Infusion Requirements Research Articles

Cost-effectiveness of iptacopan for paroxysmal nocturnal hemoglobinuria

AbstractIptacopan, a novel oral factor B inhibitor, recently obtained US Food and Drug Administration approval for treating paroxysmal nocturnal hemoglobinuria, a rare blood disorder characterized by persistent complement-mediated hemolytic anemia. The standard-of-care (SOC) has traditionally relied on complement C5 inhibitors eculizumab and ravulizumab, which are limited by persistent anemia from extravascular hemolysis and requirement for intravenous infusion. Recent publication of phase 3 studies in this arena reinforces iptacopan as an effective anticomplement monotherapy compared with SOC. Given ongoing price negotiations and limited literature showing its cost-ineffectiveness in the anti-C5–treated population, we conducted a comprehensive cost-effectiveness analysis of iptacopan monotherapy in anti-C5–treated patients from the societal perspective, as compared with C5 inhibition. The primary outcomes were the incremental net monetary benefit across a lifetime horizon and the cost-effective maximum monthly threshold price of iptacopan monotherapy compared with the SOC. The secondary outcome was time saved for patients and nurses with the use of oral iptacopan therapy. Iptacopan monotherapy and SOC accrued 12.6 and 10.8 quality-adjusted life-years at costs of $9.52 million and $13.5 million, respectively. Iptacopan remained cost saving across extensive sensitivity and all scenario analyses, including alternative parameterization for anemia resolution and aggregated individual-level utilities and transition probability matrix. Across all probabilistic sensitivity analyses, iptacopan therapy was favored over SOC in 100% of 10 000 Monte Carlo iterations. Cost-saving thresholds for iptacopan vs anti-C5 in are ∼1.1, 1.4, and 1.4 in Brazil, Japan, and the United States, respectively. Iptacopan monotherapy can improve quality-adjusted life expectancy for patients while saving health care costs across jurisdictions.

Continuous Infusion of Ketamine in Mechanically Ventilated Patients with SARS-CoV-2.

Widespread drug shortages led to higher utilization of ketamine in our intensive care unit, especially among patients with SARS-CoV-2. To evaluate the impact of continuous infusion of ketamine on vasopressor requirements in patients with SARS-CoV-2. This was a single-center, retrospective, cohort study comparing mechanically ventilated (MV), adult patients with SARS-CoV-2 receiving either propofol or ketamine for at least 72 hours. 84 patients (mean age of 61-year-old, 68% male) were analyzed. 31 patients received ketamine, and 53 patients received propofol. Mean vasopressor doses were not significantly different between ketamine and propofol groups at prespecified timepoints. However, mean arterial pressures (MAP) were higher in the ketamine group at 24 h, 48 h, and 96 h postsedative initiation. The median opioid infusion requirements were 3 vs. 12.5 mg/hr (p < 0.0001) for ketamine and propofol groups, respectively. Comparing to propofol, C-reactive protein (CRP) values were significantly lower in the ketamine group at 24 h (7.53 vs. 15.9 mg/dL, p=0.03), 48 h (5.23 vs. 14.1 mg/dL, p=0.0083), and 72 h (6.4 vs. 12.1 mg/dL, p=0.0085). In patients with SARS-CoV-2 on MV, there was no difference in the vasopressor requirement in patients receiving ketamine compared to propofol. Nevertheless, the use of ketamine was associated with higher MAP, reductions in CRP in select timepoints, and overall lower opioid requirements.

Remimazolam to prevent hemodynamic instability during catheter ablation under general anesthesia: a randomized controlled trial.

Maintaining hemodynamic stability during cardiac ablation under general anesthesia is challenging. Remimazolam, a novel ultrashort-acting benzodiazepine, is characterized by maintaining comparatively stable blood pressure and does not influence the cardiac conduction system, which renders it a reasonable choice for general anesthesia for cardiac ablation. We aimed to evaluate whether remimazolam is associated with a decreased incidence of intraoperative hypotension compared with desflurane. In this single-centre, parallel-group, prospective, single-blind, randomized clinical trial, we randomized patients (1:1) into a remimazolam group (remimazolam-based total intravenous anesthesia) or desflurane group (propofol-induced and desflurane-maintained inhalational anesthesia) during cardiac ablation procedures for arrhythmia. The primary outcome was the incidence of intraoperative hypotensive events, defined as mean arterial pressure of < 60mm Hg at any period. Overall, we enrolled 96 patients between 2 August 2022 and 19 May 2023 (47 and 49 patients in the remimazolam and desflurane groups, respectively). The remimazolam group showed a significantly lower incidence of hypotensive events (14/47, 30%) than the desflurane group (29/49, 59%; relative risk [RR], 0.5; 95% confidence interval [CI], 0.31 to 0.83; P = 0.004). Remimazolam was associated with a lower requirement for bolus or continuous vasopressor infusion than desflurane was (23/47, 49% vs 43/49, 88%; RR, 0.56; 95% CI, 0.41 to 0.76; P < 0.001). No between-group differences existed in the incidence of perioperative complications such as nausea, vomiting, oxygen desaturation, delayed emergence, or pain. Remimazolam was a viable option for general anesthesia for cardiac ablation. Remimazolam-based total intravenous anesthesia was associated with significantly fewer hypotensive events and vasopressor requirements than desflurane-based inhalational anesthesia was, without significantly more complications. ClinicalTrials.gov (NCT05486377); first submitted 1 August 2022.

