.7%) post-injury, representing a 351% relative increase over time. Among claimants receiving at least one opioid prescription, the vast majority received weak and short-acting opioids. There was a small increase from pre- to post-injury in the proportion of claimants receiving strong opioids, from 10.8% (95% CI 10.4%to 11.3%) to 14.8% (95% CI 14.4% to 15.2%). Among claimants dispensed opioids, the vast majority of claimants received codeine, while oxycodone was the second most common, both primarily dispensed as combinations with acetaminophen or acetylsalicylic acid. Less than 1% of claimants received long-acting oxycodone. The incidence proportion of claimants who received each of the three drug classes in the year after injury was 33.5% (95% CI 33.2% to 33.9%) for opioids, 45.6% (95% CI 45.3% to 46.0%) for NSAIDs, and 26.8% (95% CI 26.6% to 27.1%) for SMRs. (Table 2). Among claimants with at least one prescription in the prior year, the proportion dispensed a post-injury prescription was even higher, particularly for opioids (60.2%, 95% CI 59.5% to 60.9%) and NSAIDs (67.1%, 95% CI 66.5% to 67.8%). A greater proportion of claimants received combinations of drug classes in the post-injury period compared with only one drug class. Most claimants received only one to two dispensed prescriptions both pre- and post-injury across all drug classes (Table 2). Cumulative days supplied ranged from a median of 8 (IQR 5 to 20) and 10 days (IQR 5 to 24) pre- and post-injury, respectively,

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Included claims in data extract, 1998-2009 n=916,804

Claims with consolidated claims n=35,637 excluded

Claim Level Exclusions

<18 years of age at injury n=3,642 excluded

Not a STD claim and/or no paid STD days within first 8 weeks n=413,761 excluded

STD claim is non-accepted claim n=1,666 excluded

n=462,098 Non-LBP diagnosis and/or injury year <1998 or >2009 n=289,969 excluded

Claim Level Exclusions

n=1,088 excluded Claimant a non-BC resident and/or not registered for health n=28,170 excluded

n=5 excluded

Eligible cohort claims: n=142,993 Eligible cohort claimants: n=113,434

Claimant Level Exclusion

injury date and/or summed total of benefits paid ≤0 n=43,760 claims excluded n=14,201 claimants excluded

Eligible cohort claimants with one allowed LBP STD claim from 1998 to 2009 n=99,233

Claimant Level Exclusion

Claimants with at least 2 health care visits and/or 1 post-injury n=2,109 claimants excluded

Final cohort claimants n=97,124

Fig 1 Claim-level and claimant-level exclusions to derive the final cohort sample of workers’ compensation claimants with accepted low back pain short-term disability claims occurring between 1998 and 2009. Abbreviations: LBP ¼ low low back pain; STD ¼ short-term disability.

Table 1. Characteristics of the Cohort of Workers Compensation Claimants With an Allowed Short-Term Disability Claim for Low Back Pain Between 1998 and 2009 (n = 97,124) Variable Age at injury 18–24 25–34 35–44 45–54 55 Sex Women Men Neighborhood income quintile 1 (lowest) 2 3 4 5 (highest) Regional health authority Interior Fraser Vancouver Coastal Vancouver Island Northern Injury year 1998/1999 2000/2001 2002/2003 2004/2005 2006/2007 2008/2009 First three digits of ICD-9 diagnosis on claim 722 — intervertebral disc disorders 724 — other and unspecified disorders of back 846 — sprains and strains of sacroiliac region 847 — sprains and strains of other and unspecified parts of back Number of workers’ compensation claims within 2 years prior to injury y 0 1 2

n (%) 10,180 21,444 29,929 25,415 10,156

(10.5) (22.1) (30.8) (26.2) (10.5)

36,606 (37.7) 60,517 (62.3) 21,169 22,295 20,874 18,234 12,930

(21.8) (23.0) (21.5) (18.8) (13.3)

14,116 (14.5) 41,237 (42.5) 18,834 (19.4) 17,538 (18.1) 5,303 (5.5) 18,413 17,105 16,002 15,625 15,756 14,223

(19.0) (17.6) (16.5) (16.1) (16.2) (14.6)

2,954 (3.0) 9,763 (10.1) 21,031 (21.7) 63,376 (65.3)

65,461 (67.4) 21,984 (22.6) 9,679 (10.0)

ICD-9, International Statistical Classification of Diseases and Related Health Problems, 9th Revision. Number of claimants with data missing on the following variables: n = 1 sex; n = 1622 neighborhood income quintile; n = 96 regional health authority. y Includes all types of claims (short-term disability, long-term disability, health care only, vocational rehabilitation) for any diagnosis (not limited to low back pain claims).

for opioids, to 15 (IQR 10 to 31) and 18 days (IQR 10 to 37) for NSAIDs (Table 3). The median cumulative number of days supplied of SMRs remained steady at 10 from pre- to post-injury. On average, the last prescriptions received by claimants in the year before injury were dispensed just over 5 months prior to injury across all drug classes, while the median number of days to first prescription after injury was 6 (IQR 1 to 79), 4 (IQR 1 to 26), and 3 (IQR 1 to 13) days for opioids, NSAIDs, and SMRs, respectively (Table 3). Among those receiving strong opioids, the median time to first strong opioid prescription was 25 days (IQR 3 to 154). Among claimants with at least 1 day supply of opioids and/or SMRs with codeine, daily MED averaged approximately 31 mg/d both pre- and post-injury. Less than 1% had an average daily MED of at least 120 mg/d in either period.

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A selection of published research by CMCC faculty

Table 2. Prevalence, Incidence, and Number of Dispensed Prescriptions 1 Year Before Compared With 1 Year After the Date of a Work-Related Low Back Pain Injury Among Claimants With Short-Term Disability Claims ( n = 97,124) One Year Pre-Injury Dispensing Pattern Prevalence of at least one dispensed prescription At least one opioid, NSAID, and/or SMR Opioids ,†,‡ Weak opioids Strong opioids Short-acting opioids Long-acting opioids Codeine Oxycodone Meperidine Tramadol Hydromorphone Morphine NSAIDs ,†,‡ Naproxen Diclofenac Ketorolac Celecoxib Ibuprofen Indomethacin Rofecoxib Skeletal muscle relaxants Cyclobenzaprine Methocarbamol Baclofen

n 32,977 18,995 18,095 2,053 18,914 349 17,569 1,612 430 400 313 263 20,499 10,561 4,166 1,767 1,754 1,479 1,394 1,369 6,068 4,881 1,112 245

% (95% CI) 34.0 (33.7–34.3) 19.6 (19.3–19.8) 95.3 (95.0–95.6) 10.8 (10.4–11.3) 99.6 (99.5–99.7) 1.8 (1.7–2.0) 92.5 8.5 2.3 2.1 1.7 1.4 21.1 (20.9–21.4) 51.5 20.3 8.6 8.6 7.2 6.8 6.7 6.3 (6.1–6.4) 80.4 18.3 4.0

One Year Post-Injury n 66,051 37,639 35,772 5,566 37,499 1,085 34,459 4,345 1,200 1,586 969 838 48,714 29,208 11,426 3,524 4,927 3,096 2,053 3,687 27,603 22,858 4,834 1,054

% (95% CI) 68.0 (67.7–68.3) 38.8 (38.5–39.1) 95.0 (94.8–95.3) 14.8 (14.4–15.2) 99.6 (99.6–99.7) 2.9 (2.7–3.1) 91.6 11.5 3.2 4.2 2.6 2.2 50.2 (49.8–50.5) 60.0 23.5 7.2 10.1 6.4 4.2 7.6 28.4 (28.1–28.7) 82.8 17.5 3.8

Proportion receiving at least one post-injury dispensed prescription stratified by prescription history in the year before the work-related LBP injury No pre-injury prescriptions (incidence proportion) At least one opioid, NSAID, and/or SMR (n = 64,147) 39,767 62.0 (61.6–62.4) 26,201 33.5 (33.2–33.9) Opioids (n = 78,129) 34,955 45.6 (45.3–46.0) NSAIDs ( n = 76,625) 24,439 26.8 (26.6–27.1) SMRs ( n = 91,056) At least one pre-injury prescriptions 26,284 79.7 (79.3–80.1) At least one opioid, NSAID, and/or SMR (n = 32,977) 11,438 60.2 (59.5–60.9) Opioids (n = 18,995) 13,759 67.1 (66.5–67.8) NSAIDs ( n = 20,499) 3,164 52.1 (50.9–53.4) SMRs ( n = 6,068) Prescription combinations received among claimants dispensed at least one prescription ( n = 32,977 pre-injury, n = 66,051 post-injury) 10,880 33.0 (32.5–33.5) 15,657 23.7 (23.4–24.0) NSAIDs only 1,286 3.9 (3.7–4.1) 4,093 6.2 (6.0–6.4) SMRs only 1,816 5.5 (5.3–5.8) 8,662 13.1 (12.9–13.4) NSAIDs and SMRs 10,106 30.7 (30.2–31.1) 9,247 14.0 (13.7–14.3) Opioids only 5,923 18.0 (17.6–18.4) 13,544 20.5 (20.2–20.8) Opioids and NSAIDs only 1,086 3.3 (3.1–3.5) 3,997 6.1 (5.9–6.2) Opioids and SMRs only 1,880 5.7 (5.5–6.0) 10,851 16.4 (16.2–16.7) All three drug classes No. of prescriptions among claimants dispensed at least Opioids (n =18,995 pre-injury, n = 37,639 post-injury) 1 2 3–4 5

one prescription (60.2–61.6) (16.2–17.3) (10.0–10.8) (11.5–12.5)

20,502 6,849 4,746 5,542

54.5 (54.0–55.0) 18.2 (17.8–18.6) 12.6 (12.3–12.9) 14.7 (14.4–15.1)

NSAIDs (n = 20,499 pre-injury, n = 48,714 post-injury) 13,156 1 3,804 2 2,388 3–4 1,151 5

64.2 (63.5–64.8) 18.6 (18.0–19.1) 11.7 (11.2–12.1) 5.6 (5.3–5.9)

28,149 10,194 6,743 3,628

57.8 (57.4–58.2) 20.9 (20.6–21.3) 13.8 (13.5–14.2) 7.5 (7.2–7.7)

SMRs (n = 6,068 pre-injury, n = 27,603 post-injury) 1 2 3–4 5

75.0 (73.9–76.1) 14.5 (13.6–15.4) 6.1 (5.5–6.7) 4.4 (3.9–4.9)

19,770 4,544 2,204 1,085

71.6 (71.1–72.2) 16.5 (16.0–16.9) 8.0 (7.7–8.3) 3.9 (3.7–4.2)

11,561 3,181 1,973 2,280

4,553 879 369 267

60.9 16.8 10.4 12.0

CI, confidence interval; LBP, low back pain; NSAIDs, nonsteroidal anti-inflammatory drugs; SMRs, skeletal muscle relaxants. Most commonly dispensed drugs are described for each drug class. The denominator for the proportions presented include only individuals with at least one dispense for the relevant drug class. † The following drugs were only available during a portion of the study period: tramadol (2004–2009), celecoxib (1999–2009), and rofecoxib (1999–2004). ‡ For data on opioid strength and length of action, the denominator for the proportions presented include only individuals with at least one opioid dispense.

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TABLE 3. Other Prescription Dispensing Patterns 1 Year Before Compared With 1 Year After the Date of a Work-Related Low Back Pain Injury Among Claimants With Short-Term Disability Claims ( n = 97,124) One Year Pre-Injury Dispensing Pattern

One Year Post-Injury

Mean (SD)

95% CI

Mean (SD)

95% CI

Median

IQR

Median

IQR

27.2–28.9 5.0–20.0 23.2–24.7 4.0–17.0 50.4–58.9 5.0–37.0 34.6–36.1 10.0–31.0 24.0–26.1 7.0–24.0

29.3 (57.1) 10.0 24.7 (47.3) 10.0 45.5 (82.0) 10.0 35.7 (48.8) 18.0 22.2 (33.1) 10.0

28.7–29.9 5.0–24.0 24.2–25.2 5.0–20.0 43.3–47.6 5.0–36.0 35.2–36.1 10.0–37.0 21.8–22.6 8.0–23.0

Cumulative days supply per claimant among claimants with at least 1 day of supply Opioids (n =19,217 pre-injury, n= 37,720 post-injury) 28.0 (60.8) 8.0 Weak opioids (n =18,312 pre, n = 35,865 post) 24.0 (51.6) 7.0 Strong opioids (n=2,080 pre, n=5,569 post) 54.7 (99.0) 10.0 NSAIDs (n=21,082 pre-injury, n = 49,038 post-injury) 35.4 (54.5) 15.0 SMRs (n = 6,237 pre-injury, n= 27,710 post-injury) 25.0 (42.6) 10.0

