Pharmacokinetics of a 503B outsourcing facility-produced theophylline in dogs.

Theophylline is an important drug for treatment of canine chronic bronchitis and bradyarrhythmias, but new products require validation since pharmacokinetics in dogs can vary by formulation. A new, 503B outsourcing facility-produced theophylline product (OFT) is available for veterinary use. Outsourcing facilities have many advantages over traditional compounding sources including current good manufacturing practice compliance. The purpose of this study was to establish the pharmacokinetics of OFT in dogs. Eight healthy dogs received 11 mg/kg intravenous aminophylline and 10 mg/kg oral OFT followed by serial blood sampling in a two-way, randomized, crossover design with 7-day washout. Plasma theophylline concentrations were quantified by liquid chromatography-mass spectrometry. Bioavailability, maximum concentration, time to maximum concentration, half-life and area under the curve were: 97 ± 10%, 7.13 ± 0.71 µg/mL, 10.50 ± 2.07 h, 9.20 ± 2.87 h, and 141 ± 37.6 µg*h/mL, respectively. Steady-state predictions supported twice daily dosing of the OFT, but specific dosage recommendations are hindered by lack of a canine-specific therapeutic range for plasma theophylline concentration. These findings suggest that the OFT is well absorbed and can likely be dosed twice daily in dogs, but future pharmacodynamic and clinical studies are needed to establish a definitive therapeutic range for theophylline in this species.

Increased Potential of Bone Formation with the Intravenous Injection of a Parathyroid Hormone-Related Protein Minicircle DNA Vector.

Osteoporosis is commonly treated via the long-term usage of anti-osteoporotic agents; however, poor drug compliance and undesirable side effects limit their treatment efficacy. The parathyroid hormone-related protein (PTHrP) is essential for normal bone formation and remodeling; thus, may be used as an anti-osteoporotic agent. Here, we developed a platform for the delivery of a single peptide composed of two regions of the PTHrP protein (1-34 and 107-139); mcPTHrP 1-34+107-139 using a minicircle vector. We also transfected mcPTHrP 1-34+107-139 into human mesenchymal stem cells (MSCs) and generated Thru 1-34+107-139-producing engineered MSCs (eMSCs) as an alternative delivery system. Osteoporosis was induced in 12-week-old C57BL/6 female mice via ovariectomy. The ovariectomized (OVX) mice were then treated with the two systems; (1) mcPTHrP 1-34+107-139 was intravenously administered three times (once per week); (2) eMSCs were intraperitoneally administered twice (on weeks four and six). Compared with the control OVX mice, the mcPTHrP 1-34+107-139-treated group showed better trabecular bone structure quality, increased bone formation, and decreased bone resorption. Similar results were observed in the eMSCs-treated OVX mice. Altogether, these results provide experimental evidence to support the potential of delivering PTHrP 1-34+107-139 using the minicircle technology for the treatment of osteoporosis.

Propofol protects cardiomyocytes from hypoxia/reoxygenation injury via regulating MALAT1/miR-206/ATG3 axis.

Previous studies have shown that propofol (PPF) plays a protective role in ischemia-reperfusion (I/R) in multiple organs and tissues. This study was aimed to explore the mechanism of PPF in ameliorating myocardial ischemia-reperfusion injury (MIRI). MIRI model was established with Sprague-Dawley rats, and PPF pretreatment was performed before reperfusion. Creatine kinase isoform (CK-MB), lactate dehydrogenase (LDH), and hematoxylin and eosin stain were used to evaluate the severity of MIRI. H9c2 cells were treated with hypoxia/reoxygenation (H/R) to simulate I/R injury in vitro. Real-time quantitative polymerase chain reaction (qPCR) was employed to assess MALAT1 and microRNA (miR)-206 expressions. Autophagy-related 3 (ATG3), LC3BⅡ/LC3BⅠ, and Beclin-1 expression were examined by western blot. Apoptosis was monitored using flow cytometry. Interaction between MALAT1 and miR-206 was determined by bioinformatics analysis, dual-luciferase reporter gene assay, RIP assay, and RNA pull-down assay. PPF pretreatment remarkably reduced CK-MB level, LDH level, myocardial infarct size, and LC3BⅡ/LC3BⅠ ratio and Beclin-1 expression in the rats with MIRI, and repressed the apoptosis of H9c2 cells exposed to H/R. PPF pretreatment markedly suppressed MALAT1 expression and enhanced miR-206 expression in both in vivo and in vitro models. MiR-206 was identified as a target of MALAT1 in cardiomyocytes, and MALAT1 could increase the expression of ATG3. Additionally, the upregulation of MALAT1 partially reversed the protective effect of PPF on cardiomyocytes in vitro. PPF modulated MALAT1/miR-206/ATG3 axis to protect cardiomyocytes against I/R injury.

