Safety and Tolerability of Manual Push Administration of Subcutaneous IgPro20 at High Infusion Rates in Patients with Primary Immunodeficiency: Findings from the Manual Push Administration Cohort of the HILO Study

Abstract Purpose To evaluate the safety and tolerability of IgPro20 manual push (also known as rapid push) infusions at flow rates of 0.5–2.0 mL/min. Methods Patients with primary immunodeficiency (PID) with previous experience administering IgPro20 (Hizentra®, CSL Behring, King of Prussia, PA, USA) were enrolled in the Hizentra® Label Optimization (HILO) study (NCT03033745) and assigned to Pump-assisted Volume Cohort, Pump-assisted Flow Rate Cohort, or Manual Push Flow Rate Cohort; this report describes the latter. Patients administered IgPro20 via manual push at 0.5, 1.0, and 2.0 mL/min/site for 4 weeks each. Responder rates (percentage of patients who completed a predefined minimum number of infusions), safety outcomes, and serum immunoglobulin G (IgG) trough levels were evaluated. Results Sixteen patients were treated; 2 patients (12.5%) discontinued at the 1.0-mL/min level (unrelated to treatment). Responder rates were 100%, 100%, and 87.5% at 0.5-, 1.0-, and 2.0-mL/min flow rates, respectively. Mean weekly infusion duration decreased from 103–108 to 23–28 min at the 0.5- and 2.0-mL/min flow rates, respectively. Rates of treatment-related treatment-emergent adverse events (TEAEs) per infusion were 0.023, 0.082, and 0.025 for the 0.5-, 1.0-, and 2.0-mL/min flow rates, respectively. Most TEAEs were mild local reactions and tolerability (infusions without severe local reactions/total infusions) was 100% across flow rate levels. Serum IgG levels (mean [SD]) were similar at study start (9.36 [2.53] g/L) and end (9.58 [2.12] g/L). Conclusions Subcutaneous IgPro20 manual push infusions at flow rates up to 2.0 mL/min were well tolerated and reduced infusion time in treatment-experienced patients with PID. Trial Registration NCT03033745

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Safety and Tolerability of Subcutaneous IgPro20 at High Infusion Parameters in Patients with Primary Immunodeficiency: Findings from the Pump-Assisted Administration Cohorts of the HILO Study

Journal of Clinical Immunology ◽

10.1007/s10875-020-00912-5 ◽

2021 ◽

Author(s):

John T. Anderson ◽

Vincent R. Bonagura ◽

Juthaporn Cowan ◽

Connie Hsu ◽

S. Shahzad Mustafa ◽

...

Keyword(s):

Adverse Events ◽

Injection Site ◽

Primary Immunodeficiency ◽

Flow Rate ◽

Immunoglobulin G ◽

Randomized Study ◽

Open Label ◽

Serum Igg Levels ◽

Trough Levels ◽

Infusion Duration

Abstract Purpose To evaluate the safety and tolerability of subcutaneous IgPro20 (Hizentra®, CSL Behring, King of Prussia, PA, USA) administered at high infusion parameters (> 25 mL and > 25 mL/h per injection site) in patients with primary immunodeficiency. Methods The Hizentra® Label Optimization (HILO) study was an open-label, parallel-arm, non-randomized study (NCT03033745) of IgPro20 using a forced upward titration design for infusion parameters. Patients experienced with pump-assisted IgPro20 infusions received weekly IgPro20 infusions at a stable dose in the Pump-Assisted Volume Cohort (N = 15; 25–50 mL per injection site) and in the Pump-Assisted Flow Rate Cohort (N = 18; 25–100 mL/h per injection site). Responder rates (percentage of patients who successfully completed ≥ 75% of planned infusions), safety outcomes, and serum immunoglobulin G (IgG) trough levels were evaluated. Results Responder rates were 86.7% (13/15, 25 mL) and 73.3% (11/15, 40 and 50 mL) in the Volume Cohort, and 77.8% (14/18, 25 and 50 mL/h), 66.7% (12/18, 75 mL/h), and 61.1% (11/18, 100 mL/h) in the Flow Rate Cohort. Infusion compliance was ≥ 90% in all patients in the Volume Cohort and in 83.3% of patients in the Flow Rate Cohort. The number of injection sites (Volume Cohort) and the infusion duration (Flow Rate Cohort) decreased with increasing infusion parameters. The rate of treatment-emergent adverse events per infusion was low (0.138 [Volume Cohort] and 0.216 [Flow Rate Cohort]). Serum IgG levels remained stable during the study. Conclusion Pump-assisted IgPro20 infusions are feasible at 50 mL and 100 mL/h per injection site in treatment-experienced patients, which may result in fewer injection sites and shorter infusion times. Trial Registration NCT03033745; registered January 27, 2017

