Safety of Lipid-Lowering Therapy with Statins according to a Regional Pharmacovigilance Centre

Scientific relevance. Since statins are widely used to prevent cardiovascular diseases, the control of statin-related complications is essential from both medical and social perspectives.Aim. The study aimed to analyse unsolicited reports on adverse drug reactions (ADRs) to control the safety of statin therapy.Materials and methods. The study analysed information on ADRs observed during statin treatment from the reporting forms submitted by medical organisations in Irkutsk to the database of the Regional Centre for Drug Safety Monitoring of the Irkutsk Region in 2011–2022. The causal relationship between ADRs and statin therapy was assessed using the Naranjo scale.Results. The database contained 1068 ADR reporting forms; 12 (1.1%) were spontaneous reports of statin-related complications, including 4 cases (33.4%) of myalgia, 7 cases (58.3%) of myalgia with moderately elevated transaminase levels (3–5 times the upper limit of normal), and 1 case of rhabdomyolysis that required statin discontinuation. In all cases, a reduction in the statin dose resulted in a regression in the clinical symptoms of ADRs. Most ADRs were observed in women with comorbidities (diabetes mellitus, obesity, and hypothyroidism), but the small sample size prevented the authors from testing the identified differences for statistical significance.Conclusions. According to the study results, statins have a reliable safety profile. Adequate and patient-specific selection of statin doses and ADR prevention are important responsibilities of clinical practitioners

Our experience of monitoring of drugs safety in gerontological practice

The analysis of work on identification and registration of complications of medicinal therapy in medical institutions of the Irkutsk region showed that the frequency of undesirable medicinal reactions at inpatients is more senior than 60 years makes from 10 % to 25 %. At advanced age the special place is taken by dysfunction of a digestive tract and allergic reactions at purpose of cardiovascular medicines, and also antibacterial and the antiglaucomous medicines. The number of cases of absence of therapeutic effect of PM in this age group made 18,9 %, reactions from the digestive tract - 15,5 % of cases, thus in 6,5 % pseudomembranous colitis was registered. It is established that risk factors of emergency of such reaction were the background pain or depressive syndrome, accompanying application of more than three drugs and absence of the scheme of a titration of dosages

MONITORING OF DRUG SAFETY IN CLINICAL PRACTICE

The results of work on identification and registration of complications of medicinal therapy in medical institutions of the Irkutsk region showed that that the frequency of undesirable medicinal reactions in patients made from 10 to 30 %. The standard scheme of antibacterial therapy results in resistance of pathogenetic flora. Hospital patients have great possibility of being infected with microorganisms, the so-called hospital strains (bacteria). The drug safety monitoring showed the necessity of the policing of prescribing of cardiovascular, antibacterial and antiglaucoma drugs

Analysis of Data on Adverse Drug Reactions and Functional Flaws of the Pharmacovigilance System Associated with Self-Treatment with Antibiotics

In the Russian Federation, a substantial proportion of the population (39.3–75.7%) opts for self-treatment. Self-administration of prescription medicinal products, particularly antibiotics, can lead to serious adverse drug reactions (ADRs). The safety of medicines in circulation relies upon the proper functioning of the pharmacovigilance system, both in general and in the case of self-medication ADRs.The aim of the study was to analyse data on the serious ADRs attributed to self-treatment with antibiotics and reported to the Regional Centre for Drug Safety Monitoring of the Irkutsk Region, as well as on the pharmacovigilance problems associated with self-treatment.Materials and methods: the study analysed the suspected ADR reporting forms from the database accumulated by the Regional Centre for Drug Safety Monitoring of the Irkutsk Region in 2011–2019. The inclusion criteria for the reporting forms were full completion and a Naranjo probability score categorising antibiotic–ADR causality at least as “possible”.Results: of the total 2325 reports in the database, 790 (34%) were on the ADRs associated with the use of antibiotics. Of these, 222 reported serious ADRs caused by self-medication. The largest number of ADRs (126) was recorded in patients aged 40–70 years; the proportion of women (60.32%) was significantly higher than the proportion of men (39.68%). Hospitalisation was required for 23 patients with serious adverse events. In 80% of the studied cases, patients justified the need for self-prescription of antibiotics with cough (which they regarded as acute bronchitis), but their presumptive diagnosis coincided with that established in the hospital only in 47.83% of the cases. The reports of ADRs during self-treatment with antibiotics were mainly received from hospitals (205 cases), and much less often from outpatient clinics and directly from patients (9 and 8 cases, respectively). There were no reports from pharmacy organisations; and it may be assumed that their employees did not take active part in reporting.Conclusions: the use of antibiotics for self-medication can lead to serious ADRs; therefore, the medicinal products of this class should be used only as directed by a doctor. To reduce the incidence of ADRs, it is necessary to raise awareness of the population and medical specialists conducting antibiotic therapy. The quality of medical care will benefit from proper performance of pharmacovigilance activities by all parties to the circulation of medicines, active involvement of patients in treatment safety monitoring, inclusion of specific sections on practical functioning of the pharmacovigilance system into the training curricula of pharmaceutical professionals, and creation of a feedback system connecting pharmacovigilance organisations to medical ones and other subjects of the circulation of medicines

