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Cannabielsoin (CBE) is primarily recognized as an oxidation byproduct of cannabidiol (CBD) and a minor mammalian metabolite of CBD. The pharmacological interactions between CBE and cannabinoid receptors remain largely unexplored, particularly with respect to cannabinoid receptor type 1 (CB1). The present study aimed to elucidate the interaction dynamics of CBE in relation to CB1 by employing cyclic adenosine monophosphate (cAMP) and β-arrestin assays to assess its role as an agonist, antagonist, and positive allosteric modulator (PAM). To our knowledge, this is the first publication to investigate CBE’s receptor activity in vitro. Our findings reveal that S-CBE acts as an agonist to CB1 with EC50 = 1.23 µg/mL (3.7 µM) in the cAMP assay. No agonist activity was observed in the β-arrestin assay in concentrations up to 12 µM, suggesting a noteworthy affinity towards G-protein activation and the cAMP signaling pathway. Furthermore, in silico molecular docking simulations were conducted to provide a structural basis for the interaction between CBE and CB1, offering insights into the molecular determinants of its receptor affinity and functional selectivity.

Even slight structural differences between phytocannabinoid isomers are usually enough to cause a change in their biological properties. In this study, we used in vitro CB1 agonism/antagonism assays to compare the receptor binding functionality of THCV (tetrahydrocannabivarin) and HHC (hexahydrocannabinol) isomers and applied molecular docking to provide an explanation for the difference in the activities. No CB1 agonism was observed for ∆9- and ∆8-THCV. Instead, both isomers antagonized CP 55940, with ∆9-THCV being approximately two times more potent than the ∆8 counterpart (IC50 = 52.4 nM and 119.6 nM for ∆9- and ∆8-THCV, respectively). Docking simulations found two binding poses for THCV isomers, one very similar to ∆9-THC and one newly discovered pose involving the occupation of side pocket 1 of the CB1 receptor by the alkyl chain of the ligand. We suggested the latter as a potential antagonist pose. In addition, our results established 9R-HHC and 9S-HHC among partial agonists of the CB1 receptor. The 9R-HHC (EC50 = 53.4 nM) isomer was a significantly more potent agonist than 9S (EC50 = 624.3 nM). ∆9-THC and 9R-HHC showed comparable binding poses inside the receptor pocket, whereas 9S-HHC adopted a new and different binding posture that can explain its weak agonist activity.

Abstract Introduction Many adults hospitalised with COVID-19 have persistent symptoms such as fatigue, breathlessness and brain fog that limit day-to-day activities. These symptoms can last over 2 years. Whilst there is limited controlled studies on interventions that can support those with ongoing symptoms, there has been some promise in rehabilitation interventions in improving function and symptoms either using face-to-face or digital methods, but evidence remains limited and these studies often lack a control group. Methods and analysis This is a nested single-blind, parallel group, randomised control trial with embedded qualitative evaluation comparing rehabilitation (face-to-face or digital) to usual care and conducted within the PHOSP-COVID study. The aim of this study is to determine the effectiveness of rehabilitation interventions on exercise capacity, quality of life and symptoms such as breathlessness and fatigue. The primary outcome is the Incremental Shuttle Walking Test following the eight week intervention phase. Secondary outcomes include measures of function, strength and subjective assessment of symptoms. Blood inflammatory markers and muscle biopsies are an exploratory outcome. The interventions last eight weeks and combine symptom-titrated exercise therapy, symptom management and education delivered either in a face-to-face setting or through a digital platform ( www.yourcovidrecovery.nhs.uk ). The proposed sample size is 159 participants, and data will be intention-to-treat analyses comparing rehabilitation (face-to-face or digital) to usual care. Ethics and dissemination Ethical approval was gained as part of the PHOSP-COVID study by Yorkshire and the Humber Leeds West Research NHS Ethics Committee, and the study was prospectively registered on the ISRCTN trial registry (ISRCTN13293865). Results will be disseminated to stakeholders, including patients and members of the public, and published in appropriate journals. Article summary Strengths and limitations of this study • This protocol utilises two interventions to support those with ongoing symptoms of COVID-19 • This is a two-centre parallel-group randomised controlled trial • The protocol has been supported by patient and public involvement groups who identified treatments of symptoms and activity limitation as a top priority

