Intravenous Preparations Research Articles

Chronic Heart Failure: Clinical Implications of Iron Homeostasis Disturbances Revisited.

Iron deficiency is prevalent in chronic heart failure (CHF) patients. Nonetheless, the diagnosis is often overlooked and, often, the treatment is commenced just when overt anemia has ensued. Therefore, a better appreciation of this disease is needed, and all seasoned cardiologists should know how to approach CHF patients with iron deficiency correctly, as mandated by clinical practice guidelines. In this comprehensive review, we describe iron homeostasis, the pathophysiologic changes of iron homeostasis, and the clinical implications of iron deficiency on CHF patients. In addition, we delineate the evolution of clinical trials, ranging from the inception to the ongoing clinical trials of iron deficiency treatment in CHF patients. Iron deficiency contributes to the worse clinical outcome of the patients. Numerous studies have reported the clinical benefit of iron supplementation, particularly in intravenous preparation, in heart failure patients regarding symptoms, functional capacity, and quality of life (QoL) improvement. Therefore, the current guidelines recommend routine screening of iron status in all newly diagnosed heart failure patients. Eventually, intravenous iron replacement is recommended for symptomatic heart failure patients with iron deficiency, irrespective of anemia.

Implementation of the Comprehensive Unit-Based Safety Program to Improve Infection Prevention and Control Practices in Four Neonatal Intensive Care Units in Pune, India.

Objective: To implement the Comprehensive Unit-based Safety Program (CUSP) in four neonatal intensive care units (NICUs) in Pune, India, to improve infection prevention and control (IPC) practices.Design: In this quasi-experimental study, we implemented CUSP in four NICUs in Pune, India, to improve IPC practices in three focus areas: hand hygiene, aseptic technique for invasive procedures, and medication and intravenous fluid preparation and administration. Sites received training in CUSP methodology, formed multidisciplinary teams, and selected interventions for each focus area. Process measures included fidelity to CUSP, hand hygiene compliance, and central line insertion checklist completion. Outcome measures included the rate of healthcare-associated bloodstream infection (HA-BSI), all-cause mortality, patient safety culture, and workload.Results: A total of 144 healthcare workers and administrators completed CUSP training. All sites conducted at least 75% of monthly meetings. Hand hygiene compliance odds increased 6% per month [odds ratio (OR) 1.06 (95% CI 1.03–1.10)]. Providers completed insertion checklists for 68% of neonates with a central line; 83% of checklists were fully completed. All-cause mortality and HA-BSI rate did not change significantly after CUSP implementation. Patient safety culture domains with greatest improvement were management support for patient safety (+7.6%), teamwork within units (+5.3%), and organizational learning—continuous improvement (+4.7%). Overall workload increased from a mean score of 46.28 ± 16.97 at baseline to 65.07 ± 19.05 at follow-up (p < 0.0001).Conclusion: CUSP implementation increased hand hygiene compliance, successful implementation of a central line insertion checklist, and improvements in safety culture in four Indian NICUs. This multimodal strategy is a promising framework for low- and middle-income country healthcare facilities to reduce HAI risk in neonates.

Регистр пациентов с первичными иммунодефицитными состояниями в Иркутской области

In this paper, the main epidemiological indicators of primary immunodeficiency disorders (PIDDs) in the Irkutsk region based on analysis of data from 66 patients registered in the PIDDs database from 2010 to November 2021 were studied. The prevalence of primary immunodeficiencies in the Irkutsk region totals 2.75:100,000 of the population. The cohort of living patients is dominated by children (74%). A total of 22 nosological forms were verified in the registry of primary immunodeficiencies. Molecular genetic diagnosis was confirmed in 26% of the patients. Hematopoietic cell transplantation was performed in 21.2% of the patients. Intravenous immunoglobulin preparations are received by 19.7% of patients. The main purpose of the registry is to systematise patients with primary immunodeficiencies, provide them with the necessary treatment in a timely manner and improve their quality of life.

The effect of different intravenous lipids on free bilirubin levels in premature infants.

