Characteristics of adverse side effects of corticosteroid therapy in children with nephrotic syndrome and methods of pharmacological correction

The article discusses the issues of the long-term glucocorticosteroid therapy in children with nephrotic syndrome that results in severe adverse side effect

Risk Factors for Obesity Development in Different Periods of Childhood

Obesity is an important health problem in many countries. Obesity among the child population is growing steadily, including the Russian Federation. Development of this disease often occurs in childhood and sometimes the origin of obesity goes back to prenatal period. There are a number of endogenous and exogenous factors than play an important role in development of obesity. These are heredity, socioeconomic status of the family, factors which are revealed during pregnancy and child delivery — weight gain, administration of antibacterial drugs and hyperglycemia in mother during her pregnancy, mode of delivery, feeding type and time of complementary food introduction, excessive consumption of calories with food, improper daily routine and lack of sleep, skipping meals, use of gadgets and associated physical inactivity and excessive food intake, marketing of high-calorie foods and others. Prevailing risk factors can be identified for each age period. Study and early identification of risk factors taking into account age of a child is necessary to take timely prevention measures and inform parents and their children about possible reasons and consequences of obesity

Nightly treatment of primary insomnia with prolonged release melatonin for 6 months: a randomized placebo controlled trial on age and endogenous melatonin as predictors of efficacy and safety

<p>Background: Melatonin is extensively used in the USA in a non-regulated manner for sleep disorders. Prolonged release melatonin (PRM) is licensed in Europe and other countries for the short term treatment of primary insomnia in patients aged 55 years and over. However, a clear definition of the target patient population and well-controlled studies of long-term efficacy and safety are lacking. It is known that melatonin production declines with age. Some young insomnia patients also may have low melatonin levels. The study investigated whether older age or low melatonin excretion is a better predictor of response to PRM, whether the efficacy observed in short-term studies is sustained during continued treatment and the long term safety of such treatment.</p> <p>Methods: Adult outpatients (791, aged 18-80 years) with primary insomnia, were treated with placebo (2 weeks) and then randomized, double-blind to 3 weeks with PRM or placebo nightly. PRM patients continued whereas placebo completers were re-randomized 1:1 to PRM or placebo for 26 weeks with 2 weeks of single-blind placebo run-out. Main outcome measures were sleep latency derived from a sleep diary, Pittsburgh Sleep Quality Index (PSQI), Quality of Life (World Health Organzaton-5) Clinical Global Impression of Improvement (CGI-I) and adverse effects and vital signs recorded at each visit.</p> <p>Results: On the primary efficacy variable, sleep latency, the effects of PRM (3 weeks) in patients with low endogenous melatonin (6-sulphatoxymelatonin [6-SMT] ≤8 μg/night) regardless of age did not differ from the placebo, whereas PRM significantly reduced sleep latency compared to the placebo in elderly patients regardless of melatonin levels (-19.1 versus -1.7 min; P = 0.002). The effects on sleep latency and additional sleep and daytime parameters that improved with PRM were maintained or enhanced over the 6-month period with no signs of tolerance. Most adverse events were mild in severity with no clinically relevant differences between PRM and placebo for any safety outcome.</p> <p>Conclusions: The results demonstrate short- and long-term efficacy and safety of PRM in elderly insomnia patients. Low melatonin production regardless of age is not useful in predicting responses to melatonin therapy in insomnia. The age cut-off for response warrants further investigation.</p&gt

Adverse reactions of high-osmolar and low-osmolar radiographic contrast media in clinical practice

Introduction. Adverse drug reactions (ADR) to administration of radiographic contrast media (RCM) are observed in 10–20 % of patients. Individual tolerability of drugs is affected by RCM properties (ionicity, osmolarity). Aim. Evaluation of ADR in patients during diagnostic studies using high- and low-osmolar RCM. Methods. Analysis of 52 reports of adverse reactions to RCM registered in medical organizations of Voronezh region in 2014–2021 was performed. Group 1 included 21 patients with ADR to high-osmolar RCM (sodium amidotrizoate, yoxitalamic acid), group 2–31 patients with ADR to low-osmolar drugs (yogexol, yopromide, yopamidol, yoversol). Results. Age of patients is 6–82 years, median 48.5 years, children — 8 persons (15.4 %), women — 31 patients (59.6 %), serious reactions — 28 (53.8 %). Since 2017 there has been an increase in the number of ADRs with constant frequency of serious reactions. In 2020–2021 ADRs to low-osmolar drugs were mainly registered. Life-threatening conditions (anaphylactic shock, arterial hypotension, arrhythmia) were observed in 70.2 % of group 2, in 28.6 % of group 1 (p=0.007). One patient with initial renal dysfunction and comorbid pathology was reported to develop nephrotoxicity to yogexol. Pharmacological correction was performed in 92.3 % of cases. In 57.7 % of the patients ADR ended in recovery, in the  other cases — state improvement. Conclusion. Side effects of high-osmolar and low-osmolar RCM mainly had form of hyperergic reactions of immediate type and were reversible. High frequency of serious reactions to lowosmolar RCM against an increase in their use requires a more careful selection of patients for X-ray contrast studies

