Evaluating two steps in transcription using a fluorescence-based electrophoretic mobility shift assay.

Transcription is the critical first step in expressing a gene, during which an RNA polymerase (RNAP) synthesizes an RNA copy of one strand of the DNA that encodes a gene. Here we describe a laboratory experiment that uses a single assay to probe two important steps in transcription: (1) RNAP binding to DNA, and (2) the transcriptional activity of the polymerase. Students probe both these steps in a single experiment using a fluorescence-based electrophoretic mobility shift assay (EMSA) and commercially available Escherichia coli RNAP. As an inquiry-driven component, students add the transcriptional inhibitor rifampicin to reactions and draw conclusions about its mechanism of inhibition by determining whether it blocks polymerase binding to DNA or transcriptional activity. Depending on the curriculum and learning goals of individual courses, this experimental module could be easily expanded to include additional experimentation that mimics a research environment more closely. After completing the experiment students understand basic principles of transcription, mechanisms of inhibition, and the use of EMSAs to probe protein/DNA interactions.

A Systematic Review of Classification Systems for Cervical Ossification of the Posterior Longitudinal Ligament.

DESIGN: Systematic review. OBJECTIVE: To conduct a systematic review to (1) summarize various classification systems used to describe cervical ossification of the posterior longitudinal ligament (OPLL) and (2) evaluate the diagnostic accuracy of various imaging modalities and the reliability of these classification systems. METHODS: A search was performed to identify studies that used a classification system to categorize patients with OPLL. Furthermore, studies were included if they reported the diagnostic accuracy of various imaging modalities or the reliability of a classification system. RESULTS: A total of 167 studies were deemed relevant. Five classification systems were developed based on X-ray: the 9-classification system (0.60%); continuous, segmental, mixed, localized or focal, circumscribed and others (92.81%); hook, staple, bridge, and total types (2.40%); distribution of OPLL (2.40%); and K-line classification (4.19%). Six methods were based on computed tomography scans: free-type, contiguous-type, and broken sign (0.60%); hill-, plateau-, square-, mushroom-, irregular-, or round-shaped (5.99%); rectangular, oval, triangular, or pedunculate (1.20%); centralized or laterally deviated (1.80%); plank-, spindle-, or rod-shaped (0.60%); and rule of nine (0.60%). Classification systems based on 3-dimensional computed tomography were bridging and nonbridging (1.20%) and flat, irregular, and localized (0.60%). A single classification system was based on magnetic resonance imaging: triangular, teardrop, or boomerang. Finally, a variation of methods was used to classify OPLL associated with the dura mater (4.19%). CONCLUSIONS: The most common method of classification was that proposed by the Japanese Ministry of Health, Labour and Welfare. Other important methods include K-line (+/-), signs of dural ossification, and patterns of distribution.

A Clinical Practice Guideline for the Management of Patients With Acute Spinal Cord Injury and Central Cord Syndrome: Recommendations on the Timing (≤24 Hours Versus >24 Hours) of Decompressive Surgery.

OBJECTIVE: To develop recommendations on the timing of surgical decompression in patients with traumatic spinal cord injury (SCI) and central cord syndrome. METHODS: A systematic review of the literature was conducted to address key relevant questions. A multidisciplinary guideline development group used this information, along with their clinical expertise, to develop recommendations for the timing of surgical decompression in patients with SCI and central cord syndrome. Based on GRADE, a strong recommendation is worded as "we recommend," whereas a weak recommendation is presented as "we suggest." RESULTS: Conclusions from the systematic review included (1) isolated studies reported statistically significant and clinically important improvements following early decompression at 6 months and following discharge from inpatient rehabilitation; (2) in one study on acute central cord syndrome without instability, a marginally significant improvement in total motor scores was reported at 6 and 12 months in patients managed with early versus late surgery; and (3) there were no significant differences in length of acute care/rehabilitation stay or in rates of complications between treatment groups. Our recommendations were: "We suggest that early surgery be considered as a treatment option in adult patients with traumatic central cord syndrome" and "We suggest that early surgery be offered as an option for adult acute SCI patients regardless of level." Quality of evidence for both recommendations was considered low. CONCLUSIONS: These guidelines should be implemented into clinical practice to improve outcomes in patients with acute SCI and central cord syndrome by promoting standardization of care, decreasing the heterogeneity of management strategies, and encouraging clinicians to make evidence-informed decisions.

