Long-term Infusion Research Articles

Allergic reactions to enzyme replacement therapy in children with lysosomal storage diseases and their management.

Human recombinant enzyme replacement therapy, given to compensate for genetic enzyme deficiency in lysosomal storage diseases, delays the progression of the disease and improves the quality of life. However, enzyme replacement therapy may cause hypersensitivity reactions. Within the scope of this research, we aimed to elucidate the frequency and clinical features of hypersensitivity reactions against enzyme replacement therapy in children with lysosomal storage diseases and clarify the management of these reactions. Medical records of pediatric patients with lysosomal storage disease and receiving enzyme replacement therapy were retrospectively reviewed, and patients who experienced allergic reactions were included in the study. The demographic characteristics of the patients, their diagnosis, the responsible enzyme, the time at which the reaction started and at what dose, the signs and symptoms associated with the reaction, diagnostic tests, the management of the reaction, and the protocol applied for the maintenance of enzyme replacement therapy after the reaction were recorded. Hypersensitivity reactions developed in 18 of 71 patients (25.3 %) who received enzyme replacement therapy. The most common cutaneous findings were observed. Anaphylaxis developed in 6 of 18 patients. Patients who experienced recurrent hypersensitivity reactions with premedication or a slower infusion rate, those with positive skin test results, and patients who developed anaphylaxis were given enzyme replacement therapy with desensitization. HSR may develop during enzyme replacement therapy, which are vital in lysosomal storage diseases, and discontinuation of enzyme replacement therapy is a significant loss for patients with metabolic disorders. These reactions can be treated with premedication and long-term infusions, but some patients may require desensitization protocols for continued treatment.

Comparison of complications and indwelling time in midline catheters versus central venous catheters: A systematic review and meta-analysis.

Central venous catheters and midline catheters are commonly used as medium- to long-term intravenous infusion tools in clinical nursing. However, there is currently no reliable conclusion on whether there are differences in complications and indwelling time between these two types of catheters. To investigate whether there are differences in the incidence of complications and indwelling time between the use of midline catheters and central venous catheters as intravenous infusion tools. A systematic search was conducted across various databases including Web of Science, PubMed, Embase, Cochrane Library, CINAHL, Wanfang and China National Knowledge Infrastructure. The selection of studies and assessment of their quality was carried out independently by two reviewers. Meta-analysis was conducted using the RevMan 5.3 software. Heterogeneity was evaluated, one of the pooled analyses was performed using the random-effect model, while the others used the fixed-effect model. Mean differences or odds ratios with corresponding 95% confidence intervals were calculated. Ten studies (1,554 participants) met the inclusion criteria. Meta-analysis showed that there was a statistically significant difference in the complication rates [OR = 0.36, 95% CI (0.18, 0.70), p = 0.003], incidence of catheter-related thrombosis [OR = 0.28, 95% CI (0.11, 0.71), I2= 0%,p = 0.007], catheter-related infection[OR = 0.36, 95% CI (0.16, 0.78), I2= 27%, p = 0.007] and catheter blockage [OR = 0.21, 95% CI (0.09, 0.51), I2= 18%, p = 0.0005] between midline catheters group and central venous catheters group. There was a statistically significant difference in the catheter indwelling time between the two groups [MD = 0.9, 95% CI (0.33, 1.46), I2= 0%, p = 0.002]. There was no significant difference in other complications such as phlebitis, catheter dislodgement and leakage between the two groups. Midline catheter was superior to central venous catheter in terms of the overall complication rates and incidence of catheter-related thrombosis, catheter blockage, catheter-related infection and indwelling time.

Letter to the Editor: Impact of long-term continuous terlipressin infusion on the liver transplant waitlist in an Australian cohort.

Letter to the Editor: Impact of long-term continuous terlipressin infusion on the liver transplant waitlist in an Australian cohort.

Effect of long-term albumin infusion in patient with cirrhosis and ascites

Effect of long-term albumin infusion in patient with cirrhosis and ascites

Long-term intrathecal infusion of low-dose morphine effectively relieves symptoms of severe restless legs syndrome/Willis-Ekbom disease without inducing opioid tolerance.