Intraoperative Identification of the Shunt Point of Spinal Arteriovenous Malformations by a Selective Arterial Injection of Saline to Subtract Signals of Indocyanine Green: Technical Note.

BACKGROUND: It is crucial to identify a shunt point for spinal arteriovenous malformation (AVM) treatment. For this purpose, some intraoperative supports have been reported-intravenous injection of indocyanine green (ICG), selective arterial injection of ICG, and selective arterial injection of saline with a high frame rate digital camera. However, there are difficulties in accurately identifying the shunt point, especially if the lesion has multiple feeders. The aim of this technical note was to report a novel method, selective arterial injection of saline to subtract signals of ICG, to precisely identify perimedullary arteriovenous fistula shunt points having multiple feeding arteries. METHODS: After exposing the lesion, a 4-F catheter was cannulated into the origins of the segmental artery. ICG was injected intravenously as a first step, and then heparinized saline solution was flushed from the catheter. RESULTS: Compared with other methods, this method could identify the exact shunt point and was effective for certain shunt point obliterations. CONCLUSIONS: Despite having similar invasiveness, selective arterial injection of saline to subtract signals of ICG is superior to previously described techniques, such as selective arterial injection of ICG. Therefore, it will be useful in spinal arteriovenous malformation surgical treatment.

Early diuretic strategies and the association with In-hospital and Post-discharge outcomes in acute heart failure.

BACKGROUND: Decongestion is a primary goal during hospitalizations for decompensated heart failure (HF). However, data surrounding the preferred route and strategy of diuretic administration are limited with varying results in prior studies. METHODS: This is a retrospective analysis using patients from ASCEND-HF with a stable diuretic strategy in the first 24 hours following randomization. Patients were divided into three groups: intravenous (IV) continuous, IV bolus and oral strategy. Baseline characteristics, in-hospital outcomes, 30-day composite cardiovascular mortality or HF rehospitalization and 180-day all-cause mortality were compared across groups. Inverse propensity weighted modeling was used for adjustment. RESULTS: Among 5,738 patients with a stable diuretic regimen in the first 24 hours (80% of overall ASCEND trial), 3,944 (68.7%) patients received IV intermittent bolus administration of diuretics, 799 (13.9%) patients received IV continuous therapy and 995 (17.3%) patients with oral administration. Patients in the IV continuous group had a higher baseline creatinine (IV continuous 1.4 [1.1-1.7]; intermittent bolus 1.2 [1.0-1.6]; oral 1.2 [1.0-1.4] mg/dL; P <0.001) and high NTproBNP (IV continuous 5,216 [2,599-11,603]; intermittent bolus 4,944 [2,339-9,970]; oral 3,344 [1,570-7,077] pg/mL; P <0.001). There was no difference between IV continuous and intermittent bolus group in weight change, total urine output and change in renal function till 10 days/discharge (adjusted P >0.05 for all). There was no difference in 30 day mortality and HF readmission (adjusted OR 1.08 [95%CI: 0.74, 1.57]; P = 0.701) and 180 days mortality (adjusted OR 1.04 [95%CI: 0.75, 1.43]; P = 0.832). CONCLUSION: In a large cohort of patients with decompensated HF, there were no significant differences in diuretic-related in-hospital, or post-discharge outcomes between IV continuous and intermittent bolus administration. Tailoring appropriate diuretic strategy to different states of acute HF and congestion phenotypes needs to be further investigated.

