Multimodal Pathway Research Articles

Talking Drawings: A Multimodal Pathway for Demonstrating Learning

AbstractExpanding definitions of literacy requires classroom instruction that provides multiple pathways for students to demonstrate their understanding of the content and communicate knowledge. Privileging the use of visual and multimodal texts as valued school communication may create equitable practices for students who are new to English or struggle with literacy for a variety of reasons. The authors explore the roles that the Talking Drawings strategy played in supporting students’ content and literacy learning and in their ability to reflect on their new understandings. In seven upper elementary classrooms, students drew pictures before and after focused instruction about a topic and added written reflections about the differences between the two drawings. The results of this study demonstrate how Talking Drawings provided a multimodal pathway for students to access the curriculum, communicate new content knowledge, redirect their content misconceptions, and reflect on their learning.

Efficacy of a Novel Integrated Active Herbal Formulation in Experimentally Induced Osteoarthritis Rat Model

Abstract Objectives Osteoarthritis (OA) is a debilitating chronic illness that affects millions across the globe. Current medical treatment approaches that focus on the reduction of pain and inflammation using pharmaceutical drugs are moderately effective and associated with significant adverse events. Hence health care professionals are exploring alternative approaches that are effective and safe to treat osteoarthritis. We developed a novel integrated active formulation to alleviate symptoms of osteoarthritis using improved plant extracts from Curcumin, Ashwagandha and Boswellia and validated the efficacy of the formulation using a well-established animal model for osteoarthritis. Methods We induced OA in female Wistar rats by intra-articular injection of sodium monoiodoacetate followed by recovery for 14 days. Seven rats were included in each group. Animals were supplemented with integrated active herbal formulation of enriched extracts of Curcumin, Boswellia and Ashwagandha for 4 weeks at two different concentrations (100 and 200 mg/kg body weight) and assessment of disease was carried out by histopathology including integrity of joint architecture, and effect of supplementation on oxidative stress, inflammation and on extracellular matrix proteinases levels in joint tissue using western blot technique. Results We observed a significant restoration of joint architecture and reduction in swelling of joint as demonstrated by X-ray images and histopathology after 4 weeks of administration integrated active herbal supplement. There was a significant reduction in serum and synovial tissue malondialdehyde levels and increased superoxide dismutase, glutathione peroxidase; and catalase levels. Synovial inflammatory markers (IL-1β, IL-6, IL-10, TNF-α and CRP) and markers of cartilage damage such as COMP, collagen type 2 and MMP-3 levels were significantly reduced in synovial tissue in response to supplementation. Conclusions Our data indicate that our integrated active herbal formulation has a strong protective effect against OA in a dose dependent manner by acting through multi-modal pathways as substantiated by significant effects on histopathology, inflammation, oxidative stress and collagen degradation. Funding Sources OmniActive Health Technologies Limited.

Enhanced recovery after surgery review and urology applications in 2020.

Purpose: To explore enhanced recovery after surgery (ERAS) components and their current application to major urologic surgeries, barriers to implementation and maintenance of the associated quality improvement. Data Identification: An English language literature search was done using PubMed. Study Selection: After independent review, 55 of the original 214 articles were selected to specifically address the stated purpose. Data Extraction: Clinical trials were included, randomized trials were prioritized, but robust observational studies were also included. Results of Data Synthesis: Many ERAS components have good data to support usage in radical cystectomy (RC) patients. Most ERAS programs include multidisciplinary teams carrying out multimodal pathways to hasten recovery after a major operation. ERAS components generally include preoperative counseling and medical optimization, venous thromboembolism prophylaxis, ileus prevention, avoidance of fluid overload, normothermia maintenance, early mobilization, pain control and early feeding, all leading to early discharge without increased complications or readmissions. Although there may not be specific data pertaining to other major urologic operations, the principles remain similar and ERAS is easily applicable. Conclusion: The benefits of ERAS programs are well established for RC and principles are easily applicable to other major urology operations. Barriers to implantation and maintenance of ERAS must be recognized to continue to maintain the benefits of these programs.

Multimodal pathway for brain tumor-related epilepsy patients: Observational study.

