Infusion Protocol Research Articles

Dapagliflozin Impairs the Suppression of Endogenous Glucose Production in Type 2 Diabetes Following Oral Glucose.

To examine the effect of SGLT2 inhibitors (SGLT2i) on endogenous glucose production (EGP) in patients with type 2 diabetes after an oral glucose load. Forty-eight patients with type 2 diabetes received an 8-h [3-3H]-glucose infusion (protocol I) to assess EGP response to: 1) dapagliflozin (DAPA), 10 mg; 2) exenatide (EXE), 5 μg s.c.; 3) DAPA/EXE; and 4) placebo (PCB). After 2 weeks (protocol II), patients were restudied with a 5-h double-tracer (i.v. [3-3H]-glucose and oral [1-14C]-glucose) oral glucose tolerance test (OGTT) preceded by PCB, DAPA, EXE, or DAPA/EXE. Protocol I: EGP decreased (P < 0.01) with PCB (2.16 ± 0.15 to 1.57 ± 0.08 mg/kg/min) and EXE (2.13 ± 0.16 to 1.58 ± 0.03) and remained unchanged (P = NS) with DAPA (2.04 ± 0.17 vs. 1.94 ± 0.18) and DAPA/EXE (2.13 ± 0.10 vs. 2.09 ± 0.03). During OGTT, EGP decreased (P < 0.01) with PCB (2.30 ± 0.05 to. 1.45 ± 0.06 mg/kg/min) and EXE (2.53 ± 0.08 to 1.36 ± 0.06); with DAPA (2.20 ± 0.04 vs. 1.71 ± 0.07) and DAPA/EXE (2.48 ± 0.05 vs. 1.64 ± 0.07), the decrease in EGP was attenuated (both P < 0.05). During OGTT, the insulin/glucagon (INS/GCN) ratio increased in PCB (0.26 ± 0.03 vs. 0.71 ± 0.06 μU/mL per pg/mL), whereas in DAPA (0.26 ± 0.02 to 0.50 ± 0.04), the increase was blunted (P < 0.05). In EXE, INS/GCN increased significantly (0.32 ± 0.03 to 1.31 ± 0.08) and was attenuated in DAPA/EXE (0.32 ± 0.03 vs. 0.78 ± 0.08) (P < 0.01). These findings provide novel evidence that the increase in EGP induced by SGLT2i is present during an oral glucose load. The fact that stimulation of EGP occurs despite elevated plasma insulin and glucagon suggests that additional factors must be involved.

P37 Variable adherence to and effectiveness of a vancomycin continuous infusion protocol within ICUs at a London tertiary-care hospital: a single-centre retrospective service evaluation

BackgroundAppropriate vancomycin dosing and therapeutic monitoring is important to optimize treatment for serious Gram-positive infections. In St George's Hospital ICUs, the treatment protocol is a loading dose (<65 kg, 1000 mg; ≥65 kg, 1500 mg), followed by a continuous infusion based on creatinine clearance (CLCR). Vancomycin serum concentrations are taken daily at 0600 hours (target therapeutic range 20–25 mg/L). Non-therapeutic concentrations may negatively affect clinical outcomes and prolong length of stay.1MethodsElectronic prescribing and medicine administration data (vancomycin dose, dose timings, indication, patient biochemistry and demographics) within a 66-bed ICU service were reviewed retrospectively (July 2020–July 2021). Cockcroft-Gault CLCR was calculated using total body weight (TBW), or adjusted body weight in obese1 patients.Standards(i) Proportion of patients with a therapeutic concentration within two serum samples; and (ii) time taken to achieve therapeutic concentration.ResultsNinety-four percent (51/54) of patients received a correct protocol instructed loading dose, 31% (17/54) received a correct loading and maintenance dose, and 70% (38/54) had a vancomycin serum concentration taken. Forty-one percent (7/17) of correctly protocol dosed and monitored patients were therapeutic at their first day serum concentration, which decreased to 20% (3/15) by their second day serum concentration. Consistently therapeutically dosed patient groups included obese and normal weight patients with CLCR 10–20 mL/min and 21–50 mL/min. Whereas underweight and obese patients with CLCR >50 mL/min and 21–50 mL/min became supratherapeutic by their second day serum concentration. Obese and normal weight patients with CLCR >50 mL/min were consistently subtherapeutic. The mean time taken for non-therapeutic patients who continued treatment (n = 7) to become therapeutic after dose adjustments was 4 days. Patients (n = 17) were 82% male and of a mean age of 62 ± 17 years. Mean TBW was 79 ± 23 kg and mean CLCR 65 ± 48 mL/min. Sepsis was the most common vancomycin indication (65%).ConclusionsMultiple drug recording formats, plus adherence to and dosing of different aspects of the vancomycin protocol, requires review. This is to ensure accurate vancomycin administration documentation and that therapeutic concentrations are achieved more rapidly and consistently, whilst minimizing toxicity. A quality improvement project has been instigated to focus on protocol education, accessibility and improving IT infrastructure. Increased patient volume of distribution and renal function variability within the ICU population adds complexity to vancomycin pharmacokinetics. Research into pharmacokinetic models better representing the local ICU population and AUC24 drug monitoring is being explored based on recent international guidance.1