Effect of Recombinant Human Thrombopoietin on Platelet Reconstitution after Autologous Peripheral Blood Stem Cell Transplantation in Patients with Multiple Myeloma

To analyze the effect of recombinant human thrombopoietin (rhTPO) on platelet (PLT) reconstitution after autologous peripheral blood stem cell transplantation (APBSCT) in patients with multiple myeloma (MM). The clinical data of 147 MM patients who were diagnosed in the First Affiliated Hospital of Soochow University and received APBSCT as the first-line therapy were retrospectively analyzed. According to whether rhTPO was used during APBSCT, the patients were divided into rhTPO group (80 cases) and control group (67 cases). The time of PLT engraftment, blood product infusion requirements, the proportion of patients with PLT recovery to≥50×109/L and≥100×109/L at +14 days and +100 days after transplantation, and adverse reactions including the incidence of bleeding were compared between the two groups. There were no significant differences between the two groups in sex, age, M protein type, PLT count at the initial diagnosis, median duration of induction therapy before APBSCT, and number of CD34+ cells reinfused (all P >0.05). The median time of PLT engraftment in the rhTPO group was 10 (6-14) days, which was shorter than 11 (8-23) days in the control group (P < 0.001). The median PLT transfusion requirement in the rhTPO group during APBSCT was 15(0-50)U, which was less than 20 (0-80)U in the control group (P =0.001). At +14 days after transplantation, the proportions of patients with PLT≥50×109/L in the rhTPO group and the control group were 66.3% and 52.2%, while the proportions of patients with PLT≥100×109/L were 23.8% and 11.9%, respectively, with no significant differences (all P >0.05). At +100 days after transplantation, the proportion of patients with PLT≥50×109/L in rhTPO group and control group was 96.3% and 89.6%, respectively (P >0.05), but the proportion of patients with PLT≥100×109/L in rhTPO group was higher than that in control group (75.0% vs 55.2%, P =0.012). There was no difference in the overall incidence of bleeding events in different locations during period of low PLT level of patients between the two groups. In rhTPO group, the rhTPO administration was well tolerated, and the incidences of abnormal liver and kidney function and infection were similar to those in the control group. When MM patients undergo first-line APBSCT, subcutaneous injection of rhTPO can shorten the time of platelet engraftment, reduce the transfusion volume of blood products, and be well tolerated, moreover, more patients have achieve a high level of PLT recovery after transplantation, which is very important for ensuring the safety of APBSCT and maintenance therapy.

Resolution of insulin resistance, lactic acidosis, and decrease in mechanical support requirements in patients post orthotopic heart transplant with the use of long-acting insulin glargine

ObjectiveThis study investigates the efficacy of using a long-acting insulin analog, along with the infusion of regular insulin, in achieving appropriate glycemic control and correcting lactic acidosis in patients post orthotopic heart transplant who demonstrate severe lactic acidosis and insulin resistance.MethodsThis was a retrospective study of two cohorts (IRB FLA 20-003) of patients post orthotopic heart transplant with severe lactic acidosis and insulin resistance who were admitted to a tertiary intensive care unit and treated with (group 1) or without long-acting insulin analog (group 2) within the first 24 h of admission to the intensive care unit. Insulin resistance is defined as the requirement for intravenous regular insulin infusion of more than 20 units/h without the ability to achieve appropriate serum glucose level (120–180 mg /dL). Severe lactic acidosis is defined as arterial lactic acid of more than 10 mmol/L. The following parameters were investigated: time to correct lactic acidosis, duration of postoperative mechanical ventilation, the need for periprocedural mechanical circulatory support, and 28-day mortality.ResultsThe 28-day mortality was zero in both groups. Two patients required periprocedural mechanical support in group one, and ten patients required mechanical support in group two (RR = 0.224, 95%, confidence interval 0.052–0.95, Z = 2.029, p = 0.042). Three patients required tracheostomy in group one, and four patients required tracheostomy in group two (RR 0.84, 95 confidence interval 0.20–3.48, Z = 0.23, P = 0.81). Wilcoxon rank-sum test was used to compare time to correct lactic acidosis, with lactic acid resolution being faster in group one (X¯\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\overline{X}$$\\end{document}1 = 19.7 h, SD ± 12.6 h X¯\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\overline{X}$$\\end{document}2 = 29.3 h, SD ± 19.6 h, Z-value − 2.02, p-value 0.043). The duration of mechanical ventilation was less in group one (X¯\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\overline{X}$$\\end{document}1 = 29 h, SD ± 12.7 h, X¯\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\overline{X}$$\\end{document}2 = 55.1 h, SD ± 44.5 h, Z-value: − 1.92, p-value 0.05).ConclusionAdministration of low-dose long-acting insulin glargine led to the resolution of the lactic acidosis, insulin resistance, and decreased requirements for pressor and inotropic support, which led to decreased need for mechanical circulatory support.

