Effect of Intermediate-Dose vs Standard-Dose Prophylactic Anticoagulation on Thrombotic Events, Extracorporeal Membrane Oxygenation Treatment, or Mortality among Patients with COVID-19 Admitted to the Intensive Care Unit: The INSPIRATION Randomized Clinical Trial

Importance: Thrombotic events are commonly reported in critically ill patients with COVID-19. Limited data exist to guide the intensity of antithrombotic prophylaxis. Objective: To evaluate the effects of intermediate-dose vs standard-dose prophylactic anticoagulation among patients with COVID-19 admitted to the intensive care unit (ICU). Design, Setting, and Participants: Multicenter randomized trial with a 2 � 2 factorial design performed in 10 academic centers in Iran comparing intermediate-dose vs standard-dose prophylactic anticoagulation (first hypothesis) and statin therapy vs matching placebo (second hypothesis; not reported in this article) among adult patients admitted to the ICU with COVID-19. Patients were recruited between July 29, 2020, and November 19, 2020. The final follow-up date for the 30-day primary outcome was December 19, 2020. Interventions: Intermediate-dose (enoxaparin, 1 mg/kg daily) (n = 276) vs standard prophylactic anticoagulation (enoxaparin, 40 mg daily) (n = 286), with modification according to body weight and creatinine clearance. The assigned treatments were planned to be continued until completion of 30-day follow-up. Main Outcomes and Measures: The primary efficacy outcome was a composite of venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation, or mortality within 30 days, assessed in randomized patients who met the eligibility criteria and received at least 1 dose of the assigned treatment. Prespecified safety outcomes included major bleeding according to the Bleeding Academic Research Consortium (type 3 or 5 definition), powered for noninferiority (a noninferiority margin of 1.8 based on odds ratio), and severe thrombocytopenia (platelet count <20 �103/µL). All outcomes were blindly adjudicated. Results: Among 600 randomized patients, 562 (93.7) were included in the primary analysis (median interquartile range age, 62 50-71 years; 237 42.2% women). The primary efficacy outcome occurred in 126 patients (45.7%) in the intermediate-dose group and 126 patients (44.1%) in the standard-dose prophylaxis group (absolute risk difference, 1.5% 95% CI,-6.6% to 9.8%; odds ratio, 1.06 95% CI, 0.76-1.48; P =.70). Major bleeding occurred in 7 patients (2.5%) in the intermediate-dose group and 4 patients (1.4%) in the standard-dose prophylaxis group (risk difference, 1.1% 1-sided 97.5% CI,-� to 3.4%; odds ratio, 1.83 1-sided 97.5% CI, 0.00-5.93), not meeting the noninferiority criteria (P for noninferiority >.99). Severe thrombocytopenia occurred only in patients assigned to the intermediate-dose group (6 vs 0 patients; risk difference, 2.2% 95% CI, 0.4%-3.8%; P =.01). Conclusions and Relevance: Among patients admitted to the ICU with COVID-19, intermediate-dose prophylactic anticoagulation, compared with standard-dose prophylactic anticoagulation, did not result in a significant difference in the primary outcome of a composite of adjudicated venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation, or mortality within 30 days. These results do not support the routine empirical use of intermediate-dose prophylactic anticoagulation in unselected patients admitted to the ICU with COVID-19. Trial Registration: ClinicalTrials.gov Identifier: NCT04486508. © 2021 American Medical Association. All rights reserved

Comparison of Levetiracetam and sodium Valproate in migraine prophylaxis: A randomized placebo-controlled study

Background: Migraine is a chronic and disabling disorder. Treatment of migraine often comprises of symptomatic (abortive) and preventive (prophylactic) treatment. The current drugs used in migraine prophylaxis include antidepressant drugs (Serotonin Reuptake Inhibitors, Tricyclic antidepressants), and anti-epileptic drugs (valproate, gabapentin, etc). Objective: The objective of our study was to assess the efficacy and tolerability of levetiracetam in adult migraine prophylaxis, compared to valproate and placebo. Materials and Methods: We conducted a prospective, randomized, placebo-controlled study. A total of 85 patients were randomized to receive levetiracetam 500 mg/d (n = 27), valproate 500 mg/d (n = 32) or placebo (n = 26). The patients were evaluated for treatment efficacy after 6 months. Efficacy was assessed as a more than 50% decrease in headache frequency. Results: In levetiracetam group, 17 (63.0%) patients experienced a more than 50% decrease in headache frequency, while this efficacy number was 21 (65.6%) for valproate group and 4 (15.4%) for placebo group. The difference was not statistically significant between levetiracetam and valproate, while it was significant when comparing either levetiracetam or valproate to placebo. Conclusion: Compared to placebo, levetiracetam offers improvement in headache frequency in patients with migraine. The efficacy of levetiracetam in migraine prophylaxis is comparable to currently used drugs such as valproate

