Perioperative pain optimization in the age of the opioid epidemic.

PURPOSE OF REVIEW: The opioid epidemic remains a constant and increasing threat to our society with overdoses and overdose deaths rising significantly during the COVID-19 pandemic. Growing evidence suggests a link between perioperative opioid use, postoperative opioid prescribing, and the development of opioid use disorder (OUD). As a result, strategies to better optimize pain management during the perioperative period are urgently needed. The purpose of this review is to summarize the most recent multimodal analgesia (MMA) recommendations, summarize evidence for efficacy surrounding the increased utilization of Enhanced Recovery After Surgery (ERAS) protocols, and discuss the implications for rising use of buprenorphine for OUD patients who present for surgery. In addition, this review will explore opportunities to expand our treatment of complex patients via transitional pain services. RECENT FINDINGS: There is ample evidence to support the benefits of MMA. However, optimal drug combinations remain understudied, presenting a target area for future research. ERAS protocols provide a more systematic and targeted approach for implementing MMA. ERAS protocols also allow for a more comprehensive approach to perioperative pain management by necessitating the involvement of surgical specialists. Increasingly, OUD patients taking buprenorphine are presenting for surgery. Recent guidance from a multisociety OUD working group recommends that buprenorphine not be routinely discontinued or tapered perioperatively. Lastly, there is emerging evidence to justify the use of transitional pain services for more comprehensive treatment of complex patients, like those with chronic pain, preoperative opioid tolerance, or substance use disorder. SUMMARY: Perioperative physicians must be aware of the impact of the opioid epidemic and explore methods like MMA techniques, ERAS protocols, and transitional pain services to improve the perioperative pain experience and decrease the risks of opioid-related harm.

Developing and Validating a Novel Tool to Enhance Functional Status Assessment: The Tennessee Functional Status Questionnaire (TFSQ).

PURPOSE: Functional status is a major contributor to overall health and reflects both daily activity level (performance) and maximum attainable activity level (capacity). Existing assessment tools evaluate only 1 domain of function and do not provide insight into contributors to functional decline. We addressed these deficiencies by developing the Tennessee Functional Status Questionnaire (TFSQ), which reports activity levels in metabolic equivalents (METs) and evaluates 5 key areas: performance, capacity, activity, pain, and acute care. We validated the activity levels reported by the TFSQ against the Duke Activity Status Index (DASI). METHODS: In this prospective, observational study, 120 patients completed both the TFSQ and the DASI. TFSQ-reported functional performance and capacity was correlated with DASI-calculated METs. RESULTS: Pearson correlation between TFSQ-reported capacity and DASI-calculated METs was r = 0.69, P < .001. TFSQ capacity was significantly lower in patients who reported recently decreased activity, pain affecting function, or recent acute care exposure. CONCLUSIONS: The TFSQ is a brief and efficient assessment of patient function, standardized to METs and validated against the DASI. Our study suggests that many patients may have the functional reserve to increase daily physical activity and that factors such as changes in activity, pain, and recent acute care interaction may lower functional capacity.

Bone marrow stromal cells are sensitive to discrete surface alterations in build and post-build modifications of bioinspired Ti6Al4V 3D-printed in vitro testing constructs.

