Addressing the Opioid Crisis-The Need for a Pain Management Intervention in Community Pharmacies in Canada: A Narrative Review.

Background: The opioid crisis is a public health concern in Canada with a continued rise in deaths and presents a significant economic impact on the healthcare system. There is a need to develop and implement strategies for decreasing the risk of opioid overdoses and other opioid-related harms resulting from the use of prescription opioids. Pharmacists, as medication experts and educators, and as one of the most accessible frontline healthcare providers, are well positioned to provide effective opioid stewardship through a pain management program focused on improving pain management for patients, supporting appropriate prescribing and dispensing of opioids, and supporting safe and appropriate use of opioids to minimize potential opioid misuse, abuse, and harm. Methods: A literature search was conducted in PubMed, Embase and grey literature to determine the characteristics of an effective community pharmacy-based pain management program, including the facilitators and barriers to be considered. Discussion: An effective pain management program should be multicomponent, address other co-morbid conditions in addition to pain, and contain a continuing education component for pharmacists. Solutions to implementation barriers, including pharmacy workflow; addressing attitudes beliefs, and stigma; and pharmacy remuneration, as well as leveraging the expansion of scope from the Controlled Drugs and Substances Act exemption to facilitate implementation, should be considered. Conclusions: Future work should include the development, implementation, and evaluation of a multicomponent, evidence-based intervention strategy in Canadian community pharmacies to demonstrate the impact pharmacists can have on the management of chronic pain and as one potential solution to helping curb the opioid crisis. Future studies should measure associated costs for such a program and any resulting cost-savings to the healthcare system.

Virtual reality immersion compared to monitored anesthesia care for hand surgery: A randomized controlled trial.

INTRODUCTION: Common anesthesia practice for hand surgery combines a preoperative regional anesthetic and intraoperative monitored anesthesia care (MAC). Despite adequate regional anesthesia, patients may receive doses of intraoperative sedatives which can result in oversedation and potentially avoidable complications. VR could prove to be a valuable tool for patients and providers by distracting the mind from processing noxious stimuli resulting in minimized sedative use and reduced risk of oversedation without negatively impacting patient satisfaction. Our hypothesis was that intraoperative VR use reduces sedative dosing during elective hand surgery without detracting from patient satisfaction as compared to a usual care control. METHODS: Forty adults undergoing hand surgery were randomized to receive either intraoperative VR in addition to MAC, or usual MAC. Patients in both groups received preoperative regional anesthesia at provider discretion. Intraoperatively, the VR group viewed programming of their choice via a head-mounted display. The primary outcome was intraoperative propofol dose per hour (mg · hr-1). Secondary outcomes included patient reported pain and anxiety, overall satisfaction, functional outcome, and post anesthesia care unit (PACU) length of stay (LOS). RESULTS: Of the 40 enrolled patients, 34 completed the perioperative portion of the trial. VR group patients received significantly less propofol per hour than the control group (Mean (±SD): 125.3 (±296.0) vs 750.6 (±334.6) mg · hr-1, p<0.001). There were no significant differences between groups in patient reported overall satisfaction, (0-100 scale, Median (IQR) 92 (77-100) vs 100 (100-100), VR vs control, p = 0.087). There were no significant differences between groups in PACU pain scores, perioperative opioid analgesic dose, or in postoperative functional outcome. PACU LOS was significantly decreased in the VR group (53.0 (43.0-72.0) vs 75.0 (57.5-89.0) min, p = 0.018). CONCLUSION: VR immersion during hand surgery led to significant reductions in intraoperative propofol dose and PACU LOS without negatively impacting key patient reported outcomes.

Virtual reality as an adjunct to anesthesia in the operating room.

BACKGROUND: Advancements in virtual reality (VR) technology have resulted in its expansion into health care. Preliminary studies have found VR to be effective as an adjunct to anesthesia to reduce pain and anxiety for patients during upper gastrointestinal endoscopies, dental procedures and joint arthroplasties. Current standard care practice for upper extremity surgery includes a combination of regional anesthesia and intraoperative propofol sedation. Commonly, patients receive deep propofol sedation during these cases, leading to potentially avoidable risks of over-sedation, hypotension, upper airway obstruction, and apnea. The objective of this study is to evaluate the effectiveness of VR technology to promote relaxation for patients undergoing upper extremity surgery, thereby reducing intraoperative anesthetic requirements and improving the perioperative patient experience. METHODS: In this single-center, randomized controlled trial, 40 adult patients undergoing upper extremity orthopedic surgery will be randomly allocated to either intraoperative VR immersion or usual care. VR immersion is designed to provide patients with a relaxing virtual environment to alleviate intraoperative anxiety. All patients receive a peripheral nerve block prior to surgery. Patients in the intervention group will select videos or immersive environments which will be played in the VR headset during surgery. An anesthesia provider will perform their usual clinical responsibilities intraoperatively and can administer anesthetic medications if and when clinically necessary. Patients in the control arm will undergo perioperative anesthesia according to standard care practice. The primary outcome is the difference in intraoperative propofol dose between the groups. Secondary outcomes include postoperative analgesia requirements and pain scores, length of stay in the postanesthesia care unit, overall patient satisfaction and postoperative functional outcomes. DISCUSSION: It is unknown whether the use of VR during upper extremity surgery can reduce intraoperative anesthetic requirements, reduce perioperative complications, or improve the postoperative patient experience. A positive result from this clinical trial would add to the growing body of evidence that demonstrates the effectiveness of VR as an adjunct to anesthesia in reducing intraoperative pain and anxiety for multiple types of procedure. This could lead to a change in practice, with the introduction of a nonpharmacologic intervention potentially reducing the burden of over-sedation while still providing a satisfactory perioperative experience. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03614325. Registered on 9 July 2018.

