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Background: Tigecycline is widely used to treat infections in intensive care units. Drugs often need to be delivered to critically ill patients feeding by parenteral nutrition (PN). Before two preparations are administered in the same infusion line, the safety of this combination should be established. The objective of this study was to determine the compatibility of tigecycline with selected multichamber bag PN (MCB‐PN). Methods: Tigecycline was diluted in 0.9% sodium chloride solution and 5% glucose solution to obtain two 0.5 mg/ml solutions. Then the solutions were combined with selected MCB‐PN in appropriate proportions. The samples were visually assessed, and pH, osmolality, turbidity, particle size, and zeta potential were measured. These measurements were made immediately after combining the solutions and after 4 h of storage at 23°C ± 1°C. Results: It was determined that the pH values of the mixtures after combining with tigecycline changed by ≤0.1 unit. An increase in zeta potential was recorded, excluding one combination of tigecycline with the mixture. For all samples tested, the particle size distribution was within the acceptable range immediately after combination and after 4 h of storage. The difference in osmolality did not exceed ±3%, whereas the zeta potential decreased for only one combination. The turbidity of none of the samples exceeded a critical value. Conclusion: The physical compatibility of the tigecycline with five MCB‐PN was proved. They can therefore be administered to patients in one infusion line using the Y‐site. [ABSTRACT FROM AUTHOR]

Introduction: Treatment with topotecan is standard-of-care therapy for relapsed small-cell lung cancer (SCLC). Both oral and intravenous administrations of topotecan have been extensively researched and are found to be equally effective with less adverse events in the oral group. Case Presentation: We report a case of a patient with SCLC, who had previously received oral topotecan, with radiological stable disease with no changes in tumor or metastasis diameter size after two administrations. Subsequently, this patient received intravenous topotecan instead of oral due to supply difficulties. After one administration of intravenous topotecan, we saw significant disease regression. Conclusion: This is to our knowledge the first reported case of better response of intravenous topotecan than oral topotecan. Multiple extrinsic (e.g., food, medication) factors were investigated but could not deliver an explanation. [ABSTRACT FROM AUTHOR]

Objective: Intravenous (IV) push (IVP) is an alternative administration method for levetiracetam, but evidence evaluating it compared to IV piggyback (IVPB) for loading doses in acutely seizing patients is limited, particularly in patients with status epilepticus (SE). This study aimed to compare the efficiency and safety of IVP versus IVPB levetiracetam loading doses. Methods: This was a single‐center sequential retrospective study conducted in adult (≥18 years) patients who received an IV levetiracetam loading dose (>2000 mg or ≥20 mg/kg) for acute or suspected seizure. The primary outcome was time to administration, compared between doses given as IVP versus IVPB. Secondary outcomes included rates of adverse events (AEs), rescue benzodiazepine or antiseizure medication administration, intubation, and intensive care unit (ICU) admission between groups. Results: A total of 246 patients were included; 116 received IVP and 130 received IVPB loading doses. Median age was 56 years; most patients were male (62%) and White (60%) and had witnessed seizures (67%). Doses were administered for SE in 32 (27.5%) and 46 (35.4%) patients in the IVP and IVPB arms, respectively. Median time to administration was shorter in the IVP group (12 vs. 38 min, p <.001). Bradycardia (1.7% vs. 2.3%, p =.99), hypotension (7.8% vs. 12%, p =.30), sedation (6% vs. 12.3%, p =.09), intubation (10% vs. 8%, p =.37), ICU admission (32% vs. 39%, p =.31), and rescue medication administration (8.6% vs. 14.6% p =.10) were similar between groups. In SE patients, IVP was associated with shorter time to administration (12 vs. 44 min, p =.003) and lower odds of ICU admission after adjustment for age, dose, Status Epilepticus Severity Score, and seizure history (adjusted odds ratio =.23, 95% confidence interval =.06–.81). Significance: IVP reduced time to levetiracetam administration versus IVPB and was not associated with more AEs. Rescue agent use, intubation, and ICU admission were similar between arms, but IVP may reduce ICU admissions in SE patients. Prospective studies should assess the effectiveness of IVP versus IVPB. [ABSTRACT FROM AUTHOR]

The objective of the study was to assess the therapeutic efficacy of targeting remote zone cardiomyocytes with cardiosphere‐derived cell (CDC) extracellular vesicles (EVs) delivered via intramyocardial and intravenous routes following acute myocardial infarction (MI). Cardiomyocyte (CM) cell death plays a significant role in left ventricular (LV) remodeling and cardiac dysfunction following MI. While EVs secreted by CDCs have shown efficacy in promoting cardiac repair in preclinical models of MI, their translational potential is limited by their biodistribution and requirement for intramyocardial delivery. We hypothesized that engineering the surface of EVs to target cardiomyocytes would enhance their therapeutic efficacy following systemic delivery in a model of acute MI. CDC‐derived EVs were engineered to express a CM‐specific binding peptide (CMP) on their surface and characterized for size, morphology, and protein expression. Mice with acute MI underwent both intramyocardial and intravenous delivery of EVs, CMP‐EVs and placebo in a double‐blind study. LVEF was assessed by echo at 2‐ and 28‐days post‐MI and tissue samples processed for assessment of EV biodistribution and histological endpoints. CMP‐EVs demonstrated superior cardiac targeting and retention when compared with unmodified EVs 24 h post‐MI. Mice treated with IV delivered CMP‐EVs demonstrated a significant improvement in LVEF and a significant reduction in remote zone cardiomyocyte apoptosis when compared with IV delivered non‐targeted EVs at 28‐day post‐MI. Systemic administration of CMP‐EVs improved cardiac function and reduced remote zone cardiomyocyte apoptosis compared with IV‐administered unmodified EVs, demonstrating a strategy to optimize therapeutic EV delivery post‐MI. [ABSTRACT FROM AUTHOR]

Introduction: Breast cancer (BC) is one of the leading causes of cancer and is the first cause of death from malignant tumors among women worldwide. New cancer therapies receive regulatory approval yearly and to avoid health disparities in society, the health systems are challenged to adapt their infrastructure, methodologies, and reimbursement policies to allow broad access to these treatments. In addition, listening to patients' voices about their therapy preferences is essential. We aim to investigate the administration route preferences [subcutaneous (SC) or intravenous (IV)] among patients diagnosed with HER2 positive BC and healthcare professionals (HCPs) and to investigate healthcare resources utilization (quality and quantity) for each route of administration (SC or IV) for treating those patients. Methods: We conducted a systematic literature review focused on clinical trials and observational and economic studies, using PubMed (MEDLINE), Cochrane Library, Virtual Health Library (VHL), Scientific Electronic Library Online (SciELO), and Latin American and Caribbean Health Sciences Literature (LILACS) databases based on the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. Results: The literature review included 25 studies in the analysis. Studies have reported that patients and HCPs prefer the SC route of administration to IV because it saves time in terms of chair time, administration, and preparation and is less painful. In addition, SC administration might be a more cost-saving option when analyzing direct and indirect costs. Discussion: As BC stands as a significant global health concern and the leading cause of cancer-related deaths in women worldwide, understanding and incorporating patient and HCPs preferences in the choice of administration route become paramount. The observed preference for SC administration not only aligns with the imperative of adapting health systems to facilitate broad access to new cancer therapies but also underscores the importance of considering patient experiences and economic implications in shaping treatment strategies. These insights are crucial for healthcare policymakers, clinicians, and stakeholders in optimizing healthcare resources and enhancing the overall quality of BC care. [ABSTRACT FROM AUTHOR]

We studied the function of the auditory system in Wistar rats after repeated intravenous administration of nicotinamide riboside (NR). The functional activity of the receptor and retrocochlear parts of the auditory system were assessed by recording short-latency auditory evoked potentials (SLAEPs) and distortion-product otoacoustic emissions (DPOAEs) at baseline, immediately after NR administration, and 1 and 2 months later. Repeated intravenous NR administration (cumulative dose of 2700 mg/kg) to Wistar rats has a detrimental impact on the structures within the cochlear section of the auditory system. [ABSTRACT FROM AUTHOR]

Introduction: Treatment with topotecan is standard-of-care therapy for relapsed small-cell lung cancer (SCLC). Both oral and intravenous administrations of topotecan have been extensively researched and are found to be equally effective with less adverse events in the oral group. Case Presentation: We report a case of a patient with SCLC, who had previously received oral topotecan, with radiological stable disease with no changes in tumor or metastasis diameter size after two administrations. Subsequently, this patient received intravenous topotecan instead of oral due to supply difficulties. After one administration of intravenous topotecan, we saw significant disease regression. Conclusion: This is to our knowledge the first reported case of better response of intravenous topotecan than oral topotecan. Multiple extrinsic (e.g., food, medication) factors were investigated but could not deliver an explanation.