Safety and Efficacy of an Intensive Care Insulin Infusion Protocol Targeting a Blood Glucose of 140 to 180 mg/dL.

Despite multiple guideline recommendations of a goal blood glucose of 140 to 180 mg/dL in critically ill patients, no insulin infusion protocols (IIPs) targeting this range have been validated and published in the literature. The purpose of this study is to determine the safety and efficacy of an IIP targeting a blood glucose of 140 to 180 mg/dL in critically ill patients, with the ultimate goal of validating such a protocol. This retrospective chart review uses data of critically ill patients admitted from August 2018 to December 2018. Patient data from August 2017 to December 2017 served as a historical comparator to further assess safety outcomes. Percent of blood glucose readings within goal was the primary outcome measurement. Relevant clinical variables, insulin requirements, hypoglycemic events, and protocol adherence were also recorded. A total of 88 insulin infusions were included in analysis, 34 of which served as a historical comparator. In the IIP targeting a blood glucose 140 to 180 mg/dL, once blood glucose levels decreased below 180 mg/dL, 54% of blood glucose readings were within goal (140-180 mg/dL) and 73% of blood glucose readings were within a "clinically acceptable" range (110-180 mg/dL). The number of hypoglycemic events decreased from 70 in the historical comparator group to 4 in the current IIP (P < .0001). This IIP is both safe and effective at targeting a blood glucose of 140 to 180 mg/dL and could be used at other institutions to achieve satisfactory glycemic control.

Optimal regulation of tumour-associated neutrophils in cancer progression.

In a tumour microenvironment, tumour-associated neutrophils could display two opposing differential phenotypes: anti-tumour (N1) and pro-tumour (N2) effector cells. Converting N2 to N1 neutrophils provides innovative therapies for cancer treatment. In this study, a mathematical model for N1-N2 dynamics describing the cancer survival and immune inhibition in response to TGF-β and IFN-β is considered. The effects of exogenous intervention of TGF-β inhibitor and IFN-β are examined in order to enhance N1 recruitment to combat tumour progression. Our approach employs optimal control theory to determine drug infusion protocols that could minimize tumour volume with least administration cost possible. Four optimal control scenarios corresponding to different therapeutic strategies are explored, namely, TGF-β inhibitor control only, IFN-β control only, concomitant TGF-β inhibitor and IFN-β controls, and alternating TGF-β inhibitor and IFN-β controls. For each scheme, different initial conditions are varied to depict different pathophysiological condition of a cancer patient, leading to adaptive treatment schedule. TGF-β inhibitor and IFN-β drug dosages, total drug amount, infusion times and relative cost of drug administrations are obtained under various circumstances. The control strategies achieved could guide in designing individualized therapeutic protocols.

Wharton's jelly-derived stromal cells and their cell therapy applications in allogeneic haematopoietic stem cell transplantation.

For decades, mesenchymal stromal cells (MSCs) have been of great interest in the fields of regenerative medicine, tissue engineering and immunomodulation. Their tremendous potential makes it desirable to cryopreserve and bank MSCs to increase their accessibility and availability. Postnatally derived MSCs seem to be of particular interest because they are harvested after delivery without ethical controversy, they have the capacity to expand at a higher rate than adult‐derived MSCs, in which expansion decreases with ageing, and they have demonstrated immunological and haematological supportive properties similar to those of adult‐derived MSCs. In this review, we focus on MSCs obtained from Wharton's jelly (the mucous connective tissue of the umbilical cord between the amniotic epithelium and the umbilical vessels). Wharton's jelly MSCs (WJ‐MSCs) are a good candidate for cellular therapy in haematology, with accumulating data supporting their potential to sustain haematopoietic stem cell engraftment and to modulate alloreactivity such as Graft Versus Host Disease (GVHD). We first present an overview of their in‐vitro properties and the results of preclinical murine models confirming the suitability of WJ‐MSCs for cellular therapy in haematology. Next, we focus on clinical trials and discuss tolerance, efficacy and infusion protocols reported in haematology for GVHD and engraftment.

