Temporal cell fate determination in the spinal cord is mediated by the duration of Notch signalling.

During neural development, progenitor cells generate different types of neurons in specific time windows. Despite the characterisation of many of the transcription factor networks involved in these differentiation events, the mechanism behind their temporal regulation is poorly understood. To address this question, we studied the temporal differentiation of the simple lateral floor plate (LFP) domain in the zebrafish spinal cord. LFP progenitors generate both early-born Kolmer-Agduhr" (KA") interneuron and late-born V3 interneuron populations. Analysis using a Notch signalling reporter demonstrates that these cell populations have distinct Notch signalling profiles. Not only do V3 progenitors receive higher total levels of Notch response, but they collect this response over a longer duration compared to KA" progenitors. To test whether the duration of Notch signalling determines the temporal cell fate specification, we combined a transgene that constitutively activates Notch signalling in the ventral spinal cord with a heat shock inducible Notch signalling terminator to switch off Notch response at any given time. Sustained Notch signalling results in expanded LFP progenitors while KA" and V3 interneurons fail to specify. Early termination of Notch signalling leads to exclusively KA" cell fate, despite the high level of Notch signalling, whereas late attenuation of Notch signalling drives only V3 cell fate. This suggests that the duration of Notch signalling, not simply the level, mediates cell fate specification. Interestingly, knockdown experiments reveal a role for the Notch ligand Jag2b in maintaining LFP progenitors and limiting their differentiation into KA" and V3 interneurons. Our results indicate that Notch signalling is required for neural progenitor maintenance while a specific attenuation timetable defines the fate of the postmitotic progeny.

Complex crosstalk of Notch and Hedgehog signalling during the development of the central nervous system.

The development of the vertebrate central nervous system (CNS) is tightly regulated by many highly conserved cell signalling pathways. These pathways ensure that differentiation and migration events occur in a specific and spatiotemporally restricted manner. Two of these pathways, Notch and Hedgehog (Hh) signalling, have been shown to form a complex web of interaction throughout different stages of CNS development. Strikingly, some processes employ Notch signalling to regulate Hh response, while others utilise Hh signalling to modulate Notch response. Notch signalling functions upstream of Hh response through controlling the trafficking of integral pathway components as well as through modulating protein levels and transcription of downstream transcriptional factors. In contrast, Hh signalling regulates Notch response by either indirectly controlling expression of key Notch ligands and regulatory proteins or directly through transcriptional control of canonical Notch target genes. Here, we review these interactions and demonstrate the level of interconnectivity between the pathways, highlighting context-dependent modes of crosstalk. Since many other developmental signalling pathways are active in these tissues, it is likely that the interplay between Notch and Hh signalling is not only an example of signalling crosstalk but also functions as a component of a wider, multi-pathway signalling network.

Intra- and inter-rater reliability of an electronic health record audit used in a chiropractic teaching clinic system: an observational study.

BACKGROUND: There is a dearth of information about health education clinical file audits in the context of completeness of records and demonstrating program-wide competency achievement. We report on the reliability of an audit instrument used for electronic health record (EHR) audits in the clinics of a chiropractic college in Canada. METHODS: The instrument is a checklist built within an electronic software application designed to pull data automatically from the EHR. It consists of a combination of 61 objective (n = 20) and subjective (n = 41) elements, representing domains of standards of practice, accreditation and in-house educational standards. Trained auditors provide responses to the elements and the software yields scores indicating the quality of clinical record per file. A convenience sample of 24 files, drawn randomly from the roster of 22 clinicians, were divided into three groups of eight to be completed by one of three auditors in the span of 1 week, at the end of which they were transferred to another auditor. There were four audit cycles; audits from cycles 1 and 4 were used to assess intra-rater (test-retest) reliability and audits from cycles 1, 2 and 3 were used to assess inter-rater reliability. Percent agreement (PA) and Kappa statistics (K) were used as outcomes. Scatter plots and intraclass correlation (ICC) coefficients were used to assess standards of practice, accreditation, and overall audit scores. RESULTS: Across all 3 auditors test-retest reliability for objective items was PA 89% and K 0.75, and for subjective items PA 82% and K 0.63. In contrast, inter-rater reliability was moderate at PA 82% and K 0.59, and PA 70% and K 0.44 for objective and subjective items, respectively. Element analysis indicated a wide range of PA and K values inter-rater reliability of many elements being rated as poor. ICC coefficient calculations indicated moderate reliability for the domains of standards of practice, accreditation, and overall file scores. CONCLUSION: The file audit process has substantial test-retest reliability and moderate inter-rater reliability. Recommendations are made to improve reliability outcomes. These include modifying the audit checklist with a view of improving clarity of elements, and enhancing uniformity of auditor responses by increased training aided by preparation of an audit guidebook.