A Clinical Practice Guideline for the Management of Patients With Acute Spinal Cord Injury: Recommendations on the Use of Methylprednisolone Sodium Succinate.

INTRODUCTION: The objective of this guideline is to outline the appropriate use of methylprednisolone sodium succinate (MPSS) in patients with acute spinal cord injury (SCI). METHODS: A systematic review of the literature was conducted to address key questions related to the use of MPSS in acute SCI. A multidisciplinary Guideline Development Group used this information, in combination with their clinical expertise, to develop recommendations for the use of MPSS. Based on GRADE (Grading of Recommendation, Assessment, Development and Evaluation), a strong recommendation is worded as "we recommend," whereas a weaker recommendation is indicated by "we suggest." RESULTS: The main conclusions from the systematic review included the following: (1) there were no differences in motor score change at any time point in patients treated with MPSS compared to those not receiving steroids; (2) when MPSS was administered within 8 hours of injury, pooled results at 6- and 12-months indicated modest improvements in mean motor scores in the MPSS group compared with the control group; and (3) there was no statistical difference between treatment groups in the risk of complications. Our recommendations were: (1) "We suggest not offering a 24-hour infusion of high-dose MPSS to adult patients who present after 8 hours with acute SCI"; (2) "We suggest a 24-hour infusion of high-dose MPSS be offered to adult patients within 8 hours of acute SCI as a treatment option"; and (3) "We suggest not offering a 48-hour infusion of high-dose MPSS to adult patients with acute SCI." CONCLUSIONS: These guidelines should be implemented into clinical practice to improve outcomes and reduce morbidity in SCI patients.

A Clinical Practice Guideline for the Management of Patients With Acute Spinal Cord Injury: Recommendations on the Type and Timing of Anticoagulant Thromboprophylaxis.

INTRODUCTION: The objective of this study is to develop evidence-based guidelines that recommend effective, safe and cost-effective thromboprophylaxis strategies in patients with spinal cord injury (SCI). METHODS: A systematic review of the literature was conducted to address key questions relating to thromboprophylaxis in SCI. Based on GRADE (Grading of Recommendation, Assessment, Development and Evaluation), a strong recommendation is worded as "we recommend," whereas a weaker recommendation is indicated by "we suggest." RESULTS: Based on conclusions from the systematic review and expert panel opinion, the following recommendations were developed: (1) "We suggest that anticoagulant thromboprophylaxis be offered routinely to reduce the risk of thromboembolic events in the acute period after SCI;" (2) "We suggest that anticoagulant thromboprophylaxis, consisting of either subcutaneous low-molecular-weight heparin or fixed, low-dose unfractionated heparin (UFH) be offered to reduce the risk of thromboembolic events in the acute period after SCI. Given the potential for increased bleeding events with the use of adjusted-dose UFH, we suggest against this option;" (3) "We suggest commencing anticoagulant thromboprophylaxis within the first 72 hours after injury, if possible, in order to minimize the risk of venous thromboembolic complications during the period of acute hospitalization." CONCLUSIONS: These guidelines should be implemented into clinical practice in patients with SCI to promote standardization of care, decrease heterogeneity of management strategies and encourage clinicians to make evidence-informed decisions.

A Clinical Practice Guideline for the Management of Patients With Acute Spinal Cord Injury: Recommendations on the Role of Baseline Magnetic Resonance Imaging in Clinical Decision Making and Outcome Prediction.