Current standards in bone-facing implant fabrication by metal 3D (M3D) printing require post-manufacturing modifications to create distinct surface properties and create implant microenvironments that promote osseointegration. However, the biological consequences of build parameters and surface modifications are not well understood. This study evaluated the relative contributions of build parameters and post-manufacturing modification techniques to cell responses that impact osseointegration in vivo. Biomimetic testing constructs were created by using a M3D printer with standard titanium-aluminum-vanadium (Ti6Al4V) print parameters. These constructs were treated by either grit-blasting and acid-etching (GB + AE) or GB + AE followed by hot isostatic pressure (HIP) (GB + AE, HIP). Next, nine constructs were created by using a M3D printer with three build parameters: (1) standard, (2) increased hatch spacing, and (3) no infill, and additional contour trace. Each build type was further processed by either GB + AE, or HIP, or a combination of HIP treatment followed by GB + AE (GB + AE, HIP). Resulting constructs were assessed by SEM, micro-CT, optical profilometry, XPS, and mechanical compression. Cellular response was determined by culturing human bone marrow stromal cells (MSCs) for 7 days. Surface topography differed depending on processing method; HIP created micro-/nano-ridge like structures and GB + AE created micro-pits and nano-scale texture. Micro-CT showed decreases in closed pore number and closed porosity after HIP treatment in the third build parameter constructs. Compressive moduli were similar for all constructs. All constructs exhibited ability to differentiate MSCs into osteoblasts. MSCs responded best to micro-/nano-structures created by final post-processing by GB + AE, increasing OCN, OPG, VEGFA, latent TGFß1, IL4, and IL10. Collectively these data demonstrate that M3D-printed constructs can be readily manufactured with distinct architectures based on the print parameters and post-build modifications. MSCs are sensitive to discrete surface topographical differences that may not show up in qualitative assessments of surface properties and respond by altering local factor production. These factors are vital for osseointegration after implant insertion, especially in patients with compromised bone qualities.

Presence of Content Appealing to Youth on Cannabis-Infused Edibles Packaging.

BACKGROUND: There is a lack of consistent regulation of cannabis edibles packaging to restrict youth-appealing content in the United States. OBJECTIVE: To describe content appealing to youth on U.S. cannabis-infused edibles packaging. METHODS: We analyzed 256 photos of cannabis-infused edibles packaging collected from U.S. adults from 25 states, District of Columbia, and Puerto Rico between May 2020 to August 2021. We coded the presence of product knockoffs, human and non-human creatures, images indicating flavor, text indicating flavor, and the number of colors. We compared these codes across states' legalization status (medical and non-medical cannabis, medical cannabis only, or limited cannabis legalization). RESULTS: Overall, 15% of packages resembled product knockoffs, 23% contained human/non-human creatures, 35% contained flavor images, 91% contained flavor text, and median number of colors was 5 (range from 1 to 10+). Packages purchased in states with medical and non-medical cannabis, medical cannabis only, or limited cannabis legalization differed significantly on product knockoffs (11%, 26%, 38%, p = 0.007), human/non-human creatures (19%, 33%, 63%, p = 0.002), flavor text (93%, 81%, 100%, p = 0.046), and number of colors (median of 5, 5, and 10, p = 0.022). CONCLUSIONS: Existing laws have not adequately limited content appealing to youth on U.S. cannabis-infused edibles packaging. Robust and consistent regulations in the U.S. are needed to ensure that the packaging of such products does not contain content that appeal to youth and lead to initiation or inadvertent ingestion.

Copycat and lookalike edible cannabis product packaging in the United States.

BACKGROUND: Recent media reports have highlighted copycat/lookalike cannabis edibles as a public health concern. No empirical papers have described this phenomenon. METHODS: From May 2020-August 2021, we collected photos of cannabis products via an online survey of cannabis users and through personal contacts. Copycat/lookalike products are defined as those that use the same or similar brand name, logo, and/or imagery as an existing commercial non-cannabis counterpart (CNCC). We assessed each package for similarities with its CNCC with respect to brand name, product name, font, color, flavors, and brand/promotional characters. We examined cannabis content indicators including: THC content per package and serving, cannabis leaf symbol, product warnings, cannabis terms, cannabis motifs, activation time, and guidance on edible use. RESULTS: We collected photos of 731 cannabis products; 267 (36%) were edibles of which 22 (8%) represented 13 unique copycat/lookalike products. Eight used exact brand/product names as existing CNCCs, and five used similar names. Packages copied or imitated a mean of 3.9 of six features and indicated cannabis content with a mean of 4.1 of eight features. Thirteen packages indicated a mean THC content of 459 mg/package. Four reported THC dose per serving, with a mean dose of 47.5 mg. CONCLUSIONS: Our content analysis highlights three key concerns. First, copycat/lookalike edibles subtly indicate cannabis content while using high fidelity replication or imitation of their CNCC. Second, THC content is high and there were multiple 10 mg THC doses in the equivalent of 1 serving of a CNCC. Third, these products may be attractive to children.

AI for social good: unlocking the opportunity for positive impact.