Stereotypic generation of axial tenocytes from bipartite sclerotome domains in zebrafish.

Development of a functional musculoskeletal system requires coordinated generation of muscles, bones, and tendons. However, how axial tendon cells (tenocytes) are generated during embryo development is still poorly understood. Here, we show that axial tenocytes arise from the sclerotome in zebrafish. In contrast to mouse and chick, the zebrafish sclerotome consists of two separate domains: a ventral domain and a previously undescribed dorsal domain. While dispensable for sclerotome induction, Hedgehog (Hh) signaling is required for the migration and maintenance of sclerotome derived cells. Axial tenocytes are located along the myotendinous junction (MTJ), extending long cellular processes into the intersomitic space. Using time-lapse imaging, we show that both sclerotome domains contribute to tenocytes in a dynamic and stereotypic manner. Tenocytes along a given MTJ always arise from the sclerotome of the adjacent anterior somite. Inhibition of Hh signaling results in loss of tenocytes and enhanced sensitivity to muscle detachment. Together, our work shows that axial tenocytes in zebrafish originate from the sclerotome and are essential for maintaining muscle integrity.

Promoting the use of self-management in novice chiropractors treating individuals with spine pain: the design of a theory-based knowledge translation intervention.

BACKGROUND: Clinical practice guidelines generally recommend clinicians use self-management support (SMS) when managing patients with spine pain. However, even within the educational setting, the implementation of SMS remains suboptimal. The objectives of this study were to 1) estimate the organizational readiness for change toward using SMS at the Canadian Memorial Chiropractic College (CMCC), Toronto, Ontario from the perspective of directors and deans, 2) estimate the attitudes and self-reported behaviours towards using evidence-based practice (EBP), and beliefs about pain management among supervisory clinicians and chiropractic interns, 3) identify potential barriers and enablers to using SMS, and 4) design a theory-based tailored Knowledge Translation (KT) intervention to increase the use of SMS. METHODS: Mixed method design. We administered three self-administered questionnaires to assess clinicians' and interns' attitudes and behaviours toward EBP, beliefs about pain management, and practice style. In addition, we conducted 3 focus groups with clinicians and interns based on the Theoretical Domain Framework (TDF) to explore their beliefs about using SMS for patients with spine pain. Data were analysed using deductive thematic analysis by 2 independent assessors. A panel of 7 experts mapped behaviour change techniques to key barriers identified informing the design of a KT intervention. RESULTS: Participants showed high level of EBP knowledge, positive attitude of EBP, and moderate frequency of EBP use. A number of barrier factors were identified from clinicians (N = 6) and interns (N = 16) corresponding to 7 TDF domains: Knowledge; Skills; Environmental context and resources; Emotion; Beliefs about Capabilities; Memory, attention & decision making; and Social Influence. To address these barriers, the expert panel proposed a multifaceted KT intervention composed of a webinar and online educational module on a SMS guided by the Brief Action Planning, clinical vignettes, training workshop, and opinion leader support. CONCLUSION: SMS strategies can help maximizing the health care services for patients with spine pain. This may in turn optimize patients' health. The proposed theory-based KT intervention may facilitate the implementation of SMS among clinicians and interns.

Musculoskeletal Injury in Professional Dancers: Prevalence and Associated Factors: An International Cross-Sectional Study.

OBJECTIVE: The purpose of the study was to determine the prevalence and factors associated with injury in professional ballet and modern dancers, and assess if dancers are reporting their injuries and explore reasons for not reporting injuries. DESIGN: Cross-sectional study. SETTING: Participants were recruited from nine professional ballet and modern dance companies in Canada, Denmark, Israel, and Sweden. PARTICIPANTS: Professional ballet and modern dancers. INDEPENDENT VARIABLES: Sociodemographic variables included age, sex, height, weight, and before-tax yearly or monthly income. Dance specific characteristics included number of years in present dance company, number of years dancing professionally, number of years dancing total, and rank in the company. MAIN OUTCOME MEASURES: Self-reported injury and Self-Estimated Functional Inability because of Pain. RESULTS: A total of 260 dancers participated in the study with an overall response rate of 81%. The point prevalence of self-reported injury in professional ballet and modern dancers was 54.8% (95% CI, 47.7-62.1) and 46.3% (95% CI, 35.5-57.1), respectively. Number of years dancing professionally (OR = 4.4, 95% CI, 1.6-12.3) and rank (OR = 2.4, 95% CI, 1.2-4.8) were associated with injury in ballet dancers. More than 15% of all injured dancers had not reported their injury and their reasons for not reporting injury varied. CONCLUSIONS: The prevalence of injury is high in professional dancers with a significant percentage not reporting their injuries for a variety of reasons. Number of years dancing and rank are associated with injury in professional ballet dancers.