Background The global rise in cases of acute myocardial infarction (AMI) poses a significant health challenge, which is why adult stem cells have gained great importance in recent years, due to their potential to promote the regeneration of the flowcardiac tissue, among which multipotent mesenchymal stromal cells (MSCs) stand out, thanks to their clinical usefulness. Objectives To evaluate the effect of the dose, timing, and route of administration of MSCs on their regenerative capacity after MI. Methods We searched for randomized clinical trials and experimental studies published up to April 25, 2024, in Medline (PubMed) and Scopus. Results Nine clinical studies were included in the qualitative assessment. The main routes of application were coronary, intramyocardially, epicardial topical and systemic venous perfusion, which could have clinical effectiveness with doses of 1x10 6 MSC/Kg,1 to 3 x 10 6, 4x10 6 and those greater than 0.5x10 6, respectively. The median number of viable cells administered was 2.4x10 6 (IQR: 1.6-2.4) in the PCI group versus 1.6x10 6 in the RCVI group (p=0.167). Median ex vivo retention was 2.55% in the RCVI group, 30 days after AMI, and 39.40% in the PCI group. At 4 and 12 months of follow-up, a better left ventricular end-to-end (LVEF) was observed in the group treated with ADSCs, at 4 (51.8% ±5.4% vs. 35.5% ±1.9%) and 8 weeks (52.1%± 3.4% versus 34.2% ±4.7%, p = 0.048). Conclusions The dosing, timing of administration, and routes of administration were important factors to assess the efficacy of the MSC.

Ocular diseases create a significant economic burden and decrease in quality of life worldwide. Drugs and carrier molecules that penetrate ocular tissues after intravenous administration are needed for more efficient and patient-friendly treatment of ocular diseases. Here, ocular barrier-penetrating aptamers were selected through the utilization of in vivo SELEX and intravenous injection in rats. Three aptamers—Apt1, Apt2, and Apt5—were chosen based on their specific accumulation in vascularized ocular tissues and further characterized for their in vivo biodistribution using quantitative reverse-transcription PCR (RT-qPCR). A statistically significant difference between ΔCt values of ocular and control tissues with Apt2 (p

Objective: This study aimed to evaluate the efficacy of the topical anesthetics lidocaine and benzocaine in reducing pain associated with peripheral intravenous catheterization and in enhancing patient satisfaction in the emergency department. Materials and Methods: This randomized-controlled, parallel-group, doubleblind, experimental, and Phase III clinical trial involved 120 individuals admitted to the Emergency Department of a University Hospital. Data were collected using an Individual Information Form, Visual Analog Scale, and Patient Satisfaction Scale about Catheterization. Participants were divided into three groups (lidocaine 10% spray, benzocaine 20% spray, and placebo groups) according to a computer-generated randomization table. Results: The average pain scores were lower and satisfaction levels with catheterization were higher in the lidocaine and benzocaine groups compared to the placebo group (p<0.001). A strong negative correlation was observed between the groups' pain scores and satisfaction levels with catheterization (Lidocaine Spray Group r=-0.636 p<0.001; Benzocaine Spray Group r=-0.651 p<0.001; Placebo Group r=-0.877 p<0.001). Conclusion: Topical lidocaine and benzocaine have been proven to reduce pain from peripheral intravenous catheterization and improve patient satisfaction. These agents can be routinely used to alleviate injection pain and improve patient satisfaction with the procedure. [ABSTRACT FROM AUTHOR]

An inflammation-resolving polysialic acid-decorated PLGA nanoparticle (PolySia-NP) has been developed to treat geographic atrophy/age-related macular degeneration and other conditions caused by macrophage and complement over-activation. While PolySia-NPs have demonstrated pre-clinical efficacy, this study evaluated its systemic and intraocular safety. PolySia-NPs were evaluated in vitro for mutagenic activity using Salmonella strains and E. coli, with and without metabolic activation; cytotoxicity was evaluated based on its interference with normal mitosis. PolySia-NPs were administered intravenously in CD-1 mice and Sprague Dawley rats and assessed for survival and toxicity. Intravitreal (IVT) administration in Dutch Belted rabbits and non-human primates was assessed for ocular or systemic toxicity. In vitro results indicate that PolySia-NPs did not induce mutagenicity or cytotoxicity. Intravenous administration did not show clastogenic activity, effects on survival, or toxicity. A single intravitreal (IVT) injection and two elevated repeat IVT doses of PolySia-NPs separated by 7 days in rabbits showed no signs of systemic or ocular toxicity. A single IVT inoculation of PolySia-NPs in non-human primates demonstrated no adverse clinical or ophthalmological effects. The demonstration of systemic and ocular safety of PolySia-NPs supports its advancement into human clinical trials as a promising therapeutic approach for systemic and retinal degenerative diseases caused by chronic immune activation. [ABSTRACT FROM AUTHOR]

Purpose: Here, we aimed to study the distribution pattern of normal and cancer xenogeneic exosomes (Exos) and possible interspecies reactions in a rat model. Methods: Exos were isolated from normal Human umbilical vein endothelial cells (HUVECs) and MDA-MB-231 breast cancer cells. Diameter size and zeta potential distribution were studied using dynamic light scattering (DLS). The morphology of isolated Exos was monitored by scanning electron microscopy (SEM) images. Using western blotting, protein levels of exosomal tetraspanins were detected. For the in vivo study, Dil-labeled normal and cancer Exos were injected into the tail vein (100 µg exosomal protein/rat) three times at 1-hour intervals. After 24 hours, rats were euthanized and the cellular uptake of Exos was monitored in different organs using immunofluorescence staining (IF). Results: The size distribution and mean zeta potential of HUVEC and MDA-MB-231 cells Exos were 80±29.94 and 64.77±25.49 nm, and −7.58 and −11.8 mV, respectively. Western blotting revealed CD9, CD81, and CD63 in normal and cancer Exos. The SEM images exhibited typical nano-sized round-shape Exo particles. IF staining indicated sequestration of administrated Exos in splenic tissue and lungs. The distribution of Exo in kidneys, aorta, and hepatic tissue was less. These features were more evident in the group that received cancer Exos. We found no obvious adverse effects in rats that received normal or cancer Exos. Conclusion: Normal and cancerous xenogeneic human Exos can be sequestrated prominently in splenic tissue and lungs. Novel delivery approaches and engineering tools are helpful in the target delivery of administrated Exos to the injured sites. [ABSTRACT FROM AUTHOR]

Doxorubicin (DOX) is a potent chemotherapeutic drug, but its clinical use is hindered by significant side effects, it exerts on such vital organs as the heart, kidneys, lungs, liver, and intestines. Currently, there is a lack of effective drugs that can provide simultaneous protection of the heart and other vital organs during chemotherapy. Nicotinamide riboside (NR) holds promise as a pharmacological agent, able to ensure comprehensive protection against DOX systemic toxicity. This study was aimed to evaluate morphological characteristics of the vital organs (heart, lungs, liver, kidneys) in male SPF Wistar rats (n = 60, 283 ± 22 g) with chronic doxorubicin-induced cardiomyopathy under various intravenous NR administration modes (1800 mg/kg) as a protective agent. The rats were divided into four groups: (1) intact, (2) control (DOX), (3) combined administration mode (NR+DOX), (4) preventive administration mode (NR/NR+DOX). Post-administration follow-up period spanned two months and ended with tissue sampling with subsequent morphological analysis. The development of DOX-induced cardiotoxicity was monitored by echocardiography. DOX elicited more severe morphological alterations in the heart, kidneys, and lungs compared to the liver. Both NR administration modes demonstrated protective effects, with the preventive mode showing the greatest efficacy in safeguarding the vital organs. [ABSTRACT FROM AUTHOR]

