Central Infusion Research Articles

Effect of Central Venous Nutrition Infusion, Intravenous Fat Emulsion, and Therapeutic Agents on the Particle Size of Fat Emulsion for Simultaneous Administration of Three Drugs

Background: In Japan, therapeutic agents are often administered through the side tube of a central venous line or mixed with a total parenteral nutrition (TPN) infusion. This is expected to result in the mixture of three drugs in the infusion line: the infusion product for TPN, the fat emulsion, and the therapeutic agent. Therefore, we investigated whether various therapeutic agents affect the particle size of the fat emulsion. Methods: In model of administration A, the TPN infusion formulation was administered through the main tube, and the fat emulsion and therapeutic agents were simultaneously administered through the side tube; 21 therapeutic agents were used. In model of administration B, the TPN infusion formulation mixed with therapeutic agents was administered through the main tube, and the fat emulsion was simultaneously administered through the side tube; 20 therapeutic agents were used. The number of fine particles for each particle size range in the mixed solution was measured over time using a light-shielding automatic fine-particle measuring device. Results: In model A, the number of fine particles in the fat emulsion changed rapidly for five therapeutic agents and slowly for two therapeutic agents. In model B, this change occurred drastically for five therapeutic agents and slowly for one therapeutic agent. Conclusions: Some therapeutic agents may contribute to fat particle aggregation. Therefore, these therapeutic agents should not be concurrently administered with fat emulsions.

Trans-illumination Devices: Improving IV Insertion Accuracy and Success Rates

<h3>Background Information</h3> Difficult Venous Access (DVA) patients are a frequent cause of increased preoperative pain scores, increased delays in Preop to OR times, and decreased patient satisfaction with their perioperative experience. Expert vascular access nurses (EVANs) have had little effect changing these key issues. Use of Trans-Illumination Devices (<b>TID</b>s) has demonstrated promising results in alieving some of these issues without increased risk to the patient. <h3>Objectives of Project</h3> The TID pilot was designed to improve patient safety, comfort and satisfaction while decreasing delays in the preoperative area relating to DVA patients. Staff satisfaction with TIDs data was measured through feedback on ease of use, procedure type, and success rates. <h3>Process of Implementation</h3> Staff education was required for the use of the ACCU VEIN red light LED TID. Training included a review of the equipment, proper distancing, settings, and cleaning for patient safety. Real time training was performed on live patients with verbal consent in the Prep and PACU. Data collection included patient Vascular Access Difficulty Level (VADL), number of insertion attempts, and the procedure performed. Post training satisfaction surveys were sent to nursing and clinical technicians to provide feedback on use of the TID. <h3>Statement of Successful Practice</h3> The ACCU VEIN TID was used on 70 patients. VADL A (55) and VADL B (15). It successfully reduced the number of insertion attempts in the DVA population (1^st attempt=62, 2nd attempt=8). Calls for Anesthesia or EVANs were zero. The device gave real time information regarding the location and quality of veins being accessed. Reduction in number of insertion attempts decreased pain and improved patient satisfaction with IV starts. Staff graded the ACCU Vein ease of use (100%), being helpful (90%), and that they would use the device again (99%). <h3>Implications for Advancing the Practice of Perianesthesia Nursing</h3> Use of TIDs in areas where venous access is frequent will improve the quality of patient care and reduce the wait times associated with IV insertion of the DVA patient. Prep/PACUs, Infusion Centers, Emergency Departments, Phlebotomy, and IV therapy would all benefit having TIDs as standard equipment.

Assessment of unvaccinated and vaccinated patients with coronavirus disease 2019 (COVID-19) treated with monoclonal antibodies during the delta wave (July 1–August 20, 2021): a retrospective observational monocentric study

BackgroundMonoclonal antibodies (mAb) prevent COVID-19 progression when administered early. We compared mAb treatment outcomes among vaccinated and unvaccinated patients during Delta wave and assessed the feasibility of implementing stricter eligibility criteria in the event of mAb scarcity.MethodsWe conducted a retrospective observational study of casirivimab/imdevimab recipients with mild-to-moderate COVID-19 infection in an emergency department or outpatient infusion center (July 1–August 20, 2021). Primary outcome was all-cause hospital admission within 30 days post-treatment between vaccinated vs. unvaccinated patients during Delta surge in the Bronx, NY.ResultsA total of 250 patients received casirivimab/imdevimab (162 unvaccinated vs. 88 vaccinated). The median age was 39 years for unvaccinated patients, and 52 years for vaccinated patients (p < 0.0001). The median number of EUA criteria met was 1 for unvaccinated and 2 for vaccinated patients (p < 0.0001). Overall, 6% (15/250) of patients were admitted within 30 days post-treatment. Eleven unvaccinated patients (7%) were admitted within 30-days compared to 4 (5%) vaccinated patients (p = 0.48).ConclusionsAll-cause 30-day admission was not statistically different between vaccinated and unvaccinated patients. When federal allocation of therapies is limited, programs must prioritize patients at highest risk of hospitalization and death regardless of vaccination status.