Are non-invasive interventions effective for the management of headaches associated with neck pain? An update of the Bone and Joint Decade Task Force on Neck Pain and Its Associated Disorders by the Ontario Protocol for Traffic Injury Management (OPTIMa) Collaboration.

PURPOSE: To update findings of the 2000-2010 Bone and Joint Decade Task Force on Neck Pain and its Associated Disorders and evaluate the effectiveness of non-invasive and non-pharmacological interventions for the management of patients with headaches associated with neck pain (i.e., tension-type, cervicogenic, or whiplash-related headaches). METHODS: We searched five databases from 1990 to 2015 for randomized controlled trials (RCTs), cohort studies, and case-control studies comparing non-invasive interventions with other interventions, placebo/sham, or no interventions. Random pairs of independent reviewers critically appraised eligible studies using the Scottish Intercollegiate Guidelines Network criteria to determine scientific admissibility. Studies with a low risk of bias were synthesized following best evidence synthesis principles. RESULTS: We screened 17,236 citations, 15 studies were relevant, and 10 had a low risk of bias. The evidence suggests that episodic tension-type headaches should be managed with low load endurance craniocervical and cervicoscapular exercises. Patients with chronic tension-type headaches may also benefit from low load endurance craniocervical and cervicoscapular exercises; relaxation training with stress coping therapy; or multimodal care that includes spinal mobilization, craniocervical exercises, and postural correction. For cervicogenic headaches, low load endurance craniocervical and cervicoscapular exercises; or manual therapy (manipulation with or without mobilization) to the cervical and thoracic spine may also be helpful. CONCLUSIONS: The management of headaches associated with neck pain should include exercise. Patients who suffer from chronic tension-type headaches may also benefit from relaxation training with stress coping therapy or multimodal care. Patients with cervicogenic headache may also benefit from a course of manual therapy.

Management of neck pain and associated disorders: A clinical practice guideline from the Ontario Protocol for Traffic Injury Management (OPTIMa) Collaboration.

PURPOSE: To develop an evidence-based guideline for the management of grades I-III neck pain and associated disorders (NAD). METHODS: This guideline is based on recent systematic reviews of high-quality studies. A multidisciplinary expert panel considered the evidence of effectiveness, safety, cost-effectiveness, societal and ethical values, and patient experiences (obtained from qualitative research) when formulating recommendations. Target audience includes clinicians; target population is adults with grades I-III NAD <6 months duration. RECOMMENDATION 1: Clinicians should rule out major structural or other pathologies as the cause of NAD. Once major pathology has been ruled out, clinicians should classify NAD as grade I, II, or III. RECOMMENDATION 2: Clinicians should assess prognostic factors for delayed recovery from NAD. RECOMMENDATION 3: Clinicians should educate and reassure patients about the benign and self-limited nature of the typical course of NAD grades I-III and the importance of maintaining activity and movement. Patients with worsening symptoms and those who develop new physical or psychological symptoms should be referred to a physician for further evaluation at any time during their care. RECOMMENDATION 4: For NAD grades I-II ≤3 months duration, clinicians may consider structured patient education in combination with: range of motion exercise, multimodal care (range of motion exercise with manipulation or mobilization), or muscle relaxants. In view of evidence of no effectiveness, clinicians should not offer structured patient education alone, strain-counterstrain therapy, relaxation massage, cervical collar, electroacupuncture, electrotherapy, or clinic-based heat. RECOMMENDATION 5: For NAD grades I-II >3 months duration, clinicians may consider structured patient education in combination with: range of motion and strengthening exercises, qigong, yoga, multimodal care (exercise with manipulation or mobilization), clinical massage, low-level laser therapy, or non-steroidal anti-inflammatory drugs. In view of evidence of no effectiveness, clinicians should not offer strengthening exercises alone, strain-counterstrain therapy, relaxation massage, relaxation therapy for pain or disability, electrotherapy, shortwave diathermy, clinic-based heat, electroacupuncture, or botulinum toxin injections. RECOMMENDATION 6: For NAD grade III ≤3 months duration, clinicians may consider supervised strengthening exercises in addition to structured patient education. In view of evidence of no effectiveness, clinicians should not offer structured patient education alone, cervical collar, low-level laser therapy, or traction. RECOMMENDATION 7: For NAD grade III >3 months duration, clinicians should not offer a cervical collar. Patients who continue to experience neurological signs and disability more than 3 months after injury should be referred to a physician for investigation and management. RECOMMENDATION 8: Clinicians should reassess the patient at every visit to determine if additional care is necessary, the condition is worsening, or the patient has recovered. Patients reporting significant recovery should be discharged.