INTRODUCTION: The objective of this guideline is to outline the role of magnetic resonance imaging (MRI) in clinical decision making and outcome prediction in patients with traumatic spinal cord injury (SCI). METHODS: A systematic review of the literature was conducted to address key questions related to the use of MRI in patients with traumatic SCI. This review focused on longitudinal studies that controlled for baseline neurologic status. A multidisciplinary Guideline Development Group (GDG) used this information, their clinical expertise, and patient input to develop recommendations on the use of MRI for SCI patients. Based on GRADE (Grading of Recommendation, Assessment, Development and Evaluation), a strong recommendation is worded as "we recommend," whereas a weaker recommendation is indicated by "we suggest." RESULTS: Based on the limited available evidence and the clinical expertise of the GDG, our recommendations were: (1) "We suggest that MRI be performed in adult patients with acute SCI prior to surgical intervention, when feasible, to facilitate improved clinical decision-making" (quality of evidence, very low) and (2) "We suggest that MRI should be performed in adult patients in the acute period following SCI, before or after surgical intervention, to improve prediction of neurologic outcome" (quality of evidence, low). CONCLUSIONS: These guidelines should be implemented into clinical practice to improve outcomes and prognostication for patients with SCI.

A Clinical Practice Guideline for the Management of Patients With Acute Spinal Cord Injury: Recommendations on the Type and Timing of Rehabilitation.

INTRODUCTION: The objective of this study is to develop guidelines that outline the appropriate type and timing of rehabilitation in patients with acute spinal cord injury (SCI). METHODS: A systematic review of the literature was conducted to address key questions related to rehabilitation in patients with acute SCI. A multidisciplinary guideline development group used this information, and their clinical expertise, to develop recommendations for the type and timing of rehabilitation. Based on GRADE (Grading of Recommendation, Assessment, Development and Evaluation), a strong recommendation is worded as "we recommend," whereas a weaker recommendation is indicated by "we suggest. RESULTS: Based on the findings from the systematic review, our recommendations were: (1) We suggest rehabilitation be offered to patients with acute spinal cord injury when they are medically stable and can tolerate required rehabilitation intensity (no included studies; expert opinion); (2) We suggest body weight-supported treadmill training as an option for ambulation training in addition to conventional overground walking, dependent on resource availability, context, and local expertise (low evidence); (3) We suggest that individuals with acute and subacute cervical SCI be offered functional electrical stimulation as an option to improve hand and upper extremity function (low evidence); and (4) Based on the absence of any clear benefit, we suggest not offering additional training in unsupported sitting beyond what is currently incorporated in standard rehabilitation (low evidence). CONCLUSIONS: These guidelines should be implemented into clinical practice to improve outcomes and reduce morbidity in patients with SCI by promoting standardization of care, decreasing the heterogeneity of management strategies and encouraging clinicians to make evidence-informed decisions.

A Clinical Practice Guideline for the Management of Patients With Degenerative Cervical Myelopathy: Recommendations for Patients With Mild, Moderate, and Severe Disease and Nonmyelopathic Patients With Evidence of Cord Compression.

STUDY DESIGN: Guideline development. OBJECTIVES: The objective of this study is to develop guidelines that outline how to best manage (1) patients with mild, moderate, and severe myelopathy and (2) nonmyelopathic patients with evidence of cord compression with or without clinical symptoms of radiculopathy. METHODS: Five systematic reviews of the literature were conducted to synthesize evidence on disease natural history; risk factors of disease progression; the efficacy, effectiveness, and safety of nonoperative and surgical management; the impact of preoperative duration of symptoms and myelopathy severity on treatment outcomes; and the frequency, timing, and predictors of symptom development. A multidisciplinary guideline development group used this information, and their clinical expertise, to develop recommendations for the management of degenerative cervical myelopathy (DCM). RESULTS: Our recommendations were as follows: (1) "We recommend surgical intervention for patients with moderate and severe DCM." (2) "We suggest offering surgical intervention or a supervised trial of structured rehabilitation for patients with mild DCM. If initial nonoperative management is pursued, we recommend operative intervention if there is neurological deterioration and suggest operative intervention if the patient fails to improve." (3) "We suggest not offering prophylactic surgery for non-myelopathic patients with evidence of cervical cord compression without signs or symptoms of radiculopathy. We suggest that these patients be counseled as to potential risks of progression, educated about relevant signs and symptoms of myelopathy, and be followed clinically." (4) "Non-myelopathic patients with cord compression and clinical evidence of radiculopathy with or without electrophysiological confirmation are at a higher risk of developing myelopathy and should be counselled about this risk. We suggest offering either surgical intervention or nonoperative treatment consisting of close serial follow-up or a supervised trial of structured rehabilitation. In the event of myelopathic development, the patient should be managed according to the recommendations above." CONCLUSIONS: These guidelines will promote standardization of care for patients with DCM, decrease the heterogeneity of management strategies and encourage clinicians to make evidence-informed decisions.