Intravenous lipid emulsions are commonly used as a part of parenteral nutrition in premature infants. The potential bilirubin-displacing effects of high free fatty acid (FFA) levels during lipid infusions are known. Levels of free bilirubin (FB) predict the risk of bilirubin neurotoxicity more accurately than indirect serum bilirubin levels. In the present study, we decided to compare the effect of two different lipid solutions on free bilirubin and free fatty acids levels in premature infants. Infants were grouped into two groups according to intravenous lipid preparations: Infants in Group 1 received lipid emulsion containing olive oil + soybean oil and Group 2 received containing olive oil + soybean oil + fish oil. The blood samples were gained when lipid intake was 3.5 g/kg/day and FFA and FB levels were analyzed. Serum FFA and FB levels were similar in groups (p = 0.26 and 0.69 respectively). There were significant correlation between serum FFA and FB levels in Group 1 (r = 0.74, p < 0.001) and in Group 2 (r = 0.92, p < 0.001). Both lipid preparations seem to have similar effects on free bilirubin and free fatty acid levels in premature newborns.

Evaluation of chemotherapy preparation processes: Volumetric method reliability and gravimetric method utility within 5 US hospitals.

The primary aim of this study was to investigate the accuracy of the volumetric method for intravenous (IV) preparations and explore the utility of gravimetric methods in the medication preparation process within multiple institutions. Secondary outcomes of this study were syringe size percent variations and impact on drug expenditures. A prospective, noninterventional, multisite study was conducted between March 2015 and December 2016 to generate baseline estimates of accuracy and precision in the volumetric medication preparation process. Five hospitals in the United States were recruited for study participation. During the data collection process, technicians were required to measure the syringe at 3 different points: when the new empty syringe was connected to a closed-system transfer device (CSTD), when the filled syringe containing the prepared dose of medication was connected to a CSTD, and when the used syringe with residual medication was connected to a CSTD. The actual dose of drug dispensed (in mg) was divided by the specific gravity of the medication to determine the actual volume of medication dispensed. A total of 4,443 compounded sterile products representing 60 medications across 5 hospitals were eligible for the study. Of the evaluated preparations, 91.92% were within 5% of the prescribed dose and 96.56% were within 10% of the prescribed dose. The outliers ranged from -144.10% to 233.72%. The potential for significant over- and undertreatment of an individual patient receiving IV chemotherapy exists, indicating the need for an additional measurement method, such as real-time gravimetric verification, to ensure an accurate dose is administered to every patient.

Effect of Oral Iron Therapy in Moderately Affected Anemianic Pregnant Women

In India, Iron deficiency anemia is one of the major causes of maternal deaths, over the past years, various oral and intra muscular &amp; intravenous preparations of iron have been used for correction of iron muscular are associated with significant side effects; Intramuscular (Iron dextran) was used as an alternative to oral iron therapy for those who were not compliant to oral therapy. Iron dextran has a lot of side effects such as fever, arthralgia, even anaphylactic reactions extending to pulmonary edema and even death. Further it is not possible to achieve the target rise in Hemoglobin level in a limited time period, when the patient is approaching term. Whereas Intravenous (Iron sucrose complex) is a relatively new drug which is a BOON to medical therapy and is the BEST OPTION of iron therapy when used as an alternative to oral therapy as it restores iron stores more promptly and is able to raise the hemoglobin to satisfactory level .

Hemoglobin life-threatening value (1.9\u2009g/dl) in good general condition: a pediatric case-report

BackgroundWe report a pediatric patient presenting in good general condition despite a hemoglobin value of 1,9 g/dL, which is normally regarded as life-threatening.Case presentationAn African 5 years-old girl presented to our Emergency Department (ED) for worsening asthenia, within a clinical picture of good general condition. The hemoglobin value at admission was 1,9 g/dL. The subsequent diagnostic-therapeutic pathway highlighted the presence of two different causes, both well known to be responsible for chronic anemia (with slow reduction of hemoglobin values): iron deficiency anemia (IDA) due to a very low dietary intake of iron-rich foods, and homozygous sickle cell disease (HbSS). She received transfusions of packed red blood cells (overall 15 ml/kg) and subsequently intravenous iron preparations (total amount 200 mg) followed by oral iron supplements. The Hb value at discharge, 10 days after the admission, was 9.8 g/dL.ConclusionsWhen approaching a picture of severe anemia, we suggest pediatricians take into consideration clinical conditions rather than laboratory values and to take advantage of detailed anamnestic data in order to make the diagnosis.