IntroductionBreast cancer (BC) is one of the leading causes of cancer and is the first cause of death from malignant tumors among women worldwide. New cancer therapies receive regulatory approval yearly and to avoid health disparities in society, the health systems are challenged to adapt their infrastructure, methodologies, and reimbursement policies to allow broad access to these treatments. In addition, listening to patients’ voices about their therapy preferences is essential. We aim to investigate the administration route preferences [subcutaneous (SC) or intravenous (IV)] among patients diagnosed with HER2 positive BC and healthcare professionals (HCPs) and to investigate healthcare resources utilization (quality and quantity) for each route of administration (SC or IV) for treating those patients.MethodsWe conducted a systematic literature review focused on clinical trials and observational and economic studies, using PubMed (MEDLINE), Cochrane Library, Virtual Health Library (VHL), Scientific Electronic Library Online (SciELO), and Latin American and Caribbean Health Sciences Literature (LILACS) databases based on the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement.ResultsThe literature review included 25 studies in the analysis. Studies have reported that patients and HCPs prefer the SC route of administration to IV because it saves time in terms of chair time, administration, and preparation and is less painful. In addition, SC administration might be a more cost-saving option when analyzing direct and indirect costs.DiscussionAs BC stands as a significant global health concern and the leading cause of cancer-related deaths in women worldwide, understanding and incorporating patient and HCPs preferences in the choice of administration route become paramount. The observed preference for SC administration not only aligns with the imperative of adapting health systems to facilitate broad access to new cancer therapies but also underscores the importance of considering patient experiences and economic implications in shaping treatment strategies. These insights are crucial for healthcare policymakers, clinicians, and stakeholders in optimizing healthcare resources and enhancing the overall quality of BC care.

Objective: Neuropathic pain has been considered as one of the most serious chronic pain subtypes and causes intolerable suffering to patients physically and mentally. This study aimed to verify the analgesic effect of intravenous administration of human umbilical cord mesenchymal stem cells (HUC-MSCs) upon rats with chronic constriction injury (CCI)-induced neuropathic pain and the concomitant mechanism via modulating microglia. Methods: 30 male SD rats were randomized divided into three groups (n = 10 per group): Sham + Saline group (S&S group), CCI + Saline group (C&S group) and CCI + HUC-MSCs group (C&U group). Rats were injected with either saline or HUC-MSCs via the caudal vein on the 7th day after modelling. The paw mechanical withdrawal threshold (PMWT) and thermal withdrawal latency (TWL) of the ligation side were measured before (day 0) and after (day 1, 3, 5, 7, 9, 11, 13, and 15) modelling. On day 15 after modelling, western-blotting and immunofluorescent staining were used to assess the expressive abundance of Iba-1 (a typical biomarker of activated microglia) in the ligation side of the spinal cord dorsal horn, and ultrastructural changes of the ligation of sciatic nerve were evaluated by transmission electron microscope (TEM). Results: Compared with the S&S group, PMWT and TWL in the C&S group were significantly decreased on day 5 and then persisted to day 15 after modelling (C&S vs S&S, P

Coenzyme CoQ10 (CoQ10) is an endogenous lipid-soluble antioxidant that effectively protects lipids, proteins, and DNA from oxidation due to its ability to undergo redox transitions between oxidized and reduced forms. Various oxidative stress-associated infectious and somatic diseases have been observed to disrupt the balance of CoQ10 concentration in tissues. As a high molecular weight polar lipophilic compound, CoQ10 exhibits very limited oral bioavailability, which restrains its therapeutic potential. Nevertheless, numerous studies have confirmed the clinical efficacy of CoQ10 therapy through oral administration of high doses over extended time periods. Experimental studies have demonstrated that in emergency situations, intravenous administration of both oxidized and reduced-form CoQ10 leads to a rapid increase in its concentration in organ tissues, offering protection for organ tissues in ischemic conditions. This suggests that the cardio- and neuroprotective efficacy of intravenously administered CoQ10 forms could present new opportunities in treating acute ischemic conditions. Based on these findings, the review provides reasoning supporting further research and implementation of CoQ10 dosage forms for intravenous administration in emergency situations into clinical practice. [ABSTRACT FROM AUTHOR]

Introduction: EASIER is a multicenter, observational, cross-sectional study investigating the consumption of healthcare resources, including healthcare professional (HCP) active working time, the costs associated with the current natalizumab intravenous (IV) administration, and the potential impact of the adoption of subcutaneous (SC) route. Methods: The EASIER study has three parts: (1) time and motion study to measure healthcare resources and working time needed for natalizumab IV administration using a digital data collection tool operated directly by HCPs; (2) HCP structured questionnaire-based estimation of the potential impact of natalizumab SC vs. IV administration; and (3) patient survey on the burden of natalizumab administration. Results: Nine Italian multiple sclerosis (MS) centers measured 404 IV natalizumab administration procedures and administered 26 HCP questionnaires and 297 patient questionnaires. Patients had a mean of 52 (range 1–176) previous IV administrations and spent a mean (median, IQR) of 152 (130, 94–184) minutes in the center per each IV procedure, with IV infusion covering 50% of the total. Including patient travel time, an average of 5 h was dedicated to each IV administration. Active working time by HCP amounted to 29 min per IV administration procedure, 70% of which by nursing staff. With adoption of the SC route, HCPs estimated a 50% reduction in patient procedure time and 55% lower HCP active working time. This translated into a 63% cost reduction for the MS center per natalizumab administration procedure. Conclusions: SC natalizumab administration will consistently reduce consumption of patient and HCP times per procedure and associated costs. [ABSTRACT FROM AUTHOR]

Phage therapy has shown great promise for the treatment of multidrugresistant bacterial infections. However, the lack of a thorough and organized understanding of phage-body interactions has limited its clinical application. Here, we administered different purified phages (Salmonella phage SE_SZW1, Acinetobacter phage AB_SZ6, and Pseudomonas phage PA_LZ7) intravenously to healthy animals (rats and monkeys) to evaluate the phage-induced host responses and phage pharmacokinetics with different intravenous (IV) doses in healthy animals. The plasma and the organs were sampled after different IV doses to determine the phage biodistribution, phage-induced cytokines, and antibodies. The potential side effects of phages on animals were assessed. A non-compartment model revealed that the plasma phage titer gradually decreased over time following a single dose. Repeated doses resulted in a 2-3 Log10 decline of the plasma phage titer at 5 min compared to the first dose, regardless of the type of phage administered in rats. Host innate immune responses were activated including splenic enlargement following repeated doses. Phage-specific neutralization antibodies in animals receiving phages were detected. Similar results were obtained from monkeys. In conclusion, the mammalian bodies were well-tolerant to the administered phages. The animal responses to the phages and the phage biodistribution profiles could have a significant impact on the efficacy of phage therapy. IMPORTANCE Phage therapy has demonstrated potential in addressing multidrugresistant bacterial infections. However, an insufficient understanding of phage-host interactions has impeded its broader clinical application. In our study, specific phages were administered intravenously (IV) to both rats and monkeys to elucidate phage-host interactions and evaluate phage pharmacokinetics (PK). Results revealed that with successive IV administrations, there was a decrease in plasma phage concentrations. Concurrently, these administrations elicited both innate and adaptive immune responses in the subjects. Notably, the observed immune responses and PK profiles exhibited variation contingent upon the phage type and the mammalian host. Despite these variations, the tested mammals exhibited a favorable tolerance to the IV-administered phages. This underscores the significance of comprehending these interactions for the optimization of phage therapy outcomes. [ABSTRACT FROM AUTHOR]

