24-hour Infusion Research Articles

Results of conservative treatment of locally advanced larynx squamous cell carcinoma using intraarterial regional polychemotherapy

The study objective is to evaluate the results of organ-preserving treatment of locally advanced larynx squamous cell carcinoma.Materials and methods. Analysis of 28 patients with locally advanced larynx squamous cell carcinoma (stages III-IV) who underwent treatment at the N.N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of Russia between 2017 and 2020 was performed. At the first stage, 2-3 courses of combined inductive polychemotherapy per the DCF scheme with 21-day interval were performed (docetaxel 60 mg/m2, cisplatin 60 mg/m2 intraarterially bolus with detoxication with sodium thiosulfate, 5-fluorouracil 1000 mg/m2/day as 96-hour infusion). The second stage included external beam radiotherapy (60-70 Gy, 2 Gy per day 5 days a week) as monotreatment if complete clinical response after chemotherapy was achieved or with regional administration of cisplatin (60 mg/m2 once per 3 weeks) if after inductive stage full clinical response wasn»t observed.Results. In 20 (71.5 %) patients, complete clinical response was observed after inductive treatment; in 7 (25 %) patients, partial response was observed. Tumor stabilization was detected in 1 (3.5 %) patient. Two-year overall survival was 95.8 ± 4.1 %, progression-free survival was 90.1 ± 6.8 %.Conclusion. The proposed strategy of organ-preserving treatment of stage III-IV larynx cancer with substitution of systemic chemotherapy with regional intraarterial chemotherapy prior to radiotherapy is highly effective from the point of view of direct anti-tumor effect and recurrence-free and overall survival.

Prospective Observational Study Comparing Calcium and Sodium Levofolinate in Combination with 5-Fluorouracil in the FOLFIRI Regimen

The use of sodium levofolinate (Na-Lev) is safe in combination with continuous infusion 5-fluorouracil in patients with gastrointestinal tumors treated with the FOLFIRI regimen. A comparison with calcium levofolinate (Ca-Lev) showed a similar toxicity profile. The advantages of Na-Lev over Ca-Lev might be the faster drug preparation and the shorter time of drug administration. The objectives of this study were to compare the safety profiles of sodium levofolinate (Na-Lev) and calcium levofolinate (Ca-Lev) in combination with 5-fluorouracil (5-FU) in the FOLFIRI regimen and to measure the organizational impact of the introduction of Na-Lev on drug production and administration. The study opened in November 2015 and closed in August 2019. Patients with gastrointestinal cancers who were candidates for treatment with the FOLFIRI regimen were included in this nonrandomized study. Age ≥18 years, life expectancy >3 months, adequate bone marrow reserve, adequate hepatic and renal function, and an ECOG performance status of 0-2 were required. Patients in the Ca-Lev arm received a 2-hour infusion of Ca-Lev followed by 5-FU, whereas those in the Na-Lev arm received Na-Lev and 5-FU administered in a single 48-hour pump. Sixty patients were enrolled, 30 in each arm. Patient characteristics were balanced. Grade (G)1-2 adverse events occurred in 18 (60.0%) and 19 (63.4%) patients of Na-Lev and Ca-Lev cohorts, respectively, whereas G3-4 adverse events occurred in 12 (40.0%) and 11 (36.6%) patients, respectively. The use of Na-Lev enabled us to save approximately 13 minutes for drug preparation and 2 hours for treatment administration, per patient per cycle. Na-Lev showed a reassuring toxicity profile and a favorable impact on drug preparation and administration.

Gonadotropin response to insulin and lipid infusion reproduces the reprometabolic syndrome of obesity in eumenorrheic lean women: a randomized crossover trial

To study the reprometabolic syndrome in normal-weight, eumenorrheic women by infusing a combination of insulin and lipid. Women with obesity have been shown to have reduced gonadotropins and impaired luteinizing hormone (LH) and follicle-stimulating hormone (FSH) response to gonadotropin-releasing hormone (GnRH). Randomized crossover. Academic medical center. Fifteen women, median age 32 (interquartile ranged [IQR] 26, 36) years and body mass index 21.9 (IQR 20.2, 22.9) kg/m2 were recruited. Early follicular phase, 6-hour infusions of insulin (20-40 mU/m2 per minute) and lipid (Intralipid)-insulin/lipid infusion; or saline infusion (controls). The first 4 hours of each study assessed endogenous gonadotropins; at 4 hours, GnRH (75 ng/kg) bolus was administered and sampling continued until 6 hours. Linear mixed model analysis was used to determine differences between insulin/lipid and saline influence on endogenous LH pulse amplitude (primary outcome), mean FSH, and area under the curve (AUC) response to GnRH (secondary outcomes). Twelve women completed both intended studies and an additional 3 women completed only 1 of the 2 studies. LH pulse amplitude, mean FSH, and both AUC responses to GnRH were reduced by insulin/lipid, mean FSH and AUC for LH were at or near statistical significance. LH response to GnRH was significantly reduced when 1 participant with very high LH and antimullerian hormone levels was excluded. Acute infusion of insulin/lipid to eumenorrheic, normal-weight women recapitulated the reprometabolic syndrome of obesity. These findings imply that specific circulating factors in obese women contribute to their subfertility and thus may be amenable to discovery and treatment. NCT02653092.

