Development of the cervical myelopathy severity index: a new patient reported outcome measure to quantify impairments and functional limitations.

BACKGROUND CONTEXT: Existing degenerative cervical myelopathy (DCM) severity scales have significant shortcomings, creating a strong impetus for the development of a practical measurement tool with sound psychometric properties. PURPOSE: This work reports the item generation and reduction of the Cervical Myelopathy Severity Index (CMSI), a new DCM patient-reported outcome measure of symptoms and functional limitations. DESIGN: Prospective observational study. PATIENT SAMPLE: Adult DCM patients belonging to one of three distinct treatment groups: (1) observation cohort, (2) preoperative surgical cohort, (3) 6 to 12 months postoperative cohort. OUTCOME MEASURES: Patient-reported outcome measure of symptoms and functional limitations. METHODS: Item generation was performed using semi-structured patient focus groups emphasizing symptoms experienced and functional limitations. Readability was assessed through think-aloud patient interviews. Item reduction involved surveys of DCM patients with a spectrum of disease severity and board-certified spine surgeons experienced in the treatment of DCM. A priori criteria for item removal included: patient median importance/severity <2 (of 4), 30% or more no severity (response of zero), item severity correlations ≤ 0.80 (Spearman), item severity reliability (weighted kappa <0.60) based on a 2-week interval and clinician median importance <2 with retention of items with very high clinical importance. RESULTS: There were 42 items generated from a combination of specialist input and patient focus groups. Items captured sensorimotor symptoms and limitations related to upper and lower extremities as well as sphincter dysfunction. Ninety-eight patients (43, 30, 25 observation, pre- and postsurgery respectively) and 51 surgeons completed the assessment. Twenty-three items remained after application of median importance and severity thresholds and weighted kappa cutoffs. After elimination of highly correlated (>0.80) items and combining two similar items, the final CMSI questionnaire list included 14 items. CONCLUSIONS: The CMSI is a new DCM patient-reported clinical measurement tool developed using patient and clinician input to inform item generation and reduction. Future work will evaluate the reliability, validity, and responsiveness of the CMSI in relation to existing myelopathy measurement indices.

Earlier Tracheostomy Reduces Complications in Complete Cervical Spinal Cord Injury in Real-World Practice: Analysis of a Multicenter Cohort of 2001 Patients.

BACKGROUND AND OBJECTIVES: It is believed that early tracheostomy in patients with traumatic cervical spinal cord injury (SCI) may lessen the risk of developing complications and reduce the duration of mechanical ventilation and critical care stay. This study aims to assess whether early tracheostomy is beneficial in patients with traumatic cervical SCI. METHODS: We conducted a retrospective cohort study using data from the American College of Surgeons Trauma Quality Improvement Program database from 2010 to 2018. Adult patients with a diagnosis of acute complete (ASIA A) traumatic cervical SCI who underwent surgery and tracheostomy were included. Patients were stratified into those receiving early (at or before 7 days) and delayed tracheostomy. Propensity score matching was used to assess the association between delayed tracheostomy and the risk of in-hospital adverse events. Risk-adjusted variability in tracheostomy timing across trauma centers was investigated using mixed-effects regression. RESULTS: The study included 2001 patients from 374 North American trauma centers. The median time to tracheostomy was 9.2 days (IQR: 6.1-13.1 days), with 654 patients (32.7%) undergoing early tracheostomy. After matching, the odds of a major complication were significantly lower for early tracheostomy patients (OR: .90; 95% CI: .88-.98). Patients were also significantly less likely to experience an immobility-related complication (OR: .90; 95% CI: .88-.98). Patients in the early group spent 8.2 fewer days in the critical care unit (95% CI: -10.2 to -6.61) and 6.7 fewer days ventilated (95% CI: -9.44 to -5.23). There was significant variability in tracheostomy timeliness between trauma centers with a median odds ratio of 12.2 (95% CI: 9.7-13.7), which was not explained by case-mix and hospital-level characteristics. CONCLUSION: A 7-day threshold to implement tracheostomy seems to be associated with reduced in-hospital complications, time in the critical care unit, and time on mechanical ventilation.

Assessment of the incremental prognostic value from the modified frailty index-5 in complete traumatic cervical spinal cord injury.

Frailty, as measured by the modified frailty index-5 (mFI-5), and older age are associated with increased mortality in the setting of spinal cord injury (SCI). However, there is limited evidence demonstrating an incremental prognostic value derived from patient mFI-5. We conducted a retrospective cohort study to evaluate in-hospital mortality among adult complete cervical SCI patients at participating centers of the Trauma Quality Improvement Program from 2010 to 2018. Logistic regression was used to model in-hospital mortality, and the area under the receiver operating characteristic curve (AUROC) of regression models with age, mFI-5, or age with mFI-5 was used to compare the prognostic value of each model. 4733 patients were eligible. We found that both age (80 y versus 60 y: OR 3.59 95% CI [2.82 4.56], P < 0.001) and mFI-5 (score ≥ 2 versus < 2: OR 1.53 95% CI [1.19 1.97], P < 0.001) had statistically significant associations with in-hospital mortality. There was no significant difference in the AUROC of a model including age and mFI-5 when compared to a model including age without mFI-5 (95% CI Δ AUROC [- 8.72 × 10-4 0.82], P = 0.199). Both models were superior to a model including mFI-5 without age (95% CI Δ AUROC [0.06 0.09], P < 0.001). Our findings suggest that mFI-5 provides minimal incremental prognostic value over age with respect to in-hospital mortality for patients complete cervical SCI.