Brain tumor-related epilepsy patients (BTRE) have a complex profile due to the simultaneous presence of two pathologies: brain tumor and epilepsy. That illness and their treatments could induce physical, cognitive, emotional disturbances, and possible social isolation, with detrimental effect on patients' quality of life (QoL). Aim of this observational pilot study is to evaluate whether a multimodal rehabilitation pathway (MRP) consisting of epileptological follow-up, neurocognitive training, emotional support, and social support could produce an improvement in perceived quality of life of 33 patients with BTRE. Basal (T0) and 6month (T1) evaluation with epileptological, neuropsychological, psychological state (Symptom checklist-SCL-90), social (Social questionnaire schedule-SQS), and QoL assessment (QOLIE 31-P). MRP consisted in epileptological follow-up, supportive meeting groups, social assistance; patients with cognitive deficits could also obtain a 12-week neurocognitive training. We observed at T1 significant improvements in mean seizure/month (P=.02), verbal memory (word list immediate recall, P=.01; word list delayed recall P=.003), social aspects with regard to assistencial network's efficacy (SQS network P=.001) and quality of social relations (SQS socialization P<.0001). QOLIE 31-P showed a significant improvement in cognitive scale (P=.04) and a significant decrease in cognitive related distress (P=.04). No psychopathological symptoms were detected. After 6months, MRP produced significant improvements in seizure control, cognitive performances, quality of social relations, patients' perception to be supported and patients' perceived quality of life related to cognitive efficacy. Future randomized trial with longer follow-up is needed to further evaluate the impact of this kind of pathway on patients' QoL.

Peri-articular infiltration in the resource-restrained environment - still a worthwhile adjunct to multimodal analgesia post total knee replacement

ABSTRACT BACKGROUND: Peri-articular infiltrations (PAI) in total knee arthroplasty (TKA) offer effective analgesia, and are cost effective, safe and easy to perform. Currently there is no gold standard technique based on evidence-based medicine; described methods are based on consensus recommendations. The latest literature supports PAI including complex and multiple drug combinations, such as liposomal bupivacaine, ropivacaine and ketorolac, which are not available in all settings. This study aims to prove that a basic PAI technique using widely available and inexpensive agents offers good and effective outcomes in a resource-poor environment METHODS: A double-blind randomised control trial compared the effectiveness of PAI with a simple, widely available anaesthetic solution (bupivacaine and adrenalin) to a normal saline control group. Infiltration volumes were calculated at 1 ml/kg and the infiltration technique followed a specific protocol. Post-operative outcomes included visual analogue scores (VAS), ambulation scores, morphine use, knee range of motion (ROM) and time to discharge RESULTS: Two comparable groups of 26 patients each were included (intervention: 81% female, mean age 64.8±8.8 years vs control: 65% female, mean age 67.0±7.6 years). All pain-related measures favoured the intervention group but failed to reach statistical significance at 24 and 72 hours. Mean VAS scores at 48 hours were significantly lower in the intervention group. (VAS score 3.0±1.6 vs 4.1±1.2, p=0.013). The other parameters measured strongly favoured the intervention group but did not prove to be significant CONCLUSIONS: A volume per kilogram PAI technique making use of widely available, cost-effective agents provides a statistical reduction in VAS scores at 48 hours post TKA. This suggests that in a resource-poor environment PAI is still a valuable addition to the multimodal analgesia pathway in the post-operative management of TKA. Maximum drug doses may show even more promising results, specifically in the first 24 hours post-operatively. Further studies investigating PAI for TKA in resource-restrained environments are indicated Level of evidence: Level 2 Keywords: standardisation peri-articular infiltration, multimodal analgesia, pre-emptive analgesia

Methylprednisolone Does Not Reduce Acute Postoperative Pain After Cardiac Surgery: Subanalysis of a Randomized Clinical Trial.