Traumatic Spinal Cord Injury: Long-Term Motor, Sensory, and Urinary Outcomes

Study Design Retrospective study. Purpose To evaluate how motor, sensory, and urinary outcomes of spinal cord injury (SCI) patients were influenced in the long term. Overview of Literature SCI is a potentially disabling and devastating neurological outcome that can occur because of spinal column fractures. Most studies have not evaluated or have failed to show the influence of different surgical approaches and other parameters on neurological recovery. Methods: A thorough history regarding sensory, motor, and urinary complaints was taken from 103 patients with SCI due to vertebral fracture; patients were followed by a thorough neurological examination. Subsequently, all medical records of patients, including neurological state after trauma, trauma mechanism, treatment protocol, surgical protocol, and imaging findings, were evaluated. Results: Of the 103 patients, 73.8% were survivors of a major earthquake and 26.2% were victims of vehicle accidents; 92.2% patients were surgically treated, while 7.8% underwent conservative management. The mean follow-up duration was 10.3 years. In follow-up visits, 67.0%, 12.6%, 13.6%, and 6.8% patients showed no, partial, substantial, and complete motor improvement, respectively; 68.0%, 26.2%, and 5.8% showed no, mild, and substantial sensory improvement, respectively; and 73.8%, 17.5%, and 8.7% showed no, substantial, and complete urinary improvement, respectively. Logistic regression analysis showed that sex, age at injury time, follow-up duration, trauma mechanism, and stem cell therapy had no effect on motor, sensory, and urinary improvement. Higher initial scores on the American Spinal Injury Association (ASIA) classification, lumbar fracture level, and performance of laminectomy improved motor outcome; higher initial ASIA scores improved urinary and sensory outcomes. Conclusions: The initial ASIA score is the most important factor for prognosticating motor, sensory, and urinary improvement in SCI patients. Lumbar (L3–L5) and thoracic (T1–T10) fractures have the best and worst prognosis, respectively, in terms of motor recovery. Laminectomy during surgery improves motor function

Subtotal Resection of a Thalamic Glioblastoma Multiforme through Transsylvian Approach

Glioblastoma multiforme (GBM) is a malignant brain tumor with an ominous prognosis. The standard treatment includes maximal safe resection plus adjuvant therapy. Thalamic GBMs, however, are unfavorable for microsurgical removal because of deep location and proximity to critical structures. We present a patient presenting with progressive hemiparesis and decreased consciousness with a large thalamic GBM who underwent subtotal resection through a transsylvian approach. His clinical and neurologic condition improved after surgery and he survived nine months after surgery. This may propose that in selected cases, more aggressive microsurgery for debulking of tumors might have some impact in the final outcome.​​

Analyzing Gensini Score as a Semi-Continuous Outcome

Background: Investigators frequently encounter continuous outcomes with plenty of values clumped at zero called semi-continuous outcomes. The Gensini score, one of the most widely used scoring systems for expressing coronary angiographic results, is of this type. The aim of this study was to apply two statistical approaches based on the categorization and original scale of the Gensini score to simultaneously assess the association between covariates and the presence and severity of coronary artery disease (CAD). Methods: We considered the data on 1594 individuals admitted to Tehran Heart Center with CAD symptoms from July 2004 to February 2008. The participants’ baseline demographic and clinical characteristics were collected, and their coronary angiographic results were expressed through the Gensini score. The generalized ordinal threshold and two-part models were applied for the statistical analyses. Results: Totally, 320 (20.1%) individuals had a Gensini score of zero. The results of neither the two-part model nor the generalized ordinal threshold model showed a significant association between Factor V Leiden and the occurrence of CAD. However, based on the two-part model, Factor V Leiden was associated with the severity of CAD, such that the Gensini score increased by moving from a wild genotype to a heterozygote (β = 0.44; 95% CI: 0.20-0.69 in logarithm scale) or a homozygote mutant (β = 0.70; 95% CI: 0.28- 1.12 in logarithm scale). The proportional odds assumption was not met in our data ( = 54.26; p value < 0.001); however, a trend toward severe CAD was also observed at each category of the Gensini score using the generalized ordinal threshold model. Conclusion: We conclude that besides loss of information by sorting a semi-continuous outcome, violation from the proportional odds assumption complicates the final decision, especially for clinicians. Therefore, more straightforward models such as the two-part model should receive more attention while analyzing such outcomes

Rho-kinase inhibitors do not expand hematoma volume in acute experimental intracerebral hemorrhage

Rho-associated kinase (ROCK) is an emerging target in acute ischemic stroke. Early pre-hospital treatment with ROCK inhibitors may improve their efficacy, but their antithrombotic effects raise safety concerns in hemorrhagic stroke, precluding use prior to neuroimaging. Therefore, we tested whether ROCK inhibition affects the bleeding times, and worsens hematoma volume in a model of intracerebral hemorrhage (ICH) induced by intrastriatal collagenase injection in mice. Tail bleeding time was measured 1 h after treatment with isoform-nonselective inhibitor fasudil, or ROCK2-selective inhibitor KD025, or their vehicles. In the ICH model, treatments were administered 1 h after collagenase injection. Although KD025 but not fasudil prolonged the tail bleeding times, neither drug expanded the volume of ICH or worsened neurological deficits at 48 h compared with vehicle. Although more testing is needed in aged animals and comorbid models such as diabetes, these results suggest ROCK inhibitors may be safe for pre-hospital administration in acute stroke.NIH [NS055104]; Fondation Leducq; Heitman Foundation; Ellison FoundationOpen access journal.This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]