Estimation of absolute oral bioavailability without performing an intravenous clinical study.

The absolute oral bioavailability (BA) of drugs are yet to be determined, and intravenous pharmacokinetic studies are currently considered indispensable for determining the BA values of oral drugs. The aim of this study was to develop and validate a novel approach to estimating BA values without intravenous pharmacokinetic data. Based on the drug inclusion criteria, such as exhibiting a urinary recovery rate of (Ru) of ≥20% in a clinical study, 13 drugs were included in the present study, and pharmacokinetic data for them were collected from the literature. The fraction excreted unchanged into urine (fe) was calculated for healthy subjects by dividing the Ru value by the total recovery rate. The contribution of renal excretion to total clearance from the systemic circulation (Rren) was estimated by subjecting oral clearance and creatinine clearance to regression in subjects with normal and impaired renal function. BA was estimated as fe/Rren and compared with the observed BA (BAobs). The predicted BA values for 9 drugs fell within ±20% of their BAobs. The examined approach makes it possible to estimate BA values for drugs with mean renal excretion values in healthy subjects and oral clearance in subjects with various renal function, without intravenous pharmacokinetic data.

Modeling Brain Metastasis Via Tail-Vein Injection of Inflammatory Breast Cancer Cells.

Metastatic spread to the brain is a common and devastating manifestation of many types of cancer. In the United States alone, about 200,000 patients are diagnosed with brain metastases each year. Significant progress has been made in improving survival outcomes for patients with primary breast cancer and systemic malignancies; however, the dismal prognosis for patients with clinical brain metastases highlights the urgent need to develop novel therapeutic agents and strategies against this deadly disease. The lack of suitable experimental models has been one of the major hurdles impeding advancement of our understanding of brain metastasis biology and treatment. Herein, we describe a xenograft mouse model of brain metastasis generated via tail-vein injection of an endogenously HER2-amplified cell line derived from inflammatory breast cancer (IBC), a rare and aggressive form of breast cancer. Cells were labeled with firefly luciferase and green fluorescence protein to monitor brain metastasis, and quantified metastatic burden by bioluminescence imaging, fluorescent stereomicroscopy, and histologic evaluation. Mice robustly and consistently develop brain metastases, allowing investigation of key mediators in the metastatic process and the development of preclinical testing of new treatment strategies.

Recombinant human C1 esterase inhibitor (conestat alfa) in the prevention of severe SARS-CoV-2 infection in hospitalized patients with COVID-19: A structured summary of a study protocol for a randomized, parallel-group, open-label, multi-center pilot trial (PROTECT-COVID-19).