Association of Health Insurance Literacy With Financial Hardship in Patients With Cancer

Patient-reported financial hardship is an increasing challenge in cancer care delivery. Health insurance literacy and its association with financial hardship in patients with cancer, especially after controlling for financial literacy, have not been well examined. To examine the prevalence of and factors in the association between health insurance literacy and financial literacy as well as the overall and individual domains of financial hardship and their association with health insurance literacy, both independently and when adjusted for financial literacy, in patients with cancer. This cross-sectional survey study recruited and enrolled patients from 2 separate ambulatory infusion centers at Mayo Clinic Arizona in Phoenix, Arizona, and the University of Mississippi Medical Center in Jackson, Mississippi. Adult patients aged 18 years or older were enrolled from December 2019 to February 2020 and from August to October 2020 at Mayo Clinic Arizona (n = 299) and from September 2020 through January 2021 at the University of Mississippi Medical Center (n = 105). Survey respondents received a $5 gift card. Surveys included questions about sociodemographic characteristics, health insurance literacy and financial literacy, financial knowledge, and financial hardship and its domains (material hardship, psychological hardship, and behavioral hardship). Financial hardship was assessed using the COST-FACIT (Comprehensive Score for Financial Toxicity-Functional Assessment of Chronic Illness Therapy) measure and National Health Interview Survey questions to capture information about the domains of financial hardship. The Health Insurance Literacy Measure is a validated 21-item measure of a consumer's ability to select and use health insurance. Five questions from the National Financial Capability Study assessed financial literacy. A total of 404 participants were enrolled in the study. Median (IQR) age of the respondents was 63 (54-71) years, and 219 were women (54%), 307 were non-Hispanic White individuals (76%), 153 (38%) had private insurance, and 289 (72%) had solid tumors. Overall financial hardship (denoted by median COST-FACIT score <27 points) was reported by 49% (95% CI, 44%-53%) of the cohort. Prevalence of financial hardship was higher using the National Health Interview Survey questions, with 68% (95% CI, 63%-72%) of respondents reporting at least 1 hardship domain (n = 276). Sixty-six percent (95% CI, 60%-69%) of respondents (n = 265) had a high level of financial literacy. The mean (SD) Health Insurance Literacy Measure score was 64.9 (13.3) points. In multivariable analyses, each 10-point increase in the Health Insurance Literacy Measure score was associated with lower odds of financial hardship (odds ratio, 0.82; 95% CI, 0.68-0.99; P = .04). However, this association was no longer significant after adjusting for financial literacy. Results of this study showed that, despite a high level of health insurance literacy and financial literacy, the prevalence of financial hardship was high. Although there were lower odds of financial hardship with increased health insurance literacy, the association was no longer significant when financial literacy was added to the model, suggesting that a high level of financial literacy may help mitigate the adverse outcome of lower health insurance literacy levels in patients with cancer.

Same Day Infusion of Iron Therapy Is Associated With No Increased Risk for Adverse Events Among Patients Receiving Biological Infusions for Inflammatory Bowel Disease.

The goal of this study was to compare the relative safety of administering iron infusions on the same day as intravenous (IV) biological therapy to the administration of these treatments on different days in patients with inflammatory bowel disease (IBD). IV iron therapy is often required in patients with IBD. Many patients with IBD who receive IV iron therapy in the outpatient setting also receive biological infusion therapy for treatment of their IBD. Patients with IBD who received IV iron therapy at a single infusion center were included. We compared documented infusion-related reactions in patients with patients receiving an iron infusion on the same day as their biological infusion to those who received their iron infusion on a different day. Among 481 patients, 129 received an iron infusion on the same day as a biologic infusion. There was no significant difference in the incidence of infusion reaction when comparing patients who received biological infusion therapy in the same session as the iron infusion to those patients who received a biological infusion on a different day (5% vs. 7%, P =0.246) or any IBD-related therapy (5% vs. 8%, P =0.206). The frequency and type of infusion reactions in patients receiving IV iron therapy on the same day after IV therapy with biologics was not increased compared with patients who received a biological infusion on a different day. A sequential infusion of biological therapy followed by IV iron therapy may be a safe and cost-effective approach.

Bolus Injection of Liraglutide Raises Plasma Glucose in Normal Rats by Activating Glucagon-like Peptide 1 Receptor in the Brain.

