The administration of immune checkpoint inhibitors via an elastomeric pump versus conventional intravenous infusion: an economic perspective.

BACKGROUND: Recent studies have underscored the potential of innovative administration methods to mitigate the capacity burden on healthcare systems, without compromising the quality of care. This study assessed and compared the resource utilization and associated costs of two distinct administration modes of immune checkpoint inhibitors: the innovative elastomeric pump and conventional intravenous infusion. This comparison can inform sustainable healthcare practices and healthcare decision-making to optimize treatment efficiency in an era of escalating healthcare demands. METHODS: In this micro-costing study, data on resource use and time allocation for drug preparation and administration were collected using an observational, non-interventional study design. Data were registered at the oncology daycare unit and hospital pharmacy. Cost categories included drug acquisition, disposable materials, healthcare professional time for drug administration, drug preparation, and patient time spent at the oncology day care unit. RESULTS: Drug administration through the elastomeric pump resulted in substantially lower healthcare costs when compared to conventional infusion, particularly due to reduced labor and chair time. The elastomeric pump reduced the total chair time by 78% and nurse time by 55%. Total average costs (excluding drug costs) were €103,47 and €77.99 for conventional infusion and the elastomeric pump, respectively, showcasing potential savings of €25.48 (P < 0.001) per administration. CONCLUSIONS: This study demonstrated that the elastomeric pump not only offers substantial cost savings but also enhances the treatment capacity of the oncology day care unit. These findings support the adoption of the elastomeric pump in clinical settings as a cost-saving and efficient alternative to conventional infusion. TRIAL REGISTRATION: This study has been registered in the National Trial Register (NTR), with the reference number NTR NL9473. Registration date: 05-05-2021.

External validation and updating of the infusion rate individualization of soybean oil-based intravenous lipid emulsion: A descriptive cohort study.

BACKGROUND: Safe and efficient provision of intravenous lipid emulsion (ILE) requires a strategy to individualize infusion rates. Estimating the maximum acceptable infusion rate (MaxInfRate) of soybean oil-based ILE (SO-ILE) in individuals by using a triglyceride (TG) kinetic model was reported to be feasible. In this study, we aimed to externally validate and, if needed, update the MaxInfRate estimation. METHODS: The maximum TG concentration (TGmax) in patients receiving SO-ILE at MaxInfRate was evaluated to determine if it met the definition of being <400 mg/dl for 90th percentile of patients. The TG kinetic model was evaluated through prediction performance checks and was subsequently updated using the data set of both the previous model development and present validation studies. RESULTS: Out of 83 patients, 74 had TGmax <400 mg/dl, corresponding to a probability of 89.2% (95% CI, 81.9%-95.2%), and the 90th percentile of TGmax was 400 mg/dl (95% CI, 328-490 mg/dl), closely aligned with the theoretical values. However, the individual TGmax values were biased by the infusion rate because the covariate effects were overestimated in the TG kinetic model, requiring a minor revision. The updated MaxInfRate with the combined data set showed unbiased and more accurate predictions. CONCLUSION: The MaxInfRate was validated in external inpatients and updated with all available data. MaxInfRate estimation for individuals could be an option for the safe and efficient provision of SO-ILE.

Low-Concentration Norepinephrine Infusion for Major Surgery: A Safety and Feasibility Pilot Randomized Controlled Trial.