OBJECTIVES: Conestat alfa, a recombinant human C1 esterase inhibitor, is a multi-target inhibitor of inflammatory cascades including the complement, the kinin-kallikrein and the contact activation system. The study objective is to investigate the efficacy and safety of conestat alfa in improving disease severity and short-term outcome in COVID-19 patients with pulmonary disease. TRIAL DESIGN: This study is an investigator-initiated, randomized (2:1 ratio), open-label, parallel-group, controlled, multi-center, phase 2a clinical trial. PARTICIPANTS: This trial is conducted in 3 hospitals in Switzerland, 1 hospital in Brazil and 1 hospital in Mexico (academic and non-academic). All patients with confirmed SARS-CoV-2 infection requiring hospitalization for at least 3 calendar days for severe COVID-19 will be screened for study eligibility. INCLUSION CRITERIA: - Signed informed consent - Age 18-85 years - Evidence of pulmonary involvement on CT scan or X-ray of the chest - Duration of symptoms associated with COVID-19 ≤ 10 days - At least one of the following risk factors for progression to mechanical ventilation on the day of enrolment: 1) Arterial hypertension 2) ≥ 50 years 3) Obesity (BMI ≥ 30 kg/m2) 4) History of cardiovascular disease 5) Chronic pulmonary disease 6) Chronic renal disease 7) C-reactive protein > 35mg/L 8) Oxygen saturation at rest of ≤ 94% when breathing ambient air Exclusion criteria: - Incapacity or inability to provide informed consent - Contraindications to the class of drugs under investigation (C1 esterase inhibitor) - Treatment with tocilizumab or another IL-6R or IL-6 inhibitor before enrolment - History or suspicion of allergy to rabbits - Pregnancy or breast feeding - Active or anticipated treatment with any other complement inhibitor - Liver cirrhosis (any Child-Pugh score) - Admission to an ICU on the day or anticipated within the next 24 hours of enrolment - Invasive or non-invasive ventilation - Participation in another study with any investigational drug within the 30 days prior to enrolment - Enrolment of the study investigators, their family members, employees and other closely related or dependent persons INTERVENTION AND COMPARATOR: Patients randomized to the experimental arm will receive conestat alfa in addition to standard of care (SOC). Conestat alfa (8400 U followed by 4200 U every 8 hours) will be administered as a slow intravenous injection (5-10 minutes) over a 72-hour period (i.e. 9 administrations in total). The first conestat alfa treatment will be administered on the day of enrolment. The control group will receive SOC only. SOC treatment will be administered according to local institutional guidelines, including supplemental oxygen, antibiotics, corticosteroids, remdesivir, and anticoagulation. MAIN OUTCOMES: The primary endpoint of this trial is disease severity on day 7 after enrolment assessed by an adapted WHO Ordinal Scale for Clinical Improvement (score 0 will be omitted and score 6 and 7 will be combined) from 1 (no limitation of activities) to 7 (death). Secondary outcomes include (i) the time to clinical improvement (time from randomization to an improvement of two points on the WHO ordinal scale or discharge from hospital) within 14 days after enrolment, (ii) the proportion of participants alive and not having required invasive or non-invasive ventilation at 14 days after enrolment and (iii) the proportion of subjects without an acute lung injury (defined by PaO2/FiO2 ratio of ≤300mmHg) within 14 days after enrolment. Exploratory outcomes include virological clearance, C1 esterase inhibitor pharmacokinetics and changes in routine laboratory parameters and inflammatory proteins. RANDOMISATION: Subjects will be randomised in a 2:1 ratio to treatment with conestat alfa in addition to SOC or SOC only. Randomization is performed via an interactive web response system (SecuTrial®). BLINDING (MASKING): In this open-label trial, participants, caregivers and outcome assessors are not blinded to group assignment. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): We will randomise approximately 120 individuals (80 in the active treatment arm, 40 in the SOC group). Two interim analyses after 40 and 80 patients are planned according to the Pocock adjusted levels αp = 0.0221. The results of the interim analysis will allow adjustment of the sample size (Lehmacher, Wassmer, 1999). TRIAL STATUS: PROTECT-COVID-19 protocol version 3.0 (July 07 2020). Participant recruitment started on July 30 2020 in one center (Basel, Switzerland, first participant included on August 06 2020). In four of five study centers patients are actively recruited. Participation of the fifth study center (Mexico) is anticipated by mid December 2020. Completion of trial recruitment depends on the development of the SARS-CoV-2 pandemic. TRIAL REGISTRATION: Clinicaltrials.gov, number: NCT04414631 , registered on 4 June 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Analgesic Effects of Different κ-Receptor Agonists Used in Daytime Laparoscopic Cholecystectomy.