Antipsychotic initiation in mechanically ventilated patients in a medical intensive care unit

Objectives: Guidelines for the prevention and management of pain, agitation/sedation, delirium, immobility, and sleep disruption in adult patients (PADIS) in the intensive care unit (ICU) promote use of analgosedation to minimize pain, reduce anxiety, and facilitate care. They also suggest against routine use of antipsychotics (APs) for delirium. Our institution’s adaptation incorporates assessment-driven, protocol-based pain, and sedation management and suggests a short course of APs in patients with agitated delirium, defined as Confusion Assessment Method for the ICU (CAM-ICU) positive with Richmond Agitation Sedation Scale (RASS) ≥ +2. While the use of APs in the ICU is typically for delirium, a recent study assessed whether quetiapine reduced sedative requirements among non-delirious patients. The purpose of this study was to assess adherence to our institutional guideline for AP use and to describe sedative and opioid use in relation to AP initiation. Materials and Methods: This retrospective study included patients who were mechanically ventilated and received ≥ 3 new start AP doses. The primary outcome was adherence to our guideline for use of APs in agitated delirium. The secondary outcomes were CAM-ICU and RASS scores in relation to AP initiation and change in sedative and analgesic infusion rates following AP initiation. Results: Thirty-eight patients were included in the study. Five had APs initiated appropriately per our guideline. There was no clinically significant change in continuous infusion rates in the 24 h before and after AP initiation. Conclusion: Overall, AP use was liberal with patients being started on APs who did not have agitated delirium, thus indicating potential alternative indications for initiation. APs did not result in a clinically significant change in continuous infusion requirements in the 24 h following initiation.

Midodrine reduces new-onset acute kidney injury and hyponatremia in children with cirrhosis and ascites awaiting liver transplantation: Results from an open-label RCT.

Midodrine, an oral α-1-adrenergic receptor agonist, counters arterial hypovolemia and reduces complications in adult patients with cirrhosis. This randomized controlled trial (RCT) aimed to assess the efficacy and safety of midodrine in preventing complications and improving survival in children with cirrhosis and ascites who are awaiting liver transplantation (LT). This open-label RCT conducted from January 2022 to May 2023 included children under 18 years with cirrhosis and ascites. Patients were randomized to receive either midodrine plus standard medical therapies (SMTs) or SMT alone. The primary outcome measure was the incidence of cirrhosis-related complications within 6 months. Thirty-five subjects were enrolled and randomized. Patients in the midodrine arm had a lower incidence of new-onset acute kidney injury (AKI) compared with the SMT arm (11.1% vs. 41.2%). Patients in the midodrine arm showed a decline in serum creatinine and improvement in glomerular filtration rate, whereas no changes were observed in the SMT arm. There was a lower incidence of new-onset hyponatremia in the midodrine arm (20% vs. 56%). Midodrine led to reduction in plasma rennin activity (PRA) and improvement in systemic hemodynamics. There was no difference in the rate of resolution of ascites, recurrence of ascites, requirement of therapeutic paracentesis, cumulative albumin infusion requirement, episodes of spontaneous bacterial peritonitis, and hepatic encephalopathy between the two arms. Midodrine, when added to SMT, was effective in reducing the incidence of new-onset AKI and hyponatremia in pediatric cirrhotics awaiting LT. It also improved systemic hemodynamics and showed a trend towards reducing PRA.

Phase II Study of Danazol with Plasma Exchange and Corticosteroids for the Treatment of Thrombotic Thrombocytopenic Purpura

Background: Ahn and colleagues reported a decrease in plasma exchange (PE)/plasma infusion requirement with danazol in seven cases of thrombotic thrombocytopenic purpura (TTP) (Ahn Blood 2006;108(11):1057a). We reported an increase in platelet count (PLT) within 24 hours with danazol in two of three cases of human immunodeficiency virus-associated TTP resistant to PE (Torri Transfusion 2010;50:86a). In 2009, we initiated a phase II study of danazol with PE and corticosteroids (CS) for the treatment of TTP. This trial was approved by the institutional review board and was registered at ClinicalTrials.gov (ID# NCT00953771). We report the final results. Aims: To determine if danazol reduces number of PE's, time to remission (TR), and length of stay (LOS) when administered with standard therapy for the initial treatment of TTP. Methods: Experimental Group (EG): Patients with TTP (PLT &amp;lt; 100,000/µL and microangiopathy) receive daily PE, prednisone 1 mg/kg, and danazol 600 mg. Following remission (PLT &amp;gt; 150,000/µL for three consecutive days), PE is tapered to every other day for one week then stopped. Then prednisone is tapered weekly over four weeks then stopped. After one week danazol is tapered by 200 mg weekly then stopped. Historical controls (HC): Patients treated for TTP at St. Luke's-Roosevelt Hospital Center with PE with or without CS from 2000 to 2007 (n=20). Relapse definition: PLT &amp;lt; 100,000/µL with microangiopathy &amp;gt; 30 days after remission. Total number of PE's, TR, LOS, and continuous response rates are compared between the 2 groups. Accrual target: 16 patients to detect a 40% decrease in the number of PE's with 80% power and a level of significance of 0.05.The study was terminated in 2018 due to low accrual. Results: Nine patients were enrolled. Mean number of PE's (days) was 14.8 (EG) and 16.1 (HC), mean TR (days) was 11.4 (EG) and 11 (HC), and mean LOS (days) was 27.3 (EG) and 24.9 (HC), p &amp;gt; 0.05. Four patients in HC had a total of 6 relapses at our institution at a median of 28.25 months, range 2.75 to 97 months after the initial event. One patient in EG relapsed 43 months after study enrollment. One patient in EG died from an unrelated cause. None of the additional seven patients in EG have relapsed during a median follow-up of 49 months, range 12 to 125 months. One episode of pulmonary edema and one episode of hypotension occurred in EG, for which treatment was not discontinued. Discussion: Our study shows that danazol does not reduce PE requirement, TR, or LOS during treatment of TTP, but may prevent relapse. This pattern of response is similar to that which has been observed with rituximab. In a phase 2 study of rituximab in conjunction with PE and CS for the treatment of TTP (Scully Blood 2011), in which results were compared with historical controls who did not receive rituximab, median number of PE's (days) and median LOS (days) were 16.5 and 16.5 in the rituximab group versus 18.0 and 20 in the historical control group, p=ns. Ten percent of patients relapsed at a median of 27 months in the rituximab group whereas 57% of patients relapsed at a median of 18 months in the historical control group. Of interest, the cost of rituximab 375 mg/m 2 weekly for 4 weeks as given would have been approximately $ 25,366.50. The cost of danazol in our protocol would have been approximately $ 2196.00. Caplacizumab is a humanized monoclonal antibody fragment that inhibits von Willebrand factor binding to platelet glycoprotein lb-IX-V. In a phase 3 study (Scully N Engl J Med 2019), caplacizumab in conjunction with PE and CS for the treatment of TTP led to reduced PE's, time to normalization of platelet counts, and LOS, but increased relapses in comparison with placebo. In 2020, the International Society on Thrombosis and Haemostasis strongly recommended adding CS to PE for the treatment of TTP and conditionally recommended adding rituximab and caplacizumab to PE and CS (Zheng J Thromb Haemost 2020). Conclusion: Danazol in conjunction with PE and CS may be a low-cost option to prevent relapses of TTP.

