Safe administration of noradrenaline by the peripheral route: A systematic review. / Administración segura de noradrenalina por vía periférica: una revisión sistemática.

PURPOSE: To review and analyze the available literature on peripheral administration of noradrenaline (NA) with the aim of providing recommendations to ensure correct use and patient safety. METHODS: Systematic review on the databases PubMed, ISI Web of Science, SCOPUS and Science Direct, using the following search terms: ("Noradrenaline" [Mesh]) AND ("Norepinephrine" [Mesh]) AND ("Vasopressors" [Mesh]) AND ("Peripheral infusions" [Mesh]) OR ("Extravasations" [Mesh]). A total of 1,040 articles were identified. Animal studies and studies written in languages other than English were excluded. Finally, 83 articles were included. RESULTS: NA can be administered peripherally. The risk of extravasation should be taken into account, with phentolamine being the first pharmacological line of treatment. It has also been related to the appearance of thrombophlebitis, cellulitis, tissue necrosis, limb ischemia and gangrene, although its incidence seems to be low. The use of peripheral NA in children seems to be carried out without obvious complications. The use of standard concentrations is suggested to reduce the risk of errors. It is recommended to use 0.9% saline as the default diluent for peripheral NA. CONCLUSIONS: Peripheral infusions of NA could be a safe and beneficial option in early resuscitation provided that a number of guidelines are followed that reduce the likelihood of complications associated with this route.

Reducing agalsidase beta infusion time in Fabry patients: low incidence of antibody formation and infusion-associated reactions in an Italian multicenter study.

BACKGROUND: Fabry disease is a rare progressive X-linked lysosomal storage disease caused by mutations in the GLA gene that encodes α-galactosidase A. Agalsidase beta is a recombinant enzyme replacement therapy authorized in Europe at a standard dose of 1.0 mg/kg intravenously every other week at an initial infusion rate of ≤ 0.25 mg/min until patient tolerance is established, after which the infusion rate may be increased gradually. However, specific practical guidance regarding the progressive reduction in infusion time is lacking. This study investigated a new and specific protocol for reducing agalsidase beta infusion time in which a stable dosage of 15 mg/h is infused for the first four months, and the infusion rate is increased progressively from 15 to 35 mg/h for the subsequent four infusions. The shortest infusion time is reached after six months and maintained thereafter. The incidence of infusion-associated reactions (IARs) and the development of anti-drug antibodies were analyzed, and the disease burden and the clinical evolution of the disease at 12 months were evaluated. RESULTS: Twenty-five of the 31 patients were naïve to enzyme or chaperone treatment at baseline and six patients had been switched from agalsidase alfa. The reduced infusion time protocol was well tolerated. Only one patient exhibited an IAR, with mild symptoms that resolved with low-dose steroids. Six patients globally seroconverted during treatment (4 with a classic phenotype and 2 with late-onset disease). All but three patients were seronegative at month 12. All patients were stable at the study's end (FAbry STabilization indEX value < 20%); reducing infusion time did not negatively impact clinical outcomes in any patient. The perceived medical assessment showed that the quality of life of all patients improved. CONCLUSIONS: The study demonstrates that reducing agalsidase beta infusion time is possible and safe from both an immunogenic and clinical point of view. The use of a low infusion rate in the first months when the probability of onset of the development of antibodies is higher contributed to very limited seroconversion to antibody-positive status.

Safety and tolerability of agalsidase beta infusions shorter than 90 min in patients with Fabry disease: post-hoc analysis of a Japanese post-marketing study.