Diabetes is commonly treated with glucagon-like peptide-1 receptor (GLP-1R) agonists including liraglutide and others. However, liraglutide was found to raise plasma glucose levels in normal rats. The current study aims to determine how liraglutide causes this contentious condition in rats, both normal and diabetic. An adrenalectomy was performed to investigate the relationship between steroid hormone and liraglutide. To investigate the effect of central liraglutide infusion on blood glucose in rats, rats were intracerebroventricularly administrated with liraglutide with or without HPA axis inhibitors such as berberine and dexamethasone. The results showed that a single injection of liraglutide caused a temporary increase in blood glucose in healthy rats. Another GLP-1R agonist, Exendin-4 (Ex-4), increased blood sugar in a manner similar to that of liraglutide. The effects of liraglutide were also blocked by guanethidine pretreatment and vanished in normal rats with adrenalectomy. Additionally, central infusion of liraglutide via intracerebroventricular (icv) injection into normal rats also causes a temporary increase in blood glucose that was blocked by GLP-1R antagonists or the inhibitors such as berberine and dexamethasone. Similarly, central liraglutide treatment causes temporary increases in plasma glucose, adrenocorticotropic hormone (ACTH), and cortisol levels, which were reversed by inhibitors for the hypothalamic-pituitary-adrenal (HPA) axis. In normal rats, the temporary glucose-increasing effect of liraglutide was gradually eliminated during consecutive daily treatments, indicating tolerance formation. Additionally, liraglutide and Ex-4 cross-tolerance was also discovered in normal rats. Liraglutide was more effective in diabetic rats than in normal rats in activating GLP-1R gene expression in the isolated adrenal gland. Interestingly, the effect of liraglutide on glycemic control varied depending on whether the rats were diabetic or not. In normal rats, bolus injection of liraglutide, such as Ex-4, may stimulate the HPA axis, resulting in hyperglycemia. The cross-tolerance of liraglutide and Ex-4 provided a novel perspective on GLP-1R activation.

Effectiveness of Casirivimab-Imdevimab and Sotrovimab During a SARS-CoV-2 Delta Variant Surge

The effectiveness of monoclonal antibodies (mAbs), casirivimab-imdevimab and sotrovimab, is unknown in patients with mild to moderate COVID-19 caused by the SARS-CoV-2 Delta variant. To evaluate the effectiveness of mAb against the Delta variant compared with no mAb treatment and to ascertain the comparative effectiveness of casirivimab-imdevimab and sotrovimab. This study comprised 2 parallel studies: (1) a propensity score-matched cohort study of mAb treatment vs no mAb treatment and (2) a randomized comparative effectiveness trial of casirivimab-imdevimab and sotrovimab. The cohort consisted of patients who received mAb treatment at the University of Pittsburgh Medical Center outpatient infusion centers and emergency departments from July 14 to September 29, 2021. Participants were patients with a positive SARS-CoV-2 test result who were eligible to receive mAbs according to emergency use authorization criteria. For the trial, patients were randomized to either intravenous casirivimab-imdevimab or sotrovimab according to a system therapeutic interchange policy. For the cohort study, risk ratio (RR) estimates for the primary outcome of hospitalization or death by 28 days were compared between mAb treatment and no mAb treatment using propensity score-matched models. For the comparative effectiveness trial, the primary outcome was hospital-free days (days alive and free of hospitalization) within 28 days after mAb treatment, where patients who died were assigned -1 day in a bayesian cumulative logistic model adjusted for treatment location, age, sex, and time. Inferiority was defined as a 99% posterior probability of an odds ratio (OR) less than 1. Equivalence was defined as a 95% posterior probability that the OR was within a given bound. A total of 3069 patients (1023 received mAb treatment: mean [SD] age, 53.2 [16.4] years; 569 women [56%]; 2046 had no mAb treatment: mean [SD] age, 52.8 [19.5] years; 1157 women [57%]) were included in the prospective cohort study, and 3558 patients (mean [SD] age, 54 [18] years; 1919 women [54%]) were included in the randomized comparative effectiveness trial. In propensity score-matched models, mAb treatment was associated with reduced risk of hospitalization or death (RR, 0.40; 95% CI, 0.28-0.57) compared with no treatment. Both casirivimab-imdevimab (RR, 0.31; 95% CI, 0.20-0.50) and sotrovimab (RR, 0.60; 95% CI, 0.37-1.00) were associated with reduced hospitalization or death compared with no mAb treatment. In the clinical trial, 2454 patients were randomized to receive casirivimab-imdevimab and 1104 patients were randomized to receive sotrovimab. The median (IQR) hospital-free days were 28 (28-28) for both mAb treatments, the 28-day mortality rate was less than 1% (n = 12) for casirivimab-imdevimab and less than 1% (n = 7) for sotrovimab, and the hospitalization rate by day 28 was 12% (n = 291) for casirivimab-imdevimab and 13% (n = 140) for sotrovimab. Compared with patients who received casirivimab-imdevimab, those who received sotrovimab had a median adjusted OR for hospital-free days of 0.88 (95% credible interval, 0.70-1.11). This OR yielded 86% probability of inferiority for sotrovimab vs casirivimab-imdevimab and 79% probability of equivalence. In this propensity score-matched cohort study and randomized comparative effectiveness trial, the effectiveness of casirivimab-imdevimab and sotrovimab against the Delta variant was similar, although the prespecified criteria for statistical inferiority or equivalence were not met. Both mAb treatments were associated with a reduced risk of hospitalization or death in nonhospitalized patients with mild to moderate COVID-19 caused by the Delta variant. ClinicalTrials.gov Identifier: NCT04790786.