EFFECTIVENESS OF IRON SUCROSE AND FERRIC CARBOXYMALTOSE IN THE MANAGEMENT OF POSTPARTUM IRON DEFICIENCY ANEMIA: A SOUTH INDIAN PERSPECTIVE

BACKGROUND: Postpartum iron deciency anemia is considered as one of major public health problem with a high prevalence in developing country like India .It is associated with signicant morbidity. AIM AND METHOD: This perspective observational study was carried out to estimate the safety and effectiveness of iron sucrose and ferric carboxymaltose in treatment of postpartum iron deciency anemia. Total 100 participants diagnosed with postpartum anemia were allotted to receive either iron sucrose complex (n=50) or ferric carboxymaltose (n=50). RESULTS: Hemoglobin improvement was signicantly higher in ferric carboxymaltose than iron sucrose complex group (4.37 vs. 3.85 gm/dl, p&lt;0.001), but rise in ferritin levels was comparable between the groups (116.59 vs. 110.48 ng/ml, p=0.330). Most of the patients tolerated the preparation well, minor side effects were observed in 12% and 48% of cases among iron sucrose and ferric carboxymaltose group respectively CONCLUSION: Even though oral iron is considered as a rst line therapy, it requires a prolonged administration and is associated with suboptimal response due to gastric intolerance and poor compliance. Intravenous iron preparations are safer, more convenient and effective alternative for treatment of postpartum iron deciency anemia.

Clinical efficacy and safety of intravenous ferric carboxymaltose treatment of pediatric restless legs syndrome and periodic limb movement disorder

BackgroundIron supplementation is the most commonly considered treatment option for children with restless legs syndrome (RLS) or periodic limb movement disorder (PLMD); however, there is a scarcity of evidence on the effectiveness of intravenous preparations. In this study, we evaluated the effectiveness and tolerability of intravenous ferric carboxymaltose (IV FCM) on clinical symptoms and iron indices in children with RLS or PLMD. MethodsThis was a single-center retrospective data analysis. Children with a diagnosis of RLS or PLMD, who underwent a single infusion of IV FCM, were included. Clinical Global Impression (CGI) Scale scores, serum ferritin, and serum iron profile at baseline and after eight weeks post infusion were obtained. Adverse effects were assessed. ResultsThirty-nine children received IV FCM, 29 with RLS and 10 with PLMD. Pre-infusion CGI-Severity revealed moderate illness, with post-infusion CGI-Improvement between “very much improved” and “much improved”. Ferritin increased from 14.6 μg/L±7.01 to 112.4 μg/L±65.86 (p < 0.00001), together with improvements in iron, total iron binding capacity, and transferrin levels from baseline to post-treatment. When compared to children with RLS, those with PLMD had a similar improvement in clinical symptoms and laboratory parameters. Seven subjects (14.3%) experienced one or two adverse events; all were mild. ConclusionsChildren with RLS and PLMD responded to IV iron supplementation with improvement in both clinical severity and laboratory parameters. Treatment was well tolerated. Although larger, randomized-controlled trials are needed, IV FCM appears to be a promising alternative to oral iron supplementation for the treatment of pediatric RLS or PLMD.

