(1) Background: We aim to examine and improve phosphate prescribing as part of a quality assurance program by examining the change in the proportion of patients receiving phosphate with normal or high preceding serum phosphate concentrations before and after the introduction of the 24 h time limit to default phosphate prescription. (2) Methods: This was a quality assurance study conducted across three Australian adult intensive care units (ICUs). All adult patients with ICU lengths of stay greater than or equal to 48 h who had their serum phosphate concentrations measured were included. A 24 h time limit was introduced to the protocolised prescription in the electronic clinical information system for enteral and intravenous phosphate at participating ICUs. Patient characteristics, phosphate administration, and outcomes were compared before and after this time limit was introduced. The primary outcome was the proportion of patients to whom phosphate was prescribed after measurement of a normal or high serum phosphate level. Secondary outcomes were ICU length of stay, mortality, and discharge destination. (3) Results: A total of 1192 patients were included from three ICUs over the two periods. The proportion of patients with a normal or high measured phosphate level who then received phosphate supplementation was significantly lower in the second study period (30.3% vs. 9.9%; p < 0.001). This difference persisted when adjusted for potential confounders in a mixed-effects logistic regression model (an adjusted odds ratio for receiving phosphate with normal or high serum concentration 0.214, 95% confidence interval of 0.132-0.347; p < 0.001). No significant difference was seen in the typical ICU length of stay, in-hospital case-fatality rate, and hospital discharge destination between these groups. (4) Conclusions: This multicentre before-after study has demonstrated that the introduction of a 24 h limit on electronic phosphate prescriptions resulted in significantly fewer patients receiving phosphate when their serum phosphate concentration was normal or high, without any adverse impact on patient outcomes.

This first-in-human study assessed safety, tolerability, and pharmacokinetics (PK) of cipargamin (intravenous) in healthy adults. It included part 1, single ascending dose [SAD: 10.5 mg-210 mg; n = 8 (active: 6, placebo: 2)], and part 2, multiple ascending dose [MAD: 60 and 120 mg daily for 5 days; n = 9 (active: 6, placebo: 3)]. Last dose follow-ups were on days 3, 4, and 6 for SAD and 7, 8, and 10 for MAD. Safety and PK review was done at completion of each cohort. We explored the cipargamin use for clinical development in patients with severe malaria. In SAD part, systemic exposure (maximum measured concentration and area under the curve) increased with increasing dose (10.5 mg-210 mg) following single intravenous dose. Cipargamin was eliminated with a mean T1/2 of 21.9-38.9 h. Volume of distribution (92.9 L-154 L) and clearance (2.43 L/h-4.33 L/h) was moderate and low, respectively, across the dose range. In MAD part, the mean accumulation ratio was 1.51 (60 mg) and 2.43 (120 mg) after once-daily cipargamin administration for 5 days. After day 5, the mean T1/2 was 35.5 (60 mg) and 31.9 h (120 mg) with twofold dose increase (60-120 mg) resulting in ~2-fold increased exposure. Cipargamin was well tolerated with commonly reported mild gastrointestinal, neurological, and genitourinary events. Increasing exposure to cipargamin showed higher baseline-corrected QTcF, and model-predicted ΔΔQTcF indicated that an effect on ΔΔQTcF ≥10 ms can be excluded up to 6470 ng/mL. However, these results should be interpreted with caution due to inadequate Fridericia\'s QT correction.
RESULTS: This study is registered with ClinicalTrials.gov as NCT04321252.

BACKGROUND: Following NOVA (part 1) and the approval of the subcutaneous (SC) route of administration of natalizumab by the European Medicines Agency, an extension phase of the NOVA phase IIIb study (part 2) was initiated to collect patient preference data for SC versus intravenous (IV) dosing in patients receiving every-6-week (Q6W) dosing of natalizumab. This study was performed to evaluate patient preference for SC versus IV natalizumab administration and explore the efficacy, safety, and pharmacology characteristics of both routes of administration.
METHODS: In part 2, participants received natalizumab (Tysabri®) 300 mg via IV infusion Q6W for 36 weeks and then were randomized to 48 weeks of crossover treatment (24 weeks SC Q6W and 24 weeks IV Q6W, or vice versa). The primary endpoint was the proportion of participants who indicated a preference for natalizumab SC administration on the Patient Preference Questionnaire.
RESULTS: A total of 153 participants were randomized in NOVA part 2. Of 123 with patient preference data, 108 (87.8%) preferred the SC route of administration for natalizumab over the IV route; 102 (82.9%) specified \"requires less time in the clinic\" as the reason for the SC preference.
CONCLUSIONS: In NOVA (part 2), most participants on Q6W dosing of natalizumab preferred SC administration versus IV administration.
RESULTS: GOV: NCT03689972. INFOGRAPHIC.