Effectiveness of ZYESAMI™ (Aviptadil) in Accelerating Recovery and Shortening Hospitalization in Critically-Ill Patients with COVID-19 Respiratory Failure: Interim Report from a Phase 2B/3 Multicenter Trial

Background: There is currently no effective drug to treat critically-ill patients with COVID-19 Respiratory Failure. Vasoactive Intestinal Peptide (VIP) blocks intracellular replication of the SARS-CoV-2 virus, inhibits cytokine synthesis, prevents cytopathy, and upregulates surfactant production in human alveolar type II cells, which are the site of SARS-CoV-2 infection in the lung. Purpose: To determine the safety and efficacy of intravenous ZYESAMI™ (Aviptadil; synthetic Vasoactive Intestinal Peptide) for improving recovery from respiratory failure in patients with Respiratory Failure in Critical COVID-19.Methods: Randomized prospective double-blind placebo-controlled trial with 28 day and 60 day endpoints. Setting: Ten US-based acute care hospitals, which included 4 tertiary care teaching hospitals and 6 regional hospitals. Participants: 196 patients with PCR+ Critical COVID-19 treated with High Flow Nasal Cannula (HFNC: n=127) Non-Invasive Ventilation (NIV: n=32) or Mechanical Ventilation (MV: n=36). Intervention: Participants were randomly allocated to intravenous aviptadil (synthetic VIP) or placebo at a 2:1 ratio, in addition to maximal standard of care (SOC). Participants received 3 successive 12-hour intravenous infusions of Aviptadil at 50/100/150 pmol/kg/hr or normal saline placebo, each day for 3 consecutive days. The main outcome measure was cumulative probability of time to recovery from respiratory failure without relapse and with survival through day 28 and through day 60. Secondary endpoints included time to ICU discharge, time to hospital discharge, NIAID ordinal scale, and survival lifetable. Analysis was by intent to treat.Results: Overall, 91 of 131 Aviptadil-treated participants survived to day 28 compared to 47 of 65 placebo-treated patients (70.6% vs 71.7%; P=NS). Among those treated with HFNC (n=127), the main outcome measure demonstrated a trend in favor of the drug treated group (Hazard Ratio 1.53; P=.08). Participants treated in tertiary care hospitals demonstrated a greater effect (HR 1.84; P=.058). A 10 day median difference in hospital length of stay was seen in all HFNC patients (P=.006) and a thirteen day difference was seen in those treated in tertiary care centers (P=.004), with both differences favoring treatment with aviptadil. No drug-related serious adverse events were seen in either group. The only adverse event reported more frequently in drug- vs. placebo-treated participants was mild to moderate diarrhea (30% vs 1.5% P

Trabectedin in Advanced Sarcomas-Experience at a Tertiary Care Center and Review of Literature.

Background There is sparse literature on trabectedin in advanced soft-tissue sarcomas from developing world. It would be interesting to know about use and outcomes of trabectedin in Indian patients. Method In a retrospective study, consecutive patients treated with trabectedin from 2016 to 2019 were analyzed. Patients with L-sarcomas were treated at a dose of 1.5 mg/m 2 , while those with translocation-related sarcomas were treated at a dose of 1.2 mg/m 2 as a 24-hour infusion through peripherally inserted central catheter line. From July 2019, infusions were administered through an ambulatory elastomeric pump, while before that patients were admitted for 24 hours. We used SPSS version 23.0 for statistical calculation. Result A total of 20 patients received trabectedin with a total of 116 infusions. The median age was 46 years (range: 22–73 years). The male ( n = 11, 55%) and female patients were almost equal ( n = 9, 45%). Thirteen patients (65%) had Eastern Cooperative Oncology Group Performance Status 1. Majority of the patients had leiomyosarcoma ( n = 8, 40%); remaining comprised of liposarcoma (3, 15%), translocation-related sarcomas excluding myxoid liposarcoma ( n = 8, 40%) and others ( n = 1,5%). Most common site was extremity ( n = 11, 55%) followed by retroperitoneal ( n = 3, 15%), visceral ( n = 3, 15%), and others ( n = 3,15%). Median number of previous lines received was 2 (range: 0–4). Median number of trabectedin cycles received was 4 (range: 1–17). Best response assessed was stable disease ( n = 10, 50%), progressive disease ( n = 6, 30%), partial response ( n = 1, 5%), and not assessed in 3 patients. After a median follow-up of 19 months, median progression-free survival was 4 months. Conclusion In this heavily treated population (composed of L-sarcomas and translocation-related sarcomas) with many patients with poor performance status, the outcome with trabectedin is in synchrony with literature. However, the need of 24-hour admission might deter quality of life. Elastomeric pump seems to be a reasonable alternative to admission and can be a breakthrough in administering trabectedin, especially in developing countries.