BACKGROUND: Agalsidase beta, an enzyme replacement therapy for Fabry disease, is dosed biweekly at 1 mg/kg body weight, with increasing infusion rates based on tolerability. The US label specifies ≥ 90-min infusions for all patients; the US and EU labels require ≤ 15 mg/hr infusions in patients < 30 kg. The Japanese label allows infusions up to 30 mg/hr, allowing < 90-min dosing for some patients weighing < 45 kg. Japanese post-marketing data were analyzed for rate of infusion-associated reactions (IARs), adverse events (AEs), and serious AEs (SAEs) based on infusion rate and patient attributes (weight, antibody status). RESULTS: Data were available for 436 reduced-duration infusions (< 90 min) and 2242 standard infusions (≥ 90 min). SAEs were rare (0.6%), and the frequency of all safety events decreased over the treatment course. Little impact of infusion duration on safety outcomes was observed: IARs and AEs were numerically more common when infusion duration was ≥ 90 min compared to < 90 min (IARs: 2.0% vs 0.9%; AEs: 2.9% vs 1.4%), while the rate of SAEs was similar (0.4% vs 0.5%). IAR, AE, and SAE frequencies decreased significantly with increasing infusion rates, and this trend was consistent in patients < 30 kg. Safety events tended to be less frequent in patients < 30 kg vs those ≥ 30 kg (IARs: 1.8% vs 2.1%; AEs: 2.3% vs 3.6%; SAEs: 0.0% vs 0.6%), although the differences were not statistically significant. IARs occurred in < 1% of all infusions in the < 30 kg group, 84% of which were < 90 min. More anti-agalsidase beta antibody-positive patients experienced IARs (41.9% vs 30.7%; P = 0.0445) and AEs (61.1% vs 49.3%; P = 0.0497) vs antibody-negative patients; however, there was no significant difference in the frequency of SAEs. In patients with available data, no changes in antibody status were observed after infusion durations were reduced to < 90 min. CONCLUSIONS: The results of this post-hoc analysis demonstrated no significant impact of infusion duration on safety outcomes, and no significant difference in outcomes between patients of different weights. These findings suggest that infusion times in patients who are tolerating treatment can, with careful monitoring, be gradually decreased.

Infusion timing and sleep habits of adults receiving home parenteral and enteral nutrition: A patient-oriented survey study.

BACKGROUND: The emerging field of chrononutrition investigates the effects of the timing of nutritional intake on human physiology and disease pathology. It remains largely unknown when patients receiving home nutrition support routinely administer home parenteral nutrition (HPN) and/or home enteral nutrition (HEN). METHODS: The present descriptive study included data collected from a patient-oriented survey designed to assess the timing of infusions and sleep habits of patients receiving HPN and HEN in the United States. RESULTS: A total of 100 patients were included. Patients had a mean age of 44.1 years and 81% were female. Among 73 patients supported with HPN and 27 patients supported with HEN, 86% and 44% reported overnight infusions, respectively. The median start and end times of overnight infusions were 2100 (interquartile range [IQR] = 1900-2200) and 0800 (IQR = 0700-1000), respectively, for HPN and 2000 (IQR = 1845-2137) and 0845 (IQR = 0723-1000), respectively, for HEN. Overnight infusions started 2.0 h (IQR = 1.1-3.0) and 2.0 h (IQR = 0.6-3.3) before bedtime for HPN and HEN, respectively, and stopped 12.9 min (IQR = -21.3 to 29.1) and 30.0 min (IQR = -17.1 to 79.3) after wake time for HPN and HEN, respectively. Sleep disruption because of nutrition support or urination was most common among patients receiving infusions overnight compared with those receiving infusions continuously or during the daytime. CONCLUSIONS: Our survey study focusing on a novel and medically relevant dimension of nutrition found that most HPN-dependent and HEN-dependent patients receive infusions overnight while asleep. Our findings suggest that overnight infusions coinciding with sleep may result in sleep and circadian disruption.

Long-term results of teduglutide treatment for chronic intestinal failure - Insights from a national, multi-centric patient home-care service program.