BACKGROUND: Prevention of hypotension during the intra- and postoperative period is an important goal. Peripheral administration of low-concentration norepinephrine may be a safe and effective strategy to reduce the risk of hypotension. METHODS: We conducted a 2-center, randomized pilot feasibility trial, with a target of 60 adult patients undergoing major noncardiac surgery. We randomized patients to receive a peripheral low-concentration (10 µg/mL) norepinephrine or placebo (saline 0.9%) infusion. The study drug infusion was titrated to achieve a minimum systolic blood pressure target, preselected within 10% of baseline value and within the range limit 100 to 120 mm Hg during surgery and for up to 4 or 24 hours postoperatively. RESULTS: We achieved a high consent rate (84%), successful study drug administration throughout surgery (98% of patients) and absence of unblinding. There were no important study drug-related adverse events. The average intraoperative systolic blood pressure was 120 ± 12.6 mm Hg in the norepinephrine group and 115 ± 14.9 mm Hg in the placebo group. The mean difference between the intraoperative systolic blood pressure achieved less the preselected minimum systolic blood pressure target was 10.0 ± 12.7 mm Hg in the norepinephrine group and 2.9 ± 14.7 mm Hg in the placebo group; difference in means, 7.1 (95% confidence interval, 0.2-14.0) mm Hg. CONCLUSIONS: A future large trial evaluating the effectiveness and safety of peripheral administration of low-concentration norepinephrine during the perioperative period is feasible, and likely to achieve a minimum systolic blood pressure threshold.

Off-label use of plastic syringes with silicone oil for intravenous infusion bags of antibodies.

The formation of particulates in post-manufacture biopharmaceuticals continues to be a major concern in medical treatment. This study was designed to evaluate the content of micro-sized particles using flow imaging of antibodies in intravenous infusion bags. Intravenous immunoglobulin (IVIG) and Avastin® were selected as model drugs and plastic syringes with and without silicone oil (SO) were used to transfer the drugs into the bags (0.9% saline or 5% dextrose). Antibodies exposed to SO had significantly increased levels of microparticles in both diluents, suggesting SO accelerates particle formation, especially at a higher antibody concentration. Even before the drop stress, their count exceeded the USP guideline. Dropping the bags in the presence of SO produced larger microparticles. Meanwhile, air bubbles were retained longer in saline suggesting more protein film formation on its air-water interface. Overall, both drugs were conformationally stable and produced less particles in dextrose than in saline.

Dose individualization of intravenous busulfan in pediatric patients undergoing bone marrow transplantation: impact and in vitro evaluation of infusion lag-time.

OBJECTIVES: To apply therapeutic drug monitoring and dose-individualization of intravenous Busulfan to paediatric patients and evaluate the impact of syringe-pump induced Busulfan infusion lag-time after in vitro estimation. METHODS: 76 children and adolescents were administered 2 h intravenous Busulfan infusion every 6 h (16 doses). Busulfan plasma levels, withdrawn by an optimized sampling scheme and measured by a validated HPLC-PDA method, were used to estimate basic PK parameters, AUC, Cmax, kel, t1/2, applying Non-Compartmental Analysis. In vivo infusion lag-time was simulated in vitro and used to evaluate its impact on AUC estimation. KEY FINDINGS: Mean (%CV) Busulfan AUC, Cmax, clearance and t1/2 for pediatric population were found 962.3 µm × min (33.1), 0.95 mg/L (41.4), 0.27 L/h/kg (33.3), 2.2 h (27.8), respectively. TDM applied to 76 children revealed 6 (7.9%) being above and 25 (32.9%) below therapeutic-range (AUC: 900-1350 µm × min). After dose correction, all patients were measured below toxic levels (AUC < 1500 µm × min), no patient below 900 µm × min. Incorporation of infusion lag-time revealed lower AUCs with 17.1% more patients and 23.1% more younger patients, with body weight <16 kg, being below the therapeutic-range. CONCLUSIONS: TDM, applied successfully to 76 children, confirmed the need for Busulfan dose-individualization in paediatric patients. Infusion lag-time was proved clinically significant for younger, low body-weight patients and those close to the lower therapeutic-range limit.

A surgical method for continuous intraportal infusion of gut microbial metabolites in mice.