Platelet-Based Dose-Adjusted Low Molecular Weight Heparin Treatment Is Efficacious and Safe in Newly Diagnosed Acute Leukemia Patients with Catheter-Related Thrombosis

Introduction: Catheter-related thrombosis (CRT) is a major complication in patients with acute leukemia. Severe thrombocytopenia related to either the concomitant disease or therapy underscores the challenge of CRT management, resulting in the use of suboptimal anticoagulation, potentially leading to high rates of short-term complications, including recurrent thromboembolism and hemorrhage. Due to the paucity of data regarding the impact of reduced-dose anticoagulation on this clinical setting, the current study aimed to assess the safety and efficacy of this treatment approach to CRT management in this challenging patient population. Methods: In this retrospective, case-control study, all adult (age ≥18 years) acute leukemia patients, who had arrived at the Rambam Health Care Campus (RHCC, Haifa, Israel) between 1.11.2004-30.6.2022 to receive anti-leukemia therapy via a peripherally inserted central catheter (PICC) line were screened. The inclusion criteria were: patients with acute myeloid, promyelocytic and lymphoid leukemia (AML, APL, and ALL, respectively) and CRT confirmed by Doppler ultrasound within 3 months of leukemia diagnosis. Patients were divided into full- (i.e., 1 mg/kg bid) vs. partial-dose low molecular weight heparin (LMWH) groups. The LMWH dose was based on the platelet count with a cutoff of 50K/L, distinguishing between the selected doses. Primary endpoints: A record of venous thromboembolism (VTE; including pulmonary embolism (PE), deep vein thrombosis (DVT), and catheter-related thrombosis (CRT) recurrence within 12 months as well as a major hemorrhage (including intracranial, retinal and gastrointestinal hemorrhage) within 6 months. Secondary endpoints: blood product requirement (unit/day) before and after the CRT diagnosis (from leukemia diagnosis till CRT identification and 90 days or death (if prior) from the event, respectively) assessed in a self-controlled case series manner. Data were collected from the hospital electronic medical records. Chi-square and paired samples Wilcoxon tests were utilized for statistical analysis. Results: Overall,195 patients [aged 54±15 years; 103 (53%) males], diagnosed with CRT were included. The most frequent leukemia diagnosis was AML (n=149; 76%), with ALL and APL established in 23 (12%) patients each. CRT was diagnosed in the left upper limb in 136 (70%) patients, with 99 (46%) patients suffering from DVT. Eighty-eight (45%) patients were treated with full-dose LMWH. Recurrent VTE was identified in 11(12.5%) patients treated with full-dose LMWH vs. 9 (8.4%) receiving partial-dose LMWH (p-value 0.484), while major hemorrhage was diagnosed in 12 (13.6%) patients from the former group vs. 14 (13.0%) patients from the latter group (table 1). Similar results were documented upon stratification to deep vs. superficial CRT, and the leukemia type. The packed red blood cell (RBC) administration rate was lower in the post-CRT phase (0.12 units/day, IQR 0.06-0.20) compared to the pre-CRT phase (0.20 units/day, IQR 0-0.36; p-value &amp;lt;0.0001). Platelet utilization rates were similar in both the pre-CRT and post-CRT phases (0.05 units/day, IQR 0-0.24 and 0.06 units/day, IQR 0.01-0.16, respectively; p-value 0.126). Comparable results were observed in both full and partial-dose LMWH groups. Conclusion: LMWH dose adjustment based on platelet counts, in newly diagnosed acute leukemia patients with CRT, is not associated with higher rates of VTE recurrence. Moreover, this strategy does not result in major hemorrhagic complications even in patients with severe thrombocytopenia. Notably, RBC infusion requirements were lower in the post-CRT diagnosis phase, while platelet transfusion was similar during the pre- and post-CRT phases. This analysis, including a large number of patients, demonstrates that the adjusted therapy is safe and efficient in this challenging clinical scenario.

