Administration Of Rescue Medication Research Articles

Efficiency and safety of high-dose undiluted intravenous push levetiracetam loading doses compared to intravenous infusion in seizing patients: A retrospective cohort study.

Intravenous (IV) push (IVP) is an alternative administration method for levetiracetam, but evidence evaluating it compared to IV piggyback (IVPB) for loading doses in acutely seizing patients is limited, particularly in patients with status epilepticus (SE). This study aimed to compare the efficiency and safety of IVP versus IVPB levetiracetam loading doses. This was a single-center sequential retrospective study conducted in adult (≥18 years) patients who received an IV levetiracetam loading dose (>2000 mg or ≥20 mg/kg) for acute or suspected seizure. The primary outcome was time to administration, compared between doses given as IVP versus IVPB. Secondary outcomes included rates of adverse events (AEs), rescue benzodiazepine or antiseizure medication administration, intubation, and intensive care unit (ICU) admission between groups. A total of 246 patients were included; 116 received IVP and 130 received IVPB loading doses. Median age was 56 years; most patients were male (62%) and White (60%) and had witnessed seizures (67%). Doses were administered for SE in 32 (27.5%) and 46 (35.4%) patients in the IVP and IVPB arms, respectively. Median time to administration was shorter in the IVP group (12 vs. 38 min, p < .001). Bradycardia (1.7% vs. 2.3%, p = .99), hypotension (7.8% vs. 12%, p = .30), sedation (6% vs. 12.3%, p = .09), intubation (10% vs. 8%, p = .37), ICU admission (32% vs. 39%, p = .31), and rescue medication administration (8.6% vs. 14.6% p = .10) were similar between groups. In SE patients, IVP was associated with shorter time to administration (12 vs. 44 min, p = .003) and lower odds of ICU admission after adjustment for age, dose, Status Epilepticus Severity Score, and seizure history (adjusted odds ratio = .23, 95% confidence interval = .06-.81). IVP reduced time to levetiracetam administration versus IVPB and was not associated with more AEs. Rescue agent use, intubation, and ICU admission were similar between arms, but IVP may reduce ICU admissions in SE patients. Prospective studies should assess the effectiveness of IVP versus IVPB.

Desensitization using pegaspargase in the era of commercially available Erwinia: A single-institution report on efficacy, cost, and resource utilization.

Pegaspargase is a therapeutic enzyme that is utilized in treatment regimens targeting pediatric acute lymphoblastic leukemia. However, many patients experience hypersensitivity reactions, requiring discontinuation of the therapy. Historically, this necessitated switching to an alternative form of the drug, most commonly asparaginase Erwinia chrysanthemi; however, in recent years this was difficult due to drug shortages and eventually commercial discontinuation. We report here our experience performing pegaspargase desensitizations in patients with prior hypersensitivity reactions. Patients with a clinical hypersensitivity reaction to pegaspargase were identified. When due for their next dose, patients were admitted to the pediatric intensive care unit, bone marrow transplant unit, or oncology unit, and underwent desensitization utilizing a rigorous premedication and multistep dilution-based protocol. Serum asparaginase activity levels were drawn after desensitization to assess for therapeutic levels of enzyme activity. We identified 11 patients who underwent a total of 33 desensitizations to pegaspargase and calaspargase pegol-mknl. No patients experienced clinically significant hypersensitivity reactions necessitating stopping the infusion, nor administration of rescue medications. All serum asparaginase activity levels collected demonstrated enzyme activity levels above predefined therapeutic thresholds. Cost analysis revealed substantial savings when patients received asparaginase desensitization over the now commercially available asparaginase E. chrysanthemi (recombinant) rywn. Performing desensitization to pegaspargase in the pediatric acute lymphoblastic leukemia population is feasible, safe, and effective. It is financially advantageous over available alternative approaches, and requires fewer injections and presentations to care.

Out-of-hospital rescue medication in dogs with emergency seizure disorders: an owner perspective.

Emergency seizure disorders such as status epilepticus and cluster seizures are unlikely to cease spontaneously while prolonged seizure activity become progressively more resistant to treatment. Early administration of rescue medication in canine epileptic patients, in particular benzodiazepines, at seizure onset by the owners can be life-saving and brain protecting. Clinical studies in dogs evaluating the use of rescue medication in hospital environment exist, however, the owner perspective has not been assessed to date. To evaluate the use of rescue medication in dogs with seizure emergencies by the owner at home. Observational study based on online surveys of owners of dogs with emergency seizure disorders. The questionnaire was answered by 1,563 dog owners, of which 761 provided complete and accurate answers suitable for analysis. Of these, 71% administered diazepam, 19% midazolam, 6% levetiracetam, 3% lorazepam, and 4% more than one rescue or other medication. Overall, the success rates based on owners' perspective for intranasal midazolam and rectal diazepam were 97 and 63%, respectively. Owners reported a compliance level of 95 and 66% for intranasal midazolam and rectal diazepam administration, respectively. Even though rectal diazepam was the most used rescue medication in this survey population, intranasal midazolam was perceived by the owners as a better option regarding effectiveness, time to seizure cessation and owner compliance.

Efficacy and safety of patient-controlled thoracic epidural analgesia alone versus patient-controlled intravenous analgesia with acetaminophen after laparoscopic distal gastrectomy for gastric cancer: a propensity score-matched analysis.