Prevalence and determinants of intravenous admixture preparation errors: A prospective observational study in a university hospital

Background Intravenous admixture preparation errors (IAPEs) may lead to patient harm. Insight into the prevalence as well as the determinants associated with these IAPEs is needed to elicit preventive measures. Aim The primary aim of this study was to assess the prevalence of IAPEs. Secondary aims were to identify the type, severity, and determinants of IAPEs. Method A prospective observational study was performed in a Dutch university hospital. IAPE data were collected by disguised observation. The primary outcome was the proportion of admixtures with one or more IAPEs. Descriptive statistics were used for the prevalence, type, and severity of IAPEs. Mixed-effects logistic regression analyses were used to estimate the determinants of IAPEs. Results A total of 533 IAPEs occurred in 367 of 614 admixtures (59.8%) prepared by nursing staff. The most prevalent errors were wrong preparation technique (n = 257) and wrong volume of infusion fluid (n = 107). Fifty-nine IAPEs (11.1%) were potentially harmful. The following variables were associated with IAPEs: multistep versus single-step preparations (adjusted odds ratio [ORadj] 4.08, 95% confidence interval [CI] 2.27–7.35); interruption versus no interruption (ORadj 2.32, CI 1.13–4.74); weekend versus weekdays (ORadj 2.12, CI 1.14–3.95); time window 2 p.m.-6 p.m. versus 7 a.m.-10 a.m. (ORadj 3.38, CI 1.60–7.15); and paediatric versus adult wards (ORadj 0.14, CI 0.06–0.37). Conclusion IAPEs, including harmful IAPEs, occurred frequently. The determinants associated with IAPEs point to factors associated with preparation complexity and working conditions. Strategies to reduce the occurrence of IAPEs and therefore patient harm should target the identified determinants.

Analysis of economic efficiency of iron deficiency anemia therapy in patients with malignant tumors

Introduction. Correction of iron deficiency anemia in patients with malignant neoplasms is an important aspect affecting the quality of life and the effectiveness of special treatments. At the same time, the therapy of comorbid conditions significantly increases the cost of treating cancer patients.The aim of the study was to conduct a comparative pharmacoeconomic analysis of the two most common methods for correcting iron deficiency anemia in cancer patients: transfusion of erythrocyte suspension and intravenous iron preparations using iron carboxymaltose as an example.Materials and methods. An observational, analytical, cohort study was carried out, which included 120 cancer patients. The patients underwent laboratory examination. The tests were assessed: a general blood test with an assessment of the morphological characteristics of erythrocytes, serum iron, ferritin, CRP, total protein. An analysis of the costs of iron deficiency anemia therapy was carried out, taking into account the procurement cost of drugs.Results. It is economically more profitable to use intravenous iron preparations in comparison with transfusion of erythrocyte suspension for the treatment of iron deficiency anemia in patients with malignant neoplasms. The cost of correcting iron deficiency anemia per patient was: when treated with carboxymaltosate iron (Ferinject): 7943.96 rubles, with transfusion of erythrocyte suspension: 16856.40 rubles.Conclusion. In the treatment of anemia in patients with malignant neoplasms with blood preparations (erythrocyte suspension), an improvement in hematological parameters is noted earlier and to a greater extent than with the use of iron preparation carboxymaltozate («Ferinject»). Nevertheless, the duration of the clinical effect when using erythrocyte suspension is lower than that of a parenteral iron preparation.

The Dual Role of a Polyvalent IgM/IgA-Enriched Immunoglobulin Preparation in Activating and Inhibiting the Complement System.

Activation of the complement system is important for efficient clearance of a wide variety of pathogens via opsonophagocytosis, or by direct lysis via complement-dependent cytotoxicity (CDC). However, in severe infections dysregulation of the complement system contributes to hyperinflammation. The influence of the novel IgM/IgA-enriched immunoglobulin preparation trimodulin on the complement pathway was investigated in in vitro opsonophagocytosis, binding and CDC assays. Immunoglobulin levels before and after trimodulin treatment were placed in relation to complement assessments in humans. In vitro, trimodulin activates complement and induces opsonophagocytosis, but also interacts with opsonins C3b, C4b and anaphylatoxin C5a in a concentration-dependent manner. This was not observed for standard intravenous IgG preparation (IVIg). Accordingly, trimodulin, but not IVIg, inhibited the downstream CDC pathway and target cell lysis. If applied at a similar concentration range in healthy subjects, trimodulin treatment resulted in C3 and C4 consumption in a concentration-dependent manner, which was extended in patients with severe community-acquired pneumonia. Complement consumption is found to be dependent on underlying immunoglobulin levels, particularly IgM, pinpointing their regulative function in humans. IgM/IgA provide a balancing effect on the complement system. Trimodulin may enhance phagocytosis and opsonophagocytosis in patients with severe infections and prevent excessive pathogen lysis and release of harmful anaphylatoxins.