CLAG Regimen Composed of Continuous Intravenous Infusion of Cladribine in the Treatment of Refractory/Relapsed Acute Myeloid Leukemia

To study the efficacy and safety of continuous intravenous infusion of 2-Chlorodeoxyadenosine (2-CdA) combined with high-dose cytarabine (Ara-C) and granulocyte colony-stimulating factor (G-CSF) (CLAG regiem) in the treatment of relapsed/refractory acute myeloid leukemia (AML). Fifteen patients with refractory/relapsed AML hospitalized in 5 medical units such as Department of Hematology, the Affiliated Tumor Hospital of Zhengzhou University and received one course of CLAG regimen from June 2014 to August 2019 were analyzed retrospectively (specifically: cladribine 5 mg/M2, day 1 to day 5, continuous 24-hour intravenous infusion; Ara-C 2 g/M2, 1 time/day, day 1 to day 5, intravenous infusion; G-CSF 300 mg, 1 time/day, day 0 to day 5, subcutaneous injection). Among the 15 patients with refractory/relapsed AML, 9 males and 6 females, the median age was 35 (13-63) years old. FAB classification: 1 case of M1, 3 cases of M2a, 4 cases of M2b (including 1 case with extramedullary invasion), 1 case of M4 with extramedullary invasion, 5 cases of M5, 1 case of HAL; NCCN classification: 6 cases in intermediate risk group, 9 cases in high risk group; 8 cases refractory, 7 cases relapsed. The median time of pre-chemotherapy was 4 (2-8) (of which NO.15 had received 8 cycles of chemotherapy and received CLL1-CAR-T), and the median white blood cell count before chemotherapy was 12.27 (from 0.78 to 5.29)×109/L. After 1 course of treatment with CLAG regimen, 12 patients achieved complete remission (12/15, 80%), and the median duration of CR was 65 days (0-528) days. IV grade leukopenia and thrombocytopenia was found in all the patients after chemotherapy. The median duration of granulocytosis was 20 (14 to 33) days, and 1 patient died. Seven patients received allogeneic hematopoietic stem cell transplantation. The median EFS and OS time of 15 patients was 85 (19-558) days and 117 (19-558) days, respectively. The CLAG regimen consisting of continuous intravenous infusion of cladribine shows high CR in the treatment of AML patients, but the duration of CR is short, myelosuppression is sever, so that infection control is the key. Allogeneic hematopoietic stem cells transplantation should be performed as soon as possible after CR.

Clinical efficacy of levosimendan vs milrinone in preventing low cardiac output syndrome following pediatric cardiac surgery.

Background:Prophylactic milrinone is commonly used to prevent Low Cardiac Output Syndrome (LCOS) after pediatric cardiac surgery. This study compares the use of levosimendan with milrinone when used as the primary inotrope following pediatric cardiac surgery.Subjects and Methods:Forty infants undergoing corrective surgery for congenital heart disease were recruited during the study and randomized into two groups (group L and group M). During rewarming, a loading dose of levosimendan or milrinone was administered followed by a 24-hour infusion of the chosen inotrope. Echocardiographic variables were measured postoperatively. Statistical analysis was done with SPSS-20 computer package. Association between the variables was found by independent t test. P < 0.05 was considered statistically significant.Results:Mean age and weight of the patient in Group L was 8.55 ± 5.83 months and 6.05 ± 2.09 kgs, while that in group M was 6.85 ± 3.57 months and 5.26 ± 2.11 kgs. 4 patients (20%) treated with levosimendan had LCOS in comparison with 6 (30%) patients in those treated with milrinone. Echocardiographic parameters in both groups L and M were comparable (cardiac index 3.47 ± 0.76 vs 3.72 ± 1.05 L/min/m2, EF 66.10 ± 7.82% vs 59.34 ± 10.74%, stroke volume index 25.4 ± 6.3 vs 27.74 ± 10.35 mL/m2). The duration of ventilation, ICU stay and hospital stay were lesser in group L (12.75 ± 9.69, 35.95 ± 12.11, 119.10 ± 46.397 vs 23.60 ± 22.03, 51.20 ± 29.92, 140.20 ± 52.65 hours).Conclusions:The incidence of LCOS was lesser in those patients treated with levosimendan, when compared with those treated with milrinone. Cardiac index and stroke volume index were comparable between the two groups. Thus, levosimendan provides a non-inferior alternative to milrinone when used as the primary inotrope following pediatric cardiac surgery.