No. of days between last prescription dispensed and injury date among claimants with at least one prescription in year before injury Opioids ( n =18,995) 162.1 (108.2) 160.6–163.7 154.0 64.0–253.0 Weak opioids (n =18,095) 164.9 (107.7) 163.3–166.5 158.0 68.0–256.0 Strong opioids ( n=2,053) 152.4 (111.8) 147.6–157.3 141.0 45.0–245.0 NSAIDs ( n=20,499) 164.5 (106.2) 163.0–165.9 156.0 70.0–254.0 SMRs ( n =6,068) 175.4 (105.7) 172.8–178.1 172.0 84.0–265.0 No. of days between injury date and first prescription dispensed among claimants with at least one prescription in year after injury Opioids ( n = 37,639) 59.7 (96.5) 6.0 Weak opioids (n = 35,772) 61.8 (97.5) 7.0 Strong opioids ( n= 5,566) 87.1 (108.3) 25.0 NSAIDs ( n= 48,714) 40.3 (80.1) 4.0 SMRs ( n = 27,603) 28.7 (68.0) 3.0 Average daily MED among claimants with at least 1 day supply of opioids or SMRs containing codeine ( n =19,901 pre-injury, n= 40,573 post-injury) ,† Dispensing pattern

31.2 (31.8) 27.0

30.8–31.6 18.0–36.7

% (95% CI)

31.6 (29.0) 27.0

58.7–60.6 1.0–79.0 60.8–62.8 1.0–86.0 84.2–89.9 3.0–154.0 39.6–41.0 1.0–26.0 27.9–29.5 1.0–13.0 31.3–31.8 18.0–37.5

% (95% CI)

Average daily MED 120 mg among claimants with at least one days supply of opioids or SMRs containing codeine ( n=19,901 preinjury, n= 40,573 post-injury) ,†

157

0.8 (0.7–0.9)

308

0.8 (0.7–0.8)

At least 1 day of high MED ( 120 mg) among claimants with at least 1 day supply of opioids or SMRs containing codeine ( n =19,901 preinjury, n= 40,573 post-injury) ,†

479

2.4 (2.2–2.6)

1,336

3.3 (3.1–3.5)

CI, confidence interval; IQR, interquartile range; MED, morphine-equivalent dose; mg, milligrams; NSAIDs, nonsteroidal anti-inflammatory drugs; SD, standard deviation; SMRs, skeletal muscle relaxants. Sample size is based on individuals with at least 1 day supply of each drug class in the specific time period. Some claimants may have been dispensed a prescription outside of the period (eg, more than 1 year pre-injury), but the days supply spilled over into the relevant time period. Thus, the sample size is slightly larger than the number of claimants who received a prescription in the relevant time period. † Morphine equivalent dose was not calculated for methadone or opioids provided via parenteral or intranasal routes (less than 1% of all dispensing records).

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Fig 2 Proportion of claimants with at least one dispensed prescription in 8-week blocks from 48 weeks pre- to 48 weeks post-injury (n = 97,124). Light grey = preinjury; dark grey = -post-injury.

Prescription Dispensing Patterns From 48 Weeks Pre- to 48 Weeks Post-Injury in 8-Week Increments For all drug classes, the proportion of claimants dispensed a prescription in any given 8-week period was fairly stable leading up to the injury, with a slight dip in the immediate 8-week period prior to injury (Fig. 2). The average proportion of claimants in any given 8-week period receiving at least one opioid, NSAID, or SMR was 5.2%, 5.0%, and 1.3%, respectively (background prevalence). In the 8-week period immediately after injury, the prevalence sharply peaked, with 27.8%, 40.7%, and 24.8% of claimants receiving at least one opioid, NSAID, and SMR, respectively. The prevalence dropped immediately in the following 8-week period and continued to drop, stabilizing over time. Comparing pre- and post-injury, 2.0%, 1.1%, and 0.2% received opioids, NSAIDs, and SMRs, respectively in at least four out of the six 8-week periods pre-injury, compared with 4.0%, 2.6%, and 0.7%, respectively, post-injury. Between 41 and 48 weeks post-injury, the prevalence of receiving at least one prescription was nearly at pre-injury levels, but still slightly higher at 7.0%, 5.8%, and 1.7%, for opioids, NSAIDs, and SMRs, respectively. Comparing this to the background prevalence in the pre-injury period, this post-injury increase in opioid, NSAID, and SMR dispensing was attributable to approximately 1.8%, 0.8%, and 0.4% of claimants, respectively. Mean cumulative days supplied showed a small increasing trend leading up to the claim for all drug classes, decreasing in the immediate post 8-week period, due to an influx of claimants receiving prescriptions in this period for a short days supply (Fig. 3). Mean cumulative days supply increased thereafter and remained higher post-injury compared with pre-injury. By 41 to 48 weeks post-injury, the mean days supplied per claimant among claimants with at least one dispense was 22.0 for NSAIDs, 19.2 for SMRs, and 17.8 for opioids, compared with 18.4, 14.8, and 14.0 days, respectively, 41 to 48 weeks pre-injury.

A selection of published research by CMCC faculty

Among claimants dispensed opioid prescriptions, the proportion receiving weak and short-acting opioids declined from preinjury to post-injury, while the proportion of claimants receiving strong and long-acting opioids increased (Fig. 4). By 41 to 48 weeks post-injury, 19.0% of claimants dispensed opioids received strong opioids and 5.9% were receiving long-acting opioids. This is compared with 41 to 48 weeks pre-injury where only 11.6% and 2.6% were receiving strong and long-acting opioids, respectively. The 8-week period immediately after injury was the exception to this trend, with the proportion of claimants receiving weak and short-acting opioids increasing slightly, and the proportion dispensed strong and long-acting opioids decreasing. Average daily MED generally remained stable from pre- to post-injury (see Figure, Supplemental Digital Content 4, http://links.lww.com/JOM/A425 that depicts average daily MED per claimant pre- to post-injury for claimants with at least 1 day supplied of opioids and/or SMRs with codeine).

Discussion In this Canadian sample of workersâ&#x20AC;&#x2122; compensation claimants with LBP-related short-term disability claims, we found short courses of prescription drug classes often used in the management of LBP were commonly dispensed, both before and after the compensated LBP injury. Most claimants dispensed opioids received weak and short-acting opioids at low average daily doses. The prevalence of dispensing pre-injury was shown to be fairly stable, followed by a rapid increase in the proportion of claimants with dispensed prescriptions in the first 8 weeks after injury. Thereafter, the prevalence decreased quickly, but remained slightly elevated between 41 and 48 weeks compared with pre-injury. The small proportion of claimants continuing to receive dispensed prescriptions almost 1 year after injury tended to also receive them for longer and the proportion of claimants receiving strong and long-acting opioid formulations increased over time. Before the injury, 34% of claimants in our sample received at least one dispensed prescription for opioids, NSAIDs, and/ or SMRs, with opioids (19.6%) and NSAIDs (21.1%) most commonly dispensed. This estimate for opioids is higher than that seen in a recently published population-based study in BC, that found that approximately 12% of residents filled at least one opioid prescription in any given year from 2005 to 2013.58 Some of this discrepancy may be due to differences in sample composition, as that study included individuals of all ages and was not specific to a working population. Another Canadian survey in 2008 found that 21.6% of individuals over the age of 15 reported use of opioid pain relievers in the prior year.59 We were unable to locate published sources detailing past-year prevalence of NSAIDs and SMRs in population-based samples. However, past-month preva-lence of use among US adults from 1999 to 2010 has been estimated to be 7.0% for NSAIDs and 2.0% for SMRs,60 which is slightly higher than our prevalence estimates in any given 8-week period before injury. Not surprisingly, the dispensing prevalence for all three drug

CMCC Research Report 2015–2018

followed by NSAIDs (4 days), and opioids (6 days). When stratified by strength of opioid received, it took a median of 25 days for claimants to fill their first strong opioid prescription compared with 7 days for weak opioids. Some consideration of the context may be important. Our sample included only workers with at least 1 day of lost work time and the findings of some research suggest such workers may represent a more severe population than those who do not require time off.63,64 Nonetheless, these findings are suggestive of non-adherence to treatment guidelines that recommend against opioids and SMRs as first-line treatment for LBP.11,65 Research is needed to understand the determinants of early exposure to these drug classes among workers’ compensation claimants, including the role of the prescriber, as well as system- and workplace-level factors. Only a handful of studies have examined this, but have focused solely on opioids and mainly claimant-level factors.26,66,67 Fig 3 Mean cumulative days supply/claimant in 8-week blocks from 48 weeks pre- to 48 weeks post-injury for claimants with at least 1 day supplied of opioids and/or SMRs with codeine. SMR = skeletal muscle relax-ant.

classes increased substantially in the 1 year post-injury period. The largest increase was seen for SMRs (from 6.3% pre-injury to 28.4%post-injury), though NSAIDs and opioids remained most commonly dispensed after injury (50.2% and 38.8% of claimants, respectively). In previous studies of US workers’ compensation claimants with LBP claims, 1-year prevalence of opioid prescriptions ranged from 38% to 42% in the year after injury.24,28 A small study of US LBP claimants also found 83% and 66% received NSAIDs and SMRs, respectively, over 1 year after injury.28 Estimates from these studies were derived from prescriptions reimbursed by workers’ compensation for the compensated injury, while our study included data on all dispensed prescriptions irrespective of payment source or indication. The fact that our estimates were still similar or even lower could reflect system-level differences in reimbursement, where American workers’ compensation organizations reimburse injury-related prescriptions to a greater extent than suggested in our analysis of BC claimants.61 However, given that our data also may have included prescriptions for other indications, it is likely that true differences in prescribing patterns exist, with greater prescribing occurring in the US. These differences in prescribing may also be reflective of WorkSafeBC’s policy efforts at the time of the study period to limit the use of opioids after a workplace injury.62 The only previous Canadian study found between 7% and 10% of claimants with LBP claims in Alberta had at least one opioid prescription within a year after injury, a much lower estimate than in our study.26 Authors of this study found some evidence to suggest underestimation of strong opioid prescriptions in their data, though they were unable to verify this for weak opioids. Nonetheless, prevalence was likely underestimated. The time to first prescription was short for all drug classes, with SMRs demonstrating the shortest median time (3 days),

While overall dispensing was prevalent, the majority of claimants in this sample received one to two dispensed prescriptions both pre- and post-injury and with a short days supply. A small minority of claimants demonstrated a pattern of dispensing that was suggestive of long-term use. The proportion of claimants receiving various combinations of the three drug classes was also higher post-injury than pre-injury, where many claimants received only one of the three drug classes. This likely reflects the complex management of the injury and attempts at prescribing various drugs to ameliorate pain.

Fig 4 Proportion of claimants receiving at least one dispensed weak, strong, shortacting, or long-acting opioid prescription in 8-week blocks from 48 weeks pre- to 48 weeks post-injury for claimants with at least one dispensed opioid in the period. Light grey = pre-injury; dark grey = post-injury.

The vast majority of claimants with at least one opioid dispense received weak and short-acting formulations, namely codeine combinations with acetaminophen or acetylsalicylic acid. Historically, codeine has typically been perceived as relatively innocuous and in Canada, low dose formulations continue to be

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available over-the-counter. However, codeine poses a risk of tox-icity for some individuals68 and serious morbidity can result from its abuse.69–72 Oxycodone was the second most commonly dispensed opioid in this sample. Surprisingly, less than 1% of claimants with an opioid prescription received long-acting oxycodone, despite the fact that this analysis was conducted using data from a decade that saw rapid growth in use and abuse of OxyContin across North America.17,73,74 Average daily MED among claimants receiving opioid dispenses was approximately 31 mg/d pre- and post-injury. Among claimants receiving opioids between 41 and 48 weeks postinjury, the average daily MED was 37.8 mg/d. These values are well below WorkSafeBC’s high dose threshold of 120 mg/d at the time of the study.47 Less than 1% had an average daily MED equivalent to or exceeding 120 mg/d, a finding that suggests the vast majority of claimants were not exposed to high opioid doses that have been found to be associated with a number of serious harms, including mortality.75–77 While this finding is encouraging, it is important to note that harms have been shown to occur at lower doses, such as in a study of workers’ compensation claimants in Washington State, where most opioid poisonings and adverse effects from 2004 to 2010 occurred in cases without chronic supplies of opioids and with prescribed daily doses of less than 120 mg/d.78 The pre-injury period was relatively stable with respect to the prevalence of dispensing of each of the three drug classes. However, there was a peculiar, albeit minor, dip in prevalence in the 8 weeks before injury, particularly for opioids, that is difficult to explain. One potential explanation may be due to our selection of injury date as the inception point for our cohort that was done in an attempt to better reflect the clinical picture of the LBP injury. The median time between injury date and claim registration date was 5 days. Presumably claim registration date is valid, as it is documented upon claim submission. However, injury date may be applied retroactively and there may be some misclassification in this measure if there is any ambiguity in the timing of injury, particularly if the injury was more gradual in onset. It is possible that a subgroup of claimants may have begun to experience symptoms prior to the official injury date on claim and increased their use of over-the-counter drugs or sought non-pharmacologic measures to address their symptoms. In unpublished analyses, we found some evidence of an increase in the proportion of claimants from our cohort (with injury years 1998 to 2001) who received MSP-insured chiropractic visits leading up to the injury. Further, we lacked data on over-the-counter medications and, in Canada, a number of drugs from all three drug classes are available without prescription. Workers experiencing symptoms or already using these medications may also delay obtaining a prescription in anticipation of receiving workers’ compensation benefits, as the cost of the drugs would be covered if the claim is accepted. Another possible explanation may be related to duration of use prior to claim. Among individuals receiving these drug classes

