Клініко-економічні аспекти фібратів

Today statins are considered as first-line drugs for treating dyslipidemia. Fibrates also have a place in the treatment of dyslipidemia. Taking the above into account it is relevant to highlight the evidence of the effectiveness of these drugs in reducing unfavorable outcomes of cardiovascular diseases (CVD) and feasibility of using them in the complex therapy of dyslipidemia, as well as the study of the pharmacoeconomic characteristics of fibrates presented at the Ukrainian pharmaceutical market. Aim. To analyze the clinical efficacy of fibrates in reducing the consequences of CVD, as well as to study the range, price characteristics, availability and consumption of fibrates at the Ukrainian pharmaceutical market from 2017 to 2019.Materials and methods. The analysis of the evidence of the clinical efficacy of fibrates in patients with CVD and dyslipidemia was performed in accordance to systematic reviews from the international Pubmed database. The retrospective analysis of the assortment, prices, affordability and consumption of fibrates in Ukraine was conducted according to the data from the “PharmXplorer” analytical system of the “Morion” information retrieval company and the Compendium system. The economic affordability was assessed by the value of adequacy of paying capacity (Ca.s.), the consumption volumes – by DDDs (the number of average daily doses) and the number of packages sold during 2017-2019.Results. The evidence of the clinical efficacy of fibrates in reducing cardiovascular events in patients with CVD and DM type 2 with dyslipidemia were summarized in systematic reviews. Within 2017-2019, only 3 trade names (TNs) of foreign fenofibrate, which prices did not fluctuate significantly, were registered at the Ukrainian pharmaceutical market. Fenofibrate drug – Lipofen NS (Nobel, Turkey), caps., 250 mg, blister No. 30, was highly available for the Ukrainian consumer (Ca.s. less than 5.0 %), and Traikor® (Abbot Products GmbH, Germany), film coated tablets, 145 mg, blister No. 20 and No. 30 (Ca.s. more than 5.0 %), were moderately available. The dynamics of the sales growth (2.4 times) of fenofibrate packages in 2019 compared to 2017 was determined due to the growth in sales of Traikor® (film coated tablets, 145 mg, blister No. 20). The dynamics of the increase in consumption of fibrates by the value of DDDs was found. It generally corresponded to the dynamics of sales in the number of packages, but the consumption volumes were insignificant.Conclusions. The use of fibrates in patients with CVD and dyslipidemia for the primary or secondary prevention of risks of adverse cardiovascular events leads to their decrease; moreover, in patients with DM type 2 it helps to reduce the risk of nonfatal myocardial infarction (MI) development. The consumption of fibrates at the Ukrainian pharmaceutical market is insignificant, and is determined by their clinical efficacy and the place in the antihyperlipidemic therapy of CVD where statins prevail today.На сегодня статины относятся к препаратам первой линии терапии дислипидемий. Фибраты также занимают определённое место в лечении дислипидемий. Учитывая вышеизложенное, актуальным является освещение доказательств эффективности этих препаратов в снижении неблагоприятных последствий сердечно-сосудистых заболеваний (ССЗ) и целесообразности их применения в комплексной терапии дислипидемий, а также изучение фармакоэкономических характеристик фибратов, представленных на фармацевтическом рынке Украины. Цель исследования – проанализировать клиническую эффективность фибратов в снижении последствий ССЗ и исследовать ассортимент, ценовую характеристику, доступность и потребление фибратов на фармацевтическом рынке Украины с 2017 по 2019 годы.Материалы и методы. Анализ доказательств клинической эффективности фибратов у больных ССЗ с дислипидемией был проведен по данным систематических обзоров, представленных в международной базе Pubmed. Ретроспективный анализ ассортимента, цен, экономической доступности и потребления фибратов в Украине был проведен по данным аналитической системы «PharmXplorer» информационно-поисковой компании «Морион» и системы Compendium. Оценка экономической доступности проведена по показателю адекватности платежеспособности (Са.s.), объемов потребления по показателю DDDs (количество средних суточных доз (DDD)) и по количеству реализованных упаковок в течение 2017-2019 гг.