Use Of Therapeutic Drugs Research Articles

Insight into core -shell microporous zinc silicate adsorbent to eliminate antibiotics in aquatic environment under the COVID-19 pandemic

Under the new crown pneumonia (COVID-19) epidemic, the intensive use of therapeutic drugs has caused certain hidden danger to the safety of the water environment. Therefore, the core-shell microporous zinc silicate (SiO2@ZSO) was successfully prepared and used for the adsorption of chloroquine phosphate (CQ), tetracycline (TC) and ciprofloxacin (CIP) for eliminating the threat of COVID-19. The adsorption efficiencies of 20 mg L−1 of CQ, TC and CIP by SiO2@ZSO were all up to 60% after 5 min. The adsorption capacity of SiO2@ZSO for CQ, TC and CIP can reach 49.01 mg g−1, 56.06 mg g−1 and 104.77 mg g−1, respectively. The adsorption process is primarily physical adsorption, which is heterogeneous, spontaneous and preferential. Moreover, the effects of temperature, pH, salinity, and reusability on the adsorption of CQ, TC, and CIP on SiO2@ZSO were investigated. The adsorption mechanism mainly involves electrostatic attraction, partitioning and hydrogen bonding, which is insightful through the changes of the elements and functional groups before and after adsorption. This work provides a solution to the problems faced by the treatment of pharmaceuticals wastewater under the COVID-19 epidemic.

Therapeutic Use and Chronic Abuse of CNS Stimulants and Anabolic Drugs.

The available evidence suggests that affective disorders, such as depression and anxiety, increase risk for accelerated cognitive decline and late-life dementia in aging individuals. Behavioral neuropsychology studies also showed that cognitive decline is a central feature of aging impacting the quality of life. Motor deficits are common after traumatic brain injuries and stroke, affect subjective well-being, and are linked with reduced quality of life. Currently, restorative therapies that target the brain directly to restore cognitive and motor tasks in aging and disease are available. However, the very same drugs used for therapeutic purposes are employed by athletes as stimulants either to increase performance for fame and financial rewards or as recreational drugs. Unfortunately, most of these drugs have severe side effects and pose a serious threat to the health of athletes. The use of performance-enhancing drugs by children and teenagers has increased tremendously due to the decrease in the age of players in competitive sports and the availability of various stimulants in many forms and shapes. Thus, doping may cause serious health-threatening conditions including, infertility, subdural hematomas, liver and kidney dysfunction, peripheral edema, cardiac hypertrophy, myocardial ischemia, thrombosis, and cardiovascular disease. In this review, we focus on the impact of doping on psychopathological disorders, cognition, and depression. Occasionally, we also refer to chronic use of therapeutic drugs to increase physical performance and highlight the underlying mechanisms. We conclude that raising awareness on the health risks of doping in sport for all shall promote an increased awareness for healthy lifestyles across all generations.

A Tribute to the Pioneers of Fetal Pharmacology.

Clinical pharmacology is a branch of the field of pharmacology that evolved following the recognition that the nature, duration, and intensity of drug action depend on both the intrinsic properties of the drug and an interaction with the host to whom the drug is given. Advances in drug development have placed highly specific and extremely potent therapeutic agents in the marketplace. While these advances have progressed rapidly in adult medicine, pediatric clinical pharmacology has not kept pace and until very recently has lagged behind the research and attention paid to the proper use of therapeutic and diagnostic drugs in adults. Recognition that advances in the science of developmental pharmacology and pediatric clinical pharmacology were essential in the development of new drugs to treat children came in the 1950s and 1960s mostly through the work of 2 pioneering scientists in fetal and perinatal clinical pharmacology, Drs Sumner Yaffe and Bernard Mirkin. Here we pay a tribute to these most influential pioneers in the United States who were instrumental in paving the path for advancing the field of fetal and perinatal pharmacology concepts and their incorporation into pediatric drug development programs.

PBPK modelling to predict drug-biologic interactions with cytokine modulators: Are these relevant and is IL-6 enough?

Drugs that modulate cytokine levels are often used for the treatment of cancer as well as inflammatory or immunological disorders. Pharmacokinetic drug-biologic interactions (DBI) may arise from suppression or elevation of cytochrome P450 (CYP) enzymes caused by the increase or decrease in cytokine levels following administration of these therapies. There is in vitro and in vivo evidence that demonstrates a clear link between raised interleukin (IL)-6 levels and CYP suppression, in particular CYP3A4. However despite this, the changes in IL-6 levels in vivo rarely lead to significant drug interactions (AUC and Cmax ratios < 2-fold). The clinical significance of such interactions therefore remains questionable and is dependent on the therapeutic index of the small molecule therapy. Physiologically-based pharmacokinetic (PBPK) modelling has been used successfully to predict the impact of raised IL-6 on CYP activities. Beyond IL-6, published data show little evidence that IL-8, IL-10, and IL-17 suppress CYP enzymes. I n vitro data suggest that IL-1β, IL-2, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ can cause suppression of CYP enzymes. Despite in vivo there being a link between IL-6 levels and CYP suppression, the evidence to support a direct effect of IL-2, IL-8, IL-10, IL-17, IFN-γ, TNF-α or vascular endothelial growth factor (VEGF) on CYP activity is inconclusive. This commentary will discuss the relevance of such drug-biologic interactions and whether current PBPK models considering only IL-6 are sufficient. Significance Statement This commentary summarizes the current in vitro and in vivo literature regarding cytokine-mediated CYP suppression and compares the relative suppressive potential of different cytokines in reference to IL-6. It also discusses the relevance of drug-biologic interactions to therapeutic use of small molecule drugs and whether current PBPK models considering only IL-6 are sufficient to predict the extent of drug-biologic interactions.