Pain after cardiac surgery is largely treated with opioids, but their poor safety profile makes nonopioid medications attractive as part of multimodal pathways. Anti-inflammatory drugs reduce acute postoperative pain, but the role of steroids in reducing acute poststernotomy pain is unclear. We evaluated the association between the intraoperative administration of methylprednisolone and postoperative analgesia, defined as a composite of pain scores and opioid consumption, during the initial 24 hours after cardiac surgery. We conducted a post hoc retrospective analysis of a large clinical trial in which adults having cardiac surgery were randomized 1:1 to receive 2 intraoperative doses of 250 mg IV methylprednisolone or placebo. Pain scores and opioid consumption were collected during the initial 24 hours after surgery. Methylprednisolone was considered to be associated with better pain control than placebo if proven noninferior (not worse) on both pain scores (defined a priori with delta of 1 point) and opioid consumption (delta of 20%) and superior to placebo in at least 1 of the 2 outcomes. This test was repeated in the opposite direction (testing whether placebo is better than methylprednisolone on postoperative pain management). Of 251 eligible patients, 127 received methylprednisolone and 124 received placebo. Methylprednisolone was noninferior to placebo on pain with difference in mean (CI) pain scores of -0.25 (-0.71 to 0.21); P < .001. However, methylprednisolone was not noninferior to placebo on opioid consumption (ratio of geometric means [CI]: 1.11 [0.64-1.91]; P = .37). Because methylprednisolone was not noninferior to placebo on both outcomes, we did not proceed to superiority testing based on the a priori stopping rules. Similar results were found when testing the opposite direction. In this post hoc analysis, we could not identify a beneficial analgesic effect after cardiac surgery associated with methylprednisolone administration. There are currently no data to suggest that methylprednisolone has significant analgesic benefit in adults having cardiac surgery.

Fluid management for enhanced recovery surgery

This review article introduces some of the major concepts in perioperative fluid management and the application of these to enhanced recovery programmes (ERPs). The aim of these programmes are to implement multimodal pathways in the perioperative period in order to reduce the risk of perioperative organ dysfunction and morbidity. This article introduces some of the concepts that should be considered during ERPs in terms of perioperative fluid administration, based upon the latest recommendations and guidelines produced internationally. Inappropriate fluid management can lead to increased morbidity, increased length of stay and can have costly implications for healthcare providers. Overall concepts of fluid management include maintenance of homeostasis and euvolaemia. We have looked at how to implement this for patients in preoperative, intraoperative and postoperative states. This article is based upon recent guidelines and consensus statements published internationally. Despite the generalised concepts behind fluid administration in ERPs, patients should continue to have individualised management plans based upon their specific health requirements.

Qualitative findings from administrators of the EMPATHY (Empowering a multimodal pathway toward healthy youth) programme using the SBIRT framework

ABSTRACT Comprehensive programmes to help reduce substance misuse/mental illness in youth should combine Screening, Brief Intervention, and Referral to Treatment (SBIRT). EMPATHY, an SBIRT programme, was part of a school-based prevention initiative to reduce symptoms of substance misuse in youth in Grades 6–12, along with reducing symptoms of depression, suicidal thinking, and anxiety. To better understand the feasibility of school-based SBIRT, we retrieved perspectives of administrators primarily through interviews. The level of engagement and interest of youth in the programme was high; however, two significant barriers were: (1) the need for parental consent/involvement; and (2) a systemic gap in treatment choices for youth with mild to moderate symptomology. Therapeutic alliance with students was reportedly a significant factor contributing to benefits.

1059 Effects of HCV Eradication on Glycemic Control in Type 2 Diabetics

INTRODUCTION: A meta-analysis of 34 studies estimated that the risk was increased by almost 70 percent in HCV-infected patients compared with non-infected controls. Insulin resistance has been hypothesized to develop via a multimodal pathway. The virus itself causes this through serine and threonine phosphorylation of insulin receptor substrate-1. Hepatitis creates a ubiquitous inflammatory state by releasing proinflammatory cytokines such as interleukin-6 and tumor necrosis factor-α, which upregulates gluconeogenesis. We aimed to analyze the unique patient population cared for at Louisiana State University diagnosed with DM2 and HCV who have completed direct-acting antiviral treatment with a sustained viral response (SVR). We attempted to establish a connection between a SVR and improved glycemic control and quantify the variations in HbA1C. METHODS: Using ICD 9/10/CPT codes the study included all patients with DM2 who underwent HCV treatment with DAA. SVR was achieved in all patients using non-ribavirin and non-interferon based therapies. SVR was defined as viral load below the lower limit of quantification after the completion of treatment. Treatments varied between 8 weeks and 12 weeks. We further divded the patient population into two groups and statistically analyzed patients with Severe Fibrosis/Cirrhosis to those without. Comparative analysis and Fisher’s exact test was performed. RESULTS: The F-test for increase in Metavir score correlated with a mean drop of 0.5% in HbA1c gives a P Value of 0.01652. DM2 Pts who achieved SVR had an overal drop in HbA1C of 0.39 (P = 0.009), while Cirrhotics experieces the largest median decrease 0.65% (P = 0.004). SF/Cirrhotic patients experienced the largest drop in median Isulin requirements post-treatment, decrease of 6.32 Units (P = .206). SF/Cirrhotic patients also experienced the largest median decrease in number of classes of anti-diabetic medications (P = .445). CONCLUSION: Analysis revealed statistically signficant results in regards to reduction in HbA1C, with the greatest benefits experiened by the SF/Cirrhotic cohort.The improvement in microvascular complications in diabetics with a reduction in HbA1C has been confirmed by multiple studies. An increase in the number of investigations with similar findings can assist insurance companies in completing a risk benefit analysis in providing full treatment compensation to all HCV patients with concomitant DM2.