Gut microbe-derived metabolites influence human physiology and disease. However, establishing mechanistic links between gut microbial metabolites and disease pathogenesis in animal models remains challenging. The major route of absorption for microbe-derived small molecules is venous drainage via the portal vein to the liver. In the event of presystemic hepatic metabolism, the route of metabolite administration becomes critical. To our knowledge, we describe here a novel portal vein cannulation technique using a s.c. implanted osmotic pump to achieve continuous portal vein infusion in mice. We first administered the microbial metabolite trimethylamine (TMA) over 4 weeks, during which increased peripheral plasma levels of TMA and its host liver-derived cometabolite, trimethylamine-N-oxide, were observed when compared with a vehicle control. Next, 4-hydroxyphenylacetic acid (4-HPAA), a microbial metabolite that undergoes extensive presystemic hepatic metabolism, was administered intraportally to examine effects on hepatic gene expression. As expected, hepatic levels of 4-HPAA were elevated when compared with the control group while peripheral plasma 4-HPAA levels remained the same. Moreover, significant changes in the hepatic transcriptome were revealed by an unbiased RNA-Seq approach. Collectively, to our knowledge this work describes a novel method for administering gut microbe-derived metabolites via the portal vein, mimicking their physiologic delivery in vivo.

Outpatient therapy with piperacillin/tazobactam using elastomeric pumps in patients with Pseudomonas aeruginosa infection.

The aim of this study was to evaluate the efficacy and safety of outpatient antimicrobial therapy with piperacillin-tazobactam in continuous infusion using elastomeric pumps and to evaluate the economic impact compared with conventional hospital treatment in patients with Pseudomonas aeruginosa (PA) infections. This is an observational study. Patients with PA infection treated with continuous piperacillin-tazobactam infusion using elastomeric pumps in our hospital between January 2015 and December 2017 were included. Primary outcomes were mortality during antibiotic treatment and mortality at 30 days. Secondary outcomes were reinfection or relapse at 30 days and clinical cure rate. The cost of each episode was compared with theoretical cost of the same treatment using conventional hospitalization. 35 patients were included. One patient (2.9%) died during the treatment. Overall 30-day mortality was 5.7%. No death was related to infection by PA. One patient (2.9%) had a reinfection at 30 days. Cure was achieved in 93% of patients at the end of treatment. There were no severe complications related to elastomeric pumps. Treatment cost with outpatient antimicrobial therapy was 67% lower than theoretical cost with conventional hospital treatment. Oupatient antimicrobial therapy with piperacillin-tazobactam in continuous infusion using elastomeric pumps in patients with PA infections is safe and effective with lower costs.

Stepwise shortening of agalsidase beta infusion duration in Fabry disease: Clinical experience with infusion rate escalation protocol.

BACKGROUND: Although enzyme replacement therapy with agalsidase beta resulted in a variety of clinical benefits, life-long biweekly intravenous infusion may impact on patients' quality of life. Moreover, regular infusions are time-consuming: although a stepwise shortening of infusion duration is allowed up to a minimum of 1.5 hr, in most centers it remains ≥3 hr, and no data exists about the safety and tolerability of agalsidase beta administration at maximum tolerated infusion rate. METHODS: In this study, we reported our experience with a stepwise infusion rate escalation protocol developed in our center in a cohort of 53 Fabry patients (both already receiving and treatment-naΪve), and explored factors predictive for the infusion rate increase tolerability. RESULTS: Fifty-two patients (98%) reduced infusion duration ≤3 hr; of these, 38 (72%) even reached a duration ≤2 hr. We found a significant difference between the mean duration reached by already treated and naΪve patients (p < .01). More severely affected patients (male patients and those with lower enzyme activity) received longer infusions for higher risk of infusion-associated reactions (IARs). A significant correlation between anti-agalsidase antibodies and IARs was found. CONCLUSION: Our infusion rate escalation protocol is safe and could improve patient compliance, satisfaction and quality of life.

Ketamine Use in the Surgical Patient: a Literature Review.

PURPOSE OF REVIEW: While ketamine is an established anesthetic, its role in the management of acute surgical pain is less certain. Therefore, a literature review is warranted to examine the role of ketamine in acute pain management. RECENT FINDINGS: The use of ketamine appears to be most efficacious in larger procedures that lead to increased systemic inflammation or extensive tissue damage. In addition, ketamine seems to be most successful when administered consistently throughout a procedure, such as by an infusion instead of a single bolus, in order to have adequate dosing for an analgesic effect. Therefore, the focus of research should be on procedures that lead to moderate to severe pain using frequent dosing to determine the most effective role of ketamine. Most importantly, the current literature shows that ketamine can be used as a successful part of multimodal anesthesia with few side effects in patients undergoing major procedures associated with moderate to severe pain.