Результаты. Доказательства клинической эффективности фибратов в снижении неблагоприятных сердечно-сосудистых событий у больных с сердечно-сосудистыми заболеваниями и дислипидемией и у больных сахарным диабетом (СД) типа 2 обобщены в систематических обзорах. В течение 2017-2019 годов на фармацевтическом рынке Украины были зарегистрированы только 3 торговых наименования (ТН) фенофибрата зарубежного производства, цены на которые не подвергались существенным колебаниям. Препарат фенофибрата Липофен НС (Нобель, Турция) капс. 250 мг блистер № 30 является высокодоступным для украинского потребителя (Са.s. менее 5,0 %), а препарат Трайкор® 145 мг (Эббот Продактс ГмбХ, Германия) таб., покр. плен. обол., 145 мг блистер № 20 и № 30 (Са.s. более 5,0 %) – среднедоступным. Установлена динамика прироста объемов реализации (в 2,4 раза) упаковок фенофибрата в 2019 году по сравнению с 2017 годом за счет роста продаж препарата «Трайкор®» (таб., покр. пленоч. обол., 145 мг блистер № 20). Установлена динамика повышения потребления фибратов по показателю DDDs, что в целом соответствует динамике реализации в количестве упаковок, однако объемы потребления незначительны.Выводы. Применение фибратов у больных ССЗ с дислипидемией для первичной или вторичной профилактики рисков неблагоприятных сердечно-сосудистых событий сопровождается их уменьшением, а у больных СД типа 2 способствует снижению риска развития нефатального инфаркта миокарда (ИМ). Потребление фибратов на украинском фармацевтическом рынке является незначительным, что определено их клинической эффективностью и местом в антигиперлипидемической терапии ССЗ, где сегодня превалируют статины.На теперішній час статини входять до першої лінії терапії дисліпідемій. Фібрати також посідають певне місце в лікуванні дисліпідемій. З огляду на вищенаведене актуальним є висвітлення доказів ефективності цих препаратів щодо зниження несприятливих наслідків серцево-судинних захворювань (ССЗ) та доцільності застосування їх у комплексній терапії дисліпідемій, а також дослідження фармакоекономічних характеристик фібратів, представлених на фармацевтичному ринку України.Мета дослідження – проаналізувати клінічну ефективність фібратів щодо здатності знижувати наслідки серцево-судинних захворювань (ССЗ) та дослідити асортимент, цінову характеристику, доступність та споживання фібратів на фармацевтичному ринку України з 2017 по 2019 роки.Матеріали та методи. Аналіз доказів клінічної ефективності фібратів у хворих на ССЗ з дисліпідемією був проведений за даними систематичних оглядів, представлених у міжнародній базі Pubmed. Ретроспективний аналіз асортименту, цін, економічної доступності та споживання фібратів в Україні був проведений за даними аналітичної системи «PharmXplorer» інформаційно-пошукової компанії «Моріон» та системи Compendium. Оцінка економічної доступності проведена за показником адекватності платоспроможності (Са.s.), обсягів споживання за показником DDDs (кількість середніх добових доз (DDD)) та за кількістю реалізованих упаковок впродовж 2017-2019 рр.Результати. Докази клінічної ефективності фібратів щодо зменшення несприятливих серцево-судинних подій у хворих на ССЗ з дисліпідемією і у хворих на цукровий діабет (ЦД) типу 2 узагальнені в систематичних оглядах. Впродовж 2017-2019 рр. на фармацевтичному ринку України були зареєстровані лише 3 торгові назви (ТН) фенофібрату закордонного виробництва, ціни на які не зазнавали суттєвого коливання. Препарат фенофібрату Ліпофен СР (Нобель, Туреччина) капс. 250 мг блістер № 30 є високодоступним для українського споживача (Са.s. менше 5,0 %), а препарат Трайкор® 145 мг (Еббот Продактс ГмБх, Німеччина) таб. в/плівк. обол. 145 мг блістер № 20 та № 30 (Са.s. більше 5,0 %) – середньодоступним. Встановлена динаміка приросту обсягів реалізації (в 2,4 рази) упаковок фенофібрату в 2019 році порівняно з 2017 р. за рахунок зростання продажів препарату «Трайкор®» (таб. в/плівк. обол. 145 мг блістер № 20). Встановлена динаміка підвищення споживання фібратів за показником DDDs, що загалом відповідає динаміці реалізації в кількості упаковок, проте обсяги споживання є незначними.Висновки. Застосування фібратів у хворих на ССЗ з дисліпідемією для первинної або вторинної профілактики ризиків несприятливих серцево-судинних подій супроводжується їх зменшенням, а у хворих на ЦД типу 2 сприяє зниженню ризику розвитку нефатального інфаркту міокарда (ІМ). Споживання фібратів на українському фармацевтичному ринку є незначним, що визначено їх клінічною ефективністю та місцем в антигіперліпідемічній терапії ССЗ, де сьогодні превалюють статини