Forecasting Financial Resources for Future Traumatic Spinal Cord Injury Care Using Simulation Modeling.

Survivors of traumatic spinal cord injury (tSCI) have intense healthcare needs during acute and rehabilitation care and often through the rest of life. To prepare for a growing and aging population, simulation modeling was used to forecast the change in healthcare financial resources and long-term patient outcomes between 2012 and 2032. The model was developed with data from acute and rehabilitation care facilities across Canada participating in the Access to Care and Timing project. Future population and tSCI incidence for 2012 and 2032 were predicted with data from Statistics Canada and the Canadian Institute for Health Information. The projected tSCI incidence for 2012 was validated with actual data from the Rick Hansen SCI Registry of the participating facilities. Using a medium growth scenario, in 2032, the projected median age of persons with tSCI is 57 and persons 61 and older will account for 46% of injuries. Admissions to acute and rehabilitation facilities in 2032 were projected to increase by 31% and 25%, respectively. Because of the demographic shift to an older population, an increase in total population life expectancy with tSCI of 13% was observed despite a 22% increase in total life years lost to tSCI between 2012 and 2032. Care cost increased 54%, and rest of life cost increased 37% in 2032, translating to an additional CAD $16.4 million. With the demographics and management of tSCI changing with an aging population, accurate projections for the increased demand on resources will be critical for decision makers when planning the delivery of healthcare after tSCI.

Using Evidence To Inform Practice and Policy To Enhance the Quality of Care for Persons with Traumatic Spinal Cord Injury.

In today's economic climate, there is a need to demonstrate a return on investment for healthcare spending and for clinical practice and policy to be informed by evidence. Navigating this process is difficult for decision-makers, clinicians, and researchers alike. This article will describe how a knowledge translation framework and an evidence-based policy-making process were integrated to clarify the problem, frame options, and plan implementation, to impact clinical practice and policy in the area of traumatic spinal cord injury (tSCI). The Access to Care and Timing (ACT) project is focused on optimizing the access and timing of specialized healthcare delivery for persons sustaining a tSCI in Canada. A simulation model was developed that uses current patient data to address complex problems faced by the healthcare system. At a workshop, participants stressed the importance of linking interventions to short- and long-term outcomes to drive change. Presently, there are no national, system level indicators to monitor performance after tSCI. Although the ideal system of care after tSCI is unknown, indicator collection will establish a baseline to measure improvement. The workshop participants prioritized two indicators important from the clinician and patient perspective-timely admission to rehabilitation and meaningful community participation. The ACT simulation model for tSCI care will be used to promote the uptake of identified indicators and provide a predictive link between interventions on potential outcomes. The standardized collection of outcome-oriented indicators will help to evaluate the access and timing of care and to define the ideal system of care after SCI.

Traumatic Spinal Cord Injury Care in Canada: A Survey of Canadian Centers.

Specialized centers of care for persons sustaining a traumatic spinal cord injury (tSCI) have been established in many countries, but the ideal system of care has not been defined. The objective of this study was to describe care delivery, with a focus on structures and services, for persons with tSCI in Canada. A survey was sent to 26 facilities (12 acute, 11 rehabilitation, and three integrated) from eight provinces participating in the Access to Care and Timing project. The survey included questions about: 1) care provision; 2) structural attributes and; 3) service availability. Survey completion rate was 100%. Data sources used to complete the survey were the Rick Hansen Spinal Cord Injury Registry, other hospital databases, clinical protocols, and subject matter experts. Acute and rehabilitation care provided by integrated facilities were described separately, resulting in data from 15 acute and 14 rehabilitation facilities. The number of admissions for tSCI over a 12-month period between 2009-2011 ranged from 17 to 104 (median 39), and 11 to 96 (median 32), for acute and rehabilitation facilities, respectively. Grouping of patients was reported by 8/15 acute and 10/14 rehabilitation facilities. Criteria for admission to the inpatient rehabilitation facilities varied among facilities (25 different criteria reported). Results from the survey revealed similarities in the basic structure and the provision of general services, but also some differences in the degree of specialization of care for persons with tSCI. Continued work on the impact of specialized care for both the patient and healthcare system is needed.