Restless legs syndrome/Willis-Ekbom disease (RLS/WED) causes a strong urge to move legs while resting. Restless legs syndrome/WED is an often-inherited disease occurring in 3% to 10% of adult populations, increasing with age. Severity varies from mild disturbance of sleep to painful restless legs and arms, loss of sleep, fatigue, and risk of suicide. Dopaminergic drugs relieve symptoms, but cause augmentation, ie, initially helpful but later increase the burden of symptoms. Oral gabapentinoids and opioids are often added, but opioid tolerance and adverse effects are common. With the high prevalence and incomplete help from oral drugs, significant unmet needs exist for effective therapy for severe RLS/WED. Ongoing spinal intrathecal infusion of low-dose morphine is effective, but not generally recognized, as only 12 cases have been published since 2002. We report 7 patients suffering from severe RLS/WED, who had no relief from oral dopaminergic, gabapentinoid, or opioid drugs; they all had excellent relief during ongoing spinal intrathecal infusion of morphine at only 1 to 5 μg/h, ongoing for 1 to 21 years without need of higher doses of morphine.. We suggest that morphine may be transported with the cerebrospinal fluid reaching and readjusting malfunctioning dopamine neuronal systems in the brain and spinal cord. The effects last only as long as the infusion continues. A patient with RLS/WED and persistent genital arousal disorder (PGAD) was relieved of both RLS/WED and PGAD symptoms. These case reports suggest that intrathecal infusion of low-dose morphine is an effective treatment of severe RLS.

Long-Term Continuous Terlipressin Infusion Improves Cardiac Reserve in Patients With Decompensated Cirrhosis

Cardiac dysfunction is a key factor in the pathogenesis of hepatorenal syndrome, for which terlipressin is the recommended first-line treatment. This study investigates whether long-term terlipressin can ameliorate the subclinical cardiac dysfunction observed in decompensated cirrhosis. Twenty-two patients with decompensated cirrhosis and ascites enrolled in a prospective study of home continuous terlipressin infusion were included. Cardiac function was assessed using dobutamine stress echocardiogram before and after 12 weeks of terlipressin. The primary outcome was the impact of terlipressin on cardiac reserve; the change in cardiac output (CO) in response to stress. Median age was 61 years (IQR 56-64), median MELD score was 15 (IQR 12.3-17.0) and 72.7% were male. The increase in CO in response to low-dose dobutamine was significantly higher following terlipressin (↑4.0L/min [↑57.8%]) as compared to baseline (↑1.8L/min [21.3%], p=0.0001). The proportion of patients with impaired cardiac reserve (defined by ΔCO <25% after low-dose dobutamine) reduced from 81.8% at baseline to 40.9% after terlipressin, (p=0.02), driven primarily by improvement in inotropic function. Resting cardiac output (CO) decreased significantly after terlipressin from 8.9±2.2L/min to 7.2±1.8 L/min (p<0.001, normal range 5-6L/min), due to a decrease in stroke volume from 108 to 86mL/beat (p=0.006). Long-term continuous terlipressin infusion resulted in a significant increase in cardiac reserve and attenuation of the hyperdynamic state usually observed in decompensated cirrhosis. These data provide important mechanistic insight into the pathogenesis and reversibility of cardiac dysfunction in cirrhosis. Future studies are required to evaluate whether long-term terlipressin can prevent hepatic decompensating events such as hepatorenal syndrome in high-risk individuals. ANZCTR NUMBER: (http://www.anzctr.org.au/): ACTRN12619000891123.

Outpatient Continuous Intravenous Inotropy in the Modern Era.

The use of continuous inotropy in patients with advanced heart failure (HF) has been historically controversial due to the prevailing notion that it will increase mortality. In practice, clinicians have continued to revisit this idea as there remains a lack of treatment options for patients in stage D HF. Clinical trials in the past have generally not shown favorable effects of long-term chronic infusions of positive IV inotropic agents on symptoms and exercise tolerance. However, these older studies which indicated poor outcomes with palliative inotropes may not apply to current practice. Modern trials and case series have shown that milrinone and dobutamine may be safely used in patients who are bridging to device therapy or transplant or for palliation. Broad adoption of mortality-reducing modern guideline-directed medical therapy and implantable cardioverter defibrillators may have contributed to the positive results that contemporary trials have seen with inotrope use. For the stage D HF patient, modern use of outpatient inotropy (OI) can alleviate symptom burden and prolong time spent at home. Additionally, more recent studies and case series suggest that OI can be a reasonable alternative to left ventricular assist device placement for both bridging to transplant or as destination therapy. In the appropriate patient, and according to the patient's informed decision and preference, this may be a viable alternative therapeutic option. Contemporary data suggest that OI should be considered in patients who are being evaluated for advanced therapies.