Immunomodulatory effects of different intravenous immunoglobulin preparations in chronic lymphocytic leukemia

Hypogammaglobulinemia is the most frequently observed immune defect in chronic lymphocytic leukemia (CLL). Although CLL patients usually have low serum levels of all isotypes (IgG, IgM and IgA), standard immunoglobulin (Ig) preparations for replacement therapy administrated to these patients contain more than 95% of IgG. Pentaglobin is an Ig preparation of intravenous application (IVIg) enriched with IgM and IgA (IVIgGMA), with the potential benefit to restore the Ig levels of all isotypes. Because IVIg preparations at high doses have well-documented anti-inflammatory and immunomodulatory effects, we aimed to evaluate the capacity of Pentaglobin and a standard IVIg preparation to affect leukemic and T cells from CLL patients. In contrast to standard IVIg, we found that IVIgGMA did not modify T cell activation and had a lower inhibitory effect on T cell proliferation. Regarding the activation of leukemic B cells through BCR, it was similarly reduced by both IVIgGMA and IVIgG. None of these IVIg preparations modified spontaneous apoptosis of T or leukemic B cells. However, the addition of IVIgGMA on in vitro cultures decreased the apoptosis of T cells induced by the BCL-2 inhibitor, venetoclax. Importantly, IVIgGMA did not impair venetoclax-induced apoptosis of leukemic B cells. Overall, our results add new data on the effects of different preparations of IVIg in CLL, and show that the IgM/IgA enriched preparation not only affects relevant mechanisms involved in CLL pathogenesis but also has a particular profile of immunomodulatory effects on T cells that deserves further investigation.

Immunomodulation: Immunoglobulin Preparations Suppress Hyperinflammation in a COVID-19 Model via FcγRIIA and FcαRI.

The rapid spread of SARS-CoV-2 has induced a global pandemic. Severe forms of COVID-19 are characterized by dysregulated immune response and “cytokine storm”. The role of IgG and IgM antibodies in COVID-19 pathology is reasonably well studied, whereas IgA is neglected. To improve clinical outcome of patients, immune modulatory drugs appear to be beneficial. Such drugs include intravenous immunoglobulin preparations, which were successfully tested in severe COVID-19 patients. Here we established a versatile in vitro model to study inflammatory as well as anti-inflammatory processes by therapeutic human immunoglobulins. We dissect the inflammatory activation on neutrophil-like HL60 cells, using an immune complex consisting of latex beads coated with spike protein of SARS-CoV-2 and opsonized with specific immunoglobulins from convalescent plasma. Our data clarifies the role of Fc-receptor-dependent phagocytosis via IgA-FcαRI and IgG-FcγR for COVID-19 disease followed by cytokine release. We show that COVID-19 associated inflammation could be reduced by addition of human immunoglobulin preparations (IVIG and trimodulin), while trimodulin elicits stronger immune modulation by more powerful ITAMi signaling. Besides IgG, the IgA component of trimodulin in particular, is of functional relevance for immune modulation in this assay setup, highlighting the need to study IgA mediated immune response.