BACKGROUND: Infusion failure may have severe consequences for patients receiving critical, short-half-life infusions. Continued interruptions to infusions can lead to subtherapeutic therapy.
OBJECTIVE: This study aims to identify and rank determinants of the longevity of continuous infusions administered through syringe drivers, using nonlinear predictive models. Additionally, this study aims to evaluate key factors influencing infusion longevity and develop and test a model for predicting the likelihood of achieving successful infusion longevity.
METHODS: Data were extracted from the event logs of smart pumps containing information on care profiles, medication types and concentrations, occlusion alarm settings, and the final infusion cessation cause. These data were then used to fit 5 nonlinear models and evaluate the best explanatory model.
RESULTS: Random forest was the best-fit predictor, with an F1-score of 80.42, compared to 5 other models (mean F1-score 75.06; range 67.48-79.63). When applied to infusion data in an individual syringe driver data set, the predictor model found that the final medication concentration and medication type were of less significance to infusion longevity compared to the rate and care unit. For low-rate infusions, rates ranging from 2 to 2.8 mL/hr performed best for achieving a balance between infusion longevity and fluid load per infusion, with an occlusion versus no-occlusion ratio of 0.553. Rates between 0.8 and 1.2 mL/hr exhibited the poorest performance with a ratio of 1.604. Higher rates, up to 4 mL/hr, performed better in terms of occlusion versus no-occlusion ratios.
CONCLUSIONS: This study provides clinicians with insights into the specific types of infusion that warrant more intense observation or proactive management of intravenous access; additionally, it can offer valuable information regarding the average duration of uninterrupted infusions that can be expected in these care areas. Optimizing rate settings to improve infusion longevity for continuous infusions, achieved through compounding to create customized concentrations for individual patients, may be possible in light of the study\'s outcomes. The study also highlights the potential of machine learning nonlinear models in predicting outcomes and life spans of specific therapies delivered via medical devices.

OBJECTIVE: Constipation is a common adverse event of opioid use that is often difficult to treat. Methylnaltrexone is a therapeutic option for opioid-induced constipation (OIC) approved for oral and subcutaneous use in adults. These administration routes are not always feasible in the pediatric population. The primary objective of this research was to quantify the response rate of methylnaltrexone in pediatric patients when it was administered via the intravenous (IV) route.
METHODS: This retrospective study evaluated patients ages <18 years who received IV methylnaltrexone between January 1, 2013, and June 30, 2020, for OIC. Efficacy was evaluated through documentation of bowel evacuation within 4 hours of methylnaltrexone administration. Adverse events observed within 24 hours of administration were attributed to methylnaltrexone.
RESULTS: Methylnaltrexone was administered to 134 unique patients during the study period. Of these, 46 met exclusion criteria, resulting in 88 patients being included in the study. Patients with an underlying hematology/oncology diagnosis consisted of 77% of the study population, and 23% of patients had an -underlying medical/surgical diagnosis. The response rate to IV methylnaltrexone was 25% (CI, 16-34).
CONCLUSIONS: The results of this retrospective chart review demonstrate the potential role of IV methylnaltrexone in the pediatric population. Despite the overall lower response rate relative to that reported in adults, IV methylnaltrexone possesses a unique mechanism of action that may serve as an alternative treatment option for patients unable to use the oral and subcutaneous administration routes. There were no significant adverse events seen in the study.