Acute infusion effects in relapsing multiple sclerosis patients receiving alemtuzumab under a modified prophylaxis regimen

BackgroundUse of alemtuzumab in relapsing multiple sclerosis (RMS) is limited by safety concerns, notably risk of rare, serious vascular events. Along with other vital sign (VS) changes, acute increase in systolic blood pressure (SBP) is monitored as a marker of vascular risk. Peri-infusion prophylaxis is used to manage clinical risk by moderating cytokine release; protocols are not fully specified and vary across sites. Here, we report a modified prophylaxis regimen developed at Maritime Neurology. This single-center observational cohort study (NCT04633967) aimed to examine acute responses (VS events and infusion-associated reactions) in RMS patients receiving alemtuzumab infusion under this regimen. In a post hoc analysis, we examined incidence of acute SBP increase at this clinic versus the Bayshore network of Canadian infusion centers, where a standard prophylaxis regimen is used. MethodsAlemtuzumab was infused on 5 consecutive days (Course 1; n = 29) and 3 consecutive days one year later (Course 2; n = 28). In addition to intravenous methylprednisolone 500mg on each infusion day, patients received daily prophylactic treatment with oral prednisone 50mg from 5 days before to 5 days after treatment (infusion days excepted) and oral H1 and H2 antihistaminics from 7 days before to 7 days after treatment. Excursions in SBP and other VS were relative to prespecified ranges; persistent excursions were those for which two sequential measurements were outside these ranges. In comparing VS events at Maritime Neurology and the Bayshore centers, acute SBP increase was defined as ≥20 mmHg increase in mean SBP, or any SBP reading ≥20% over patient's pre-course baseline. ResultsMean (SD) VS were within range at pre-course and all other daily baselines. VS changes, including persistent excursions, were generally subclinical; all infusion-associated reactions were mild. One patient discontinued treatment after Course 1 due to immune thrombocytopenia purpura. Acute SBP increase occurred in 11/28 (39%) Maritime Neurology versus 367/610 (60%) Bayshore (p = 0.028). ConclusionThe modified peri-infusion prophylaxis regimen was well tolerated and may reduce incidence of acute SBP increase. FundingThis project was funded by Sanofi, Canada.

Immunogenicity of BNT162b2 Vaccine Booster Dose in Patients With Inflammatory Bowel Disease Receiving Infliximab Combination Therapy: A Prospective Observational Study.

IntroductionFew data exist regarding the immunogenicity of the third dose of BNT162b2 relative to the second dose in patients with inflammatory bowel disease (IBD) on different immunosuppressive therapies. We investigated the immunogenicity of BNT162b2 vaccine booster dose in patients with IBD on infliximab combination therapy.MethodThis is a prospective single-center observational study conducted from January 1, 2022 to February 28, 2022. Patients were recruited at the time of attendance at the infusion center. Eligibility criteria included patients with a confirmed diagnosis of IBD who are receiving infliximab with azathioprine or 6-mercaptopurine. Patients who received two doses of BNT162b2 vaccine (second dose group) were compared to patients who had received three doses of BNT162b2 vaccine [third dose (booster) group]. Patients were excluded if they were infected or had symptoms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) previously since the start of the pandemic or received other vaccines than the BNT162b2. Our primary outcome was the concentrations of SARS-CoV-2 antibodies Immunoglobulin G (IgG) and neutralizing antibodies 40–45 weeks from the first dose of BNT162b2 vaccine in patients with IBD receiving infliximab combination therapy. Medians with interquartile range (IQR) were calculated.ResultsIn total, 162 patients with IBD and receiving infliximab combination therapy were recruited, and the number of patients in both the second dose group and third dose (booster) group was 81. Mean age was 35 years old in both groups. Median (IQR) SARS-CoV-2 IgG levels were significantly lower after the second dose [125 BAU/ml (43, 192)] compared to patients who received the third booster dose [207 BAU/ml (181, 234)] (P = 0.003). Neutralizing antibody levels were also lower after the second dose [80% (21, 95)] compared to patients who received the third booster dose [96% (93, 99)] (P ≤ 0.001). The percentage of patients who achieved positive SARS-CoV-2 IgG levels in the third (booster) dose group was 96.3%, whereas it was 86.4% in the second dose group. The percentage of participants who received the third (booster) dose and achieved a positive SARS-CoV-2-neutralizing antibody level was 100%, whereas it was 88.9% in the participants who received the second dose only.ConclusionMost patients with IBD on infliximab combination therapy had positive SARS-CoV-2 IgG and neutralizing antibody concentrations 40–45 weeks post BNT162b2 vaccination. However, SARS-CoV-2 IgG and neutralizing antibody concentrations were lower in patients who received two doses only compared to patients who received a third dose. A longer follow-up study is needed to evaluate decay in antibodies over time.

Optimizing Multidisciplinary Treatment-Related Adverse Effects Detection and Reduction in Patients Undergoing Active Cancer Treatments in Ambulatory Infusion Centers.