Prediction of Outcome Following Surgical Treatment of Cervical Myelopathy Based on Features of Ossification of the Posterior Longitudinal Ligament: A Systematic Review.

BACKGROUND: Ossification of the posterior longitudinal ligament (OPLL) is defined as ectopic bone formation within the posterior longitudinal ligament. Although various OPLL features (including the extent, shape, and thickness of the OPLL as well as the presence of dural ossification) have been defined in the literature, we are not aware of any systematic reviews that have summarized the associations between these features and clinical outcomes following surgery. The objective of the present study was to conduct a systematic review of the literature to determine whether OPLL characteristics are predictive of outcome in patients undergoing surgery for the treatment of cervical myelopathy. METHODS: An extensive search was performed using 4 electronic databases: MEDLINE, MEDLINE In-Process, Embase, and the Cochrane Central Register of Controlled Trials. Our search terms were OPLL and cervical. We identified studies in English or Japanese that evaluated the association between cervical OPLL features and surgical outcome. The overall body of evidence was assessed with use of a scoring system developed by the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group with recommendations from the Agency for Healthcare Research and Quality (AHQR). The present systematic literature review is formatted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. RESULTS: The search yielded a total of 2,318 citations. A total of 28 prognostic cohort studies were deemed relevant following a rigorous review process. Among them, only 7 retrospective studies involved a multivariate analysis that controlled for potential confounding variables. Sample sizes ranged from 47 to 133 patients. The main outcome was the postoperative Japanese Orthopaedic Association (JOA) score and/or recovery rate in 6 studies and the Nurick grade in 1. Of these, 2 were rated as Level-II evidence and 5 were rated as Level-III evidence. On the basis of our results, there was low evidence that patients with a hill-shaped ossification have a worse postoperative JOA score following laminoplasty than those with a plateau-shaped lesion; low evidence that the space available for the spinal cord cannot predict postoperative JOA scores; moderate evidence that there is no association between the occupying ratio and improvement on the Nurick scale; and insufficient evidence to determine the association between JOA outcomes and the type of OPLL, the presence of dural ossification, and the occupying ratio. CONCLUSIONS: Patients with hill-shaped OPLL have a worse postoperative JOA score than those with plateau-shaped ossification after laminoplasty. Because of limited evidence, it is unclear whether the occupying ratio, the type of OPLL, and the presence of dural ossification are predictive of surgical outcomes following either anterior or posterior decompression. A limited number of studies have used a multivariate analysis to evaluate the association between clinical outcomes and OPLL features. Additional studies representing high-quality evidence are needed. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Methodology of the Access to Care and Timing Simulation Model for Traumatic Spinal Cord Injury Care.

Despite the relatively low incidence of traumatic spinal cord injury (tSCI), the management and care of persons with tSCI can be resource intensive and complex, spanning multiple phases of care and disciplines. Using a simulation model built with a system level view of the healthcare system allows for prediction of the impact of interventions on patient and system outcomes from injury through to community reintegration after tSCI. As has been previously described, the Access to Care and Timing (ACT) project developed a simulation model for tSCI care using techniques from operations research. The objective of this article is to briefly describe the methodology and the application of the ACT Model, as it was used in several of the articles in this focus issue. The approaches employed in this model provide a framework to look into the complexity of interactions both within and among the different SCI programs, sites, and phases of care.

Optimizing Clinical Decision Making in Acute Traumatic Spinal Cord Injury.