CN6 - E-health effectiveness to increase patient adherence for immunotherapy: A cost-benefit study

BackgroundE-health incorporates a range of standards, tools and activities that use electronic to deliver information, resources and services in relation to health care. Final goal is improve quality of health information, strengthening national health systems and ensuring accessible health for population with reduce costs.Imuno-oncology uses the power of the body’s own immune system to prevent, target, control, and eliminate cancer. Most of Immune related Adverse Events are moderate, reversible if detected early and properly. Teleoncology can decrease the existing gaps between care provider and patients. Allow patients to contact with professionals, permit communication, emotional support, regular assessment and, patient empowerment during and after treatment which rise patient adherence. MethodsDescribe the use of e-health systems to promote cancer care. How e-health technology can improve cancer nurse practise and empower cancer patients receiving Immunotherapy? 3 phases: first literature review searching for e-health nurses interventions with cancer patients in last years. Second; to recruit nurses’ priorities in the 2 countries (Portugal, Spain) to assess and control adherence. Finally a multimodal pathway using e-health technology to provide a checklist for professionals will be develop. ResultsThe intended results are to provide a standardized system in order to facilitate the use of e-health, for cancer patients and professionals. Display evidence-based models using a process for framing a question, locating, assessing, evaluating, and repeating it as needed. Is projected to recognize professionals needed skills to improve e-Health technologies to support cancer care, specify e-health interventions for the management of immunotherapy side effects and factors that users perceive or experience as facilitators or barriers to the uptake and implementation of eHealth technologies. ConclusionsTechnology-based interventions could be suitable for immunotherapy treatment. The study will recognize the necessary skills and e-health best system to improve nursing care, adherence and promote quality of life. Further research is required to fully assess the impact of technology as an information and support mechanism for carers. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

A multimodal pathway including the basal ganglia in the feline brain.

The purpose of this paper is to give an overview of our present knowledge about the feline tecto-thalamo-basal ganglia cortical sensory pathway. We reviewed morphological and electrophysiological studies of the cortical areas, located in ventral bank of the anterior ectosylvian sulcus as well as the region of the insular cortex, the suprageniculate nucleus of the thalamus, caudate nucleus, and the substantia nigra. Microelectrode studies revealed common receptive field properties in all these structures. The receptive fields were extremely large and multisensory, with pronounced sensitivity to motion of visual stimuli. They often demonstrated directional and velocity selectivity. Preference for small visual stimuli was also a frequent finding. However, orientation sensitivity was absent. It became obvious that the structures of the investigated sensory loop exhibit a unique kind of information processing, not found anywhere else in the feline visual system.

Systematic scoping review of enhanced recovery protocol recommendations targeting return of gastrointestinal function after colorectal surgery.

Post-operative ileus (POI) and delayed return of gastrointestinal (GI) function are common complications after colorectal surgery. There is a lack of uniformity in enhanced recovery protocols (ERPs) with regards to interventions used to target these complications. This systematic review aims to categorize and summarize management recommendations available from published ERPs. A systematic search of Ovid MEDLINE, Embase, Cochrane Library and PubMed databases was performed from January 1990 to May 2018. All studies publishing enhanced recovery or fast-track or multimodal pathway protocols for colorectal surgery in their full-text were included. Data on interventions aimed at reducing the duration of POI were extracted, as well as references quoted to support specific interventions. Of 481 manuscripts screened, 37 published ERPs were identified from 37 studies (18 cohort, seven historical-control, five guidelines, four randomized controlled trials, one randomized controlled trial protocol, one case series and one narrative review). The most commonly recommended interventions were magnesium-based laxatives (18 of 37, 48.6%), chewing gum (13 of 37, 35.1%), Alvimopan (6 of 37, 16.2%), lactulose (4 of 37, 10.8%), neostigmine (2 of 37, 5.4%) and bisacodyl (2 of 37, 5.4%). Geographical trends were noted for the various interventions, but high-quality evidence was only referenced to support the use of Alvimopan. ERP recommendations specific to interventions targeting POI and return of GI function are varied. While laxatives are the most commonly recommended intervention, there is only weak evidence reported to support this practice.