Is the combination of conventional ultrafiltration and modified ultrafiltration superior to modified ultrafiltration in pediatric open-heart surgery?

ABSTRACT Background: Cardiopulmonary bypass (CPB) during open-heart surgery is associated with increased body fluids as a consequence of hemodilution due to the use of CPB. Ultrafiltration (UF) is a method used to decrease the body fluid volume on CPB. Aims and Objectives: This study aimed to compare the effects of combined conventional UF (CUF) and modified UF (MUF) versus MUF on the clinical outcomes of pediatric patients undergoing open-heart surgery for congenital heart disease. Materials and Methods: This was a prospective, single-center, randomized, and double-blinded clinical study that involved 74 pediatric patients undergoing open-heart surgery on CPB. Patient management was standardized. Preoperative Aristotle comprehensive complexity level, ultrafiltrate volumes, hematocrit, hemodynamic data, transesophageal echocardiographically (TEE) determined ejection fraction (EF), fractional area change (FAC), temperature drift, arterial oxygenation, time of extubation, ventilation, comparison of inotropic drugs, postoperative chest tube drainage, cardiac care unit (CCU), and hospital length of stay (LOS) were recorded in both groups. The analysis was conducted using SPSS-23.0, IBM, Armonk, NY, USA. Results: There was no mortality in both groups. Technical difficulties prevented the completion of MUF in two patients out of 37 in the CUF + MUF group. In this study, there were 43.26% of females and 56.75% of males, with a median age of 439 days, a mean weight of 9.98 kg, and an Aristotle Comprehensive Complexity score of level 2. Group CUF + MUF had a greater ultrafiltrate volume of 122 ± 39.7 ml (P = 0.036). The duration of ventilatory support was 11.2 ± 6.4 h versus 34.4 ± 5.7 h (P = 0.013), average CCU LOS was 4.3 ± 3.5 days versus 7.2 ± 3.6 days (P = 0.008), and chest tube drain in the first 48 h was 89.76 ± 34.82 ml versus 106.65 ± 47.29 ml (P = 0.029) in groups CUF + MUF and MUF, respectively. Inotropic infusion requirements were significantly lower in the CUF + MUF group compared to the MUF group. EF and FAC were 14% and 5% higher at 45 min in group CUF + MUF, respectively. Conclusions: The advantage of combining CUF and MUF over MUF is the significant improvement in the hemodynamic status of patients, which significantly decreases the duration of mechanical ventilation, average CCU LOS, inotrope requirements after surgery, and chest tube drain in the first 48 h.

Requirements and challenges for infusion of SHM systems within Digital Twin platforms

The need for measurable data from physical assets to actively feed a living Digital Twin (DT) is paramount. The requirements and needs that the gathered data should fulfill in order to be practically implemented in the stream data pipeline are heterogeneous, some of them general and other case-specific. This article summarizes a set of identified challenges and requirements for a seamless infusion of well-established Structural Health Monitoring (SHM) systems within DT platforms, without the objective of solve all of them. This identification is performed based on a review of traditional SHM systems with a vast array of information sources as well as on the review of techniques for the systematic digitalization of existing assets. On the other hand, ten real demo cases belonging to Ashvin, an H2020 Research and Innovation project, are providing real world testing beds for an active development of SHM infused in DT systems. Multiple information sources are studied in those sites, which also enriches with more realism, the identification of requirements and challenges presented herein. These assets provide a perspective to researchers about practical implications of these needs.

Outpatient administration of paclitaxel, ifosfamide, and cisplatin (TIP) for germ cell tumor.

The combination of paclitaxel, ifosfamide, and cisplatin (TIP) is frequently used for the treatment of metastatic germ cell tumors. Due to complex supportive care and infusion requirements, TIP is typically given in the inpatient setting. This analysis describes the development and implementation of a protocol for complete outpatient administration of TIP chemotherapy. From July 2020 to June 2021, adults receiving TIP for germ cell tumor at University of Michigan Rogel Cancer Center were evaluated for outpatient administration. The primary outcome was number of inpatient bed days saved by giving outpatient TIP chemotherapy, with the goal of giving 75% of TIP cycles outpatient. Patients receiving outpatient TIP were also assessed for chemotherapy dose reduction or delays and acute toxicities of kidney injury, encephalopathy, and hemorrhagic cystitis. From July 2020 to July 2021, three patients received 13 cycles of TIP. Ten cycles (77%) were administered in the outpatient setting, resulting in a savings of 50 inpatient bed days in one year. No patients required a dose reduction or delay in chemotherapy or experienced acute kidney injury, encephalopathy, or hemorrhagic cystitis during outpatient TIP treatment. Despite logistic and supportive care challenges, TIP can be administered completely in the outpatient setting.

