A minimum data set-Core outcome set, core data elements, and core measurement set-For degenerative cervical myelopathy research (AO Spine RECODE DCM): A consensus study.

BACKGROUND: Degenerative cervical myelopathy (DCM) is a progressive chronic spinal cord injury estimated to affect 1 in 50 adults. Without standardised guidance, clinical research studies have selected outcomes at their discretion, often underrepresenting the disease and limiting comparability between studies. Utilising a standard minimum data set formed via multi-stakeholder consensus can address these issues. This combines processes to define a core outcome set (COS)-a list of key outcomes-and core data elements (CDEs), a list of key sampling characteristics required to interpret the outcomes. Further "how" these outcomes should be measured and/or reported is then defined in a core measurement set (CMS). This can include a recommendation of a standardised time point at which outcome data should be reported. This study defines a COS, CDE, and CMS for DCM research. METHODS AND FINDINGS: A minimum data set was developed using a series of modified Delphi processes. Phase 1 involved the setup of an international DCM stakeholder group. Phase 2 involved the development of a longlist of outcomes, data elements, and formation into domains. Phase 3 prioritised the outcomes and CDEs using a two-stage Delphi process. Phase 4 determined the final DCM minimal data set using a consensus meeting. Using the COS, Phase 5 finalised definitions of the measurement construct for each outcome. In Phase 6, a systematic review of the literature was performed, to scope and define the psychometric properties of measurement tools. Phase 7 used a modified Delphi process to inform the short-listing of candidate measurement tools. The final measurement set was then formed through a consensus meeting (Phase 8). To support implementation, the data set was then integrated into template clinical research forms (CRFs) for use in future clinical trials (Phase 9). In total, 28 outcomes and 6 domains (Pain, Neurological Function, Life Impact, Radiology, Economic Impact, and Adverse Events) were entered into the final COS. Thirty two outcomes and 4 domains (Individual, Disease, Investigation, and Intervention) were entered into the final CDE. Finally, 4 outcome instruments (mJOA, NDI, SF-36v2, and SAVES2) were identified for the CMS, with a recommendation for trials evaluating outcomes after surgery, to include baseline measurement and at 6 months from surgery. CONCLUSIONS: The AO Spine RECODE-DCM has produced a minimum data set for use in DCM clinical trials today. These are available at https://myelopathy.org/minimum-dataset/. While it is anticipated the CDE and COS have strong and durable relevance, it is acknowledged that new measurement tools, alongside an increasing transition to study patients not undergoing surgery, may necessitate updates and adaptation, particularly with respect to the CMS.

Influence of health insurance on withdrawal of life sustaining treatment for patients with isolated traumatic brain injury: a retrospective multi-center observational cohort study.

BACKGROUND: Healthcare inequities for patients with traumatic brain injury (TBI) represent a major priority area for trauma quality improvement. We hypothesized a relationship between health insurance status and timing of withdrawal of life sustaining treatment (WLST) for adults with severe TBI. METHODS: This multicenter retrospective observational cohort study utilized data collected between 2017 and 2020. We identified adult (age ≥ 16) patients with isolated severe TBI admitted participating Trauma Quality Improvement Program centers. We determined the relationship between insurance status (public, private, and uninsured) and the timing of WLST using a competing risk survival analysis framework adjusting for baseline, clinical, injury and trauma center characteristics. Multivariable cause-specific Cox regressions were used to compute adjusted hazard ratios (HR) reflecting timing of WLST, accounting for mortality events. We also quantified the between-center residual variability in WLST using the median odds ratio (MOR) and measured insurance status association with access to rehabilitation at discharge. RESULTS: We identified 42,111 adults with isolated severe TBI treated across 509 trauma centers across North America. There were 10,771 (25.6%) WLST events in the cohort and a higher unadjusted incidence of WLST events was evident in public insurance patients compared to private or uninsured groups. After adjustment, WLST occurred earlier for publicly insured (HR 1.07, 95% CI 1.02-1.12) and uninsured patients (HR 1.29, 95% CI 1.18-1.41) compared to privately insured patients. Access to rehabilitation was lower for both publicly insured and uninsured patients compared to patients with private insurance. Accounting for case-mix, the MOR was 1.49 (95% CI 1.43-1.55), reflecting significant residual between-center variation in WLST decision-making. CONCLUSIONS: Our findings highlight the presence of disparate WLST practices independently associated with health insurance status. Additionally, these results emphasize between-center variability in WLST, persisting despite adjustments for measurable patient and trauma center characteristics.