A selection of published research by CMCC faculty

before injury date, there was a trend towards an increase in mean cumulative days supply and it could be that claimants receiving these prescriptions were receiving them for longer periods of time, thus leading to fewer dispensed prescriptions. However, these are all hypothetical explanations and this observation requires verification in other samples. Dispensing peaked in the first 8 weeks after injury, decreasing quickly thereafter. This pattern suggests that, for most claimants, prescriptions were new and exposure was acute in nature. However, dispensing remained slightly elevated through 48 weeks compared with pre-injury. This increase in opioid, NSAID, and SMR dispensing was attributable to approximately 1.8%, 0.8%, and 0.4% of claimants, respectively. Claimants who continued to be dispensed these prescriptions in the later periods after injury were also receiving them for slightly longer periods of time than seen pre-injury and, for claimants receiving opioids, increasingly more claimants were receiving stronger and long-acting formulations as time passed after injury, similar to observations from a US study of LBP claimants.23 Therefore, while most claimants in our cohort appeared to be exposed to these prescription drugs for a short window of time, there appears to be a very small proportion of claimants who may be struggling with recovery. This is consistent with other studies that found most claimants do not go on to long-term use, but those that do have greater work loss and little improvement in pain and function.24,29 Importantly, this group may also be particularly vulnerable to drug-related harms from prolonged use of these drug classes. To our knowledge, there are no other published studies examining pre- to post-injury prescription patterns of workers’ compensation claimants to which we can compare our results. Our findings are, however, generally consistent with those of two previous studies of claimants with musculoskeletal injuries examining health care utilization patterns.33,34 In both, health care utilization peaked immediately after claim, decreased, but remained elevated compared with pre-injury. Researchers in Australia also recently compared opioid dispensing 1 year before a motor vehicle accident with that 18 months after and found a sustained increase in total morphine equivalent amounts at 18 months compared with pre-injury.79 Unlike Koehoorn et al,33 who found an increase in health care utilization leading up to claim, we saw very little evidence to suggest an increase in prescription dispensing preceding the injury date on the claim. There are a number of strengths of our study. We have provided a comprehensive picture of dispensing of prescription drugs commonly used for LBP in a large sample of workers’ compensation claimants from a broad range of injury years. Unlike previous studies in this area, we have been able to contrast preand post-injury prescription dispensing patterns. Our study also provides estimates from a Canadian sample as a comparator to the many studies from the United States. Our prescription data comes from a comprehensive prescription monitoring program that

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provides detailed information on all drugs dispensed in community pharmacies, allowing us to capture drugs paid by workers’ compensation, as well as those paid through all other means. Our study also has limitations not yet described. The generalizability of findings to other jurisdictions, to nonworkers’ compensation claimants, or to claimants without lost work time is unknown. This study was also conducted using data from 1998 to 2009 and current dispensing patterns may differ. Prescription data were based on dispensing records and we do not know whether the prescriptions were actually consumed. Therefore, exposure may have been overestimated. However, the findings still likely reflect clinical practice patterns in this population. We also did not have data on drugs received in hospital and this likely led to underestimation of exposure, though likely this was minor since we excluded individuals with LBP-related hospitalizations in the first 5 days after injury, a period of extensive dispensing activity in our sample. The prescription-related measures derived in our study were also based on prescription dispensing records irrespective of indication or payment source (eg, workers’ compensation, personal insurance) and, therefore, post-injury prescriptions cannot necessarily be attributed to the LBP injury. However, we believe it is still important to identify the drugs to which claimants are exposed regardless of indication and the pattern of dispensing suggests that, for most claimants, prescriptions were new.

Conclusion In this Canadian sample of workers’ compensation LBP claimants, dispensing of prescription opioids, NSAIDs, and SMRs was common both pre- and post-injury and occurred quickly after injury. Most claimants receiving opioids received low doses of weak and short-acting formulations. Dispensing patterns also suggest that for most, injuries were acute and treatment was time limited. However, the small, sustained increase in post-injury dispensing compared with pre-injury and the increase in dispensing of strong and long-acting opioids and days supply across all drug classes suggests a small proportion of workers struggle with recovery and will continue to use these medications almost a year after injury. A more empirical examination of the factors associated with post-injury prescription drug patterns, particularly for the active early injury period and for sustained exposure, is needed. Confirmation of our findings in other samples using comprehensive and more recent prescription data is also warranted.

Acknowledgements The authors wish to thank Hyunmi Lee for her indispensable assistance with data cleaning, management, and analysis. This research was supported with funding from WorkSafeBC through the Research at Work program (fund number RS2011-OG12) and from the Canadian Institutes of Health Research (CIHR) Open Operating Grant program (fund number 115032). The BC Ministry of Health, WorkSafeBC, and PharmaNet approved

access to and use of the data delivered by Population Data BC in this analysis. Nancy Carnide was supported by a CIHR Vanier Canada Graduate Scholarship during the course of this work. The research was undertaken, in part, thanks to funding from the CIHR Canada Research Chairs program to Pierre Côté (CIHR Chair in Disability Prevention and Rehabilitation) and Mieke Koehoorn (CIHR Chair in Gender, Work and Health) and the CIHR New Investigator Award program to Andrea Furlan.

References 1. Blackwell DL, Lucas JW, Clarke TC. Summary health statistics for U.S. adults: national health interview survey, 2012. Vital Health Stat 10. 2014; 1–161. 2. Collins JJ, Baase CM, Sharda CE, et al. The assessment of chronic health conditions on work performance, absence, and total economic impact for employers. J Occup Environ Med. 2005;47:547–557. 3. Zhang W, McLeod C, Koehoorn M. The relationship between chronic conditions and absenteeism and associated costs in Canada. Scand J Work Environ Health. 2016;42:413–422. 4. Guo HR, Tanaka S, Halperin WE, Cameron LL. Back pain prevalence in US industry and estimates of lost workdays. Am J Public Health. 1999; 89:1029–1035. 5. Ricci JA, Stewart WF, Chee E, Leotta C, Foley K, Hochberg MC. Back pain exacerbations and lost productive time costs in United States workers. Spine. 2006;31:3052–3060. 6. Stewart WF, Ricci JA, Chee E, Morganstein D, Lipton R. Lost productive time and cost due to common pain conditions in the US workforce. JAMA. 2003;290:2443–2454. 7. Wynne-Jones G, Cowen J, Jordan JL, et al. Absence from work and return to work in people with back pain: a systematic review and meta-analysis. Occup Environ Med. 2014;71:448–456. 8. Hart LG, Deyo RA, Cherkin DC. Physician office visits for low back pain. Frequency, clinical evaluation, and treatment patterns from a U.S. national survey. Spine. 1995;20:11–19. 9. Ivanova JI, Birnbaum HG, Schiller M, Kantor E, Johnstone BM, Swindle RW. Real-world practice patterns, health-care utilization, and costs in patients with low back pain: the long road to guideline-concordant care. Spine J. 2011;11:622–632. 10. Vogt MT, Kwoh CK, Cope DK, Osial TA, Culyba M, Starz TW. Analgesic usage for low back pain: impact on health care costs and service use. Spine. 2005;30:1075–1081. 11. Wong JJ, Côte P, Sutton DA, et al. Clinical practice guidelines for the noninvasive management of low back pain: a systematic review by the Ontario Protocol for Traffic Injury Management (OPTIMa) Collaboration. Eur J Pain. 2017;21:201–216. 12. Ritzwoller DP, Crounse L, Shetterly S, Rublee D. The association of comorbidities, utilization and costs for patients identified with low back pain. BMC Musculoskelet Disord. 2006;7:72.

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13. Abdel Shaheed C, Maher CG, Williams KA, Day R, McLachlan AJ. Efficacy, tolerability, and dose-dependent effects of opioid analgesics for low back pain: a systematic review and metaanalysis. JAMA Intern Med. 2016;176: 958–968. 14. Chou R, Qaseem A, Snow V, et al. Diagnosis and treatment of low back pain: a joint clinical practice guideline from the American College of Physicians and the American Pain Society. Ann Intern Med. 2007;147:478–491. 15. van Tulder MW, Touray T, Furlan AD, Solway S, Bouter LM. Muscle relaxants for non-specific low back pain. Cochrane Database Syst Rev. 2003;CD004252. 16. Wong JJ, Côté P, Ameis A, et al. Are non-steroidal antiinflammatory drugs effective for the management of neck pain and associated disorders, whip-lash-associated disorders, or non-specific low back pain? A systematic review of systematic reviews by the Ontario Protocol for Traffic Injury Management (OPTIMa) Collaboration. Eur Spine J. 2016;25:34–61. 17. Cicero TJ, Inciardi JA, Munoz A. Trends in abuse of Oxycontin and other opioid analgesics in the United States: 2002-2004. J Pain. 2005;6:662–672. 18. Dart RC, Surratt HL, Cicero TJ, et al. Trends in opioid analgesic abuse and mortality in the United States. N Engl J Med. 2015;372:241–248. 19. Gomes T, Mamdani MM, Dhalla IA, Cornish S, Paterson JM, Juurlink DN. The burden of premature opioid-related mortality. Addiction. 2014; 109: 1482–1488. 20. Murphy Y, Goldner EM, Fischer B. Prescription opioid use, harms and interventions in Canada: a review update of new developments and findings since 2010. Pain Physician. 2015;18:E605–E614. 21. Vowles KE, McEntee ML, Julnes PS, Frohe T, Ney JP, van der Goes DN. Rates of opioid misuse, abuse, and addiction in chronic pain: a systematic review and data synthesis. Pain. 2015;156:569–576. 22. Busse JW, Ebrahim S, Heels-Ansdell D, Wang L, Couban R, Walter SD. Association of worker characteristics and early reimbursement for physical therapy, chiropractic and opioid prescriptions with workers’ compensation claim duration, for cases of acute low back pain: an observational cohort study. BMJ Open. 2015;5:e007836. 23. Cifuentes M, Webster B, Genevay S, Pransky G. The course of opioid prescribing for a new episode of disabling low back pain: opioid features and dose escalation. Pain. 2010;151: 22–29. 24. Franklin GM, Rahman EA, Turner JA, Daniell WE, FultonKehoe D. Opioid use for chronic low back pain: a prospective, population-based study among injured workers in Washington state, 2002–2005. Clin J Pain. 2009;25: 743–751. 25. Franklin GM, Stover BD, Turner JA, Fulton-Kehoe D, Wickizer TM, Disability Risk Identification Study C. Early opioid prescription and subsequent disability among workers with back injuries: the Disability Risk Identification Study Cohort. Spine. 2008;33:199–204.

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26. Gross DP, Stephens B, Bhambhani Y, Haykowsky M, Bostick GP, Rashiq S. Opioid prescriptions in Canadian workers’ compensation claimants: prescription trends and associations between early prescription and future recovery. Spine. 2009;34:525–531. 27. Lee SS, Choi Y, Pransky GS. Extent and impact of opioid prescribing for acute occupational low back pain in the Emergency Department. J Emerg Med. 2016;50:376.e1–384.e2. 28. Mahmud MA, Webster BS, Courtney TK, Matz S, Tacci JA, Christiani DC. Clinical management and the duration of disability for work-related low back pain. J Occup Environ Med. 2000;42:1178–1187. 29. Volinn E, Fargo JD, Fine PG. Opioid therapy for nonspecific low back pain and the outcome of chronic work loss. Pain. 2009;142:194–201. 30. Webster BS, Verma SK, Gatchel RJ. Relationship between early opioid prescribing for acute occupational low back pain and disability duration, medical costs, subsequent surgery and late opioid use. Spine. 2007;32: 2127–2132. 31. Shafer LA, Raymond C, Ekuma O, Kraut A. The impact of opioid prescription dose and duration during a workers compensation claim, on post-claim continued opioid use: a retrospective population-based study. Am J Ind Med. 2015;58:650–657. 32. Sheppard T, Lipton B, Robertson J. The Relationship Between Accident Report Lag and Claim Cost in Workers Compensation Insurance. Florida: National Council on Compensation Insurance; 2015. Available at: https://www. ncci.com/Articles/Documents/II_Relationship-AccidentReport-Lag-Claim-Cost-WC-Insurance.pdf. Accessed January 17, 2017. 33. Koehoorn M, Cole DC, Hertzman C, Lee H. Health care use associated with work-related musculoskeletal disorders among hospital workers. J Occup Rehabil. 2006;16:411–424. 34. Côté P, Yang X, Kristman V, et al. The association between workers’ compensation claims involving neck pain and future health care utilization: a population-based cohort study. J Occup Rehabil. 2013;23:547–556. 35. Canadian Institute for Health Information [creator] (2013): Discharge Abstract Database (Hospital Separations). V2. Population Data BC [publisher]. Data Extract. CIHI; 2013. 36. British Columbia Ministry of Health [creator] (2012): PharmaNet. V2. British Columbia Ministry of Health [publisher]. Data Extract. Data Stewardship Committee; 2013.British Columbia Ministry of Health [creator] (2013): Consolidation File (MSP Registration & Premium Billing). V2. Population Data BC [publisher]. Data Extract. MOH; 2013. 37. British Columbia Ministry of Health [creator] (2013): Medical Services Plan (MSP) Payment Information File. V2. Population Data BC [publisher]. Data Extract. MOH; 2013. 38. WorkSafeBC [creator] (2012): WorkSafeBC Claims and Firm Level Files. V2. Population Data BC [publisher]. Linked Data Set. WorkSafeBC; 2013. 39. Population Data BC; 2017. Available at: https://www.popdata. bc.ca/. Accessed March 3, 2017.