BACKGROUND & AIMS: Teduglutide is a Glucagon-like peptide-2 (GLP-2) agonist indicated for the treatment of patients with parenteral support (PS) dependent short bowel syndrome (SBS) with chronic intestinal failure (cIF). Its application is accompanied by a structured nation-wide home-care service program in Germany. We investigated care characteristics and outcome parameters in a clinical real-world observational setting. METHODS: Data generated within a therapy-accompanying home-care service program for adult SBS-cIF patients were analyzed retrospectively for patients treated up to 1 year (data cut: April 2020). RESULTS: In total, 52 teduglutide-treated patients were included by 6 German cIF centers. At teduglutide administration start, 49/52 patients were on PS, 3 of them without macronutrients. The majority of patients received individualized parenteral nutrition (PN) (n = 32/46), while 13/46 were on commercial premixed bags. PS application was done by patients themselves (37%), home-care nurses (19%), relatives (8%) or by a combination of those (16%). In patients with PS dependency at baseline and available follow-up data (n = 40-44), teduglutide treatment resulted in significantly reduced PN days, caloric needs, infusion time, and infusion volume after 6 and 12 months. After 1 year, reduction of infusion time was positively correlated with a reduction of PN calories and volume; 30 patients (68%) were responders (PS-volume reduction ≥20%), and 6 patients (14%) were completely weaned off PS. Sleep disturbances per night were significantly reduced after 3 months of treatment and stool characteristics improved in consistency and significantly in frequency, while meal frequency remained stable. CONCLUSIONS: Teduglutide treatment associated reduction in PS volume and calories was accompanied by reduced infusion days, infusion times, sleep disturbances, stable oral intake surrogates, and improved stool characteristics, all of these potential parameters for improving quality of life. Furthermore, analyzed care characteristics reflect SBS-cIF treatment as a complex, resource-intensive and demanding task for both, healthcare system and patients.

Extraction Kinetics and Reaction Rates of Sacred Lotus Stamen Tea Infusion-Derived Flavonoids in Relation with Its Antioxidant Capacity.

Stamen tea from Nelumbo nucifera Gaertn. (or the so-called sacred lotus) is widely consumed, and its flavonoids provide various human health benefits. The method used for tea preparation for consumption, namely the infusion time, may affect the levels of extractable flavonoids, ultimately affecting their biological effects. To date, there is no report on this critical information. Thus, this study aims to determine the kinetics of solid liquid extraction of flavonoid from sacred lotus stamen using the traditional method of preparing sacred lotus stamen tea. Phytochemical composition was also analyzed using high-performance liquid chromatography (HPLC). The antioxidant potential of stamen tea was also determined. The results indicated that the infusion time critically affects the concentrations of flavonoids and the antioxidant capacity of sacred lotus stamen tea, with a minimum infusion time of 5-12 min being required to release the different flavonoids from the tea. The extraction was modeled using second order kinetics. The rate of release was investigated by the glycosylation pattern, with flavonoid diglycosides, e.g., rutin and Kae-3-Rob, being released faster than flavonoid monoglycosides. The antioxidant activity was also highly correlated with flavonoid levels during infusion. Taken together, data obtained here underline that, among others, the infusion time should be considered for the experimental design of future epidemiological studies and/or clinical trials to reach the highest health benefits.

Pharmacokinetics and Safety of Doripenem in Healthy Chinese Subjects and Monte Carlo Dosing Simulations.

The aim of this study was to investigate the pharmacokinetics (PK) of doripenem in healthy Chinese subjects and evaluate the optimal dosage regimens of doripenem. A randomized, single-dose, three-period, self-crossover controlled extended-infusion clinical trial was conducted with 12 healthy Chinese subjects. Plasma and urine samples were collected to determine doripenem concentrations. Non-compartmental and population PK analysis were performed to characterize the PK of doripenem. The Monte Carlo simulation was employed to optimize dosing regimens based on the probability of target attainment of doripenem against pathogens with different minimum inhibitory concentrations (MIC). All 12 healthy Chinese subjects completed the study, and the doripenem was well tolerated. The study showed linearity relationships in the peak plasma concentration and the area under the concentration-time curve after intravenous infusion of doripenem from 0.25 g to 1.0 g. The cumulative urinary recovery rate of doripenem was 68.1-72.0% within 24 h. PPK modeling showed a two-compartmental model, with first-order elimination presenting the best fit for doripenem PK. Monte Carlo simulation results showed that 1.0 g q12h or 0.5 g q8h was an optimal regimen for pathogens susceptible to doripenem (MIC ≤ 1 mg/L); while high dose and extended infusion (1 g, q8h, 4 h infusion) was proposed for unsusceptible pathogens (2 ≤ MIC ≤ 8 mg/L). In the dose range of 0.25 to 1.0 g, doripenem showed linear pharmacokinetics. Doripenem at 1.0 g with a prolonged infusion time of 4 h was predicted to be effective against pathogens with MICs as high as 8 mg/L.