Effect of enhanced recovery after surgery (ERAS) pathway on the postoperative outcomes of elbow arthrolysis: A randomized controlled trial.

Enhanced recovery after surgery (ERAS) protocols aim to improve perioperative outcomes and facilitate recovery for the patient through multimodal pathways. While implementation of ERAS has improved outcomes in numerous surgical specialties, benefits specific to elbow arthrolysis have not been investigated. The purpose of this study was to determine the effects of an evidence-based ERAS pathway on: (1) reducing pain intensity and postoperative complications compared to conventional care, and (2) improving range of motion (ROM) and function of the elbow after open arthrolysis. A randomized controlled study was performed between September 2017 and January 2018. Fifty patients with post-traumatic stiff elbow scheduled for surgery were randomly divided into ERAS group (25 patients) and conventional care group (25 patients). Duration of surgery, pre- and post-surgery ROM, Mayo Elbow Performance Score (MEPS), and visual analog scale (VAS) pain scores at rest and in motion were measured postoperatively at 1 through 5 days, 6-weeks, and 6-months. Complications were recorded 6-months postoperatively. VAS pain score values at rest and in motion in the ERAS group were consistently significantly lower than those in the conventional care group at 1 through 5 postoperatively days (P < 0.05). At 6-weeks and 6-months after surgery, pain score values at rest and in motion were similar between the 2 groups (P > 0.05). ROM was consistently significantly better in the ERAS group compared with the conventional care group (P < 0.05). No significant differences in MEPS or complications were found between the 2 groups (P > 0.05). ERAS pathway is feasible to implement in elbow arthrolysis and can result in clinically meaningful improvements in levels of pain (at rest and in motion) and ROM without an increase in the rate of postoperative complications.

An Update in Enhanced Recovery Following Radical Cystectomy.

The purpose of the study is to review and summarize major additions to the literature as pertains to enhanced recovery protocols after radical cystectomy in the past year. Enhanced recovery after surgery protocols is multimodal pathways that include elements to optimize all stages of care including preoperative, intraoperative and postoperative measures. Several authors have recently presented their results with initial implementation of an enhanced recovery protocol after radical cystectomy, while others have begun to examine outcomes beyond the index admission and to refine the various targeted components of the protocol. Enhanced recovery after surgery protocols has revolutionized patient care following radical cystectomy, a procedure still burdened by high complication rates and lengthy hospital stay. Although still lacking in universal implementation and standardization of the protocol, significant advancements are made each year as we move towards best practice.

Hypothalamic CNTF volume transmission shapes cortical noradrenergic excitability upon acute stress

Stress‐induced cortical alertness is maintained by a heightened excitability of noradrenergic neurons innervating, notably, the prefrontal cortex. However, neither the signaling axis linking hypothalamic activation to delayed and lasting noradrenergic excitability nor the molecular cascade gating noradrenaline synthesis is defined. Here, we show that hypothalamic corticotropin‐releasing hormone‐releasing neurons innervate ependymal cells of the 3rd ventricle to induce ciliary neurotrophic factor (CNTF) release for transport through the brain's aqueductal system. CNTF binding to its cognate receptors on norepinephrinergic neurons in the locus coeruleus then initiates sequential phosphorylation of extracellular signal‐regulated kinase 1 and tyrosine hydroxylase with the Ca2+‐sensor secretagogin ensuring activity dependence in both rodent and human brains. Both CNTF and secretagogin ablation occlude stress‐induced cortical norepinephrine synthesis, ensuing neuronal excitation and behavioral stereotypes. Cumulatively, we identify a multimodal pathway that is rate‐limited by CNTF volume transmission and poised to directly convert hypothalamic activation into long‐lasting cortical excitability following acute stress.