Characteristics of blood pressure level in children with different body weight

BACKGROUND: Essential arterial hypertension (AH) develops more often in children with accompanying risk factors — obesity, overweight, positive heredity and genetic predisposition.AIM: Study of peculiarities of arterial hypertension clinical course in adolescents with normal body weight, overweight and obesity.MATERIALS AND METHODS: The study was conducted on children with arterial hypertension who received treatment in two hospitals in Voronezh in 2016–2020. A retrospective analysis of the children’s case histories was carried out taking into account the anamnesis, clinical laboratory and instrumental examination data and the pharmacotherapy. Some children underwent polymerase chain reaction genetic testing to determine pathological alleles of genes regulating blood pressure (BP).RESULTS: 96 patients aged 9 to 17 took part in the study. The group with normal body weight included 38 children (39.6%), median age 16.4 (aged 10.7; 17.9), with overweight — 33 people (34.4%), median age 15.2 (aged 12.0; 17.9), with obesity — 25 children (26.0%), median age 14.5 (aged 9.2; 17.9). Obese children developed arterial hypertension at earlier age (p = 0.023). According to blood pressure daily monitoring (BPDM), pathological values of systolic blood pressure (SBP) during the day (above the 95th percentile) among children with normal body weight were observed in 17 patients (44.7%), with excess body weight — in 14 people (42.4%), with obesity — in 16 people (64%), p = 0.031. Accurate difference values between the groups were obtained in terms of time index (TI) of SBP at night (p = 0.006). Time index of diastolic BP during the day > 50% was observed only in the obese children group — 4 people (16%) (p = 0.042). Pathological alleles of the angiotensinogen gene (AGT: 704 T>C), aldosterone synthase gene (CYP11B2: -344 C>T) and endothelial nitrogen synthase type 3 (NOS3: -786 T> C) were identified most frequently during genetic testing in some patients.CONCLUSION: Children with obesity developed earlier arterial hypertension compared to the same-age children with normal body weight and more often had unfavorable type of arterial hypertension according to BPDM. These results can be used to choose individual therapy and to develop special attention as regards certain target organs damage