The effectiveness and safety of corticosteroid therapy for IgA nephropathy with crescents: a prospective, randomized, controlled study

BackgroundPozzi protocol (methylprednisolone intravenous infusion in 1st-3rd-5th months and oral steroid for 6 months) has been thought to be the classic therapy for IgA nephropathy (IgAN) patients with proteinuria> 1.0 g/24 h. There is no consensus on the treatments for IgAN with active pathological changes, especially for IgAN patients with crescents proportion < 50%. This study aimed to evaluate the effectiveness and safety of the treatment protocol of methylprednisolone intravenous infusion at the 1st-2nd-3rd months for IgAN patients with crescents.MethodsIn this prospective, randomized, controlled, non-blind study, 68 IgAN patients with crescents proportion < 50% were divided into the 1–2-3 group receiving 0.25 g/d methylprednisolone intravenously for 3 consecutive days in the 1st-2nd-3rd months, and oral prednisone 0.5 mg/kg/d on consecutive days for 6 months and the 1–3-5 group with the same intravenous methylprednisolone treatment in the 1st-3rd-5th months, and the same oral prednisone. The primary outcome measure was remission of proteinuria (complete or partial); while the secondary outcome measures were deterioration of renal function (evidenced by a 50% rise from baseline serum creatinine levels, or a 25% decline from baseline eGFR levels).ResultsThere was no significant difference in incidence of crescents (median 14.66% vs. 11.45%, p = 0.143) between the 1–2-3 and 1–3-5 groups. From month 1 to month 6, there was a decreasing trend in the levels of urine protein and serum creatinine and an increasing trend in eGFR in both groups. The mean period of remission in the 1–2-3 group seemed shorter. Overall, there were 55 (80.89%) patients meeting remission. The rates of remission in the 1–2-3 group and 1–3-5 group were 85.3 and 76.47%, respectively (P = 0.644). The 1–2-3 group had lower creatinine and higher eGFR than the 1–3-5 group, but the difference was not significant. The complication rate was 11.11 and 15.79% in the two groups, respectively. There was no significant difference in the complications between groups.ConclusionsBoth the 1st-3rd-5th and 1st-2nd-3rd protocols can effectively alleviate proteinuria and protect renal function in IgAN patients with crescents but the 1st-2nd-3rd protocol seemed to have better effectiveness.Trial registrationClinicalTrials.gov, Identifier: NCT02160132, Registered June 10, 2014.

Simplified Graded Infusion Strategy for Mitigation of Oxaliplatin Hypersensitivity

BackgroundHypersensitivity reactions (HSRs) to oxaliplatin present a therapeutic challenge. The standard desensitization protocol consists of 12 infusion steps with 3 drug dilutions, often in an inpatient setting. Several years ago we implemented a simplified outpatient graded infusion protocol for oxaliplatin with 2 drug dilutions and 3 infusion steps. Materials and MethodsWe performed a retrospective analysis of our experience to define the safety and outcomes associated with this simplified, ambulatory, graded infusion strategy. ResultsBetween January 1, 2011 and December 1, 2020, 374 patients who had experienced an oxaliplatin-related HSR were treated via a 3-step graded infusion in the outpatient setting. Of these 374 patients, 283 (76%) did not experience a subsequent HSR, while 91 (24%) did experience a breakthrough HSR. Of the 374 patients, 19 (5%) experienced a grade 3 or 4 HSR. Three patients (0.8%) were hospitalized. There was no grade 5 (fatal) HSRs. Overall, the 374 patients received a median additional 3 cycles of oxaliplatin (range 1-41). The most common reasons for treatment discontinuation were disease progression (35%), breakthrough HSRs (24%), completion of treatment (21%), and toxicity other than HSR (20%). Fifteen patients who experienced breakthrough HSRs during a graded infusion were subsequently treated with the standard 12-step desensitization. Five of these 15 patients had an HSR during their initial desensitization and 5 developed an HSR on subsequent 12-step desensitizations. Thus, treatment was discontinued in 67% of these 15 patients due to persistent HSRs. ConclusionOur data indicate that the simplified 3-step graded infusion protocol is a safe outpatient strategy for patients with a history of HSR to oxaliplatin.