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Study design of a prospective, open-label study comparing increased infusion parameters of a 20% subcutaneous immunoglobulin (IgPro20) in patients with primary immunodeficiency

10.21203/rs.2.16903/v1 ◽

2019 ◽

Author(s):

Mikhail Rojavin ◽

Jutta Hofmann ◽

Michaela Praus

Keyword(s):

United States ◽

Injection Site ◽

Primary Immunodeficiency ◽

Flow Rate ◽

Infusion Pump ◽

The United States ◽

Responder Rate ◽

Prospective Clinical Study ◽

Flow Rates ◽

Study Results

Abstract Background: Immunoglobulin G (IgG) replacement therapy can be administered subcutaneously (SCIG) using an infusion pump or by manual push. Both methods have shown similar serum IgG trough levels for the same total weekly/monthly dose as well as safety and tolerability profiles. The currently approved infusion parameters for the SCIG Hizentra® (IgPro20, CSL Behring, King of Prussia, PA, USA) in primary immunodeficiency (PID) in the United States are volumes of ≤25 mL and flow rates of ≤25 mL/h per injection site. Previously, clinical studies and case reports had demonstrated use of higher infusion parameters than those approved, but safety and tolerability of these have not been systematically evaluated. In the absence of regulatory guidance, we have developed a novel prospective clinical study applying forced upward titration design to evaluate the safety and tolerability of high infusion parameters of IgPro20 in PID patients using pump-assisted and manual push techniques (NCT03033745). Results: A total of 45 patients were planned for inclusion. Primary endpoints were defined as the proportion of patients successfully infusing certain infusion parameters (responder rate). The study included three cohorts (n=15 planned per group): 1) Pump-assisted Volume Cohort with weekly infusions at volumes of 25, 40 and 50 mL per injection site; 2) Pump-assisted Flow Rate Cohort with weekly infusions at flow rates of 25, 50, 75 and 100 mL/h per injection site, and 3) Manual Push Flow Rate Cohort with 2 to 7 infusions at flow rates 30, 60 and 120 mL/h per injection site. Each infusion parameter level was tested for 4 weeks, after which those who successfully infused at the current level (responders) were switched to the next level. Responder rate, safety and tolerability were assessed. Study results will be available in early 2020. Conclusions: This study applied a novel and rigorous prospective evaluation of individual safety and tolerability levels of pump-assisted and manual push SCIG at higher infusion parameters than currently approved in the United States and demonstrated their safety and tolerability.

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Hydraulic model of a water cooling system in a chemical plant

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc19880788 ◽

1988 ◽

Vol 53 (4) ◽

pp. 788-806

Author(s):

Miloslav Hošťálek ◽

Jiří Výborný ◽

František Madron

Keyword(s):

Flow Rate ◽

Cooling System ◽

Cooling Water ◽

Graph Algorithm ◽

Automatic Generation ◽

Hydraulic Calculation ◽

Return Flow ◽

Flow Rates ◽

Pressure Losses ◽

Controlled Flow

Steady state hydraulic calculation has been described of an extensive pipeline network based on a new graph algorithm for setting up and decomposition of balance equations of the model. The parameters of the model are characteristics of individual sections of the network (pumps, pipes, and heat exchangers with armatures). In case of sections with controlled flow rate (variable characteristic), or sections with measured flow rate, the flow rates are direct inputs. The interactions of the network with the surroundings are accounted for by appropriate sources and sinks of individual nodes. The result of the calculation is the knowledge of all flow rates and pressure losses in the network. Automatic generation of the model equations utilizes an efficient (vector) fixing of the network topology and predominantly logical, not numerical operations based on the graph theory. The calculation proper utilizes a modification of the model by the method of linearization of characteristics, while the properties of the modified set of equations permit further decrease of the requirements on the computer. The described approach is suitable for the solution of practical problems even on lower category personal computers. The calculations are illustrated on an example of a simple network with uncontrolled and controlled flow rates of cooling water while one of the sections of the network is also a gravitational return flow of the cooling water.