Multicenter retrospective cohort study of the association between surgery for odontoid fractures in the elderly and in-hospital outcomes.

Odontoid fractures are increasingly prevalent in older adults and associated with high morbidity and mortality. Optimal management remains controversial. Our study aims to investigate the association between surgical management of odontoid fractures and in-hospital mortality in a multi-center geriatric cohort. We identified patients 65 years or older with C2 odontoid fractures from the Trauma Quality Improvement Program database. The primary study outcome was in-hospital mortality. Secondary outcomes were in-hospital complications and hospital length of stay. Generalized estimating equation models were used to compare outcomes between operative and non-operative cohorts. Among the 13,218 eligible patients, 1100 (8.3%) were treated surgically. The risk of in-hospital mortality did not differ between surgical and non-surgical groups, after patient and hospital-level adjustment (OR: 0.94, 95%CI: 0.55-1.60). The risks of major complications and immobility-related complications were higher in the operative cohort (adjusted OR: 2.12, 95%CI: 1.53-2.94; and OR: 2.24, 95%CI: 1.38-3.63, respectively). Patients undergoing surgery had extended in-hospital length of stay compared to the non-operative group (9 days, IQR: 6-12 days vs. 4 days, IQR: 3-7 days). These findings were supported by secondary analyses that considered between-center differences in rates of surgery. Among geriatric patients with odontoid fractures surgical management was associated with similar in-hospital mortality, but higher in-hospital complication rates compared to non-operative management. Surgical management of geriatric patients with odontoid fractures requires careful patient selection and consideration of pre-existing comorbidities.

Analysis of recovery trajectories in degenerative cervical myelopathy to facilitate improved patient counseling and individualized treatment recommendations.

OBJECTIVE: There is a need to better understand and predict postsurgical outcomes for degenerative cervical myelopathy (DCM) patients, particularly to support treatment decisions for patients with mild DCM. The goal of this study was to identify and predict outcome trajectories for DCM patients up to 2 years postsurgery. METHODS: The authors analyzed two North American multicenter prospective DCM studies (n = 757). Functional recovery and physical health component quality of life were assessed in DCM patients at baseline, 6 months, and 1 and 2 years postoperatively using the modified Japanese Orthopaedic Association (mJOA) score and Physical Component Summary (PCS) of the SF-36, respectively. Group-based trajectory modeling was used to identify recovery trajectories for mild, moderate, and severe DCM. Prediction models for recovery trajectories were developed and validated in bootstrap resamples. RESULTS: Two recovery trajectories were identified for the functional and physical components of quality of life: good recovery and marginal recovery. Depending on outcome and myelopathy severity, one-half to three-fourths of the study patients followed the good recovery trajectory characterized by improvement in mJOA and PCS scores over time. The remaining one-half to one-fourth of patients followed the marginal recovery trajectory, experiencing little improvement and, in certain cases, worsening postoperatively. The prediction model for mild DCM had an area under the curve of 0.72 (95% CI 0.65-0.80), with preoperative neck pain, smoking, and posterior surgical approach noted as dominant predictors of marginal recovery. CONCLUSIONS: Surgically treated DCM patients follow distinct recovery trajectories in the first 2 years postoperatively. While most patients experience substantial improvement, a significant minority experience little improvement or worsening. The ability to predict DCM patient recovery trajectories in the preoperative setting facilitates the formulation of individualized treatment recommendations for patients with mild symptoms.

Does intrathecal nicardipine for cerebral vasospasm following subarachnoid hemorrhage correlate with reduced delayed cerebral ischemia? A retrospective propensity score-based analysis.