Continuous-Infusion Foscarnet Facilitates Administration in Hematopoietic Stem Cell Transplantation Patients

Infections due to herpesviruses resistant to first-line antivirals remains an ever-present and serious complication in recipients of hematopoietic cell transplantation (HCT) and other cellular therapies. Foscarnet is the most common therapy for patients who have resistant herpesvirus infections or intolerable cytopenias due to ganciclovir or valganciclovir; however, the widespread use of foscarnet is limited by its associated nephrotoxicity and challenges in administration. In the earliest published small case series investigating the optimal infusion modality, patients with acquired immunodeficiency syndrome (AIDS) due to the human immunodeficiency virus (HIV) received either continuous infusion or intermittent dosing of foscarnet. Moreover, there was no standardization of hydration strategies to minimize side effects. Eventually, intermittent foscarnet infusions became the standard of care; however, the true impact of hydration and infusion duration on nephrotoxicity has not been adequately studied, and the reports of foscarnet administration in HCT patients has been limited primarily to intermittent infusions. In this report, we characterize the administration of foscarnet as a 24-hour continuous infusion in both the inpatient and outpatient settings compared with intermittent infusion in HCT recipients. This retrospective, single-center, observational study at Stanford University Medical Center assessed HCT recipients who received foscarnet between January 2009 and May 2019. Twenty-eight of 45 patients (62.2%) who received continuous-infusion foscarnet experienced an acute kidney injury (AKI) as defined by the Kidney Disease Improving Global Outcomes classification, compared with 39 of 62 patients (62.9%) who received conventional infusion (P=.94). The average duration of outpatient antiviral days for the continuous infusion group was 9 days (range, 0 to 121 days), compared with 6.3 days (range, 0 to 70 days) in the intermittent infusion group (P=.54). Our findings suggest that foscarnet given as a continuous infusion or as an intermittent infusion have similar rates of adverse reactions, most notably similar rates of AKI. Administering foscarnet as a continuous infusion is a feasible option to facilitate outpatient treatment.

Evaluation of Meropenem‐Ciprofloxacin Combination Dosage Regimens for the Pharmacokinetics of Critically Ill Patients With Augmented Renal Clearance

Augmented renal clearance (ARC, creatinine clearance >130mL/min) makes difficult achievement of effective concentrations of renally cleared antibiotics in critically ill patients. This study examined the synergistic killing and resistance suppression for meropenem-ciprofloxacin combination dosage regimens against Pseudomonas aeruginosa isolates within the context of ARC. Clinically relevant meropenem and ciprofloxacin concentrations, alone and in combinations, were studied against three clinical isolates with a range of susceptibilities to each of the antibiotics. Isolate Pa1280 was susceptible to both meropenem and ciprofloxacin, Pa1284 had intermediate susceptibility to meropenem and was susceptible to ciprofloxacin, and CR380 was resistant to meropenem and had intermediate susceptibility to ciprofloxacin. Initially, isolates were studied in 72-h static-concentration time-kill studies (SCTK). Subsequently, the pharmacokinetic profiles expected in patients with ARC receiving dosage regimens, including at the highest approved daily doses (meropenem 6 g daily divided and administered as 0.5-h infusions every 8 h, or as a continuous infusion; ciprofloxacin 0.4 g as 1-h infusions every 8 h), were examined in a dynamic hollow-fiber infection model (HFIM) over 7-10 days. In both SCTK and HFIM, combination regimens were generally synergistic and suppressed growth of less-susceptible subpopulations, these effects being smaller for isolate CR380. The time-courses of total and less-susceptible bacterial populations in the HFIM were well described by mechanism-based models which enabled conduct of Monte Carlo simulations to predict likely effectiveness of approved dosage regimens at different creatinine clearances. Optimized meropenem-ciprofloxacin combination dosage regimens may be a viable consideration for P. aeruginosa infections in critically ill patients with ARC.