A single-cohort retrospective analysis of factors associated with morbidity and mortality in 193 anesthetized domestic goats

ObjectiveTo define the morbidity and mortality rates in goats undergoing general anesthesia at a large animal teaching hospital. Study designRetrospective, single-cohort, observational study. AnimalsRecords of 193 client-owned goats. MethodsData were collected from 218 medical records on 193 goats undergoing general anesthesia between January 2017 and December 2021. Demographic data, anesthetic management, recovery period and perianesthetic complications were recorded. Perianesthetic death was defined as anesthesia-related or anesthesia-contributory death occurring within 72 hours after recovery. Records of goats that were euthanized were reviewed to ascertain the cause of euthanasia. Each explanatory variable was individually investigated by univariable penalized maximum likelihood logistic regression, followed by multivariable analysis. Statistical significance was set at p < 0.05. ResultsPerianesthetic mortality was 7.3%, but was 3.4% when considering only goats undergoing elective procedures. Multivariable analysis showed that gastrointestinal surgeries [odds ratio (OR) 19.17, standard error (SE) 12.99, 95% confidence interval (CI) 5.08–72.33; p < 0.01] and requirement for perianesthetic norepinephrine infusion (OR 10.85, SE 8.82, 95% CI 2.21–53.33; p < 0.01) were associated with increased mortality. Maintaining other variables equal, the use of perianesthetic ketamine infusion was associated with decreased mortality (OR 0.09, SE 0.09, 95% CI 0.01–0.73; p = 0.02). Anesthesia-related or anesthesia-contributory complications included hypothermia (52.4%), bradycardia (38.1%), hypotension (35.3%), hypoxemia (14.8%), regurgitation/aspiration (7.3%), azotemia/acute renal failure (4.6%), myopathies/neuropathies (4.1%) and fever of unknown origin (2.7%). Conclusions and clinical relevanceIn this population, gastrointestinal surgeries and the requirement for perianesthetic norepinephrine infusion were associated with increased mortality in goats undergoing general anesthesia, while ketamine infusion may have a protective effect.

Optimization of infusion supply using the probabilistic economic order quantity (EOQ) method at Sanglah Center General Hospital

Inventory planning is important to avoid the advantages or lack of goods. Hospitals as health care providers also have a share in the stock of goods, one of which is infusion. This study aims to optimize infusion supply at Sanglah Central General Hospital using Economic Order Quantity (EOQ) method with (q, r) model. The forecasting method used in forecasting infusion requirements at Sanglah Hospital is an Autoregressive Integrated Moving Average (ARIMA) method. The results of this study indicate the amount of infusion of NaCl 0.9% 500 ml and 5% 500 ml glucose infusion which is expected to be ordered by Sanglah Hospital at the beginning of the booking period is 11,921 and 560 units. Sanglah Hospital need to re-order when the stock of infusion of NaCl 0.9% 500 ml touched the number 3,593 and 5% 500 ml glucose infusion stock touched 202 units. To anticipate the spike of demand, Sanglah Hospital is expected to provide infusion as a safety reserve of 190 units for infusion of NaCl type 0.9% 500 ml and 21 units for glucose type 5% 500 ml. The total inventory cost of the infusion to be issued by Sanglah Hospital in the planning of the infusion needs for 6 months is also obtained.

Insulin Requirements for Patients With COVID-19 Presenting With Diabetic Ketoacidosis.

Introduction Recent literature has shown that patients with COVID-19 and diabetic ketoacidosis may require more aggressive treatment than those with diabetic ketoacidosis alone. The primary objective of this study was to assess if intravenous regular human insulin infusion requirements in patients with diabetic ketoacidosis differed between patients with or without COVID-19. Methods This retrospective cohort study evaluated patients with diabetic ketoacidosis who received intravenous regular human insulin infusion during the COVID-19 pandemic. The primary outcome was the amount of intravenous regular human insulin infusion requirements needed during the diabetic ketoacidosis episode. Results Of the 77 patients that met inclusion criteria, 35 were positive for COVID-19 and 42 were negative. The primary outcome of total intravenous regular human insulin infusion requirements needed during the diabetic ketoacidosis episode was not statistically significant and resulted in 1.79±0.61 units/kg/day in the COVID-19 positive group and 1.81±0.6 units/kg/day in the negative group (p=1). Secondary outcomes that were statistically significant between groups were the amount of fluids received in the first 24 hours, potassium supplementation, phosphate supplementation, acute kidney injury, and hypokalemia. Conclusion There was no difference in intravenous regular human insulin infusion requirements in the setting of diabetic ketoacidosis (DKA) between COVID-19 positive and negative patients.

Perioperative Management in Pediatric Neurosurgery

Appropriate perioperative management can facilitate good outcomes in pediatric neurosurgical patients. This section discusses infusion therapy, prophylactic antibiotics, and antiepileptic drugs in the perioperative management of pediatric neurosurgical patients. Fluid requirements were calculated using the Holiday and Segar formula and the 4-2-1 rule for determining hourly infusion requirements based on metabolic rate and body weight. Recently, the risk of hyponatremia with the use of hypotonic solutions has been reported, and an isotonic electrolyte solution with 1-2.5% glucose is recommended for maintenance infusions in the perioperative period. Pediatric perioperative prophylactic antibiotics have been recommended as follows: application of cephazolin(30 mg/kg)with a redosing interval of 3 h intraoperatively and continuation for 48 h or less postoperatively. However, even for shunt surgery, there are currently no evidence-based protocols regarding specific antibiotic recommendations or the duration of prophylactic antibiotics. Early antiepileptic prophylaxis is recommended in cases of severe head trauma in children, especially infants. Available intravenous antiepileptic drugs should be used with an understanding of their indications, characteristics, and side effects.