UNASSIGNED: Intravenous (IV) infusion therapy is commonly used in health care settings. However, IV therapy at home can be challenging because it relies on the patient\'s ability to manage multiple medications correctly, which may lead to decreased treatment adherence.
UNASSIGNED: We aimed to assess the usability and accuracy of the IVsight monitor in capturing IV infusion data compared to manual recording.
UNASSIGNED: A prospective, single-center, usability study involving patients receiving IV infusion therapy at one of the BJC\'s Home Infusion suites was conducted to evaluate the accuracy, performance, and acceptability of the device IVsight as a monitor for IV infusions.
UNASSIGNED: Of the 15 participants, the median (IQR) age was 46 years (36-55), 8 (53%) were female, and 13 (87%) were non-Hispanic white. Each participant received a median (IQR) of 4 (4-5) infusions during the study, and 68 infusions were observed overall. The intraclass correlation coefficient between the IVsight measurement and manual recording of infusion duration in seconds was excellent (ICC 0.97, 95% confidence interval 0.96-0.98). The Bland-Altman plot visually showed an acceptable limit of agreement for the 2 measurements, and the linear regression analysis revealed no significant proportional bias between the 2 methods for measuring the IV infusion time. None of the participants thought that IVsight was difficult to hold, use, clean, or store. Only one participant was concerned that the device could interfere with the IV infusion, and all participants felt comfortable with the device transmitting data to their health care providers.
UNASSIGNED: The IVsight infusion monitoring device showed near-perfect agreement on the recorded IV infusion duration compared with manual recording, and good acceptability among the study participants.

UNASSIGNED: Fluids administered as drug diluents with intravenous (IV) medicine constitute a substantial fraction of fluids in inpatients. Are physicians aware of fluid volumes administered with IV antibiotics for patients with suspected infections? Does addressing this lead to adjustments in 24-hour fluid administration/antibiotics?
UNASSIGNED: This cross-sectional interview-based study was conducted in three emergency departments. Physicians were interviewed after prescribing around-the-clock IV antibiotics for ³24 hours to patients with suspected infection. A structured interview guide assessed the physicians\' awareness, considerations, and practices when prescribing IV antibiotics. The 24-hour antibiotic fluid volume was calculated.
UNASSIGNED: We interviewed 100 physicians. The 24-hour fluid volume administered with IV antibiotics was 400mL (interquartile range: 300-400). Totally, 53% of physicians (n=53) were unaware of the fluid volume administered with IV antibiotics. 76% (n=76) did not account for the antibiotic fluid volume in the 24-hour fluid administration. 96% (n=96) indicated that they would not adjust prescribed fluids after receiving information about 24-hour antibiotic fluid volume administered for their specific patient; no comorbidities associated with fluid intolerance was primary reason for not adjusting prescribed fluids/antibiotics. 79% (n=79) opted for visibility of fluid volumes administered with IV antibiotics in the medical record.
UNASSIGNED: The majority of physicians were unaware of fluid volumes administered as a drug diluent with IV antibiotics. The majority chose not to make post-prescribing adjustments to their planned fluid administration; they regarded their patient as fluid tolerable. The physicians opted for visibility of fluid volumes administered as diluents during the prescribing process.

OBJECTIVE: To compare the efficacy of lidocaine administered intravenously, intranasally or as an infraorbital nerve block in dogs undergoing rostral rhinoscopy.
METHODS: Randomized clinical trial.
METHODS: A total of 43 client-owned dogs.
METHODS: After premedication with medetomidine 0.01 mg kg-1 and methadone 0.2 mg kg-1 intramuscularly, anaesthesia was induced with propofol and maintained with isoflurane in oxygen. Dogs were randomly allocated to receive 2 mg kg-1 of 2% lidocaine as a bilateral infraorbital nerve block (INB) via the caudal intraoral approach, via bilateral topical intranasal administration (TIA) or as an intravenous bolus (IVB). At 5 minutes following lidocaine administration, responses to rhinoscopy (RR) and biopsies (RB) were evaluated using a simple scoring system (0: no reaction; 1: reaction). Response to the rhinoscopy in the recovery period (RE) was recorded. Recovery quality was scored using a simple descriptive score. Heart rate, respiratory rate and noninvasive arterial blood pressure were recorded. Intravenous (IV) fentanyl 0.001 mg kg-1 was administered if an increase > 20% in any variable occurred. Gross movement was attenuated using propofol 0.5 mg kg-1 IV. Scores were analysed using the Chi-square test with Monte Carlo method. Cardiorespiratory changes among and overtime between groups were compared using one-way anova and one-way anova for repeated measures, respectively, or the correspondent non-parametric tests; p < 0.05.
RESULTS: Of the 43 dogs, 42 completed the study. No statistically significant differences were detected in either physical reactions or changes in cardiorespiratory variables for RR, RB, RE or recovery quality, although RB tended to be higher in group TIA (7/10 versus 1/10 INB and 3/13 IVB).Various cardiorespiratory variables changed overtime within groups.
CONCLUSIONS: In dogs, all three investigated techniques attenuated responses during rostral rhinoscopy in dogs, although INB and IVB were more efficacious when biopsies were taken.