Spinal cord injury (SCI) is a devastating event causing lifelong disability that results in a significant decrease in quality of life and immense cost to the health care system, individuals and their families. Providing specialized and timely care can improve recovery and reduce costs, but to make this a reality requires understanding of the current care delivery processes and the care journey. The objective of this focus issue is to examine the current state of health care delivery and discover opportunities to improve access and timing to specialized care for individuals with tSCI. This issue provides an overview of care throughout the SCI continuum and its impact on individuals with tSCI using pan-Canadian data. The issue also presents findings from the RHI Access to Care and Timing (ACT) Project, a multi-center research study involving a multi-disciplinary team of Canadian researchers and clinicians. The initial articles describe the current state of the tSCI care journey including a comparison of environmental barriers, health status, and quality-of-life outcomes between patients living in rural and urban settings. The issue concludes with an article describing the national knowledge translation efforts of using the evidence from the articles published here to inform practice and policy change. Overall, this focus issue will be an excellent reference to guide and optimize evidence informed decision-making in the care of those with tSCI. The evidence can be transferred to care in non-traumatic SCI and other conditions that benefit from timely access to specialized care such as stroke and traumatic brain injury.

The modified Japanese Orthopaedic Association scale: establishing criteria for mild, moderate and severe impairment in patients with degenerative cervical myelopathy.

PURPOSE: We aimed to determine cut-offs between mild, moderate and severe myelopathy on the modified Japanese Orthopedic Association (mJOA) score. METHODS: Between December 2005 and January 2011, 757 patients with clinically diagnosed DCM were enrolled in the prospective AOSpine North America (n = 278) or International (n = 479) study at 26 sites. Functional status and quality of life were evaluated at baseline using a variety of outcome measures. Using the Nurick score as an anchor, receiver operating curve (ROC) analysis was conducted to determine cut-offs between mild, moderate and severe disease. The validity of the identified cut-offs was evaluated by examining whether patients in different severity groups differed in terms of impairment, disability, quality of life and number of signs and symptoms. RESULTS: A mJOA of 14 was determined to be the cut-off between mild and moderate myelopathy and a mJOA of 11 was the cut-off score between moderate and severe disease. Patients in the severe myelopathy group (n = 254) had significantly reduced quality of life and functional status and a greater number of signs and symptoms compared to patients classified as mild (n = 190) or moderate (n = 296). CONCLUSIONS: Mild myelopathy can be defined as mJOA from 15 to 17, moderate as mJOA from 12 to 14 and severe as mJOA from 0 to 11. These categories should be adopted worldwide to standardize clinical assessment of DCM.

Impact of Depression and Bipolar Disorders on Functional and Quality of Life Outcomes in Patients Undergoing Surgery for Degenerative Cervical Myelopathy: Analysis of a Combined Prospective Dataset.

STUDY DESIGN: Analysis of a combined prospective dataset. OBJECTIVE: To compare clinical outcomes in patients with and without preexisting depression or bipolar disorder undergoing surgery for degenerative cervical myelopathy (DCM). SUMMARY OF BACKGROUND DATA: Psychiatric comorbidities, including depression, have been associated with worse clinical outcomes after lumbar spine surgery; however, it is unclear whether these psychiatric disorders are also predictive of outcomes in patients undergoing surgery for the treatment of DCM. METHODS: Four hundred and one patients with symptomatic DCM were enrolled in the prospective AOSpine International or North America study at twelve North American sites. Patients were evaluated preoperatively and at 6, 12, and 24 months using the modified Japanese Orthopedic Association scale (mJOA), Nurick score, Neck Disability Index (NDI), and Short- Form 36v2 (SF-36v2) Health Survey. A mixed model analytic approach was used to evaluate differences in outcomes at 24 months among patients with and without psychiatric disorders, while controlling for relevant baseline characteristics and surgical factors. RESULTS: Ninety-seven patients (24.19%) were diagnosed with preexisting depression or bipolar disorder. There were more females (65.98%) with these psychiatric disorders than males (34.02%) (P < 0.0001). Patients with psychiatric comorbidities were more likely to have cardiovascular (P = 0.0177), respiratory (P < 0.0001), gastrointestinal (P < 0.0001), rheumatologic (P = 0.0109), and neurologic (P = 0.0309) disorders. At 24 months after surgery, patients in both groups demonstrated significant improvements on the mJOA, Nurick, NDI, and SF-36v2 Physical Component Score (PCS). Patients with depression or bipolar disorder, however, did not exhibit a significant or clinically important change on the SF-36v2 Mental Component Score (MCS). There were no differences in mJOA and Nurick scores at 24 months among patients in each group. Improvement in NDI, SF-36v2 PCS, and MCS, however, were smaller in patients with depression or bipolar disorder than those without. CONCLUSION: Patients with depression or bipolar disorder have smaller functional and quality of life improvements after surgery compared to patients without psychiatric comorbidities. LEVEL OF EVIDENCE: 2.