A Preliminary, Single-Center Retrospective Chart Review of Infusion Times of Intravenous Immune Globulin in Kawasaki Disease and Clinical Outcomes.

OBJECTIVE: Patients diagnosed with Kawasaki disease (KD) are at a high risk of developing coronary artery aneurysms. Intravenous immune globulin (IVIG) given in combination with aspirin is the standard of treatment for the prevention of coronary aneurysm. IVIG is recommended to be administered as a dose of 2 g/kg infused during 10 to 12 hours for the prevention of coronary aneurysms in KD; however, this does not always occur in practice. We aimed to investigate if an infusion time of <10 hours is associated with more coronary artery aneurysms than the recommended infusion time of 10 to 12 hours. METHODS: Patients with a diagnosis of and treated for KD with IVIG at the University of Chicago Medicine Comer Children's Hospital were identified by drug use reports that included patients who received IVIG between September 2008 and August 2018. Data were collected though chart review and patients were divided into 2 groups based on duration of infusion (<10 hours and 10-12 hours). The primary outcome was the incidence of coronary artery aneurysm. The secondary outcome was the time to defervescence. The safety outcome was the development of renal dysfunction. RESULTS: A total of 70 patients were screened and 44 were included in the analysis. Coronary aneurysm occurred in 2 of 33 patients (6.0%) in the <10-hour group and no patients in the 10- to 12-hour group (p = 0.558). The median time to defervescence was 0.5 hours in the <10-hour group and 0.95 hours in the 10- to 12-hour group (p = 0.166). The incidence of acute kidney injury was 6% (2 of 33 patients) in the 10-hour group and 9.1% (1 of 11 patients) in the 10- to 12-hour group (p = 0.588). CONCLUSIONS: All incidences of coronary artery aneurysm occurred in the patients who received IVIG with an infusion time of <10 hours. The incidence of acute kidney injury was numerically higher in the 10- to 12-hour group. Based on the recommendations in the American Heart Association KD guideline, our internal hospital policy, and our results, we recommend the infusion of IVIG be administered at a rate of 10 to 12 hours.

Ravulizumab 100 mg/mL formulation reduces infusion time and frequency, improving the patient and caregiver experience in the treatment of atypical haemolytic uraemic syndrome.

WHAT IS KNOWN AND OBJECTIVE: The C5 inhibitor eculizumab is the standard of care for treatment of atypical haemolytic uraemic syndrome (aHUS). Ravulizumab, a next-generation C5 inhibitor, was engineered to have a longer terminal half-life than eculizumab. We describe practical benefits of the advanced ravulizumab 100 mg/mL formulation. COMMENT: Use of ravulizumab results in fewer maintenance infusions per year (25%-50%) compared with eculizumab. Maintenance infusion time of ravulizumab 100 mg/mL is 2-4 times shorter than ravulizumab 10 mg/mL in all weight cohorts and approximately half that of eculizumab for patients weighing <40 kg. Ravulizumab 100 mg/mL requires fewer vials annually than eculizumab in most weight cohorts. WHAT IS NEW AND CONCLUSION: With ravulizumab 100 mg/mL, patients and caregivers experience fewer infusions per year and decreased annual infusion times, improving infusion experience. Infusion centres can expect corresponding decreases in resource utilization.

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.

Scheduling patient appointment in an infusion center: a mixed integer robust optimization approach.

Infusion centers are experiencing greater demand, resulting in long patient wait times. The duration of chemotherapy treatment sessions often varies, and this uncertainty also contributes to longer patient wait times and to staff overtime, if not managed properly. The impact of such long wait times can be significant for cancer patients due to their physical and emotional vulnerability. In this paper, a mixed integer programming infusion appointment scheduling (IAS) mathematical model is developed based on patient appointment data, obtained from a cancer center of an academic hospital in Central Virginia. This model minimizes the weighted sum of the total wait times of patients, the makespan and the number of beds used through the planning horizon. A mixed integer programming robust slack allocation (RSA) mathematical model is designed to find the optimal patient appointment schedules, considering the fact that infusion time of patients may take longer than expected. Since the models can only handle a small number of patients, a robust scheduling heuristic (RSH) is developed based on the adaptive large neighborhood search (ALNS) to find patient appointments of real size infusion centers. Computational experiments based on real data show the effectiveness of the scheduling models compared to the original scheduling system of the infusion center. Also, both robust approaches (RSA and RSH) are able to find more reliable schedules than their deterministic counterparts when infusion time of patients takes longer than the scheduled infusion time.

