Cost-effectiveness analysis of tocilizumab in combination with methotrexate for rheumatoid arthritis: A Markov model based on data from Serbia, country in socioeconomic transition

Background/Aim. Recent studies have shown that biological treatments for rheumatoid arthritis can change the course of rheumatoid arthritis and improve functional ability of patients with rheumatoid arthritis. In spite of this fact, use of biological therapy is still limited by high prices of these medicines, especially in countries in socioeconomic transition. The aim of our study was to compare costeffectiveness of a combination of tocilizumab and methotrexate with methotrexate alone for rheumatoid arthritis in Serbia, a country in socioeconomic transition. Methods. For the purpose of our study we designed a Markov model using data on therapy efficacy from the available literature, and data on the costs of health states calculated from records of actual patients treated in the Clinical Center Kragujevac, Serbia. The duration of one cycle in our model was set at one month, and the time horizon was 480 months (40 years). The study was done from the social perspective, and all the costs and outcomes were discounted for 3% per year. Results. Treating rheumatoid arthritis with diseasemodifying antirheumatic drugs (DMARDs) alone was more cost-effective in comparison with a combination of biologic treatment with tocilizumab and DMARDs. The total costs for treating a patient with DMARDs for one year were on average 261,945.42 RSD, or 2,497.70 Euro and the total costs for treatment with tocilizimab plus DMARDs were on average 1,959,217.44 RSD, or 18,659.20 Euro. However, these results are susceptible to changes in costs and treatment effects of tocilizumab in patients with more severe forms of rheumatoid arthritis. Conclusion. Our results show that the use of tocilizumab for rheumatoid arthrits in economic environment of Serbia is not cost-effective. Use of tocilizumab for treating rheumatoid arthritis can become affordable, if costs of its use become lower. In order to start using expensive biologic medicines in patients in transitional countries, special strategy and pricing policy of international pharmaceutical companies are necessary, which would include calculation of prices of biologic medicines on the basis of local pharmacoeconomic studies

Chemical composition and antimicrobial activity of the essential oil from Satureja horvatii Šilić (Lamiaceae)

The present paper describes the chemical composition and antimicrobial activity of the essential oil of the endemic species Satureja horvatii Šilić, collected in Montenegro. The essential oil was obtained from the aerial parts of the plant by hydrodistillation and analyzed by GC–MS. From the 34 compounds representing 100 % of the oil, the major compound was the phenolic monoterpene thymol (63.37 %). The oil contained smaller amounts of g-terpinene (7.49 %), carvacrol methyl ether (4.92 %), carvacrol (4.67 %), p-cymene (4.52%), a-terpinene (1.81 %), borneol (1.58 %), a-thujene (1.56 %), b-caryophyllene (1.55 %) and b-myrcene (1.44 %). The antimicrobial activity of the essential oil of S. horvatii was evaluated using the agar diffusion and broth microdilution methods. The essential oil exhibited antimicrobial activity to varying degrees against all the tested strains. The maximum activity of S. horvatii oil was observed against Gram-positive bacteria (Micrococcus luteus, Staphylococcus epidermidis, Staphylococcus aureus and Enterococcus faecalis) and against the yeast (Candida albicans). The oil exhibited moderate activity against the Gram-negative bacteria Escherichia coli and Klebsiella pneumoniae and weak activity against Pseudomonas aeruginosa. This study confirms that the essential oil of S. horvatii possesses antimicrobial activities in vitro against medically important pathogens

A commentary on the inhibition of human TPC2 channel by the natural flavonoid naringenin: methods, experiments, and ideas

: Human endo-lysosomes possess a class of proteins called TPC channels on their membrane, which are essential for proper cell functioning. This protein family can be functionally studied by expressing them in plant vacuoles. Inhibition of hTPC activity by naringenin, one of the main flavonoids present in the human diet, has the potential to be beneficial in severe human diseases such as solid tumor development, melanoma, and viral infections. We attempted to identify the molecular basis of the interaction between hTPC2 and naringenin, using ensemble docking on molecular dynamics (MD) trajectories, but the specific binding site remains elusive, posing a challenge that could potentially be addressed in the future by increased computational power in MD and the combined use of microscopy techniques such as cryo-EM