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40. Pencarrick Hertzman C, Meagher N, McGrail KM. Privacy by Design at Population Data BC: a case study describing the technical, administrative, and physical controls for privacysensitive secondary use of personal information for research in the public interest. J Am Med Inform Assoc. 2013;20:25–28. 41. WorkSafeBC. Who does and doesn’t need coverage? 2017. Available at: https://www.worksafebc.com/en/insurance/ need-coverage/who-needs-coverage. Accessed November 23, 2016. 42. Association of Workers’ Compensation Boards of Canada (AWCBC) Customized KSM Report. Percentage of Workforce Covered [%]. British Columbia. 2000-2009 [data file]. Association of Workers’ Compensation Boards of Canada (AWCBC); 2013. Available at: http://awcbc.org/ ?page_ id=9755. Accessed February 11, 2017. 43. World Health Organization. The International Statistical Classification of Diseases and Related Health Problems, Ninth Revision (ICD-9). Geneva, CH: World Health Organization; 1977. 44. Canadian Institute for Health Information. Canadian Coding Standards for Version 2012 ICD-10-CA and CCI. Ottawa, ON: Canadian Institute for Health Information; 2012. 45. American Hospital of Hospital Pharmacists. AHFS Drug Information. Bethesda, MD: Published by authority of the Board of Directors of the American Society of Hospital Pharmacists; 2011. 46. WorkSafeBC Compensation Practice & Quality Department. Practice Directive #C10-1. Claims With Opioids Prescribed. Richmond, BC: WorkSafeBC; 2009. 47. Equianalgesic Dosing of Opioids for Pain Management. PL Detail Document. Stockton, CA: Therapeutic Research Center; 2015. 48. Washington State Agency Medical Directors’ Group (AMDG). Interagency Guideline on Prescribing Opioids for Pain; 2015. Available at: http://www.agencymeddirectors.wa.gov Files/2015AMDGOpioidGuideline.pdf. Accessed September 2, 2015. 49. American Pain Society. Principles of Analgesic Use in the Treatment of Acute Pain and Cancer Pain. 6th ed. Glenview, IL; 2008. 50. Compendium of pharmaceuticals and specialties, online version (e-CPS)[Internet]. Available at: https://www. pharmacists.ca/products-services/compendium-ofpharmaceuticals-and-specialties/. Accessed March 12, 2015. 51. National Opioid Use Guideline Group (NOUGG). Canadian Guideline for Safe and Effective Use of Opioids for Chronic Non-Cancer Pain. Part B. Recommendations for Practice. Appendix B-8. Hamilton, ON: National Pain Centre, McMaster University; 2010. 52. Svendsen K, Borchgrevink P, Fredheim O, Hamunen K, Mellbye A, Dale O. Choosing the unit of measurement counts: the use of oral morphine equivalents in studies of opioid consumption is a useful addition to defined daily doses. Palliat Med. 2011;25:725–732.

53. Turner BJ, Liang Y. Drug overdose in a retrospective Cohort with non-cancer pain treated with opioids, antidepressants, and/or sedative-hypnotics: interactions with mental health disorders. J Gen Intern Med. 2015;30: 1081–1096. 54. Von Korff M, Saunders K, Thomas Ray G, et al. De facto long-term opioid therapy for noncancer pain. Clin J Pain. 2008;24:521–527. 55. Ministry of Health. Health Authorities. Government of British Columbia. Available at: http://www2.gov.bc.ca/gov/content/ health/about-bc-s-health-care-system/partners/healthauthorities. Accessed: September 20, 2017. 56. Statistics Canada. Postal Code Conversion File Plus (PCCFR) (82F0086X). Available at: http://www5.statcan.gc.ca/olc-cel/ olc.action?lang=en&Ob-jId=82F0086X&ObjType=2. Accessed February 1, 2017. 57. Smolina K, Gladstone E, Morgan SG. Determinants of trends in prescription opioid use in British Columbia, Canada, 20052013. Pharmacoepidemiol Drug Saf. 2016;25:553–559. 58. Health Canada. Archived - Canadian Alcohol and Drug Use Monitoring Survey. Summary of Results for 2008. Ottawa, ON: Health Canada; 2009. Available at: http://www.hc-sc.gc.ca/ hc-ps/drugs-drogues/stat/_2008/sum-mary-sommaire-eng. php. Accessed January 28, 2017. 59. Kantor ED, Rehm CD, Haas JS, Chan AT, Giovannucci EL. Trends in prescription drug use among adults in the United States From 1999-2012. JAMA. 2015;314:1818–1831. 60. Hogg-Johnson S, Carnide N, Côté P, Furlan AD, Koehoorn M. Early Opioid Prescriptions for Work-Related Musculoskeletal Disorders of the Back: Understanding Utilization Patterns, Determinants and Impact on Work Disability. Final Report. WorkSafeBC Grant # RS2011-OG12. Toronto, ON: Institute for Work & Health; 2016. 61. WorkSafeBC. The Prescription of Narcotics and Other Drugs of Addiction. Richmond, BC: WorkSafeBC; 1989. 62. Smith JM, Bombardier C, Frank JW, et al. Clinical profile of cases in a worksite study of low back pain according to WCB claim and lost-time status at baseline and 26 weeks. Arthritis Rheum. 1997;40:S263. 63. Hogg-Johnson S, Bombardier C, Guzman J, et al. A comparison of symptoms and disability from acute low back pain (LBP) among three study settings. Arthritis Rheum. 1997;40:S263. 64. Dagenais S, Tricco AC, Haldeman S. Synthesis of recommendations for the assessment and management of low back pain from recent clinical practice guidelines. Spine J. 2010;10:514–529. 65. Stover BD, Turner JA, Franklin G, et al. Factors associated with early opioid prescription among workers with low back injuries. J Pain. 2006;7:718–725. 66. Webster BS, Cifuentes M, Verma S, Pransky G. Geographic variation in opioid prescribing for acute, work-related, low back pain and associated factors: a multilevel analysis. Am J Ind Med. 2009;52:162–171. 67. Madadi P, Amstutz U, Rieder M, et al. Clinical practice guideline: CYP2D6 genotyping for safe and efficacious codeine therapy. J Popul Ther Clin Pharmacol. 2013;20:e369–e396.

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A selection of published research by CMCC faculty

68. Frei MY, Nielsen S, Dobbin MD, Tobin CL. Serious morbidity associated with misuse of over-the-counter codeineibuprofen analgesics: a series of 27 cases. Med J Aust. 2010;193:294–296. 69. McAvoy BR, Dobbin MD, Tobin CL. Over-the-counter codeine analgesic misuse and harm: characteristics of cases in Australia and New Zealand. NZ Med J. 2011;124:29–33. 70. Roxburgh A, Hall WD, Burns L, et al. Trends and characteristics of accidental and intentional codeine overdose deaths in Australia. Med J Aust. 2015;203:299. 71. Sproule BA, Busto UE, Somer G, Romach MK, Sellers EM. Characteristics of dependent and nondependent regular users of codeine. J Clin Psycho-pharmacol. 1999;19:367–372. 72. Dhalla IA, Mamdani MM, Sivilotti ML, Kopp A, Qureshi O, Juurlink DN. Prescribing of opioid analgesics and related mortality before and after the introduction of long-acting oxycodone. CMAJ. 2009;181:891–896. 73. Van Zee A. The promotion and marketing of oxycontin: commercial triumph, public health tragedy. Am J Public Health. 2009;99:221–227. 74. Bohnert AS, Valenstein M, Bair MJ, et al. Association between opioid prescribing patterns and opioid overdoserelated deaths. JAMA. 2011; 305:1315–1321. 75. Gomes T, Mamdani MM, Dhalla IA, Paterson JM, Juurlink DN. Opioid dose and drug-related mortality in patients with nonmalignant pain. Arch Intern Med. 2011;171:686–691. 76. Gomes T, Redelmeier DA, Juurlink DN, Dhalla IA, Camacho X, Mamdani MM. Opioid dose and risk of road trauma in Canada: a population-based study. JAMA Intern Med. 2013;173:196–201. 77. Fulton-Kehoe D, Garg RK, Turner JA, et al. Opioid poisonings and opioid adverse effects in workers in Washington state. Am J Ind Med. 2013; 56:1452–1462. 78. Berecki-Gisolf J, Hassani-Mahmooei B, Collie A, McClure R. Prescription opioid and benzodiazepine use after road traffic injury. Pain Med. 2016; 17:304–313.

Originally published in the Journal of Occupational and Environmental Medicine, 2018 Jul;60(7):644-655. Reproduced with permission from Walters Kluwer Group. Access Online: https://doi.org/10.1097/JOM.0000000000001311

CMCC Research Report 2015–2018

Knowledge Translation and Health Policy

Patients’ Experiences with Vehicle Collision to Inform the Development of Clinical Practice Guidelines: A Narrative Inquiry Lindsay GM1, Mior SA 2,3, Côté P1,2,3, Carroll LJ4, Shearer HM2,3 University of Ontario Institute of Technology, 2Canadian Memorial Chiropractic College, 3 University of Ontario Institute of Technology, UOIT-CMCC Centre for the Study of Disability Prevention and Rehabilitation, University of Ontario Institute of Technology (UOIT) and Canadian Memorial Chiropractic College (CMCC), 4University of Alberta 1 3

Abstract Objective: The purpose of this narrative inquiry was to explore the experiences of persons who were injured in traffic collisions and seek their recommendations for the development of clinical practice guideline (CPG) for the management of minor traffic injuries. Methods: Patients receiving care for traffic injuries were recruited from 4 clinics in Ontario, Canada resulting in 11 adult participants (5 men, 6 women). Eight were injured while driving cars, 1 was injured on a motorcycle, 2 were pedestrians, and none caused the collision. Using narrative inquiry methodology, initial interviews were audiotaped, and follow-up interviews were held within 2 weeks to extend the story of experience created from the first interview. Narrative plotlines across the 11 stories were identified, and a composite story inclusive of all recommendations was developed by the authors. The research findings and composite narrative were used to inform the CPG Expert Panel in the development of new CPGs. Results: Four recommended directions were identified from the narrative inquiry process and applied. First, terminology that caused stigma was a concern. This resulted in modified language (“injured persons”) being adopted by the Expert Panel, and a new nomenclature categorizing layers of injury was identified. Second, participants valued being engaged as partners with health care practitioners. This resulted in inclusion of shared

decision-making as a foundational recommendation connecting CPGs and care planning. Third, emotional distress was recognized as a factor in recovery. Therefore, the importance of early detection and the ongoing evaluation of risk factors for delayed recovery were included in all CPGs. Fourth, participants shared that they were unfamiliar with the health care system and insurance industry before their accident. Thus, repeatedly orienting injured persons to the system was advised. Conclusion: A narrative inquiry of 11 patients’ experiences with traffic collision and their recommendations for clinical guidelines informed the Ontario Protocol for Traffic Injury Management Collaboration in the development of new Minor Injury Guidelines. The values and findings of the qualitative inquiry were interwoven into each clinical pathway and embedded within the final guideline report submitted to government.

Originally published in the Journal of Manipulative and Physiological Therapeutics, 2016 Mar-Apr;39(3):218-2, Epub 2016 Feb 28. Reproduced with permission from Elsevier. Access Online: https://doi.org/10.1016/j.jmpt.2016.01.005

A selection of published research by CMCC faculty

Attitudes Toward Chiropractic: A Survey of Canadian Obstetricians Weis CA1, Stuber K1, Barrett J2, Greco A 2, Kipershlak A 2, Glenn T2, Desjardins R2, Nash J3, Busse J1,3 Canadian Memorial Chiropractic College, 2 Sunnybrook Health Sciences Centre, 3 Mcmaster University

Abstract We assessed the attitudes of Canadian obstetricians toward chiropractic with a 38-item cross-sectional survey. Ninetyone obstetricians completed the survey, for a response rate of 14% (91 of 659). Overall, 30% of respondents held positive views toward chiropractic, 37% were neutral, and 33% reported negative views. Most (77%) reported that chiropractic care was effective for some musculoskeletal complaints, but 74% disagreed that chiropractic had a role in treatment of nonmusculoskeletal conditions. Forty percent of respondents referred at least some patients for chiropractic care each year, and 56% were interested in learning more about chiropractic care. Written comments from respondents revealed concerns

regarding safety of spinal manipulation and variability among chiropractors. Canadian obstetricians’ attitudes toward chiropractic are diverse and referrals to chiropractic care for their patients who suffer from pregnancy-related low back pain are limited. Improved interprofessional relations may help optimize care of pregnant patients suffering from low back pain.