Traditional life cycle assessment (LCA) is too data intensive and time consuming to be used during typical building design processes. Conducting an LCA during the building design process therefore requires simplifications and assumptions. Such “screening LCAs” are quicker and can be used with less data but introduce greater uncertainty. Unfortunately, uncertainty is not reflected in standard deterministic LCA calculations, which produce single-point values in LCA results. Thus, in this study, data quality scoring has been incorporated into a screening LCA to produce probabilistic predictions of environmental performance based on limited data. The approach has been applied during the design process of a bio-based wall panel designed for a circular economy. A combination of ecoinvent and material data sheets were used to analyse a wide range of novel bio-based insulation materials. The screening LCA analysed global warming potential and identified a short-list of promising materials that were then subjected to a detailed LCA for further consideration in the design. The method uses publicly available information and can be applied at material or building-element level. The method thus helps designers estimate environmental impacts without hindering the design process.

Abstract Background A functioning vascular access (VA) is crucial to providing adequate hemodialysis (HD) and considered a critically important outcome by patients and healthcare professionals. A validated, patient-important outcome measure for VA function that can be easily measured in research and practice to harvest reliable and relevant evidence for informing patient-centered HD care is lacking. Vascular Access outcome measure for function: a vaLidation study In hemoDialysis (VALID) aims to assess the accuracy and feasibility of measuring a core outcome for VA function established by the international Standardized Outcomes in Nephrology (SONG) initiative. Methods VALID is a prospective, multi-center, multinational validation study that will assess the accuracy and feasibility of measuring VA function, defined as the need for interventions to enable and maintain the use of a VA for HD. The primary objective is to determine whether VA function can be measured accurately by clinical staff as part of routine clinical practice (Assessor 1) compared to the reference standard of documented VA procedures collected by a VA expert (Assessor 2) during a 6-month follow-up period. Secondary outcomes include feasibility and acceptability of measuring VA function and the time to, rate of, and type of VA interventions. An estimated 612 participants will be recruited from approximately 10 dialysis units of different size, type (home-, in-center and satellite), governance (private versus public), and location (rural versus urban) across Australia, Canada, Europe, and Malaysia. Validity will be measured by the sensitivity and specificity of the data acquisition process. The sensitivity corresponds to the proportion of correctly identified interventions by Assessor 1, among the interventions identified by Assessor 2 (reference standard). The feasibility of measuring VA function will be assessed by the average data collection time, data completeness, feasibility questionnaires and semi-structured interviews on key feasibility aspects with the assessors. Discussion Accuracy, acceptability, and feasibility of measuring VA function as part of routine clinical practice are required to facilitate global implementation of this core outcome across all HD trials. Global use of a standardized, patient-centered outcome measure for VA function in HD research will enhance the consistency and relevance of trial evidence to guide patient-centered care. Trial registration Clinicaltrials.gov: NCT03969225. Registered on 31st May 2019.

Abstract Objectives The objective of this study is to investigate the variations in mineral content of tap drinking water across major Australian cities, compared with bottled still and sparkling water, and discuss the possible implications on kidney stone disease (KSD). Materials and Methods The mineral composition of public tap water from 10 metropolitan and regional Australian cities was compared using the drinking water quality reports published from 2019 to 2021 by the respective water service utilities providers. Specifically, average levels of calcium, bicarbonate, magnesium, sodium, potassium, and sulphates were compared with published mineral content data from bottled still and sparkling drinking water in Australia. Results The median or mean (depending on report output) mineral composition was highly variable for calcium (range 1.3 to 20.33 mg/L), magnesium (range 1.1 to 11.2 mg/L), bicarbonate (range 12 to 79 mg/L), sodium (range 3 to 47.1 mg/L), potassium (range 0.4 to 3.23 mg/L) and (sulphates range