The objective of this study was to describe the implementation of an interdisciplinary supportive care program for treatment-related adverse effects (TRAEs) of patients with cancer in two ambulatory infusion centers affiliated with a major health system. A management program of TRAEs was developed on the basis of the collaboration between oncologists, infusion center oncology nurses, and a board-certified oncology clinical pharmacist for patients with cancer in two outpatient infusion centers. Patients received multidisciplinary interventions or oncologist-driven interventions on the basis of their reported symptoms during their cancer treatments. They were followed prospectively at regular intervals for further symptom management interventions. To evaluate this program, a retrospective chart review was performed, and data were collected regarding the number and nature of these TRAEs. The outcomes of their interventions were assessed up to 3 months since initial encounters. Data for patient satisfaction were also collected before and after implementation of the program. A total of 308 patients received 469 interventions initiated either by the multidisciplinary team or by oncologists over a 3-year period. Compared with oncologist-led interventions, multidisciplinary interventions were statistically significant in the number of interventions (P = .004; 95% CI, 17.9 to 36.2) and in reducing occurrences of TRAEs (P = .03; 95% CI, 33.8 to 72.4) such as dermatological toxicities, diarrhea, immune-related adverse effects, mucositis, and nausea or vomiting after 1-month follow-up. Multidisciplinary team captured approximately 40% of TRAEs of all grades that were escalated to oncologists for further management, which led to an overall improvement in management of TRAEs. Multidisciplinary care for patients in infusion centers led to improvement in treatment-related toxicities.

Oxytocin-Cholinergic Central Interaction: Implications for Non-Social Memory Formation

Oxytocin (OT) and vasopressin (AVP) are two closely related neuropeptides implicated in learning and memory processes, anxiety, nociception, addiction, feeding behavior and social information processing. Regarding learning and memory, OT has induced long-lasting impairment in different behaviors, while the opposite was observed with AVP. We have previously evaluated the effect of peripheral administration of OT or its antagonist (AOT) on the inhibitory avoidance response of mice and on the modulation of cholinergic mechanisms. Here, we replicate and validate those results, but this time through central administration of neuropeptides, considering their poor passage through the blood–brain barrier (BBB). When we delivered OT (0.10 ng/mouse) and its antagonist (0.10 ng/mouse) through intracerebroventricular (ICV) injections, the neuropeptide impaired and AOT enhanced the behavioral performance on an inhibitory avoidance response evaluated 48 h after training in a dose-dependent manner. On top of that, we investigated a possible central interaction between OT and the cholinergic system. Administration of anticholinesterases inhibitors with access to the central nervous system (CNS), the activation of muscarinic acetylcholine (Ach) receptors and the increase of evoked ACh release using linopirdine (Lino) (3–10 µg/kg, IP), reversed the impairment of retention performance induced by OT. Besides, either muscarinic or nicotinic antagonists with unrestricted access to the CNS reduced the magnitude of the performance-facilitating effect of AOT’s central infusion. We suggest that OT might induce a cholinergic hypofunction state, resulting in an impairment of IA memory formation, a process for which the cholinergic system is crucially necessary.

Chronic Central Leptin Infusion Promotes an Anti-Inflammatory Cytokine Profile Related to the Activation of Insulin Signaling in the Gastrocnemius of Male Rats.

Leptin is involved in the modulation of insulin signaling in peripheral tissues, being closely associated with changes in lipid metabolism. This adipokine modifies inflammatory pathways that can interact with insulin targets in peripheral organs; however, the mechanisms remain unclear. Inflammatory and insulin signaling targets, cytokines, adiponectin, irisin and non-esterified fatty acid (NEFA) levels and enzymes of fatty acid anabolism were studied in the gastrocnemius of chronic centrally infused leptin (L), pair-fed and control rats. The phosphorylation of signal transducer and activator of transcription 3 (STAT3) and c-Jun N-terminal kinase (JNK) was reduced in L rats (59% and 58%, respectively). The phosphorylation of the insulin receptor and Akt and adiponectin and irisin content was increased in L rats (154%, 157%, 308% and 329%, respectively). The levels of glucose-6-phosphate dehydrogenase, the mRNA content of acetyl Co-A carboxylase and NEFA concentrations were diminished in the muscles of L rats (59%, 50% and 61%, respectively). The activation of JNK correlated positively with STAT3 phosphorylation, tumoral necrosis factor-α and NEFA and negatively with irisin and Akt phosphorylation. These data suggest that the activation of insulin signaling targets and a decrease in NEFA content are associated with a reduction in muscle inflammation parameters, suggesting that leptin may integrate these pathways.