Intravenous Infusion of Lidocaine Can Accelerate Postoperative Early Recovery in Patients Undergoing Surgery for Obstructive Sleep Apnea.

Obstructive sleep apnea (OSA) is defined by intermittent and recurrent episodes of partial or complete obstruction of the upper airway during sleep. Intermittent and recurrent hypoxia/reoxygenation is the main pathophysiological mechanism of OSA. Its consequences include systemic inflammation, activation of the sympathetic nervous system, and release of oxygen free radicals. Infusion of intravenous (IV) lidocaine has anti-inflammatory, antihyperalgesic, and analgesic properties, supporting its use as an anesthetic adjuvant. Lidocaine can reduce nociception and/or cardiovascular responses to surgical stress, as well as postoperative pain and/or analgesic requirements. Because of the high prevalence of OSA in obese patients, the use of opioids to manage postoperative pain in that population is often accompanied by the development of adverse respiratory events, such as hypoventilation and hypoxemia. IV infusion of lidocaine has been shown to enhance the quality of early recovery after laparoscopic bariatric and upper airway surgery. However, limited evidence exists regarding its use in patients undergoing surgery for OSA. In addition, whether IV infusion of lidocaine can improve postoperative early recovery in patients undergoing surgery for OSA remains unknown. Therefore, we hypothesized that IV infusion of lidocaine can improve postoperative early recovery in patients undergoing surgery for OSA. Perioperative infusion also may be a promising analgesic adjunct to enhanced recovery after surgery (ERAS) protocols.

Time de acesso vascular e terapia infusional: satisfação da equipe de saúde em hospital pediátrico / Vascular access and infusional therapy team: satisfaction of the health team at pediatric hospital / Equipo de acceso vascular y terapia infusional: satisfacción del equipo de salud en hospital pediátrico

Objetivos: Conhecer a satisfação e qualidade do serviço sobre time de acesso vascular e terapia infusional (TAVTI) e identificar a importância do TAVTI para a equipe de saúde. Metodo: Trata-se de uma pesquisa de campo exploratória, descritiva, com abordagem quantitativa e qualitativa. Aplicamos formulários para 149 profissionais. Resultados: Dos participantes, 46,97%(n:70) refere total satisfação frente ao TAVTI; a minoria 0,67%(n:1) demonstra insatisfação total; a maioria considera o serviço muito importante 71,14%(n:106) e excelente atuação para 44,96%(n:67). Apenas 1,34%(2) dos profissionais considerou a qualidade do trabalho regular. Dos participantes, 126 declararam: serviço humanizado; seguro para o paciente; necessita de capacitação e treinamento; material seguro; período integral. Conclusão: A atuação do TAVTI demonstra ser efetiva. Constatou-se a satisfação da equipe de saúde e a importância na pediatria devido à preservação do acesso venoso e o desejo dos profissionais em manter o TAVTI período integral. Frente ao percentual de qualidade considerado, excelente e ótimo.(AU)

Objectives: To know the satisfaction and quality of service on the vascular access and infusional therapy team (TAVTI) and to identify the importance of TAVTI for the health team. Methodo: This is an exploratory, descriptive field research, with a quantitative and qualitative approach. We apply forms to 149 professionals. Results: Of the participants, 46.97% (n: 70) reported total satisfaction with TAVTI; the minority 0.67% (n: 1) shows total dissatisfaction; the majority considered the service very important 71.14% (n: 106) and excellent performance for 44.96% (n: 67). Only 1.34% (2) of the professionals considered the quality of work to be regular. Of the participants, 126 declared: humanized service; safe for the patient; needs qualification and training; safe material; Full time. Conclusion: The performance of TAVTI proves to be effective. The satisfaction of the health team and the importance in pediatrics were found due to the preservation of venous access and the desire of professionals to maintain TAVTI full time. In view of the percentage of quality considered, excellent and great.(AU)