BACKGROUND: Comparing the effect of two different κ-receptor agonists, nalbuphine and oxycodone, and regular morphine in patients for prophylactic analgesia of acute pain after daytime laparoscopic cholecystectomy. METHODS: One hundred and twenty-four patients undergoing laparoscopic cholecystectomy were randomly allocated to receive nalbuphine (group N), oxycodone (group O), and morphine (group M). The three groups were all given intravenous injection (iv.) of 0.15 mg/kg injection before incision and 0.05 mg/kg injection at the end of pneumoperitoneum. The Visual Analogue Scale (VAS) scores (incision, visceral, and shoulder) and Ramsay sedation scores at 1, 2, 4, 8, 12, 16, 20, and 24 hours after surgery, the time of extubation, the incidence of postoperative adverse events, the satisfaction of pain treatment, and the duration of stay after surgery were all recorded. RESULTS: Compared with group M, the VAS scores of visceral pain at rest decreased in group N and group O at 1-8 h after surgery (P < 0.05). The VAS scores of visceral pain at movement in group N decreased longer than those in group O (P < 0.05). Compared with that of group M, the postoperative time in Ramsay sedation score of group O increased longer than that of group N (P < 0.05). Compared with group N, patients had worse sleep quality in group O, longer length of stay in group M, and lower satisfaction in both groups. CONCLUSION: Compared with morphine, prophylactic use of the κ-receptor agonists, nalbuphine and oxycodone, during laparoscopic cholecystectomy can reduce postoperative visceral pain. Furthermore, the nalbuphine group had fewer adverse reactions, better analgesia, and better satisfaction.

Intravital Dynamic and Correlative Imaging of Mouse Livers Reveals Diffusion-Dominated Canalicular and Flow-Augmented Ductular Bile Flux.

BACKGROUND AND AIMS: Small-molecule flux in tissue microdomains is essential for organ function, but knowledge of this process is scant due to the lack of suitable methods. We developed two independent techniques that allow the quantification of advection (flow) and diffusion in individual bile canaliculi and in interlobular bile ducts of intact livers in living mice, namely fluorescence loss after photoactivation and intravital arbitrary region image correlation spectroscopy. APPROACH AND RESULTS: The results challenge the prevailing "mechano-osmotic" theory of canalicular bile flow. After active transport across hepatocyte membranes, bile acids are transported in the canaliculi primarily by diffusion. Only in the interlobular ducts is diffusion augmented by regulatable advection. Photoactivation of fluorescein bis-(5-carboxymethoxy-2-nitrobenzyl)-ether in entire lobules demonstrated the establishment of diffusive gradients in the bile canalicular network and the sink function of interlobular ducts. In contrast to the bile canalicular network, vectorial transport was detected and quantified in the mesh of interlobular bile ducts. CONCLUSIONS: The liver consists of a diffusion-dominated canalicular domain, where hepatocytes secrete small molecules and generate a concentration gradient and a flow-augmented ductular domain, where regulated water influx creates unidirectional advection that augments the diffusive flux.

Percepção da criança hospitalizada acerca do brinquedo terapêutico instrucional na terapia intravenosa / Percepción del niño hospitalizado acerca del juguete terapéutico instructivo en la terapia intravenosa / Perception of the hospitalized child about the instructional therapeutic play in intravenous therapy

Resumo Objetivo analisar a percepção da criança hospitalizada quanto ao uso do brinquedo terapêutico instrucional no preparo para a terapia intravenosa. Método estudo descritivo, com abordagem qualitativa, realizado em um hospital pediátrico público no município de Juazeiro do Norte - Ceará, entre os meses de julho a setembro de 2019. Participaram do estudo 31 crianças em idade pré-escolar e escolar. Os dados foram coletados por meio de uma entrevista semiestruturada e, posteriormente, analisados por meio do software IRAMUTEQ. Resultados diante da percepção das crianças acerca da terapia intravenosa, foi averiguado que elas compreenderam a técnica a partir da utilização do brinquedo terapêutico instrucional. Quando a criança tem a oportunidade de brincar e dramatizar a terapia intravenosa, por meio do brinquedo terapêutico instrucional, a ansiedade, a dor, a angústia, a solidão, o medo e o choro são atenuados. Conclusões e implicações para a prática orientar as crianças quanto à realização da terapia intravenosa favorece sua compreensão quanto aos reais benefícios desta técnica para a sua saúde, possibilitando, ainda, a compreensão do enfermeiro quanto às condições que representam riscos para a criança e intervenha em tempo hábil por meio da utilização de estratégias que favoreçam a recuperação da saúde e a minimização de traumas subsequentes advindos da hospitalização.