P452 Oral ciclosporin is a convenient, effective and safe rescue therapy in steroid refractory Acute Severe Ulcerative Colitis: A single tertiary centre experience

Abstract Background Parenteral ciclosporin (CsA) is an effective rescue therapy for acute severe ulcerative colitis (ASUC) and has similar efficacy to infliximab (IFX). Although CsA is cheaper and can facilitate bridging to any IBD therapy, including newer biologics, its use is limited by variable pharmacokinetics and possibility of significant systemic toxicity particularly associated with the intravenous preparation. Despite favourable pharmacokinetics and bioavailability, the use of lipid-emulsified oral CsA in steroid-refractory ASUC is undefined. Methods All patients who received oral CsA (Neoral®) rescue therapy for ASUC at Addenbrooke’s Hospital, Cambridge, UK from Nov 2014 to May 2020 were identified from electronic healthcare records. Baseline data and outcomes were extracted and compared to patients who received IFX rescue therapy. Statistical significance was assessed using non-parametric tests. Survival estimates were computed using the Kaplan-Meier method. Results A total of 37 patients received oral CsA for refractory ASUC. Median time from admission to CsA initiation was 5 days (IQR 4–6 d) and median initial dose was 8 mg/kg/d (IQR 7–8 mg/kg/d). At admission, the median CRP was 26 (IQR 14–95) and Truelove and Witt’s severity criteria met in 21/37 (57%). 70% of patients (26/37) avoided colectomy during the index admission. No parameters were demonstrated to predict need for acute colectomy. Median follow-up after hospital discharge was 3 years (IQR 2-5years). For those who avoided acute colectomy, median duration of therapy was 4 months (IQR 2.5-5months) with bridging to azathioprine (24/26, 92%), vedolizumab (1/26, 4%), or 5-ASA (1/26, 4%). Estimated colectomy-free survival in responders were 84%, 84% and 78% at 12, 24, and 60 months. No parameters were shown to predict colectomy-free survival. Comparable colectomy-free outcomes were obtained for contemporaneous IFX-treated ASUC patients in our hospital. 9 of 26 patients remained biologic-naïve and colectomy-free after a median of 3 years. Estimated colectomy and biologic-free survival were 51%, 47% and 18% at 12, 24, and 60 months. 15 patients experienced adverse events, which were all mild and self-limiting. There were 3 infective complications. No patients required drug cessation and no serious adverse events associated with parenteral CsA occurred. Conclusion In this cohort, oral CsA was a safe, well tolerated and effective rescue therapy for steroid-refractory ASUC. A proportion of patients remain biologic and colectomy-free for up to 5 years. Given the feasibility to bridge to effective maintenance therapies, including newer biologics, oral CsA should be considered as a rescue therapy in ASUC and avoids many of the side effects associated with intravenous CsA.

Xuebijing inhibit inflammation, oxidative stress and promote apoptosis in human synovial cells via inhibition of MEK1/2 and NF-ĸB pathway

Abstract Rheumatoid arthritis (RA) is categorized as an autoimmune disease that leads to bone or joint deformity due to altered immune response. Studies have concluded the role of inflammation and oxidative stress in the progression of RA and agents inhibiting these processes showed benificial effect against the disease. Xuebijing (XBJ) injection is an intravenous patent preparation made from five-traditional Chinese medicines. Previous studies showed its excellent pharmacological activities, such as against sepsis, inflammation, and oxidative stress which has encouraged us to investigate the protective effect of XBJ against rheumatoid arthritis cell line (MH7A). For this purpose, the effect of XBJ was quantified on several parameters on the human synovial MH7A cell line activated with tumor necrosis factor-α (TNF-α). The results of the study showed that the level of tested interleukines (IL- 1β, IL- 6, IL- 8) and collagenases 1, and 13, and matrix metallo-proteinases 1, and 13 (MMP-1, and MMP-13) were found significantly reduced in XBJ treated group as compared to TNF-α treated MH7A cells. The XBJ treated group showed reduction in mRNA protein expression of COX-2 and iNOS in RT-qPCR assay. The rate of cellular apoptosis was found increased in XBJ treated group with reduction of cell viability of MH7A cells. The XBJ also showed attenuation of the expression of p-MEK/1/2 and p-p65 in MH7A cells in a western blot analysis. Our results demonstrated that XBJ significantly inhibits the inflammatory response, prevents cell viability, and induces apoptosis in human RA synovial cells by preventing the activation of the MEK/NF-κB pathway.