Lung squamous cell carcinoma (LUSC) is a type of lung cancer with a dismal prognosis that lacks adequate therapies and actionable targets. This disease is characterized by a sequence of low- and high-grade preinvasive stages with increasing probability of malignant progression. Increasing our knowledge about the biology of these premalignant lesions (PMLs) is necessary to design new methods of early detection and prevention, and to identify the molecular processes that are key for malignant progression. To facilitate this research, we have designed XTABLE (Exploring Transcriptomes of Bronchial Lesions), an open-source application that integrates the most extensive transcriptomic databases of PMLs published so far. With this tool, users can stratify samples using multiple parameters and interrogate PML biology in multiple manners, such as two- and multiple-group comparisons, interrogation of genes of interests, and transcriptional signatures. Using XTABLE, we have carried out a comparative study of the potential role of chromosomal instability scores as biomarkers of PML progression and mapped the onset of the most relevant LUSC pathways to the sequence of LUSC developmental stages. XTABLE will critically facilitate new research for the identification of early detection biomarkers and acquire a better understanding of the LUSC precancerous stages.

Crithidia fasiculata belongs to the trypanosomatidae order of protozoan parasites, bearing close relation to other kinetoplastid parasites such as Trypanosoma brucei and Leishmania spp. As an early diverging lineage of eukaryotes, the study of kinetoplastid parasites has provided unique insights into alternative mechanisms to traditional eukaryotic metabolic pathways. Crithidia are a monogenetic parasite for mosquito species and have two distinct lifecycle stages both taking place in the mosquito gut. These consist of a motile choanomastigote form and an immotile amastigote form morphologically similar to amastigotes in Leishmania. Owing to their close relation to Leishmania, Crithidia are a growing research tool, with continuing interest in its use as a model organism for kinetoplastid research with the added benefit that they are non-pathogenic to humans and can be grown with no special equipment or requirements for biological containment. Although comparatively little research has taken place on Crithidia, similarities to other kinetoplast species has been shown in terms of energy metabolism and genetics. Crithidia also show similarities to kinetoplastids in their production of the monosaccharide D-arabinopyranose similar to Leishmania, which is incorporated into a lipoarabinogalactan a major cell surface GPI-anchored molecule. Additionally, Crithidia have been used as a eukaryotic expression system to express proteins from other kinetoplastids and potentially other eukaryotes including human proteins allowing various co- and post-translational protein modifications to the recombinant proteins. Despite the obvious usefulness and potential of this organism very little is known about its lipid metabolism. Here we describe a detailed lipidomic analyses and demonstrate the possible placidity of Crithidia’s lipid metabolis. This could have important implications for biotechnology approaches and how other kinetoplastids interact with, and scavenge nutrients from their hosts.

In this study, we focus on the effects of fuel bed representation and fire heat and smoke distribution in a coupled fire-atmosphere simulation platform for two landscape-scale fires: the 2018 Camp Fire and the 2021 Caldor Fire. The fuel bed representation in the coupled fire-atmosphere simulation platform WRF-Fire currently includes only surface fuels. Thus, we enhance the model by adding canopy fuel characteristics and heat release, for which a method to calculate the heat generated from canopy fuel consumption is developed and implemented in WRF-Fire. Furthermore, the current WRF-Fire heat and smoke distribution in the atmosphere is replaced with a heat-conserving Truncated Gaussian (TG) function and its effects are evaluated. The simulated fire perimeters of case studies are validated against semi-continuous, high-resolution fire perimeters derived from NEXRAD radar observations. Furthermore, simulated plumes of the two fire cases are compared to NEXRAD radar reflectivity observations, followed by buoyancy analysis using simulated temperature and vertical velocity fields. The results show that while the improved fuel bed and the TG heat release scheme have small effects on the simulated fire perimeters of the wind-driven Camp Fire, they affect the propagation direction of the plume-driven Caldor Fire, leading to better-matching fire perimeters with the observations. However, the improved fuel bed representation, together with the TG heat smoke release scheme, leads to a more realistic plume structure in comparison to the observations in both fires. The buoyancy analysis also depicts more realistic fire-induced temperature anomalies and atmospheric circulation when the fuel bed is improved.