Objetivos: Conocer la satisfacción y calidad del servicio del equipo de acceso vascular y terapia infusional (TAVTI) e identificar la importancia de TAVTI para el equipo de salud. Metodo: Se trata de una investigación de campo exploratoria, descriptiva, con enfoque cuantitativo y cualitativo. Aplicamos formularios a 149 profesionales. Resultados: De los participantes, el 46,97% (n: 70) reportaron satisfacción total con TAVTI; la minoría 0,67% (n: 1) muestra total insatisfacción; la mayoría consideró el servicio muy importante 71,14% (n: 106) y excelente desempeño para el 44,96% (n: 67). Solo el 1,34% (2) de los profesionales consideró regular la calidad del trabajo. De los participantes, 126 declararon: servicio humanizado; seguro para el paciente; necesita cualificación y formación; material seguro; período integral. Conclusión: La actuación de TAVTI demuestra ser eficaz. La satisfacción del equipo de salud y la importancia en pediatría se encontraron debido a la preservación del acceso venoso y el deseo de los profesionales de mantener TAVTI a tiempo completo. En vista del porcentaje de calidad considerado, excelente y óptimo.(AU)

Intravenous infusion of mesenchymal stem cells delays disease progression in the SOD1G93A transgenic amyotrophic lateral sclerosis rat model.

ALS is a devastating neurodegenerative disease with few curative strategies. Both sporadic and familial ALS display common clinical features that show progressive paralysis. The pathogenesis remains unclear, but disruption of the blood-spinal cord barrier (BSCB) may contribute to the degeneration of motor neurons. Thus, restoration of the disrupted BSCB and neuroprotection for degenerating motor neurons could be therapeutic targets. We tested the hypothesis that an intravenous infusion of MSCs would delay disease progression through the preservation of BSCB function and increased expression of a neurotrophic factor, neurturin, in SOD1G93A ALS rats. When the open-field locomotor function was under 16 on the Basso, Beattie, and Bresnahan (BBB) scoring scale, the rats were randomized into two groups; one received an intravenous infusion of MSCs, while the other received vehicle alone. Locomotor function was recorded using BBB scoring and rotarod testing. Histological analyses, quantitative reverse transcription-polymerase chain reaction (qRT-PCR), were performed. The MSC group exhibited reduced deterioration of locomotor activity compared to the vehicle group, which displayed progressive deterioration of hind limb function. We observed the protection of motor neuron loss and preservation of microvasculature using Evans blue leakage and immunohistochemical analyses in the MSC group. Confocal microscopy revealed infused green fluorescent protein+ (GFP+) MSCs in the spinal cord, and the GFP gene was detected by nested PCR. Neurturin expression levels were significantly higher in the MSC group. Thus, restoration of the BSCB and the protection of motor neurons might be contributing mechanisms to delay disease progression in SOD1G93A ALS rats.

Safety of two-hour intermittent intravenous infusions of tacrolimus in the allogeneic hematopoietic stem cell transplantation unit.

At our institution, tacrolimus is used as a second-line agent for the prevention and treatment of graft-versus-host-disease in the allogeneic hematopoietic stem cell transplantation (HSCT) unit after patients have experienced a serious or intolerable adverse event to cyclosporine. As per our standard practice, tacrolimus is administered via 2-h intermittent IV infusions (IIVs) every 12 h rather than continuous IV infusion. Shorter infusion times are cautioned due to concerns of higher rates of nephrotoxicity, neurotoxicity and infusion-related reactions, although there is a paucity of data to support this claim. Our primary objective was to evaluate the safety of a 2-h IIV of tacrolimus in an adult HSCT population. We retrospectively reviewed the charts of 104 patients who received tacrolimus by IIV (3574 doses; median = 22, range 1-158, IQR = 28) from 2002 to 2016. Primary outcomes collected include rates of nephrotoxicity, neurotoxicity and infusion-related reactions. One (0.9%) grade 2 infusion-related reaction occurred and resolved without discontinuation of tacrolimus. Of 16 incidences (13.6%) of nephrotoxicity, all but 10 (8.5%) cases resolved. Precipitating factors for nephrotoxicity unrelated to tacrolimus were identified in all 10 cases. There were 41 incidences (35%) of neurotoxicity, of which, 8 (6.8%) were considered serious. All neurotoxicity reverted to baseline or resolved completely. We propose that a 2-h IIV of tacrolimus is a safe method of administration in the adult HSCT setting.