Clinical grade production of IL-15 stimulated NK cells for early infusion in adult AML patients undergoing haploidentical stem cell transplantation with post-transplant cyclophosphamide.

Allogeneic stem cell transplantation is the treatment of choice for acute myeloid leukemia (AML) patients. Unmanipulated haploidentical transplantation (Haplo-HSCT) is commonly used for those AML patients who need a timely transplant and do not have a suitable matched donor, but relapse rates are still high, and improvements are needed. Adoptive immunotherapy using natural killer cells (NK cells) could be a promising tool to improved Haplo-HSCT but, to date, no optimal infusion and manufacturing protocols have been developed. In this study, we describe a quick and reproducible protocol for clinical-grade production of haploidentical donor NK cells using double immunomagnetic depletion and enrichment protocol and overnight IL-15 stimulation. Thus, we have obtained 8 viable and functional NK cell products that have been safely infused to five AML patients undergoing unmanipulated Haplo-HSCT. Our results demonstrate the safety and feasibility of manufactured NK IL15 cells obtained from an adult allogeneic donor in the setting of haploidentical transplantation for AML patients.

Delaying an infliximab infusion by more than 3 days is associated with a significant reduction in trough levels but not with clinical worsening

Background:Higher infliximab trough levels (TLs) correlate with better clinical, inflammatory, and endoscopic outcomes among inflammatory bowel disease (IBD) patients. Although standard scheduled infliximab therapy regimen consists of infusions at pre-defined time-points (weeks 0, 2, 6, and every 8 weeks), short-period deviations from therapeutic schedule are common in ‘real life’, but the pharmacokinetic impact of these deviations has not been explored. In this study, we aim to determine whether short-period deviations from infusion schedule affect infliximab-TL.Methods:A retrospective analysis of all IBD patients receiving infliximab maintenance therapy every 8 weeks was conducted in a tertiary medical center. Patients with anti-drug antibodies, deliberate interval shortening and <3 sequential maintenance sera available were excluded. Associations between time since last infusion and TL were studied. Statistical analysis was performed using generalized estimating equations.Results:Out of over 10,000 sera, 2088 sera of 302 maintenance period stable infliximab-therapy-patients met inclusion criteria (median TL 4.1 μg/mL, interquartile range (IQR) 2.3–6.5 μg/mL). A delay beyond 3 days in infusion schedule (n > 59 days since last infusion) was found to significantly affect TL (mean difference in TL 0.9 μg/mL, 95% confidence interval (CI): 0.03–1.9 μg/mL, p < 0.04). Furthermore, among patients with delayed infusions, 80% had TL below 5 μg/mL, in comparison to 55% of patients who were not late (odds ratio (OR): 2.81, CI: 2.02–3.92, p < 0.0001).Conclusion:Real-life delays of ⩽3 days from infusion protocol can probably be allowed. Delays >3 days culminate in measurable decrease of TL, although effect on clinical outcome is unclear. This needs to be taken into account when interpreting drug-level test results.Summary:A total of 2088 sera of 302 maintenance period inflammatory bowel disease (IBD) patients treated with infliximab were analyzed, to assess effect of small deviations from infusion schedule on TLs. A significant decline in patients’ trough level (TL) was noted as early as 3 days after scheduled infusion.

Sedation with dexmedetomidine and propofol in children with Fontan circulation undergoing cardiac catheterization: A descriptive study.

Background:A combination of dexmedetomidine and propofol is considered advantageous for maintaining spontaneous breathing with a satisfactory depth of anesthesia. However, the incidence of upper airway obstruction under sedation with dexmedetomidine and propofol in patients with Fontan circulation remains unanswered. This study aimed to evaluate upper airway patency and oxygen desaturation during sedation with dexmedetomidine and propofol for cardiac catheterization in pediatric patients with Fontan circulation.Methods:In this descriptive study, we reviewed medical records of patients with Fontan circulation who underwent cardiac catheterization between December 2018 and August 2020 at a single-center 200-bed academic children's hospital in Japan.Results:A total of 35 patients with Fontan circulation sedated with a departmental protocol of dexmedetomidine and propofol infusion for cardiac catheterization were reviewed. Overall, the incidence of airway interventions and oxygen desaturation were 31.4% and 28.6%, respectively. In children with a history of snoring and additional use of intravenous midazolam, the rates of airway interventions were 50% and 100%, respectively. In patients ≤2 years old with recent upper respiratory infection (URI) symptoms, oxygen desaturation rate was 75%.Conclusions:In children with Fontan circulation, the incidence rate of upper airway obstruction was high under sedation with dexmedetomidine and propofol during cardiac catheterization, which is commonly considered safe in children without Fontan circulation. A history of snoring, an additional bolus of IV midazolam, and the presence of recent URI symptoms in patients ≤2 years old are potential risks for upper airway obstruction.