Src family kinase inhibitor bosutinib enhances retinoic acid-induced differentiation of HL-60 leukemia cells.

The acute promyelocytic leukemia (APL) has been treated with all-trans retinoic acid (RA) for decades. While RA has largely been ineffective in non-APL AML subtypes, co-treatments combining RA and other agents are currently in clinical trials. Using the RA-responsive non-APL AML cell line HL-60, we tested the efficacy of the Src family kinase (SFK) inhibitor bosutinib on RA-induced differentiation. HL-60 has been recently shown to bear fidelity to a subtype of AML that respond to RA. We found that co-treatment with RA and bosutinib enhanced differentiation evidenced by increased CD11b expression, G1/G0 cell cycle arrest, and respiratory burst. Expression of the SFK members Fgr and Lyn was enhanced, while SFK activation was inhibited. Phosphorylation of several sites of c-Raf was increased and expression of AhR and p85 PI3K was enhanced. Expression of c-Cbl and mTOR was decreased. Our study suggests that SFK inhibition enhances RA-induced differentiation and may have therapeutic value in non-APL AML.

Altering spacer material affects bone regeneration in the Masquelet technique in a rat femoral defect.

The Masquelet technique depends on pre-development of a foreign-body membrane to support bone regeneration with grafts over three times larger than the traditional maximum. To date, the procedure has always used spacers made of bone cement, which is the polymer polymethyl methacrylate (PMMA), to induce the foreign-body membrane. This study sought to compare (i) morphology, factor expression, and cellularity in membranes formed by PMMA, titanium, and polyvinyl alcohol sponge (PVA) spacers in the Masquelet milieu and (ii) subsequent bone regeneration in the same groups. Ten-week-old, male Sprague-Dawley rats were given an externally stabilized, 6 mm femur defect, and a pre-made spacer of PMMA, titanium, or PVA was implanted. All animals were given 4 weeks to form a membrane, and those receiving an isograft were given 10 weeks post-implantation to union. All samples were scanned with microCT to measure phase 1 and phase 2 bone formation. Membrane samples were processed for histology to measure membrane morphology, cellularity, and expression of the factors BMP2, TGFß, VEGF, and IL6. PMMA and titanium spacers created almost identical membranes and phase 1 bone. PVA spacers were uniformly infiltrated with tissue and cells and did not form a distinct membrane. There were no quantitative differences in phase 2 bone formation. However, PMMA induced membranes supported functional union in 6 of 7 samples while a majority of titanium and PVA groups failed to achieve the same. Spacer material can alter the membrane enough to disrupt phase 2 bone formation. The membrane's role in bone regeneration is likely more than just as a physical barrier. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

Remnant Woven Bone and Calcified Cartilage in Mouse Bone: Differences between Ages/Sex and Effects on Bone Strength.

INTRODUCTION: Mouse models are used frequently to study effects of bone diseases and genetic determinates of bone strength. Murine bones have an intracortical band of woven bone that is not present in human bones. This band is not obvious under brightfield imaging and not typically analyzed. Due to the band's morphology and location it has been theorized to be remnant bone from early in life. Furthermore, lamellar and woven bone are well known to have differing mechanical strengths. The purpose of this study was to determine (i) if the band is from early life and (ii) if the woven bone or calcified cartilage contained within the band affect whole bone strength. WOVEN BONE ORIGIN STUDIES: In twelve to fourteen week old mice, doxycycline was used to label bone formed prior to 3 weeks old. Doxycycline labeling and woven bone patterns on contralateral femora matched well and encompassed an almost identical cross-sectional area. Also, we highlight for the first time in mice the presence of calcified cartilage exclusively within the band. However, calcified cartilage could not be identified on high resolution cone-beam microCT scans when examined visually or by thresholding methods. MECHANICAL STRENGTH STUDIES: Subsequently, three-point bending was used to analyze the effects of woven bone and calcified cartilage on whole bone mechanics in a cohort of male and female six and 13 week old Balb/C mice. Three-point bending outcomes were correlated with structural and compositional measures using multivariate linear regression. Woven bone composed a higher percent of young bones than older bones. However, calcified cartilage in older bones was twice that of younger bones, which was similar when normalized by area. Area and/or tissue mineral density accounted for >75% of variation for most strength outcomes. Percent calcified cartilage added significant predictive power to maximal force and bending stress. Calcified cartilage and woven bone could have more influence in genetic models where calcified cartilage percent is double our highest value.