RA03.03: THE IMPACT OF ENHANCED RECOVERY AFTER SURGERY (ERAS) ON PATIENTS UNDERGOING OESOPHAGECTOMY

Abstract Background Enhanced recovery after surgery (ERAS) is defined as a multimodal care pathway designed to achieve early recovery for patients undergoing surgery. For patients undergoing oesophagectomy such pathways are complex and must involve a wide multi-disciplinary team. The importance of peri-operative nutrition is especially relevant in this patient group. We describe our experience of the impact of an ERAS pathway in a high volume oesophago-gastric unit on both short and medium term patient outcomes. Methods Consecutive patients undergoing open 2 phase subtotal oesophagectomy with two field lymphadenectomy in a 12 month period following the introduction of an ERAS pathway were included in the study. Outcomes were compared with consecutive patients undergoing the same procedure over a 12 month period prior to the introduction of the ERAS pathway. All patients were treated in a single UK unit. Adherence to the ERAS pathway was monitored by a dedicated ERAS coordinator. All data were collected prospectively. Statistical analysis was performed using the Mann-Whitney U test for continuous and Chi2 for categorical data. Results 189 patients were included (97 pre-ERAS and 92 ERAS). There were no demographic differences between the patient groups. The rate of severe post-operative complications (Accordion score 3 + ) was identical between groups (29%). Median length of hospital stay was significantly reduced with ERAS (10 days v 14 days pre-ERAS (P &lt; 0.001)) as was the total readmission rate (21% v 39% P = 0.006). Weight loss following surgery was significantly reduced with ERAS. At 2 weeks 1% of patients had lost over 10% of their pre-operative weight compared with 32% pre-ERAS (P &lt; 0.001). A significant difference was maintained at 6 weeks (9% v 55%), 3 months (19% v 66%) and 6 months (35% v 71%). Conclusion Our results demonstrate the positive impact of ERAS for patients undergoing oesophagectomy. Despite no reduction in post-operative complication rates, both hospital stay and readmission rates were reduced, suggesting a positive impact of ERAS on patients’ response to complications. Far fewer patients were readmitted for nutritional reasons/failure to thrive following the introduction of ERAS. Implementing an ERAS pathway requires a dedicated multi-disciplinary team to provide the required peri-operative care both in the hospital and community. Disclosure All authors have declared no conflicts of interest.

Major lower limb amputation audit - introduction and implementation of a multimodal perioperative pain management guideline.

Lower limb amputation is a frequent surgical intervention. It is well known to be associated with postoperative pain. Optimisation of perioperative pain has been shown to reduce the risk of chronic pain. There are no national guidelines for the perioperative pain management of lower limb amputations. Following a baseline audit, we devised a multimodal perioperative pain management guideline, which included the insertion of a local anaesthetic perineural catheter. All patients undergoing an elective or emergency above, through and below knee amputation were reviewed prior and following the implementation of this guideline. Patient postoperative pain scores and opiate usage were analysed. One hundred and twenty-four patients were reviewed (68 patients prior to the implementation of the guideline and 56 patients following the guideline introduction). Following the implementation of the guideline, a greater proportion of patient's pain scores were reported as 0 (i.e. no pain) compared to patients prior to its implementation (78% vs 61%). Pain scores were lower at all time intervals 6 days postoperatively following the guideline introduction. Statistically significant (Kendall's tau-b analysis) (p < 0.05) reduction in pain scores was found upon admission to the ward, 6, 12, 24 hours and 2 days postoperatively. Fewer patients required the use of opioid patient controlled of analgesia after the guideline was introduced (26% vs 4%). The implementation of a perioperative pain management guideline improved pain scores and reduced opioid consumption in patients undergoing lower limb amputations. We suggest a holistic and collaborative, multimodal pathway towards the perioperative pain management of lower limb amputations.