A Phase 1 Study of the Safety, Tolerability, and Pharmacokinetics of Biapenem in Healthy Adult Subjects.

The pharmacokinetics and safety of biapenem were studied in 36 healthy adult subjects in a randomized, placebo-controlled, double blind, sequential single and multiple-ascending dose study using doses from 250 to 1250 mg administered three times a day using 3-hour infusions. Maximum concentrations for biapenem were achieved at the end of the 3-hour infusion. Biapenem exposure (AUC) increased in a slightly greater than dose-proportional manner following single and multiple doses with no evidence of accumulation with multiple doses. Plasma AUCs increased from 18 mg*h/L at 250 mg to 150 mg*h/L at 1250 mg. Urinary recovery ranged from 14.2% at 250 mg to 42.3% at 1250 mg. Biapenem was well tolerated up to 1000 mg administered every 8 hours by 3-hour infusion for 7 days; however, a higher incidence of nausea, vomiting, and rash was reported at 1250 mg. There were no serious adverse events (SAEs) reported following either single or multiple doses of biapenem and all AEs were mild or moderate in severity.

Abstract P3: Andexanet Alfa for Acute Bleeding During Treatment With Edoxaban

Introduction: We previously reported results of a prospective cohort study evaluating andexanet alfa (andexanet) for anticoagulation reversal in patients with acute bleeding on a factor Xa inhibitor. Study enrollment continued to accumulate additional data on patients on edoxaban, which are presented here. Methods: Patients with acute major bleeding within 18 hours of edoxaban intake were prospectively enrolled. Patients received a 400 or 800 mg bolus and a 480 or 960 mg 2-hour follow-on infusion of andexanet, depending on edoxaban dosage and time of last dose. The co-primary efficacy outcomes were change in anti-factor Xa activity and the rate of excellent or good hemostasis, 12 hours after andexanet treatment, as determined by an independent adjudication committee. Efficacy was analyzed in patients with confirmed major bleeding and baseline anti-factor Xa activity ≥75 ng/mL. Safety was analyzed in all patients. Results: A total of 36 patients (mean age 82 years, 61.1% male and 91.7% with atrial fibrillation) with acute major bleeding on edoxaban received andexanet. The primary site of bleeding was intracranial in 29 (80.6%) patients. In the efficacy population (n=20), median anti-factor Xa activity decreased from 160.5 (interquartile range [IQR] 106.2-222.2) ng/mL at baseline to 50.9 (IQR 19.9-119.4) ng/mL at the end of bolus (median decrease 69.2%, 95% confidence interval [CI] 25.5-80.2%). Excellent or good hemostasis at 12 hours was achieved in 75.0% (95% CI 50.9-91.3%) of patients overall and in 81.3% (95% CI 54.4-96.0%) of those with intracranial hemorrhage (ICH). Within 30 days, a total of 4 (11.1%) patients experienced at least one thrombotic event and 4 (11.1%) others died. Conclusions: In patients with acute bleeding on edoxaban, andexanet significantly decreased anti-factor Xa activity. Excellent or good hemostasis at 12 hours was observed in 75.0% of patients overall and 81.3% of those with ICH. Thrombotic events occurred at a rate expected in such patients.

Treatment of Primary Aldosteronism Increases Plasma Epoxyeicosatrienoic Acids.

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RANDOMIZED PHASE III TRIAL COMPARING EPIRUBICIN/ DOXORUBICIN PLUS DOCETAXEL AND EPIRUBICIN/ DOXORUBICIN PLUS PACLITAXEL AS FIRST LINE TREATMENT IN WOMEN WITH ADVANCED BREAST CANCER