Resumen Objetivo Analizar la percepción del niño hospitalizado cuanto al uso del juguete terapéutico instructivo en la preparación para la terapia intravenosa. Método Estudio descriptivo, con enfoque cualitativo, realizado en un hospital pediátrico público de la ciudad de Juazeiro do Norte - Ceará, entre julio y septiembre de 2019. Participaron 31 niños en edad preescolar y escolar. Los datos se recogieron mediante entrevista semiestructurada, posteriormente analizados con el software IRAMUTEQ. Resultados En vista de la percepción de los niños acerca de la terapia intravenosa, se encontró que ellos comprendieron la técnica a partir del uso del juguete terapéutico instructivo. Cuando tienen la oportunidad de jugar y dramatizar la terapia intravenosa, a través del juguete terapéutico instructivo, la ansiedad, el dolor, la angustia, la soledad, el miedo y el llanto son mitigados. Conclusiones e implicaciones para la práctica Orientar a los niños sobre la realización de la terapia intravenosa favorece su comprensión sobre los beneficios reales de esta técnica para su salud, permitiendo además que la enfermera comprenda las condiciones que suponen riesgos para el niño e intervenga de forma oportuna, mediante el uso de estrategias que favorezcan la recuperación de la salud y la minimización de traumas posteriores a la hospitalización.

Abstract Objective to analyze the perception of the hospitalized child regarding the use of the instructional therapeutic play in preparation for intravenous therapy. Method descriptive study, with a qualitative approach, performed in a public pediatric hospital in the city of Juazeiro do Norte - Ceará, between the months of July and September 2019. A total of 31 pre-school and school children participated in the study. The data were collected through a semi-structured interview, and later analyzed through IRAMUTEQ software. Results in view of the children's perception of intravenous therapy, it was found that they understood the technique, from the use of the instructional therapeutic play. When the child has the opportunity to play and dramatize intravenous therapy, through the instructional therapeutic play, the anxiety, the pain, the anguish, the loneliness, the fear and the crying are mitigated. Conclusion and implications for practice Orienting children in the performance of intravenous therapy favors their understanding of the real benefits of this technique for their health, allowing the nurse to understand the conditions that pose risks to the child, and intervene in a timely manner, through the use of strategies that favor the recovery of health and the minimization of subsequent trauma from hospitalization.

Adenosine, Lidocaine, and Magnesium Support a High Flow, Hypotensive, Vasodilatory State With Improved Oxygen Delivery and Cerebral Protection in a Pig Model of Noncompressible Hemorrhage.

BACKGROUND: Noncompressible hemorrhage is the leading cause of preventable death in military and civilian trauma. Our aim was to examine the effect of adenosine, lidocaine, and magnesium (Mg2+; ALM) on cardiovascular and cerebral function in a porcine hepatic hemorrhage model. MATERIALS AND METHODS: Pigs (59.1 ± 0.34 kg) were anesthetized, instrumented, and randomly assigned into sham (n = 6), saline controls (n = 10) or ALM (n = 10) groups before laparoscopic liver resection. After 30 min, groups received 4 mL/kg 3% NaCl ± ALM bolus (Phase 1) followed 60 min later with 3 mL/kg/h 0.9% NaCl ± ALM drip (4 h; Phase 2), then transfusion. Hemodynamics, carotid artery flow, and intracranial pressure were measured continuously. Microdialysis samples were analyzed for metabolites. RESULTS: Saline controls had 20% mortality (mean survival time: 307 ± 38 min) with no ALM deaths over 6 h. Bolus administration increased mean arterial pressure (MAP) in both groups, and drip led to further increases to 62 ± 10 mmHg in controls compared with a steady fall to 47 ± 8 mmHg in ALM group at 240 min. The lower MAP was associated with a dramatic fall in systemic vascular resistance and improved oxygen delivery. ALM drip significantly increased cardiac output and stroke volume with lower dP/dtMin, indicating a less stiff heart. ALM drip also significantly decreased cerebral perfusion pressure, reduced cerebral oxygen consumption (28%), and reduced brain glycerol (60%), lactate (47%), and relative expression of hypoxia-inducible factor (38%) compared with saline controls. CONCLUSIONS: ALM therapy improved cardiac function and oxygen delivery by lowering systemic vascular resistance after noncompressible hemorrhage. ALM also appeared to protect the brain at hypotensive MAPs with significantly lower cerebral perfusion pressure, lower O2 consumption, and significantly lower cortical lactate and glycerol levels compared to saline controls.