OBJECTIVE: Cerebral vasospasm and delayed cerebral ischemia (DCI) contribute to poor outcome following subarachnoid hemorrhage (SAH). With the paucity of effective treatments, the authors describe their experience with intrathecal (IT) nicardipine for this indication. METHODS: Patients admitted to the Emory University Hospital neuroscience ICU between 2012 and 2017 with nontraumatic SAH, either aneurysmal or idiopathic, were included in the analysis. Using a propensity-score model, this patient cohort was compared to patients in the Subarachnoid Hemorrhage International Trialists (SAHIT) repository who did not receive IT nicardipine. The primary outcome was DCI. Secondary outcomes were long-term functional outcome and adverse events. RESULTS: The analysis included 1351 patients, 422 of whom were diagnosed with cerebral vasospasm and treated with IT nicardipine. When compared with patients with no vasospasm (n = 859), the treated group was significantly younger (mean age 51.1 ± 12.4 years vs 56.7 ± 14.1 years, p < 0.001), had a higher World Federation of Neurosurgical Societies score and modified Fisher grade, and were more likely to undergo clipping of the ruptured aneurysm as compared to endovascular treatment (30.3% vs 11.3%, p < 0.001). Treatment with IT nicardipine decreased the daily mean transcranial Doppler velocities in 77.3% of the treated patients. When compared to patients not receiving IT nicardipine, treatment was not associated with an increased rate of bacterial ventriculitis (3.1% vs 2.7%, p > 0.1), yet higher rates of ventriculoperitoneal shunting were noted (19.9% vs 8.8%, p < 0.01). In a propensity score comparison to the SAHIT database, the odds ratio (OR) to develop DCI with IT nicardipine treatment was 0.61 (95% confidence interval [CI] 0.44-0.84), and the OR to have a favorable functional outcome (modified Rankin Scale score ≤ 2) was 2.17 (95% CI 1.61-2.91). CONCLUSIONS: IT nicardipine was associated with improved outcome and reduced DCI compared with propensity-matched controls. There was an increased need for permanent CSF diversion but no other safety issues. These data should be considered when selecting medications and treatments to study in future randomized controlled clinical trials for SAH.

Rescue therapy for vasospasm following aneurysmal subarachnoid hemorrhage: a propensity score-matched analysis with machine learning.

OBJECTIVE: Rescue therapies have been recommended for patients with angiographic vasospasm (aVSP) and delayed cerebral ischemia (DCI) following subarachnoid hemorrhage (SAH). However, there is little evidence from randomized clinical trials that these therapies are safe and effective. The primary aim of this study was to apply game theory-based methods in explainable machine learning (ML) and propensity score matching to determine if rescue therapy was associated with better 3-month outcomes following post-SAH aVSP and DCI. The authors also sought to use these explainable ML methods to identify patient populations that were more likely to receive rescue therapy and factors associated with better outcomes after rescue therapy. METHODS: Data for patients with aVSP or DCI after SAH were obtained from 8 clinical trials and 1 observational study in the Subarachnoid Hemorrhage International Trialists repository. Gradient boosting ML models were constructed for each patient to predict the probability of receiving rescue therapy and the 3-month Glasgow Outcome Scale (GOS) score. Favorable outcome was defined as a 3-month GOS score of 4 or 5. Shapley Additive Explanation (SHAP) values were calculated for each patient-derived model to quantify feature importance and interaction effects. Variables with high SHAP importance in predicting rescue therapy administration were used in a propensity score-matched analysis of rescue therapy and 3-month GOS scores. RESULTS: The authors identified 1532 patients with aVSP or DCI. Predictive, explainable ML models revealed that aneurysm characteristics and neurological complications, but not admission neurological scores, carried the highest relative importance rankings in predicting whether rescue therapy was administered. Younger age and absence of cerebral ischemia/infarction were invariably linked to better rescue outcomes, whereas the other important predictors of outcome varied by rescue type (interventional or noninterventional). In a propensity score-matched analysis guided by SHAP-based variable selection, rescue therapy was associated with higher odds of 3-month GOS scores of 4-5 (OR 1.63, 95% CI 1.22-2.17). CONCLUSIONS: Rescue therapy may increase the odds of good outcome in patients with aVSP or DCI after SAH. Given the strong association between cerebral ischemia/infarction and poor outcome, trials focusing on preventative or therapeutic interventions in these patients may be most able to demonstrate improvements in clinical outcomes. Insights developed from these models may be helpful for improving patient selection and trial design.

Nicardipine Prolonged Release Implants for Prevention of Delayed Cerebral Ischemia after Aneurysmal Subarachnoid Hemorrhage: A Meta-Analysis.

OBJECTIVES: A paucity of treatments to prevent delayed cerebral ischemia (DCI) has stymied recovery after aneurysmal subarachnoid hemorrhage (aSAH). Nicardipine has long been recognized as a potent cerebrovascular vasodilator with a history off-label use to prevent vasospasm and DCI. Multiple centers have developed nicardipine prolonged release implants (NPRI) that are directly applied during clip ligation to locally deliver nicardipine throughout the vasospasm window. Here we perform a systematic review and meta-analysis to assess whether NPRI confers protection against DCI and improves functional outcomes after aSAH. MATERIALS AND METHODS: A systematic search of PubMed, Ovid Embase, and Cochrane databases was performed for studies reporting the use of NPRI after aSAH published after January 1, 1980. We included all studies assessing the association of NPRI with DCI and or functional outcomes. Findings from studies with control arms were analyzed using a random effects model. A separate network meta-analysis was performed, including controlled NPRI studies, single-arm NPRI reports, and the control-arms of modern aSAH randomized clinical trials as additional comparators. RESULTS: The search identified 214 unique citations. Three studies with 284 patients met criteria for the random effects model. The pooled summary odds ratio for the association of NPRI and DCI was 0.21 (95% CI 0.09-0.49, p = 0.0002) with no difference in functional outcomes (OR 1.80, 95% CI 0.63 - 5.16, p = 0.28). 10 studies of 866 patients met criteria for the network meta-analysis. The pooled summary odds ratio for the association of NPRI and DCI was 0.30 (95% CI 0.13-0.89,p = 0.017) with a trend towards improved functional outcomes (OR 1.68, 0.63 - 4.13 95% CI, p = 0.101). CONCLUSIONS: In these meta-analyses, NPRI decreases the incidence of DCI with a non-significant trend towards improvement in functional outcomes. Randomized trials on the role of intrathecal calcium channel blockers are warranted to evaluate these observations in a prospective manner.