The interchangeability of drugs from line items of pharmaceutical compliance and clinical efficiency and safety

Questions of replacement of original medicines with generic are discussed. The sintesation of identical medicine is a complex challenge from the technological point of view. It is caused by distinctions in production of substances, influence of the variable pharmaceutical factors giving change of the size of particles, a different amorphous forms, a deviation of structure and quantitative content of impurity. Auxiliary substantion characteristics of a production process of ready dosage forms matter. Data on pharmacokinetic equivalence of each generic to original are necessary. For carrying out pharmacotherapy original medicine which receive as a result of the researches executed under the regulated protocol needs data on comparative therapeutic efficiency and shipping the generic of drugs

Off-Label Prescribing in Paediatric Cardiology: Regulatory Aspects and Safety Assessment by Spontaneous Reporting

In paediatrics, it is a common practice to use pharmaceuticals outside the approved Summary of Product Characteristics (i.e. off-label). According to the literature, up to 45% of inpatient paediatric prescriptions and 10–20% of outpatient ones are for off-label uses. It is essential to analyse such uses, as it helps medical practitioners act reasonably and professionally.The aim of the study was to explore the possibility of using spontaneous reports to assess the risks of the off-label use of cardiac medicinal products in children in the Irkutsk region.Materials and methods. The authors analysed 25 reporting forms on adverse drug reactions (ADRs) in paediatric cardiac patients from the database of the Regional Centre for Drug Safety Monitoring of the Irkutsk Region and regional data from the Automated Information System (AIS) of the Federal Service for Surveillance in Healthcare of the Russian Federation (Roszdravnadzor) submitted in 2009–2020. The inclusion criterion for reporting forms was a causal relationship between the off-label use of a medicinal product and the ADR that was scored as “possible” or higher on the Naranjo probability scale.Results. According to the reporting forms, the off-label use of cardiac medicinal products in children was associated with ADRs, such as angiooedema, cutaneous symptoms, and bronchospasm. The majority of ADRs (84%) were considered severe. The medicinal products were prescribed for heart failure, arterial hypertension, and cardiac arrhythmias. The majority of ADR reports (75%) were submitted by inpatient medical organisations.Conclusions. The analysis of spontaneous ADR reporting databases is a simple and informative method for studying the safety of medicinal products. It is necessary to raise awareness of ADRs associated with off-label prescribing amongst paediatric cardiologists in order to reduce the incidence of ADRs. The following contributions will improve the quality of medical care: all parties involved with pharmaceuticals should adhere to good pharmacovigilance practices, medical practitioners should be actively involved in treatment safety monitoring, and the professional training curricula of paediatric cardiologists and paediatricians should include specific units on the practical functioning of pharmacovigilance

Clinical and pharmacological monitoring of drug safety in pediatrics

The 95 cases of adverse drug reactions in children were registered in the Centre of Drug Safety Monitoring of Irkutsk Region from 2009 to 2015. In 21.4 % of cases, the coexistent affections developed. Children were allergic three times more often than adults. In 14.7 % of cases severe allergic reactions were registered. Most often allergies occurred after taking immunotropic (62.2 %), antimicrobial (16.2 %) and nonsteroidal anti-inflammatory drugs (10.8 %). 10.5 % of cases concerned inefficient drug use in children under 3 years; and 36.8 % of cases concerned children aged 3 to 18 years. The following risk factors of inefficient antibiotic therapy in children with urinary system infections were determined: the duration of the disease up to 5 years, isolation of two or more infectious agents and concomitant infections of upper and lower urinary tract. Adverse drug reaction occurred more often when more than three drugs were prescribed at the same time. Such cases were generally registered in patients with infectious diseases and epilepsy. Risk of adverse reaction increased with the off-label drug use. Introduction of monitoring methods and prediction algorithms allowing to reveal with high probability and to prevent adverse drug reactions in children improved efficiency and quality of pharmacotherap

Новые препараты в лечении метастатического колоректального рака: обзор литературы

This article provides an overview of drugs for metastatic colorectal cancer that are currently being evaluated in clinical trials. We discuss possible drug combinations and outlooks of their use in different lines of therapy. In addition to VEGF and EGFR inhibitors, we describe the molecules with fundamentally new mechanisms of action that can significantly expand the list of anticancer agents and increase the number of possible lines of therapy.В статье представлен обзор препаратов для лечения метастатического колоректального рака, находящихся в фазе клинических исследований. Представлены данные о возможных комбинациях, перспективах использования в различных линиях терапии. Помимо новых вариантов ингибиторов VEGFи EGFRрассматриваются молекулы с принципиально новыми механизмами действия, которые могут значительно расширить арсенал лекарственного лечения и потенциально увеличить число возможных линий терапии