Laparoscopic gastrectomy is a common procedure for early gastric cancer treatment. Improving postoperative pain control enhances patient recovery after surgery. The use of multimodal analgesia can potentially enhance the analgesic effect, minimize side effects, and change the postoperative management. The purpose of this study was to evaluate and compare the efficacies of the use of patient-controlled intravenous analgesia with regular acetaminophen (PCIA + Ace) and patient-controlled thoracic epidural analgesia (PCEA) for postoperative pain control. We retrospectively collected the data of 226 patients who underwent laparoscopic distal gastrectomy (LDG) with delta-shaped anastomosis between 2016 and 2019. After 1:1 propensity-score matching, we compared 83 patients who used PCEA alone (PCEA group) with 83 patients who used PCIA + Ace (PCIA + Ace group). Postoperative pain was assessed using a numeric rating scale (NRS) with scores ranging from 0 to 10. An NRS score ≥ 4 was considered the threshold for additional intravenous rescue medication administration. Although NRS scores at rest were comparable between the PCEA and PCIA + Ace groups, NRS scores of patients in the PCIA + Ace group during coughing or movement were significantly better than those of patients in the PCEA group on postoperative days 2 and 3. The frequency of additional rescue analgesic use was significantly lower in the PCIA + Ace group than in the PCEA group (1.1 vs. 2.7, respectively, p < 0.001). The rate of reduction or interruption of the patient-controlled analgesic dose was higher in the PCEA group than in the PCIA + Ace group (74.6% vs. 95.1%, respectively, p = 0.0002), mainly due to hypotension occurrence in the PCEA group. Physical recovery time, postoperative complication occurrence, and liver enzyme elevation incidence were not significantly different between groups. PCIA + Ace can be safely applied without an increase in complications or deterioration in gastrointestinal function; moreover, PCIA + Ace use may provide better pain control than PCEA use in patients following LDG.

Automated feedback modestly improves perioperative treatment adherence of postoperative nausea and vomiting

Study objectiveExtensive evidence demonstrates that medical record modernization and a vast amount of available data have not overcome the gap between recommended and delivered care. This study aimed to evaluate the use of clinical decision support (CDS) in conjunction with feedback (post-hoc reporting) to improve PONV medication administration compliance and postoperative nausea and vomiting (PONV) outcomes. DesignSingle center, prospective observational study between January 1, 2015, and June 30, 2017. SettingPerioperative care at a university-affiliated tertiary care center. Patients57,401 adult patients who received general anesthesia in a non-emergency setting. InterventionA multi-phased intervention that consisted of post-hoc reporting for individual providers by email about PONV occurrences in their patients, followed by directive CDS through preoperative daily case emails that provided therapeutic PONV prophylaxis recommendations based on patients' PONV risk scores. MeasurementCompliance with PONV medication recommendations, as well as hospital rates of PONV were measured. Main resultOver the study period, there was a 5.5% (95% CI, 4.2% to 6.4%; p < 0.001) improvement in the compliance of PONV medication administration along with an 8.7% (95% CI, 7.1% to 10.2%, p < 0.001) reduction in PONV rescue medication administration in the PACU. However, there was no statistically or clinically significant reduction in the prevalence of PONV in the PACU. The prevalence of PONV rescue medication administration decreased during the Intervention Rollout Period (odds ratio 0.95 [per month]; 95% CI, 0.91 to 0.99; p = 0.017), and during the Feedback with CDS Recommendation Period (odds ratio, 0.96 [per month]; 95% CI, 0.94 to 0.99; p = 0.013). ConclusionPONV medication administration compliance modestly improves with CDS in conjunction with post-hoc reporting; however, no improvement in PACU rates of PONV occurred.

IF IM in a crisis: Intranasal fentanyl versus intravenous morphine in adult vaso-occlusive crisis

ImportanceStudies have demonstrated the benefits of INF in reducing pain scores in pediatric patients with VOC due to sickle cell disease (SCD) and in adult patients with chronic pain conditions other than VOC, such as cancer. However, there is limited literature that exists describing the role of INF in adult patients with VOC due to SCD. Current literature demonstrates that the use of IV morphine for VOC patients leads to reduced pain. Therefore, comparing the use of INF with IV morphine will establish the degree of effectiveness of INF for VOC patients. ObjectiveTo determine if intranasal fentanyl is equally as effective as IV morphine for treating VOC-associated pain in adult SCD patients. DesignThis study was a retrospective non-inferiority cohort study. Electronic health records were utilized to identify eligible patients between January 1, 2021 to February 28, 2022. Patients who received INF as an initial opioid upon presentation to the ED where allocated to the intervention group. On the other hand, individuals who received IV morphine as an initial opioid upon presentation to the ED were allocated to the control group. SettingA multi-site healthcare system containing five hospitals. ParticipantsPatients 18 years of age or older, admitted to the ED with VOC due to SCD, and received INF or IV morphine as an initial opioid upon presentation to the ED. Main outcomes and measuresThe primary outcome was to evaluate the percent change in pain reduction after the initial dose of opiate between groups. Secondary outcomes include time to first rescue medication, total morphine milligram equivalent (MME) of IV opiates, hypotension, bradycardia, respiratory distress requiring opiate reversal within 6 h post- study drug administration, readmission within 48 h, and ED disposition. ResultsA total of 230 patients were reviewed within the study period, 95 subjects met inclusion criteria, 31 subjects were included in the INF arm and 64 subjects in the IV morphine arm. The primary outcome showed an average percent pain reduction of 17.25% in the INF arm and 17.15% in the IV morphine arm. The point estimate difference was 0.1% (95% CI −9.3%–9.5%; non-inferiority (p < 0.0001). The median dose of IV opiates was 8 MME in the INF group, and 6 MME in the IV morphine group (p = 0.0268). The time from study drug to first rescue medication administration was 22.4 min and 27.3 min in the INF and IV morphine groups, respectively (p = 0.2231). There was no incidence of hypotension or respiratory distress requiring opiate reversal in either arm. Bradycardia occurred in 12.9% and 7.7% (p = 0.2042), readmission rates within 48 h due to VOC was 6.5% and 20.9% (p = 0.0553), and discharge from the ED to home was 16% and 66% (p = 0.0196) in INF and IV morphine arms, respectively. ConclusionINF provided similar pain reduction compared to IV morphine in the treatment of adults with VOC presenting to the ED. IV morphine arm showed a statistically significant difference in discharge to home from the ED, however there was a trend in readmission within 48 h. The study showed no significant difference in hypotension, respiratory distress, or bradycardia between the groups. The INF group had no significant impact on time to drug administration compared to IV morphine, however it was within 1 h of patient presentation which complies with American Society of Hematology (ASH) guidelines. In conclusion, our study showed that INF was non-inferior when compared to IV morphine in reducing pain scores after drug administration. Therefore, INF is an effective alternative to IV morphine for pain management in adults presenting to the ED for VOC particularly in those with limited IV access.