Antithrombin III infusion improves anticoagulation in congenital diaphragmatic hernia patients on extracorporeal membrane oxygenation.

Achieving effective anticoagulation during neonatal extracorporeal membrane oxygenation (ECMO) without increasing the risk of hemorrhage remains challenging. The use of antithrombin III (AT-III) for this purpose has been examined, but studies have been limited to intermittent bolus dosing. We aimed to evaluate the efficacy and safety of an institutionally developed AT-III continuous infusion protocol in neonates receiving ECMO for the treatment of congenital diaphragmatic hernia (CDH). In this single center, retrospective study, all neonates with a CDH who received ECMO support during the study period were included. Data on anticoagulation labs and therapy, life-threatening bleeding, and circuit changes were analyzed. Eleven patients were divided into two groups: patients with AT-III continuous infusion (n = 5) and without (n = 6). There were no differences in the gestational age (p = 0.29), sex (p = 1.00), ECMO duration (p = 0.59), or initial AT-III levels (p = 0.76) between groups. Patients in the AT-III infusion group had on average 18.5% higher AT-III levels (p < 0.0001). Patients receiving continuous AT-III infusions spent a significantly higher percentage of ECMO time within the therapeutic range, measured using anti-Factor Xa levels (64.9±4.2% vs. 29.1±8.57%, p = 0.008), and required fewer changes to the heparin infusion rate (6.48±0.88 vs 2.38±0.36 changes/day changes/day, p = 0.005). Multivariate analysis revealed continuous infusion of AT-III did not increase the rate of intracranial or surgical bleeding (p = 0.27). AT-III as a continuous infusion in CDH neonates on ECMO provides a decreased need to modify heparin infusion and more consistent therapeutic anticoagulation without increasing the risk of life-threatening bleeding.

Evaluation of Butorphanol-lidocaine-ketamine and fentanyl-lidocaine-ketamine constant rate infusion protocols for pain management in small animal orthopaedic patients

Butorphanol-Lidocaine-Ketamine and Fentanyl-Lidocaine-Ketamine constant rate infusion (CRI) protocols for pain management in small animal orthopaedic patients have not been well-documented in the literature. The present study aimed to define the optimal dosage of these combinations for CRI in dogs for pain management and its effects on physiological body parameters.

Endogenous Oxalate Production in Primary Hyperoxaluria Type 1 Patients.

Primary hyperoxaluria type 1 (PH1) is an inborn error of glyoxylate metabolism, characterized by increased endogenous oxalate production. The metabolic pathways underlying oxalate synthesis have not been fully elucidated, and upcoming therapies require more reliable outcome parameters than the currently used plasma oxalate levels and urinary oxalate excretion rates. We therefore developed a stable isotope infusion protocol to assess endogenous oxalate synthesis rate and the contribution of glycolate to both oxalate and glycine synthesis in vivo . Eight healthy volunteers and eight patients with PH1 (stratified by pyridoxine responsiveness) underwent a combined primed continuous infusion of intravenous [1- 13 C]glycolate, [U- 13 C 2 ]oxalate, and, in a subgroup, [D 5 ]glycine. Isotopic enrichment of 13 C-labeled oxalate and glycolate were measured using a new gas chromatography-tandem mass spectrometry (GC-MS/MS) method. Stable isotope dilution and incorporation calculations quantified rates of appearance and synthetic rates, respectively. Total daily oxalate rates of appearance (mean [SD]) were 2.71 (0.54), 1.46 (0.23), and 0.79 (0.15) mmol/d in patients who were pyridoxine unresponsive, patients who were pyridoxine responsive, and controls, respectively ( P =0.002). Mean (SD) contribution of glycolate to oxalate production was 47.3% (12.8) in patients and 1.3% (0.7) in controls. Using the incorporation of [1- 13 C]glycolate tracer in glycine revealed significant conversion of glycolate into glycine in pyridoxine responsive, but not in patients with PH1 who were pyridoxine unresponsive. This stable isotope infusion protocol could evaluate efficacy of new therapies, investigate pyridoxine responsiveness, and serve as a tool to further explore glyoxylate metabolism in humans.