Fungal planet description sheets: 951–1041

Novel species of fungi described in this study include those from various countries as follows: Antarctica , Apenidiella antarctica from permafrost, Cladosporium fildesense fromanunidentifiedmarinesponge. Argentina , Geastrum wrightii onhumusinmixedforest. Australia , Golovinomyces glandulariae on Glandularia aristigera, Neoanungitea eucalyptorum on leaves of Eucalyptus grandis, Teratosphaeria corymbiicola on leaves of Corymbia ficifolia, Xylaria eucalypti on leaves of Eucalyptus radiata. Brazil, Bovista psammophila on soil, Fusarium awaxy on rotten stalks of Zea mays, Geastrum lanuginosum on leaf litter covered soil, Hermetothecium mikaniae-micranthae (incl. Hermetothecium gen. nov.)on Mikania micrantha, Penicillium reconvexovelosoi in soil, Stagonosporopsis vannaccii from pod of Glycine max. British Virgin Isles , Lactifluus guanensis onsoil. Canada , Sorocybe oblongispora on resin of Picea rubens. Chile, Colletotrichum roseum on leaves of Lapageria rosea. China, Setophoma caverna fromcarbonatiteinKarstcave. Colombia , Lareunionomyces eucalypticola on leaves of Eucalyptus grandis. Costa Rica, Psathyrella pivae onwood. Cyprus , Clavulina iris oncalcareoussubstrate. France , Chromosera ambigua and Clavulina iris var. occidentalis onsoil. French West Indies , Helminthosphaeria hispidissima ondeadwood. Guatemala , Talaromyces guatemalensis insoil. Malaysia , Neotracylla pini (incl. Tracyllales ord. nov. and Neotra- cylla gen. nov.)and Vermiculariopsiella pini on needles of Pinus tecunumanii. New Zealand, Neoconiothyrium viticola on stems of Vitis vinifera, Parafenestella pittospori on Pittosporum tenuifolium, Pilidium novae-zelandiae on Phoenix sp. Pakistan , Russula quercus-floribundae onforestfloor. Portugal , Trichoderma aestuarinum from salinewater. Russia , Pluteus liliputianus on fallen branch of deciduous tree, Pluteus spurius on decaying deciduouswoodorsoil. South Africa , Alloconiothyrium encephalarti, Phyllosticta encephalarticola and Neothyrostroma encephalarti (incl. Neothyrostroma gen. nov.)onleavesof Encephalartos sp., Chalara eucalypticola on leaf spots of Eucalyptus grandis × urophylla, Clypeosphaeria oleae on leaves of Olea capensis, Cylindrocladiella postalofficium on leaf litter of Sideroxylon inerme , Cylindromonium eugeniicola (incl. Cylindromonium gen. nov.)onleaflitterof Eugenia capensis , Cyphellophora goniomatis on leaves of Gonioma kamassi , Nothodactylaria nephrolepidis (incl. Nothodactylaria gen. nov. and Nothodactylariaceae fam. nov.)onleavesof Nephrolepis exaltata , Falcocladium eucalypti and Gyrothrix eucalypti on leaves of Eucalyptus sp., Gyrothrix oleae on leaves of Olea capensis subsp. macrocarpa , Harzia metro sideri on leaf litter of Metrosideros sp., Hippopotamyces phragmitis (incl. Hippopota- myces gen. nov.)onleavesof Phragmites australis , Lectera philenopterae on Philenoptera violacea , Leptosillia mayteni on leaves of Maytenus heterophylla , Lithohypha aloicola and Neoplatysporoides aloes on leaves of Aloe sp., Millesimomyces rhoicissi (incl. Millesimomyces gen. nov.) on leaves of Rhoicissus digitata , Neodevriesia strelitziicola on leaf litter of Strelitzia nicolai , Neokirramyces syzygii (incl. Neokirramyces gen. nov.)onleafspots o

The Gravitational Universe

The last century has seen enormous progress in our understanding of the Universe. We know the life cycles of stars, the structure of galaxies, the remnants of the big bang, and have a general understanding of how the Universe evolved. We have come remarkably far using electromagnetic radiation as our tool for observing the Universe. However, gravity is the engine behind many of the processes in the Universe, and much of its action is dark. Opening a gravitational window on the Universe will let us go further than any alternative. Gravity has its own messenger: Gravitational waves, ripples in the fabric of spacetime. They travel essentially undisturbed and let us peer deep into the formation of the first seed black holes, exploring redshifts as large as z ~ 20, prior to the epoch of cosmic re-ionisation. Exquisite and unprecedented measurements of black hole masses and spins will make it possible to trace the history of black holes across all stages of galaxy evolution, and at the same time constrain any deviation from the Kerr metric of General Relativity. eLISA will be the first ever mission to study the entire Universe with gravitational waves. eLISA is an all-sky monitor and will offer a wide view of a dynamic cosmos using gravitational waves as new and unique messengers to unveil The Gravitational Universe. It provides the closest ever view of the early processes at TeV energies, has guaranteed sources in the form of verification binaries in the Milky Way, and can probe the entire Universe, from its smallest scales around singularities and black holes, all the way to cosmological dimensions