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Geometrical Optimization of a Venturi-Type Microbubble Generator Using CFD Simulation and Experimental Measurements

Designs ◽

10.3390/designs5010004 ◽

2021 ◽

Vol 5 (1) ◽

pp. 4

Author(s):

Dillon Alexander Wilson ◽

Kul Pun ◽

Poo Balan Ganesan ◽

Faik Hamad

Keyword(s):

Water Flow ◽

Flow Rate ◽

Cfd Simulation ◽

Air Flow ◽

Bubble Diameter ◽

Diameter Ratio ◽

Experimental Measurements ◽

Cfd Model ◽

Flow Rates ◽

Throat Diameter

Microbubble generators are of considerable importance to a range of scientific fields from use in aquaculture and engineering to medical applications. This is due to the fact the amount of sea life in the water is proportional to the amount of oxygen in it. In this paper, experimental measurements and computational Fluid Dynamics (CFD) simulation are performed for three water flow rates and three with three different air flow rates. The experimental data presented in the paper are used to validate the CFD model. Then, the CFD model is used to study the effect of diverging angle and throat length/throat diameter ratio on the size of the microbubble produced by the Venturi-type microbubble generator. The experimental results showed that increasing water flow rate and reducing the air flow rate produces smaller microbubbles. The prediction from the CFD results indicated that throat length/throat diameter ratio and diffuser divergent angle have a small effect on bubble diameter distribution and average bubble diameter for the range of the throat water velocities used in this study.

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Comparison of different models to calculate the viscosity of biogas and biomethane in order to accurately measure flow rates for conformity assessment

Scientific Reports ◽

10.1038/s41598-021-81052-7 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Karine Arrhenius ◽

Oliver Büker

Keyword(s):

Binary Mixtures ◽

Flow Rate ◽

Correction Method ◽

Gas Mixtures ◽

Conformity Assessment ◽

Flow Rates ◽

Unknown Composition

AbstractThe study presents an optimised method to correct flow rates measured with a LFE flowmeter pre-set on methane while used for gas mixtures of unknown composition at the time of the measurement. The method requires the correction of the flow rate using a factor based on the viscosity of the gas mixtures once the composition is accurately known. The method has several different possible applications inclusive for the sampling of biogas and biomethane onto sorbent tubes for conformity assessment for the determination of siloxanes, terpenes and VOC in general. Five models for the calculation of the viscosity of the gas mixtures were compared and the models were used for ten binary mixtures and four multi-component mixtures. The results of the evaluation of the different models showed that the correction method using the viscosity of the mixtures calculated with the model of Reichenberg and Carr showed the smallest biases for binary mixtures. For multi-component mixtures, the best results were obtained when using the models of Lucas and Carr.

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Assessment of the Use of Humidified Nasal Cannulas for Oxygen Therapy in Patients with Epistaxis

ORL ◽

10.1159/000514460 ◽

2021 ◽

pp. 1-5

Author(s):

Jingjing Liu ◽

Tengfang Chen ◽

Zhenggang Lv ◽

Dezhong Wu

Keyword(s):