Rapid-Infusion Rituximab in a Pediatric Population.

OBJECTIVES: The use of rapid rituximab infusion in certain pediatric populations has generally been regarded as safe. The safety of our institution's rapid rituximab protocol was evaluated. METHODS: The primary end point was the number of and severity of adverse drug reactions. Secondary end points included a description of the patient population defined by the indication, dose, and number of rituximab infusions administered. Additionally, the difference in infusion times in hours of those receiving rapid rituximab infusions versus the theoretical infusion time of subsequent administration rate schedules was defined. RESULTS: A total of 88 infusions for 22 patients were reviewed. No dose-limiting adverse reactions were observed. Three patients experienced grade 1 isolated infusion-related adverse events during a single infusion encounter. Two of the three patients received additional doses of rapid rituximab infusions without incident, whereas the other patient no longer required rituximab therapy. CONCLUSIONS: The use of a 90-minute rituximab infusion protocol in pediatric patients with non-rheumatic diseases was well tolerated.

Antithymocyte globulin in pediatric allogeneic hematopoietic stem cell transplantation: Infusion time and tolerability.

Antithymocyte globulin is a major drug in transplantation. rATG has been successfully used to prevent graft-versus-host disease in allogeneic HSCT. However, its first infusion is associated with reactions ranging from simple fevers to distributive shocks and may interfere with the transplant conditioning. To evaluate the impact of rATG infusion rate on clinical tolerability, we conducted a retrospective study of all pediatric allogeneic HSCT patients who received rATG (Thymoglobulin®) as part of their conditioning at Lille University Hospital from 2003 to 2018. Until 2012, patients received rATG with a theoretical infusion time of 12 hours (12H group, n = 33). From 2012, they had a theoretical infusion time of 4 hours (4H group, n = 43). Patients from the 12H arm presented more ≥ grade 3 infusion-related reactions at first dose (70% versus 44%, P = .027), had significantly higher fever (median of 39.6°C versus 39.2°C, P = .002), and needed a greater use of symptomatic treatments. However, they received a slightly higher first dose of rATG (median of 2.7 versus 2.3 mg/kg, P = .042). In view of these results, a rATG infusion time of 4 hours can be a relevant option for pediatric transplant centers to avoid interference with the conditioning regimen and facilitate medical surveillance.

Systematic Review on Infusion Reactions to and Infusion Rate of Monoclonal Antibodies Used in Cancer Treatment.

BACKGROUND: Patients with cancer who are treated with monoclonal antibodies are at risk for developing infusion reactions. However, for some monoclonal antibodies, the incidence of infusion reactions is low or can be lowered by the use of adequate premedication schedules. It is often feasible to increase the infusion rate/lower the post-administration observation time. This review gives an overview of infusion reactions and the possibility of accelerating infusion rates. MATERIALS AND METHODS: Data on infusion reactions and infusion rates for all monoclonal antibodies that are licensed in the European Union for treatment of solid tumors or hematological malignancies, found by a literature search, were included in this review. RESULTS: For 11 out of the 21 monoclonal antibodies data exceeding the registration text were found and described. Faster infusion schedules are possible for bevacizumab, ipilimumab, nivolumab, panitimumab, and rituximab. CONCLUSION: We propose optimal infusion schedules for each drug.

Extended drip infusion of peripheral parental nutrition containing amino acids might be associated with Bacillus cereus bloodstream infection.

In some Japanese hospitals, patients using infusion bags for parenteral nutrition containing amino acids have developed Bacillus cereus bloodstream infections. We considered that proliferation of contaminated B cereus in the bag during prolonged drip infusion might be one of the causes of infection. This study indicated that 8 h is the maximum appropriate drip infusion time for peripheral parental nutrition containing amino acids to prevent B cereus bloodstream infections.