БЕЗОПАСНОСТЬ ДЛИТЕЛЬНОЙ ГЛЮКОКОРТИКОСТЕРОИДНОЙ ТЕРАПИИ У ДЕТЕЙ С НЕФРОТИЧЕСКИМ СИНДРОМОМ

Background: Long-term corticosteroid therapy in children leads to plenty of adverse effects with negative influence on health. Objective: analysis of adverse effects of corticosteroids in children with steroid-sensitive  nephrotic syndrome and development of recommendations of their early detection.Methods: A retrospective study is conducted on children with this syndrome aged 3–18 who applied to Voronezh Regional Children’s Clinical Hospital № 1 in 2011–2014.  Complications  of corticosteroid  therapy revealed during clinical examination of children were taken into account. Data on 118 healthy children examined in 2012–2014 were used to calculate integral index.Results: The study analyses treatment results of 18 children who received glucocorticosteroids  during 6 months before hospitalization and 13 children who were withdrawn from glucocorticosteroids  for 6 months or more before hospitalization. Among adverse reactions in group 1 there prevailed overweight/obesity  (78%), reactive pancreatitis (72%), leukemoid reactions (67%), liver damage (61%), Cushingoid syndrome (44%), chronic gastroduodenitis  (33%). Hyperglycemia (11%), hypertension (6%) and infection (6%) were less common. In group 2 only 2 (15%) patients had chronic gastroduodenitis,  other complications were not documented. Indices that change in children with nephrotic syndrome during corticosteroid treatment (body mass index, blood serum glucose and amylase) were measured by a single scale using modifications coefficients. Average value of the coefficients is suggested to be a new diagnostic criterion (metabolic reaction index) which allows to reveal corticosteroid adverse effects before any clinical manifestations.Conclusion: Most adverse reactions of glucocorticosteroids are short-term and continue after 6 months in a small number of patients.Длительная  глюкокортикостероидная терапия у детей с нефротическим синдромом является причиной развития многочисленных побочных реакций, негативно влияющих на здоровье ребенка.Цель исследования — изучить нежелательные побочные реакции  глюкокортикостероидной терапии  у детей  со стероидчувствительным  нефротическим  синдромом и разработать  рекомендации по их раннему выявлению.Методы.  В ретроспективном  исследовании  изучали результаты лечения детей в возрасте 3–18 лет со стероидчувствительным  нефротическим синдромом, госпитализированных  в стационар в 2011–2014  гг. Учитывали  осложнения  терапии, выявленные при клинико-лабораторном и инструментальном обследовании.  Для расчета интегрального  индекса метаболических реакций использовали данные 118 здоровых детей,        165 обследованных  в 2012–2014 гг.Результаты. Проанализированы  данные 18 детей, получавших глюкокортикостероиды в течение 6 мес до госпитализации,  и 13 детей, завершивших лечение  глюкокортикостероидами за 6 мес и более  до госпитализации.  У больных первой группы в числе побочных реакций чаще всего определяли избыточную массу тела или ожирение  (78%), реактивный панкреатит (72%), лейкемоидные  реакции (67%), поражение  печени (50%), кушингоидный синдром (44%) и хронический гастродуоденит (33%). Относительно редко встречались гипергликемия (11%), артериальная гипертензия (6%), инфекционное  заболевание  (6%). У больных второй группы только  у 2 (15%) сохранялись проявления хронического гастродуоденита. На основании значений индекса массы тела, уровня глюкозы и амилазы сыворотки крови рассчитывали  индекс метаболических  реакций — интегральный  показатель  риска возникновения  побочных эффектов глюкокортикостероидой терапии.Заключение. Большинство побочных реакций глюкокортикостероидной терапии являются краткосрочными и сохраняются по прошествии 6 мес у небольшого числа больных

Breastfeeding challenges in infants with nasal breathing difficulties: alternative supplemental feeding methods

This review article highlights the features of breastfeeding in case of obstructed nasal breathing in infants, special attention is paid to non-sucking or alternative methods of bottle feeding with expressed breast milk for the period when breastfeeding is not possible or formula supplementation is necessary as an addition to breastfeeding.Breathing through the mouth is considered a pathological adaptation due to difficulty in nasal breathing and is associated with the development of many pathological conditions. There is an evidence base that prolonged breastfeeding is associated with nasal breathing at an older age, as well as the correct formation of the bite. The anatomical and physiological features of the structure of the upper respiratory tract in infants predispose to a more frequent occurrence of difficult nasal breathing compared to adults, which causes difficulties in breastfeeding, up to the refusal of the child’s breast. Therefore, knowledge of modern methods of supplementary feeding with expressed breast milk for this period, as well as ways to effectively and safely deal with nasal congestion in infants, will help doctors and parents to overcome the difficult period of the disease, accompanied by nasal congestion without loss and maintain breastfeeding for as long as possible, in the light of modern data on influence of breast milk on the subsequent life of mother and child.The main method of treatment for nasal congestion of various etiologies is irrigation-elimination therapy. According to the literature, good tolerability and no side effects were found when using a nasal aspirator used in conjunction with isotonic saline

Finite-size scaling from self-consistent theory of localization

Accepting validity of self-consistent theory of localization by Vollhardt and Woelfle, we derive the finite-size scaling procedure used for studies of the critical behavior in d-dimensional case and based on the use of auxiliary quasi-1D systems. The obtained scaling functions for d=2 and d=3 are in good agreement with numerical results: it signifies the absence of essential contradictions with the Vollhardt and Woelfle theory on the level of raw data. The results \nu=1.3-1.6, usually obtained at d=3 for the critical exponent of the correlation length, are explained by the fact that dependence L+L_0 with L_0>0 (L is the transversal size of the system) is interpreted as L^{1/\nu} with \nu>1. For dimensions d\ge 4, the modified scaling relations are derived; it demonstrates incorrectness of the conventional treatment of data for d=4 and d=5, but establishes the constructive procedure for such a treatment. Consequences for other variants of finite-size scaling are discussed.Comment: Latex, 23 pages, figures included; additional Fig.8 is added with high precision data by Kramer et a