Originally published in the Journal of Evidence-Based Integrative Medicine, 2016 Apr;21(2):92-104.. Epub 2015 Sep 8. Reproduced with permission from Sage Journals. Access Online: https://doi.org/10.1177/2156587215604073

Building Multidisciplinary Health Workforce Capacity to Support the Implementation of Integrated, People-Centred Models of Care for Musculoskeletal Health Chehade MJ1, Gill TK 2, Kopansky-Giles D3 , Schuwirth L 4, Karnon J2, McLiesh P1,2, Alleyne J4, Woolf AD5 Royal Adelaide Hospital, 2The University of Adelaide, 3Canadian Memorial Chiropractic College, 4Flinders University, University of Exeter Medical School

1 5

Abstract To address the burden of musculoskeletal (MSK) conditions, a competent health workforce is required to support the implementation of MSK models of care. Funding is required to create employment positions with resources for service delivery and training a fit-for-purpose workforce. Training should be aligned to define “entrustable professional activities”, and include collaborative skills appropriate to integrated and people-centred care and supported by shared education resources. Greater emphasis on educating MSK healthcare workers as effective trainers of peers, students and patients is required. For quality, efficiency and sustainability of service delivery, education and research capabilities must be integrated across disciplines and within the workforce, with funding models developed based on measured performance indicators from all

three domains. Greater awareness of the societal and economic burden of MSK conditions is required to ensure that solutions are prioritised and integrated within healthcare policies from local to regional to international levels. These healthcare policies require consumer engagement and alignment to social, economic, educational and infrastructure policies to optimise effectiveness and efficiency of implementation.

Originally published in Best Practice & Clinical Research Rheumatology, 2016 Jun;30(3):559-584. Reproduced with permission from Elsevier. Access Online: https://doi.org/10.1016/j.berh.2016.09.005

CMCC Research Report 2015–2018

Exploring Approaches to Patient Safety: The Case of Spinal Manipulation Therapy Rozmovits L1, Mior S2, Boon H3 Private Research Consulting , 2Canadian Memorial Chiropractic College, 3 University of Toronto

Abstract Background: The purpose of this study was to gain insight into the current safety culture around the use of spinal manipulation therapy (SMT) by regulated health professionals in Canada and to explore perceptions of readiness for implementing formal mechanisms for tracking associated adverse events. Methods: Fifty-six semi-structured telephone interviews were conducted with professional leaders and frontline practitioners in chiropractic, physiotherapy, naturopathy and medicine, all professions regulated to perform SMT in the provinces of Alberta and Ontario Canada. Interviews were digitally audiorecorded for verbatim transcription. Transcripts were entered into HyperResearch software for qualitative data analysis and were coded for both anticipated and emergent themes using the constant comparative method. A thematic, descriptive analysis was produced. Results: The safety culture around SMT is characterized by substantial disagreement about its actual rather than putative risks. Competing intra- and inter-professional narratives further cloud the safety picture. Participants felt that safety talk is sometimes conflated with competition for business in the context of feefor-service healthcare delivery by several professions with overlapping scopes of practice. Both professional leaders and frontline practitioners perceived multiple barriers to the implementation of an incident reporting system for SMT.

Conclusion: The established ‘measure and manage’ approach to patient safety is difficult to apply to care which is geographically dispersed and delivered by practitioners in multiple professions with overlapping scopes of practice, primarily in a fee-forservice model. Collaboration across professions on models that allow practitioners to share information anonymously and help practitioners learn from the reported incidents is needed.

Originally published in BMC Complementary and Alternative Medicine, 2016 Jun 2;16:164. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line. Access Online: https://doi.org/10.1186/s12906-016-1149-2

A selection of published research by CMCC faculty

Core and Complementary Chiropractic: Lowering Barriers to Patient Utilization of Services Triano JJ, McGregor M Canadian Memorial Chiropractic College

Abstract Objective: The use of chiropractic services has stalled while interest in accessing manipulation services is rising. The purpose of this paper is to consider this dilemma in the context of the dynamics of professional socialization, surveys of public attitudes, and a potential strategic action. Discussion: This is a reflection work grounded in the literature on professional socialization and the attitudes held regarding chiropractic in modern society, to include its members, and in original data on training programs. Data were interpreted on the background of the authorsâ&#x20AC;&#x2122; cross-cultural experiences spanning patient care, research, education, and interprofessional collaboration. Recommendation on a strategic action to counter barriers in patient referrals was synthesized. Professional socialization is the process by which society enables professional privilege. Illustration of typical and divergent professional socialization models emerged that explain cognitive dissonance toward the profession. Questions of trust are commensurate with the experiences during patient encounters rather than with a common identity for the profession. Diversity among encounters perpetuates the uncertainty that affects referral sources. Commonality as an anchor for consistent professional identity and socialization through the content of core chiropractic, defined by training and practice, offers a means to offset uncertainty. Complementary chiropractic, analogous to complementary medicine, provides an outlet under professional socialization for the interests to explore additional methods of care.

Conclusion: The practice workplace is an effective lever for altering barriers to the use of services. Clarifying rhetoric through conceptualization of core and complementary practices simplifies the socialization dynamic. Further, it takes advantage of accepted cultural semantics in meaningful analogy while continuing to empower practical diversity in care delivery in response to evolving scientific evidence.

Originally published in the Journal of Chiropractic Humanities, 2016 Sep 15;23(1):1-13. eCollection 2016 Dec. Reproduced with permission from Elsevier. Access Online: https://doi.org/10.1016/j.echu.2016.07.001

CMCC Research Report 2015–2018

Who will have Sustainable Employment After a Back Injury? The Development of a Clinical Prediction Model in a Cohort of Injured Workers Shearer HM1,2, Côté P1,2,3,4, Boyle E4,5, Hayden JA6, Frank J7, Johnson WG8 UOIT-CMCC Center for the Study of Disability Prevention and Rehabilitation, University of Ontario Institute of Technology, Canadian Memorial Chiropractic College, 2Canadian Memorial Chiropractic College, 3University of Ontario Institute of Technology, 4University of Toronto, 5University of Southern Denmark, 6Dalhousie University, 7University of Edinburgh, 8 Arizona State University 1

Abstract Purpose: Our objective was to develop a clinical prediction model to identify workers with sustainable employment following an episode of work-related low back pain (LBP). Methods: We used data from a cohort study of injured workers with incident LBP claims in the USA to predict employment patterns 1 and 6 months following a workers’ compensation claim. We developed three sequential models to determine the contribution of three domains of variables: (1) basic demographic/clinical variables; (2) health-related variables; and (3) work-related factors. Multivariable logistic regression was used to develop the predictive models. We constructed receiver operator curves and used the c-index to measure predictive accuracy. Results: Seventy-nine percent and 77 % of workers had sustainable employment at 1 and 6 months, respectively. Sustainable employment at 1 month was predicted by initial back pain intensity, mental health-related quality of life, claim litigation and employer type (c-index = 0.77). At 6 months, sustainable employment was predicted by physical and mental healthrelated quality of life, claim litigation and employer type (c-index = 0.77). Adding health-related and work-related variables to models improved predictive accuracy by 8.5 and 10 % at 1 and 6 months respectively.

Conclusion: We developed clinically-relevant models to predict sustainable employment in injured workers who made a workers’ compensation claim for LBP. Inquiring about back pain intensity, physical and mental health-related quality of life, claim litigation and employer type may be beneficial in developing programs of care. Our models need to be validated in other populations.

Originally published in the Journal of Occupational Rehabilitation, 2017 Sep;27(3):445-455. Reproduced with permission from Springer Nature. Access Online: https://doi.org/10.1007/s10926-016-9678-6

A selection of published research by CMCC faculty

Spinal Manipulative Therapy and Other Conservative Treatments for Low Back Pain: A Guideline from the Canadian Chiropractic Guideline Initiative Bussières AE1, Stewart G2, Al-Zoubi F1, Decina P3, Descarreaux M4, Haskett D5, Hincapié C6, Pagé I4, Passmore S7, Srbely J5, Stupar M3, Weisberg J2, Ornelas J8 McGill University, 2Private Practice, 3Canadian Memorial Chiropractic College, 4Université du Québec à Trois-Rivières, 5University of Guelph, St. Michael’s Hospital, 7University of Manitoba, 8Rush University

1 6

Abstract Objective: The objective of this study was to develop a clinical practice guideline on the management of acute and chronic low back pain (LBP) in adults. The aim was to develop a guideline to provide best practice recommendations on the initial assessment and monitoring of people with low back pain and address the use of spinal manipulation therapy (SMT) compared with other commonly used conservative treatments. Discussion: The topic areas were chosen based on an Agency for Healthcare Research and Quality comparative effectiveness review, specific to spinal manipulation as a nonpharmacological intervention. The panel updated the search strategies in Medline. We assessed admissible systematic reviews and randomized controlled trials for each question using A Measurement Tool to Assess Systematic Reviews and Cochrane Back Review Group criteria. Evidence profiles were used to summarize judgments of the evidence quality and link recommendations to the supporting evidence. Using the Evidence to Decision Framework, the guideline panel determined the certainty of evidence and strength of the recommendations. Consensus was achieved using a modified Delphi technique. The guideline was peer reviewed by an 8-member multidisciplinary external committee.

Results: For patients with acute (0-3 months) back pain, we suggest offering advice (posture, staying active), reassurance, education and self-management strategies in addition to SMT, usual medical care when deemed beneficial, or a combination of SMT and usual medical care to improve pain and disability. For patients with chronic (>3 months) back pain, we suggest offering advice and education, SMT or SMT as part of a multimodal therapy (exercise, myofascial therapy or usual medical care when deemed beneficial). For patients with chronic back-related leg pain, we suggest offering advice and education along with SMT and home exercise (positioning and stabilization exercises). Conclusion: A multimodal approach including SMT, other commonly used active interventions, self-management advice, and exercise is an effective treatment strategy for acute and chronic back pain, with or without leg pain.

Originally published in the Journal for Manipulative and Physiological Therapeutics, 2018 May;41(4):265-293. Epub 2018 Mar 30. Reproduced with permission from Elsevier. Access Online: https://doi.org/10.1016/j.jmpt.2017.12.004

CMCC Research Report 2015–2018

The Global Spine Care Initiative: a Summary of the Global Burden of Low Back and Neck Pain Studies Hurwitz EL1, Randhawa K 2,3, Yu H2,3, Côté P2,3, Haldeman S 4,5,6 University of Hawaii, 2University of Ontario Institute of Technology, 3UOIT-CMCC Centre for Disability Prevention and Rehabilitation, 4University of California Los Angeles, 5University of California, Irvine, 6World Spine Care 1

Abstract Purpose: This article summarizes relevant findings related to low back and neck pain from the Global Burden of Disease (GBD) reports for the purpose of informing the Global Spine Care Initiative. Methods: We reviewed and summarized back and neck pain burden data from two studies that were published in Lancet in 2016, namely: “Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015” and “Global, regional, and national disability-adjusted life years (DALYs) for 315 diseases and injuries and healthy life expectancy (HALE), 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015.” Results: In 2015, low back and neck pain were ranked the fourth leading cause of disability-adjusted life years (DALYs) globally just after ischemic heart disease, cerebrovascular disease, and lower respiratory infection {low back and neck pain DALYs [thousands]: 94 941.5 [95% uncertainty interval (UI) 67 745.5-128 118.6]}. In 2015, over half a billion people worldwide had low back pain and more than a third of a billion had neck pain of more than 3 months duration. Low back and neck pain are the leading causes of years lived with disability in most countries and age groups.

Conclusion: Low back and neck pain prevalence and disability have increased markedly over the past 25 years and will likely increase further with population aging. Spinal disorders should be prioritized for research funding given the huge and growing global burden. These slides can be retrieved under Electronic Supplementary Material.

Originally published in the European Spine Journal, 2018 Sep;27(Suppl 6):796-801. Epub 2018 Feb 26. Reproduced with permission from Springer Nature. Access Online: https://doi.org/10.1007/s00586-017-5432-9

A selection of published research by CMCC faculty

Conference Proceedings 2015 – 2016 Academic Year Taylor R. Achieving Harmony in elearning Development: A Collaborative Discussion. 15 Jun 15; Vancouver, BC: STLHE 2015: Achieving Harmony: Tuning into Practice. Howarth S, Grondin D, Cox J, La Delfa N, Potvin JR. Low back physical demands during a simulated dental hygiene task. 15 Aug 5; Columbus OH: 39th Annual Meeting of the American Society of Biomechanics. Gooyers CE, Beach TAC, Frost DM, Howarth SJ, Callaghan JP. The Influence of Interactions between External Task Demands in Lifting on Estimates of In Vivo Low Back Joint Loads. 15 Aug 5; Columbus OH: 39th Annual Meeting of the American Society of Biomechanics. Triano JJ. Manual Spinal Therapy: Does Procedure Matter? 15 Aug 19; Chicago, IL: Spine Monthly Research Seminar of the Department of Orthopedic Surgery, Rush Medical College, Rush University in Chicago. McGregor M. The social dilemma of chiropractic factions: their role and impact. 15 Sep 10; Crans-Montana, Switzerland: ChiroSuisse Continuing Education Convention, Integrated Health Care. McGregor M. Research using the simulation laboratory. 15 Sep 10; Crans-Montana, Switzerland: ChiroSuisse Continuing Education Convention, Integrated Health Care. Triano JJ. Mechanobiology – underpinnings that inform practice. 15 Sep 10; Crans-Montana, Switzerland: ChiroSuisse Continuing Education Convention, Integrated Health Care.