Effect of Glucose-Insulin-Potassium Infusion on Hemodynamics in Patients with Septic Shock

BACKGROUND: Glucose-insulin-potassium (GIK) demonstrates a cardioprotective effect by providing metabolic support and anti-inflammatory action, and may be useful in septic myocardial depression. AIM: The aim of this study was to assess role of GIK infusion in improving hemodynamics in patients with septic shock in addition to its role in myocardial protection and preventing occurrence of sepsis-induced myocardial dysfunction and sepsis-induced arrhythmias. METHODS: This study was conducted on 75 patients admitted to the Critical Care Department in Cairo University Hospital with the diagnosis of septic shock during the period from January 2019 to December 2019. Patients were divided into two groups; first group was managed according to the last guidelines of surviving sepsis campaign and was subjected to the GIK infusion protocol while second group was managed following the last guidelines of surviving sepsis campaign only without adding GIK infusion. RESULTS: Patients in the GIK group showed better lactate clearance (50% vs. 46.7%) and less time needed for successful weaning of vasopressors than the control group (3.57±1.16 vs. 3.6±1.45 days) thought not reaching statistical significance. There was no statistically significant difference between both groups regarding development of septic-induced cardiomyopathy (16.7% in the control group vs. 13.3% in the GIK group); however, patients with hypodynamic septic shock showed better improvement in hemodynamic profile in the GIK group. Sepsis-induced arrhythmias occurred more in patients of the control group than in patients of the GIK group with no statistically significant difference between both groups (33.3% vs. 20%, p = 0.243). Few side effects were developed as a result of using GIK infusion protocol. CONCLUSIONS: GIK may help in improving hemodynamics and weaning of vasopressors in patients with refractory septic shock and those with septic induced cardiomyopathy. The use of GIK was well tolerated with minimal adverse reactions.

Evaluation of heparin infusion rates in patients with intravenous drug misuse.

To evaluate the hypothesis that patients with a history of intravenous drug misuse (IVDM) initiated on weight-based heparin infusions require higher than expected infusion rates to achieve therapeutic activated partial thromboplastin time (aPTT). This study is a multicenter, retrospective chart review of patients with a history of IVDM who were admitted to an acute care site between 10/1/2015 and 9/30/2020 and treated with continuous heparin infusions. Patients were identified using ICD9 and ICD10 codes and included if they had a documented history of IVDM within the past six months. Variables of particular interest included: median heparin infusion rates to maintain therapeutic aPTT, average time to reach therapeutic aPTT, and International Society of Thrombosis and Haemostasis Criteria for moderate to severe bleeding. Of the 41 patients who met the inclusion and exclusion criteria, 39 achieved therapeutic aPTT while on a weight-based heparin infusion. All heparin infusions were initiated at a rate of 18 units/kg/hr then titrated per institutional heparin infusion protocols. The mean time to therapeutic aPTT was 38.48 h ± 26.4 h with a mean infusion rate of 27.64 ± 7.14 units/kg/hr. To maintain therapeutic anticoagulation, infusion rates 150% higher than the initial rate were required. Of the 39 patients who achieved therapeutic aPTT, 85% (33) met criteria for heparin resistance, defined as greater than 35,000 units of heparin daily. No statistical significance could be derived from this retrospective chart review as therapeutic heparin rates were evaluated in comparison to initial infusion rate, rather than a control group. The findings in this study demonstrate a possible clinical association of the reduced antithrombin activity previously described in opiate misusers. To efficiently achieve therapeutic anticoagulation, it may be appropriate to consider use of heparin antiXa monitoring in place of aPTT or utilization of increased initial heparin infusion rates.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11239-021-02615-z.

Non-wetting Liquid-Infused Slippery Paper.

Liquid-infused slippery surfaces have replaced structural superhydrophobic surfaces in a plethora of emerging applications, hallmarked by their favorable self-healing and liquid-repelling characteristics. Their ease of fabrication on different types of materials and increasing demand in various industrial applications have triggered research interests targeted toward developing an environmental-friendly, flexible, and frugal substrate as the underlying structural and functional backbone. Although many expensive polymers such as polytetrafluoroethylene have so far been used for their fabrication, these are constrained by their compromised flexibility and non-ecofriendliness due to the use of fluorine. Here, we explore the development and deployment of a biodegradable, recyclable, flexible, and an economically viable material in the form of a paper matrix for fabricating liquid-infused slippery interfaces for prolonged usage. We show by controlled experiments that a simple silanization followed by an oil infusion protocol imparts an inherent slipperiness (low contact angle hysteresis and low tilting angle for sliding) to the droplet motion on the paper substrate and provides favorable anti-icing characteristics, albeit keeping the paper microstructures unaltered. This ensures concomitant hydrophobicity, water adhesion, and capillarity for low surface tension fluids, such as mustard oil, with an implicit role played by the paper pore size distribution toward retaining a stable layer of the infused oil. With demonstrated supreme anti-icing characteristics, these results open up new possibilities of realizing high-throughput paper-based substrates for a wide variety of applications ranging from biomedical unit operations to droplet-based digital microfluidics.