A systematic review of clinical and surgical predictors of complications following surgery for degenerative cervical myelopathy.

OBJECTIVE: Although generally safe and effective, surgery for the treatment of cervical spondylotic myelopathy (CSM) is associated with complications in 11%-38% of patients. Several predictors of postoperative complications have been proposed but few are used to detect high-risk patients. A standard approach to identifying "at-risk" patients would improve surgeons' ability to prevent and manage these complications. The authors aimed to compare the complication rates between various surgical procedures used to treat CSM and to identify patient-specific, clinical, imaging, and surgical predictors of complications. METHODS: The authors conducted a systematic review of the literature and searched MEDLINE, MEDLINE in Process, EMBASE, and Cochrane Central Register of Controlled Trials from 1948 to September 2013. Cohort studies designed to evaluate predictors of complications and intervention studies conducted to compare different surgical approaches were included. Each article was critically appraised independently by 2 reviewers, and the evidence was synthesized according to the principles outlined by the Grading of Recommendation Assessment, Development and Evaluation (GRADE) Working Group. RESULTS: A total of 5472 citations were retrieved. Of those, 60 studies met the inclusion criteria and were included in the review. These studies included 36 prognostic cohort studies and 28 comparative intervention studies. High evidence suggests that older patients are at a greater risk of perioperative complications. Based on low evidence, other clinical factors such as body mass index, smoking status, duration of symptoms, and baseline severity score, are not predictive of complications. With respect to surgical factors, low to moderate evidence suggests that estimated blood loss, surgical approach, and number of levels do not affect rates of complications. A longer operative duration (moderate evidence), however, is predictive of perioperative complications and a 2-stage surgery is related to an increased risk of major complications (high evidence). In terms of surgical techniques, higher rates of neck pain were found in patients undergoing laminoplasty compared with anterior spinal fusion (moderate evidence). In addition, with respect to laminoplasty techniques, there was a lower incidence of C-5 palsy in laminoplasty with concurrent foraminotomy compared with nonforaminotomy (low evidence). CONCLUSIONS: The current review suggests that older patients are at a higher risk of perioperative complications. A longer operative duration and a 2-stage surgery both reflect increased case complexity and can indirectly predict perioperative complications.

Defining the Pathway to Definitive Care and Surgical Decompression after Traumatic Spinal Cord Injury: Results of a Canadian Population-Based Cohort Study.

Early access to specialized care after acute traumatic spinal cord injury (SCI) is associated with improved outcomes. However, many SCI patients do not receive timely access to such care. To characterize and quantify patients' pathway to definitive care and surgery post SCI, and to identify factors that may delay expeditious care, a population based cohort study was performed in Ontario. Using provincial administrative health data, adult patients with acute traumatic SCI who underwent surgery between 2002 and 2011 were identified using SCI specific ICD-10 codes. The relationship between predictor variables and a) time to arrival at the site of definitive care and b) time to surgery was statistically evaluated. Of 1,111 patients meeting eligibility criteria, mean times to arrival at the site of definitive care and to surgery were 8.1 ± 25.5 and 49.4 ± 65.0 hours respectively, with 53.3% of patients having surgery prior to 24 hours. While most patients (88.4%) reached the site of definitive care within 6 hours, only 34.2% reached surgery within 12 hours of arrival. Older age (IRR = 1.01; 95% CI: 1.01, 1.02), increased number of stops at intermediate health care centers (IRR = 7.70; 95% CI: 7.54, 7.86), higher comorbidity index (IRR = 1.43; 95% CI: 1.14, 1.72) and fall related SCI etiology (IRR = 1.16; 95% CI: 1.02, 1.29) were associated with increased time to arrival at definitive care. For surgery, increased age (OR = 1.02; 95% CI: 1.01, 1.03) and stops at intermediate health centers (OR = 2.48; 95% CI: 1.35, 4.56) were associated with a greater odds of undergoing late surgery (>24hrs). These results can inform policy decisions and facilitate creation of a streamlined path to specialized care for patients with acute SCI.