In 2013, the National Institute of Food and Agriculture supported the creation of a professional development and technical assistance center to promote strong implementation and evaluation of University-led, community-based projects serving low-resource populations. Within this center, a coaching cadre was established to provide proactive and responsive technical assistance. Formative evaluation involving coaches and their primary contacts was used for refinement of coaching practices. Initially, coaches were encouraged to build strong interpersonal rapport. This set the stage for trusting, reciprocal interactions, but coaches recognized a need for targeted support and more tools for quality programming, evaluation, and sustainability. Greater emphasis was placed on goal-focused collaboration. Coaches received training and resources on topics such as goal setting, program quality, reduction of barriers (e.g., participant recruitment), and sustainability strategies. To assess coaching model enhancements, a survey of projects was expanded to gauge logic model usage, goal setting, strength of coaching relationships, and project implementation and sustainability progress. Overall, coaching was rated more favorably and effective when contact was consistent, inclusive of face-to-face interaction, met technical needs, and involved collaborative brainstorming and planning. Findings indicate coaching relationships strengthen over time and demand a collaborative, action-orientation to set goals, reduce barriers, and drive stronger outcomes.

Polyethyleneimine (PEI) is a flocculent that is widely used in the downstream purification of monoclonal antibodies. It is an in-process residual that is carried through the drug purification process and strongly inhibits residual DNA quantitation by real-time quantitative PCR assay. Very high sample dilutions (e.g., 1:10,000) can overcome the interference of PEI, but at the cost of DNA assay sensitivity. Diluting samples poses a significant risk to the assay sensitivity needed to satisfy regulatory requirements on the quantitation of residual genomic DNA present per dose (i.e., 10 ng/dose). Removing PEI while retaining DNA, by the use of sodium dodecyl sulfate, heparin and/or sarkosyl can overcome the interference of PEI and allow a more accurate quantitation of residual DNA.

Abstract Background Anti‐platelet factor 4 (PF4) antibodies that activate platelets via FcγRIIA drive the pathophysiology of vaccine‐induced immune thrombocytopenia and thrombosis (VITT). Evolution of these antibodies and their ability to activate platelets after initial treatment remains unknown. Objectives To assess how clinical and platelet parameters, anti‐PF4 antibody levels, and patient serum reactivity changes during follow‐up after VITT presentation. Methods We describe cases of seven discharged VITT patients that were followed from diagnosis up to 280 days (range 199–280) after vaccination. We measured anti‐PF4 antibodies and PF4 levels in patient serum during follow‐up and tested the ability of patient serum to activate healthy donor platelets and patient platelets over time. Results Anti‐PF4 immunoglobulin G antibody levels are very high at diagnosis (0.9–2.6 OD) and remain relatively high (>1.0 OD) in all patients, except one treated with rituximab, at 7 months post vaccination. All patients were on direct oral anticoagulants throughout follow‐up and no patients had recurrent thrombosis. Patients’ platelets during follow‐up have normal FcγRIIA levels and responsiveness to platelet agonists. Patient diagnostic serum strongly activated control platelets, either alone or with PF4. Most follow‐up serum alone was weaker at stimulating donor and patient platelets. However, follow‐up serum beyond 150 days still strongly activated platelets with PF4 addition in three patients. Patient serum PF4 levels were lower than controls at diagnosis but returned within normal range by day 50. Conclusions Explanations for reduced platelet activation during follow‐up, despite similar total anti‐PF4 antibody levels, remains unclear. Clinical implications of persistent anti‐PF4 antibodies in VITT require further study.