DUET: A phase 2 study evaluating the efficacy and safety of sparsentan in patients with FSGS

Background: We evaluated and compared the effects of sparsentan, a dual endothelin type A (ETA) and angiotensin II type 1 receptor antagonist, with those of the angiotensin II type 1 receptor antagonist irbesartan in patients with primary FSGS. Methods: In this phase 2, randomized, double-blind, active-control Efficacy and Safety of Sparsentan (RE-021), a Dual Endothelin Receptor and Angiotensin Receptor Blocker, in Patients with Focal Segmental Glomerulosclerosis (FSGS): A Randomized, Double-blind, Active-Control, Dose-Escalation Study (DUET), patients aged 8-75 yearswith biopsy-proven FSGS, eGFR>30ml/min per 1.73m2, and urinary protein-to-creatinine ratio (UP/C)≥1.0 g/g received sparsentan (200, 400, or 800 mg/d) or irbesartan (300mg/d) for 8 weeks, followed by open-label sparsentan only. End points atweek 8 were reduction from baseline inUP/C(primary) and proportion of patients achieving FSGS partial remission end point (FPRE) (UP/C:≤1.5 g/g and>40%reduction [secondary]). Results: Of 109 patients randomized, 96 received study drugs and had baseline and week 8 UP/C measurements. Sparsentan-treated patients had greater reductions in UP/C than irbesartan-treated patients didwhen all doses (45%versus 19%; P=0.006) or the 400 and 800mg doses (47%versus 19%; P=0.01) were pooled for analysis. The FSGS partial remission end point was achieved in 28% of sparsentan-treated and 9% of irbesartan-treated patients (P=0.04). After 8 weeks of treatment, BP was reduced with sparsentan but not irbesartan, and eGFR was stable with both treatments. Overall, the incidence of adverse events was similar between groups. Hypotension and edema were more common among sparsentan-treated patients but did not result in study withdrawals. Conclusions: Patients with FSGS achieved significantly greater reductions in proteinuria after 8 weeks of sparsentan versus irbesartan. Sparsentan was safe and well tolerated

Sunlight-Exposed Biofilm Microbial Communities Are Naturally Resistant to Chernobyl Ionizing-Radiation Levels

BACKGROUND: The Chernobyl accident represents a long-term experiment on the effects of exposure to ionizing radiation at the ecosystem level. Though studies of these effects on plants and animals are abundant, the study of how Chernobyl radiation levels affect prokaryotic and eukaryotic microbial communities is practically non-existent, except for a few reports on human pathogens or soil microorganisms. Environments enduring extreme desiccation and UV radiation, such as sunlight exposed biofilms could in principle select for organisms highly resistant to ionizing radiation as well. METHODOLOGY/PRINCIPAL FINDINGS: To test this hypothesis, we explored the diversity of microorganisms belonging to the three domains of life by cultivation-independent approaches in biofilms developing on concrete walls or pillars in the Chernobyl area exposed to different levels of radiation, and we compared them with a similar biofilm from a non-irradiated site in Northern Ireland. Actinobacteria, Alphaproteobacteria, Bacteroidetes, Acidobacteria and Deinococcales were the most consistently detected bacterial groups, whereas green algae (Chlorophyta) and ascomycete fungi (Ascomycota) dominated within the eukaryotes. Close relatives to the most radio-resistant organisms known, including Rubrobacter species, Deinococcales and melanized ascomycete fungi were always detected. The diversity of bacteria and eukaryotes found in the most highly irradiated samples was comparable to that of less irradiated Chernobyl sites and Northern Ireland. However, the study of mutation frequencies in non-coding ITS regions versus SSU rRNA genes in members of a same actinobacterial operational taxonomic unit (OTU) present in Chernobyl samples and Northern Ireland showed a positive correlation between increased radiation and mutation rates. CONCLUSIONS/SIGNIFICANCE: Our results show that biofilm microbial communities in the most irradiated samples are comparable to non-irradiated samples in terms of general diversity patterns, despite increased mutation levels at the single-OTU level. Therefore, biofilm communities growing in sunlight exposed substrates are capable of coping with increased mutation rates and appear pre-adapted to levels of ionizing radiation in Chernobyl due to their natural adaptation to periodical desiccation and ambient UV radiation