Effects of adding a neurokinin-1 receptor antagonist to 5\xa0mg olanzapine, a 5-hydroxytryptamine-3 receptor antagonist, and dexamethasone for preventing carboplatin-induced nausea and vomiting: a propensity score-matched analysis

BackgroundOlanzapine has been reported to be an effective antiemetic in patients receiving carboplatin-based chemotherapy. However, the efficacy of a neurokinin-1 receptor antagonist (NK1RA) added to olanzapine, a 5-hydroxytryptamine-3 receptor antagonist (5-HT3RA), and dexamethasone (DEX) has not been proven. This study aimed to assess the efficacy and safety of NK1RA, in combination with three-drug antiemetic regimens containing olanzapine, in preventing nausea and vomiting induced by carboplatin-based chemotherapy.MethodsData were pooled for 140 patients receiving carboplatin-based chemotherapy from three multicenter, prospective, single-arm, open-label phase II studies that evaluated the efficacy and safety of olanzapine for chemotherapy-induced nausea and vomiting. The propensity score of the co-administration of NK1RA was estimated for each patient using a logistic regression model that included age, sex, and carboplatin dose. We analyzed a total of 62 patients, who were treated without NK1RA (non-NK1RA group: 31 patients) and with NK1RA (NK1RA group: 31 patients). The patients were selected using propensity score matching.ResultsThe complete response rate (without emetic episodes or with no administration of rescue medication) in the overall period (0–120 h post carboplatin administration) was 93.5% in the non-NK1RA group and 96.8% in the NK1RA group, with a difference of -3.2% (95% confidence interval, -18.7% to 10.9%; P = 1.000). In terms of safety, there was no significant difference between the groups in daytime sleepiness and concentration impairment, which are the most worrisome adverse events induced by olanzapine.ConclusionsThe findings suggest that antiemetic regimens consisting of olanzapine, 5HT3RA, and DEX without NK1RA may be a treatment option for patients receiving carboplatin-based chemotherapy.

Journal Club: Efficacy and Safety of Voclosporin Versus Placebo for Lupus Nephritis (AURORA 1): A Double-Blind, Randomized, Multicenter, Placebo-Controlled, Phase 3 Trial.

ObjectiveVoclosporin, a novel calcineurin inhibitor approved for the treatment of adults with lupus nephritis (LN), improved complete renal response rates in patients with LN in a phase 2 trial. This study aimed to evaluate the efficacy and safety of voclosporin for the treatment of LN.MethodsThis multicenter, double‐blind, randomized phase 3 trial was done in 142 hospitals and clinics across 27 countries. Patients with a diagnosis of systemic lupus erythematosus and LN, according to the American College of Rheumatology criteria, who had undergone a kidney biopsy within 2 years that showed class III, IV, or V (alone or in combination with class III or IV) were eligible for this study. Patients were randomly assigned (1:1) to receive oral voclosporin (23.7 mg twice daily) or a placebo, on a background of mycophenolate mofetil (1 g twice daily) and rapidly tapered low‐dose oral steroids, by use of an interactive web response system. The primary endpoint was complete renal response at 52 weeks, defined as a composite of urine protein creatinine ratio of 0.5 mg/mg or less, stable renal function (defined as estimated glomerular filtration rate [eGFR] ≥60 ml/min/1.73m2 or no confirmed decrease from baseline in eGFR of > 20%), no administration of rescue medication, and no more than 10 mg prednisone equivalent per day for 3 or more consecutive days or 7 or more days during Week 44 through Week 52 (just before the primary endpoint assessment). Safety was also assessed. Efficacy analysis was by intention to treat, and safety analysis was by randomized patients receiving at least one dose of study treatment.ResultsBetween April 13, 2017, and October 10, 2019, 179 patients were assigned to the voclosporin group and 178 were assigned to the placebo group. The primary endpoint of complete renal response at Week 52 was achieved in significantly more patients in the voclosporin group than in the placebo group (73 [41%] of 179 patients vs 40 [23%] of 178 patients; odds ratio, 2.65; 95% confidence interval [CI] 1.64‐4.27; P < 0·0001). The adverse event profile was balanced between the two groups; serious adverse events occurred in 37 (21%) of 178 patients in the voclosporin group and 38 (21%) of 178 patients in the placebo group. The most frequent serious adverse event involving infection was pneumonia, occurring in seven (4%) patients in the voclosporin group and in eight (4%) patients in the placebo group. A total of six patients died during the study or study follow‐up period (one [<1%] patient in the voclosporin group and five [3%] patients in the placebo group). None of the events leading to death were considered by the investigators to be related to the study treatments.ConclusionVoclosporin in combination with mycophenolate mofetil (MMF) and low‐dose steroids led to a clinically and statistically superior complete renal response rate versus MMF and low‐dose steroids alone, with a comparable safety profile. This finding is an important advancement in the treatment of patients with active LN.