Three-dimensional printing (3DP) allows production of novel fast dissolving oral films (FDFs). However, mechanical properties of the films may not be desirable when certain excipients are used. This work investigated whether adding chitosan micro-ribbons or cellulose microfibres will achieve desired FDFs by fused deposition modelling 3DP. Filaments containing polyvinyl alcohol (PVA) and paracetamol as model drug were manufactured at 170 °C. At 130 °C, filaments containing polyvinylpyrrolidone (PVP) and paracetamol were also created. FDFs were printed with plain or mesh patterns at temperatures of 200 °C (PVA) or 180 °C (PVP). Both chitosan micro-ribbons and cellulose micro-fibres improved filament mechanical properties at 1% w/w concentration in terms of flexibility and stiffness. The filaments were not suitable for printing at higher concentrations of chitosan micro-ribbons and cellulose micro-fibres. Furthermore, mesh FDFs containing only 1% chitosan micro-ribbons disintegrated in distilled water within 40.33 ± 4.64 s, while mesh FDFs containing only 7% croscarmellose disintegrated in 55.33 ± 2.86 s, and croscarmellose containing films showed signs of excipient scorching for PVA polymer. Cellulose micro-fibres delayed disintegration of PVA mesh films to 108.66 ± 3.68 s at 1% w/w. In conclusion, only chitosan micro-ribbons created a network of hydrophilic channels within the films, which allowed faster disintegration time at considerably lower concentrations.

Several regulations and standards have been developed to reduce the carbon footprint of buildings, but these have failed to provide a clear pathway to a net zero future. Hence, we recently introduced the Active Building Code (ABCode). This provides guidance on reducing the environmental impact of the next generation of buildings, termed Active Buildings (ABs), through their synergy with the grid. This paper aims to illuminate the regulatory landscape, justify our initial proposal for the ABCode, and reveal opportunities and challenges to the popularisation of ABs. Twelve online focus group discussions were conducted, with thirty stakeholders in total, all selected on the basis of their expertise. A grounded theory approach identified five core themes in such discussions. These strongly overlap with what is incorporated in the ABCode, suggesting the code successfully captures issues important to experts. Stakeholders defined ABs as responsive buildings and proposed both energy and carbon are considered in their assessment. They hence aligned with the definition and evaluation framework proposed by the ABCode. Finally, stakeholders considered people’s tendency to prioritise capital cost as the greatest challenge to the popularisation of ABs, and the increasing demand for healthy environments as its greatest opportunity.