Therapeutic Drug Monitoring as a Tool for Therapy Optimization.

The use of pharmacotherapy for improving healthcare in society is increasing. A vast majority of patients have either received subtherapeutic treatment (which could result from low pharmacokinetic) or experienced adverse effects due to the toxic levels of the drug. The medicines used to treat chronic conditions, such as epilepsy; cardiovascular diseases; and oncological, neurological, and psychiatric disorders, require routine monitoring. New targeted therapies suggest an individualized treatment that can slowly move practitioners away from the concept of a one-size-fits-all-fixed-dosing approach. Therapeutic drug use can be monitored based on pharmacokinetic, pharmacodynamic, and pharmacometric methods. Based on the experiences of therapeutic drug monitoring of various agents across the globe, we can look ahead to the possible developments of therapeutic drug monitoring in India.

Nanocrystals: An Approachable Delivery System for Anticancer Therapeutics.

Cancer accounts for the high mortality rate and limits the life expectancy of an individual. As per the WHO report of 2020, cancer accounts for >10 million deaths globally. Scientists are continuously pitching toward the development of novel techniques to combat this menace and enhance the efficacy of prevailing molecules. In the early phases of the drug development process, >40% of promising new therapeutic molecules are hydrophobic. Low aqueous solubility results in compromised bioavailability on administration. This limitation is a major drawback for the therapeutic use of anticancer drugs. Drug nanocrystals (NCs) have sparked a lot of interest in drug delivery. This might be due to their excellent physicochemical characteristics like tailored dissolution, high drug loading efficiency, extended circulation period, and high structural stability. There are 'n' a number of the characteristics that make drug nanocrystals a promising formulation for the treatment of cancer. In the last few years, many hydrophobic or lipophilic drugs like camptothecin, paclitaxel, cyclosporin, busulfan, and thymectacin have been formulated as drug nanocrystals against anticancer therapeutics. Various formulation technologies have been developed in conjunction with nanocrystal development. This includes top-down approaches, bottom-up approaches, as well as combination technology. In this article, we will focus on the various manufacturing processes, biological fate and therapeutic applications of NCs, and future perspectives in the management of cancer.

Multifunctional Gel Films of Marine Polysaccharides Cross-Linked with Poly-Metal Ions for Wound Healing.

The development of an efficient and convenient material to improve skin tissue regeneration is a major challenge in healthcare. Inspired by the theory of moist wound healing, portable chitooligosaccharide (COS)/sodium alginate (SA) dual-net gel films containing multiple metal ions were prepared by a casting and in-situ spray method, which can be used to significantly promote wound healing without the use of therapeutic drugs. A variety of divalent cations was introduced in this experiment to improve the advantages of each metal ion by forming metal ion chelates with COS. Moreover, the physicochemical properties and antioxidant properties of nIon2+-COS/SA gel films were systematically characterized and evaluated by in vitro experiments. The gel films showed good antibacterial activity against Gram-negative and Gram-positive bacteria. In addition, the gel films showed good cytocompatibility in cellular experiments, and the gel films with Zn2+ and Sr2+ addition significantly accelerated wound healing in whole skin defect model experiments. Therefore, this nIon2+-COS/SA gel film is an ideal candidate material for wound dressing.

Citrus maxima and tea regulate AMPK signaling pathway to retard the progress of nonalcoholic fatty liver disease.

BackgroundNonalcoholic fatty liver disease (NAFLD) is a chronic metabolic disease that easily induces hepatitis, cirrhosis, and even liver cancer. The long-term use of NAFLD therapeutic drugs produces toxicity and drug resistance. Therefore, it is necessary to develop high efficiency and low-toxicity active ingredients to alleviate NAFLD.ObjectiveThis study aimed to reveal the role and mechanism of a new functional food CMT in alleviating NAFLD.ResultsIn the ob/ob fatty liver mice models, the CMT extracts significantly inhibited the weight gain of the mice and reduced the accumulation of white fat. The anatomical and pathological results showed that CMT relieved fatty liver in mice and reduced excessive lipid deposition and inflammatory infiltration. Serological and liver biochemical indicators suggest that CMT reduced dyslipidemia and liver damage caused by fatty liver. CMT obviously activated the adenosine 5′-monophosphate-activated protein kinase (AMPK)/acetyl-coA carboxylase (ACC) and AMPK/fatty acid synthase (FAS) signaling pathways, promoted fat oxidation, and inhibited synthesis. Moreover, CMT regulated the expression of inflammatory factors to relieve hepatitis caused by NAFLD.ConclusionThe study explained the role and mechanism of CMT in alleviating NAFLD and suggested that the active ingredients of CMT might be beneficial in NAFLD therapy.