Little is known about whether preventative practices for post-contrast acute kidney injury (PC-AKI) recommended in guidelines have been adopted in clinical practice and translated into a lower incidence of PC-AKI. The aim of this study was to examine the yearly trends in the incidence of PC-AKI, and comorbidities and care practices associated with PC-AKI in hospitalized patients who received intravenous administration of iodinated contrast medium (ICM). Adult patients receiving intravenous ICM at the Second Xiangya Hospital of Central South University in China between 2015 and 2021 were included. Temporal trends in the incidence and risk factors for PC-AKI were evaluated using logistic regression analyses with adjustments for relevant variables. The incidence of PC-AKI has declined significantly from 5.3% in 2015 to 4.1% in 2021 (p < 0.001). This decreasing trend persisted after extensive multivariable adjustments. Of the comorbidities associated with PC-AKI, the proportion of patients with congestive heart failure or hypertension increased, while the proportion of patients older than 75 years, or with an estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2, diabetic nephropathy, or renal stone disease decreased. Among the care practices associated with PC-AKI, the proportion of patients using nephrotoxic drugs decreased, whereas the proportion of patients receiving intravenous fluids > 1000 mL on the day of ICM administration or using iso-osmolar ICM increased. In conclusion, a declining trend in PC-AKI incidence was observed in patients receiving intravenous ICM between 2015 and 2021, which may be related to increased awareness and efforts to prevent PC-AKI. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the impact of switch therapy of antimicrobials on cost reduction (pharmacoeconomic analysis) and hospital waste generation by switching from intravenous to oral therapy. This is a cross-sectional, observational, and retrospective study. Data from 2019, 2020, and 2021, provided by the clinical pharmacy service of a teaching hospital in the interior of Rio Grande do Sul, were analyzed. The variables analyzed were intravenous and oral antimicrobials, frequency, duration of use, and total treatment time according to the institutional protocols. An estimate of the amount of waste not generated from the change of administration route was calculated by weighing the kits using a precision balance in grams. During the analyzed period, 275 switch therapy of antimicrobials were performed, resulting in US$ 55,256.00 of savings. The main antimicrobial classes that underwent changes were cephalosporins (25.1%), penicillins (22.55%), and quinolones (17.45%). Changing from intravenous to oral therapy avoided the generation of 170,631 g of waste, including needles, syringes, infusion bags, equipment, reconstituted solution bottles, and medication. The change from intravenous to the oral route of antimicrobials is safe for the patient, economically effective, and significantly reduces waste generation. [Display omitted] • Pharmacy promotes safe medication use and lowers health care costs. • IV-to-PO switch is a significant intervention. • IV-to-PO switch is a practical strategy to prevent catheter-related infections. • IV-to-PO switch avoided the generation of 170,631 g of waste. • Institutional protocols guide switch therapy prescription eligibility criteria. [ABSTRACT FROM AUTHOR]

Meng Cai,1,&ast; Jie Liu,2,&ast; Xiao-Feng Lei,1 Yun-Long Li,3 Jin Yu1 1Department of Anesthesiology, Women and Children’s Hospital of Chongqing Medical University, Chongqing Health Center for Women and Children, Chongqing, People’s Republic of China; 2Department of Respiratory, The Affiliated Banan Hospital of Chongqing Medical University, People’s Hospital of Chongqing Banan District, Chongqing, People’s Republic of China; 3Department of Obstetrics and Gynecology, Women and Children’s Hospital of Chongqing Medical University, Chongqing Health Center for Women and Children, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jin Yu, Department of Anesthesiology, Women and Children’s Hospital of Chongqing Medical University, Chongqing Health Center for Women and Children, No. 120, Longshan Road, Yubei District, Chongqing, 401147, People’s Republic of China, Tel +86-18623117820, Fax +86-23-63702844, Email dodoes@qq.comBackground: Intravenous labor analgesia is recommended as an alternative for parturients who have contraindications to epidural analgesia. There are several opioid analgesics and different administering regimens used in the clinic. This study aimed to compare the effectiveness and safety of two intravenous remifentanil dosage regimens in the first labor stage.Patients and Methods: One hundred and fifteen parturients with a contraindication to epidural analgesia but were willing to receive systemic labor analgesia were randomized into group A received a fixed dose of remifentanil throughout the first stage of labor, and group B received an elevated dose of remifentanil during the active phase of the first stage both by patient-controlled analgesia (PCA). Maternal numerical rating scale (NRS) pain score and oxygen desaturation, sedation efficacy, satisfaction, as well as maternal and fetal adverse reactions were recorded and compared.Results: The mean NRS pain scores before analgesia and in the latent phase showed no statistically significant difference between the two groups (P > 0.05). However, during the active phase, group B demonstrated significantly lower mean NRS pain scores and lowest pain score compared to group A (P < 0.05). Furthermore, group B exhibited higher overall sedation scores and satisfaction scores in comparison to group A (P < 0.05). The incidence of adverse reactions between the two groups was similar (P > 0.05).Conclusion: Relatively elevated intravenous dosage of remifentanil with PCA during the active phase in the first stage of labor is safe and more effective than a fixed-dosage regimen for labor analgesia.Trial Registration: This study was registered with ChiCTR on 24/08/2021 with trial identification number: ChiCTR2100050247. First participant was recruited on 31/08/2021. The last patient was recruited on 12/08/2022.Graphical Abstract: Keywords: patient-controlled analgesia, PCA, remifentanil, labor analgesia, intravenous administration, opioids

Yi Zhen Tan,1 Lucy R Thomsen,1 Nensi Shrestha,1 Adalberto Camisasca,2 Silvia Giordani,2 Rhonda Rosengren1 1Department of Pharmacology and Toxicology, University of Otago, Dunedin, 9016, New Zealand; 2School of Chemical Sciences, Dublin City University, Glasnevin, Dublin, D09 NA55, IrelandCorrespondence: Rhonda Rosengren, Department of Pharmacology and Toxicology, 18 Frederick Street, Dunedin, 9016, New Zealand, Tel +64 3 479 9141, Fax +64 3 479 9140, Email rhonda.rosengren@otago.ac.nzBackground: A nanoscale drug carrier could have a variety of therapeutic and diagnostic uses provided that the carrier is biocompatible in vivo. Carbon nano-onions (CNOs) have shown promising results as a nanocarrier for drug delivery. However, the systemic effect of CNOs in rodents is unknown. Therefore, we investigated the toxicity of CNOs following intravenous administration in female BALB/c mice.Results: Single or repeated administration of oxi-CNOs (125, 250 or 500 μg) did not affect mouse behavior or organ weight and there was also no evidence of hepatotoxicity or nephrotoxicity. Histological examination of organ slices revealed a significant dose-dependent accumulation of CNO aggregates in the spleen, liver and lungs (p< 0.05, ANOVA), with a trace amount of aggregates appearing in the kidneys. However, CNO aggregates in the liver did not affect CYP450 enzymes, as total hepatic CYP450 as well as CYP3A catalytic activity, as meased by erythromycin N-demethylation, and protein levels showed no significant changes between the treatment groups compared to vehicle control. CNOs also failed to act as competitive inhibitors of CYP3A in vitro in both mouse and human liver microsomes. Furthermore, CNOs did not cause oxidative stress, as indicated by the unchanged malondialdehyde levels and superoxide dismutase activity in liver microsomes and organ homogenates.Conclusion: This study provides the first evidence that short-term intravenous administration of oxi-CNOs is non-toxic to female mice and thus could be a promising novel and safe drug carrier.Keywords: carbon nano-onions, drug carriers, intravenous administration, toxicity, accumulation, drug metabolism, oxidative stress

Intravenous ibuprofen (IBF) is indicated for short-term acute moderate pain and fever management. Limited data concerning the compatibility of intravenous IBF and other parenteral medications makes it inconvenient to use in polypharmacy-required patients. The simultaneous administration of two incompatible drugs is a health- or even life-threatening medical error. This study was performed to evaluate the physical compatibility of two intravenous IBF doses (600 mg/100 mL, 400 mg/100 mL) during Y-site administration with common parenteral medications. Eight infusion fluids, seven ready-to-use solutions for infusion, and thirty concentrates or powders for solutions for infusion were examined. All these drugs, if relevant, were reconstituted and diluted following the manufacturer's instructions to achieve concentrations found most commonly in clinical practice. Samples were prepared by mixing IBFs and selected drug product solutions at the 1:1 volume ratio. All samples underwent visual inspection and determination of pH and turbidity before combining with IBF and in time points (0, 30, 60, and 120 minutes) after simulated Y-site administration with IBF. In the case of propofol, which is an emulsion for infusion, lipid droplet size, zeta potential, and polydispersity index were also determined. The incompatibilities were observed for IBF combinations with amiodarone, ciprofloxacin, clemastine, gentamicin, vinpocetine, and calcium chloride.