The Effectiveness of Multimodal Care for the Management of Soft Tissue Injuries of the Shoulder: A Systematic Review by the Ontario Protocol for Traffic Injury Management (OPTIMa) Collaboration.

OBJECTIVE: The purpose of this systematic review was to evaluate the effectiveness of multimodal care for the management of soft tissue injuries of the shoulder. METHODS: We conducted a systematic review and searched MEDLINE, EMBASE, CINAHL, PsycINFO, and the Cochrane Central Register of Controlled Trials from 1990 to 2015. Two independent reviewers critically appraised studies using the Scottish Intercollegiate Guidelines Network criteria. We used best evidence synthesis to synthesize evidence from studies with low risk of bias. RESULTS: We screened 5885 articles, and 19 were eligible for critical appraisal. Ten randomized controlled trials had low risk of bias. For persistent subacromial impingement syndrome, multimodal care leads to similar outcomes as sham therapy, radial extracorporeal shock-wave therapy, or surgery. For subacromial impingement syndrome, multimodal care may be associated with small and nonclinically important improvement in pain and function compared with corticosteroid injections. For rotator cuff tendinitis, dietary-based multimodal care may be more effective than conventional multimodal care (exercise, soft tissue and manual therapy, and placebo tablets). For nonspecific shoulder pain, multimodal care may be more effective than wait list or usual care by a general practitioner, but it leads to similar outcomes as exercise or corticosteroid injections. CONCLUSIONS: The current evidence suggests that combining multiple interventions into 1 program of care does not lead to superior outcomes for patients with subacromial impingement syndrome or nonspecific shoulder pain. One randomized controlled trial suggested that dietary-based multimodal care (dietary advice, acupuncture, and enzyme tablets) may provide better outcomes over conventional multimodal care. However, these results need to be replicated.

The effectiveness of noninvasive interventions for musculoskeletal thoracic spine and chest wall pain: a systematic review by the Ontario Protocol for Traffic Injury Management (OPTIMa) collaboration.

OBJECTIVE: The purpose of this study was to critically appraise and synthesize evidence on the effectiveness of noninvasive interventions, excluding pharmacological treatments, for musculoskeletal thoracic pain. METHODS: Randomized controlled trials (RCTs), cohort studies, and case-control studies evaluating the effectiveness of noninvasive interventions were eligible. We searched MEDLINE, EMBASE, PsycINFO, and the Cochrane Central Register of Controlled Trials accessed through Ovid Technologies, Inc, and CINAHL Plus with Full Text accessed through EBSCOhost from 1990 to 2015. Our search strategies combined controlled vocabulary relevant to each database (eg, MeSH for MEDLINE) and text words relevant to our research question and the inclusion criteria. Random pairs of independent reviewers screened studies for relevance and critically appraised relevant studies using the Scottish Intercollegiate Guidelines Network criteria. Studies with a low risk of bias were synthesized following best evidence synthesis principles. RESULTS: We screened 6988 articles and critically appraised 2 studies. Both studies had a low risk of bias and were included in our synthesis. One RCT compared thoracic spinal manipulation, needle acupuncture, and placebo electrotherapy for recent thoracic spine pain. There were statistically significant but clinically nonimportant short-term reductions in pain favoring manipulation. There were no differences between acupuncture and placebo electrotherapy. Another RCT compared a multimodal program of care and a session of education for recent musculoskeletal chest wall pain. The multimodal care resulted in statistically significant but clinically nonimportant short-term reductions in pain over education. However, participants receiving multimodal care were more likely to report important improvements in chest pain. CONCLUSIONS: Quality evidence on the management of musculoskeletal thoracic pain is sparse. The current evidence suggests that compared to placebo, spinal manipulation is associated with a small and clinically nonimportant reduction in pain intensity and that acupuncture leads to similar outcomes as placebo. Furthermore, a multimodal program of care (ie, manual therapy, soft tissue therapy, exercises, heat/ice, and advice) and a single education session lead to similar pain reduction for recent-onset musculoskeletal chest wall pain. However, patients who receive multimodal care are more likely to report pain improvements.