UK framework for basic epilepsy training and oromucosal midazolam administration

BackgroundUK wide Oromucosal Midazolam is used as an emergency treatment in community for seizures administered by family/carers with the right training. The Joint Epilepsy Council (JEC) UK which produced the training guidelines disbanded in 2016. PurposeProvide standards for basic epilepsy education and rescue medication (Midazolam) administration. MethodsThe Epilepsy Nurses Association (ESNA), The International League against Epilepsy, British Chapter (ILAE) and the Royal college of Psychiatrists (RCPsych), used the Delphi process to update guidelines for the administration of oromucosal midazolam including developing a voluntary on-line test for carers. During 2017–2019 a facilitator worked with two ESNA committees to update the existing guidance and another to develop a question-bank. Both committee outputs were circulated to the ESNA membership, then ILAE and RCPsych for review. Patient-facing organizations and charities’ opinions were solicited. All feedback was assimilated. A private provider was contracted to deliver the test. ResultsA consensus process involving two task and finish groups of 19 people each compared, reflected, debated, and engaged with stakeholders across three stages. The updated ratified guidelines were circulated nationally. The Delphi process highlighted many regions and individuals had local assessment tools and procedures in place, while others (around 50%) had no assessment provision. 278 carers with a 95% pass-rate and 100% positive feedback have undertaken the online test (10/2020). ConclusionThe UK-wide care provision gap in basic epilepsy-training and safe rescue medication administration is now addressed. A two-yearly update to the guidelines and test is planned.

Assessment Of Hypersensitivity Reactions and Feasibility Of a 60 Minute Rapid Infusion Rituximab Protocol At a Comprehensive Cancer Center

IntroductionRituximab (R) is a chimeric monoclonal antibody with approved indications for non-hodgkin's lymphoma (NHL) and chronic lymphocytic leukemia (CLL). Infusion reactions among patients with NHL are common during the first infusion (incidence of 77%), but decrease with subsequent infusions. Consequently, infusions have been gradually titrated, which may take more than three hours for completion depending on dose and tolerability. However, emerging data suggest that rapid infusion protocols may be safe for patients who receive the first dose with minimal infusion toxicity. MethodsThe purpose of this study was to assess the feasibility of a rapid infusion R protocol in a comprehensive cancer center's outpatient infusion center. The primary outcome measure was the incidence of grade 3 and 4 hypersensitivity reactions during a 60 minute infusion protocol of R in patients with B-cell malignancies. Secondary objective included infusion time savings of a 60 minute infusion of R versus a standard titration schedule, as well as nursing satisfaction. Patients were enrolled in this prospective, single institution, single arm study which was approved by the investigational review board. Inclusion criteria included age >18 years, diagnosis of indolent or intermediate grade B-cell malignancy, second R infusion within 3 months of first infusion, and planned outpatient treatment with a regimen including R therapy at a dose of 375mg/m2. Patients were excluded for diagnosis of an aggressive lymphoma histology, absolute lymphocyte count > 10 x 103/µL, enrollment on another clinical trial, allergy to murine-containing medications, exposure to R (<6 months from first dose) prior to enrollment in this study, or grade 3 or 4 hypersensitivity reaction during first R infusion. All patients received the first dose of R by the standard titration schedule as described in the package insert. The investigational protocol was instituted for the second R administration. The infusion began at 100mg/hr administered over 15 minutes and the remaining dose was given over 45 minutes. All patients received 50mg of oral diphenhydramine and 650mg of oral acetaminophen as premedication. To calculate time savings between rapid infusion and standard titration, each patient served as their own control. Nursing data collection included monitoring vitals every 15 minutes (blood pressure, heart rate, temperature, respiratory rate), start and stop times of R infusion, description and grade of hypersensitivity reactions, administration of rescue medications during infusion, and survey assessment of nursing satisfaction. ResultsFrom October 2010 to April 2013, 52 patients were enrolled to the study. Fifty received rapid infusion over 60 minutes during the second R administration. The 2 patients who did not continue on study were deemed ineligible. Patient 1 expired secondary to disease progression after signing consent and patient 2 experienced a grade 3 reaction following end of first infusion. The median age was 63 years (19-85) with 60% female. Chemotherapy regimens included: R-cyclophosphamide, doxorubicin, vincristine, prednisone (RCHOP, n = 19), single-agent R (n = 14), R-bendamustine (BR, n=7), R-cyclophosphamide, vincristine, prednisone (RCVP, n=4), R-gemcitabine, oxaliplatin (RGEMOX, n=3), R-fludarabine, cyclophosphamide (FCR, n=1), R-pentostatin, cyclophosphamide (PCR, n=1) and R-bortezomib (n=1). The rate of infusion related reactions (all grades) observed with the rapid infusion protocol was 0% (1-sided 97.5% CI 0-7.1%). The mean time for the rapid R infusion was 62.4 (95% CI 61.2-63.6) minutes. When compared to the standard second dose infusion recommendations, a mean time of 94.2 (95% 90-98.4) minutes was saved with rapid infusion. Post infusion nursing surveys demonstrated 100% satisfaction with administration of rapid infusion over standard titration practice. ConclusionsA 60 minute rapid rituximab infusion can be safely administered in an outpatient infusion center. The faster infusion allows for less resource utilization and increased nursing satisfaction. Disclosures:No relevant conflicts of interest to declare.