Lived experience-centred word clouds may improve research uncertainty gathering in priority setting partnerships.

INTRODUCTION: AO Spine RECODE-DCM was a multi-stakeholder priority setting partnership (PSP) to define the top ten research priorities for degenerative cervical myelopathy (DCM). Priorities were generated and iteratively refined using a series of surveys administered to surgeons, other healthcare professionals (oHCP) and people with DCM (PwDCM). The aim of this work was to utilise word clouds to enable the perspectives of people with the condition to be heard earlier in the PSP process than is traditionally the case. The objective was to evaluate the added value of word clouds in the process of defining research uncertainties in National Institute for Health Research (NIHR) James Lind Alliance (JLA) Priority Setting Partnerships. METHODS: Patient-generated word clouds were created for the four survey subsections of the AO Spine RECODE-DCM PSP: diagnosis, treatment, long-term management and other issues. These were then evaluated as a nested methodological study. Word-clouds were created and iteratively refined by an online support group of people with DCM, before being curated by the RECODE-DCM management committee and expert healthcare professional representatives. The final word clouds were embedded within the surveys administered at random to 50% of participants. DCM research uncertainties suggested by participants were compared pre- and post-word cloud presentation. RESULTS: A total of 215 (50.9%) participants were randomised to the word cloud stream, including 118 (55%) spinal surgeons, 52 (24%) PwDCM and 45 (21%) oHCP. Participants submitted 434 additional uncertainties after word cloud review: word count was lower and more uniform across each survey subsections compared to pre-word cloud uncertainties. Twenty-three (32%) of the final 74 PSP summary questions did not have a post-word cloud contribution and no summary question was formed exclusively on post-word cloud uncertainties. There were differences in mapping of pre- and post-word cloud uncertainties to summary questions, with greater mapping of post-word cloud uncertainties to the number 1 research question priority: raising awareness. Five of the final summary questions were more likely to map to the research uncertainties suggested by participants after having reviewed the word clouds. CONCLUSIONS: Word clouds may increase the perspective of underrepresented stakeholders in the research question gathering stage of priority setting partnerships. This may help steer the process towards research questions that are of highest priority for people with the condition.

Factors influencing withdrawal of life-supporting treatment in cervical spinal cord injury: a large multicenter observational cohort study.

BACKGROUND: Traumatic spinal cord injury (SCI) leads to profound neurologic sequelae, and the provision of life-supporting treatment serves great importance among this patient population. The decision for withdrawal of life-supporting treatment (WLST) in complete traumatic SCI is complex with the lack of guidelines and limited understanding of practice patterns. We aimed to evaluate the individual and contextual factors associated with the decision for WLST and assess between-center differences in practice patterns across North American trauma centers for patients with complete cervical SCI. METHODS: This retrospective multicenter observational cohort study utilized data derived from the American College of Surgeons Trauma Quality Improvement Program database between 2017 and 2020. The study included adult patients (> 16 years) with complete cervical SCI. We constructed a multilevel mixed effect logistic regression model to adjust for patient, injury and hospital factors influencing WLST. Factors associated with WLST were estimated through odds ratios with 95% confidence intervals. Hospital variability was characterized using the median odds ratio. Unexplained residual variability was assessed through the proportional change in variation between models. RESULTS: We identified 5070 patients with complete cervical SCI treated across 477 hospitals, of which 960 (18.9%) had WLST. Patient-level factors associated with significantly increased likelihood of WLST were advanced age, male sex, white race, prior dementia, low presenting Glasgow Coma Scale score, having a pre-hospital cardiac arrest, SCI level of C3 or above, and concurrent severe injury to the head or thorax. Patient-level factors associated with significantly decreased likelihood of WLST included being racially Black or Asian. There was significant variability across hospitals in the likelihood for WLST while accounting for case-mix, hospital size, and teaching status (MOR 1.51 95% CI 1.22-1.75). CONCLUSIONS: A notable proportion of patients with complete cervical SCI undergo WLST during their in-hospital admission. We have highlighted several factors associated with this decision and identified considerable variability between hospitals. Further work to standardize WLST guidelines may improve equity of care provided to this patient population.