Engell S, Triano JJ. Paraspinal Soft-Tissue Layer Differential Movement from Spinal Manipulative Therapy (SMT) Preload Forces. 15 Sep 20; Washington, DC: Fourth International Fascia Research Congress, Basic Science Implications for Conventional and Complementary Health Care. Chung C, Bain L, Kopansky-Giles D, Peranson J. Lessons from the development and implementation of an interprofessional education (IPE) program on the collaborative management of low back pain. 15 Sep 29; Roanoke, VA: Collaborating Across Borders V. La Delfa NJ, Grondin DE, Cox J, Potvin JR, Howarth SJ. Physical demands of manual scaling on the shoulders & neck of dental hygienists. 15 Oct 6; Waterloo, ON: 46th Annual Conference of the Association of Canadian Ergonomists. Kopansky-Giles D, Chehade M. Reforming health professionals’ education and training on musculoskeletal conditions. The role of the Education Task Force. 15 Oct 8; Oslo, Norway Global Alliance for Musculoskeletal Health (G-Musc) World Summit. Kopansky-Giles D. Making musculoskeletal health a global priority. 15 Oct 8; Oslo, Norway Global Alliance for Musculoskeletal Health (G-Musc) World Summit. Kopansky-Giles D, Chehade M. Integrated models of education to develop a workforce to deliver integrated care. 15 Oct 8; Oslo, Norway: Bone and Joint Decade World Summit and the Norwegian Musculoskeletal Research Network Conference. Hook A. Pleomorphic undifferentiated sarcoma arising within an intramedullary bone infarct.15 Oct 21; Rosemont, IL: ACCR Annual Workshop.

Triano JJ. Managing change: advancing chiropractic in integrated health care. (workshop) 15 Sep 10; Crans-Montana, Switzerland: ChiroSuisse Continuing Education Convention, Integrated Health Care.

Dion S. Soft tissue lipoma. 15 Oct 21; Rosemont, IL: ACCR Annual Workshop.

Bussières A, Maiers M, Grondin D, Brockusen S. Selecting and training opinion leaders: Experience from the Canadian Chiropractic Guideline Initiative. 15 Sep 18; Niagara Falls, ON: CCA National Convention & Tradeshow.

Olesen K, Howard P, Xing S, Leung F-H, Kopansky-Giles D. Health Professional Perspectives Regarding the use of Patient-Reported Outcome Measures in an Integrated Primary Care Health Centre – A Pilot Project. 15 Oct 28; Toronto, ON: Association of Family Health Teams of Ontario (AFHTO) Conference 2015.

David R, Wickes D, Olin G, Kopansky-Giles D, Bussières. Winning the battle for chiropractic in Canada: Where we were, where we are, and where we are going. 15 Sep 18; Niagara Falls, ON: CCA National Convention & Tradeshow.

Kopansky-Giles D, Peranson, J. Humphreys K, Newton C, Greenwood D. Working together to enhance primary care delivery in Canada. 15 Nov 6; Victoria, BC: British Columbia Chiropractic Association Annual Conference.

Kopansky-Giles D, Peranson J. Chiropractic integration into mainstream healthcare – Perspectives from the front line. 15 Sep 18; Niagara Falls, ON: CCA National Convention & Tradeshow. (workshop)

CMCC Research Report 2015–2018

Kopansky-Giles D, Peranson J. Enhancing primary healthcare delivery in the inner city through interprofessional team work. 15 Nov 6; Victoria, BC: British Columbia Chiropractic Association Annual Conference.

Ellul N, Azad A, Gleberzon B. Student perceptions of Force Sensing Table Technology™ integration in the classroom: a controlled cohort study at college x. 16 Mar 16; Orlando, FL: ACC-RAC 2016.

Kopansky-Giles D, Newton C, Eyre A, Balkou S. Teaching and Assessing the Collaborator Role: An interactive workshop with a national focus. 15 Nov 11; Toronto, ON: Family Medicine Forum.

Erwin WM, Matta A, Karim MZ, Zhou S. Soluble Factors Obtained from the Notochordal Cell-Rich Intervertebral Disc Nucleus Pulposus Regenerate the Degenerative Disc: A Pre-Clinical Animal Model proof of Principal Study. 16 Mar 16; Orlando, FL: ACC-RAC 2016.

Kopansky-Giles D, Peranson J. Supporting health professional educators in family medicine teaching. 15 Nov 11; Toronto, ON: Family Medicine Forum. (workshop) Kopansky-Giles D, Newton C. Training health professionals in the collaborator role. 15 Nov 11; Toronto, ON: Family Medicine Forum. (workshop) Peranson J, Kopansky-Giles D, Waters I. Recognizing your Hidden Faculty: Integrating and supporting the role of health professional educators in family medicine. 15 Nov 11; Toronto, ON: Family Medicine Forum. Haldeman S, Nordin M, Outerbridge G, Hurwitz E, Hondras M, Brady O, Kopansky-Giles D, Ford T, Acaroglu E. Delivering sustainable spine care in underserved communities: the World Spine Care Charity. 15 Nov 19; Mexico City, Mexico: 3rd World Congress on Integrated Care. Kopansky-Giles D, Leung F-H, Peranson J, Horner K, Lee K. Enhancing primary healthcare delivery in the inner city through interprofessional teamwork and service innovation. 15 Nov 19; Mexico City, Mexico: 3rd World Congress on Integrated Care. Adeboyejo A, Erwin WM, Matta A, Karim MZ, Zhou S. Degenerative disc disease: regenerative effects of stem cell therapy. 16 Mar 16; Orlando, FL: ACC-RAC 2016. Azad A, Ellul N, McGregor M, Gleberzon B. Computerized text analysis of emergent themes from responses to curricular change. 16 Mar 16; Orlando, FL: ACC-RAC 2016. Budgell B, Dafa A, McInnis V. Planning interdisciplinary interventions in low-resource environments using GIS technology. 16 Mar 16; Orlando, FL: ACC-RAC 2016. Budgell B, Sovak G. TENS inhibits inflammatory cytokine synthesis in neuronal cell cultures. 16 Mar 16; Orlando, FL: ACC-RAC 2016. Cramer G, Bora P, Ross JK, Selby S. Assessing sound and vibration from zygapophyseal joints during motion and spinal manipulation: a feasibility study. 16 Mar 16; Orlando, FL: ACC-RAC 2016.

Gleberzon B, Roecker C, Blum C, Cooperstein R, Good C. Toward the development of a standardized chiropractic technique program. 16 Mar 16; Orlando, FL: ACC-RAC 2016. (workshop) Gleberzon B, Yeganeh S, Aghigh I, Babin J, Ashhadi F, Bachar C. Use of chiropractic terminology and perception of chiropractic’s identity: A survey of chiropractic students and faculty at college x. 16 Mar 16; Orlando, FL: ACC-RAC 2016. Howarth SJ, Bell S, Triano JJ, D’Angelo K, Kawchuk G. Procedure selection and patient positioning influence spine kinematics during high-velocity low-amplitude spinal manipulation applied to the low back. 16 Mar 16; Orlando, FL: ACC-RAC 2016. Howarth SJ, D’Angelo K, Triano JJ, Bell S, Kawchuk G. Comparing biomechanical parameters between two common low back spinal manipulation procedures. 16 Mar 16; Orlando, FL: ACC-RAC 2016. Lester S, Starmer D, Ruhr G, Giuliano D, Stainsby B, Labelle N, Triano JJ. Differences in force development rate of HVLA based on computation method. 16 Mar 16; Orlando, FL: ACC-RAC 2016. Liu D, Engel G, Bentley R, Crawford S, Leung K. The effect of spinal manipulative therapy on paraspinal skin rolling tenderness in the thoracic spine. 16 Mar 16; Orlando, FL: ACC-RAC 2016. McGregor M, Nielsen A, Chung C, Fillery M, Wakeland W, Mior SA. Chiropractic care in a system dynamics model for minimizing opioid abuse for chronic non-malignant pain patients. 16 Mar 16; Orlando, FL: ACC-RAC 2016. Pohlman K, O’Beirne M, Mior SA, Thiel H, Jacobs C, Tibbles A, Funabashai M, Vohra S. Evaluation and comparison of patient safety dimensions and quality improvement items at chiropractic teaching clinics. 16 Mar 16; Orlando, FL: ACC-RAC 2016. Stainsby B, Dulay D, Brown P, Smith WD. The effects of spinal manipulation on vertical jump height: A pilot study. 16 Mar 16; Orlando, FL: ACC-RAC 2016. Stainsby B, Johnston C, Mayberry K, Mahony E, Okrainetz J, Rae B. Conservative care of concussions: A systematic review. 16 Mar 16; Orlando, FL: ACC-RAC 2016.

A selection of published research by CMCC faculty

Starmer D, Lester S, Labelle N, Ruhr G, Giuliano D, Stainsby B, McGregor M. Examining different methods of integrating Force Sensing Table Technology™ into the classroom – Qualitative Analysis. 16 Mar 16; Orlando, FL: ACC-RAC 2016. Tavares P, Landsman V, Gomez N, Ferreiras Martinez A, Lopez R. Association of venous leg ulcers with ankle range of motion in a socioeconomically disadvantaged population attending chiropractic mobile clinics in the Dominican Republic. 16 Mar 16; Orlando, FL: ACC-RAC 2016. Tavares P, Landsman V, Wiltshire L. Intra-examiner reliability of measurements of ankle range of motion using a modified inclinometer: a pilot study. 16 Mar 16; Orlando, FL: ACC-RAC 2016. (poster) Weis CA, Batley S, Corso M, Ho S, Wishloff K, Landsman V, Tavares P, Barrett J. Prevalence of low back pain, pelvic girdle pain and combination pain in a postpartum Canadian population. 16 Mar 16; Orlando, FL: ACC-RAC 2016. (poster) Weis CA, Ngo K, Huynh T, Draper C, Landsman V, Tavares P, Leung J, Barrett J. Prevalence of low back pain, pelvic girdle pain and combination pain in a pregnant Canadian population. 16 Mar 16; Orlando, FL: ACC-RAC 2016. (poster) Bakaa N, Erwin WM, Karim MZ, Grundy K. A journey into the spinal cord: a regenerative stem cell therapy for ALS. 16 Mar 16; Orlando, FL: ACC-RAC 2016. (poster) Beliveau P, Wong JJ, Simon N, Bussières A, Mior SA, French S. Utilization of chiropractic services, reasons for seeking care, patient profiles, and treatment provided: a scoping review. 16 Mar 16; Orlando, FL: ACC-RAC 2016. (poster) Chow A, Teodorczyk-Injeyan J, Injeyan HS. The effect of spinal manipulative therapy (SMT) on the production of Interleukin-6 (IL6) in patients with low back pain. 16 Mar 16; Orlando, FL: ACC-RAC 2016. (poster) Mior SA, Wong JJ, Sutton D, Beliveau P, Bussières A, French S. Ontario Chiropractic Observation and Analysis Study (O-COAST): improving quality of care through better understanding of current chiropractic practice. 16 Mar 16; Orlando, FL: ACC-RAC 2016. (poster)

Kinsinger S, McAulay B. Facilitating professional identity formation. 16 Mar 16; Orlando, FL: ACC-RAC 2016. (workshop) Pohlman K, Tibbles A, Jacobs C, Bodnar P, Funabashi M. Quality improvement and patient safety: Where to start? 16 Mar 16; Orlando, FL: ACC-RAC 2016. (workshop) Newton C, Walczac A, Oandasan I, Balkou S, Silveira J, KopanskyGiles D, Eyre A, Magee T. Teaching and Assessing the Collaborator Role in Family Medicine Residency Training Programs. 16 Apr 16; Montreal, QC: Canadian Conference on Medical Education. Newton C, Kopansky-Giles D, Eyre A, Balkou S. Teaching and assessing the collaborator role in family medicine residency training programs - a state of the nation. 16 Apr 18; Montreal, QC: Canadian Conference on Medical Education. Leverman M, Letovsky S, Peranson J, Kopansky-Giles D. Statusonly Faculty Appointments Process for Health Professional Educators. 16 Apr 21; Toronto, ON: University of Toronto, Department of Family and Community Medicine Annual Conference. (workshop) Haldeman S, Nordin M, Outerbridge G, Kopansky-Giles D, Vlok I, Setlhare V. Interdisciplinary management of non-surgical spine pain patients. 16 Apr 22; Mahalpye, Botswana: 2nd International Spine Care Conference. Haldeman S, Kopansky-Giles D, Nordin M, Vlok I, Mmopelwa T. Interdisciplinary management of surgical spine pain patients. 16 Apr 22; Mahalpye, Botswana: 2nd International Spine Care Conference. Kopansky-Giles D. People-centred and integrated spine care delivery – a new paradigm for the 21st century. 16 Apr 22; Mahalpye, Botswana: 2nd International Spine Care Conference. Outerbridge G, Ford T, Brady O, Hondras M, Haldeman S, Kopansky-Giles D, Nordin M. Development of an outcomes questionnaire for low literacy patients in underserved populations. The World Spine Care (WSC) Charity. 16 May 17; Singapore: International Society for the Study of the Lumbar Spine. (eposter)

Murray A, Wiesner D, Dunlop B, Bell E, Starmer D. The effects of chiropractic care on horses: a literature synthesis. 16 Mar 16; Orlando, FL: ACC-RAC 2016. (poster)

Langins M, Kopansky-Giles D, Johnstone R, Bradbury E, Lawrence T, Borgermans L. Strengthening a competent health workforce for the provision of coordinated/integrated health services. 16 May 25; Barcelona, Spain: International Conference on Integrated Care.