Advances in machine learning (ML) and artificial intelligence (AI) present an opportunity to build better tools and solutions to help address some of the world's most pressing challenges, and deliver positive social impact in accordance with the priorities outlined in the United Nations' 17 Sustainable Development Goals (SDGs). The AI for Social Good (AI4SG) movement aims to establish interdisciplinary partnerships centred around AI applications towards SDGs. We provide a set of guidelines for establishing successful long-term collaborations between AI researchers and application-domain experts, relate them to existing AI4SG projects and identify key opportunities for future AI applications targeted towards social good.

The Case for Drone-assisted Emergency Response to Cardiac Arrest: An Optimized Statewide Deployment Approach.

BACKGROUND Despite evidence linking rapid defibrillation to out-of-hospital cardiac arrest (OHCA) survival, bystander use of automatic external defibrillators (AEDs) remains low, due in part to AED placement and accessibility. AED-equipped drones may improve time-to-defibrillation, yet the benefits and costs are unknown.METHODS We designed drone deployment networks for the state of North Carolina using mathematical optimization models to select drone stations from existing infrastructure by specifying the number of stations and the targeted AED arrival time. Expected outcomes were evaluated over the drone's lifespan (4 years). We estimated the following parameters: proportion of OHCAs within a targeted AED delivery time, bystander utilization of AEDs, survival/neurological status, and incremental cost per quality-adjusted life year (QALY).RESULTS Statewide, 16,503 adults aged 18 or older were expected to experience OHCA with an attempted resuscitation over 4 years. Compared to no drone network, all proposed drone networks were expected to improve survival outcomes. For example, assuming 46% of OHCAs have bystanders willing to use an AED, a 500-drone network decreased the median time of defibrillator arrival from 7.7 to 2.7 minutes compared to no drone network. Expected survival rates doubled (24.5% versus 12.3%), resulting in an additional 30,267 QALYs ($858/incremental QALY). If just 4.5% of OHCAs had willing bystanders, 13.8% of victims would have survived. Sensitivity analysis demonstrated that an AED drone network remained cost-effective over a wide range of assumptions.CONCLUSIONS With proper integration into existing systems, large-scale networks for drone AED delivery have the potential to substantially improve OHCA survival rates while remaining cost-effective. Public health researchers should consider advocating for feasibility studies and policy development surrounding drones.

Delivery of Automated External Defibrillators (AED) by Drones: Implications for Emergency Cardiac Care.

PURPOSE OF REVIEW: Out-of-hospital cardiac arrest (OHCA) remains a significant health problem in the USA and only 8.6% of victims survive with good neurological function, despite advances in emergency cardiac care. The likelihood of OHCA survival decreases by 10% for every minute without resuscitation. RECENT FINDINGS: Automatic external defibrillators (AEDs) have the potential to save lives yet public access defibrillators are underutilized (< 2% of the time) because they are difficult to locate and rarely available in homes or residential areas, where the majority (70%) of OHCA occur. Even when AEDs are within close proximity (within 100 m), they are not used 40% of the time.

A RhoG-mediated signaling pathway that modulates invadopodia dynamics in breast cancer cells.

One of the hallmarks of cancer is the ability of tumor cells to invade surrounding tissues and metastasize. During metastasis, cancer cells degrade the extracellular matrix, which acts as a physical barrier, by developing specialized actin-rich membrane protrusion structures called invadopodia. The formation of invadopodia is regulated by Rho GTPases, a family of proteins that regulates the actin cytoskeleton. Here, we describe a novel role for RhoG in the regulation of invadopodia disassembly in human breast cancer cells. Our results show that RhoG and Rac1 have independent and opposite roles in the regulation of invadopodia dynamics. We also show that SGEF (also known as ARHGEF26) is the exchange factor responsible for the activation of RhoG during invadopodia disassembly. When the expression of either RhoG or SGEF is silenced, invadopodia are more stable and have a longer lifetime than in control cells. Our findings also demonstrate that RhoG and SGEF modulate the phosphorylation of paxillin, which plays a key role during invadopodia disassembly. In summary, we have identified a novel signaling pathway involving SGEF, RhoG and paxillin phosphorylation, which functions in the regulation of invadopodia disassembly in breast cancer cells.