Proteomic Portraits Reveal Evolutionarily Conserved and Divergent Responses to Spinal Cord Injury.

Despite the emergence of promising therapeutic approaches in preclinical studies, the failure of large-scale clinical trials leaves clinicians without effective treatments for acute spinal cord injury (SCI). These trials are hindered by their reliance on detailed neurological examinations to establish outcomes, which inflate the time and resources required for completion. Moreover, therapeutic development takes place in animal models whose relevance to human injury remains unclear. Here, we address these challenges through targeted proteomic analyses of cerebrospinal fluid and serum samples from 111 patients with acute SCI and, in parallel, a large animal (porcine) model of SCI. We develop protein biomarkers of injury severity and recovery, including a prognostic model of neurological improvement at 6 months with an area under the receiver operating characteristic curve of 0.91, and validate these in an independent cohort. Through cross-species proteomic analyses, we dissect evolutionarily conserved and divergent aspects of the SCI response and establish the cerebrospinal fluid abundance of glial fibrillary acidic protein as a biochemical outcome measure in both humans and pigs. Our work opens up new avenues to catalyze translation by facilitating the evaluation of novel SCI therapies, while also providing a resource from which to direct future preclinical efforts.

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.

Predicting the minimum clinically important difference in patients undergoing surgery for the treatment of degenerative cervical myelopathy.

OBJECTIVE The minimum clinically important difference (MCID) is defined as the minimum change in a measurement that a patient would identify as beneficial. Before undergoing surgery, patients are likely to inquire about the ultimate goals of the operation and of their chances of experiencing meaningful improvements. The objective of this study was to define significant predictors of achieving an MCID on the modified Japanese Orthopaedic Association (mJOA) scale at 2 years following surgery for the treatment of degenerative cervical myelopathy (DCM). METHODS Seven hundred fifty-seven patients were prospectively enrolled in either the AOSpine North America or International study at 26 global sites. Fourteen patients had a perfect preoperative mJOA score of 18 and were excluded from this analysis (n = 743). Data were collected for each participating subject, including demographic information, symptomatology, medical history, causative pathology, and functional impairment. Univariate log-binominal regression analyses were conducted to evaluate the association between preoperative clinical factors and achieving an MCID on the mJOA scale. Modified Poisson regression using robust error variances was used to create the final multivariate model and compute the relative risk for each predictor. RESULTS The sample consisted of 463 men (62.31%) and 280 women (37.69%), with an average age of 56.48 ± 11.85 years. At 2 years following surgery, patients exhibited a mean change in functional status of 2.71 ± 2.89 points on the mJOA scale. Of the 687 patients with available follow-up data, 481 (70.01%) exhibited meaningful gains on the mJOA scale, whereas 206 (29.98%) failed to achieve an MCID. Based on univariate analysis, significant predictors of achieving the MCID on the mJOA scale were younger age; female sex; shorter duration of symptoms; nonsmoking status; a lower comorbidity score and absence of cardiovascular disease; and absence of upgoing plantar responses, lower-limb spasticity, and broad-based unstable gait. The final model included age (relative risk [RR] 0.924, p < 0.0001), smoking status (RR 0.837, p = 0.0043), broad-based unstable gait (RR 0.869, p = 0.0036), and duration of symptoms (RR 0.943, p = 0.0003). CONCLUSIONS In this large multinational prospective cohort, 70% of patients treated surgically for DCM exhibited a meaningful functional gain on the mJOA scale. The key predictors of achieving an MCID on the mJOA scale were younger age, shorter duration of symptoms, nonsmoking status, and lack of significant gait impairment.

Economic evaluation of decompressive craniectomy versus barbiturate coma for refractory intracranial hypertension following traumatic brain injury.