Comparison between dexmedetomidine and fentanyl bolus in attenuating the stress response to laryngoscopy and tracheal intubation: a randomized double-blind trial

Background and objectivesLaryngoscopy and tracheal intubation lead to a sympathoadrenal response. We compared the efficacy of dexmedetomidine with fentanyl bolus to attenuate this response. MethodsOne hundred patients admitted for routine surgical procedures under general anesthesia were enrolled in this double blind, randomized, controlled study. Patients were randomly assigned to two groups: Group F received injection of fentanyl 2 μg.kg-1 and Group D received injection of dexmedetomidine 0.5 μg.kg-1 diluted up to 5 mL by adding normal saline intravenously over 60 seconds. Five minutes thereafter, following induction with propofol and vecuronium, tracheal intubation was performed after 3 minutes of mask ventilation. Hemodynamic parameters were observed at an interval of 2 minutes before tracheal intubation and at an interval of 1 minute for 5 minutes after tracheal tube cuff inflation. Continuous variables are presented as mean with 95% confidence interval, and t-test was applied for comparing the difference of means between two groups after checking the normality condition. Chi-square test was applied to test the independence of attributes of categorical variables. Repeated measures two-way ANOVA was performed to compare the outcome variables between the two groups. ResultsThe difference in heart rate and mean arterial pressure of patients in two groups after laryngoscopy and intubation was not statistically significant at any point of time. The hemodynamic changes did not require any intervention in the form of administration of rescue medication. ConclusionsDexmedetomidine 0.5 μg.kg-1 is as effective as fentanyl 2 μg.kg-1 in attenuating the hemodynamic response accompanying laryngoscopy and tracheal intubation. Clinical trial number & registry URLCTRI/2017/09/009857 [ctri.nic.in]

Efficacy and safety of voclosporin versus placebo for lupus nephritis (AURORA 1): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial

Voclosporin, a novel calcineurin inhibitor approved for the treatment of adults with lupus nephritis, improved complete renal response rates in patients with lupus nephritis in a phase 2 trial. This study aimed to evaluate the efficacy and safety of voclosporin for the treatment of lupus nephritis. This multicentre, double-blind, randomised phase 3 trial was done in 142 hospitals and clinics across 27 countries. Patients with a diagnosis of systemic lupus erythematosus with lupus nephritis according to the American College of Rheumatology criteria, and a kidney biopsy within 2 years that showed class III, IV, or V (alone or in combination with class III or IV) were eligible. Patients were randomly assigned (1:1) to oral voclosporin (23·7 mg twice daily) or placebo, on a background of mycophenolate mofetil (1 g twice daily) and rapidly tapered low-dose oral steroids, by use of an interactive web response system. The primary endpoint was complete renal response at 52 weeks defined as a composite of urine protein creatinine ratio of 0·5 mg/mg or less, stable renal function (defined as estimated glomerular filtration rate [eGFR] ≥60 mL/min/1·73 m2 or no confirmed decrease from baseline in eGFR of >20%), no administration of rescue medication, and no more than 10 mg prednisone equivalent per day for 3 or more consecutive days or for 7 or more days during weeks 44 through 52, just before the primary endpoint assessment. Safety was also assessed. Efficacy analysis was by intention-to-treat and safety analysis by randomised patients receiving at least one dose of study treatment. The trial is registered with ClinicalTrials.gov, NCT03021499. Between April 13, 2017, and Oct 10, 2019, 179 patients were assigned to the voclosporin group and 178 to the placebo group. The primary endpoint of complete renal response at week 52 was achieved in significantly more patients in the voclosporin group than in the placebo group (73 [41%] of 179 patients vs 40 [23%] of 178 patients; odds ratio 2·65; 95% CI 1·64-4·27; p<0·0001). The adverse event profile was balanced between the two groups; serious adverse events occurred in 37 (21%) of 178 in the voclosporin group and 38 (21%) of 178 patients in the placebo group. The most frequent serious adverse event involving infection was pneumonia, occurring in 7 (4%) patients in the voclosporin group and in 8 (4%) patients in the placebo group. A total of six patients died during the study or study follow-up period (one [<1%] patient in the voclosporin group and five [3%] patients in the placebo group). None of the events leading to death were considered by the investigators to be related to the study treatments. Voclosporin in combination with MMF and low-dose steroids led to a clinically and statistically superior complete renal response rate versus MMF and low-dose steroids alone, with a comparable safety profile. This finding is an important advancement in the treatment of patients with active lupus nephritis. Aurinia Pharmaceuticals.