BACKGROUND: Glucocorticoids have been widely used in perioperative period for postoperative pain relief after total knee arthroplasty (TKA). However, the optimal administration protocols of glucocorticoids remain controversial. This study aims to compare the efficacy of glucocorticoids between intravenous and periarticular injection on clinical outcomes.
METHODS: A total of 114 patients were randomly assigned to intravenous (IV) group (n = 57) and periarticular injection (PI) group (n = 57). The IV group received 10 mg dexamethasone intravenously and the PI group received periarticular injection of 10 mg dexamethasone during the procedure. The clinical outcomes were assessed using visual analogue scale (VAS), knee society score (KSS), range of motion (ROM), knee swelling, inflammation markers and complications after TKA.
RESULTS: The VAS score during walking at 2nd day postoperatively was lower in the PI group compared with the IV group (2.08 ± 1.45 vs 2.73 ± 1.69, p = .039), and there was no significant difference at the other time points of VAS score in two groups. The inflammation markers, knee swelling, knee ROM and KSS score were not statistically different. Vomiting and other complications occurrence were not significantly different between the two groups.
CONCLUSIONS: Intraoperative periarticular injection of glucocorticoids has similar analgesic effect compared to intravenous in the postoperative period following TKA and may be even more effective on the second postoperative day. In addition, periarticular injection of glucocorticoids does not impose an excess risk or complication on patients.

BACKGROUND: Subcutaneous atezolizumab is approved for the treatment of various solid tumors. Previous results from the IMscin001 study (NCT03735121) revealed that the pharmacokinetics, efficacy, immunogenicity, and safety of subcutaneous and intravenous atezolizumab were consistent (data cutoff: April 26, 2022). We present updated data from this trial (data cutoff: January 16, 2023).
METHODS: Eligible patients aged above or equal to 18 years with locally advanced or metastatic NSCLC were randomized (2:1) to receive atezolizumab subcutaneously (1875 mg, n = 247) or intravenously (1200 mg, n = 124) every 3 weeks. Here, we present updated efficacy (overall survival [OS]; progression-free survival; objective response rate; duration of response), safety, and immunogenicity end points, alongside patient-reported outcomes and health care practitioner (HCP) perspectives.
RESULTS: In this updated analysis, the median survival follow-up was 9.5 months. Median subcutaneous injection time was 7.1 minutes, with an average subcutaneous injection time of 4 to 8 minutes in most patients (75.7%). OS data were mature: median OS was similar between treatment arms, at 10.7 and 10.1 months in the subcutaneous and intravenous arms, respectively (hazard ratio: 0.88; 95% confidence interval: 0.67-1.16). Other efficacy end points, as well as immunogenicity, patient-reported outcomes, and safety, were similar between arms. Most HCPs found subcutaneous administration convenient (79.5%), easy to administer (89.7%), and were satisfied with the treatment (84.6%); 75.0% of HCPs agreed that administering atezolizumab subcutaneously compared with intravenously could save time.
CONCLUSIONS: In this analysis, mature OS data were similar between treatments. The updated efficacy and safety profile of subcutaneous atezolizumab is consistent with previous findings and equivalent to intravenous atezolizumab.