The Pharmacokinetics of Crushed Levetiracetam Tablets Administered to Neonates.

Intravenous phenobarbital remains the first-line therapy in the management of neonatal seizures. Shortages of intravenous phenobarbital in South Africa necessitated the addition of oral levetiracetam as part of management of neonatal seizures. We evaluated the pharmacokinetics of crushed immediate-release levetiracetam tablets administered to neonates to terminate seizures. A prospective, observational study of neonates admitted with seizures to Tygerberg Hospital. Participants received crushed levetiracetam (diluted in saline) given orally or via naso-/orogastric tube. At steady-state, pharmacokinetic sampling was performed at pre-dose, 1.5, 2.5 and 4 h post-dose. Maximum concentration (Cmax), time to Cmax (Tmax), trough concentrations (Ctrough) and area under the concentration-time curve (AUC0-12) were calculated using non-compartmental analysis. Seizure termination and safety profiles were documented. Nineteen participants were grouped into three dosing ranges: (i) 5-15 mg/kg/12-hourly, (ii) 15-25 mg/kg/12-hourly and (iii) 25-35 mg/kg/12-hourly. Range 1 demonstrated AUC0-12 167.0 ± 45.6 h*μg/mL, Cmax 19.19 ± 4.12 μg/mL and Ctrough 9.99 ± 3.86 µg/mL. Range 2, AUC0-12 316.5 ± 108.4 h*μg/mL, Cmax 35.12 ± 10.54 µg/mL and Ctrough 19.25 ± 8.48 µg/mL. Range 3, AUC0-12 290.9 (range 176.14-405.59) h*μg/mL, Cmax 36.11 (range 27.58-44.64) µg/mL and Ctrough 13.03 (2.98-23.07) µg/mL. Seizures terminated in 17/19 (90%) neonates by day 3 and 19/19 (100%) by day 4 post-levetiracetam initiation. Crushed levetiracetam has comparable pharmacokinetics to historical data. No pharmacokinetic differences were observed between oral vs. naso-/orogastric administration. Crushed levetiracetam tablets can be considered for neonates in low-resource settings where intravenous and syrup access is limited. Intravenous preparations of antiepileptic medications are used in the management of neonatal seizures. Various established standard of care intravenous antiepileptic medicines are unavailable nationally and internationally due to reasons outside our control. This stock shortage included intravenous phenobarbitone which is the first-line treatment for paediatric seizures. Due to phenobarbital shortage, levetiracetam has been identified by the neonatologists at Tygerberg Hospital, Cape Town, South Africa, as a suitable treatment option due to its efficacy and safety profile. However, intravenous levetiracetam and oral syrup is not registered in South Africa. Levetiracetam tablets are being crushed, dissolved and administered to neonates. There are no data available on the absorption of crushed levetiracetam tablets administered to neonates via a nasogastric tube. This study characterized the pharmacokinetic profile of crushed levetiracetam administered to neonates. We selected neonates receiving levetiracetam from the neonatal wards at Tygerberg hospital and drew blood to analyse the levetiracetam concentrations at 4 different time points. We found that the overall exposure of crushed levetiracetam tablets were comparable to the exposures achieved in historical data of the unaltered formulations. We concluded that crushed levetiracetam tablets can be considered for neonates in low resource settings where intravenous and syrup access is limited.

Iron deficiency in heart failure.

Iron deficiency is a major heart failure co‐morbidity present in about 50% of patients with stable heart failure irrespective of the left ventricular function. Along with compromise of daily activities, it also increases patient morbidity and mortality, which is independent of anaemia. Several trials have established parenteral iron supplementation as an important complimentary therapy to improve patient well‐being and physical performance. Intravenous iron preparations, in the first‐line ferric carboxymaltose, demonstrated in previous clinical trials superior clinical effect in comparison with oral iron preparations, improving New York Heart Association functional class, 6 min walk test distance, peak oxygen consumption, and quality of life in patients with chronic heart failure. Beneficial effect of iron deficiency treatment on morbidity and mortality of heart failure patients is waiting for conformation in ongoing trials. Although the current guidelines for treatment of chronic and acute heart failure acknowledge importance of iron deficiency correction and recommend intravenous iron supplementation for its treatment, iron deficiency remains frequently undertreated and insufficiently diagnosed in setting of the chronic heart failure. This paper highlights the current state of the art in the pathophysiology of iron deficiency, associations with heart failure trajectory and outcome, and an overview of current guideline‐suggested treatment options.