Seizure action plans in the pediatric population with epilepsy: Uptake, determinants, and parental interest in a mobile application

BackgroundStatus epilepticus (SE) is a common pediatric neurological emergency that requires timely treatment to minimize morbidity and mortality, yet administration of rescue medications is often delayed and underdosed. Seizure action plans (SAPs) outline the steps that should be taken by parents and caregivers in case of SE in order to optimize patient outcomes. Our study determined the uptake of SAPs in a pediatric population with epilepsy and assessed parental interest in a SAP mobile application. MethodsA survey was distributed to parents of patients with epilepsy aged 1 month to 19 years at British Columbia Children’s Hospital. Following chart review, univariate and multivariate analyses were performed to identify variables that predict whether patients have SAPs. A systematic search of available mobile applications for epilepsy management was conducted. ResultsOf 192 participants, 62% have SAPs. On univariate analysis, history of prior SE and male gender increased likelihood of SAP. On logistic regression, Nagelkerke R2 was 0.204 and our model correctly predicted 82% of patients with SAPs. 83% of parents were interested in a SAP mobile application. There are currently 40 mobile applications available for epilepsy management, but only 15% of respondents reported using them. ConclusionsThere is a need to increase the percentage of patients with epilepsy with SAPs, particularly in those at greater risk of SE. Most parents would find a SAP mobile application valuable in their child’s epilepsy management. There is a gap between the high parental interest in mobile applications for epilepsy management and their current use of such applications.

Empowering seizure management skills: Knowledge, attitudes, and experiences of school staff trained in administering rescue drugs in Northern Italy

PurposeThe administration of rescue medication at school concerns students for which it may be essential, on doctor's prescription, to take therapy during school hours. In this case, since the parents are absent, the first rescuer is necessarily the school staff, who should be properly trained because prolonged seizures can cause severe harm and even death. MethodsEvery year, the Local Health Unit “TO3” in Northern Italy, provides training for school staff to administrate rescue medication at school. From December 2019 to February 2020, the same questionnaire was administered to school staff trained for seizures at the end of the course, while the staff trained for other diseases completed it before the course. ResultsAbout 60% of the sample (N = 123) had been trained in seizure management at least once in their lifetime. Median knowledge score in subjects with no seizures training was 7 (Q25/Q75: 5/8), while it was 9 (Q25/Q75: 6/10) in subjects with seizures training (p < 0.001). The self-reported level of confidence in their skills to administer rescue medication was high in 10.2% of subjects not trained for seizures and in 62.9% of those trained (p < 0.001). ConclusionResults suggest that medical training for school staff increases knowledge scores and levels of self-confidence relating to the administration of rescue medication. Moreover, after the training, the school staff changed attitude toward seizures, no longer considering them a problem, and became more aware, less fearful, and more inclined to act in case of need, making school a better place for all students.

Empowering seizures awareness: knowledge, attitudes and fears of school staff trained in rescue drugs

Abstract Background The administration of rescue medication at school concerns, in all Europe, students suffering from chronic pathologies for which it may be essential, on doctor's prescription, to take therapy during school hours. About 16% of the school's emergency calls are related to a seizure crisis. In this case, since the parents are absent, the first rescuer is necessarily the school staff, who should be properly trained because prolonged seizures can cause severe harm and even death. Methods Every year, the Local Health Unit “TO3”, in Northern Italy, provides training for school staff to administrate rescue medication at school. A questionnaire survey on knowledge, attitudes and fears towards seizures was conducted during the school year 2019/2020. The same questionnaire was administered to school staff trained for seizures at the end of the course, while the staff trained for other diseases such as diabetes, allergies and asthma completed it before the course. Results 110 questionnaires have been completed. About 60% of the sample had been trained in seizure management at least once in their lifetime. The respondents had a mean age of 48.7±9.6 years and a mean job experience of 17.4±11.2 years. Most of them were females (83%). Median knowledge score (10 points max) in subjects with no seizures training was 6, while it was 8.5 in subjects with seizures training (p &amp;lt; 0.001). The self-reported level of confidence in their own skills to administer rescue medication was high in 10.4% of subjects not trained for seizures and in 63.8% of those trained (p &amp;lt; 0.001). Conclusions Results suggest that medical training for school staff boosts knowledge scores and levels of self-confidence relating to the administration of rescue medication. Moreover, after the training, the school staff changed attitude towards seizures, no longer considered as a problem, and became more aware, less fearful, and more inclined to act in case of need, making school a safer place for all students. Key messages School staff trained in the administration of rescue medication are fundamental to guarantee the right to education for students suffering from chronic pathologies such as seizures. Empowering seizures awareness in schools is very important to change the attitude of school staff no longer considering seizures as a problem, making school a safer place for all European students.