Design and application of a multiple combination portable auxiliary device for infusion

Intravenous infusion is an important route of drug therapy, and infusion safety is an important issue for medical staff. Long-term and multiple infusion routes at the same time bring inconvenience to patients. Multiple three-way switches in parallel infusion may lead to interruption of the liquid route, which can seriously endanger the life of patients. To address these clinical issues, medical staff from the School of Basic Medical Sciences of Hebei Medical University and the Emergency Department of the Second Hospital of Hebei Medical University designed a multiple combination portable infusion assistance device and obtained the National Utility Model Patent of China (ZL 2022 2 0226073.2). The device is mainly composed of adhesive tape sticker, fixed slots and pipelines, and also includes a three-way valve and a mixing chamber, and different modes of infusion assist devices can be selected according to clinical needs. The device is simple and convenient to operate, solves the problem of multiple liquid infusion blockages, improves the safety and comfort of infusion, and can meet the needs of liquid infusion in various clinical situations.

Long-term glucocorticoid infusion impairs epididymal adipocyte metabolism and maturation and affects miR-150–5p actions

The most common form of hypercortisolism is iatrogenic Cushing's syndrome. Lipodystrophy and metabolic disorders can result from the use of exogenous glucocorticoids (GC). Adipocytes play an important role in the production of circulating exosomal microRNAs, and knockdown of Dicer promotes lipodystrophy. The aim of this study is to investigate the effect of GCs on epididymal fat and to assess their influence on circulating microRNAs associated with fat turnover. The data indicate that despite the reduction in adipocyte volume due to increased lipolysis and apoptosis, there is no difference in tissue mass, suggesting that epididymal fat pad, related to animal size, is not affected by GC treatment. Although high concentrations of GC have no direct effect on epididymal microRNA-150–5p expression, GC can induce epididymal adipocyte uptake of microRNA-150–5p, which regulates transcription factor Ppar gamma during adipocyte maturation. In addition, GC treatment increased lipolysis and decreased glucose-derived lipid and glycerol incorporation. In conclusion, the similar control and GC epididymal fat mass results from increased dense fibrogenic tissue and decreased adipocyte volume induced by the lipolytic effect of GC. These findings demonstrate the complexity of epididymal fat. They also highlight how this disease alters fat distribution. This study is the first in a series published by our laboratory showing the detailed mechanism of adipocyte turnover in this disease.

Bile Acid-Targeted Hyaluronic Acid Nanoparticles for Enhanced Oral Absorption of Deferoxamine.

Patients with β-thalassemia and sickle cell disease often rely on blood transfusions which can lead to hemochromatosis and chronic oxidative stress in cells and tissues. Deferoxamine (DFO) is clinically approved to treat hemochromatosis but is suboptimal to patients due to its poor pharmacokinetics which requires long-term infusion regimens. Although the oral route is preferable, DFO has limited oral bioavailability. Studies have shown that hyaluronic acid (HA) and bile acid (BA) can enhance the oral absorption of poorly absorbed drugs. To improve upon the oral delivery of DFO, we report on the synthesis and characterization of HA (MW 15 kD) conjugated to two types of BA, deoxycholic acid (DOCA) and taurocholic acid (TCA), and DFO. The resulting seven polymeric conjugates all formed self-assembled nanoparticles. The degree of BA and DFO conjugation to the HA polymer was confirmed at each step through nuclear magnetic resonance, Fourier transform infrared spectroscopy, and UV-Vis spectroscopy. The best formulations for further in vitro testing were determined based on physicochemical characterizations and included HA-DFO, TCA9-HA-DFO, and DOCA9-HA-DFO. Results from in vitro assays revealed that TCA9-HA-DFO enhanced the permeation of DFO the most and was also less cytotoxic to cells compared to the free drug DFO. In addition, ferritin reduction studies indicated that the conjugation of DFO to TCA9-HA did not compromise its chelation efficiency at equivalent free DFO concentrations. This research provides supportive data for the idea that TCA conjugated to HA may enhance the oral absorption of DFO, improve its cytocompatibility, and maintain its iron chelation efficiency.