ABSTRACTLung cancer remains among the most difficult-to-treat malignancies and is the leading cause of cancer-related deaths worldwide. The introduction of targeted therapies and checkpoint inhibitors has improved treatment outcomes; however, most patients with advanced-stage non-small cell lung cancer (NSCLC) eventually fail these therapies. Therefore, there is a major unmet clinical need for checkpoint refractory/resistant NSCLC. Here, we tested the combination of aPD-1 and adenovirus armed with TNFα and IL-2 (Ad5-CMV-mTNFα/mIL-2) in an immunocompetent murine NSCLC model. Moreover, although local delivery has been standard for virotherapy, treatment was administered intravenously to facilitate clinical translation and putative routine use. We showed that treatment of tumor-bearing animals with aPD-1 in combination with intravenously injected armed adenovirus significantly decreased cancer growth, even in the presence of neutralizing antibodies. We observed an increased frequency of cytotoxic tumor-infiltrating lymphocytes, including tumor-specific cells. Combination treatment led to a decreased percentage of immunosuppressive tumor-associated macrophages and an improvement in dendritic cell maturation. Moreover, we observed expansion of the tumor-specific memory T cell compartment in secondary lymphoid organs in the group that received aPD-1 with the virus. However, although the non-replicative Ad5-CMV-mTNFα/mIL-2 virus allows high transgene expression in the murine model, it does not fully reflect the clinical outcome in humans. Thus, we complemented our findings using NSCLC ex vivo models fully permissive for the TNFα and IL-2- armed oncolytic adenovirus TILT-123. Overall, our data demonstrate the ability of systemically administered adenovirus armed with TNFα and IL-2 to potentiate the anti-tumor efficacy of aPD-1 and warrant further investigation in clinical trials.

As of now, the COVID-19 pandemic has spread to over 770 million confirmed cases and caused approximately 7 million deaths. While several vaccines and monoclonal antibodies (mAb) have been developed and deployed, natural selection against immune recognition of viral antigens by antibodies has fueled the evolution of new emerging variants and limited the immune protection by vaccines and mAb. To optimize the efficiency of mAb, it is imperative to understand how they neutralize the variants of concern (VoCs) and to investigate the mutations responsible for immune escape. In this study, we show the in vitro neutralizing effects of a previously described monoclonal antibody (STE90-C11) against the SARS-CoV-2 Delta variant (B.1.617.2) and its in vivo effects in therapeutic and prophylactic settings. We also show that the Omicron variant avoids recognition by this mAb. To define which mutations are responsible for the escape in the Omicron variant, we used a library of pseudovirus mutants carrying each of the mutations present in the Omicron VoC individually. We show that either 501Y or 417K point mutations were sufficient for the escape of Omicron recognition by STE90-C11. To test how escape mutations act against a combination of antibodies, we tested the same library against bispecific antibodies, recognizing two discrete regions of the spike antigen. While Omicron escaped the control by the bispecific antibodies, the same antibodies controlled all mutants with individual mutations. [ABSTRACT FROM AUTHOR]

Multilineage-differentiating stress-enduring (Muse) cells are newly established pluripotent stem cells. The aim of the present study was to examine the potential of the systemic administration of Muse cells as an effective treatment for subacute SCI. We intravenously administered the clinical product "CL2020" containing Muse cells to a rat model two weeks after mid-thoracic spinal cord contusion. Eight experimental animals received CL2020, and twelve received the vehicle. Behavioral analyses were conducted over 20 weeks. Histological evaluations were performed. After 20 weeks of observation, diphtheria toxin was administered to three CL2020-treated animals to selectively ablate human cell functions. Hindlimb motor functions significantly improved from 6 to 20 weeks after the administration of CL2020. The cystic cavity was smaller in the CL2020 group. Furthermore, larger numbers of descending 5-HT fibers were preserved in the distal spinal cord. Muse cells in CL2020 were considered to have differentiated into neuronal and neural cells in the injured spinal cord. Neuronal and neural cells were identified in the gray and white matter, respectively. Importantly, these effects were reversed by the selective ablation of human cells by diphtheria toxin. Intravenously administered Muse cells facilitated the therapeutic potential of CL2020 for severe subacute spinal cord injury. [ABSTRACT FROM AUTHOR]

In order to compare the clinical efficacy and safety of prolonged versus intermittent antipseudomonal beta-lactam antibiotic infusion for the treatment of severe acute infections in adult patients, a meta-analysis of randomized controlled trials (RCTs) was performed. We systematically searched MEDLINE and Cochrane Library databases until December 2022. The outcomes were all-cause mortality, clinical success, microbiological eradication and adverse events. The pooled risk ratios (RR) were estimated by the fixed or random effect methods according to heterogeneity statistics. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to evaluate the certainty of evidence for each outcome. Twenty eligible RCTs with 2081 participants were included in the meta-analysis. The risk of all-cause mortality was significantly lower in the prolonged infusion group than in the intermittent infusion group (RR 0.77, 95% confidence interval [CI] 0.63–0.95, p = 0.01, I2 = 0%; moderate certainty). Treatment with prolonged infusion showed significant benefit in clinical success (RR 1.09, 95% CI 1.02–1.17, p = 0.008, I2 = 19%; moderate certainty). There were no significant differences in microbiological eradication (RR 1.12, 95% CI 0.99–1.28, p = 0.07, I2 = 49%; low certainty), any adverse events (RR 0.96, 95% CI 0.86–1.08, p = 0.50, I2 = 27%; moderate certainty) and serious adverse events (RR 0.99, 95%CI 0.70–1.39 p = 0.95, I2 = 0%; low certainty). Prolonged antipseudomonal beta-lactam infusion probably decreases all-cause mortality. Additionally, it probably increases clinical success in adults with severe acute infections. This infusion strategy may result in little to no difference in microbiological eradication and is probably not associated with a rise in any adverse events.The evidence suggests that prolonged infusion may not increase serious adverse events. [ABSTRACT FROM AUTHOR]

Background Seizures after stroke can negatively affect the prognosis of ischemic stroke and cause a decrease in quality of life. The efficacy of intravenous (IV) recombinant tissue plasminogen activator (rt-PA) treatment in acute ischemic stroke has been demonstrated in many studies, and IV rt-PA treatment has been increasingly used around the world. The SeLECT score is a useful score for the prediction of late seizures after stroke and includes the severity of stroke (Se), large artery atherosclerosis (L), early seizure (E), cortical involvement (C), and the territory of the middle cerebral artery (T). However, the specificity and sensitivity of the SeLECT score have not been studied in acute ischemic stroke patients that received IV rt-PA treatment.

Background: Gastric cancer (GC) stands as one of the most prevalent cancer types worldwide, holding the position of the second leading cause of cancer-related deaths. Gastric lesions represent pathological alterations to the gastric mucosa, with an elevated propensity to advance to gastric cancer. Limited research has explored the potential of stem cells in the treatment of gastric lesions. Methods: This study aimed to explore the potential of intravenous transplantation of labeled bone marrow-derived mesenchymal stem cells (BMMSCs) to inhibit the progression of precancerous gastric lesions. Results: In the gastric lesion disease model group, the rat tissue exhibited noteworthy mucosal atrophy, intestinal metaplasia, dysplasia, and inflammatory cell infiltration. Following the infusion of BMMSCs, a notable decrease in gastric lesions was found, with atrophic gastritis being the sole remaining lesion, which was confirmed by morphological and histological examinations. BMMSCs that were colonized at gastric lesions could differentiate into epithelial and stromal cells, as determined by the expression of pan-keratin or vimentin. The expression of vascular endothelial growth factor was significantly elevated following BMMSC transplantation. BMMSCs could also upregulate the production of humoral immune response cytokines, including interleukin (IL)-4 and IL-10, and downregulate the production of IL-17 and interferon-gamma, which could be highly associated with the cellular immune response and inflammation severity of the lesions. Conclusions: BMMSC transplantation significantly reduced inflammation and reversed gastric lesion progression.