MO019AURORA PHASE 3 TRIAL DEMONSTRATES VOCLOSPORIN STATISTICAL SUPERIORITY OVER STANDARD OF CARE IN LUPUS NEPHRITIS (LN)

Abstract Background and Aims Voclosporin (VCS) is a novel high potency calcineurin inhibitor (CNI) with a favorable metabolic profile and a consistent predictable dose response potentially eliminating the need for therapeutic drug monitoring. The Aurinia Renal Response in Active Lupus with Voclosporin (AURORA) study, involving 357 patients with active LN, was a Phase 3 global, double-blind, placebo-controlled RCT designed to evaluate the efficacy and safety of VCS (23.7mg BID) vs placebo in combination with mycophenolate (MMF, 2 g/day) and rapidly tapered low dose oral steroids. Method The primary endpoint was renal response (RR) at 52 weeks. RR was defined as UPCR of ≤ 0.5 mg/mg, eGFR ≥ 60 mL/min, or no confirmed decrease from baseline in eGFR of &amp;gt; 20%, presence of sustained, low dose steroids and no administration of rescue medication. Results AURORA met its primary endpoint, achieving statistically superior RR rates of 40.8% for voclosporin vs. 22.5% for the control (OR 2.65, 95% CI; p &amp;lt; 0.001). The benefits of VCS were also seen for all predetermined secondary endpoints, achieving statistical significance in favor of VCS for RR at 24 weeks, partial renal response (PRR) at 24 and 52 weeks, time to achieve UPCR ≤ 0.5, and time to 50% reduction in UPCR. Prespecified confirmed eGFR decreases &amp;gt;30% were similar in both groups, with 10.1% reported in the VCS group and 10.2% in the control arm (p= 0.971). No significant differences were seen at any timepoints in the study. Furthermore, all pre-specified subgroup analyses (age, sex, race, biopsy class, region, and prior MMF use) also favored VCS. VCS was well tolerated with no unexpected safety signals. Similar SAEs were reported in the VCS group (20.8%) and in the control arm (21.3%). Infection was the most commonly reported SAE with 10.1% of VCS patients versus 11.2% of patients in the control arm. Overall mortality in the trial was low, with 6 deaths observed; 1 in the VCS arm and 5 in the control group. Additionally, the VCS arm showed no significant decrease at week 52 in eGFR or increase in BP, lipids or glucose. Conclusion While maintaining a comparable safety profile, VCS plus standard therapy achieved a statistically superior RR over one year compared to placebo plus standard therapy in adults with active LN.

OP0277 AURORA PHASE 3 STUDY DEMONSTRATES VOCLOSPORIN STATISTICAL SUPERIORITY OVER STANDARD OF CARE IN LUPUS NEPHRITIS (LN)

Background:Voclosporin (VCS) is a novel high potency calcineurin inhibitor (CNI) with a favorable metabolic profile and a consistent predictable dose response potentially eliminating the need for therapeutic drug monitoring. LN occurs more frequently and is more severe in Hispanic/Latino ethnicity SLE patients. The recently completed phase 3 AURORA study builds on the favorable efficacy seen in the Phase IIb AURA-LV study in patients with active LN.Objectives:Document efficacy and safety of VCS vs placebo over one year when used with 2 grams of MMF daily and a rapid steroid taper in patients with active LN.Methods:AURORA is a Phase III multicenter, randomized, double-blind, placebo-controlled 52-week study of active LN patients. Patients were randomized 1:1 to VCS (23.7 mg BID) or placebo in combination with mycophenolate (MMF, 1 g BID) and rapidly tapered oral steroids. The primary endpoint was renal response (RR) at 52 weeks, defined as UPCR of ≤ 0.5 mg/mg, eGFR ≥ 60 mL/min, or no confirmed decrease from baseline in eGFR of &gt; 20%, presence of sustained, low dose steroids and no administration of rescue medication. Ethnicity subgroup analyses of RR was also undertaken given the higher severity of disease in the Hispanic/Latino LN patients.Results:There were 357 patients enrolled, 88% female, median age of 31 and 33% of Hispanic/Latino ethnicity. Renal response by intention to treat analysis at 52 weeks was 40.8% for the voclosporin arm and 22.5% for the control arm (OR: 2.65; 95% CI: 1.64, 4.27; p&lt; 0.001); therefore, AURORA met its primary endpoint. These findings were consistent with those observed in the previously completed pivotal AURA-LV study. Ethnicity subgroup analysis of RR at 52 weeks noted benefit of VCS in both Hispanic/Latino (VCS 38.6% and control 18.6%, p=0.0062, OR 3.45) and non-Hispanic/Latino patients (VCS 41.8% and control 24.6%, p=0.0045, OR 2.29). The benefits of VCS were also seen for all pre-specified hierarchical secondary endpoints: RR at 24 weeks, partial renal response (PRR) at 24 and 52 weeks, time to achieve UPCR ≤ 0.5, and time to 50% reduction in UPCR. Furthermore, all pre-specified subgroup analyses (age, sex, race, biopsy class, region, and prior MMF use) favored VCS. VCS was well tolerated with no unexpected safety signals. The overall incidence of SAEs were similar in both groups (VCS 20.8% and control 21.3%); with infection most commonly reported (VCS 10.1% and control 11.2%). Overall mortality in the trial was low, with one death in the voclosporin arm and five in the control arm. Additionally, the VCS arm showed no significant decrease at week 52 in eGFR or increase in BP, lipids, or glucose.Conclusion:The AURORA study met its primary endpoint and VCS was efficacious in Hispanic/Latino ethnicity patients, a difficult to treat group.Disclosure of Interests:Cristina Arriens Grant/research support from: - BMS: Investigator Initiated Trial Research Funding, GSK: Investigator Initiated Trial Research Funding, Exagen: Research Grant, Consultant of: AstraZeneca (Sci Ad Board Dec 2017), GSK (Sci Ad Board Oct 2018), BMS (Sci Ad Board April 2019), Svetlana Polyakova: None declared, Igor Adzerikho: None declared, Simrat Randhawa Shareholder of: Aurinia Pharmaceuticals, Inc. stock, Employee of: Aurinia Pharmaceuticals, Inc., Neil Solomons Shareholder of: Aurinia Pharmaceuticals, Inc. stock, Employee of: Aurinia Pharmaceuticals.