A Novel Protocol for Rituximab Administration with Reduced Incidence of Severe Infusion-Related Adverse Reactions in Patients with B-Cell Non-Hodgkin Lymphoma

Introduction: Rituximab is widely used as the standard treatment for most types of B-cell non-Hodgkin lymphomas (B-NHL). However, infusion-related reactions (IRRs), such as fever, chills, nausea, rashes, rigors, or hypotension, are a significant burden to patients and oncology practitioners. Thus, we developed a novel protocol on the rituximab administration to avoid severe IRRs during a short-time infusion in the outpatient chemotherapy center of Nihon University Itabashi Hospital.Methods: This observational study aimed to establish an effective dosing schedule for safely administering rituximab within a short time for patients with various B-NHL types. Rituximab was diluted to a concentration of 1 mg/mL and intravenously administered to patients at a dose of 375 mg/m 2. Before the rituximab administration, prophylactic premedications were given per guidelines. We stratified patients into low (n = 0), moderate (n = 1), or high risk (n = 2) groups according to the observed number of risk factors for IRRs identified in our previous study, i.e., indolent histology and presence of bulky disease (>10cm) (Hayama et al. 2017, PMID: 28144804). In the low- and moderate-risk groups, the infusion rate of rituximab was set at 25 mg/h (first 1h), 100 mg/h (next 1h), and a maximum of 200 mg/h thereafter (conventional infusion #1, approx. 4.3h). In the high-risk group, the infusion rate of rituximab was set at 25 mg/h (first 1h) and a maximum of 100 mg/h thereafter (long infusion, approx. 6.8h). The second infusion of rituximab was dependent on the occurrence of IRRs in the first cycle. If a patient in the low-risk group did not have IRRs in the first cycle, the infusion rate of rituximab in the second cycle was then started at 100 mg/h for the first 30min and increased by 100 mg/h every 30min to a maximum of 400 mg/h thereafter (short infusion, approx. 2.3h). Also, for a patient in the moderate-risk group without any grade of IRRs in the first cycle, the infusion rates of second rituximab was set at 100 mg/h (first 1h) and a maximum of 200 mg/h thereafter (conventional infusion #2, approx. 3.5h). Finally, a patient in the high-risk group without IRRs in the first cycle received the second rituximab as per the conventional infusion #1. If patients experienced any grades of IRR in the first cycle, the next rituximab was administered on the same schedule as the first cycle. The infusion procedure for the third cycle was at the discretion of attending physicians (Figure). The primary endpoint was the incidence of IRRs during the first and second doses of rituximab in each risk group. The secondary endpoints were; overall incidence of IRRs in the first and second doses of rituximab; infusion rates of rituximab at the IRRs; conversion rate of the short infusion at the third cycle in each group; overall conversion rate of the short infusion at the third cycle.Results: A total of 81 B-NHL patients treated with rituximab in 2018 and 2019 at Nihon University Itabashi Hospital was evaluated. The incidence of IRRs during the first and second cycles in each risk group was 31%, 20%, and 57% in the low- (n = 39), moderate- (n = 35), and high-risk (n = 7) groups, respectively, with no significant difference among the three risk groups (p = 0.1407). The overall incidence of IRRs was 28% without grade 3 or higher severity. The IRRs occurred most frequently at the infusion rate of 100 mg/h (n = 16). Conversion rates to the short infusion at the third cycle of rituximab were 82%, 29%, and 29%, in the low-, moderate-, and high-risk groups, respectively, with a significant imbalance between the groups (p <0.0001). The overall conversion rate of the short infusion in the third cycle was 54%, without any grades of IRRs (Table).Conclusions: Our step-by-step infusion protocol of rituximab provided a safe and comfortable drug administration for both patients and oncology practitioners. In addition, the protocol can reduce unexpected, severe adverse reactions to rituximab that typically require hospital admission and medical expenses (UMIN-CTR, UMIN000032309). [Display omitted] DisclosuresMiura: Chugai: Honoraria; Kyowa Kirin: Honoraria. Hatta: Pfizer Japan Inc.: Honoraria; Novartis KK: Honoraria; Bristol-Myers Squibb: Honoraria; Otsuka Pharmaceutical.: Honoraria.