Most antimicrobial drugs need an intravenous (IV) administration to achieve maximum efficacy against target pathogens. IV administration is related to complications, such as tissue infiltration and thrombo-phlebitis. This systematic review aims to provide practical recommendations about diluent, pH, osmolarity, dosage, infusion rate, vesicant properties, and phlebitis rate of the most commonly used antimicrobial drugs evaluated in randomized controlled studies (RCT) till 31 March 2023. The authors searched for available IV antimicrobial drugs in RCT in PUBMED EMBASE®, EBSCO® CINAHL®, and the Cochrane Controlled Clinical trials. Drugs' chemical features were searched online, in drug data sheets, and in scientific papers, establishing that the drugs with a pH of <5 or >9, osmolarity >600 mOsm/L, high incidence of phlebitis reported in the literature, and vesicant drugs need the adoption of utmost caution during administration. We evaluated 931 papers; 232 studies were included. A total of 82 antimicrobials were identified. Regarding antibiotics, 37 reach the "caution" criterion, as well as seven antivirals, 10 antifungals, and three antiprotozoals. In this subgroup of antimicrobials, the correct vascular access device (VAD) selection is essential to avoid complications due to the administration through a peripheral vein. Knowing the physicochemical characteristics of antimicrobials is crucial to improve the patient's safety significantly, thus avoiding administration errors and local side effects. [ABSTRACT FROM AUTHOR]

Copyright of Arquivos de Ciências da Saúde da UNIPAR is the property of Associacao Paranaense de Ensino e Cultura and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Scientific evidence has rarely, if at all, been reported in the literature demonstrating analytical confirmation of the physical compatibility and stability of glycopyrrolate and rocuronium combined. The purpose of this experiment was to determine if glycopyrrolate and rocuronium are physically compatible. Glycopyrrolate and rocuronium were combined in various containers, observed over a 60-minute period, and compared against positive and negative controls. Measured metrics included color change, precipitate formation, Tyndall beam test, turbidity, and pH. Statistical analyses were used to assess significance of data trends. The combination of glycopyrrolate and rocuronium did not result in any color change, precipitate formation, a positive Tyndall beam test, or a significantly positive turbidity and did not result in any significant change in pH, regardless of container. Per the protocol used in this study, glycopyrrolate and rocuronium were determined to be physically compatible. [ABSTRACT FROM AUTHOR]

Background: Tranexamic acid (TXA) is widely used in hip and knee arthroplasty to reduce perioperative bleeding. Recently, its use has been expanded to arthroscopic surgery. The purpose of this study was to evaluate the efficacy of preoperative use of TXA in arthroscopic rotator cuff repair (RCR). Methods: A cohort comprising 129 consecutive patients who underwent arthroscopic primary RCR at our institution was retrospectively investigated according to whether they received TXA (April 2018 to December 2020, TXA group, n = 64) or did not receive TXA (April 2016 to March 2018, non-TXA group, n = 65). TXA was administered at a dose of 1 g intravenously. Rotator cuff tears were repaired by the suture bridge technique. Videos of the arthroscopic procedures were reviewed and rated for visual clarity using a 10-point numeric rating scale. Arthroscopic procedures were divided into glenohumeral, resection of bursal tissue and acromioplasty, and RCR steps. Each step was rated separately. Age, sex, body mass index, hemoglobin level before and on days 1 and 7 after surgery, operating time, mean arterial pressure, tear size, and number of anchors used for cuff repair were compared between the two groups. Results: There were no statistically significant differences in the patient demographic data. The operating time was significantly shorter in the TXA group than in non-TXA group (97.8 ± 21.8 min vs 116.2 ± 26.0 min). The clarity of the visual field was similar between the two groups during the glenohumeral phase but was significantly higher in the TXA group during the resection of bursal tissue and acromioplasty and RCR phases. Hemoglobin level was not significantly different between the groups on postoperative day 1 but was significantly higher in the TXA group on day 7. Conclusion: Administration of a single intravenous dose of TXA improved visual clarity in arthroscopic RCR, decreased the total operating time, and reduced hemoglobin loss on postoperative day 7.

Background Due to its abuse potential, propofol has been classified as a controlled substance since February 2011 in South Korea. Healthcare workers are exposed to propofol abuse considering their easy access to this substance in hospitals. Therefore, we aimed to investigate propofol abuse among healthcare workers through the database of the Supreme Court in South Korea. Methods We retrospectively analyzed adjudicated criminal cases related to propofol abuse among healthcare workers from January 1, 2013, to December 31, 2020, using the database of the Supreme Court of South Korea’s judgments. We collected the clinical characteristics and punishment-related information of healthcare workers who abused propofol. Results Of the 194 cases collected using the search term ‘propofol,’ 20 were included in the final analysis. The most common healthcare workers who abused propofol were nursing aides (n = 15). Among them, 40% (n = 8) of the defendants had previously been punished for substance abuse, and 35% (n = 7) had a history of psychological disease. Of the defendants, 65% (n = 13) self-administered propofol more than twice, and the median number of self-administrations was three. Except for two, the defendants were sentenced to imprisonment, including suspended sentences, and the median values of their duration of prison and probation were 9 months and 24 months. Conclusions Despite propofol being strongly regulated as a controlled substance in South Korea, its abuse among healthcare workers remains. Healthcare workers should be vigilant against its abuse among themselves.

The glymphatic system is a brain‐wide network of perivascular pathways along which cerebrospinal fluid and interstitial fluid rapidly exchange, facilitating solute and waste clearance from the brain parenchyma. The characterization of this exchange process in humans has relied primarily upon serial magnetic resonance imaging following intrathecal gadolinium‐based contrast agent injection. However, less invasive approaches are needed. Here, we administered a gadolinium‐based contrast agent intravenously in eight healthy participants and acquired magnetic resonance imaging scans prior to and 30, 90, 180, and 360 min post contrast injection. Using a region‐of‐interest approach, we observed that peripheral tissues and blood vessels exhibited high enhancement at 30 min after contrast administration, likely reflecting vascular and peripheral interstitial distribution of the gadolinium‐based contrast agent. Ventricular, grey matter and white matter enhancement peaked at 90 min, declining thereafter. Using k‐means clustering, we identify distinct distribution volumes reflecting the leptomeningeal perivascular network, superficial grey matter and deep grey/white matter that exhibit a sequential enhancement pattern consistent with parenchymal contrast enhancement via the subarachnoid cerebrospinal fluid compartment. We also outline the importance of correcting for (otherwise automatic) autoscaling of signal intensities, which could potentially lead to misinterpretation of gadolinium‐based contrast agent distribution kinetics. In summary, we visualize and quantify delayed tissue enhancement following intravenous administration of gadolinium‐based contrast agent in healthy human participants. [ABSTRACT FROM AUTHOR]

Bloodstream infections (BSIs) due to Gram‐positive organisms have traditionally been treated with prolonged courses of intravenous antimicrobials. However, this dogma is associated with substantial burden to the patient and health care system. Consequently, there is growing interest in the utilization of oral stepdown therapy, defined as the transition of intravenous therapy to an active oral agent, for this indication. This review highlights available literature examining oral stepdown in adult patients with BSI due to commonly encountered Gram‐positive pathogens, including Staphylococcus aureus, Streptococcus spp., and Enterococcus spp. Support for oral stepdown in this setting is primarily derived from observational studies subject to selection bias. Nevertheless, this treatment strategy exhibits promising potential in carefully selected patients as it is consistently associated with reductions in hospital length of stay without jeopardizing clinical cure or survivability. Prospective, randomized trials are needed for validation of oral stepdown in Gram‐positive BSI and to identify the optimal patient population and regimen. [ABSTRACT FROM AUTHOR]

Copyright of Arquivos de Neuro-Psiquiatria is the property of Thieme Medical Publishing Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The delivery of curcumin (CUR) using the solid dispersion system (CUR solid dispersions; C-SDs) has been shown to improve CUR bioavailability. However, it is unclear how different particle sizes of C-SDs affect the bioavailability and biological activities of CUR. Hence, we prepared C-SDs in different sizes using food-grade excipients and evaluated their bioavailability and biological activities. By pulverizing large particle sizes of C-SDs using zirconia beads, we successfully prepared C-SDs I-IV (particle size: (I) 120, (II) 447, (III) 987, (IV) 1910 nm). When administrated orally in rats, the bioavailability of CUR was increased with decreasing C-SDs size, most likely by improving its solubility in micelles. When administrated intravenously in rats, blood concentrations of CUR were increased with increasing particle size, suggesting that larger C-SDs presumably control the metabolic conversion of CUR. In RAW264 cells, more CUR was taken up by cells as their sizes reduced, and the more potent their anti-inflammatory activities were, suggesting that smaller C-SDs were taken up through a number of cellular uptake pathways. Altogether, the present study showed an evident effect of C-SDs size on their bioavailability and anti-inflammatory activities—information that serves as a basis for improving the functionality of CUR. [ABSTRACT FROM AUTHOR]