Cannabis use is associated with a small increase in the risk of postoperative nausea and vomiting: a retrospective machine-learning causal analysis

BackgroundCannabis legalization may contribute to an increased frequency of chronic use among patients presenting for surgery. At present, it is unknown whether chronic cannabis use modifies the risk of postoperative nausea and vomiting (PONV).MethodsThis study was a retrospective cohort study conducted at 2 academic medical centers. Twenty-seven thousand three hundred eighty-eight adult ASA 1–3 patients having general anesthesia for non-obstetric, non-cardiac procedures and receiving postoperative care in the Post Anesthesia Care Unit (PACU) were analyzed in the main dataset, and 16,245 patients in the external validation dataset. The main predictor was patient reported use of cannabis in any form collected during pre-anesthesia evaluation and recorded in the chart. The primary outcome was documented PONV of any severity prior to PACU discharge, including administration of rescue medications in PACU. Relevant clinical covariates (risk factors for PONV, surgical characteristics, administered prophylactic antiemetic drugs) were also recorded.Results10.0% of patients in the analytic dataset endorsed chronic cannabis use. Using Bayesian Additive Regression Trees (BART), we estimated that the relative risk for PONV associated with daily cannabis use was 1.19 (95 CI% 1.00–1.45). The absolute marginal increase in risk of PONV associated with daily cannabis use was 3.3% (95% CI 0.4–6.4%). We observed a lesser association between current, non-daily use of cannabis (RR 1.07, 95% CI 0.94–1.21). An internal validation analysis conducted using propensity score adjustment and Bayesian logistic modeling indicated a similar size and magnitude of the association between cannabis use and PONV (OR 1.15, 90% CI 0.98–1.33). As an external validation, we used data from another hospital in our care system to create an independent model that demonstrated essentially identical associations between cannabis use and PONV.ConclusionsCannabis use is associated with an increased relative risk and a small increase in the marginal probability of PONV.

GP.04 Prevalence and determinants of seizure action plans in a pediatric epilepsy population

Background: Status epilepticus (SE) is the most common pediatric neurological emergency. Timely treatment is crucial, yet administration of rescue medications is often delayed and under-dosed. We aim to improve SE management by ensuring that every child at risk of SE in our province has an individualized seizure action plan (SAP) outlining the steps that should be taken during SE. Methods: A survey was distributed to parents of epilepsy patients aged 1 month to 19 years. Primary outcome was percentage of patients with SAPs. Secondary outcome was parental interest in a SAP mobile application. Following chart review, univariate and multivariate analysis was performed to identify variables that predict whether patients have SAPs. Results: Of 192 participants, 61.5% have SAPs. On univariate analysis, history of prior SE and male gender increased likelihood of having a SAP. On logistic regression, Nagelkerke R2 was 0.204 and our model correctly predicted 82.2% of patients with SAPs. 83.3% of parents were interested in a SAP mobile application. Conclusions: This is one of the first studies to examine SAP prevalence in a pediatric epilepsy population. There is a need to increase the percentage of epilepsy patients with SAPs. Most parents would find a SAP mobile application valuable in their child’s management.

An open-label randomized trial of intramuscular olanzapine versus oral clonidine for symptomatic treatment of opioid withdrawal in the emergency department*

Background: Patients with opioid withdrawal often present to the Emergency Department (ED), but many EDs do not have the infrastructure in place to initiate treatment with opioid agonists (methadone or buprenorphine). Therefore, ED management often entails symptomatic control. The purpose of this study was to compare olanzapine to clonidine for the treatment of opioid withdrawal symptoms.Methods: This was a prospective, randomized clinical trial comparing 10 mg of IM olanzapine to 0.3 mg of oral clonidine for symptoms of opioid withdrawal. Adult (18 years and older) ED patients reporting a history of opioid use and symptoms consistent with withdrawal were eligible. Patients were excluded if they had already received treatment during the ED encounter, were pregnant, incarcerated, or unable to provide consent. Patients were randomized 1:1 to receive olanzapine or clonidine for their initial treatment. A baseline Clinical Opiate Withdrawal Scale (COWS) score was calculated. After 30 min, the patient could receive any additional treatment at the ED physician’s discretion. The primary outcome was need for additional medication (rescue) within 1 h of study medication administration. Secondary outcomes included change in COWS score and adverse reactions.Results: We enrolled 63 patients (33 olanzapine, 30 clonidine). Demographic characteristics were similar for both groups (median age 45, range 21–67, 54% male) as well as baseline COWS score (median score 11). The median time since last opiate use was 48 h for both groups (range 4–116). Rescue was given within 1 h for olanzapine for 9 (27%) patients and for clonidine in 19 (63%) patients (difference 36%, 95% CI 13–59%). Decrease in COWS score at 1 h was 8.3 for olanzapine and 5.1 for clonidine (difference 3.2, 95% CI 0.3–6). Adverse events were uncommon: akathisia (1, olanzapine), hypotension (2, clonidine), respiratory depression (0).Conclusions: Treatment of opioid withdrawal symptoms with 10 mg of IM olanzapine results in a lower incidence of rescue medication administration and improved symptoms (COWS score) compared to 0.3 mg of oral clonidine.