Cardiotoxicity with carfilzomib at doses greater than 27 mg/m2: A case series.

Carfilzomib is a second-generation proteasome inhibitor that irreversibly inhibits chymotrypsin-like (CT-L) activities of the proteasome, and is indicated for relapsed or refractory multiple myeloma. Cardiotoxicity is a well-established adverse effect of carfilzomib. The extent of cardiac toxicity in the literature spans anywhere from palpitations to cardiac arrest, with the most commonly reported manifestation being new-onset or worsening heart failure. A pre-clinical study of the pharmacokinetics and pharmacodynamics of carfilzomib given via intravenous bolus or 30-minute infusion in rats showed that carfilzomib can strongly induce apoptosis and potently damage cardiac myocytes at clinically relevant concentrations. Moreover, the mortality rate with the bolus administration was 44% whereas the same dose administered as a 30-minute infusion did not result in mortality. There remains limited clinical data regarding the safety of carfilzomib at doses of 27-56 mg/m2 based on infusion times as these doses have not been well studied. This retrospective review was conducted to evaluate the safety of carfilzomib at doses >27 mg/m2 at all infusion times.

A real-world, multi-site, observational study of infusion time and treatment satisfaction with rheumatoid arthritis patients treated with intravenous golimumab or infliximab.

OBJECTIVES: To assess real-world infusion times for golimumab (GLM-IV) and infliximab (IFX) for rheumatoid arthritis (RA) patients and factors associated with treatment satisfaction. METHODS: An observational study assessed infusion time including: clinic visit duration, RA medication preparation and infusion time, and infusion process time. Satisfaction was assessed by a modified Treatment Satisfaction Questionnaire for Medication (patient) and study-specific questionnaires (patient and clinic personnel). Comparative statistical testing for patient data utilized analysis of variance for continuous measures, and Fisher's exact or Chi-square test for categorical measures. Multivariate analysis was performed for the primary time endpoints and patient satisfaction. RESULTS: One hundred and fifty patients were enrolled from six US sites (72 GLM-IV, 78 IFX). The majority of patients were female (80.0%) and Caucasian (88.7%). GLM-IV required fewer vials per infusion (3.7) compared to IFX (4.9; p = .0001). Clinic visit duration (minutes) was shorter for GLM-IV (65.1) compared to IFX (153.1; p < .0001), as was total infusion time for RA medication (32.8 GLM-IV, 119.5 IFX; p < .0001) and infusion process times (45.8 GLM-IV, 134.1 IFX; p < .0001). Patients treated with GLM-IV reported higher satisfaction ratings with infusion time (p < .0001) and total visit time (p = .0003). Clinic personnel reported higher satisfaction with GLM-IV than IFX specific to medication preparation time, ease of mixing RA medication, frequency of patients requiring pre-medication, and infusion time. LIMITATIONS: Findings may not be representative of care delivery for all RA infusion practices or RA patients. CONCLUSIONS: Shorter overall clinic visit duration, infusion process, and RA medication infusion times were observed for GLM-IV compared to IFX. A shorter duration in infusion time was associated with higher patient and clinic personnel satisfaction ratings.

Safety profile of nivolumab administered as 30-min infusion: analysis of data from CheckMate 153.

PURPOSE: Nivolumab has been administered using a 60-min infusion time. Reducing this time to 30 min would benefit both patients and infusion facilities. This analysis compared the safety of 30- and 60-min infusions of nivolumab in patients with previously treated advanced non-small cell lung cancer. METHODS: CheckMate 153 is an open-label, phase 3b/4, predominantly community-based study ongoing in the United States and Canada. Patients with stage IIIB/IV disease with progression/recurrence after at least one prior systemic therapy received nivolumab 3 mg/kg every 2 weeks over 30 or 60 min for 1 year or until disease progression. The primary outcome overall was to estimate the incidence of grade 3-5 treatment-related select adverse events; a retrospective objective was to estimate the incidence of hypersensitivity/infusion-related reactions (IRRs) with the 30-min infusion. Exploratory pharmacokinetic analyses were performed using a population pharmacokinetics model. RESULTS: Of 1420 patients enrolled, 369 received only 30-min infusions and 368 received only 60-min infusions. Similar frequencies of hypersensitivity/IRRs were noted in patients receiving 30-min [2% (n = 8)] and 60-min [2% (n = 7)] infusions. Grade 3-4 treatment-related hypersensitivity/IRRs led to treatment discontinuation in < 1% of patients in each group; < 1% of patients in each group received systemic corticosteroids. Hypersensitivity/IRRs were managed by dosing interruptions, with minimal impact on total dose received. Nivolumab pharmacokinetics were predicted to be similar in the two groups. CONCLUSIONS: Nivolumab infused over 30 min had a comparable safety profile to the 60-min infusion, including a low incidence of IRRs.