Opis przypadku — występujący rodzinnie wewnątrzczaszkowo germinoma

Background. Intracranial germinomas (ICG) are uncommon brain neoplasms with extremely rare familial occurance. Since ICG invades hypothalamus and/or pituitary, the endocrine dysfunction is one of the common determinants of these tumors. We presented two brothers with the history of ICG. Patient 1 is a 25-year-old male who had been suffering from the weakness of the right half of his body at the age of 18. Cranial MRI revealed mass lesion in the left thalamus. He underwent neurosurgery, tumor was removed completely. Histopathological (HP) and immunohistochemical analyses verified the diagnosis of pure germinoma. He experienced complete remission of the tumor after a radiation therapy. At the age of 22 the diagnosis of isolated growth hormone deficiency (IGHD) was established and GH replacement was initiated. Patient 2 is a 20-year old boy who was presented with diabetes insipidus at the age of 12. MRI detected tumor in the third ventricle and pineal region. After the endoscopic tumor biopsy the HP diagnosis was pure germinoma. He received chemotherapy followed by radiotherapy, and treated with GH during childhood. At the age of 18 GH replacement was reintroduced. A six month follow-up during the next two years in both brothers demonstrated the IGF1 normalization with no MRI signs of tumor recurrence. Conclusion. To the best of our knowledge so far, only six reports have been published related to familial ICG. The presented two brothers are the first report of familial ICG case outside of Japan. They are treated successfully with GH therapy in adult period. Wstęp: Rozrodczaki wewnątrzczaszkowe (intracranial germinomas, ICG) to rzadkie nowotwory mózgu, a szczególnie rzadko stwierdza się ich występowanie rodzinne. W związku z tym, że ICG zajmuje podwzgórze i/lub przysadkę mózgową, zaburzenia endokrynologiczne są jednym z najczęstszych wyznaczników obecności tych guzów. W pracy przedstawiono dwóch braci z ICG. Pacjent 1 to 25-letni mężczyzna, u którego w wieku 18 lat wystąpiło osłabienie mięśni po lewej stronie ciała. Badanie metodą rezonansu magnetycznego (MRI) czaszki ujawniło masę w lewym wzgórzu. Chorego poddano zabiegowi neurochirurgicznemu, podczas którego guz został całkowicie usunięty. Badania histopatologiczne i immunohistochemiczne potwierdziły rozpoznanie czystej postaci rozrodczaka. Po radioterapii nastąpiła całkowita remisja guza. W wieku 22 lat u chorego zdia­gnozowano izolowany niedobór hormonu wzrostu (isolated growth hormone deficiency, IGHD) i wdrożono terapię zastępczą hormonem wzrostu (growth hormone, GH). Genetyczna analiza molekularna tkanki guza wykazała mutację w eksonie 2 w genie KRAS. Pacjent 2 to 20-letni mężczyzna, u którego w wieku 12 lat stwierdzono moczówkę prostą. W badaniu MRI wykryto guz w okolicy trzeciej komory i szyszynki. Po ocenie histopatologicznej materiału pobranego za pomocą biopsji endoskopowej postawiono diagnozę czystego rozrod­czaka. U chorego zastosowano chemioterapię, a następnie radioterapię, a także podawano GH w okresie dzieciństwa. W wieku 18 lat u chorego wznowiono terapię GH. Sześciomiesięczna obserwacja obu braci w następnych 2 latach wykazała normalizację IGF1 przy braku objawów nawrotu guza w badaniu MRI. Wnioski: Według najlepszej wiedzy autorów dotychczas opublikowano 6 doniesień na temat rodzinnego występowania ICG. Przed­stawieni w niniejszej pracy bracia są pierwszym opisanym przypadkiem rodzinnego ICG poza Japonią. W okresie dorosłym chorzy są leczeni GH z dobrym skutkiem

Addressing the inter-individual variation in response to consumption of plant food bioactives : Towards a better understanding of their role in healthy aging and cardiometabolic risk reduction

Bioactive compounds in plant-based foods have health properties that contribute to the prevention of age-related chronic diseases, particularly cardiometabolic disorders. Conclusive proof and understanding of these benefits in humans is essential in order to provide effective dietary recommendations but, so far, the evidence obtained from human intervention trials is limited and contradictory. This is partly due to differences between individuals in the absorption, distribution, metabolism and excretion of bioactive compounds, as well as to heterogeneity in their biological response regarding cardiometabolic health outcomes. Identifying the main factors underlying inter-individual differences, as well as developing new and innovative methodologies to account for such variability constitute an overarching goal to ultimately optimize the beneficial health effects of plant food bioactives for each and every one of us. In this respect, this position paper from the COST Action FA1403-POSITIVe examines the main factors likely to affect the individual responses to consumption of plant food bioactives and presents perspectives for assessment and consideration of inter-individual variability.Peer reviewe

Management of anaphylaxis due to COVID-19 vaccines in the elderly

Older adults, especially men and/or those with diabetes, hypertension, and/or obesity, are prone to severe COVID-19. In some countries, older adults, particularly those residing in nursing homes, have been prioritized to receive COVID-19 vaccines due to high risk of death. In very rare instances, the COVID-19 vaccines can induce anaphylaxis, and the management of anaphylaxis in older people should be considered carefully. An ARIA-EAACI-EuGMS (Allergic Rhinitis and its Impact on Asthma, European Academy of Allergy and Clinical Immunology, and European Geriatric Medicine Society) Working Group has proposed some recommendations for older adults receiving the COVID-19 vaccines. Anaphylaxis to COVID-19 vaccines is extremely rare (from 1 per 100,000 to 5 per million injections). Symptoms are similar in younger and older adults but they tend to be more severe in the older patients. Adrenaline is the mainstay treatment and should be readily available. A flowchart is proposed to manage anaphylaxis in the older patients.Peer reviewe

ARIA digital anamorphosis : Digital transformation of health and care in airway diseases from research to practice

Digital anamorphosis is used to define a distorted image of health and care that may be viewed correctly using digital tools and strategies. MASK digital anamorphosis represents the process used by MASK to develop the digital transformation of health and care in rhinitis. It strengthens the ARIA change management strategy in the prevention and management of airway disease. The MASK strategy is based on validated digital tools. Using the MASK digital tool and the CARAT online enhanced clinical framework, solutions for practical steps of digital enhancement of care are proposed.Peer reviewe

Cabbage and fermented vegetables : From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT(1)R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT(1)R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.Peer reviewe

Nrf2-interacting nutrients and COVID-19 : time for research to develop adaptation strategies

There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPAR gamma:Peroxisome proliferator-activated receptor, NF kappa B: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2 alpha:Elongation initiation factor 2 alpha). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT(1)R axis (AT(1)R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity

ARIA digital anamorphosis: Digital transformation of health and care in airway diseases from research to practice

Digital anamorphosis is used to define a distorted image of health and care that may be viewed correctly using digital tools and strategies. MASK digital anamorphosis represents the process used by MASK to develop the digital transformation of health and care in rhinitis. It strengthens the ARIA change management strategy in the prevention and management of airway disease. The MASK strategy is based on validated digital tools. Using the MASK digital tool and the CARAT online enhanced clinical framework, solutions for practical steps of digital enhancement of care are proposed