Task-evoked simultaneous FDG-PET and fMRI data for measurement of neural metabolism in the human visual cortex

Understanding how the living human brain functions requires sophisticated in vivo neuroimaging technologies to characterise the complexity of neuroanatomy, neural function, and brain metabolism. Fluorodeoxyglucose positron emission tomography (FDG-PET) studies of human brain function have historically been limited in their capacity to measure dynamic neural activity. Simultaneous [18 F]-FDG-PET and functional magnetic resonance imaging (fMRI) with FDG infusion protocols enable examination of dynamic changes in cerebral glucose metabolism simultaneously with dynamic changes in blood oxygenation. The Monash vis-fPET-fMRI dataset is a simultaneously acquired FDG-fPET/BOLD-fMRI dataset acquired from n = 10 healthy adults (18–49 yrs) whilst they viewed a flickering checkerboard task. The dataset contains both raw (unprocessed) images and source data organized according to the BIDS specification. The source data includes PET listmode, normalization, sinogram and physiology data. Here, the technical feasibility of using opensource frameworks to reconstruct the PET listmode data is demonstrated. The dataset has significant re-use value for the development of new processing pipelines, signal optimisation methods, and to formulate new hypotheses concerning the relationship between neuronal glucose uptake and cerebral haemodynamics.

Nine year experience of the Northern Ireland Inherited Cardiac Conditions Service (NI ICC of slow vs. rapid ajmaline infusion protocols for the diagnosis of Brugada syndrome (BrS)

Abstract Background BrS is diagnosed in patients with ST-segment elevation with type1 morphology ≥2mm in one or more leads among the right precordial leads V1 and/or V2 positioned in the second, third or fourth intercostal space, occurring either spontaneously or after provocative drug test with intravenous administration of sodium channel blockers (ie. ajmaline, flecainide, procainamide or pilsicainide). The specific protocol for Ajmaline provocation testing for diagnosis of BrS has been debated between ICC services worldwide. Concerns regarding safety and false positive rates are perceived to be associated with a more rapid infusion protocol. This retrospective observational cohort study describes the safety and positivity rates for patients undergoing ajmaline provocation challenge by both protocols over nine years. Method Consecutive adults undergoing ajmaline challenge test from Mach 2011 to Feb 2020 were retrospectively collected. Data on patient demographics, indication for testing, genetic information, adverse events and positivity rates were compared by test protocol used. Slow protocol was defined as total dose of 1mg/kg ajmaline capped at 100mg given at rate of 10mg/min over 10 minutes. Rapid protocol was defined as 1mg/kg ajmaline capped at 100mg given over 5 minutes. Results A total of 350 ajmaline challenges were included (275 (73%) slow vs. 75 (27%) rapid protocol) [Mean age 40±15 years; 53% male]. Indication for conducting the test was a) Family history of Brugada syndrome 164 (43%) b) Family history of SADS/SUD 103 (28%), c) OOHCA 22 (6%) d) abnormal ECG 39 (11%) and e) syncope 22 (6%). Among the positive test group, average time for test positivity is 5.92 minutes and average dose was 55mgs (p&amp;lt;0.05). There were no differences between positivity rate between the two protocols, group A vs. group B, p=0.45, ns. Comparison between all patients with positive vs. negative results regardless of the protocol, showed no statistical differences. Predominantly male in both groups (p=0.71, ns) and mean age of patients in their 40's (p=0.93, ns). There is a trend that positive patients likely to have family history of BrS p=0.08, ns). 2 patients had experience jaundice at later stage which resolved. Conclusion In NI ICC service to date, we have performed 350 Ajmaline test over the last nine years. Our positivity rate was 21% (75/350). We did not identify any significant evidence of ventricular dysrhythmia (0) or QRS broadening (2) that resulting in early termination of the protocol. Abnormal ECG with absence of symptoms yields low. Therefore we will continue fast protocol in our service for efficiency in our unit. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): Belfast Health and Social Care TrustCormac Felowship

Rapid infusion protocol of iron polymaltose saves cost in management of iron deficiency anaemia

Rapid infusion protocol of iron polymaltose saves cost in management of iron deficiency anaemia