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The current review demonstrates relatively few investigations seeking to characterize the neuropharmacologic suitability of DISE agents. Compared to propofol and midazolam, dexmedetomidine's mechanism of action appears most likely to induce natural sleep pathways. Further study of its effect on upper airway collapsibility (critical closing pressure) and pharyngeal muscle tone (genioglossus electrode electromyography) are needed. Laryngoscope, 2016 Laryngoscope, 127:273-279, 2017.

Ketamine is a promising treatment for chronic neuropathic pain. "

Following the publication of the article, the authors realized that the Whirlin cDNA (NCBI accession no. AY739114) used in the study contains two synonymous variants (Leu476Leu (CTC to CTT), and Thr537Thr (ACA to ACG)) and one non-synonymous variant (Gly550Arg (GGA to AGA)). The authors regret this error. We corrected all three variants to conform to the wild type mouse sequence (accession number AY739114) and repeated the inner ear gene therapy experiments in the whirler mutant mice (Whrn wi/wi ) as published in the original study. The corrected AAV8-whirlin was delivered via the posterior canal approach and caused a partial improvement in the auditory function in the Whrn wi/wi mice (mean ABR thresholds of 97.5 ± 1.64, 81.9 ± 5.08, 95.0 ± 2.67, and 95.7 ± 2.59 at stimulus frequencies of 4 kHz, 8 kHz, 16 kHz, and 32 kHz, respectively, n=5). The magnitudes of ABR threshold improvement are similar to our previously published results (p = 0.27, ANOVA). The corrected AAV8-whirlin delivered via the posterior canal approach also led to an improvement in the vestibular function in the Whrn wi/wi mice, as indicated by a reduction in circling behavior (7.20 ± 0.43 rotations per 2 min). This improvement in vestibular function is also similar to our previously published results (p = 0.41, t-test). Thus, correction of the variants that were present in the original whirlin cDNA did not alter the conclusions of the study.

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Background Approximately 12 million Americans are affected with cancer. Of these, 53% experience pain at all stages of cancer. Pain may remain uncontrolled despite high-dose opioid therapy, and opioids have many well-documented harmful side effects. Intranasal ketamine has been shown to be effective in controlling breakthrough noncancer pain in a double-blind randomized control trial (DBRCT) by Carr et al in 2003 as well as to help with depression in a DBRCT by Lapidus et al in 2014. We seek to obtain preliminary data on the safety, feasibility, and utility of this novel technique for the treatment of uncontrolled cancer pain. Objective This study aimed to obtain preliminary data via a clinical trial addressing the safety, feasibility, pharmacokinetics, and pharmacodynamics of intranasal ketamine. These initial findings will be applied to a subsequent trial to determine the effectiveness and associated toxicities of ketamine in a larger sample of cancer patients and to address the compelling need to identify new, successful management therapies for cancer pain. Methods This is an institutional review board– and investigational new drug–approved, prospective phase I/II trial to investigate the safety and use of intranasal ketamine in patients with uncontrolled pain related to cancer or cancer treatment. Informed consent will be obtained prior to all study procedures. All patients will be assigned to the same investigational treatment arm. After patient selection via inclusion/exclusion criteria, patients will be seen over 5 visits, with each visit conducted 2-7 days apart. Patients will be administered ketamine on visits 1-4 and monitored for 240 minutes with continuous pulse oximetry and regular blood pressure checks. Blood samples as well as patient-reported outcomes will be collected at set time points at baseline and after drug delivery. Patients will receive 10 mg intranasal ketamine on visit 1, 10 mg intravenous ketamine on visit 2, 30 mg intranasal ketamine on visit 3, and 50 mg intranasal ketamine on visit 4. On visit 5, an addition blood sample will be drawn. Results As of March 2019, enrollment is in progress, and a total of 7 subjects have completed the study. Enrollment is expected to be completed by April 2019. Final data analysis will commence soon after, and the results are expected to be submitted for publication in 2019. Conclusions If intranasal ketamine can be utilized for pain control in cancer patients, it could provide superior analgesia and better quality of life, without the risk of significant respiratory depression and constipation associated with opioid medications. These findings will be an important initial step toward testing the effectiveness of intranasal ketamine as a nonopioid medication for cancer pain and as potential maintenance outpatient therapy. Trial Registration ClinicalTrials.gov NCT03146806; https://clinicaltrial...

Background: Perioperative opioids are problematic following craniotomy as they can impede neurological examination because of excessive sedation and mask surgical complications. Multimodal anesthetic techniques including nerve blocks have been used successfully to deliver opioid-free anesthesia in other surgical populations; however, no clinical data evaluating opioid-free anesthesia for craniotomy exists within the current body of literature.Materials and Methods: Six prospectively identified patients underwent supratentorial craniotomy at Emory University Hospital using a multimodal opioid-free anesthetic (OFA) technique consisting of preoperative scalp block, dexmedetomidine and intravenous acetaminophen. These opioid-free patients were matched by age, sex, incision length, and incision location to 18 retrospectively identified control patients who underwent craniotomy using conventional, opioid-based anesthetic techniques. Postoperative opioid consumption and pain scores were compared and analyzed for noninferiority.Results: Noninferiority of the OFA technique was demonstrated for opioid consumption at all measured intervals from postanesthesia care unit arrival to 24 hours postoperatively. Noninferiority was also demonstrated with respect to average postoperative pain scores from 0 to 12 hours, 0 to 24 hours, as well as length of postanesthesia care unit stay. Noninferiority was not shown for time to first rescue opioid postoperatively, pain scores for the 12 to 24 hours postoperative period, or time to emergence from anesthesia.Conclusions: This pilot study demonstrates the feasibility of an OFA technique for patients undergoing supratentorial craniotomy and suggests that larger prospective randomized controlled trials are indicated to examine the role of multimodal anesthetic techniques for craniotomy.

Study Objective: The objective of our study was to determine safety and pharmacology (pharmacokinetics and preliminary efficacy) of intranasal (IN) ketamine for uncontrolled cancer-related pain. Design: Dose escalation clinical trial. Setting: Outpatient. Patients: Ten adult patients with uncontrolled cancer-related pain. Intervention: Each patient received escalating doses of ketamine over four visits, each 2-5 days apart: 10 mg IN at visit 1, 10 mg intravenous (IV) at visit 2, 30 mg IN at visit 3, and 50 mg IN at visit 4. Measurements: Pain was measured before and after drug administration for up to 4 h using the 11 point (0-10) Numerical Pain Rating Scale (NPRS).Main Results: All subjects had advanced cancer, with intractable pain, despite being on moderate dosage of opioids. There was a statistically significant reduction in median NPRS by 1.5 (1-4), 3 (2-3), and 4 (3-5) points at 60 min after receiving the medication and remained decreased by 1.5 (1-2), 2 (1-2) and 1 (1-4) points at the end of the study visit (240 min) with the 10 mg, 30 mg and 50 mg IN dosage, respectively. The