Abstract 386: Non-intrusive, non-invasive and patient friendly focused ultrasound device as a delivery vehicle for CNS tumors

Abstract A major impediment to treatment of brain cancers is the inability to transport drugs across the blood-brain barrier (BBB). The development of an effective, targeted, and non-invasive method to penetrate the BBB to deliver cancer therapeutics is an unmet need in the treatment of brain cancers. Large molecular weight chemo- and immuno-therapies such as doxorubicin and others may be potentially effective against brain cancers if such drugs are sufficiently bioavailable in the brain. Focused ultrasound techniques can safely and transiently open the BBB but current techniques require invasive/intrusive or expensive and high-touch procedures and are not optimal for wide adoption. To address this unmet need, we are developing an innovative technique to non-intrusively, non-invasively and transiently open the BBB in a specified location within the brain using guided ultrasound (US). Our device consists of a proprietary US generator that is controlled by a highly portable system that has a small physical footprint, enabling the US generator and system to be placed in confined spaces such as chemotherapy infusion centers. The US generator is cap-shaped device that is placed on a patient’s head. It includes multiple sets of ultrasound transducers that are distributed within the cap according to the anatomy of the skull. With our proprietary technique, we calculate the position of the cap in relation to the internal anatomy in a real-time manner with a non-intrusive and a non-invasive manner. We have recently concluded an extensive study that resulted in algorithms that can accurately guide the US to various targets within the brain across a spectrum of patients. We also have completed a pilot preclinical study on a large animal demonstrating our ability to open the BBB non-invasively and deposit a drug proxy (gadolinium and Evans Blue). Citation Format: Bhaskar Ramamurthy, Mallika Keralapura, Jack Marshall, Dan Need, Ryan Dittamore, Santosh Kesari, Ekokobe Fonkem. Non-intrusive, non-invasive and patient friendly focused ultrasound device as a delivery vehicle for CNS tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 386.

A quality improvement project reduces time spent at an inflammatory bowel disease infusion center with accelerated infliximab infusion protocol.

Background and AimPatients with inflammatory bowel disease (IBD) requiring infliximab frequently spend hours to attend treatment. Through quality improvement (QI) methodology, we aimed to shorten the time spent in the biologics infusion center using the accelerated infusion protocol and describe patient outcomes, safety, and associated cost savings.MethodsFrom September 2018 through December 2019, eligible IBD patients receiving infliximab were recruited. We implemented interventions including the accelerated infusion protocol, and modifying collection location of infliximab. Statistical process control charts were created. Patients' clinical outcome and cost savings data were analyzed using descriptive statistics and Pearson's chi‐square.ResultsDuring the study period, a total of 60 patients with IBD receiving infliximab were recruited. A total of 315 infusions were administered—152 were under accelerated infusion protocol and 163 under standard protocol. The mean infliximab infusion time was reduced by 47%, from 2.4 h (142 ± 14 min) to 1.2 h (75 ± 10 min) (142 min vs 75 min, P < 0.001), with total time spent in the infusion center reduced by 52%, from 3.6 h (214 ± 25 min) to 1.7 h (102 ± 14 min) (214 vs 106 min, P < 0.001). Three mild infusion‐related reactions (3/152 = 1.97%) were recorded. Estimated cost savings over the 16‐month project period was SGD $6721.4 (nursing) and SGD $23 560 (patients). A high level of satisfaction (4.84 out of 5) with the protocol was reported.ConclusionOur QI project shortened the infliximab infusion time and total time spent in the infusion center, without compromising patient safety. Estimated cost savings were substantial. The protocol helps reduce work productivity loss.

Burden of cremophor-related paclitaxel therapy on patients with ovarian cancer: A patient focused study from the United Kingdom, Germany, and Spain.

e17576 Background: Cremophor EL (CrEL) is a solubilizer used in paclitaxel and is associated with side effects (i.e., hypersensitivity reactions, peripheral neuropathy). Current CrEL-containing therapies require long infusion times (2-4 hours) and pre-medication with steroids to manage these side-effects. However, the holistic burden of CrEL on patients is not well studied. This study aimed to characterize the burden associated with CrEL-paclitaxel treatment on patients with ovarian cancer, including clinical, safety, and quality of life (QoL) implications. Methods: This quantitative, Institutional Review Board (IRB) approved, cross-sectional survey of patients (≥18 years) who received ≥3 cycles of CrEL-containing paclitaxel within the prior 6 months was conducted in UK, Germany, and Spain in 2021. Data were collected via a web-enabled instrument including a screener, questionnaire, and validated Functional Assessment of Cancer Therapy (FACT)-Taxane scale. Results are reported overall for the 3 countries. Results: Of the 90 patients surveyed, the mean age was 38.8 years. Most patients reported improvement of QoL (77%), treatment effectiveness (77%), less need for pre-medications (74%), and manageable/less disruptive infusion times and schedules (71%) as extremely desirable treatment attributes. Prior to or during chemotherapy, 41% of patients reported receiving steroids. Most patients (71%) experienced 3-6 side effects related to ovarian cancer treatment. Of the patients that experienced neuropathy (27%), the side effect lasted for up to 1 week for 54% of patients, and over multiple cycles of treatment (&gt; 3 weeks) for 13% of patients. Of the 82% of patients eligible to complete the FACT-Taxane scale, 62% were somewhat to very much bothered by the side effects of paclitaxel. Half of these patients reported tingling/numbness in their hands/feet, moderately or very often. Patients reported an average of 4.8 hours as the time taken for their travels to/from the infusion center and receive their medication. Additionally, 91% of patients needed caregiver support for an average of 16 hours per week. 51% of patients reduced their work hours due to treatment and 58% reported a substantial impact on work productivity. To cover treatment costs, 63% purchased supplemental insurance. Conclusions: The patient-reported burden of treatment associated with CrEL-containing paclitaxel is significant and complex. Multiple treatment side effects occur in most patients which are burdensome and can recur and/or persist with future treatment cycles. There is an unmet need for an effective therapy that reduces treatment burden for patients and improves tolerability through fewer side effects, a reduced need for premedication, and shorter infusion time.