Background: The purpose of this study was to compare Epirubicin/ doxorubicin plus docetaxel and Epirubicin/ doxorubicin plus paclitaxel as first line treatment in women with advanced breast cancer.&#x0D; Patients and methods: previously untreated patients with advanced breast cancer randomly assigned to recieve Epirubicin 75mg/m2 and docetaxel 75 mg/m2 (ED) 1-hour intravenous (IV) infusion every 21 days, Epirubicin 75 mg/m2 and paclitaxel 175 mg/m2 (EP) 3-hour IV infusion every 21 days, Intravenous bolus injections of doxorubicin 50 mg/m2 and docetaxel 75 mg/m2 (DD) administered as a 1-hour intravenous infusion every 21 days and doxorubicin 50 mg/m2 and paclitaxel 175 mg/m2 (DP) administered as a 1-hour intravenous infusion every 21 days. Previous anthracycline-based neo-adjuvant chemotherapy was allowed if completed ? 1 year before entering the study.&#x0D; Results: Ten women patients were treated on arm ED &amp;EP and median TTP was 10 versus 11 months, 50 women patients were trated on DD &amp; DP cand median TTP was 8.5 versus 9 months respectively. Severe toxicity include grade 3-4 leukopenia (4% versus 2%), neutropenia (20% versus 22%) , anemia (38% versus 34%), thrombocytopenia (18% versus 24%), neurotoxicity (2% versus 6%) with DD and DP, respectively.&#x0D; Conclusion: The DD and DP regimens have similar efficacy but different toxicity. Either regimen can be used as front- line treatment of ABC. But in case of ED and EP regimen was difficult to compare the result due to very small sample size.&#x0D; Keywords: Epirubicin, doxorubicin, docetaxel, paclitaxel, advanced breast cancer, chemotherapy, neurotoxicity.

Intermittent outpatient administration of levosimendan improves right ventricular-pulmonary arterial coupling in ambulatory patients with advanced heart failure

Abstract Funding Acknowledgements Type of funding sources: None. Background Intermittent infusions of levosimendan in an outpatient setting have been associated with improved symptoms and reduced hospitalizations in patients with advanced heart failure (HF). Little is known on the potential effect of intermittent levosimendan infusions on right ventricle (RV)-pulmonary arterial (PA) coupling in ambulatory patients with advanced HF. Purpose Aim of the present study was to explore the effects of intermittent levosimendan infusions on the ratio between tricuspid annular plane systolic excursion (TAPSE) and pulmonary artery systolic pressure (PAPs), an echocardiographic measure of RV/PA coupling, in ambulatory patients with advanced HF, and on left ventricular arterial coupling (VAC), expressed as the relationship between arterial elastance (Ea) and ventricular elastance (Ees). Methods 17 ambulatory patients with advanced HF treated with intermittent levosimendan (6-hour intravenous infusion, 0.2 ug/kg/min without bolus) received baseline clinical, biochemical and echocardiographic evaluation and changes in TAPSE/PAPs ratio were assessed from baseline to 48 hours after the infusion, based on the pharmacokinetic profile of levosimendan. VAC, expressed as Ea/Ees ratio, was obtained by a calculator (iElastance) designed for non-invasive single beat measure of end-systolic Ees and Ea according to Chen"s method. Results After 48 hours from levosimendan infusion, there was a significant improvement of TAPSE/PAPs ratio (p = 0.04), stroke voume (SV) (p = 0.05) and cardiac output (CO)(p = 0.04). We observed a significant reduction of Ea (p = 0.007) and of Ees (p = 0.01) and a non significant improvement of VAC (p = 0.4)(Tab.1). Conclusion. Our results show that an intermittent 6-hour levosimendan infusion at 0.2 ug/kg/min improves after 48 hours RV-PA coupling, SV, CO, Ea and Ees in ambulatory patients with advanced HF. Further studies including more patients are necessary to confirm these preliminary findings. Tab.1 Baseline 48h afterlevosimendan infusion p value NT-proBNP (pg/mL) 5607 ± 4300 3868 ± 3856 &amp;lt;0.001 LVEF (%) 24.1 ± 7.7 25.7 ± 7.3 0.5 SV (mL) 36.8 ± 12.4 46.1 ± 14.8 0.05 CO (L/min)36.8 ± 12.4 2.6 ± 0.7 3.2 ± 0.9 0.05 TAPSE/PAPs (mm/mmHg) 0.38 ± 0.13 0.49 ± 0.16 0.04 Ea (mmHg/mL/m2) 2.9 ± 0.9 2.1 ± 0.6 0.007 Ees (mmHg/mL/m2) 1.3 ± 0.4 1.0 ± 0.2 0.01 VAC 2.2 ± 0.6 2.0 ± 0.4 0.4

24-Hour Levodopa-Carbidopa Intestinal Gel: Clinical Experience and Practical Recommendations.