Pharmacokinetics and exposure-safety relationship of ciprofol for sedation in mechanically ventilated patients in the intensive care unit.

Ciprofol (HSK3486) is a newly developed, highly selective γ-aminobutyric acid-A (GABAA) receptor potentiator that is recently approved for a new indication of sedation for patients in the intensive care unit (ICU) in China. This analysis aimed to characterize the population pharmacokinetics (PopPKs) of ciprofol and evaluate the relationship of exposure with hypotension in mechanically ventilated patients in the ICU. A total of 462 subjects with 3918 concentration measurements from two clinical trials of mechanically ventilated patients in the ICU, four clinical trials of elective surgical patients, and six clinical trials of healthy subjects were used in the PopPK analysis. Exposure-safety relationship for hypotension was evaluated based on the data gathered from 112 subjects in two clinical trials of mechanically ventilated patients in the ICU. Ciprofol pharmacokinetics (PKs) was adequately described by a three-compartment linear disposition model with first-order elimination. Body weight, age, sex, blood sampling site (vein vs. arterial), study design (long-term infusion vs. short-term infusion), and patient population (ICU vs. non-ICU) were identified as statistically significant covariates on the PKs of ciprofol. Within the exposure range of the mechanically ventilated ICU patient population, no meaningful association was observed between ciprofol exposure and the incidence of hypotension. These results support the dosing regimen currently used in mechanically ventilated patients in the ICU.

The Role of Transjugular Intrahepatic Portosystemic Shunt for the Management of Ascites in Patients with Decompensated Cirrhosis.

The development and progression of ascites represent a crucial event in the natural history of patients with cirrhosis, predisposing them to other complications and carrying a heavy impact on prognosis. The current standard of care for the management of ascites relies on various combinations of diuretics and large-volume paracenteses. Periodic long-term albumin infusions on top of diuretics have been recently shown to greatly facilitate the management of ascites. The insertion of a transjugular intrahepatic portosystemic shunt (TIPS), an artificial connection between the portal and caval systems, is indicated to treat patients with refractory ascites. TIPS acts to decrease portal hypertension, thus targeting an upstream event in the pathophysiological cascade of cirrhosis decompensation. Available evidence shows a significant benefit on ascites control/resolution, with less clear results on patient survival. Patient selection plays a crucial role in obtaining better clinical responses and avoiding TIPS-related adverse events, the most important of which are hepatic encephalopathy, cardiac overload and failure, and liver failure. At the same time, some recent technical evolutions of available stents appear promising but deserve further investigations. Future challenges and perspectives include (i) identifying the features for selecting the ideal candidate to TIPS; (ii) recognizing the better timing for TIPS placement; and (iii) understanding the most appropriate role of TIPS within the framework of all other available treatments for the management of patients with decompensated cirrhosis.

Recent developments in the management of ascites in cirrhosis.

In recent years, advances have been made for treating ascites in patients with cirrhosis. Recent studies have indicated that several treatments that have been used for a long time in the management of portal hypertension may have beneficial effects that were not previously identified. Long-term albumin infusion may improve survival in patients with cirrhosis and ascites while beta-blockers may reduce ascites occurrence. Transjugular intrahepatic porto-systemic shunt (TIPS) placement may also improve survival in selected patients in addition to the control with ascites. Low-flow ascites pump insertion can be another option for some patients with intractable ascites. In this review, we summarize the latest data related to the management of ascites occurring in cirrhosis. There are still unanswered questions, such as the optimal use of albumin as a long-term therapy, the place of beta-blockers, and the best timing for TIPS placement to improve the natural history of ascites, as well as the optimal stent diameter to reduce the risk of shunt-related side-effects. These issued should be addressed in future studies.

Continuous intrafemoral artery infusion of urokinase improves diabetic foot ulcers healing and decreases cardiovascular events in a long-term follow-up study

IntroductionDiabetic foot ulcer (DFU) is a disabling complication of diabetes mellitus. Here, we attempted to assess whether long-term intrafemoral artery infusion of low-dose urokinase therapy improved DFUs and decreased cardiovascular...