Hypophosphatémie et fer injectable : à propos d’un cas et revue de la littérature

Iron deficiency and iron-deficiency anemia are common medical conditions. Management of the etiology and iron supplementation are both necessary to treat this condition. Use of intravenous iron preparations is increasing due to its advantages over oral iron. Indeed, the total dose required can be provided in a single infusion, and it is more effective and increases hemoglobin levels more quickly than oral iron. Hypophosphatemia, sometimes severe, following intravenous iron administration, has been described in literature these past years, in particular with ferric carboxymaltose. We report here a case of severe hypophosphatemia with ferric carboxymaltose and carry out a literature review to determine the incidence of hypophosphatemia and to precise its clinical presentation, its pathophysiological mechanisms and its treatment. We found that hypophosphatemia is frequent with ferric carboxymaltose. Most of the time, there are no clinical manifestations, but cases of symptomatic osteomalacia have been described. Duration of hypophosphatemia is variable, from a few weeks to several months in case of prolonged administration. Hypophosphatemia owing to renal phosphate wasting is caused by an increase in intact fibroblast growth factor 23 (FGF-23) levels. However, the mechanism of ferric carboxymaltose- induced increase in intact FGF-23 is still unknown.

Oxytocin and Misoprostol With Diclofenac in the Preparation for Magnetic Resonance–Guided High-Intensity Ultrasound Treatment of Symptomatic Uterine Fibroids: A Prospective Cohort Study

Uterine fibroids (UFs) are very common benign tumors of the female reproductive tract. According to recent reports, magnetic resonance–guided high-intensity ultrasound (MR-HIFU) appears to be a well-tolerated and efficient treatment option for UFs. However, MR-HIFU still presents several limitations. The treatment is rarely associated with achieving complete non-perfused volume (NPV). Not all patients are qualified for a final procedure, and selected women obtain very good results in such treatment. The primary objective of this experimental study was to assess the effect of transvaginal misoprostol and intravenous oxytocin preparation on UF volume change, sonication time and NPV after MR-HIFU procedure in women of reproductive age with symptomatic UFs. Secondary outcomes included the effect on the peri-procedural effectiveness of misoprostol and oxytocin. This study enrolled 247 women with symptomatic UFs; based on gynecologic examinations and magnetic resonance imaging (MRI) scans, 128 women qualified for MR-HIFU without pharmacologic treatment, 57 women qualified for the misoprostol/diclofenac group and 62 women qualified for the oxytocin group. Pharmacologic pre-treatment improved NPV compared with non-pharmacologic treatment (average NPV: controls 61.9% ± 25.8%; oxytocin 76.8% ± 20.7%; misoprostol/diclofenac 85.2% ± 15.1%; average sonication time: controls 120 min ± 56.4%; oxytocin 111 min ± 45.4%; misoprostol/diclofenac 80 min ± 47.7%). Statistical analysis did not reveal significant intergroup differences in UF volume changes after 6 mo (controls: n = 40, 37.4% ± 27.5%; oxytocin n = 25, 45.8% ± 31%; misoprostol/diclofenac n = 19, 33.4% ± 23.2%). The misoprostol/diclofenac group, which achieved the highest NPV immediately after the MR-HIFU procedure, was characterized by the lowest UF volume change percentages 6 mo later. The administration of vasoconstrictor drugs (oxytocin and misoprostol/diclofenac) to support MR-HIFU in UF treatment is a new issue that may improve the total effectiveness of this method. Randomized controlled trials are necessary to estimate the real effect of vasoconstrictors on MR-HIFU.