Pohlman K, O’Beirne M, Thiel H, Mior SA, Tibbles A, Jacobs C, Funabashai M, Vohra S. Evaluation of barriers to implementing patient safety reporting and learning systems at two chiropractic teaching clinics. 16 Mar 16; Orlando, FL: ACC-RAC 2016. (poster)

Menta R, Beach T, Robb A, Howarth S. Relating lead hip internal rotation during the golf swing to passive capacity for joint movement. 16 May 31; Boston, MA: 63rd Annual Meeting of the American College of Sports Medicine.

CMCC Research Report 2015–2018

Conference Proceedings 2016 – 2017 Academic Year Fewster KM, Gallagher KM, Howarth SJ, Callaghan JP. Changes in centre of pressure regularity following prolonged standing. 16 Jul 19; Hamilton, ON: 19th Conference and Symposia of the Canadian Society for Biomechanics. Zabihhoseinian M, Holmes M, Howarth S, Ferguson B, Murphy B. Impact of neck muscle fatigue on scapulohumeral kinematics in subclinical neck pain vs asymptomatic controls. 16 Jul 5; Chicago, IL: 21st International Society of Electrophysiology and Kinesiology Congress.

Peranson J, Kopansky-Giles D, Ghavam-Rassoul A, Slater M. Teaching Teams to Teach: program evaluation results from an interprofessional faculty development program in academic Family Medicine. 16 Oct 17; Toronto, ON: Association of Family Health Teams of Ontario (AFHTO) Conference. Haldeman S, Nordin M, Kopansky-Giles D, Hurwitz E. The Development and Implementation of an Evidence-Based Model of Care for Spinal Disorders: Proceedings of the Global Spine Care Initiative. 16 October 26; Boston, MA: North American Spine Society (NASS) Annual Meeting.

Beaudette SM, Howarth SJ, Graham RB, Brown SH. Factors to consider when using the Euclidean norm of 3D kinematic data for time-delayed Lyapunov analysis. 16 Jul 19; Hamilton, ON: 19th Conference and Symposia of the Canadian Society for Biomechanics.

Kopansky-Giles D, Newton C, Balkou S, Eyre A. A ‘How-to-Guide’ for Teaching and Assessing the Collaborator Role Competencies in Family Medicine Residency Training. 16 Nov 9; Vancouver, BC: Family Medicine Forum. (workshop)

McGregor M, Fillery M, Chung C. Utilizing the Beer Game to Rethink the Organization of Interdisciplinary Research. 17 Jul 17; Delft, Netherlands: 34th International System Dynamics Society Conference.

Peranson J, Kopansky-Giles D, Waters I. Health Professional Educator (HPE) Faculty Leads: Role Implementation, Early Impact and Future Directions. 16 Nov 9; Vancouver, BC: Family Medicine Forum. (poster)

McGregor M, Neilsen A, Chung C, Fillery M, Wakeland W, Mior S. A System Dynamics Model of Opioid Use for Chronic Non-Malignant Pain Incorporating Complementary and Alternative Care. 17 Jul 17; Delft, Netherlands: 34th International System Dynamics Society Conference.

Hawk C, Schneider M, Haas M, Dougherty P, Killinger L, Gleberzon BJ. Update of consensus “best practices” for chiropractic care for older adults. 16 Nov; Denver, CO: American Public Health Association.

Kopansky-Giles D, Newton C. An Interprofessional How-To Guide for Teaching and Assessing the Collaborator Role competencies in Family Medicine Residency Training. 16 Sep 6; Oxford, England: All Together Better Health VIII. (workshop) Kopansky-Giles D, Skiffington A, Beavers L, Dewhurst N, Whelan L, Leung FH, Newbold E, Porretta K. Development, evaluation and implementation of an Interprofessional Collaboration Competency Framework – Experiences from an Inner City Teaching Hospital. 16 Sep 6; Oxford, England: All Together Better Health VIII. (poster) Kopansky-Giles D, Peranson J, Waters I. Recognizing your Hidden Faculty: Integrating and Supporting the Role of Health Professional Educators in Family Medicine. 16 Sep 6; Oxford, England: All Together Better Health VIII. (poster) Kopansky-Giles D. Person-centred integrated care - current models. 16 Sep 27; Shanghai, China: Asia Pacific League of Associations for Rheumatology Congress.

Kazemi M, Vora K, Bogumil M. Concussion knowledge among sport chiropractors. 17 Mar 15; Washington, DC: FICS Assembly and Symposium. Beliveau P, McIsaac M, Mior S, French S. Do chiropractors undertake weight management interventions? 17 Mar 15; Washington, DC: DC2017. Matta A, Karim MZ, Isenman D, Erwin WM. Regeneration of the intervertebral disc: evidence using a defined molecular approach based upon the notochordal cell secretome. 17 Mar 15; Washington, DC: DC2017. Chow N, Southerst D, Kopansky-Giles D, Ammendolia C. Clinical outcomes in neurogenic claudication using a multimodal program for lumbar spinal stenosis: a long-term follow-up study. 17 Mar 15; Washington, DC: DC2017. Ammendolia C, Côté P, Rampersaud YR, Southerst D, Budgell B, Bombardier C, Hawker G. Boot camp programs for spinal stenosis: a randomized controlled clinical trial comparing outcomes following a comprehensive versus a self-directed non-surgical approach. 17 Mar 15; Washington, DC: DC2017.

A selection of published research by CMCC faculty

Engell S, Howarth S, Triano JJ. Neck loading during thoracic high-velocity low amplitude (HVLA) manipulation: an investigation of regional interdependence. 17 Mar 15; Washington, DC: DC2017. Lester S, Starmer D, Barbaro L, Fraser B, Landry J, Stock K. The effect of a training program on speed development for students delivering prone thoracic manipulations. 17 Mar 15; Washington, DC: DC2017. Cramer G, Budavitch M, Bora P, Ross JK. Zygapophyseal (Z) joint crepitus before and after spinal manipulation: a pilot study. 17 Mar 15; Washington, DC: DC2017. Tavares P, Azad A, Ellul N. Success without compromise: building a dream practice. 17 Mar 15; Washington, DC: DC2017. Gold P. Cranio-cervical dysfunction as a cause of trigeminal impingement: a case report. 17 Mar 15; Washington, DC: DC2017. Ammendolia C, Schneider M, Williams K, Zickmund S, Hamm M, Stuber K, Tomkins-Lane C, Rampersaud R. The physical and mental impact of neurogenic claudication: the patient’s perspective. 17 Mar 15; Washington, DC: DC2017. da Silva-Oolup S, Nordin M, Côté P, Stern P, Outerbridge G. A case series of patients with musculoskeletal conditions presenting to a World Spine Care clinic in Moca, Dominican Republic. 17 Mar 15; Washington, DC: DC2017. Mastragostino P, Lee AD, Battaglia P. Perianal abscess mimicking levator ani syndrome: a case report and approach to the differential diagnosis of anorectal pain. 17 Mar 15; Washington, DC: DC2017. Stainsby B, Quattrocchi L, Turner C, Yaworski J. Chiropractic utilization of exercise in the treatment plan: a cross-sectional study. 17 Mar 15; Washington, DC: DC2017. Vernon H, Crawford J, Ercolao L. A controlled study of cervical dysfunction in concussion vs. whiplash patients. 17 Mar 15; Washington, DC: DC2017. Weis CA, Barrett J, Bauer S, Huang A, Stewart C, Well C, Hillier J, Draper C. Multifidus and abdominal muscle thickness in women immediately following pregnancy: a pilot study. 17 Mar 15; Washington, DC: DC2017. Lemeunier, Shearer H, Wong JJ. Diagnosing neck pain: which tests provide useful information? 17 Mar 15; Washington, DC: DC2017. Killinger L, Gleberzon B. Clinical considerations in the care of seniors. 17 Mar 15; Washington, DC: DC2017.

Kinsinger S. A clinician’s approach to doctor-patient boundaries. 17 Mar 15; Washington, DC: DC2017. Kopansky-Giles D, Skiffington A, Dewhurst N, Whelan L, Leung FH, Newbold E, Beavers L. Development, evaluation and implementation of an Interprofessional Collaboration Competency Framework – experiences from an inner-city teaching hospital. 17 Mar 15; Washington, DC: DC2017. Ellul N, Starmer D. Student exam performance: lecture versus e-learning. 17 Mar 15; Washington, DC: DC2017. Gleberzon B, Giuliano D. Students’ perception of changes made to the testing of psychomotor (technique) skills during the 2015-16 academic year at the Canadian Memorial Chiropractic College. 17 Mar 15; Washington, DC: DC2017. Gleberzon B, Roecker C, Good C, Blum C, Cooperstein R. Toward a standardized chiropractic technique program: consensus results of two inter-collegiate workshops. 17 Mar 15; Washington, DC: DC2017. Weis CA, Draper C, Stuber K, Hawk C, Pohlman K. Best chiropractic practices for pregnancy and post-partum populations. 17 Mar 15; Washington, DC: DC2017. Hawk C, Schneider M, Haas M, Dougherty P, Gleberzon B, Killinger L, Katz P, Weeks J. Best practices for chiropractic care for older adults: a consensus update. 17 Mar 15; Washington, DC: DC2017. Peranson J, Kopansky-Giles D, Slater M, Ghavam-Rassoul A. Teaching teams to teach: program evaluation results from an interprofessional faculty development program in academic family medicine. 17 Mar 15; Washington, DC: DC2017. Pohlman K, Mior S, Funabashi M, DeCarvalho D, El-Bayoumi M, Haig B, Kelly K, Wade D, O’Beirne M, Vohra S. Patient safety culture evaluation of chiropractors in three Canadian provinces: preliminary findings. 17 Mar 15; Washington, DC: DC2017. Mior S, Wong JJ, Beliveau P, Bussieres A, French S. Profiling chiropractic practices and their patients: Ontario Chiropractic Observation and Analysis Study (O-COAST). 17 Mar 15; Washington, DC: DC2017. Weis CA, Cheung G, Dion L, Garven J, Robinson M, Bennett S, Busse J. Attitudes toward chiropractic: a survey of Ontario midwives. 17 Mar 15; Washington, DC: DC2017. Johnson C, Haldeman S, Kopansky-Giles D, Green B, Outerbridge G. Applying evidence-based spine care in everyday practice: Global Spine Care Initiative (GSCI) clinical care pathway for spinal disorders. 17 Mar 15; Washington, DC: DC2017.

CMCC Research Report 2015–2018

Aartun E, Yu H, Côté P. A scoping review of the literature on functioning and disability in manual medicine using the International Classification of Functioning, Disability and Health (ICF). 17 Mar 15; Washington, DC: DC2017. Coulter I, Vernon H, Hurwitz E, Crawford C, Whitley M, Booth M. Appropriateness of spinal manipulation/mobilization for chronic neck pain patients: a systematic review. 17 Mar 15; Washington, DC: DC2017. Coulter I, Hurwitz E, Vernon H, Crawford C, Khorsan R, Whitley M, Booth M. Appropriateness of spinal manipulation/mobilization for chronic low back pain: systematic review. 17 Mar 15; Washington, DC: DC2017. Funabashi M, Pohlman K, Mior S, Thiel H, Cassidy JD, Westway M, Yager J, Hurwitz E, Kawchuk G, O’Beirne M, Vohra S. Preliminary findings from an active surveillance reporting system among chiropractors. 17 Mar 15; Washington, DC: DC2017. Grondin D. A scoping study of knowledge translation theory and factors influencing research evidence use related to the Canadian chiropractic setting. 17 Mar 15; Washington, DC: DC2017.

Parnell Prevost C, Gleberzon B, Carleo B, Anderson K, Pohlman K. Manual therapy for the pediatric population: a systematic review. 17 Mar 15; Washington, DC: DC2017. Stuber K, Langweiler M, Mior S, McCarthy P. A study of patientcentred care in patients with chronic health conditions attending chiropractic practice: outcome of a pilot of the protocol. 17 Mar 15; Washington, DC: DC2017. Weis CA, Baas E, Ciesla K, Kimpinski C. Ontario chiropractors’ knowledge of exercise guidelines for pregnant populations. 17 Mar 15; Washington, DC: DC2017. Stuber K, Bussieres A, Kawchuk G. Research resources in Canada: taking inventory before setting priorities. 17 Mar 15; Washington, DC: DC2017. Vernon H, Crawford J, Ercalao L. A controlled stuy of the presence of upper cervical dysfunction in concussion and whiplash patients. 17 May 23; Halifax, NS: The Canadian Pain Society Annual Scientific Meeting.

Kazemi M, Vora K, Bogumil M. Concussion knowledge among sport chiropractors. 17 Mar 15; Washington, DC: DC2017. Lee AD, Szabo K, McDowell K, Granger S. Opinions of sports clinical practice chiropractors, with sports specialty training and those without, about chiropractic research priorities in sports health care: a centering resonance analysis. 17 Mar 15; Washington, DC: DC2017.