The relationship between patient-reported distress and healthcare utilization in mNSCLC.

e24138 Background: Distress has a negative impact on the patient experience of cancer. We previously demonstrated that patients with metastatic non-small cell lung cancer (mNSCLC) face significant and sustained distress during first-line treatment. However, the association between distress and unplanned healthcare utilization (HCRU) is not well understood. Here we examine this association. Methods: We conducted secondary analyses of data from 152 adult patients with mNSCLC treated at Duke Cancer Institute who were part of a retrospective chart review study (3/15-6/20). For the original investigation, demographic, clinical, and distress data were abstracted. NCCN Distress Thermometer (DT) scores were recorded at each clinic visit from start of first-line therapy to end of first year, change in therapy or death. The DT is an 11-point ordinal scale, with a 39-item Problem List, assessing overall distress. DT scores of &gt; = 4 indicate actionable distress. Further HCRU data were analyzed, including unplanned hospitalizations, 30-day readmissions, length of stay, clinic visits, infusion center visits, emergency department (ED) visits, and death. Descriptive statistical analyses were performed for sources of distress and HCRU. To examine the association between distress and HCRU, we utilized an adjusted frailty model (for baseline demographics, metastatic site, and National Cancer Institute Index). This Cox proportional hazards model allowed for multiple HCRU events per patient and included actionable distress as a time-dependent covariate. Results: First, the proportion of actionable DT scores (423/1652, 25.6%) was strikingly high. Most DTs included report of at least one physical problem (n = 1593, 96.4%), regardless of distress level. However, emotional problems (e.g., worry, nervousness, depression) were reported much more frequently when the DT score was actionable (61.9% vs. 20.8%). At the patient level (n = 152), actionable distress was associated with increased HCRU. For example, a larger proportion of those with an average DT score &gt; = 4 had at least one hospitalization (n = 22, 53.7%), infusion center visit (n = 11, 26.8%) or ED visit (n = 28, 68.3%) compared to patients with a non-actionable average DT score. Furthermore, HCRU was 54% more likely to occur after a patient reporting actionable distress compared to a patient reporting lower distress levels any time during treatment (adjusted HR 1.54; CI 1.20, 1.97). A one-point increase in distress was associated with an 8% increase in risk of HCRU (HR 1.08; CI 1.03, 1.13) at any point during treatment. Conclusions: Patients with mNSCLC experience high levels of distress, with actionable distress appearing to be driven significantly by emotional problems. Patient-reported distress is also associated with HCRU. Intervention development and testing is needed to address the unmet psychological needs in lung cancer care and their potential impact on unplanned HCRU.

Hydrogen sulfide ameliorated preeclampsia via suppression of toll-like receptor 4-activated inflammation in the rostral ventrolateral medulla of rats

This study aims to determine whether toll-like receptor 4 (TLR4)-mediated inflammation in rostral ventrolateral medulla (RVLM) causes sympathetic overactivity leading to preeclampsia (PE) and if TLR4 inhibition with hydrogen sulfide (H2S) would reduce PE severity. Thirty patients with PE and 30 pregnant controls were involved. PE in rats was induced through deoxycorticosterone acetate and normal saline. NaHS (donor of H2S), lipopolysaccharide (LPS) (TLR4 agonist), and TAK-242 (TLR4 inhibitor) were injected in lateral cerebral ventricle to investigate their effect on microglia-mediated inflammation in RVLM, sympathetic activation, and PE symptoms. In patients with PE, plasma levels of NE, TNF-α, and interleukin-1β were high compared with those of controls, whereas levels of H2S were low. Rats with PE showed an increased amount of renal sympathetic nerve activity and plasma levels of NE, with decreased H2S levels in RVLM. Microglia-mediated inflammation was observed in the RVLM of PE rats. Central infusion of LPS in pregnant rats induced microglia-mediated inflammation, sympathetic nervous tension, and PE-like symptoms, whereas TAK-242 reduced PE symptoms. NaHS treatment lessened microglia-mediated inflammation in the RVLM, sympathetic tension, and symptoms of PE both in PE rats and LPS-treating pregnant rats.These results suggest that inflammation in the RVLM caused by microglial activation might contribute to the progression of PE via an overactive sympathetic system. H2S could reduce PE via inhibiting inflammation in the RVLM. These results might provide a new target for the treatment of PE.