Quality of recovery after intrathecal morphine for elective Caesarean deliveries

Background: Recent supply issues with diamorphine have meant a change in practice to use of intrathecal morphine. The Obstetric Anaesthetists’ Association (OAA)1 guidelines state that intrathecal diamorphine or morphine provides adequate analgesia after Caesarean section. They discourage the use of parenteral opioids in women who have received neuraxial opioids, owing to the increased risk of respiratory depression. Other side-effects such as nausea and vomiting and pruritus may differ in severity for each drug. We reviewed the side-effects and adherence to the enhanced recovery pathway in elective deliveries receiving intrathecal morphine. Methods: Prospective data were collected for 50 women undergoing Caesarean section with intrathecal opioid analgesia (fentanyl 15 μg and morphine 100 μg) within a 5-week period. Data were collected at Day 1 and Day 2 postoperatively. These included: pain score, postoperative nausea and vomiting (PONV), pruritus, oral opioid use, anti-emetic use, chlorphenamine use, time spent in recovery, and occurrence of urinary retention. Pain score, nausea and vomiting, and pruritus were recorded using a verbal rating scale (VRS). Results: The majority (56.5%) of patients reported only mild pain, 37% reported moderate to severe pain, but of these most (94.7%) only required 20–40 mg of oral morphine in addition to simple analgesia. In addition, the majority (58.7%) of patients reported no PONV. Meanwhile, 45.7% of patients reported mild pruritus, and 43.5% reported no pruritus. Only three of the 50 women did not follow the enhanced recovery pathway. Two remained as inpatients for monitoring after obstetric haemorrhage, and one for intravenous antibiotics. There was no reported respiratory depression. Time spent in recovery was between 1 and 4 h. Although the reason for prolonged recovery stay was not audited, it was thought that requirement for oxytocin infusion increased recovery stay as the ward did not accept patients on an infusion. Conclusions: Our results show an acceptable side-effect profile after elective Caesarean delivery using intrathecal morphine, with adherence to the current enhanced recovery pathway. We aim to implement updated Caesarean delivery guidelines which include prescription of regular ondansetron and chlorphenamine as required, in conjunction with patient education, to try and reduce the incidence of bothersome PONV and pruritus. 1. Obstetric Anaesthetists’ Association, OAA commentary on alternatives to intrathecal and epidural diamorphine for caesarean section analgesia, 2018. Available from: https://www.oaa-anaes.ac.uk/ui/content/content.aspx?ID=4717

311.4: Every 2-Month Belatacept Maintenance Therapy in Kidney Transplant Recipients: 3-Year Follow-up of a Randomized, Non-inferiority Trial

Introduction: Maintenance immunosuppression with belatacept following kidney transplantation results in improved long-term graft function as compared to calcineurin inhibitors. However, broad application of belatacept has been limited, in part related to logistical barriers surrounding a monthly (q1m) IV infusion requirement. Our center conducted a randomized, non-inferiority trial comparing every 2-month (q2m) dosing to standard q1m maintenance. At twelve month follow up, q2m dosing was noninferior to standard q1m dosing as determined by renal function (eGFR). Two-month dosing was safe and well tolerated without a significant incidence of immunologic events in subjects adherent to the study protocol, but longer term follow-up is of interest to better elucidate patient and graft outcomes. Here, we present the 3-year outcomes from this study. Methods: Low immunologic risk, stable renal transplant recipients a minimum of 1 year post-transplant were randomized to q1m or q2m belatacept maintenance therapy. 36-month follow-up was conducted as intention-to-treat on the population that initiated the study protocol. An autoregressive model using baseline-adjusted means with a random effect for subject was used to compare renal function between groups. Kaplan Meier survival analysis was performed for analysis of adverse and immunologic events. Results: 163 patients initiated the study protocol and received treatment in the q1m control group (n=82) or q2m study group (n=81). Renal allograft function as measured by baseline adjusted eGFR was not significantly different between groups at 36 months (mean [95% CI], q1m: 73.43[70.37, 76.49] vs. q2m: 72.46[69.08, 75.84].There were no statistically significant differences in time to death or graft loss (cumulative survival at 36 months, q1m: 92.6%, q2m: 95.0%, p=0.49; freedom from rejection (q1m: 98.7%, q2m: 92.4%, p=0.06), or freedom from DSA (q1m: 98.7%, q2m: 92.4%, p=0.06). During the extended 12-36 month follow-up period, 3 deaths, 1 graft loss occurred in the q1m group, compared to 2 deaths, 2 graft losses in the q2m group. In the q1m group, one patient developed DSA and acute rejection. In the q2m group, 3 patients developed DSA, 2 associated with acute rejection. All acute rejections in both groups were associated with documented medication nonadherence.Conclusions: Based on similar renal function and adverse event rates at 36 months compared to q1m, q2m belatacept is a viable and safe maintenance immunosuppressive strategy in low immunologic risk kidney transplant recipients with potential to facilitate increased clinical utilization of costimulation blockade-based immunosuppression. (ClinicalTrials.gov NCT02560558) James O. Robbins Foundation. James M. Cox Foundation. Carlos and Marguerite Mason Trust.