Trajectory-Based Classification of Recovery in Sensorimotor Complete Traumatic Cervical Spinal Cord Injury.

OBJECTIVE: To test the hypothesis that sensorimotor complete traumatic cervical spinal cord injury is a heterogenous clinical entity comprising several subpopulations that follow fundamentally different trajectories of neurologic recovery. METHODS: We analyzed demographic and injury data from 655 patients who were pooled from 4 prospective longitudinal multicenter studies. Group based trajectory modeling was applied to model neurologic recovery trajectories over the initial 12-months postinjury and to identify predictors of recovery trajectories. Neurologic outcomes included: Upper Extremity Motor Score, Total Motor Scores and AIS grade improvement. RESULTS: The analysis identified 3 distinct trajectories of neurologic recovery. These clinical courses included: (1) Marginal recovery trajectory: characterized by minimal or no improvement in motor strength or change in AIS grade status (remained grade A); (2) Moderate recovery trajectory: characterized by low baseline motor scores that improved approximately 13 points; or AIS conversion of one grade point; (3) Good recovery trajectory: characterized by baseline motor scores in the upper quartile that improved to near maximum values within 3 months of injury. Patients following the moderate or good recovery trajectories were of younger age, had more caudally located injuries, a higher degree of preserved motor and sensory function at baseline examination and exhibited a greater extent of motor and sensory function in the zone of partial preservation. CONCLUSION: Cervical complete SCI can be classified into one of 3 distinct subpopulations with fundamentally different trajectories of neurologic recovery. This study defines unique clinical phenotypes based on potential for recovery, rather than baseline severity of injury alone. This approach may prove beneficial in clinical prognostication and in the design and interpretation of clinical trials in SCI.

The Effect of Older Age on the Perioperative Outcomes of Spinal Fusion Surgery in Patients With Lumbar Degenerative Disc Disease With Spondylolisthesis: A Propensity Score-Matched Analysis.

BACKGROUND: Degenerative spondylolisthesis (DS) is often treated with lumbar spinal fusion (LSF). However, there is concern that the morbidity of LSF may be prohibitively high in older adults. OBJECTIVE: To evaluate the impact of advanced age on the safety of LSF for DS. METHODS: Patients who underwent LSF for DS were retrospectively identified from National Surgical Quality Improvement Program datasets for 2011 to 2015 using Current Procedural Terminology codes. Data on demographic characteristics, comorbidities, surgical factors, and 30-d morbidity and mortality were collected. Propensity score matching (nearest neighbor) was performed with age (<70 vs ≥70 yr) as the dependent variable and sex, type of fusion procedure, number of levels fused, diabetes, smoking, hypertension, and chronic steroid use as covariates. Outcomes were compared between age <70 and ≥70 groups. RESULTS: The study cohort consisted of 2238 patients (n = 1119, age <70; n = 1119, age ≥70). The 2 age groups were balanced for key covariates including sex, race, diabetes, hypertension, CHF, smoking, chronic steroid use, type of fusion, and number of levels. Rates of all complications were similar between younger and older age groups, except urinary tract infection, which was more frequent among the ≥70 age group (OR 2.32, P = .009). Further, patients in the older age group were more likely to be discharged to a rehabilitation (OR 2.94, P < .001) or skilled care (OR 3.66, P < .001) facility, rather than directly home (OR 0.25, P < .001). CONCLUSION: LSF may be performed safely in older adults with DS. Our results suggest older age alone should not exclude a patient from undergoing lumbar fusion for DS.

Comparison of the Inpatient Complications and Health Care Costs of Anterior versus Posterior Cervical Decompression and Fusion in Patients with Multilevel Degenerative Cervical Myelopathy: A Retrospective Propensity Score-Matched Analysis.