Flow Rate ◽

Oxygen Therapy ◽

Preliminary Investigation ◽

Nasal Cannula ◽

Low Flow ◽

Antiplatelet Drugs ◽

Flow Rates ◽

The Past ◽

Oxygen Inhalation ◽

Significant Difference

Introduction: In China, nasal cannula oxygen therapy is typically humidified. However, it is difficult to decide whether to suspend nasal cannula oxygen inhalation after the nosebleed has temporarily stopped. Therefore, we conducted a preliminary investigation on whether the use of humidified nasal cannulas in our hospital increases the incidence of epistaxis. Methods: We conducted a survey of 176,058 inpatients in our hospital and other city branches of our hospital over the past 3 years and obtained information concerning their use of humidified nasal cannulas for oxygen inhalation, nonhumidified nasal cannulas, anticoagulant and antiplatelet drugs, and oxygen inhalation flow rates. This information was compared with the data collected at consultation for epistaxis during these 3 years. Results: No significant difference was found between inpatients with humidified nasal cannulas and those without nasal cannula oxygen therapy in the incidence of consultations due to epistaxis (χ2 = 1.007, p > 0.05). The same trend was observed among hospitalized patients using anticoagulant and antiplatelet drugs (χ2 = 2.082, p > 0.05). Among the patients with an inhaled oxygen flow rate ≥5 L/min, the incidence of ear-nose-throat (ENT) consultations due to epistaxis was 0. No statistically significant difference was found between inpatients with a humidified oxygen inhalation flow rate <5 L/min and those without nasal cannula oxygen therapy in the incidence of ENT consultations due to epistaxis (χ2 = 0.838, p > 0.05). A statistically significant difference was observed in the incidence of ENT consultations due to epistaxis between the low-flow nonhumidified nasal cannula and nonnasal cannula oxygen inhalation groups (χ2 = 18.428, p < 0.001). The same trend was observed between the 2 groups of low-flow humidified and low-flow nonhumidified nasal cannula oxygen inhalation (χ2 = 26.194, p < 0.001). Discussion/Conclusion: Neither high-flow humidified nasal cannula oxygen inhalation nor low-flow humidified nasal cannula oxygen inhalation will increase the incidence of recurrent or serious epistaxis complications; the same trend was observed for patients who use anticoagulant and antiplatelet drugs. Humidification during low-flow nasal cannula oxygen inhalation can prevent severe and repeated epistaxis to a certain extent.

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Net-exergetic, hydraulic and thermal optimization of coaxial heat exchangers using fixed flow conditions instead of fixed flow rates

Geothermal Energy ◽

10.1186/s40517-021-00201-3 ◽

2021 ◽

Vol 9 (1) ◽

Author(s):

Tobias Blanke ◽

Markus Hagenkamp ◽

Bernd Döring ◽

Joachim Göttsche ◽

Vitali Reger ◽

...

Keyword(s):

Reynolds Number ◽

Laminar Flow ◽

Mass Flow ◽

Flow Rate ◽

Heat Exchangers ◽

Circular Ring ◽

Flow Conditions ◽

Flow Rates ◽

Mass Flow Rates ◽

Pipe Radius

AbstractPrevious studies optimized the dimensions of coaxial heat exchangers using constant mass flow rates as a boundary condition. They show a thermal optimal circular ring width of nearly zero. Hydraulically optimal is an inner to outer pipe radius ratio of 0.65 for turbulent and 0.68 for laminar flow types. In contrast, in this study, flow conditions in the circular ring are kept constant (a set of fixed Reynolds numbers) during optimization. This approach ensures fixed flow conditions and prevents inappropriately high or low mass flow rates. The optimization is carried out for three objectives: Maximum energy gain, minimum hydraulic effort and eventually optimum net-exergy balance. The optimization changes the inner pipe radius and mass flow rate but not the Reynolds number of the circular ring. The thermal calculations base on Hellström’s borehole resistance and the hydraulic optimization on individually calculated linear loss of head coefficients. Increasing the inner pipe radius results in decreased hydraulic losses in the inner pipe but increased losses in the circular ring. The net-exergy difference is a key performance indicator and combines thermal and hydraulic calculations. It is the difference between thermal exergy flux and hydraulic effort. The Reynolds number in the circular ring is instead of the mass flow rate constant during all optimizations. The result from a thermal perspective is an optimal width of the circular ring of nearly zero. The hydraulically optimal inner pipe radius is 54% of the outer pipe radius for laminar flow and 60% for turbulent flow scenarios. Net-exergetic optimization shows a predominant influence of hydraulic losses, especially for small temperature gains. The exact result depends on the earth’s thermal properties and the flow type. Conclusively, coaxial geothermal probes’ design should focus on the hydraulic optimum and take the thermal optimum as a secondary criterion due to the dominating hydraulics.