Inherent and modifiable risk factors for peripheral venous catheter failure during cancer treatment: a prospective cohort study.

PURPOSE: To identify modifiable and non-modifiable risk factors for peripheral intravenous catheter (PIV) failure among patients requiring intravenous treatment for oncology and haematology conditions. METHODS: A single-centre prospective cohort study was conducted between October 2017 and February 2019. Adult in-patients requiring a PIV for therapy were prospectively recruited from two cancer units at a tertiary hospital in Queensland, Australia. The primary outcome was a composite of complications leading to PIV failure (local and bloodstream infection; occlusion; infiltration/extravasation; leakage; dislodgement; and/or phlebitis). Secondary outcomes were (i) PIV dwell time; (ii) insertion and (iii) failure of a CVAD; (iv) adverse events; (v) length of hospital stay. Outcomes were investigated using Bayesian multivariable linear regression modelling and survival analysis. RESULTS: Of 200 participants, 396 PIVs were included. PIV failure incidence was 34.9%; the most common failure type was occlusion/infiltration (n = 74, 18.7%), then dislodgement (n = 33, 8.3%), and phlebitis (n = 30, 7.6%). While several patient and treatment risk factors were significant in univariable modelling, in the final multivariable model, only the use of non-sterile tape (external to the primary dressing) was significantly associated with decreased PIV dislodgement (hazard ratio 0.06, 95% confidence interval 0.01, 0.48; p = 0.008). CONCLUSION: PIV failure rates among patients receiving cancer treatment are high, the sequelae of which may include delayed treatment and infection. Larger studies on risk factors and interventions to prevent PIV failure in this population are needed; however, the use of secondary securements (such as non-sterile tape) to provide further securement to the primary PIV dressing is particularly important. TRIAL REGISTRATION: Study methods were registered prospectively with the Australian New Zealand Clinical Trials Registry on the 27th March 2017 (ACTRN12617000438358); https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=372191&isReview=true.

Application of transesophageal echocardiography for localization in totally implantable venous access port implantation through subclavian approach in children.

A totally implantable venous access port (TIVAP) is important in children who need intravenous infusion for a long time. A number of studies have shown methods for locating the tip of the TIVAP catheter. To explore whether transesophageal echocardiography (TEE) can be used to accurately locate the TIVAP catheter tip through a subclavian approach and to improve the rate of correct TIVAP catheter placement and reduce complications of TIVAP placement. In 36 children who needed TIVAP implantation surgery, we used real-time TEE guidance to place the catheter tip around the crista terminalis. In all children, chest X-rays were used to figure out whether the catheter tip as localized by TEE was within the T5-T7 segment. Then, we compared the length of the catheter calculated by the height formula and the actual catheter length applied under TEE guidance. The medical records, surgical details, nursing records, and recorded complications were collected during the follow-up. The success rate of TIVAP implantation was 100% in all enrolled patients and no hemopneumothorax or pinch-off syndrome occurred. Compared with TEE, chest X-ray showed a coincidence rate of 80.56% in correctly detecting the TIVAP catheter tip locate. The height-derived catheter length (11.0 [9.6, 11.8]) cm and the TEE-derived catheter length (10.0 [9.3, 10.8]) cm were significantly different (p < .001). TEE can be used to guide TIVAP catheter positioning through a left subclavian approach in children accurately and successfully and more accurate than chest X-ray and height calculation formula.