Effects of a novel method for enteral nutrition infusion involving a viscosity-regulating pectin solution: A multicenter randomized controlled trial.

BACKGROUND & AIMS: The initial complications associated with infusion of enteral nutrition (EN) for clinical and nutritional care are vomiting, aspiration pneumonia, and diarrhea. There are many recommendations to prevent these complications. A novel method involving a viscosity-regulating pectin solution has been demonstrated. In Japan, this method along with the other so-called "semi-solid EN" approaches has been widely used in practice. However, there has been no randomized clinical trial to prove the efficiency and safety of a viscosity-regulating pectin solution in EN management. Therefore, we planned and initiated a multicenter randomized controlled trial to determine the efficiency and safety. METHODS: This study included 34 patients from 7 medical institutions who participated. Institutional review board (IRB) approval was obtained from all participating institutions. Patients who required EN management were enrolled and randomly assigned to the viscosity regulation of enteral feeding (VREF) group and control group. The VREF group (n = 15) was managed with the addition of a viscosity-regulating pectin solution. The control group (n = 12) was managed with conventional EN administration, usually in a gradual step-up method. Daily clinical symptoms of pneumonia, fever, vomiting, and diarrhea; defecation frequency; and stool form were observed in the 2 week trial period. The dose of EN and duration of infusion were also examined. RESULTS: A favorable trend for clinical symptoms was noticed in the VREF group. No significant differences were observed in episodes of pneumonia, fever, vomiting, and diarrhea between the 2 groups. An apparent reduction in infusion duration and hardening of stool form were noted in the VREF group. CONCLUSIONS: The novel method involving a viscosity-regulating pectin solution with EN administration can be clinically performed safely and efficiently, similar to the conventional method. Moreover, there were benefits, such as improvement in stool form, a short time for EN infusion, and a reduction in vomiting episodes, with the use of the novel method. This indicates some potential advantages in the quality of life among patients receiving this novel method.

Comparison of Hypersensitivity Reactions to Carboplatin Retreatment in Gynecologic Cancer Patients between One and Two Hour Infusions: a Randomized Trial Study

Objective: To compare the incidence rate of carboplatin hypersensitivity reactions (HSRs) in gynecologic cancer patients receiving one-hour or two-hour carboplatin retreatment infusions. Setting: A Prospective Randomized Controlled Trial. Methods: Recurrent gynecologic cancer patients 25 to 80-years of age who were scheduled to receive carboplatin retreatment after previously receiving at least six cycles of carboplatin without a history of platinum allergy were invited to enroll. They were randomized to receive either a one-hour or two-hour carboplatin infusion in each cycle. The nurses recorded any occurrence of HSR. Patients who developed carboplatin HSR were discontinued from the study. Results: Forty-five patients were enrolled and randomized to receive either a one-hour carboplatin infusion arm in 69 cycles or a two-hour infusion arm in 67 cycles. Both groups were well balanced regarding median age, body mass index, type of cancer, history of drug allergy, median platinum free interval time, median total number of previous carboplatin cycles, premedication type, regimen and median total dose of carboplatin. Five (3.67%) of the 136 cycles resulted in carboplatin HSR, all of which were Grade 1. Of these, four cycles developed HSR during the one-hour infusion and only one cycle with a two-hour infusion (P=0.37). The onset of carboplatin HSR occurred within 30-105 minutes after infusion start. Conclusion: Extending the carboplatin infusion time to two hours from one hour did not significantly decrease carboplatin HSR.