Experience of long-term use of denosumab in women with osteoporosis and various concomitant diseases

Background: Possible differences in the results of planned RCTs and real clinical practice were the reason for the analysis of long-term therapy with denosumab in patients with osteoporosis (OP) of various origins on an outpatient basis.Aim: To assess the effectiveness of long-term administration of denosumab in terms of the effect on BMD and markers of bone metabolism, tolerance and consequences of drug withdrawal in patients with OP of various etiologies.Materials And Methods: A retrospective analysis of the outpatient records of women with OP of various etiology, who were observed at the FSBI «NMRC TPM» from 1 to 10 years and regularly received denosumab 60 mg once every 6 months subcutaneously (at least 2 injections), was carried out. All completed examination and anthropometric research; DXA of the lumbar spine and proximal femur (PF); laboratory tests: marker of bone resorption CTx (β-crosslaps) in blood serum; survey on the presence of adverse events.Results: The study included 148 patients who were divided into 2 groups: 1 (N=98) - did not take anti-osteoporotic therapy (AT), 2 (N=50) - who took AT before the appointment of denosumab. Long-term therapy with denosumab was associated with a steady and reliable increase in BMD in the spine and PF, as well as a decrease in the concentration of CTx of both those who didn’t take and who previously took AT. In 54% of patients BMD in the spine reached values of osteopenia, in 43.4% of women target BMD values in the femoral neck were determined. During the first year of therapy, there was a decrease in the concentration of CTx by 67% in those who didn’t take AT and by 58% in those who had previously taken AT. Discontinuation of denosumab therapy without subsequent administration of AT was associated with a significant decrease in BMD in the spine (by 4.4-8.2%) during the first year after discontinuation of the drug.Conclusion: Denosumab therapy effectively increases BMD in the spine and PF and decreases CTx levels both in untreated patients and in those who previously received AT. It is necessary to discontinue therapy, further management of the patient should be discussed to prevent «withdrawal syndrome».

PSVIII-20 Heterologous lactobacilli feed additive impact on microflora in Cobb-500 broiler laying hens

Experiment was carried out on introducing eggshells from an experimental group of laying hens of lactobacilli strains with anti-C.jejuni activity. Eggs were incubated for 21 days to obtain broiler chickens containing auto-strains of lactobacilli with anti-C.jejuni activity in the blind processes of the intestine. It should be noted that most of the incubation eggs were observed in the 2nd group, in which the eggs were laid for subsequent administration of probiotic bacteria. Check was carried out for the presence of auto-strains of lactobacilli with anti-C.jejuni activity in the intestines of broiler chickens and the timing of their persistence for 1–35 days. The objective of the study was a comparative analysis of the following DNA samples: DNA from a feed supplement containing strains of lactobacilli with anti-C.jejuni activity; DNA samples from litter of laying hens of the parent herd receiving heterologous lactobacilli as part of the feed; isolated DNA from washes from hatching eggs; DNA samples from the contents of the digestive tract of chicken embryos; DNA samples from the intestines of broiler chickens. DNA samples from groups of birds and their embryos obtained without the use of heterologous lactobacilli were used as controls. The microflora of the contents of blind processes was taken from chickens on the 22nd day and on the 35th day of growing. In total, 343 different bacterial OTUs were identified in this study, belonging to 13 types, 26 classes, 51 orders, 106 families and 172 genera. Assessment of the biodiversity of bacterial ensembles in the samples of the contents of blind processes of chickens revealed fundamental differences already at the level of growing time and type. The study was performed at the FGBOU VO “St. Petersburg State University of Veterinary Medicine» with the aid of the Russian Science Foundation Grant (Project No. 18-76-10017).