Conference Proceedings: 2017-2018 Academic Year Wong JJ. Time Trends of the Incidence, Prevalence, and PostDiagnosis Mortality of Parkinsonism. 17 Jun 2; Banff, AB: Canadian Society for Epidemiology and Biostatistics Biennial Conference. Kopansky-Giles D. Teaching teams to teach: program evaluation results from an interprofessional faculty development program in academic family medicine. 17 Jun 9; Toronto, ON: Department of Family and Community Medicine Annual Conference. (poster) Kopansky-Giles D. Recognizing our Hidden Faculty: Integrating and Supporting the Role of Health Professional Educators in Family Medicine. 17 Jun 9; Toronto, ON: Department of Family and Community Medicine Annual Conference. (poster) Kazemi M. Weight Cycling: To Be or Not To Be? 18 Jun 29; Muju, South Korea: 6th International Symposium for Taekwondo Studies.

Kazemi M. Concussion Knowledge among Sport Chiropractors. 18 Jun 29; Muju, South Korea: 6th International Symposium for Taekwondo Studies. Badley E, Canizares M, Perruccio A, Hogg-Johnson S, Gignac M. Cohort effects in disability: Implications for more disability in old age and in recent generations? Innovation in Aging, 17 Jul 23; San Francisco, CA: 21st International Association of Gerontology and Geriatrics (IAGG) World Congress. Harmath D, Howarth SJ, Hogg-Johnson S. Reliability of centre of pressure measurements during standing balance in healthy subjects using sample entropy. 17 Jul 27; San Francisco, CA: 39th World Congress of Chiropractic Students Annual General Meeting. (poster) Smith P, Sim M, LaMontagne A, Lilley R, Hogg-Johnson S. The potential impact of three workplace actions on return to work

A selection of published research by CMCC faculty

after a work-related musculoskeletal or psychological injury. 17 Aug 28; Edinburgh, Scotland: EPICOH the 26th International Epidemiology in Occupational Health Conference - “Eliminating Occupational Disease: Translating Research into Action”.

Newton C, Kopansky-Giles D, Eyre A, Balkou S, Silveira J, Magee T, Walczak A, Oandasan I. A How-to Guide for Teaching and Assessing Collaborator Competencies in Family Medicine. 17 Nov 14; Montreal, QC: Family Medicine Forum. (workshop)

Koehoorn M, Tamburic L, Hogg-Johnson S, Lippel K, McLeod C. Are gender differences in disability duration for work-related musculoskeletal injuries explained by health care utilization? 17 Aug 28; Edinburgh, Scotland: EPICOH the 26th International Epidemiology in Occupational Health Conference - “Eliminating Occupational Disease: Translating Research into Action”.

Gleberzon B, Pohlman K, Russell E. Comparison of chiropractic lexicon at two chiropractic institutions: a cross-sectional study. 18 Mar 8; Dallas, TX: ACC-RAC 2018.

Macpherson R, Koehoorn M, Quirke W, Fan J, Amick B, Mustard C, Hogg-Johnson S, Kraut A, McLeod C. How do gender and jurisdiction interact with work disability duration? 17 Aug 28; Edinburgh, Scotland: EPICOH the 26th International Epidemiology in Occupational Health Conference - “Eliminating Occupational Disease: Translating Research into Action”. Cancelliere C, Sutton D, Côté P, French S, Mior SA. A scoping review of implementation strategies and outcomes of programs of care for the management of musculoskeletal disorders in the active military. 17 Sep 25; Toronto, ON: Canadian Institute of Military and Veteran Research (CIMVHR) 8th Annual Military and Veteran Health Research Forum. (poster) Mior SA, Vogel E, Sutton D, French S, Côté P, Nordin M, Loisel P, Laporte A. Exploring Chiropractic Services in the Canadian Forces Health Services—Opportunities and Challenges. 17 Sep 25; Toronto, ON: Canadian Institute of Military and Veteran Research (CIMVHR) 8th Annual Military and Veteran Health Research Forum. (poster) To D. Common Condition, Uncommon Location. 17 Oct 11; Minneapolis, MI: American Chiropractic College of Radiology Annual Resident Day and Workshop. Kumar V. ACCR Workshop Exchange Case 2017: A Cervical Confusion. 17 Oct 11; Minneapolis, MI: American Chiropractic College of Radiology Annual Resident Day and Workshop. Kinsinger S, Dubois J. Comparing four professions’ prevalence of patient sexual abuse. 17 Oct 21; Kansas City, MO: American Society for Bioethics and Humanities. Howitt S, Mercer A, Simpson K, Suderman D, Rutherford S, deGraauw C. Exercise as a vital sign: A preliminary study in a chiropractic setting. 17 Oct 25; Winnipeg, MA: Canadian Society for Exercise Physiology Conference. Alleyne J, Kopansky-Giles D, Peranson J. Spine Tools: An interprofessional approach to managing back and neck pain. 17 Nov 14; Montreal, QC: Family Medicine Forum. (workshop)

Ciolfi M, Azad A, Al-Azdee M. Perceptions of Ontario Chiropractors on Business Education in Chiropractic Schools. 18 Mar 8; Dallas, TX: ACC-RAC 2018. Bussières A, Stewart G, Al Zoubi F, Decina P, Descarreaux M, Haskett D, Hincapie C, Page I, Passmore S, Srbely J, Stupar M, Weisberg J, Ornelas J. Spinal manipulative therapy for the management of low back pain: A guideline from the Canadian Chiropractic Guideline Initiative. 18 Mar 8; Dallas, TX: ACC-RAC 2018. Kinsinger S. Doctor-patient boundary crossing.18 Mar 8; Dallas, TX: ACC-RAC 2018. Osterbauer P, Lester S, Starmer D. Force sensing feedback decreased force variability after a coaching session during simulated, prone, thoracic adjustments on a manikin. 18 Mar 8; Dallas, TX: ACC-RAC 2018. Pohlman K, Stuber K, Abbas A, Morales V, Mior S. Assessment of Student Attitudes toward Patient Centered Care at a Chiropractic College. 18 Mar 8; Dallas, TX: ACC-RAC 2018. Wang S, Starmer D, Hammerich K. Restructuring a Chiropractic Principles and Practice Course. 18 Mar 8; Dallas, TX: ACC-RAC 2018. Weis CA, Pohlman K, da Silva-Oolup S, Draper C, Stuber K, Murnaghan K, Hawk C. Chiropractic care for pregnancy and postpartum: a systematic review. 18 Mar 8; Dallas, TX: ACC-RAC 2018. Carleo B, Prevost C, Gleberzon B, Anderson K, Pohlman K. Patient-centered outcomes utilized in clinical pediatric manual therapy research studies. 18 Mar 8; Dallas, TX: ACC-RAC 2018. (poster) Colacino L, Martins R, McAleese J, Greenwood J, Starmer D, Wang S. Effects of high and low-power poses on maximal force production during a prone Carver thoracic adjustment performed on a mannequin atop Force Sensing Table Technology™. 18 Mar 8; Dallas, TX: ACC-RAC 2018. (poster) da Silva-Oolup S, O’Shaughnessy J. A case report of osteomyelitis secondary to Kingella kingae in a 17-month old. 18 Mar 8; Dallas, TX: ACC-RAC 2018. (poster)

CMCC Research Report 2015–2018

Kang R, Lau T, Cho JH, Ayoola-amale O, Khayyam H, Starmer D. Trends in the utilization of force sensing technology outside of the curriculum in open practice hours. 18 Mar 8; Dallas, TX: ACC-RAC 2018. (poster)

Stuber K, Thistle S. Research Symposium: Integrating Evidence – Chiropractic in Modern Healthcare. 18 Apr 27; Calgary, AB: Canadian Chiropractic Association National Convention and Tradeshow.

Mior S, Vogel E, French S, Nordin M, Loisel P, Laporte A, Sutton D. Exploring Chiropractic Services in the Canadian Forces Health Services—Opportunities and Challenges. 18 Mar 8; Dallas, TX: ACC-RAC 2018. (poster)

Kopansky-Giles D, McMorland G, Merepeza A, Newton C. Integrative Care in Pain Management, A Team Game. 18 Apr 27; Calgary, AB: Canadian Chiropractic Association National Convention and Tradeshow.

Shipka P, Gushaty B, Teitelbaum A, Semeniuk P. Utilization of acupuncture for the management of neuropathy related to Frieberg’s Disease: a case study. 18 Mar 8; Dallas, TX: ACC-RAC 2018. (poster)

Howitt S, Konczak C, McMorland G, Tibbles A. Grand Rounds Discussions: Chronic/Complex Musculoskeletal Pain. 18 Apr 27; Calgary, AB: Canadian Chiropractic Association National Convention and Tradeshow.

Perle S, Stuber K, Budgell B. Improving Scientific Writing by Becoming a Better Peer-Reviewer. 18 Mar 8; Dallas, TX: ACC-RAC 2018. (workshop) Dunham S, Russell E, Lawrence D. Enhanced Teacher Education through implementation of hybrid/online Faculty Development workshops. 18 Mar 8; Dallas, TX: ACC-RAC 2018. (workshop) Gleberzon B, Roecker C, Blum C, Good C, Cooperstein R. Toward the Development of a Standardized Chiropractic Technique Program. 18 Mar 8; Dallas, TX: ACC-RAC 2018. (workshop) Hollandsworth D, Russell E, Lester S, Osterbauer P, Wilson J. The Force Within You: Using Force-Time Profiles in Chiropractic Education. 18 Mar 8; Dallas, TX: ACC-RAC 2018. (workshop) Lester S, Good C, Hollandsworth D, Grande S, Osterbauer P. Low Tech Strategies to Enhance Spinal Manipulation Performance. 18 Mar 8; Dallas, TX: ACC-RAC 2018. (workshop) Kinsinger S, McAulay B. Professional Identity Formation: Values of Professionalism. 18 Mar 8; Dallas, TX: ACC-RAC 2018. (workshop) Mior SA. Advancing Patient Safety Research through Collaborations. 18 Mar 8; Dallas, TX: ACC-RAC 2018. Corr B. Chiropractic Radiography - Essential Expectations. 18 Apr 12; Port of Spain, Trinidad and Tobago: ISRRT 20th World Congress. Azad A, Forrester R, Holman R, MacAdam K, Wright D. Women Chiropractors – A Growing Force. 18 Apr 27; Calgary, AB: Canadian Chiropractic Association National Convention and Tradeshow. Blanchette MA, Mior SA, Stuber K, Thistle S. Measuring Chiropractic’s Status – A Delphi Project. 18 Apr 27; Calgary, AB: Canadian Chiropractic Association National Convention and Tradeshow.

Kopansky-Giles D, McMorland G, Newton C. Delivering Integrated Care – A Skills Building Workshop on Interprofessional Collaboration. 18 Apr 27; Calgary, AB: Canadian Chiropractic Association National Convention and Tradeshow. (workshop) Fowles J, Howitt S. Exercise is Medicine in Clinical Care. 18 Apr 27; Calgary, AB: Canadian Chiropractic Association National Convention and Tradeshow. (workshop) Mior S, Stuber K. The Patient-Centred Tool Kit for Chiropractors. 18 Apr 27; Calgary, AB: Canadian Chiropractic Association National Convention and Tradeshow. (workshop) Young J. Evaluation of the construct validity of the Questionnaire to Identify Knee Symptoms among individuals across Canada with chronic knee pain. 18 Apr 27; Calgary, AB: Canadian Chiropractic Association National Convention and Tradeshow. (poster) Batley S. The Association between Psychological and Social Factors and Spinal Pain in a Population of 1300 Danish Adolescents Aged 11-13. 18 Apr 27; Calgary, AB: Canadian Chiropractic Association National Convention and Tradeshow. (poster) Carnide N, Hogg-Johnson S, Furlan AD, Côté P, Koehoorn M. The relationship between early prescription dispensing patterns and work disability in a cohort of low back pain workers’ compensation claimants. 18 Apr 29; Dublin, Ireland: 32nd International Congress on Occupational Health (ICOH 2018). Funabashi M, Pohlman KA, Mior SA, Thiel H, Hill MD, Cassidy JD, Westaway M, Yager J, Hurwitz E, Kawchuk G, O’Beirne M, Vohra S. Preliminary findings from an active surveillance reporting system for spinal manipulative therapy regulated providers and low back pain patients. 18 May 14; Banff, AB: The International Society for the Study of the Lumbar Spine 45th annual Meeting.

The CMCC Research Report 2015-2018 is produced by the Division of Marketing and Communications. AVP. Institutional Advancement + Communications: Mara Bartolucci Copyeditor: Margaret McCallen Designer: Liberty Farhoud Contributors: Mark Fillery, Margaret McCallen To request a copy, contact the Division of Marketing and Communications at: Phone: 416 482 2340 Fax: 416 482 3629 Email: communications@cmcc.ca Canadian Memorial Chiropractic College 6100 Leslie Street, Toronto, ON, M2H 3J1 www.cmcc.ca Copyright 2019 Canadian Memorial Chiropractic College

Canadian Memorial Chiropractic College 6100 Leslie Street, Toronto, Ontario M2H 3J1 Telephone: 416 482 2340 www.cmcc.ca