Intravenous ibuprofen (IBF) is indicated for short-term acute moderate pain and fever management. Limited data concerning the compatibility of intravenous IBF and other parenteral medications makes it inconvenient to use in polypharmacy-required patients. The simultaneous administration of two incompatible drugs is a health- or even life-threatening medical error. This study was performed to evaluate the physical compatibility of two intravenous IBF doses (600 mg/100 mL, 400 mg/100 mL) during Y-site administration with common parenteral medications. Eight infusion fluids, seven ready-to-use solutions for infusion, and thirty concentrates or powders for solutions for infusion were examined. All these drugs, if relevant, were reconstituted and diluted following the manufacturers' instructions to achieve concentrations found most commonly in clinical practice. Samples were prepared by mixing IBFs and selected drug product solutions at the 1 : 1 volume ratio. All samples underwent visual inspection and determination of pH and turbidity before combining with IBF and in time points (0, 30, 60, and 120 minutes) after simulated Y-site administration with IBF. In the case of propofol, which is an emulsion for infusion, lipid droplet size, zeta potential, and polydispersity index were also determined. The incompatibilities were observed for IBF combinations with amiodarone, ciprofloxacin, clemastine, gentamicin, vinpocetine, and calcium chloride. [ABSTRACT FROM AUTHOR]

Coenzyme CoQ10 (CoQ10) is an endogenous lipid-soluble antioxidant that effectively protects lipids, proteins, and DNA from oxidation due to its ability to undergo redox transitions between oxidized and reduced forms. Various oxidative stress-associated infectious and somatic diseases have been observed to disrupt the balance of CoQ10 concentration in tissues. As a high molecular weight polar lipophilic compound, CoQ10 exhibits very limited oral bioavailability, which restrains its therapeutic potential. Nevertheless, numerous studies have confirmed the clinical efficacy of CoQ10 therapy through oral administration of high doses over extended time periods. Experimental studies have demonstrated that in emergency situations, intravenous administration of both oxidized and reduced-form CoQ10 leads to a rapid increase in its concentration in organ tissues, offering protection for organ tissues in ischemic conditions. This suggests that the cardio- and neuroprotective efficacy of intravenously administered CoQ10 forms could present new opportunities in treating acute ischemic conditions. Based on these findings, the review provides reasoning supporting further research and implementation of CoQ10 dosage forms for intravenous administration in emergency situations into clinical practice.

BackgroundNiemann-Pick Disease Type C (NPC) is an inherited, often fatal neurovisceral lysosomal storage disease characterized by cholesterol accumulation in every cell with few known treatments. Defects in cholesterol transport cause sequestration of unesterified cholesterol within the endolysosomal system. The discovery that systemic administration of hydroxypropyl-beta cyclodextrin (HPβPD) to NPC mice could release trapped cholesterol from lysosomes, normalize cholesterol levels in the liver, and prolong life, led to expanded access use in NPC patients. HPβCD has been administered to NPC patients with approved INDs globally since 2009.ResultsHere we present safety, tolerability and efficacy data from 12 patients treated intravenously (IV) for over 7 years with HPβCD in the US and Brazil. Some patients subsequently received intrathecal (IT) treatment with HPβCD following on average 13 months of IV HPβCD. Several patients transitioned to an alternate HPβCD. Moderately affected NPC patients treated with HPβCD showed slowing of disease progression. Severely affected patients demonstrated periods of stability but eventually showed progression of disease. Neurologic and neurocognitive benefits were seen in most patients with IV alone, independent of the addition of IT administration. Physicians and caregivers reported improvements in quality of life for the patients on IV therapy. There were no safety issues, and the drug was well tolerated and easy to administer.ConclusionsThese expanded access data support the safety and potential benefit of systemic IV administration of HPβCD and provide a platform for two clinical trials to study the effect of intravenous administration of HPβCD in NPC patients.

Abstract Aim To understand the experience of critical care nurses when performing common, yet error‐prone, programming tasks on two unfamiliar intravenous smart pumps. Design A qualitative descriptive study using data collected during a previous quantitative pilot study. Methods Following completion of common intravenous programming tasks each participant was interviewed using a semi‐structured interview guide. All interview data were coded line‐by‐line and thematic analysis revealed themes across all participants' interviews. Results The following four themes were identified: appreciation for attractive design features, the need for efficiency, the importance of intuitive use and concern for patient outcomes. Overall, these themes provide evidence that nurses strongly prefer a more usable intravenous smart pump interface that integrates safeguards to efficiently improve patient outcomes. Findings support the need for intravenous smart pump technology to be developed with an intuitive interface that decreases the level of cognitive demand and will lead to improved patient safety.

Aim. To examine effectiveness of intraoperative lidocaine administration in the intraoperative period as a component of combined anesthesia and in the early postoperative period in patients after extended liver resection. Materials and methods. There were 86 patients with various pathologies enrolled after hepatic resection with 30–60 % of parenchymal preservation. The patients were divided into three groups depending on the complex anesthesia used. The control group (ІІІ) consisted of 10 patients who received standard complex anesthesia and pain management including opioid and non-opioid analgesics in the post-operative period. The main group (ІІ) comprised 9 patients who received the method developed, and there was the additional comparison group (І) composed of 67 patients who received standard complex anesthesia with thoracic epidural anesthesia (TEA). Results. Having elaborated the fentanyl mean cumulation dose during the operation, we herewith declare that patients of group I received in general 1005.2 ± 417.8 µgr, group II – 1771.1 ± 735.5 µgr and III group – 2090.0 ± 636.7 µgr of fentanyl. When detailing and comparing the groups with each other, we see significantly lower usage of fentanyl intraoperatively in TEA group in comparison to both other groups (I vs II, 76 % greater need in group II, and I vs III, 108 % greater need in group ІІI). At the same time, the difference in the need for intraoperative fentanyl between patients of the intravenous lidocaine group and the control group was only 18 % – there was a tendency to a decrease in the dose when using intravenous lidocaine. Based on the data comparison results between groups, it could be asserted that between patients of groups I and II, the difference in the VAS score on day one after surgery was only 10 %. On the first day postoperatively, patients in group I noted maximum daily value of 4.5 ± 2.0 points on the VAS scale, in group II – 5.0 ± 2.3 and in group III – 7.6 ± 1.0 points. In contrast, there was a significantly higher level of pain in group III patients compared to both groups I and II. The intergroup difference in the time of the first dose of analgesics administration after surgery was insignificant: in group I – after 313.5 ± 128.9 minutes, in group II – 287.7 ± 101.6 minutes, and in group III – 217.0 ± 120.3 minutes. The provided data confirm the efficacy of the pain management method in patients after hepatic resection. Conclusions. Both the use of TEA and intravenous lidocaine are safe methods of pain management in patients after liver resection. In the postoperative period, intravenous use of lidocaine is not inferior in its effectiveness to TEA and can be recommended for use. TEA has a greater efficiency in intraoperative analgesia, however, if it is contraindicated for administration, intraoperative use of lidocaine is a potentially effective alternative. Further studies in a larger group of patients are needed to confirm or disprove this trend.