Category: Midfoot/Forefoot Introduction/Purpose: Hallux rigidus is a common arthritic condition seen by foot and ankle specialists. Historically, surgical treatment options have varied from an isolated cheilectomy to first metatarsophalangeal joint fusion. More recently, first metatarsophalangeal (MTP) joint hemiarthroplasty with a polyvinyl alcohol (PVA) hydrogel implant (Cartiva) has become a popular surgical option. A randomized clinical trial sponsored by the manufacturers of the implant showed equivalent pain relief and functional outcome scores at 2 year follow-up when compared to patients undergoing first MTP fusion. In addition, the study reported no bone loss, implant wear or loosening. We retrospectively reviewed 1 year PROMIS score outcomes, clinical outcomes and implant survivorship of patients treated with first MTP hemiarthroplasty with the Cartiva implant at an academic, multi-surgeon center. Methods: We retrospectively reviewed 54 consecutive patients that underwent first MTP hemiarthroplasty with Cartiva for hallux rigidus between January 1, 2017 and December 1, 2017. Minimum follow-up criteria was 1 year, with the average being 1.37 years and maximum follow-up of 1.9 years. The Coughlin radiographic grading of disease severity averaged 2.18 at the time of implantation on a scale of 0 to 4. Surgery was performed by 8 fellowship-trained orthopedic foot and ankle surgeons at an academic institution. Baseline PROMIS scores (physical function, pain interference, global function, global mental, depression) and PROMIS scores acquired at 1 year postoperative were compared and evaluated using the Wilcoxon signed t-test. Clinical outcomes and postoperative complications/events were documented through review of electronic medical records. At the time of the study, 49 patients had reached 1 year follow-up with an average age of 56 (range, 33 - 74) years at the time of implantation. Results: Physical function, pain interference, global function and depression scores all demonstrated clinically and statistically significant improvement at 1 year postoperative. Global mental score did not show significant improvement at the one year follow-up. One patient underwent revision surgery to a 1st MTP fusion for persistent pain. Three patients had postoperative soft tissue swelling requiring prolonged retained sutures. Five patients underwent therapeutic injection with steroid between 2 - 11 months postoperative for persistent discomfort which improved. Five patients were prescribed orthotics between 3 - 6 months follow-up. One patient sustained a metatarsal fracture during the application of the implant requiring ORIF but retained the implant. Implant retention at 1 year was 98% (48/49). No correlation between preoperative radiographic grading and the incidence of poor clinical outcomes. Conclusion: To our knowledge, this is the first study that demonstrates the outcomes of synthetic cartilage implants using a large series of surgeons without affiliation or consultation for the implant company. One year following first MTP hemiarthroplasty with PVA hydrogel implant (Cartiva), functional and pain scores improved significantly, but did not show significant improvement with global mental scores. The implant displayed excellent survivorship at the 1 year time point, with only one patient undergoing surgical revision. Treatment of hallux rigidus with the PVA hydrogel implant - Cartiva, shows improved patient outcomes and has reassuring results at one year.

The effect of the wider social-environment on physical and emotional health has long been an area of study. Extrapolating the impact of the individual's immediate environment, such as living with a smoker or caring for a chronically-ill child, would potentially reduce confounding effects in health-related research. Surveys, including the UK Census, are beginning to collect data on household composition. However, these surveys are expensive, time consuming, and, as such, are only completed by a subsection of the population. Large-scale, linked databanks, such as the SAIL Databank at Swansea University, which hold routinely collected secondary use clinical and administrative datasets, are broader in scope, both in terms of the nature of the data held, and the population. The SAIL databank includes demographic data and a geographic indicator that makes it possible to identify groups of people that share accommodation, and in some cases the familial relationships among them. This paper describes a method for creating households, including considerations for how that information can be securely shared for research purposes. This approach has broad implications in Wales and beyond, opening up possibilities for more detailed population-level research that includes consideration of residential social interactions.

Objectives Children requiring cortisol replacement therapy are often prescribed hydrocortisone doses of 2.5 mg, but as this is commercially unavailable 10 mg tablets, with functional break lines, are split commonly in an attempt to deliver the correct dose. This study aimed to determine the dose variation obtained from quartered hydrocortisone tablets when different operators performed the splitting procedure and to ascertain whether better uniformity could be attained from mini-tablets as an alternative formulation.Methods Hydrocortisone 10 mg tablets were quartered by four different operators using a standard pill splitter. Hydrocortisone 2.5 mg mini-tablets (3 mm diameter) were formulated using a wet granulation method and manufactured using a high-speed rotary press simulator. The weight and content uniformity of the quartered tablets and mini-tablets were assessed according to pharmacopoeial standards. The physical strength and dissolution profiles of the mini-tablets were also determined.Results More than half of all quartered 10 mg tablets were outside of the ±10% of the stated US Pharmacopoeia hydrocortisone content (mean 2.34 mg, SD 0.36, coefficient of variation (CV) 15.18%) and more than 40% of the quartered tablets were outside the European Pharmacopoeia weight variation. Robust mini-tablets (tensile strengths of >4 MPa) were produced successfully. The mini-tablets passed the pharmacopoeial weight and content uniformity requirements (mean 2.54 mg, SD 0.04, CV 1.72%) and drug release criteria during in vitro dissolution testing.Conclusion This study confirmed that quartering 10 mg hydrocortisone tablets produces unacceptable dose variations and that it is feasible to produce 3 mm mini-tablets containing more accurate doses for paediatric patients.