Infusion of levodopa-carbidopa intestinal gel (LCIG; also designated carbidopa-levodopa enteral suspension) for 16 hours is a standard treatment for patients with advanced Parkinson’s disease, and clinical observations suggest that 24-hour LCIG infusion may further reduce symptoms. This review provides practical advice on the management of patients transitioning to 24-hour LCIG infusion. We review available clinical data for 24-hour infusion and discuss adjustments to dosing, recommendations for monitoring, and management of patient concerns, based on our clinical experience. Data from multiple studies suggest that LCIG may improve non-motor symptoms. Although few studies have examined 24-hour LCIG infusion, available data indicate that certain patients may benefit from around-the-clock treatment. Studies of 24-hour LCIG infusion are limited by small sample sizes and open-label study designs, which may hamper translation to clinical practice. In our experience, we have found that patients may benefit from 24-hour infusion when reductions in nocturnal symptoms and improvements to quality of sleep are needed. Levodopa-unresponsive freezing of gait or poorly controlled troublesome dyskinesias may also indicate a patient may benefit from 24-hour infusion. Dose adjustments, especially of the nocturnal rate, are typically necessary and, as with 16-hour infusion, patients should be monitored for autonomic dysfunction; overnight wearing off symptoms; weight changes; fluctuations in plasma levels of vitamins B6/B12, folate, and homocysteine; changes in sleep patterns; or worsening of hallucinations, delusions, and/or nightmares. Available data and our clinical experience suggest that 24-hour LCIG may be warranted among selected patients who have poorly controlled nocturnal fluctuations or early morning “off” symptoms.

Medication overuse headache: The effectivity of iv lidocaine - magnesium.

The detoxification process in medication overuse headache is the most difficult process for the patient. We aimed to investigate the effectiveness of the combination of low dose IV lidocaine and magnesium (100 mg lidocaine and 1.25 mg magnesium) in patients with medication overuse headache during the detoxification process. A total of 30 patients were included in the study; 15 received 24 hours of IV hydration, 15 received 1-hour lidocaine-magnesium infusion at the onset of pain in addition to the 24 hours of IV hydration. Headache severity (numeric rating scale, NRS), attack durations, onset of headache, monthly analgesic/triptan intakes, numbers of monthly headache days data were documented. We evaluated the severity of headache before and after daily treatment of two groups for one week. When both groups were compared, there was no significant difference in the pre-treatment NRS values, whe-reas, in the group receiving IV lidocaine-magnesium combination, there was a statistically significant decrease in the post-treatment NRS values in the first five days (p <0.05). An 1-hour combined infusion of lidocaine-magnesium may be considered as an alternative option for the patient to have a more quality detoxification process during the hospital stay, so that in parallel to the reduction in the use of multiple treatments (such as neuroleptics, benzodiazepines, antiemetics and opioids) and duration length of stay, the economic costs can also be reduced. The administration of combination will bring fewer side effects compared to their administration separately.

Malignant hyperthermia: a case report with good outcome.

Malignant hyperthermia: a case report with good outcome.

210. Vancomycin Infusion Frequency and Intensity: Analysis of Real-World Data Generated from Automated Infusion Devices

BackgroundAutomated infusion devices captures actual infused medication administration data in real-time. Vancomycin use is now recommended to be driven by AUC (area under the curve) dosing. We evaluated automated infusion device data to depict vancomycin administration practices in acute care hospitals.Figure 1. Distribution of vancomycin infusion dosing Figure 2. Distribution of time intervals between each vancomycin infusion session (mostly around 8 or 12 hours) MethodsWe analyzed archived vancomycin infusion data from 2,417 patients captured by automated infusion systems from 3 acute care hospitals. The infusion device informatics software recorded a variety of events during infusion – starting and stopping times, alarms and alerts, vancomycin dose, and other forms of timestamped usage information. We evaluated infusion session duration and dosing, using data-driven clustering algorithms.ResultsA total of 13,339 vancomycin infusion sessions from 2,417 unique adult patients were analyzed. Approximately 26.1% of patients had just one infusion of vancomycin. For the rest of the patients, the median number of infusion sessions per patient was 4; the interquartile range was 3 and 8. The most common dose was 1.0 gram (53.7%) or 1.5 gram (24.6%) (see Figure 1). The distribution of infusion session duration (hours) was 4.2% (≤1.0 hh); 40.1% (1.01–1.5 hh); 29.1% (1.51–2.0 hh); and 26.6% (>2.0 hh). The dosing frequency was 39.5% (q8 hh), 42.9% (q12 hh), 11.1% (q24 hh), and 6.5% (>q24 hh) (Figure 2), demonstrating clinical interpretability.ConclusionA considerable number of patients received just one vancomycin infusion during their hospital stay, suggesting a potential overuse of empiric vancomycin. The majority of infusion doses were between 1 to 1.5 grams and most infusion sessions were administered every 8 or 12 hours. The actual infusion duration for each dose often exceeds the prescribed 1- or 2-hour infusion orders, which may be due to known instances of infusion interruptions due to patient movement, procedures or IV access compromise. The data generated by infusion devices can augment insights on actual antimicrobial administration practices and duration. As vancomycin AUC dosing becomes more prevalent, real world infusion data may aid timely data-driven antimicrobial stewardship and patient safety interventions for vancomycin and other AUC dosed drugs.DisclosuresCynthia Yamaga, PharmD, BD (Employee) David L. Bostick, PhD, Becton, Dickinson and Co. (Employee) Ying P. Tabak, PhD, Becton, Dickinson and Co. (Employee) Ann Liu-Ferrara, PhD, Becton, Dickinson and Co. (Employee) Didier Morel, PhD, Becton, Dickinson and Co. (Employee) Kalvin Yu, MD, Becton, Dickinson and Company (Employee)GlaxoSmithKline plc. (Other Financial or Material Support, Funding)