Optimal Timing of Surgical Decompression for Acute Traumatic Central Cord Syndrome: A Systematic Review of the Literature.

BACKGROUND: Traumatic central cord syndrome (TCCS) is an incomplete spinal cord injury defined by greater weakness in upper versus lower extremities, variable sensory loss, and variable bladder, bowel, and sexual dysfunction. The optimal timing of surgery for TCCS remains controversial. OBJECTIVE: To determine whether timing of surgery for TCCS predicts neurological outcomes, length of stay, and complications. METHODS: Five databases were searched through March 2015. Articles were appraised independently by 2 reviewers, and the evidence synthesized according to Grading of Recommendation Assessment, Development and Evaluation principles. RESULTS: Nine studies (3 prognostic, 5 therapeutic, 1 both) satisfied inclusion criteria. Low level evidence suggests that patients operated on <24 hours after injury exhibit significantly greater improvements in postoperative American Spinal Injury Association motor scores and the functional independence measure at 1 year than those operated on >24 hours after injury. Moderate evidence suggests that patients operated on <2 weeks after injury have a higher postoperative Japanese Orthopaedic Association score and recovery rate than those operated on >2 weeks after injury. There is insufficient evidence that lengths of hospital or intensive care unit stay differ between patients who undergo early versus delayed surgery. Furthermore, there is insufficient evidence that timing between injury and surgery predicts mortality rates or serious or minor adverse events. CONCLUSION: Surgery for TCCS <24 hours after injury appears safe and effective. Although there is insufficient evidence to provide a clear recommendation for early surgery (<24 hours), it is preferable to operate during the first hospital admission and <2 weeks after injury.

Degenerative Cervical Myelopathy: Epidemiology, Genetics, and Pathogenesis.

STUDY DESIGN: Review. OBJECTIVE: To formally introduce "degenerative cervical myelopathy" (DCM) as the overarching term to describe the various degenerative conditions of the cervical spine that cause myelopathy. Herein, the epidemiology, pathogenesis, and genetics of conditions falling under this hypernym are carefully described. SUMMARY OF BACKGROUND DATA: Nontraumatic, degenerative forms of cervical myelopathy represent the commonest cause of spinal cord impairment in adults and include cervical spondylotic myelopathy, ossification of the posterior longitudinal ligament, ossification of the ligamentum flavum, and degenerative disc disease. Unfortunately, there is neither a specific term nor a specific diagnostic International Classification of Diseases, Tenth Revision code to describe this collection of clinical entities. This has resulted in the inconsistent use of diagnostic terms when referring to patients with myelopathy due to degenerative disease of the cervical spine. METHODS: Narrative review. RESULTS: The incidence and prevalence of myelopathy due to degeneration of the spine are estimated at a minimum of 41 and 605 per million in North America, respectively. Incidence of cervical spondylotic myelopathy-related hospitalizations has been estimated at 4.04/100,000 person-years, and surgical rates seem to be rising. Pathophysiologically, myelopathy results from static compression, spinal malalignment leading to altered cord tension and vascular supply, and dynamic injury mechanisms. Occupational hazards, including transportation of goods by weight bearing on top of the head, and other risk factors may accelerate DCM development. Potential genetic factors include those related to MMP-2 and collagen IX for degenerative disc disease, and collagen VI and XI for ossification of the posterior longitudinal ligament. In addition, congenital anomalies including spinal stenosis, Down syndrome, and Klippel-Feil syndrome may predispose to the development of DCM. CONCLUSION: Although DCMs can present as separate diagnostic entities, they are highly interrelated, frequently manifest concomitantly, present similarly from a clinical standpoint, and seem to be in part a response to compensate and improve stability due to progressive age and wear of the cervical spine. The use of the term "degenerative cervical myelopathy" is advocated. LEVEL OF EVIDENCE: 5.