The effectiveness of exercise for the management of musculoskeletal disorders and injuries of the elbow, forearm, wrist, and hand: a systematic review by the Ontario Protocol for Traffic Injury Management (OPTIMa) collaboration.

OBJECTIVE: The purpose of this systematic review was to evaluate the effectiveness of exercise compared to other interventions, placebo/sham intervention, or no intervention in improving self-rated recovery, functional recovery, clinical, and/or administrative outcomes in individuals with musculoskeletal disorders and injuries of the elbow, forearm, wrist, and hand. METHODS: We searched MEDLINE, EMBASE, CINAHL, PsycINFO, and the Cochrane Central Register of Controlled Trials from 1990 to 2015. Paired reviewers independently screened studies for relevance and assessed the risk of bias using the Scottish Intercollegiate Guidelines Network criteria. We synthesized the evidence using the best evidence synthesis methodology. RESULTS: We identified 5 studies with a low risk of bias. Our review suggests that, for patients with persistent lateral epicondylitis, (1) adding concentric or eccentric strengthening exercises to home stretching exercises provides no additional benefits; (2) a home program of either eccentric or concentric strengthening exercises leads to similar outcomes; (3) home wrist extensor strengthening exercises lead to greater short-term improvements in pain reduction compared to "wait and see"; and (4) clinic-based, supervised exercise may be more beneficial than home exercises with minimal improvements in pain and function. For hand pain of variable duration, supervised progressive strength training added to advice to continue normal physical activity provides no additional benefits. CONCLUSION: The relative effectiveness of stretching vs strengthening for the wrist extensors remains unknown for the management of persistent lateral epicondylitis. The current evidence shows that the addition of supervised progressive strength training does not provide further benefits over advice to continue normal physical activity for hand pain of variable duration.

Are work disability prevention interventions effective for the management of neck pain or upper extremity disorders? A systematic review by the Ontario Protocol for Traffic Injury Management (OPTIMa) collaboration.

PURPOSE: We conducted a systematic review to critically appraise and synthesize literature on the effectiveness of work disability prevention (WDP) interventions in workers with neck pain, whiplash-associated disorders (WAD), or upper extremity disorders. METHODS: We searched electronic databases from 1990 to 2012. Random pairs of independent reviewers critically appraised eligible studies using the Scottish Intercollegiate Guidelines Network criteria. Scientifically admissible studies were summarized and synthesized following best-evidence synthesis methodology. RESULTS: Of the 6,359 articles retrieved, 16 randomized controlled trials were eligible for critical appraisal and five were admissible. We found that a return-to-work coordination program (including workplace-based work hardening) was superior to clinic-based work hardening for persistent rotator cuff tendinitis. Workplace high-intensity strength training and workplace advice had similar outcomes for neck and shoulder pain. Mensendieck/Cesar postural exercises and strength and fitness exercises had similar outcomes for non-specific work-related upper limb complaints. Adding a brief job stress education program to a workplace ergonomic intervention was not beneficial for persistent upper extremity symptoms. Adding computer-prompted work breaks to ergonomic adjustments and workplace education benefited workers' recovery from recent work-related neck and upper extremity complaints. CONCLUSIONS: At present, no firm conclusions can be drawn regarding the effectiveness of WDP interventions for managing neck pain, WAD, and upper extremity disorders. Our review suggests a return-to-work coordination program is more effective than clinic-based work hardening. Also, adding computer-prompted breaks to ergonomic and workplace interventions benefits workers' recovery. The current quality of evidence does not allow for a definitive evaluation of the effectiveness of ergonomic interventions.

The prevalence of anxiety, stress and depressive symptoms in undergraduate students at the Canadian Memorial Chiropractic College.

Objective (1) Determine the one-week prevalence of moderate to extreme symptoms of anxiety, stress and depression in chiropractic undergraduate students. (2) Determine whether the prevalence varies across gender and year of study. Participants: Undergraduate students at the Canadian Memorial Chiropractic College (CMCC). Methods: A cross-sectional study was conducted in fall 2017 to measure self-reported symptoms of anxiety, stress and depression using the DASS-21. Results: The participation rate was 67.0% (510/766). The one-week prevalence of moderate to extreme symptoms was 19.0% (95% CI: 13.0-25.0) for depression; 32.6% (95% CI: 24.7-40.3) for anxiety and 21.8% (95% CI: 15.6-28.1) for stress. The prevalence of stress varied significantly across gender: 25.4% (95% CI: 20.5-30.3) for females versus 16.3% (95% CI: 11.2-21.3) for males. The one-week prevalence of depressive (24.8%; 95% CI: 17.6-32.0) and anxiety (40.9%; 95% CI: 32.6-49.1) symptoms peaked in second year. Conclusions: Self-reported symptoms of anxiety, stress and depression are common in CMCC students.

