Safety and Efficacy of Riluzole in Acute Spinal Cord Injury Study (RISCIS): A Multi-Center, Randomized, Placebo-Controlled, Double-Blinded Trial.

Riluzole is a sodium-glutamate antagonist that attenuates neurodegeneration in amyotrophic lateral sclerosis (ALS). It has shown favorable results in promoting recovery in pre-clinical models of traumatic spinal cord injury (tSCI) and in early phase clinical trials. This study aimed to evaluate the efficacy and safety of riluzole in acute cervical tSCI. An international, multi-center, prospective, randomized, double-blinded, placebo-controlled, adaptive, Phase III trial (NCT01597518) was undertaken. Patients with American Spinal Injury Association Impairment Scale (AIS) A-C, cervical (C4-C8) tSCI, and <12 h from injury were randomized to receive either riluzole, at an oral dose of 100 mg twice per day (BID) for the first 24 h followed by 50 mg BID for the following 13 days, or placebo. The primary efficacy end-point was change in Upper Extremity Motor (UEM) scores at 180 days. The primary efficacy analyses were conducted on an intention to treat (ITT) and completed cases (CC) basis. The study was powered at a planned enrolment of 351 patients. The trial began in October 2013 and was halted by the sponsor on May 2020 (and terminated in April 2021) in the face of the global COVID-19 pandemic. One hundred ninety-three patients (54.9% of the pre-planned enrolment) were randomized with a follow-up rate of 82.7% at 180 days. At 180 days, in the CC population the riluzole-treated patients compared with placebo had a mean gain of 1.76 UEM scores (95% confidence interval: -2.54-6.06) and 2.86 total motor scores (CI: -6.79-12.52). No drug-related serious adverse events were associated with the use of riluzole. Additional pre-planned sensitivity analyses revealed that in the AIS C population, riluzole was associated with significant improvement in total motor scores (estimate: standard error [SE] 8.0; CI 1.5-14.4) and upper extremity motor scores (SE 13.8; CI 3.1-24.5) at 6 months. AIS B patients had higher reported independence, measured by the Spinal Cord Independence Measure score (45.3 vs. 27.3; d: 18.0 CI: -1.7-38.0) and change in mental health scores, measured by the Short Form 36 mental health domain (2.01 vs. -11.58; d: 13.2 CI: 1.2-24.8) at 180 days. AIS A patients who received riluzole had a higher average gain in neurological levels at 6 months compared with placebo (mean 0.50 levels gained vs. 0.12 in placebo; d: 0.38, CI: -0.2-0.9). The primary analysis did not achieve the predetermined end-point of efficacy for riluzole, likely related to insufficient power. However, on pre-planned secondary analyses, all subgroups of cervical SCI subjects (AIS grades A, B and C) treated with riluzole showed significant gains in functional recovery. The results of this trial may warrant further investigation to extend these findings. Moreover, guideline development groups may wish to assess the possible clinical relevance of the secondary outcome analyses, in light of the fact that SCI is an uncommon orphan disorder without an accepted neuroprotective treatment.

The Impact of Halting Elective Admissions in Anticipation of a Demand Surge Due to the Coronavirus Pandemic (COVID-19).

BACKGROUND: In anticipation of a demand surge for hospital beds attributed to the coronavirus pandemic (COVID-19) many US states have mandated that hospitals postpone elective admissions. OBJECTIVES: To estimate excess demand for hospital beds due to COVID-19, the net financial impact of eliminating elective admissions in order to meet demand, and to explore the scenario when demand remains below capacity. RESEARCH DESIGN: An economic simulation to estimate the net financial impact of halting elective admissions, combining epidemiological reports, the US Census, American Hospital Association Annual Survey, and the National Inpatient Sample. Deterministic sensitivity analyses explored the results while varying assumptions for demand and capacity. SUBJECTS: Inputs regarding disease prevalence and inpatient utilization were representative of the US population. Our base case relied on a hospital admission rate reported by the Center for Disease Control and Prevention of 137.6 per 100,000, with the highest rates in people aged 65 years and older (378.8 per 100,000) and 50-64 years (207.4 per 100,000). On average, elective admissions accounted for 20% of total hospital admissions, and the average rate of unoccupied beds across hospitals was 30%. MEASURES: Net financial impact of halting elective admissions. RESULTS: On average, hospitals COVID-19 demand for hospital bed-days fell well short of hospital capacity, resulting in a substantial financial loss. The net financial impact of a 90-day COVID surge on a hospital was only favorable under a narrow circumstance when capacity was filled by a high proportion of COVID-19 cases among hospitals with low rates of elective admissions. CONCLUSIONS: Hospitals that restricted elective care took on a substantial financial risk, potentially threatening viability. A sustainable public policy should therefore consider support to hospitals that responsibly served their communities through the crisis.

Response to the Coronavirus Disease 2019 Pandemic by the Spine Division at a Level-I Academic Referral Center.

Coronavirus disease 2019 (COVID-19) is a ubiquitous health concern and a global pandemic. In an effort to slow the disease spread and protect valuable healthcare resources, cessation of nonessential surgery, including many orthopaedic procedures, has become commonplace. This crisis has created a unique situation in the care of spine patients as we must balance the urgency of patient evaluation, surgical intervention, and continued training against the risk of disease exposure and resource management. The spine division of an orthopaedic surgery department has taken an active role in enacting protocol changes in anticipation of COVID-19. In the initial 4 weeks of the COVID-19 pandemic the spine division went from an average of 60.4 cases to 10 cases during the same timeframe. Clinic visits decreased from 417.4 to 322 with new patient visits decreasing from 28% to 20%. Three hundred eighteen of the 322 (98.7%) clinic visits were performed via telehealth. Although these changes have been forced upon us by necessity, we feel that our division and department will emerge in a more responsive, agile, and stronger state. As we look to the coming months and beyond, it will be important to continue to adapt to the changing landscape during unprecedented times.