Variable strength of forest stand attributes and weather conditions on the questing activity of Ixodes ricinus ticks over years in managed forests

Given the ever-increasing human impact through land use and climate change on the environment, we crucially need to achieve a better understanding of those factors that influence the questing activity of ixodid ticks, a major disease-transmitting vector in temperate forests. We investigated variation in the relative questing nymph densities of Ixodes ricinus in differently managed forest types for three years (2008–2010) in SW Germany by drag sampling. We used a hierarchical Bayesian modeling approach to examine the relative effects of habitat and weather and to consider possible nested structures of habitat and climate forces. The questing activity of nymphs was considerably larger in young forest successional stages of thicket compared with pole wood and timber stages. Questing nymph density increased markedly with milder winter temperatures. Generally, the relative strength of the various environmental forces on questing nymph density differed across years. In particular, winter temperature had a negative effect on tick activity across sites in 2008 in contrast to the overall effect of temperature across years. Our results suggest that forest management practices have important impacts on questing nymph density. Variable weather conditions, however, might override the effects of forest management practices on the fluctuations and dynamics of tick populations and activity over years, in particular, the preceding winter temperatures. Therefore, robust predictions and the detection of possible interactions and nested structures of habitat and climate forces can only be quantified through the collection of long-term data. Such data are particularly important with regard to future scenarios of forest management and climate warming

Rights and obligations of regulators, drug manufacturers, doctors, pharmacists, patients, and insurance companies in the case of off label use of medicinal products

For many years, the off-label use of drugs has been a debated issue for healthcare administrators, regulators, pharmaceutical manufacturers, doctors, pharmacists, insurance companies, and patients. The mechanism for monitoring and regulating the off-label use of drugs must have sound scientific evidence and principles that provide for discouraging their use in the absence of convincing and evidence-based clinical justification and the availability of alternatives. Regulatory authorities (FDA and others) are very strict about manufacturing standards and documentation of the safety and efficacy of drugs, but they do not regulate the way they are prescribed. Thus, doctors can prescribe drugs off-label if their medical knowledge and the patient's condition allow it. The decision to use the drug off -label is not illegal if the doctor does not abuse his official position and does not violate the rules for its prescription

Sexually Selected Infanticide in a Polygynous Bat

Background: Adult individuals of many species kill unrelated conspecific infants for several adaptive reasons ranging from predation or resource competition to the prevention of misdirected parental care. Moreover, infanticide can increase the reproductive success of the aggressor by killing the offspring of competitors and thereafter mating with the victimized females. This sexually selected infanticide predominantly occurs in polygynous species, with convincing evidence for primates, carnivores, equids, and rodents. Evidence for bats was predicted but lacking. Methodology/Principal Findings: Here we report the first case, to our knowledge, of sexually selected infanticide in a bat, the polygynous white-throated round-eared bat, Lophostoma silvicolum. Behavioral studies in a free-living population revealed that an adult male repeatedly attacked and injured the pups of two females belonging to his harem, ultimately causing the death of one pup. The infanticidal male subsequently mated with the mother of the victimized pup and this copulation occurred earlier than any other in his harem. Conclusions/Significance: Our findings indicate that sexually selected infanticide is more widespread than previously thought, adding bats as a new taxon performing this strategy. Future work on other bats, especially polygynous species in the tropics, has great potential to investigate the selective pressures influencing the evolution of sexually selecte

What a Plant Sounds Like: The Statistics of Vegetation Echoes as Received by Echolocating Bats

A critical step on the way to understanding a sensory system is the analysis of the input it receives. In this work we examine the statistics of natural complex echoes, focusing on vegetation echoes. Vegetation echoes constitute a major part of the sensory world of more than 800 species of echolocating bats and play an important role in several of their daily tasks. Our statistical analysis is based on a large collection of plant echoes acquired by a biomimetic sonar system. We explore the relation between the physical world (the structure of the plant) and the characteristics of its echo. Finally, we complete the story by analyzing the effect of the sensory processing of both the echolocation and the auditory systems on the echoes and interpret them in the light of information maximization. The echoes of all different plant species we examined share a surprisingly robust pattern that was also reproduced by a simple Poisson model of the spatial reflector arrangement. The fine differences observed between the echoes of different plant species can be explained by the spatial characteristics of the plants. The bat's emitted signal enhances the most informative spatial frequency range where the species-specific information is large. The auditory system filtering affects the echoes in a similar way, thus enhancing the most informative spatial frequency range even more. These findings suggest how the bat's sensory system could have evolved to deal with complex natural echoes