A Multimodal Analgesic Pathway Improves Postpartum Pain Management Scores as Reflected by HCAHPS scores

Background: Postpartum pain is an important issue in obstetrics. A standardized method of monitoring pain scores is provided by the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) national survey. In an effort to improve pain management ans subsequently improve HCAHPS scores in our obstetrics unit, we implemented a multimodal analgesic pathway with the intent to maximize analgesia while minimizing opioid use. Methods: Traditional postpartum analgesia methods were replaced with a multimodal pathway, including patientcontrolled epidural anesthesia for the first 12-24 hours after cesarean delivery plus acetaminophen and ketorolac IV as needed. Upon initiation of oral intake, scheduled acetaminophen and ibuprofen are administered. Transdermal lidocaine patches and opioids are added as needed. The oral medication pathway is initiated following vaginal delivery. Baseline and post-implementation responses to HCAHPS pain management questions 1) How often was your pain well controlled? 2) How often did the hospital staff do everything they could to help you with your pain were compared. Results: Prior to analgesia protocol implementation, pain management scores were below the desired benchmark of 78%. Post-implementation, responses of “Always” or “Top-box” for Question 1 significantly increased [73% versus 65%; p=0.05]. Post-intervention Top-box responses for Question 2 increased from 82% to 89% (p<0.03). Conclusions: The development of a postpartum multimodal analgesic regimen resulted in significantly improved pain management scores, reflected by HCAHPS scores. No other systematic intervention occurred to explain these positive changes.

Decreasing Postoperative Narcotics in Reconstructive Pelvic Surgery: A Randomized Controlled Trial

(Abstracted from Am J Obstet Gynecol 2017;217:325.e1–325.e10) In recent years, there has been increasing emphasis on creation of programs for enhanced recovery, fast-track, or multimodal pathways to improve perioperative care. Decreasing discharge narcotic use may be important to maximize patient safety and satisfaction, decrease postoperative complications at home, and expedite return to baseline functional status.

Abstract 4587: A human hybrid immuno-oncology construct targeting the TWEAK receptor Fn14 and containing the serine protease granzyme B

Abstract Targeting immune effector cells to tumors has recently emerged as a clinically-relevant approach for therapy. The underlying mechanism for immune effector killing involves T or B-cell-mediated delivery of the serine protease granzyme B to the target cells. The cell-surface receptor Fn14 for the TNF-related cytokine TWEAK has emerged as a potentially valuable target for cancer therapy because its expression is low in most normal tissues but significantly elevated in a variety of solid tumor types. The serine protease Granzyme B (GrB) is a highly cytotoxic component of human immune effector cells and induces multiple, intense pro-apoptotic signals when delivered to the cytoplasm of target cells. This protein has been well-studied, operating through multimodal pathways which are both caspase-dependent and caspase-independent. Our laboratory has designed series of new Fn14-targeted fusion constructs containing an engineered GrB payload. The GrB-Fc-IT4 construct is a completely human homodimer (~200kDa) containing an IgG Fc domain for prolonged serum half-life. This construct displays high-level protein production in an HEK293E expression system. It exhibits high affinity and selective cytotoxicity within the nanomolar range (IC50 ranged from 4 to 284 nM) when tested against a panel of 25 Fn14-positive human cancer cell lines. We are currently assessing a panel of 100 annotated NSCLC cell lines to try to define a molecular fingerprint related to cellular sensitivity or resistance to the GrB payload. Pharmacokinetic studies in mice revealed that GrB-Fc-IT4 exhibited a bi-exponential clearance from plasma with a rapid initial clearance (t ½α = 0.36 hours) followed by a prolonged terminal-phase plasma half-life (t 1/2β = 35 hours). Mice bearing MDA-MB-231 orthotopic tumor xenografts were intravenously treated with saline, or GrB-Fc-IT4 construct (QODX5). On average, tumors from saline-treated mice grew about 10-fold over 40 days. In contrast, tumors from mice treated with GrB-FC-IT4 did not grow during this period and remained the same size as at the onset of treatment. Moreover, 3/5 mice treated with GrB-Fc-IT4 showed complete tumor regression lasting beyond day 80 (end of the study). Overall, treatment with GrB-FC-IT4 was well-tolerated by mice (no loss of body weight) and resulted in significant anti-tumor efficacy. Toxicology and bio-distribution studies are ongoing and will be presented. Research conducted, in part, by the Clayton Foundation for Research. Citation Format: Ana Alvarez de Cienfuegos, Lawrence H. Cheung, Khalid A. A. Mohamedali, Jeffrey A. Winkles, Michael G. Rosenblum. A human hybrid immuno-oncology construct targeting the TWEAK receptor Fn14 and containing the serine protease granzyme B [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4587. doi:10.1158/1538-7445.AM2017-4587