Tachycardia during Treatment with Risperidone and Paliperidone Palmitate in a Patient without Previous Cardiovascular Disease

Here, we present the case of a patient who initiated risperidone and developed persistent tachycardia, which was exacerbated by subsequent administration of paliperidone palmitate despite treatment with propranolol. This patient’s experience emphasizes the need for psychiatrists to regularly monitor vital signs after risperidone/paliperidone initiation, dosage increase, or overdose to identify and appropriately manage this potentially harmful side effect. Increasing clinician awareness of this rare side effect will help protect patients with serious mental illness who regularly rely upon these medications, particularly in their long-acting injectable formulations.

Management of Disorders of Homeostasis With Saline Enteral Solution in Acute Poisoning With Psychopharmacological Drugs

Background. In acute poisoning, accompanied by a violation of the parameters of homeostasis, the problem of its management by the enteral route has been insufficiently studied.Purpose of the study. To assess the possibility of correcting electrolyte and volemic disorders of the body using an enteral solution (ER) in case of poisoning with psychopharmacological drugs.Material and methods. The study involved 120 patients who underwent intestinal lavage (IL) with ER on the 1st day in complex therapy. In the following days, 40 of them received infusion therapy, and 80 — drank glucose enteral solution (GES), 3–4 liters per day.Results. IL had a corrective effect on the electrolyte composition of the blood, volemic and hemorheological parameters, as well as on central and peripheral hemodynamics. The subsequent administration of GER had a stabilizing effect on these indicators, comparable to that of infusion therapy.Conclusion. In case of poisoning with psychopharmacological drugs, the use of saline enteral solution in the form of intestinal lavage and subsequent oral administration of the same solution in a daily volume of 3–4 liters, but with the addition of glucose, provides correction of impaired homeostasis indicators and may be an alternative to infusion therapy.

Personification of infusion therapy in patients with ischemic stroke depending on the severity of the violation of energy-structural status

Objective. To determine the tactics of infusion therapy in patients with ischemic stroke (IS) depending on the severity of the violation of energy-structural status (ESST). Materials and methods. A study of 32 patients with severe IS on the National Institutes of Health Stroke Scale (16,7±1,5), who were in the department of anesthesiology with intensive therapy units of the Municipal Non-Profit Enterprise «City Hospital № 9» Zaporizhzhia City Council. Of these, 11 were men (34,4 %; the average age – 68,2±2,5 years), 21 were women (65,6 %; average age – 72,1±1,6). Results and discussion. In patients with IS, disorders ESST were defined as hyperergic damage at values of cardiac index (CI) of 4,45-5,09 L×min-1×m-2 and oxygen consumption index (IVO2) 186-210 ml×min-1×m-2, and at values of CI ≥5,10 L×min-1×m-2 and IVO2 ≥211 ml×min-1×m-2 – as hyperergic insufficiency. While hypoergic damage ESST occurred at values of CI 2,33-1,82 L×min-1×m-2 and IVO2 104-85 ml×min-1×m-2, and at CI ≤1,81 L×min-1×m-2 and IVO2 ≤84 ml×min-1×m-2 hypoergic insufficiency of ESST was observed. The daily fluid requirement of a patient with IS was calculated according to the formula 4+2+1: for the first 10 kg of weight – 4 ml×kg-1×h-1; from 11 to 20 kg – 2 ml×kg-1×h-1; from 21 kg – on 1 ml×kg-1×h-1 (Park G.R., Roe P.G., 2005; Netyazhenko V.Z., Halushko O.A., 2012). Infusion therapy in patients with IS and hyperergic damage ESST was performed with 0,9 % sodium chloride solution according to the formula 4+2+1 on the background of the use of esmolol intravenously bolus 250 mg and subsequent administration of 50 mсg×kg-1×min-1, and in hyperergic insufficiency 500 mg of esmolol intravenously bolus and subsequent administration of 100 mсg×kg-1×min-1. While in hypoergic damage ESST on the background of infusion therapy used dopamine or dobutamine 1-5 mсg×kg-1×min-1, and in hypoergic insufficiency, the dose of dopamine or dobutamine was increased to achieve the desired effect. Conclusions. The personification of infusion therapy depending on the severity of the violation of ESST can improve the results of treatment of patients with IS in the most acute period.