Promoting the use of a self-management strategy among novice chiropractors treating individuals with spine pain: A mixed methods pilot clustered-clinical trial.

BACKGROUND: The uptake of Self-Management Support (SMS) among clinicians is suboptimal. To date, few studies have tested knowledge translation (KT) interventions to increase the application of SMS in chiropractic teaching clinics. STUDY OBJECTIVE: Evaluate the feasibility of implementing a KT intervention to promote the use of a SMS strategy among chiropractic interns, their supervisors, and individuals with spine pain compared to controls. METHODS: Mixed methods pilot clustered-clinical trial. Clusters of 16 Patient Management Teams were allocated to a complex KT intervention (online and workshop training). Primary feasibility outcomes for clinicians, interns and patients were rates of recruitment, retention, and adherence to protocol. A nominal group technique and interviews were used to seek end-users' views on the implementation process, and generate possible solutions. RESULTS: In total, 16 (84%) clinicians, 65 (26%) interns and 42 patients agreed to participate. All clinicians in the intervention group completed all KT intervention components, 23 interns (85%) completed the online training and 14 interns (51.8%) attended the workshop training. All clinicians in the intervention and seven (78%) in the control group completed all outcome measures at baseline and 6-month follow-up, while 15 (55.6%) and 23 (60.5%) interns in the intervention and control groups completed the questionnaires at baseline and 6-month follow-up, respectively. Among patients, 10 (52.6%) and 12 (52.2%) in the intervention and control groups respectively completed the questionnaires at the end of the study. Based on interview findings, solutions to improve the feasibility of conducting a full trial include: making SMS a part of the internship, changing the time of introducing the study to the interns, and having more training on SMS. CONCLUSION: Recruitment and retention of chiropractic interns and patients for a larger implementation trial in a single outpatient teaching clinic may be challenging.

Protocol for an economic evaluation alongside the University Health Network Whiplash Intervention Trial: cost-effectiveness of education and activation, a rehabilitation program, and the legislated standard of care for acute whiplash injury in Ontario.

BACKGROUND: Whiplash injury affects 83% of persons in a traffic collision and leads to whiplash-associated disorders (WAD). A major challenge facing health care decision makers is identifying cost-effective interventions due to lack of economic evidence. Our objective is to compare the cost-effectiveness of: 1) physician-based education and activation, 2) a rehabilitation program developed by Aviva Canada (a group of property and casualty insurance providers), and 3) the legislated standard of care in the Canadian province of Ontario: the Pre-approved Framework Guideline for Whiplash developed by the Financial Services Commission of Ontario. METHODS/DESIGN: The economic evaluation will use participant-level data from the University Health Network Whiplash Intervention Trial and will be conducted from the societal perspective over the trial's one-year follow-up. Resource use (costs) will include all health care goods and services, and benefits provided during the trial's 1-year follow-up. The primary health effect will be the quality-adjusted life year. We will identify the most cost-effective intervention using the incremental cost-effectiveness ratio and incremental net-benefit. Confidence ellipses and cost-effectiveness acceptability curves will represent uncertainty around these statistics, respectively. A budget impact analysis will assess the total annual impact of replacing the current legislated standard of care with each of the other interventions. An expected value of perfect information will determine the maximum research expenditure Canadian society should be willing to pay for, and inform priority setting in, research of WAD management. DISCUSSION: Results will provide health care decision makers with much needed economic evidence on common interventions for acute whiplash management. TRIAL REGISTRATION: http://ClinicalTrials.gov identifier NCT00546806 [Trial registry date: October 18, 2007; Date first patient was randomized: February 27, 2008].

Noninvasive management of soft tissue disorders of the shoulder: A clinical practice guideline from the Ontario Protocol for Traffic Injury Management (OPTIMa) collaboration.