Higher plasma asparaginase activity after intramuscular than intravenous Erwinia asparaginase.

It is unclear if dosing intervals for Erwinase can be extended with intramuscular (i.m.) versus intravenous (i.v.) dosing. Children with acute lymphoblastic leukemia received Erwinase at 30 000-42 000 IU/m2 i.v. or i.m. I.m. Erwinase (n = 22) achieved activity above 0.1 IU/mL for longer than i.v. Erwinase (n = 33) (3.4 vs 2.9 days, P = 0.0007). With 30 000 IU/m2 Monday, Wednesday, Friday, more patients achieved adequate concentrations over the weekend with i.m. vs i.v. dosing (P = 5 × 10-36 ). A schedule with i.v. doses on Monday and Wednesday and i.m. doses on Friday of 30 000 IU/m2 maintained activity > 0.1 IU/mL over the weekend in 80% of patients.

Dilution is no solution.

Some nurses continue to routinely dilute I.V. push medications, a practice associated with a high risk of errors. This article reviews correct practices for administering I.V. push medications.

Performance of single-use syringe versus multi-use MR contrast injectors: a prospective comparative study.

The goal of this study was to compare performance parameters of a single-use syringe and a multi-use MR contrast injector. We compared preparation time, cost for disposables and volumes of contrast material used for a single-use (SI) and a multi-use (MI) MR contrast injector in a prospective cross-over trial. During the first study period all consecutive patients eligible for dynamic MR on two systems were included during a period of 20 working days. After 10 days, the injector was switched. Radiographer satisfaction was evaluated using a questionnaire. Contrast usage and waste on system MI was optimised by extra instructions for our radiographers and measured during the second study period of 10 consecutive working days. A total of 202 and 163 patients for systems SI and MI were included, respectively. Average preparation time was 4:55 min for SI and 2:24 min for MI (p < 0.05). Contrast waste for SI was 13% using 7.5 ml syringes. Contrast waste for MI was 5% for 7.5 ml containers. Costs for disposables were lower for MI if more than 5 patients per day were injected. Radiographer satisfaction was higher for MI (4.7 versus 2.8 on a 5-point scale; p < 0.05). The multi-use MR contrast injector led to higher radiographer satisfaction, shorter preparation time, and lower cost if more than 5 patients were injected per day. In addition, cheaper contrast containers of 15 or 30 ml could be used for the first patients if more than 2 or more than 4 injections are performed per day, potentially leading to lower contrast waste.

Double-chamber syringe versus classic syringes for peripheral intravenous drug administration and catheter flushing: a study protocol for a randomised controlled trial.

BACKGROUND: The prevention of catheter-related complications is nowadays an important topic of research. Flushing catheters is considered an important clinical procedure in preventing malfunction and several complications such as phlebitis or infection. Considering the latest guidelines of the Infusion Nurses Society, the flushing should be carried out both pre- and post-drug administration, requiring different syringes (with associated overall increased times of preparation/administration of intravenous medication by nurses, and also increasing the need for manipulation of the venous catheter). METHODS/DESIGN: A multi-centre, two-arm randomised controlled trial with partially blinded outcome assessment of 146 adult patients. After eligibility analysis and informed consent, participants will receive usual intravenous administration drugs with flushing procedures, with a double-chamber syringe (arm A) or with classic syringes (arm B). The outcomes assessment will be performed on a daily basis by an unblinded ward team, with the same procedures in both groups. Some main outcomes, such as phlebitis and infiltration, will also be evaluated by nurses from a blinded research team and registered once a day. DISCUSSION: The study outlined in this protocol will provide valuable insight regarding the effectiveness and safety of this new medical device. The development of this medical device (dual-chamber syringe, for drug and flush solution) seems to be an important step to facilitate nurses' adoption of good clinical practices in intravenous procedures, reducing catheter manipulations. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04046770. Registered 13 August 2019.