Timing of adjuvant chemotherapy initiation and mortality among colon cancer patients at a safety-net health system

BackgroundPrior studies reported survival benefits from early initiation of adjuvant chemotherapy for stage III colon cancer, but this evidence was derived from studies that may be sensitive to time-related biases. Therefore, we aimed to estimate the effect of initiating adjuvant chemotherapy ≤8 or ≤ 12 weeks on overall and disease-free survival among stage III colon cancer patients using a study design that helps address time-related biases.MethodsWe used institutional registry data from JPS Oncology and Infusion Center, a Comprehensive Community Cancer Program. Eligible patients were adults aged < 80 years, diagnosed with first primary stage III colon cancer between 2011 and 2017, and received surgical resection with curative intent. We emulated a target trial with sequential eligibility. We subsequently pooled the trials and estimated risk ratios (RRs) along with 95% confidence limits (CL) for all-cause mortality and recurrence or death at 5-years between initiators and non-initiators of adjuvant chemotherapy ≤8 or ≤ 12 weeks using pseudo-observations and a marginal structural model with stabilized inverse probability of treatment weights.ResultsOur study population comprised 222 (for assessing initiation ≤8 weeks) and 310 (for assessing initiation ≤12 weeks) observations, of whom the majority were racial/ethnic minorities (64–65%), or uninsured with or without enrollment in our hospital-based medical assistance program (68–71%). Initiation of adjuvant chemotherapy ≤8 weeks of surgical resection did not improve overall survival (RR for all-cause mortality = 1.04, 95% CL: 0.57, 1.92) or disease-free survival (RR for recurrence or death = 1.07, 95% CL: 0.61, 1.88). The results were similar for initiation of adjuvant chemotherapy ≤12 weeks of surgical resection.ConclusionsOur results suggest that the overall and disease-free survival benefits of initiating adjuvant chemotherapy ≤8 or ≤ 12 weeks of surgical resection may be overestimated in prior studies, which may be attributable to time-related biases. Nevertheless, our estimates were imprecise and differences in population characteristics are an alternate explanation. Additional studies that address time-related biases are needed to clarify our findings.

Analysis of Drop Sensor Accuracy in Central Infusion Peristaltic Monitoring Based on Computer Using Wireless Communication HC-11

In some hospitals, the infusion is still done manually, where medical personnel observe the liquid droplets directly and then control the rate using a mechanical resistor (clamp). This method is certainly far from accurate. An infusion pump is a medical aid that functions to control and ensure the correct dose of infusion fluid given to patients treated. The purpose of this study was to analyze the accuracy of the infrared photodiode as a drop sensor based on the readings of the infusion pump monitoring system. This module consists of a photodiode infrared drop sensor module, a comparator circuit, a monostable circuit, a stepper motor, an L298N motor driver, and an ATmega328 microcontroller. The droplets were detected by an infrared photodiode sensor, then compared with a comparator and monostable circuit as an oscillator developer, and then the flow rate and residual volume readings were generated by the ATmega328 microcontroller. Next, this data has sent to the computer via the HC-11 wireless. The results of the flowrate module measurement show the highest error value of 3% at the 30 ml/hour setting and the lowest error value of 2.5% at the 60 ml/hour setting. Meanwhile, the results of the flow rate measurement using an infusion device analyzer obtained the highest error value of 4% at the setting of 30 ml/hour and 60 ml/hour, and the lowest error value of 0.8% at the setting of 100 ml/hour. Monitoring the infusion pump was designed centrally to facilitate the nurse's task in monitoring the infusion dose given to the patient accurately. Based on this research, the accuracy of the infrared sensor and photodiode is very good by looking at the existing error rate.

ENTIMOS: A Discrete Event Simulation Model for Maximising Efficiency of Infusion Suites in Centres Treating Multiple Sclerosis Patients.

BackgroundImproved multiple sclerosis (MS) diagnosis and increased availability of intravenous disease-modifying treatments can lead to overburdening of infusion centres. This study was focused on developing a decision-support tool to help infusion centres plan their operations.MethodsA discrete event simulation model (‘ENTIMOS’) was developed using Simul8 software in collaboration with clinical experts. Model inputs included treatment-specific clinical parameters, resources such as infusion chairs and nursing staff, and costs, while model outputs included patient throughput, waiting time, queue size, resource utilisation, and costs. The model was parameterised using characteristics of the Charing Cross Hospital Infusion Centre in London, UK, where 12 infusion chairs were deployed for 170 non-MS and 860 MS patients as of March 2021. The number of MS patients was projected to increase by seven new patients per week.ResultsThe model-estimated waiting time for an infusion is, on average, 8 days beyond clinical recommendation in the first year of simulation. Without corrective action, the delay in receiving due treatment is anticipated to reach 30 days on average at 30 months from the start of simulation. Such system compromise can be prevented either by adding one infusion chair annually or switching 7% of existing patients or 24% of new patients to alternative MS treatments not requiring infusion.ConclusionENTIMOS is a flexible model of patient flow and care delivery in infusion centres serving MS patients. It allows users to simulate specific local settings and therefore identify measures that are necessary to avoid clinically significant treatment delay resulting in suboptimal care.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40258-022-00733-0.