Two Novel Parvoviruses in Frugivorous New and Old World Bats

Bats, a globally distributed group of mammals with high ecological importance, are increasingly recognized as natural reservoir hosts for viral agents of significance to human and animal health. In the present study, we evaluated pools of blood samples obtained from two phylogenetically distant bat families, in particular from flying foxes (Pteropodidae), Eidolon helvum in West Africa, and from two species of New World leaf-nosed fruit bats (Phyllostomidae), Artibeus jamaicensis and Artibeus lituratus in Central America. A sequence-independent virus discovery technique (VIDISCA) was used in combination with high throughput sequencing to detect two novel parvoviruses: a PARV4-like virus named Eh-BtPV-1 in Eidolon helvum from Ghana and the first member of a putative new genus in Artibeus jamaicensis from Panama (Aj-BtPV-1). Those viruses were circulating in the corresponding bat colony at rates of 7–8%. Aj-BtPV-1 was also found in Artibeus lituratus (5.5%). Both viruses were detected in the blood of infected animals at high concentrations: up to 10E8 and to 10E10 copies/ml for Aj-BtPV-1 and Eh-BtPV-1 respectively. Eh-BtPV-1 was additionally detected in all organs collected from bats (brain, lungs, liver, spleen, kidneys and intestine) and spleen and kidneys were identified as the most likely sites where viral replication takes place. Our study shows that bat parvoviruses share common ancestors with known parvoviruses of humans and livestock. We also provide evidence that a variety of Parvovirinae are able to cause active infection in bats and that they are widely distributed in these animals with different geographic origin, ecologies and climatic ranges

Differential responses to woodland character and landscape context by cryptic bats in urban environments

© 2015 Lintott et al. Urbanisation is one of the most dramatic forms of land use change which relatively few species can adapt to. Determining how and why species respond differently to urban habitats is important in predicting future biodiversity loss as urban areas rapidly expand. Understanding how morphological or behavioural traits can influence species adaptability to the built environment may enable us to improve the effectiveness of conservation efforts. Although many bat species are able to exploit human resources, bat species richness generally declines with increasing urbanisation and there is considerable variation in the responses of different bat species to urbanisation. Here, we use acoustic recordings from two cryptic, and largely sympatric European bat species to assess differential responses in their use of fragmented urban woodland and the surrounding urban matrix. There was a high probability of P. pygmaeus activity relative to P. pipistrellus in woodlands with low clutter and understory cover which were surrounded by low levels of built environment. Additionally, the probability of recording P. pygmaeus relative to P. pipistrellus was considerably higher in urban woodland interior or edge habitat in contrast to urban grey or non-wooded green space. These results show differential habitat use occurring between two morphologically similar species; whilst the underlying mechanism for this partitioning is unknown it may be driven by competition avoidance over foraging resources. Their differing response to urbanisation indicates the difficulties involved when attempting to assess how adaptable a species is to urbanisation for conservation purposes

A Systems Biology Approach Identifies Molecular Networks Defining Skeletal Muscle Abnormalities in Chronic Obstructive Pulmonary Disease

Chronic Obstructive Pulmonary Disease (COPD) is an inflammatory process of the lung inducing persistent airflow limitation. Extensive systemic effects, such as skeletal muscle dysfunction, often characterize these patients and severely limit life expectancy. Despite considerable research efforts, the molecular basis of muscle degeneration in COPD is still a matter of intense debate. In this study, we have applied a network biology approach to model the relationship between muscle molecular and physiological response to training and systemic inflammatory mediators. Our model shows that failure to co-ordinately activate expression of several tissue remodelling and bioenergetics pathways is a specific landmark of COPD diseased muscles. Our findings also suggest that this phenomenon may be linked to an abnormal expression of a number of histone modifiers, which we discovered correlate with oxygen utilization. These observations raised the interesting possibility that cell hypoxia may be a key factor driving skeletal muscle degeneration in COPD patients

Consequences of a large-scale fragmentation experiment for Neotropical bats : disentangling the relative importance of local and landscape-scale effects

Context Habitat loss, fragmentation and degradation are widespread drivers of biodiversity decline. Understanding how habitat quality interacts with landscape context, and how they jointly affect species in human-modified landscapes, is of great importance for informing conservation and management. Objectives We used a whole-ecosystem manipulation experiment in the Brazilian Amazon to investigate the relative roles of local and landscape attributes in affecting bat assemblages at an interior-edge-matrix disturbance gradient. Methods We surveyed bats in 39 sites, comprising continuous forest (CF), fragments, forest edges and intervening secondary regrowth. For each site, we assessed vegetation structure (local-scale variable) and, for five focal scales, quantified habitat amount and four landscape configuration metrics. Results Smaller fragments, edges and regrowth sites had fewer species and higher levels of dominance than CF. Regardless of the landscape scale analysed, species richness and evenness were mostly related to the amount of forest cover. Vegetation structure and configurational metrics were important predictors of abundance, whereby the magnitude and direction of response to configurational metrics were scale-dependent. Responses were ensemble-specific with local-scale vegetation structure being more important for frugivorous than for gleaning animalivorous bats. Conclusions Our study indicates that scale-sensitive measures of landscape structure are needed for a more comprehensive understanding of the effects of fragmentation on tropical biota. Although forest fragments and regrowth habitats can be of conservation significance for tropical bats our results further emphasize that primary forest is of irreplaceable value, underlining that their conservation can only be achieved by the preservation of large expanses of pristine habitat