Category: Other Introduction/Purpose: Neuraxial anesthesia is often viewed as superior to general anesthesia (GA), but there are concerns that it may prolong length of stay (LOS). Most studies comparing the two anesthesias were performed in the absence of peripheral nerve blocks (PNBs), which when used as an analgesic adjunct may overcome the associated negative side effects of GA and allow decreased LOS. We hypothesized that patients given PNBs and GA would be discharged sooner than patients given PNBs and spinal anesthesia plus sedation, without increased incidence of adverse side effects such as pain, opioid administration and nausea. Methods: A single-center triple-blinded randomized controlled trial of 36 consecutive patients receiving elective F&A surgery predicted to take 1-3 hours under planned PNB with either spinal or GA was performed (see table 1. for demographics).The primary outcome was time to meet criteria for home discharge. The a priori clinically relevant difference with 80% power was determined to be 45 minutes. Patients were assessed after admission to the PACU and at 15-minute intervals thereafter. Once an Aldrete score=9 (scale signifying patient no longer needs intensive monitoring) was obtained, patients were transferred to Phase II and assessed until the post anesthesia discharge scoring system, a home readiness scale, was =9. Actual time to discharge was also recorded.Additional outcomes included a series of baseline characterizations which were assessed pre-and post-operatively, and again during Phase II.The primary outcome was compared using multivariable unconditional quantile regression. Various regressions were performed on secondary outcomes. Results: After adjustment for age and surgical duration, patients given GA plus PNB were ready for discharge from PACU 39 minutes prior to patients given neuraxial anesthesia plus PNB, but this difference did not reach the clinically relevant a priori selected difference of 45 minutes (Table 1). However, the adjusted median time to meet ambulation discharge criteria was 52 minutes fewer (p = 0.003) (Table 1). Patients met discharge criteria substantially sooner than their time until actual discharge which was not different between groups (Table 1). Pain scores at rest were higher among GA patients at 1 hour in the PACU (adjusted difference in means [95% CI]: 2.1 [1.0, 3.2], p < 0.001). Subsequent pain scores and all other secondary outcomes were not different. Conclusion: GA with PNB patients were ready for discharge 39 minutes earlier, but that difference may not be clinically significant. Although patients met criteria for discharge sooner due to a significantly more rapid ability to ambulate, they were not discharged sooner because PACU staff was not acclimated to the earlier readiness and so did not push for earlier discharge. These findings suggest that GA plus PNB leads to earlier discharge with similar side effects as spinal plus PNB. Therefore, the use of GA with PNB for foot and ankle surgeries could save the hospital and the patient time and resources.