Extended enzymatic stability of reconstituted lyophilized PEG-asparaginase in vials

Asparaginase (ASNase) use as a tumour-inhibitor drug has changed completely the natural course of paediatric acute lymphoblastic leukaemia (ALL) in such a way that it represents a paradigm shift in ALL management. ASNase treatment emergence has significantly improved pathologic responses and increased survival rates of ALL patients. Although different ASNase forms are currently available, only the pegylated form (PEG-ASNase) is recommended by relevant clinic guides. PEG-ASNase form shows longer elimination half-life, reducing the number of administrations, along with an enhanced safety profile. In spite of all of these advantages, PEG-ASNase elevated cost limits enormously its use. PEG-ASNase is commercialised as a lyophilised powder which according to the manufacturer it is stable for 24 hours once reconstituted, as a result, the leftover is usually discarded. In this study we analysed the enzymatic stability of reconstituted PEG-ASNase after conservation in three different temperature conditions for 5 and 14 days, aiming to take advantage of the remaining leftover for the subsequent administration. Our results have shown that PEG-ASNase is stable at 4°C, −20°C and −80°C for at least 14 days, retaining the 95% from the initial enzymatic activity in all three storage temperatures. According to our results, it is feasible to reuse the remaining content of PEG-ASNase vial after reconstitution, which means a 50% reduction of its cost for paediatric patient treatment and, consequently, removes the main barrier to use this drug in a wider population.

Repairing the Damage from Illegal Acts of State

The United States is only just beginning to grapple with the fallout from the program known as Rendition, Detention and Interrogation (RDI), an illegal interrogation practice designed to further the United States counter-terrorism efforts against al-Qaeda and the Taliban. One of the most consequential legacies of the program stems from the way it was justified: lawyers for the Bush administration sought to legitimize the program through distorted legal doctrines, some of which remained in currency even after the RDI program was finally abandoned. The attempt to justify illegal conduct with false legal arguments, along with the failure of the subsequent administration to hold the principal architects of the program responsible, has eroded the rule of law in the United States and done permanent damage to norms of armed conflict as well as to domestic and international law. This chapter discusses the consequences of the RDI program, with particular attention paid to the impact of legal manipulations used to justify the program as well as the failure of accountability that resulted. In Part IV, this chapter addresses the question whether torture has been permanently eliminated from U.S. law, or whether the practice is likely to return. In this connection, the chapter raises concerns about the McCain-Feinstein Amendment that tied permissible interrogation methods to the Army Field Manual (AFM), which continues to authorize the psychologically and emotionally damaging techniques of sensory and sleep deprivation through Appendix M. The chapter finally discusses ways to repair the damage the RDI program and its aftermath inflicted on the rule of law.

The First Pediatric Case of Acute Generalized Exanthematous Pustulosis Caused by Hydroxychloroquine

Introduction: Acute generalized exanthematous pustulosis (AGEP) is a generalized, non-follicular sterile pustular rash, categorized as a severe cutaneous adverse reaction, which usually has a favorable prognosis. In a majority of cases (90%), AGEP is drug induced and different drugs are reported as cause of AGEP. Hydroxychloroquine (HCQ) is an antimalarial drug that is also used in some dermatologic and rheumatic diseases due to its immunosuppressive actions. Some cases of AGEP induced by HCQ are reported in literature but only in adults. Materials, Methods and Results: We describe the first case of AGEP caused by HCQ in a child affected by juvenile Sjögren syndrome. After withdrawal of HCQ and subsequent administration, the patient experienced the same cutaneous reaction. An allergy work-up was performed and patch test showed an ectopic flare of AGEP eruption. Conclusion: Our patient represents the first pediatric case of AGEP to HCQ, posing such a drug as a possible trigger also in children. Therefore, an accurate drug medical history is mandatory in order to rule out potential drug reactions when facing a sudden rash.