OBJECTIVES: Decompressive craniectomy and barbiturate coma are often used as second-tier strategies when intracranial hypertension following severe traumatic brain injury is refractory to first-line treatments. Uncertainty surrounds the decision to choose either treatment option. We investigated which strategy is more economically attractive in this context. DESIGN: We performed a cost-utility analysis. A Markov Monte Carlo microsimulation model with a life-long time horizon was created to compare quality-adjusted survival and cost of the two treatment strategies, from the perspective of healthcare payer. Model parameters were estimated from the literature. Two-dimensional simulation was used to incorporate parameter uncertainty into the model. Value of information analysis was conducted to identify major drivers of decision uncertainty and focus future research. SETTING: Trauma centers in the United States. SUBJECTS: Base case was a population of patients (mean age = 25 yr) who developed refractory intracranial hypertension following traumatic brain injury. INTERVENTIONS: We compared two treatment strategies: decompressive craniectomy and barbiturate coma. MEASUREMENTS AND MAIN RESULTS: Decompressive craniectomy was associated with an average gain of 1.5 quality-adjusted life years relative to barbiturate coma, with an incremental cost-effectiveness ratio of $9,565/quality-adjusted life year gained. Decompressive craniectomy resulted in a greater quality-adjusted life expectancy 86% of the time and was more cost-effective than barbiturate coma in 78% of cases if our willingness-to-pay threshold is $50,000/quality-adjusted life year and 82% of cases at a threshold of $100,000/quality-adjusted life year. At older age, decompressive craniectomy continued to increase survival but at higher cost (incremental cost-effectiveness ratio = $197,906/quality-adjusted life year at mean age = 85 yr). CONCLUSIONS: Based on available evidence, decompressive craniectomy for the treatment of refractory intracranial hypertension following traumatic brain injury provides better value in terms of costs and health gains than barbiturate coma. However, decompressive craniectomy might be less economically attractive for older patients. Further research, particularly on natural history of severe traumatic brain injury patients, is needed to make more informed treatment decisions.

Early surgery compared to nonoperative management for mild degenerative cervical myelopathy: a cost-utility analysis.

BACKGROUND CONTEXT: Degenerative cervical myelopathy (DCM) is a form of acquired spinal cord compression and contributes to reduced quality of life secondary to neurological dysfunction and pain. There remains uncertainty regarding optimal management for individuals with mild myelopathy. Specifically, owing to lacking long-term natural history studies in this population, we do not know whether these individuals should be treated with initial surgery or observation. PURPOSE: We sought to perform a cost-utility analysis to examine early surgery for mild degenerative cervical myelopathy from the healthcare payer perspective. STUDY DESIGN/SETTING: We utilized data from the prospective observational cohorts included in the Cervical Spondylotic Myelopathy AO Spine International and North America studies to determine health related quality of life estimates and clinical myelopathy outcomes. PATIENT SAMPLE: We recruited all patients that underwent surgery for DCM enrolled in the Cervical Spondylotic Myelopathy AO Spine International and North America studies between December 2005 and January 2011. OUTCOME MEASURES: Clinical assessment measures were obtained using the Modified Japanese Orthopedic Association scale and health-related quality of life measures were obtained using the Short Form-6D utility score at baseline (preoperative), 6 months, 12 months and 24 months postsurgery. Cost measures inflated to January 2015 values were obtained using pooled estimates from the hospital payer perspective for surgical patients. METHODS: We employed a Markov state transition model with Monte Carlo microsimulation using a lifetime horizon to obtain an incremental cost utility ratio associated with early surgery for mild myelopathy. Parameter uncertainty was assessed through deterministic means using one-way and two-way sensitivity analyses and probabilistically using parameter estimate distributions with microsimulation (10,000 trials). Costs and utilities were discounted at 3% per annum. RESULTS: Initial surgery for mild degenerative cervical myelopathy was associated with an incremental lifetime increase of 1.26 quality-adjusted life years (QALY) compared to observation. The associated cost incurred to the healthcare payer over a lifetime horizon was $12,894.56, resulting in a lifetime incremental cost-utility ratio of $10,250.71/QALY. Utilizing a willingness to pay threshold in keeping with the World Health Organization definition of "very cost-effective" ($54,000 CDN), the probabilistic sensitivity analysis demonstrated that 100% of cases were cost-effective. CONCLUSIONS: Surgery compared to initial observation for mild degenerative cervical myelopathy was cost-effective from the Canadian healthcare payer perspective and was associated with lifetime gains in health-related quality of life.