A simple nomogram for predicting infectious diseases in adult kidney transplantation recipients.

ObjectiveTo investigate the risk factors of infectious diseases in adult kidney transplantation recipients and to establish a simple and novel nomogram to guide the prophylactic antimicrobial therapy.MethodsPatients who received kidney transplantation between January 2018 and October 2021 were included in the study and were divided into a training and a testing set at a 1:1 ratio. Risk factors correlated to infectious diseases were selected using a Least Absolute Shrinkage and Selection Operator (LASSO) regression model. The prediction model was built by incorporating the variables selected by the LASSO model into a logistic regression equation. Calibration curves and receiver operating characteristic (ROC) curves were also applied to assess the model calibration and discrimination. A nomogram consisting of the selected factors was established to provide individualized risks of developing infections. Decision curve analysis (DCA) was adopted to estimate the net benefit and reduction in interventions for a range of clinically reasonable risk thresholds.ResultsIn all, 863 adult kidney recipients were included in the study, and 407 (47.16%) of them developed infectious diseases during the 3-year follow–up period. A total of 8 variables were selected using LASSO regression and were retained for subsequent model construction and infection prediction. The area under the curve (AUC) was 0.83 and 0.81 in the training and testing sets, with high F scores of 0.76 and 0.77, sensitivity of 0.76 and 0.81, and specificity of 0.88 and 0.74, respectively. A novel nomogram was developed based on 8 selected predictors (requirement for albumin infusion, requirement for red blood cell infusion, triglyceride, uric acid, creatinine, globulin, neutrophil percentage, and white blood cells). The net benefit indicated that the nomogram would reduce unnecessary interventions at a wide range of threshold probabilities in both sets.ConclusionsAdult kidney transplantation recipients are high-risk hosts for infectious diseases. The novel nomogram consisting of 8 factors reveals good predictive performance and may promote the reasonable antimicrobial prescription. More external validations are required to confirm its effectiveness for further clinical application.

Short-term prognostic value of clinical data in hospitalized patients with intermediate-risk acute pulmonary embolism

BackgroundIntermediate-risk acute pulmonary embolism (APE) patients are usually defined as hemodynamically stable, comprehending a great therapeutic dilemma. Although anticoagulation therapy is sufficient for most intermediate-risk APE patients, some patients can deteriorate and eventually require a systemic fibrinolytic agent or thrombectomy. Hence, this study aimed to evaluate the predictive value of differences in clinical data for the short-term prognosis of intermediate-risk APE patients.MethodsA retrospective cohort of 74 intermediate-risk APE patients confirmed by computed tomography pulmonary angiography was analyzed in the present study. Adverse clinical event outcomes included PE-related in-hospital deaths, critical systolic blood pressure consistently under 90 mmHg, refractory to volume loading and vasopressor infusion requirements, mechanical ventilation, and cardiopulmonary resuscitation. The APE patients were stratified into two groups: adverse outcome (n = 25) and control (n = 49) groups. Then, the clinical data of the two groups were compared. Receiver operating characteristic (ROC) curves were used to explore the predictive value of white blood cell (WBC) counts and the right to left ventricular short-axis (RV/LV) ratio. Model calibration was assessed using the Hosmer–Lemeshow goodness-of-fit statistic.ResultsThe brain natriuretic peptide, WBC count, and the RV/LV ratio were higher in patients with adverse outcomes compared to controls. The APE patients with adverse outcomes presented significantly higher rates of syncope, Negative T waves (NTW) in V1–V3, intermediate-high risk, thrombolytic therapy, and low arterial oxygen saturation (SaO2) compared to controls. In the multivariate logistic regression analysis, the SaO2 < 90%, [odds ratio (OR) 5.343, 95% confidence interval (CI) 1.241–23.008; p = 0.024], RV/LV ratio (OR 7.429, 95% CI 1.145–48.209; p = 0.036), Syncope (OR 12.309, 95% CI 1.702–89.032; p = 0.013), NTW in V1–V3 (OR 5.617, 95% CI 1.228–25.683; p = 0.026), and WBC count (OR 1.212, 95% CI 1.035–1.419; p = 0.017) were independent predictors of in-hospital adverse outcomes among APE patients. The ROC curve analysis indicated that the RV/LV ratio can be used to predict adverse outcomes (AUC = 0.748, p < 0.01) and calibration (Hosmer–Lemeshow goodness of fit test, p = 0.070). Moreover, an RV/LV ratio > 1.165 was predictive of adverse outcomes with sensitivity and specificity of 88.00 and 59.20%, respectively. The WBC counts were also able to predict adverse outcomes (AUC = 0.752, p < 0.01) and calibration (Hosmer–Lemeshow goodness of fit test, p = 0.251). A WBC count > 9.05 was predictive of adverse outcomes with sensitivity and specificity of 68.00 and 73.50%, respectively.ConclusionOverall, a SaO2 < 90%, RV/LV ratio, Syncope, NTW in V1–V3, and WBC counts could independently predict adverse outcomes in hospitalized intermediate-risk APE patients.