OBJECTIVES: Objective of this study is to develop an evidence-based guideline for the noninvasive management of soft tissue disorders of the shoulder (shoulder pain), excluding major pathology. METHODS: This guideline is based on high-quality evidence from seven systematic reviews. Multidisciplinary experts considered the evidence of effectiveness, safety, cost-effectiveness, societal and ethical values, and patient experiences when formulating recommendations. Target audience is clinicians; target population is adults with shoulder pain. RESULTS: When managing patients with shoulder pain, clinicians should (a) rule out major structural or other pathologies as the cause of shoulder pain and reassure patients about the benign and self-limited nature of most soft tissue shoulder pain; (b) develop a care plan in partnership with the patient; (c) for shoulder pain of any duration, consider low-level laser therapy; multimodal care (heat/cold, joint mobilization, and range of motion exercise); cervicothoracic spine manipulation and mobilization for shoulder pain when associated pain or restricted movement of the cervicothoracic spine; or thoracic spine manipulation; (d) for shoulder pain >3-month duration, consider stretching and/or strengthening exercises; laser acupuncture; or general physician care (information, advice, and pharmacological pain management if necessary); (e) for shoulder pain with calcific tendinitis on imaging, consider shock-wave therapy; (f) for shoulder pain of any duration, do not offer ultrasound; taping; interferential current therapy; diacutaneous fibrolysis; soft tissue massage; or cervicothoracic spine manipulation and mobilization as an adjunct to exercise (i.e., range of motion, strengthening and stretching exercise) for pain between the neck and the elbow at rest or during movement of the arm; (g) for shoulder pain >3-month duration, do not offer shock-wave therapy; and (h) should reassess the patient's status at each visit for worsening of symptoms or new physical, mental, or psychological symptoms, or satisfactory recovery. CONCLUSIONS: Our evidence-based guideline provides recommendations for non-invasive management of shoulder pain. The impact of the guideline in clinical practice requires further evaluation. SIGNIFICANCE: Shoulder pain of any duration can be effectively treated with laser therapy, multimodal care (i.e., heat/cold, joint mobilization, range of motion exercise), or cervicothoracic manipulation and mobilization. Shoulder pain (>3 months) can be effectively treated with exercises, laser acupuncture, or general physician care (information, advice, and pharmacological pain management if necessary).

Notch signalling maintains Hedgehog responsiveness via a Gli-dependent mechanism during spinal cord patterning in zebrafish.

Spinal cord patterning is orchestrated by multiple cell signalling pathways. Neural progenitors are maintained by Notch signalling, whereas ventral neural fates are specified by Hedgehog (Hh) signalling. However, how dynamic interactions between Notch and Hh signalling drive the precise pattern formation is still unknown. We applied the PHRESH (PHotoconvertible REporter of Signalling History) technique to analyse cell signalling dynamics in vivo during zebrafish spinal cord development. This approach reveals that Notch and Hh signalling display similar spatiotemporal kinetics throughout spinal cord patterning. Notch signalling functions upstream to control Hh response of neural progenitor cells. Using gain- and loss-of-function tools, we demonstrate that this regulation occurs not at the level of upstream regulators or primary cilia, but rather at the level of Gli transcription factors. Our results indicate that Notch signalling maintains Hh responsiveness of neural progenitors via a Gli-dependent mechanism in the spinal cord.

Promoting the use of self-management in patients with spine pain managed by chiropractors and chiropractic interns: barriers and design of a theory-based knowledge translation intervention.

Background: The literature supports the effectiveness of self-management support (SMS) to improve health outcomes of patients with chronic spine pain. However, patient engagement in SMS programs is suboptimal. The objectives of this study were to: 1) assess participation in self-care (i.e. activation) among patients with spine pain, 2) identify patients' barriers and enablers to using SMS, and 3) map behaviour change techniques (BCTs) to key barriers to inform the design of a knowledge translation (KT) intervention aimed to increase the use of SMS. Methods: In summer 2016, we invited 250 patients with spine pain seeking care at the Canadian Memorial Chiropractic College in Ontario, Canada to complete the Patient Activation Measure (PAM) survey to assess the level of participation in self-care. We subsequently conducted individual interviews, in summer 2017, based on the Theoretical Domains Framework (TDF) in a subset of patients to identify potential challenges to using SMS. The interview guide included 20 open-ended questions and accompanying probes. Findings were deductively analysed guided by the TDF. A panel of 7 experts mapped key barriers to BCTs, designed a KT intervention, and selected the modes of delivery. Results: Two hundred and twenty-three patients completed the PAM. Approximately 24% of respondents were not actively involved in their care. Interview findings from 13 spine pain patients suggested that the potential barriers to using SMS corresponded to four TDF domains: Environmental Context and Resources; Emotion; Memory, Attention & Decision-Making; and Behavioural Regulation. The proposed theory-based KT intervention includes paper-based educational materials, webinars and videos, summarising and demonstrating the therapeutic recommendations including exercises and other lifestyle changes. In addition, the KT intervention includes Brief Action Planning, a SMS strategy based on motivational interviewing, along with a SMART plan and reminders. Conclusions: Almost one quarter of study participants were not actively engaged in their spine care. Key barriers likely to influence uptake of SMS among patients were identified and used to inform the design of a theory-based KT intervention to increase their participation level. The proposed multi-component KT intervention may be an effective strategy to optimize the quality of spine pain care and improve patients' health-outcomes.