BACKGROUND: The optimal surgical approach for multilevel degenerative cervical myelopathy (DCM) is unclear, and there is significant variation in practice patterns. We sought to compare inpatient complications and costs of anterior (ACDF) versus posterior cervical decompression and fusion (PCDF). METHODS: Patients who underwent multilevel ACDF or PCDF for DCM were identified from the National Inpatient Sample for 2004-2014 using ICD-9-CM codes. Propensity score matching was performed with age, sex, comorbidities, hospital bed size, and use of intraoperative monitoring as covariates. Hospitalization charges/costs, length of stay (LOS), discharge disposition, and inpatient morbidity/mortality were compared between matched ACDF and PCDF groups. RESULTS: Propensity score matching generated a cohort of 13,884 patients (n = 6,942 ACDF; n = 6,942 PCDF). PCDF was associated with greater LOS (mean difference [MD] +1.7 days, P < 0.001) and less frequent routine discharge home (odds ratio [OR] 0.26, P < 0.01). With regard to complications, PCDF had a higher rate of myocardial infarction (OR 1.6, P = 0.007), pulmonary embolism (OR 2.6, P = 0.009), deep vein thrombosis (OR 3.7, P < 0.001), neurological complications (OR 1.7, P = 0.037), hardware-related complications (OR 2.7, P < 0.001), wound infection/breakdown (OR 6.8, P < 0.001), and cerebrospinal fluid leak (OR 1.7, P = 0.011). By contrast, rates of postoperative hematoma (OR 0.61, P = 0.007), hoarseness (OR 0.13, P < 0.001), and dysphagia (OR 0.20, P < 0.001) were higher after ACDF. Mortality was comparable. Hospital charges (MD +$26,259, P < 0.001) and costs (MD +$7,728, P < 0.001) were significantly higher for PCDF. CONCLUSIONS: At a national level, for multilevel DCM, we found PCDF to be associated with greater LOS, in-hospital costs, and general medical and surgical complications. ACDF carried higher risk of postoperative hematoma, hoarseness, and dysphagia.

Between-center and between-country differences in outcome after aneurysmal subarachnoid hemorrhage in the Subarachnoid Hemorrhage International Trialists (SAHIT) repository.

OBJECTIVE: Differences in clinical outcomes between centers and countries may reflect variation in patient characteristics, diagnostic and therapeutic policies, or quality of care. The purpose of this study was to investigate the presence and magnitude of between-center and between-country differences in outcome after aneurysmal subarachnoid hemorrhage (aSAH). METHODS: The authors analyzed data from 5972 aSAH patients enrolled in randomized clinical trials of 3 different treatments from the Subarachnoid Hemorrhage International Trialists (SAHIT) repository, including data from 179 centers and 20 countries. They used random effects logistic regression adjusted for patient characteristics and timing of aneurysm treatment to estimate between-center and between-country differences in unfavorable outcome, defined as a Glasgow Outcome Scale score of 1-3 (severe disability, vegetative state, or death) or modified Rankin Scale score of 4-6 (moderately severe disability, severe disability, or death) at 3 months. Between-center and between-country differences were quantified with the median odds ratio (MOR), which can be interpreted as the ratio of odds of unfavorable outcome between a typical high-risk and a typical low-risk center or country. RESULTS: The proportion of patients with unfavorable outcome was 27% (n = 1599). The authors found substantial between-center differences (MOR 1.26, 95% CI 1.16-1.52), which could not be explained by patient characteristics and timing of aneurysm treatment (adjusted MOR 1.21, 95% CI 1.11-1.44). They observed no between-country differences (adjusted MOR 1.13, 95% CI 1.00-1.40). CONCLUSIONS: Clinical outcomes after aSAH differ between centers. These differences could not be explained by patient characteristics or timing of aneurysm treatment. Further research is needed to confirm the presence of differences in outcome after aSAH between hospitals in more recent data and to investigate potential causes.

Acute Adverse Events After Spinal Cord Injury and Their Relationship to Long-term Neurologic and Functional Outcomes: Analysis From the North American Clinical Trials Network for Spinal Cord Injury.

OBJECTIVES: There are few contemporary, prospective multicenter series on the spectrum of acute adverse events and their relationship to long-term outcomes after traumatic spinal cord injury. The goal of this study is to assess the prevalence of adverse events after traumatic spinal cord injury and to evaluate the effects on long-term clinical outcome. DESIGN: Multicenter prospective registry. SETTING: Consortium of 11 university-affiliated medical centers in the North American Clinical Trials Network. PATIENTS: Eight-hundred one spinal cord injury patients enrolled by participating centers. INTERVENTIONS: Appropriate spinal cord injury treatment at individual centers. MEASUREMENTS AND MAIN RESULTS: A total of 2,303 adverse events were recorded for 502 patients (63%). Penalized maximum logistic regression models were fitted to estimate the likelihood of neurologic recovery (ASIA Impairment Scale improvement ≥ 1 grade point) and functional outcomes in subjects who developed adverse events at 6 months postinjury. After accounting for potential confounders, the group that developed adverse events showed less neurologic recovery (odds ratio, 0.55; 95% CI, 0.32-0.96) and was more likely to require assisted breathing (odds ratio, 6.55; 95% CI, 1.17-36.67); dependent ambulation (odds ratio, 7.38; 95% CI, 4.35-13.06) and have impaired bladder (odds ratio, 9.63; 95% CI, 5.19-17.87) or bowel function (odds ratio, 7.86; 95% CI, 4.31-14.32) measured using the Spinal Cord Independence Measure subscores. CONCLUSIONS: Results from this contemporary series demonstrate that acute adverse events are common and are associated with worsened long-term outcomes after traumatic spinal cord injury.

Emotional expressions associated with therapeutic inertia in multiple sclerosis care.