Intravenous Infusion of the β3-Adrenergic Receptor Antagonist APD418 Improves Left Ventricular Systolic Function in Dogs With Systolic Heart Failure

BackgroundUnlike β1- and β2-adrenergic receptors (ARs), β3-AR stimulation inhibits cardiac contractility and relaxation. In the failing left ventricular (LV) myocardium, β3-ARs are upregulated, and can be maladaptive in the setting of decompensation by contributing to LV dysfunction. This study examined the effects of intravenous infusions of the β3-AR antagonist APD418 on cardiovascular function and safety in dogs with systolic heart failure (HF). Methods and ResultsThree separate studies were performed in 21 dogs with coronary microembolization-induced HF (LV ejection fraction [LVEF] of approximately 35%). Studies 1 and 2 (n = 7 dogs each) were APD418 dose escalation studies (dosing range, 0.35–15.00 mg/kg/h) designed to identify an effective dose of APD418 to be used in study 3. Study 3, the sustained efficacy study, (n = 7 dogs) was a 6-hour constant intravenous infusion of APD418 at a dose of 4.224 mg/kg (0.70 mg/kg/h) measuring key hemodynamic endpoints (e.g., EF, cardiac output, the time velocity integral of the mitral inflow velocity waveform representing early filling to time-velocity integral representing left atrial contraction [Ei/Ai]). Studies 1 and 2 showed a dose-dependent increase of LVEF and Ei/Ai, the latter being an index of LV diastolic function. In study 3, infusion of APD418 over 6 hours increased LVEF from 31 ± 1% to 38 ± 1% (P < .05) and increased Ei/Ai from 3.4 ± 0.4 to 4.9 ± 0.5 (P < .05). Vehicle had no effect on the LVEF or Ei/Ai. In study 3, APD418 had no significant effects on the HR or the systemic blood pressure. ConclusionsIntravenous infusions of APD418 in dogs with systolic HF elicit significant positive inotropic and lusitropic effects. These findings support the development of APD418 for the in-hospital treatment of patients with an acute exacerbation of chronic HF.

Intracellular vincristine levels in lymphoblasts affect treatment outcome in childhood B‐lymphoblastic leukaemia: Ma‐Spore ALL 2010 study

Vincristine (VCR) is a key drug in the successful multidrug chemotherapy for childhood acute lymphoblastic leukaemia (ALL). However, it remains unclear how VCR pharmacokinetics affects its antileukaemic efficacy. The objective of this study is to explore the VCR pharmacokinetic parameters and intracellular VCR levels in an up-front window of Ma-Spore ALL 2010 (MS2010) study. We randomised 429 children with newly diagnosed ALL to 15-minute vs 3-hour infusion for the first dose of VCR to study if prolonging the first dose of VCR infusion improved response. In a subgroup of 115 B-ALL and 20 T-ALL patients, we performed VCR plasma (n = 135 patients) and intracellular (n = 66 patients) pharmacokinetic studies. The correlations between pharmacokinetic parameters and intracellular VCR levels with early treatment response, final outcome and ABCB1 genotypes were analysed. There was no significant difference between 15-minute and 3-hour infusion schedules in median Day 8 peripheral or bone marrow blast response. Plasma VCR pharmacokinetic parameters did not predict outcome. However, in B-ALL, Day 33 minimal residual disease (MRD) negative patients and patients in continuous complete remission had significantly higher median intracellular VCR24h levels (P = .03 and P = .04, respectively). The median VCR24h intracellular levels were similar among the common genetic subtypes of ALL (P = .4). Patients homozygous for wild-type ABCB1 2677GG had significantly higher median intracellular VCR24h (P = .04) than 2677TT. We showed that in childhood B-ALL, the intracellular VCR24h levels in lymphoblasts affected treatment outcomes. The intracellular VCR24h level was independent of leukaemia subtype but dependent on host ABCB1 G2677T genotype.