Is a government-regulated rehabilitation guideline more effective than general practitioner education or preferred-provider rehabilitation in promoting recovery from acute whiplash-associated disorders? A pragmatic randomised controlled trial.

OBJECTIVE: To evaluate the effectiveness of a government-regulated rehabilitation guideline compared with education and activation by general practitioners, and to a preferred-provider insurance-based rehabilitation programme on self-reported global recovery from acute whiplash-associated disorders (WAD) grade I-II. DESIGN: Pragmatic randomised clinical trial with blinded outcome assessment. SETTING: Multidisciplinary rehabilitation clinics and general practitioners in Ontario, Canada. PARTICIPANTS: 340 participants with acute WAD grade I and II. Potential participants were sampled from a large automobile insurer when reporting a traffic injury. INTERVENTIONS: Participants were randomised to receive one of three protocols: government-regulated rehabilitation guideline, education and activation by general practitioners or a preferred-provider insurance-based rehabilitation. PRIMARY AND SECONDARY OUTCOME MEASURES: Our primary outcome was time to self-reported global recovery. Secondary outcomes included time on insurance benefits, neck pain intensity, whiplash-related disability, health-related quality of life and depressive symptomatology at 6 weeks and 3, 6, 9 and 12 months postinjury. RESULTS: The median time to self-reported global recovery was 59 days (95% CI 55 to 68) for the government-regulated guideline group, 105 days (95% CI 61 to 126) for the preferred-provider group and 108 days (95% CI 93 to 206) for the general practitioner group; the difference was not statistically significant (Χ2=3.96; 2 df: p=0.138). We found no clinically important differences between groups in secondary outcomes. Post hoc analysis suggests that the general practitioner (hazard rate ratio (HRR)=0.51, 95% CI 0.34 to 0.77) and preferred-provider groups (HRR=0.67, 95% CI 0.46 to 0.96) had slower recovery than the government-regulated guideline group during the first 80 days postinjury. No major adverse events were reported. CONCLUSIONS: Time-to-recovery did not significantly differ across intervention groups. We found no differences between groups with regard to neck-specific outcomes, depression and health-related quality of life. TRIAL REGISTRATION NUMBER: NCT00546806.

Non-pharmacological management of persistent headaches associated with neck pain: A clinical practice guideline from the Ontario protocol for traffic injury management (OPTIMa) collaboration.

OBJECTIVES: To develop an evidence-based guideline for the non-pharmacological management of persistent headaches associated with neck pain (i.e., tension-type or cervicogenic). METHODS: This guideline is based on systematic reviews of high-quality studies. A multidisciplinary expert panel considered the evidence of clinical benefits, cost-effectiveness, societal and ethical values, and patient experiences when formulating recommendations. Target audience includes clinicians; target population is adults with persistent headaches associated with neck pain. RESULTS: When managing patients with headaches associated with neck pain, clinicians should (a) rule out major structural or other pathologies, or migraine as the cause of headaches; (b) classify headaches associated with neck pain as tension-type headache or cervicogenic headache once other sources of headache pathology has been ruled out; (c) provide care in partnership with the patient and involve the patient in care planning and decision making; (d) provide care in addition to structured patient education; (e) consider low-load endurance craniocervical and cervicoscapular exercises for tension-type headaches (episodic or chronic) or cervicogenic headaches >3 months duration; (f) consider general exercise, multimodal care (spinal mobilization, craniocervical exercise and postural correction) or clinical massage for chronic tension-type headaches; (g) do not offer manipulation of the cervical spine as the sole form of treatment for episodic or chronic tension-type headaches; (h) consider manual therapy (manipulation with or without mobilization) to the cervical and thoracic spine for cervicogenic headaches >3 months duration. However, there is no added benefit in combining spinal manipulation, spinal mobilization and exercises; and (i) reassess the patient at every visit to assess outcomes and determine whether a referral is indicated. CONCLUSIONS: Our evidence-based guideline provides recommendations for the conservative management of persistent headaches associated with neck pain. The impact of the guideline in clinical practice requires validation. SIGNIFICANCE: Neck pain and headaches are very common comorbidities in the population. Tension-type and cervicogenic headaches can be treated effectively with specific exercises. Manual therapy can be considered as an adjunct therapy to exercise to treat patients with cervicogenic headaches. The management of tension-type and cervicogenic headaches should be patient-centred.