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Effects of Sprinkler Flow Rate on Physiological, Behavioral and Production Responses of Nili Ravi Buffaloes during Subtropical Summer

Animals ◽

10.3390/ani11020339 ◽

2021 ◽

Vol 11 (2) ◽

pp. 339

Author(s):

Musa Bah ◽

Muhammad Afzal Rashid ◽

Khalid Javed ◽

Talat Naseer Pasha ◽

Muhammad Qamer Shahid

Keyword(s):

Heat Stress ◽

Milk Yield ◽

Flow Rate ◽

Rectal Temperature ◽

Latin Square ◽

Flow Rates ◽

Group Water ◽

Humidity Index ◽

Daily Milk Yield ◽

Daily Milk

Water buffaloes wallow in water to combat heat stress during summer. With the decreasing reservoirs for wallowing, the farmers use sprinklers to cool the buffaloes in Pakistan. These sprinklers use a large quantity of groundwater, which is becoming scarce. The objective of the current study was to determine the effect of different sprinkler flow rates on the physiological, behavioral, and production responses of Nili Ravi buffaloes during summer. Eighteen buffaloes were randomly subjected to three sprinkler flow rate treatments in a double replicated 3 × 3 Latin square design. The flow rates were 0.8, 1.25, and 2.0 L/min. During the study, the average afternoon temperature humidity index was 84.6. The 1.25 and 2.0 L/min groups had significantly lower rectal temperature and respiratory rates than the 0.8 L/min group. Water intake was significantly higher in the 0.8 L/min group. Daily milk yield was higher in the 1.25 and 2.0 L/min groups than in the 0.8 L/min group. These results suggested that the sprinkler flow rates > 0.8 L/min effectively cooled the buffaloes. The sprinkler flow rate of 1.25 L/min appeared to be more efficient, as it used 37.5% less water compared to the 2.0 L/min.

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Laser-Doppler Velocimetry Measurements Inside a Backward Curved Centrifugal Fan

International Journal of Rotating Machinery ◽

10.1155/s1023621x01000161 ◽

2001 ◽

Vol 7 (3) ◽

pp. 173-181

Author(s):

Tong-Miin Liou ◽

Meng-Yu Chen

Keyword(s):

Flow Rate ◽

Turbulence Intensity ◽

Laser Doppler Velocimetry ◽

Reverse Flow ◽

Flow Region ◽

Design Flow ◽

Laser Doppler ◽

Centrifugal Fan ◽

Doppler Velocimetry ◽

Flow Rates

Laser-Doppler velocimetry (LDV) measurements are presented of relative mean velocity and turbulence intensity components inside the impeller passage of a centrifugal fan with twelve backward curved blades at design, under-design, and over-design flow rates. Additional LDV measurements were also performed at the volute outlet to examine the uniformity of the outlet flow for the three selected flow rates. Complementary flow visualization results in the tongue region are further presented. It is found that the number of characteristic flow regions and the average turbulence level increase with decreasing air flow rate. For the case of under-design flow rate, there are a through-flow region on the suction side, a reverse flow region on the pressure side, and a shear layer region in between. The corresponding average turbulence intensity is as high as 9.1% of blade tip velocity.

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Simultaneous Measuring Method for Both Volumetric Flow Rates of Air-Water Mixture Using a Turbine Flowmeter

Journal of Energy Resources Technology ◽

10.1115/1.2792689 ◽

1996 ◽

Vol 118 (1) ◽

pp. 29-35 ◽

Cited By ~ 9

Author(s):

K. Minemura ◽

K. Egashira ◽

K. Ihara ◽

H. Furuta ◽

K. Yamamoto

Keyword(s):

Pressure Drop ◽

Flow Rate ◽

Volumetric Flow Rate ◽

Oil Field ◽

Liquid Density ◽

Water Mixture ◽

Rotor Speed ◽

Flow Rates ◽

Field Development ◽

Turbine Flowmeter

A turbine flowmeter is employed in this study in connection with offshore oil field development, in order to measure simultaneously both the volumetric flow rates of air-water two-phase mixture. Though a conventional turbine flowmeter is generally used to measure the single-phase volumetric flow rate by obtaining the rotational rotor speed, the method proposed additionally reads the pressure drop across the meter. After the pressure drop and rotor speed measured are correlated as functions of the volumetric flow ratio of the air to the whole fluid and the total volumetric flow rate, both the flow rates are iteratively evaluated with the functions on the premise that the liquid density is known. The evaluated flow rates are confirmed to have adequate accuracy, and thus the applicability of the method to oil fields.

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