Gene transfer to skeletal muscle using hydrodynamic limb vein injection: current applications, hurdles and possible optimizations.

Hydrodynamic limb vein injection is an in vivo locoregional gene delivery method. It consists of administrating a large volume of solution containing nucleic acid constructs in a limb with both blood inflow and outflow temporarily blocked using a tourniquet. The fast, high pressure delivery allows the musculature of the whole limb to be reached. The skeletal muscle is a tissue of choice for a variety of gene transfer applications, including gene therapy for Duchenne muscular dystrophy or other myopathies, as well as for the production of antibodies or other proteins with broad therapeutic effects. Hydrodynamic limb vein delivery has been evaluated with success in a large range of animal models. It has also proven to be safe and well-tolerated in muscular dystrophy patients, thus supporting its translation to the clinic. However, some possible limitations may occur at different steps of the delivery process. Here, we have highlighted the interests, bottlenecks and potential improvements that could further optimize non-viral gene transfer following hydrodynamic limb vein injection.

Effect of bolus administration of non-ionic radiopaque contrast media on blood pressure variation.

INTRODUCTION: Haemodynamic changes may occur with the rapid intravenous injection of contrast media due to the osmolality of such pharmaceuticals. This study sought to evaluate the effect of bolus administration of intravenous contrast media on blood pressure variation during the Contrast-Enhanced Computed Tomography (CECT) of the abdomen. METHODS: The study included 74 patients who underwent abdominal CECT and they were placed in the first group receiving a maximum of 80 ml of iodinated contrast via pressure injector (4 ml/s). A further 74 patients, who underwent non-contrast enhanced abdominal CT, were placed in the second group in which 80 ml of normal saline was administered via the same manner. Patients with hypertension and who were on anti-hypertensive drugs were excluded from the study. Non-invasive blood pressure was monitored before the injection of contrast media/saline and immediately after the portal venous phase for the CECT scan and after 45 s following the administration of normal saline in the non-contrast CT group. Mean systolic and diastolic blood pressures from both groups were compared to find out the effect of contrast bolus administration on blood pressure variation. RESULTS: Both systolic and diastolic blood pressure increased with the injection of contrast media among CECT scan group. No significant changes in systolic and diastolic blood pressure were found before and after the scan in the non-contrast group. CONCLUSION: Bolus administration of 80 ml saline has no effect on blood pressure. The increased blood pressure in contrast enhanced studies was induced by the iodinated contrast media and not by the bolus effect.

Dramatic thrombolysis after rapid injection of tissue plasminogen activator: A case report.

RATIONALE: The regimen of the recombinant tissue plasminogen activator (rt-PA) is identical in every case where it is indicated in the treatment of cerebral infarction. We report a case of efficient recanalization of large arterial occlusion after rapid injection of rt-PA. PATIENT CONCERNS: A 78-year-old man was admitted with right-sided hemiplegia and global aphasia that occurred an hour ago. DIAGNOSES: His brain computed tomography (CT) revealed no hemorrhage, suggesting cerebral infarction. INTERVENTIONS: Ten percent of a total rt-PA dose was injected over 1 minute promptly. The remainder of rt-PA was designed to be infused for 60 minutes. Unexpectedly, during the study of CT angiography, administration of rt-PA was completed within 5 minutes. CT angiography showed occlusion from carotid bifurcation to the middle cerebral artery. OUTCOMES: After 2 hours of rt-PA administration, the patient began to regain strength in his right arm and leg. By the next day, he had only mild dysarthria and aphasia. Follow-up CT angiography revealed recanalized internal cervical artery and severe residual stenosis with a plaque. He was discharged without any neurologic symptoms. LESSONS: The infusion protocol of rt-PA administration is established in 1995 and has not changed. Successful recanalization of long segmental large vessel occlusion with only intravenous rt-PA is relatively low. In our case, a high concentration of rt-PA may have influenced the successful dissemination of large thrombus in the whole internal cervical artery. Our case is of significance as it raises the question of unanswered efficacy of diverse injection protocol according to thrombus size and bleeding risk.