Category: Pain Management, Anesthetic Advances Introduction/Purpose: The number of opioid prescriptions in the United States has significantly increased over the past 20 years, including those given after low-risk surgery. Unintentional opioid overdoses have also dramatically risen. Excess pills are widely acknowledged as a source of diversion, which accounts for up to 40% of opioid-related overdoses. In the foot and ankle literature, there are no studies looking at the quantity of pain medications that should be prescribed following outpatient surgery. Furthermore, with the increasing use of peripheral nerve blocks, their effect on quantities of narcotics needed after these surgeries have not been explored. This study aims to determine prescribing patterns for common outpatient foot and ankle surgery and whether patients are over or under-prescribed opioids and if so, by how much. Methods: 57 patients undergoing outpatient foot and ankle surgeries were prospectively enrolled. Patients received a spinal neuraxial block and a long-acting popliteal peripheral nerve block, and did not receive ketorolac perioperatively. Patients were excluded if they had a history of chronic pain, or were currently using opioids or muscle relaxers. Enrolled patients received a standard post-operative prescription regimen of 60 tablets of narcotics, 3 days of scheduled ibuprofen, aspirin 81 mg twice a day (or alternate based on risk factors) for DVT prophylaxis, and ondansetron taken as needed. Patients used a pain diary to record when their block wore off and the quantity of narcotic taken. They received surveys at post-operative day (POD) 3, 7, and 14 detailing how many days they took the medication and how many pills were consumed, how their actual pain compared to their expected level of pain, and if they were satisfied with their pain control. Results: At POD 3, compared to their expected level of pain 36 patients had less pain, 15 had the same pain, and 3 had more pain than expected. The mean pain score was 4. Patients first started feeling the block wear off at 0.9 days. Patients averaged 10.3 pills of narcotics in the first 3 days and rated their overall satisfaction with pain control at 8.5. Between days 4-7, patients took an average of 7 pills, and on POD 7, 22 patients were still taking narcotics. At POD 14, patients experienced 74.4% relief of pain compared to their expected pain, and rated their overall satisfaction at 8.2. Patients had an average of 33.5 remaining pills on POD 14 and 13 patients (22.8%) were still taking narcotics. Conclusion: Patients receiving spinal and long-acting popliteal blocks, followed by the prescription regimen described above had excellent pain control after outpatient foot and ankle surgeries. Patients had a high level of satisfaction with their pain control, with many patients describing better pain relief than expected. However, 60 tablets of narcotics were excessive in most cases. We suggest that in patients receiving spinal and long-acting popliteal blocks, 30 tablets of a narcotic would cover the pain needs of most patients. This would provide a small excess in case of need, but would help minimize the risk of narcotic related complications and diversion.

Category: Other Introduction/Purpose: Few authors have investigated patients’ expectations from foot and ankle surgery, and standardized means of assessing expectations are lacking. Managing patients’ preoperative expectations may help improve their ultimate satisfaction with surgery. In a previous study (in press), we developed a valid and reliable patient-derived expectations survey for patients undergoing foot and ankle surgery. In this study, we aimed to examine relationships between patients’ preoperative expectations and their demographic and clinical characteristics. We hypothesized that patients with more disability and those with anxiety or depressive symptoms would have greater expectations. Methods: All adult patients scheduled for elective foot or ankle surgery by one of six orthopaedic foot and ankle surgeons were screened for inclusion over eight months. Preoperatively, patients completed the Foot & Ankle Surgery Expectations Survey in addition to the Foot & Ankle Outcome Score (FAOS), Short Form (SF)-12, Patient Health Questionnaire (PHQ)-8, Generalized Anxiety Disorder 7-item scale (GAD-7), and pain visual analog scale (VAS). The expectations survey contains 23 expectations categories, each with five answer choices ranging from I do not have this expectation to complete improvement expected. It is scored from 0-100; higher scores indicate greater expectations. Differences in expectations score with categorical variables were assessed with t-tests and single factor analysis of variance (ANOVA). Differences in number of expectations and number of expectations with complete improvement expected were assessed with Mann-Whitney U and Kruskal Wallis tests. Relationships between expectations and continuous variables were assessed with linear regression. Results: 352 patients (average age 55 ± 15, range 18 to 86) were enrolled. Expectations were not significantly related to age. Women expected to achieve complete improvement more often than men (p = 0.011). Other factors significantly associated with higher expectations (p < 0.05) included non-Caucasian race, workers’ compensation, use of a cane or other assistive device, diagnosis of ankle instability or osteochondral lesion, and greater medical comorbidity (Table). Patients with a history of prior orthopaedic surgery were less likely to expect complete improvement. Worse function and quality of life (as assessed by all FAOS subscales and SF-12 physical and mental components), more depressive and anxiety symptoms, and higher pain VAS scores were associated with higher expectations scores and more expectations (p < 0.001 for all). Conclusion: The results of this study may help inform surgeons’ preoperative discussions with their patients regarding realistic expectations from surgery. Generally patients with worse function and more disability had higher expectations from surgery. Addressing these patients’ expectations preoperatively may help improve their ultimate satisfaction with surgery.