The role of oxygenation in kidney and liver machine perfusion

Background. Organ transplantation is the optimal decision for patients in the end stage of many diseases. Certain conditions are required for the transportation and preservation of a donor organ after explantation, including factors such as temperature, pressure, and preservative solution. All currently available methods of preservation of donor organs are aimed at maximizing the complete preservation of the functional state of the graft from the moment of its removal to implantation and reperfusion in the recipient's body.Aim. The purpose of this review is to provide up-to-date information on the results of the studies performed in order to decide on the preferred method of organ preservation.Material and methods. An analysis of literature sources in English and Russian from 2009 to 2023 on this topic was performed in the databases PubMed, MEDLINE, Google Scholar. The review highlights the results of preclinical (on animal models) and clinical studies, as well as achievements in the field of ex-vivo machine perfusion with an emphasis on machine hypothermic perfusion and modified oxygenated hypothermic machine perfusion, subnormothermic machine perfusion and machine normothermic perfusion.Results. The daily increase in the number of patients in need of organ transplantation delays the timely selection and search for a donor. Organ donation after cardiac death is a promising step in an attempt to overcome the disbalance between the number of patients and organs, but the risk of developing early graft damage increases. The criteria for selecting donors and donor organs are being expanded, as a result, elderly donors and not-optimal grafts are included, but they are less resistant to ischemic damage. In this connection, there is a need for long-term infusion support through machine perfusion.Conclusion. In recent years, research has focused on alternative preservation methods, studying hypothermic, subnormothermic and normothermic machine perfusion. The use of machine perfusion has become the most widespread among kidney transplants and has shown good results. Further development is expected in the field of studying and improving this method of organ preservation, which allows not only transporting, but also improving the functional state of the graft.

Comparison of bolus administration and short-term infusion versus long-term infusion of doxorubicin in terms of cardiotoxicity and efficacy.

Cardiotoxicity caused by anthracyclines chemotherapy is one of the leading causes of mortality and morbidity in cancer survivors. Continuous infusion (CI) instead of bolus (BOL) injection is one of the methods that seem to be effective in reducing doxorubicin (DOX) cardiotoxicity. Due to the variety of results, we decided to compare these two approaches regarding toxicity and efficacy and report the final results for different cancers. We included 21 studies (four preclinical and seventeen clinical trials) up to May 15, 2023. In children with acute lymphoblastic leukemia (ALL) and adults with chronic lymphoblastic leukemia (CLL) and gastric cancer, results were in favor of BOL injection, without increase in cardiotoxicity. On the other hand, CI showed to be better option in patients with small-cell lung cancer (SCLC) and breast cancer. Various results were also observed in adult patients with sarcoma. Overall, it can be concluded that the benefits of CI, especially in adults, outweigh its disadvantages. However, due to the variety of results and heterogeneity of studies, further clinical trials with a larger sample size and a longer duration of follow-up are needed to make a more accurate comparison between CI and BOL injection.

Population pharmacokinetic/pharmacodynamic modeling and exposure-response analysis of ciprofol in the induction and maintenance of general anesthesia in patients undergoing elective surgery: A prospective dose optimization study

AimThis study aimed to establish a population pharmacokinetic and pharmacodynamic (PK-PD) model to explore the optimal maintenance dose and appropriate starting time of maintenance dose after induction of ciprofol and investigate the efficacy and safety of ciprofol for general anesthesia induction and maintenance in patients undergoing elective surgery. MethodA total of 334 subjects with 3092 concentration measurements from nine clinical trials and 115 subjects with 5640 bispectral index (BIS) measurements from two clinical trials were used in the population PK-PD analysis. Exposure-response relationships for both efficacy endpoints (duration of anesthesia successful induction, time to recovery from anesthesia, time to respiratory recovery, and time from discontinuation to the 1st/3rd consecutive Aldrete score ≥ 9) and safety variables (hypotension, bradycardia, and injection site pain) were evaluated based on the data gathered from 115 subjects in two clinical trials. ResultCiprofol pharmacokinetics (PK) were adequately described by a three-compartment model with first-order elimination from the central compartment and redistribution from the deep and shallow peripheral compartments. An inhibitory sigmoidal Emax model best described the relationship between ciprofol effect-site concentrations and BIS measurements. Body weight, age, sex, blood sampling site, and study type (short-term infusion vs long-term infusion) were identified as statistically significant covariates on the PK of ciprofol. No covariates were found to have a significant effect on the pharmacodynamic (PD) parameters. The PK-PD simulation results showed that the optimal maintenance dose was 0.8 mg/kg/h and the appropriate time to start the maintenance dose was 4–5 mins after the induction dose of ciprofol. Within the exposure range of this study, no meaningful correlations between ciprofol exposures and efficacy or safety endpoints were observed. ConclusionA population PK-PD model was successfully developed to describe the ciprofol PK and BIS changes. Efficacy was consistent across the exposure range with a well-tolerated safety profile indicating no maintenance dose adjustment is required for patients undergoing elective surgery.