BACKGROUND: Emotions play a critical role in our daily decisions. However, it remains unclear how and what sort of emotional expressions are associated with therapeutic decisions in multiple sclerosis (MS) care. Our goal was to evaluate the relationship between emotions and affective states (as captured by muscle facial activity and emotional expressions) and TI amongst neurologists caring for MS patients when making therapeutic decisions. METHODS: 38 neurologists with expertise in MS were invited to participate in a face-to-face study across Canada. Participants answered questions regarding their clinical practice, aversion to ambiguity, and the management of 10 simulated case-scenarios. TI was defined as lack of treatment initiation or escalation when there was clear evidence of clinical and radiological disease activity. We recorded facial muscle activations and their associated emotional expressions during the study, while participants made therapeutic choices. We used a validated machine learning algorithm of the AFFDEX software to code for facial muscle activations and a predefined mapping to emotional expressions (disgust, fear, surprise, etc.). Mixed effects models and mediation analyses were used to evaluate the relationship between ambiguity aversion, facial muscle activity/emotional expressions and TI measured as a binary variable and a continuous score. RESULTS: 34 (89.4%) neurologists completed the study. The mean age [standard deviation (SD)] was 44.6 (11.5) years; 38.3% were female and 58.8% self-identified as MS specialists. Overall, 17 (50%) participants showed TI in at least one case-scenario and the mean (SD) TI score was 0.74 (0.90). Nineteen (55.9%) participants had aversion to ambiguity in the financial domain. The multivariate analysis adjusted for age, sex and MS expertise showed that aversion to ambiguity in the financial domain (OR 1.56, 95%CI 1.32-1.86) was associated with TI. Most common muscle activations included mouth open (23.4%), brow furrow (20.9%), brow raise (17.6%), and eye widening (13.1%). Most common emotional expressions included fear (5.1%), disgust (3.2%), sadness (2.9%), and surprise (2.8%). After adjustment for age, sex, and physicians' expertise, the multivariate analysis revealed that brow furrow (OR 1.04; 95%CI 1.003-1.09) and lip suck (OR 1.06; 95%CI 1.01-1.11) were associated with an increase in TI prevalence, whereas upper lip raise (OR 0.30; 95%CI 0.15-0.59), and chin raise (OR 0.90; 95%CI 0.83-0.98) were associated with lower likelihood of TI. Disgust and surprise were associated with a lower TI score (disgust: p < 0.001; surprise: p = 0.008) and lower prevalence of TI (ORdisgust: 0.14, 95%CI 0.03-0.65; ORsurprise: 0.66, 94%CI 0.47-0.92) after adjusting for covariates. The mediation analysis showed that brow furrow was a partial mediator explaining 21.2% (95%CI 14.9%-38.9%) of the association between aversion to ambiguity and TI score, followed by nose wrinkle 12.8% (95%CI 8.9%-23.4%). Similarly, disgust was the single emotional expression (partial mediator) that attenuated (-13.2%, 95%CI -9.2% to -24.3%) the effect of aversion to ambiguity on TI. CONCLUSIONS: TI was observed in half of participants in at least one case-scenario. Our data suggest that facial metrics (e.g. brow furrow, nose wrinkle) and emotional expressions (e.g. disgust) are associated with physicians' choices and partially mediate the effect of aversion to ambiguity on TI.

Association of Pneumonia, Wound Infection, and Sepsis with Clinical Outcomes after Acute Traumatic Spinal Cord Injury.

Pneumonia, wound infections, and sepsis (PWS) are the leading causes of acute mortality after traumatic spinal cord injury (SCI). However, the impact of PWS on neurological and functional outcomes is largely unknown. The present study analyzed participants from the prospective North American Clinical Trials Network (NACTN) registry and the Surgical Timing in Acute SCI Study (STASCIS) for the association between PWS and functional outcome (assessed as Spinal Cord Independence Measure subscores for respiration and indoor ambulation) at 6 months post-injury. Neurological outcome was analyzed as a secondary end-point. Among 1299 participants studied, 180 (14%) developed PWS during the acute admission. Compared with those without PWS, participants with PWS were mostly male (76% vs. 86%; p = 0.007), or presented with mostly American Spinal Injury Association Impairment Scale (AIS) grade A injury (36% vs. 61%; p < 0.001). There were no statistical differences between participants with or without PWS with respect to time from injury to surgery, and administration of steroids. Dominance analysis showed injury level, baseline AIS grade, and subject pre-morbid medical status collectively accounted for 77.7% of the predicted variance of PWS. Regression analysis indicated subjects with PWS demonstrated higher odds for respiratory (odds ratio [OR] 3.91, 95% confidence interval [CI]: 1.42-10.79) and ambulatory (OR 3.94, 95% CI: 1.50-10.38) support at 6 month follow-up in adjusted analysis. This study has shown an association between PWS occurring during acute admission and poorer functional outcomes following SCI.

Procarbazine, CCNU and vincristine (PCV) versus temozolomide chemotherapy for patients with low-grade glioma: a systematic review.