OBJECTIVE: To evaluate the physical intravenous Y-site compatibility of 29 combinations of medications at commonly used pediatric concentrations using both existing and novel techniques. METHODS: Medication combinations included were selected by a varied group of pediatric inpatient pharmacists, and then assessed by 3 independent reviewers for existing literature. For each combination, 2 different medications were mixed together in a 1:1 ratio and incubated at room temperature for 4 hours to simulate Y-site administration. Each sample was then analyzed using the US Pharmacopeia (USP) <788> recommended analytical technique of light obscuration (LO) in addition to novel flow imaging (FI) microscopy and backgrounded membrane imaging (BMI). Physical compatibility was determined using USP chapter <788> large volume particle count limits for all techniques. RESULTS: A total of 29 different medication combinations were studied. Five combinations met criteria for compatibility by all 3 techniques. The remaining 24 combinations reached the threshold to be considered incompatible by at least 1 of the 3 techniques. Light obscuration, BMI, and FI identified 14%, 59%, and 76% of combinations as incompatible, respectively. All samples deemed incompatible by LO were also incompatible by at least 1 of the other 2 techniques. Flow imaging and BMI results agreed in 69% of samples tested. CONCLUSIONS: Most combinations tested were found to be incompatible by at least 1 of the 3 instruments used. Light obscuration appears to have reduced accuracy for identifying particulate resulting in physical medication incompatibility when compared with the novel techniques of FI and BMI. [ABSTRACT FROM AUTHOR]

Lung cancer remains among the most difficult-to-treat malignancies and is the leading cause of cancer-related deaths worldwide. The introduction of targeted therapies and checkpoint inhibitors has improved treatment outcomes; however, most patients with advanced-stage non-small cell lung cancer (NSCLC) eventually fail these therapies. Therefore, there is a major unmet clinical need for checkpoint refractory/resistant NSCLC. Here, we tested the combination of aPD-1 and adenovirus armed with TNFα and IL-2 (Ad5-CMV-mTNFα/mIL-2) in an immunocompetent murine NSCLC model. Moreover, although local delivery has been standard for virotherapy, treatment was administered intravenously to facilitate clinical translation and putative routine use. We showed that treatment of tumor-bearing animals with aPD-1 in combination with intravenously injected armed adenovirus significantly decreased cancer growth, even in the presence of neutralizing antibodies. We observed an increased frequency of cytotoxic tumor-infiltrating lymphocytes, including tumor-specific cells. Combination treatment led to a decreased percentage of immunosuppressive tumor-associated macrophages and an improvement in dendritic cell maturation. Moreover, we observed expansion of the tumor-specific memory T cell compartment in secondary lymphoid organs in the group that received aPD-1 with the virus. However, although the non-replicative Ad5-CMV-mTNFα/mIL-2 virus allows high transgene expression in the murine model, it does not fully reflect the clinical outcome in humans. Thus, we complemented our findings using NSCLC ex vivo models fully permissive for the TNFα and IL-2- armed oncolytic adenovirus TILT-123. Overall, our data demonstrate the ability of systemically administered adenovirus armed with TNFα and IL-2 to potentiate the anti-tumor efficacy of aPD-1 and warrant further investigation in clinical trials. [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis (ALS) is characterized by progressive loss of motor neurons. Multilineage-differentiating stressenduring (Muse) cells are unique endogenous stem cells that show therapeutic effects on motor function in ALS mouse models. We conducted a single-center open phase II clinical trial to evaluate the safety and clinical effects of repeated intravenous injections of an allogenic Muse cell-based product, CL2020, in patients with ALS. Five patients with ALS received CL2020 intravenously once a month for a total of six doses. The primary endpoints were safety and tolerability, and the secondary endpoint was the rate of change in the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) score. In addition, serum tumor necrosis factor-a (TNF-a), interleukin-6 (IL-6), sphingosine-1-phosphate (S1P), cerebrospinal fluid chitotriosidase-1 (CHIT-1), and neurofilament light chain (NfL) levels were evaluated. The CL2020 treatment was highly tolerated without serious side effects. The ALSFRS-R score change trended upward at 12 months post-CL2020 treatment compared with that at 3 months pre-administration, but the difference was not statistically significant. Among five patients diagnosed with ALS, three exhibited a decrease in the rate of ALSFRS-R score change, one demonstrated an increase, and another showed no change. In addition, the patients' serum IL-6 and TNF-a levels and cerebrospinal fluid CHIT-1 and NfL levels increased for up to 6 months post-treatment; however, their serum S1P levels continuously decreased over 12 months. These findings indicate a favorable safety profile of CL2020 therapy. In the near future, a double-blind study of a larger number of ALS patients should be conducted to confirm the efficacy of ALS treatment with CL2020. [ABSTRACT FROM AUTHOR]

The intravenous (IV) usage of diuretics such as furosemide may cause changes in clinical variables, electrocardiographic (ECG) indices and some serum electrolytes concentrations in miniature donkeys. The purpose of this study was to evaluate the effects of double intravenous (IV) administration of furosemide at different doses on the clinical variables, ECG indices and serum electrolytes levels in miniature donkeys. A total of 21 clinically and para-clinically healthy miniature donkeys with a mean age of 6.00 ± 1.00 years and weight of 95.00 ± 5.00 kg were used. The animals were randomly divided into three groups of control (normal saline) and low- (1.00 mg kg-1) and high-dose (2.00 mg kg-1) of furosemide. Two IV injections with 12-hr interval were administered in each animal. The clinical and ECG parameters were measured at 0 (baseline), 2 (T2), 24 (T24) and 48 (T48) hr after drug administration. Serum concentrations of electrolytes were measured at T0, T24 and T48. The results of this study showed no changes in clinical variables (heart rate, rectal temperature and respiratory rate) and ECG indices (amplitude and duration of P, QRS and T waves and duration of PR, QT and RR intervals) as well as no significant changes in serum electrolytes (sodium, potassium, chloride, phosphorus, calcium and magnesium) levels. Although no significant effect on clinical variables, electrolytes levels and ECG indices after double IV administration of furosemide (1.00 and 2.00 mg kg-1) in miniature donkeys was observed, absence of these effects does not mean that furosemide had no pharmacological effect. [ABSTRACT FROM AUTHOR]

Magnetic nanoparticles (MNPs) present outstanding properties making them suitable as therapeutic agents for hyperthermia treatments. Since the main safety concerns of MNPs are represented by their inherent instability in a biological medium, strategies to both achieve long-term stability and monitor hazardous MNP degradation are needed. We combined a dynamic approach relying on flow field flow fractionation (FFF)-multidetection with conventional techniques to explore frame-by-frame changes of MNPs injected in simulated biological medium, hypothesize the interaction mechanism they are subject to when surrounded by a saline, protein-rich environment, and understand their behaviour at the most critical point of intravenous administration. In the first moments of MNPs administration in the patient, MNPs change their surrounding from a favorable to an unfavorable medium, i.e., a complex biological fluid such as blood; the particles evolve from a synthetic identity to a biological identity, a transition that needs to be carefully monitored. The dynamic approach presented herein represents an optimal alternative to conventional batch techniques that can monitor only size, shape, surface charge, and aggregation phenomena as an averaged information, given that they cannot resolve different populations present in the sample and cannot give accurate information about the evolution or temporary instability of MNPs. The designed FFF method equipped with a multidetection system enabled the separation of the particle populations providing selective information on their morphological evolution and on nanoparticle–proteins interaction in the very first steps of infusion. Results showed that in a dynamic biological setting and following interaction with serum albumin, PP-MNPs retain their colloidal properties, supporting their safety profile for intravenous administration. [ABSTRACT FROM AUTHOR]

Alpha-particle radiotherapy has gained considerable attention owing to its potent anti-cancer effect. 211At, with a relatively short half-life of 7.2 h, emits an alpha particle within a few cell diameters with high kinetic energy, which damages cancer cells with high biological effectiveness. In this study, we investigated the intravenous injection of 211At-labeled gold nanoparticles (AuNPs) for targeted alpha-particle therapy (TAT). Different kinds of surface-modified gold nanoparticles can be labeled with 211At in high radiochemical yield in 5 min, and no purification is necessary. The in vivo biodistribution results showed the accumulation of 5 nm 211At-AuNPs@mPEG at 2.25% injection dose per gram (% ID/g) in tumors within 3 h via the enhanced permeability and retention (EPR) effect. Additionally, we observed a long retention time in tumor tissues within 24 h. This is the first study to demonstrate the anti-tumor efficacy of 5 nm 211At-AuNPs@mPEG that can significantly suppress tumor growth in a pancreatic cancer model via intravenous administration. AuNPs are satisfactory carriers for 211At delivery, due to simple and efficient synthesis processes and high stability. The intravenous administration of 5 nm 211At-AuNPs@mPEG has a significant anti-tumor effect. This study provides a new framework for designing nanoparticles suitable for targeted alpha-particle therapy via intravenous injection. [ABSTRACT FROM AUTHOR]