EXTH-54. GB13 IS A POTENT TREATMENT FOR IL13RA2-EXPRESSING GBM AND DMG AND IMPROVES STANDARD-OF-CARE THERAPY

Abstract GB13 is a novel biologic therapy in the final stages of preclinical development for the treatment of glioblastoma (GBM) and H3 K27-altered diffuse midline glioma (DMG) that has received Orphan Drug Designation by the Food and Drug Administration for treatment of malignant gliomas. GB13 targets a specific tumor-restricted receptor of interleukin 13 called interleukin 13 receptor alpha 2 (IL13Rα2). IL13Rα2 is highly expressed in malignant gliomas and, importantly, is not expressed on non-cancerous cells of the brain. GB13 consists of an engineered proprietary mutant of IL13, which binds exclusively to IL13Rα2, and is fused to a highly cytotoxic exotoxin molecule. In vitro data demonstrate that GB13 potently kills IL13Rα2+ cancer cells while sparing non-cancerous cells. These characteristics make GB13 an attractive agent for safe and efficacious targeting of tumor cells expressing IL13Rα2 in upcoming clinical trials. In the current studies, we employed patient-derived GBM and DMG cell and animal models to provide key conclusions that support GB13 as an effective treatment option for gliomas in the clinic. First, we demonstrated that single acute infusions of GB13 by enhanced delivery (CED) is effective at decreasing orthotopic tumor volumes and increasing animal survival and that a long-term infusion can more significantly extend animal survival. Second, we determined that IL13Rα2 is requisite for GB13 activity as tumors that do not express the receptor are insensitive to the cytotoxic effects of GB13, demonstrating a precise and clear biomarker for clinical trial patient selection. Finally, we determined that GB13 works in concert with clinical standard-of-care radiation therapy to increase cell death, compared to radiation alone. Based on this work, we and our clinical collaborators are confident that the current work confirms GB13 has many important characteristics as an exciting therapy, which continues development towards a Phase I clinical trial for both GBM and pediatric DMG.

Safety and tolerability of long-term apomorphine infusion in advanced Parkinson's disease: an Indian multi-center (APO-IND) experience

Advanced Parkinson’s Disease (APD) is complicated by the emergence of motor and non-motor fluctuations, which are initially predictable and eventually become unpredictable, in part due to erratic gastric absorption and short half of oral levodopa. Attempts to manage such fluctuations with oral dopaminergic drugs often lead to disabling dyskinesias. Continuous Subcutaneous Apomorphine Infusion (CSAI), despite being approved for the treatment of APD since 1993, was approved in India only in 2019. We studied the safety, tolerability and efficacy of CSAI in Indian patients with APD in a registry design to raise local awareness of this important treatment. We conducted a prospective registry-based observational audit at 10 centers across different states of India. Patients with APD, not responding to or with significant side effects from oral dopaminergic therapy, were assessed at baseline and at month 6 and 12 following CSAI infusion. Fifty-one patients completed the study, CSAI significantly reduced the functional impact of dyskinesia (p < 0.01 at 6 months and p < 0.001 at 12 months). There was a significant improvement in the OFF-state from baseline (p < 0.01 at 6 months and p < 0.001 at 12 months) No discernible side effects were observed apart from mild site reaction (n = 7), nausea (n = 7) skin nodules (n = 2). CSAI demonstrated safety, efficacy, tolerability and improved quality of life in patients with APD, as shown in previous studies. Our study highlighted current existing inequalities in treatment availability, lack of awareness, knowledge gap, affordability and cost remains a concern regarding apomorphine use in Indian PD population.

4.47 Case Series: The Benefit and Tolerance of Long-Term Maintenance Ketamine Infusion for Treatment-Resistant Depression in Adolescent Patients

4.47 Case Series: The Benefit and Tolerance of Long-Term Maintenance Ketamine Infusion for Treatment-Resistant Depression in Adolescent Patients