Low-grade gliomas (LGG) encompass a heterogeneous group of tumors that are clinically, histologically and molecularly diverse. Treatment decisions for patients with LGG are directed toward improving upon the natural history while limiting treatment-associated toxiceffects. Recent evidence has documented a utility for adjuvant chemotherapy with procarbazine, CCNU (lomustine), and vincristine (PCV) or temozolomide (TMZ). We sought to determine the comparative utility of PCV and TMZ for patients with LGG, particularly in context of molecular subtype. A literature search of PubMed was conducted to identify studies reporting patient response to PCV, TMZ, or a combination of chemotherapy and radiation therapy (RT). Eligibility criteria included patients 16 years of age and older, notation of LGG subtype, and report of progression-free survival (PFS), overall survival (OS), and treatment course. Level I, II, and III data were included. Adjuvant therapy with PCV resulted in prolonged PFS and OS in patients with newly diagnosed high-risk LGG. This benefit was accrued most significantly by patients with tumors harboring 1p/19q codeletion and IDH1 mutation. Adjuvant therapy with temozolomide was associated with lower toxicity than therapy with PCV. In patients with LGG with an unfavorable natural history, such as with intact 1p/19q and wild-type IDH1, RT/TMZ plus adjuvant TMZ may be the best option. Patients with biologically favorable high-risk LGG are likely to derive the most benefit from RT and adjuvant PCV.

Patient phenotypes associated with outcome following surgery for mild degenerative cervical myelopathy: a principal component regression analysis.

BACKGROUND CONTEXT: Predictors of outcome after surgery for degenerative cervical myelopathy (DCM) have been determined previously through hypothesis-driven multivariate statistical models that rely on a priori knowledge of potential confounders, exclude potentially important variables because of restrictions in model building, cannot include highly collinear variables in the same model, and ignore intrinsic correlations among variables. PURPOSE: The present study aimed to apply a data-driven approach to identify patient phenotypes that may predict outcomes after surgery for mild DCM. STUDY DESIGN: This is a principal component analysis of data from two related prospective, multicenter cohort studies. PATIENT SAMPLE: The study included patients with mild DCM, defined by a modified Japanese Orthopaedic Association score of 15-17, undergoing surgical decompression as part of the AOSpine CSM-NA or CSM-I trials. OUTCOME MEASURES: Patient outcomes were evaluated preoperatively at baseline and at 6 months, 1 year, and 2 years after surgery. Quality of life (QOL) was evaluated by the Neck Disability Index (NDI) and Short Form-36 version 2 (SF-36v2). These are both patient self-reported measures that evaluate health-related QOL, with NDI being specific to neck conditions and SF-36v2 being a generic instrument. MATERIALS AND METHODS: The analysis included 154 patients. A heterogeneous correlation matrix was created using a combination of Pearson, polyserial, and polychoric regressions among 67 variables, which then underwent eigen decomposition. Scores of significant principal components (PCs) (with eigenvalues>1) were included in multivariate logistic regression analyses for three dichotomous outcomes of interest: achievement of the minimum clinically important difference [MCID] in (1) NDI (≤-7.5), (2) SF-36v2 Physical Component Summary (PCS) score (≥5), and (3) SF-36v2 Mental Component Summary (MCS) score (≥5). RESULTS: Twenty-four significant PCs accounting for 75% of the variance in the data were identified. Two PCs were associated with achievement of the MCID in NDI. The first (PC 1) was dominated by variables related to surgical approach and number of operated levels; the second (PC 21) consisted of variables related to patient demographics, severity and etiology of DCM, comorbid status, and surgical approach. Both PC 1 and PC 21 also correlated with SF-36v2 PCS score, in addition to PC 4, which described patients' physical profile, including gender, height, and weight, as well as comorbid renal disease; PC 6, which received large loadings from variables related to cardiac disease, impaired mobility, and length of surgery and recovery; and PC 9, which harbored large contributions from features of upper limb dysfunction, cardiorespiratory disease, surgical approach, and region. In addition to PC 21, a component profiling patients' socioeconomic status and support systems and degree of physical disability (PC 24) was associated with achievement of the MCID in SF-36 MCS score. CONCLUSIONS: Through a data-driven approach, we identified several phenotypes associated with disability and physical and mental health-related QOL. Such data reduction methods may separate patient-, disease-, and treatment-related variables more accurately into clinically meaningful phenotypes that may inform patient care and recruitment into clinical trials.

Minimum Clinically Important Difference in SF-36 Scores for Use in Degenerative Cervical Myelopathy.

STUDY DESIGN: Post-hoc analysis of 606 patients enrolled in the AOSpine CSM-NA or CSM-I prospective, multicenter cohort studies. OBJECTIVE: The aim of this study was to determine the minimum clinically important difference (MCID) in SF-36v2 Physical Component Summary (PCS) and Mental Component Summary (MCS) scores in patients undergoing surgery for degenerative cervical myelopathy (DCM). SUMMARY OF BACKGROUND DATA: There has been a shift toward focus on patient-reported outcomes (PROs) in spine surgery. However, the numerical scores of PROs lack immediate clinical meaning. The MCID adds a dimension of interpretability to PRO scales; by defining the smallest change, a patient would consider meaningful. METHODS: The MCID of the SF-36v2 PCS and MCS were determined by distribution- and anchor-based methods comparing preoperative to 12-month scores. Distribution-based approaches included calculation of the half standard deviation and standard error of measurement (SEM). Change in Neck Disability Index (NDI) served as the anchor: "worse" (ΔNDI>7.5); "unchanged" (7.5≥ΔNDI>-7.5); "slightly improved" (-7.5≥ΔNDI>-15); and "markedly improved" (ΔNDI ≤-15). Receiver operating characteristic (ROC) analysis was performed to determine the change score for the MCID with even sensitivity and specificity to distinguish patients who were "slightly improved" versus "unchanged" on the NDI. RESULTS: The MCID for the SF-36v2 PCS and MCS were 4.6 and 6.8 by half standard deviation and 2.9 and 4.3 by SEM, respectively. By ROC analysis, the MCID was 3.9 for the SF-36v2 PCS score and 3.2 for the SF-36v2 MCS score. Using a cutoff of 4 points, the SF-36v2 PCS had a sensitivity of 72.2% and specificity of 68.1%, and MCS 61.9% and 64.6%, respectively, in separating patients who were "markedly improved" or "slightly improved" from those who were "unchanged" or "worse." CONCLUSION: We found the MCID of the SF-36v2 PCS and MCS to be 4 points. This will facilitate use of the SF-36v2 as an outcome in future studies of DCM. LEVEL OF EVIDENCE: 3.

Natural History, Predictors of Outcome, and Effects of Treatment in Thoracic Spinal Cord Injury: A Multi-Center Cohort Study from the North American Clinical Trials Network.

The course, treatment response, and recovery potential after acute traumatic spinal cord injury (SCI) have been shown to differ depending on the neurological level of injury. There are limited data focused on thoracic-level injuries, however. A cohort of 86 patients from the prospectively maintained North American Clinical Trials Network SCI registry were identified and studied to characterize the patterns of neurological recovery and to determine rates of acute hospital death and pulmonary complications. Regression analyses were used to examine the relationship between timing of surgery and administration of methylprednisolone on neurologic and clinical outcomes. Neurological conversion (≥1 American Spinal Injury Association Impairment Scale [AIS] grade improvement) was poorest for AIS grade A patients; 14.3% converted at last available follow-up (mean eight months). While rates of conversion were more optimistic for AIS-B patients (54.5%) and AIS C injuries (77.8%) at the same time point, none of the AIS grade D patients converted to AIS E. At last available follow-up (mean eight months), the magnitudes of lower motor extremity score (LEMS) change were highest for AIS C injuries (21.9 points), then AIS B (17.7 points), AIS D (16.4 points), and finally AIS A (2.5 points) (p < 0.05). Early surgical intervention (<24 h post-injury) was independently associated with an additional seven points in motor recovery and a 60% decreased incidence of pulmonary events (p < 0.05). Methylprednisolone administration was not an independent predictor of neurological outcome or pulmonary complications. Evaluation of this cohort obtained from a modern multi-center SCI registry provides an update on the natural history, acute death, and incidence of pulmonary complications after traumatic thoracic SCI. Although small sample size limited the extent of analyses possible, early surgical treatment was associated with significantly larger motor recovery and lower rates of pulmonary complications.

Development and validation of outcome prediction models for aneurysmal subarachnoid haemorrhage: the SAHIT multinational cohort study.

OBJECTIVE: To develop and validate a set of practical prediction tools that reliably estimate the outcome of subarachnoid haemorrhage from ruptured intracranial aneurysms (SAH). DESIGN: Cohort study with logistic regression analysis to combine predictors and treatment modality. SETTING: Subarachnoid Haemorrhage International Trialists' (SAHIT) data repository, including randomised clinical trials, prospective observational studies, and hospital registries. PARTICIPANTS: Researchers collaborated to pool datasets of prospective observational studies, hospital registries, and randomised clinical trials of SAH from multiple geographical regions to develop and validate clinical prediction models. MAIN OUTCOME MEASURE: Predicted risk of mortality or functional outcome at three months according to score on the Glasgow outcome scale. RESULTS: Clinical prediction models were developed with individual patient data from 10 936 patients and validated with data from 3355 patients after development of the model. In the validation cohort, a core model including patient age, premorbid hypertension, and neurological grade on admission to predict risk of functional outcome had good discrimination, with an area under the receiver operator characteristics curve (AUC) of 0.80 (95% confidence interval 0.78 to 0.82). When the core model was extended to a "neuroimaging model," with inclusion of clot volume, aneurysm size, and location, the AUC improved to 0.81 (0.79 to 0.84). A full model that extended the neuroimaging model by including treatment modality had AUC of 0.81 (0.79 to 0.83). Discrimination was lower for a similar set of models to predict risk of mortality (AUC for full model 0.76, 0.69 to 0.82). All models showed satisfactory calibration in the validation cohort. CONCLUSION: The prediction models reliably estimate the outcome of patients who were managed in various settings for ruptured intracranial aneurysms that caused subarachnoid haemorrhage. The predictor items are readily derived at hospital admission. The web based SAHIT prognostic calculator (http://sahitscore.com) and the related app could be adjunctive tools to support management of patients.