Increased Demand for Therapeutic Drugs in Pediatric Ulcerative Colitis Patients With Extraintestinal Manifestations.

BackgroundUlcerative colitis (UC) is a systemic inflammatory disease with a gut predominance, which may involve other organs. The presence of extraintestinal manifestation (EIM) is an important symptom for clinicians as it alters the treatment decisions. In this study, we aimed to evaluate the initial clinical presentation and disease severity of pediatric UC patients with EIMs.MethodsOne hundred forty-two patients under the age of 18 years who were diagnosed with UC from January 2003 to November 2021 were included in this study. Forty-seven patients with confirmed EIMs and 95 patients without EIMs were divided into two groups and their differences were analyzed.ResultsThe most common EIM was peripheral arthritis. The disease extent at the time of diagnosis shows a higher rate of pancolitis in the EIM-positive group (65.9%) than that of the EIM-negative group (33.7%) (p < 0.001). More than 90% of EIM-positive patients had moderate to severe disease activity on the Mayo endoscopic subscore. In the EIM-positive group, the cumulative use of systemic steroids, immunosuppressants, and biological agents from diagnosis to 1 year follow-up were significantly higher than those of the EIM-negative group (p = 0.009, 0.001, and < 0.001, respectively). About 80% of patients in the EIM-negative group reached remission, but only about 50% of the EIM-positive patients reached remission (p = 0.005). The relapse occurred more frequently in the EIM-positive group than in the EIM-negative group with statistical significance (p < 0.001).ConclusionPediatric UC with EIMs had higher disease severity and often manifested upper gastrointestinal tract involvement. Despite EIMs treatment, the occurrence of new EIMs was observed repeatedly. Cumulative drug demand (steroids, immunosuppressants, and biological agents) for the treatment increased steadily over time, and frequent relapses occurred despite the combinatory use of therapeutic drugs.

АНАЛИЗ ЭФФЕКТИВНОСТИ ПРИМЕНЕНИЯ ЛЕЧЕБНО-ПРОФИЛАКТИЧЕСКИХ СРЕДСТВ У ПАЦИЕНТОВ С ЛАБОРАТОРНО ПОДТВЕРЖДЕННЫМ ДИАГНОЗОМ SARS-COV-2

To date, there is a limited amount of literature that describes the use of oral therapeutic and prophylactic drugs in patients with a confirmed diagnosis of SARS-CoV-2. Therefore, this topic is relevant. Thus, the purpose of this study was to study the effectiveness of the use of therapeutic and prophylactic agents in patients with a laboratory-confirmed diagnosis of mild to moderate SARS-CoV-2, with or without concomitant oral co-infection.&#x0D; The data of the conducted study will constitute an important stage in the algorithm of specialized therapy.&#x0D; Materials and methods. A comparative analysis of the use of therapeutic and prophylactic agents for the oral cavity in patients with a confirmed diagnosis of SARS-CoV-2 was carried out. The conclusions are based on the results of a clinical study that compared the effectiveness of the use of therapeutic and prophylactic agents in 90 patients aged 20 to 87 years with mild to moderate Sars-CoV-2 with oral co-infection and 15 patients aged from 20 to 87 years of age with mild to moderate Sars-CoV-2 without coinfection.&#x0D; Results. During the study, the following results were obtained. The most effective drug was a solution of aqueous chlorhexidine 0.5%, but there was a side effect in the form of xerostomia. The Miramistin solution also had high efficiency, and the lowest efficiency was observed when using the Rotokan solution.&#x0D; Conclusions. The data of the conducted study will constitute an important stage in the algorithm of specialized therapy.

Potential to Use Fingerprints for Monitoring Therapeutic Levels of Isoniazid and Treatment Adherence

A fingerprint offers a convenient, noninvasive sampling matrix for monitoring therapeutic drug use. However, a barrier to widespread adoption of fingerprint sampling is the fact that the sample volume is uncontrolled. Fingerprint samples (n = 140) were collected from patients receiving the antibiotic isoniazid as part of their treatment, as well as from a drug-naive control group (n = 50). The fingerprint samples were analyzed for isoniazid (INH) and acetylisoniazid (AcINH), using liquid chromatography high-resolution mass spectrometry. The data set was analyzed retrospectively for metabolites known to be present in eccrine sweat. INH or AcINH was detected in 89% of the fingerprints collected from patients and in 0% of the fingerprints collected from the control group. Metabolites lysine, ornithine, pyroglutamic acid, and taurine were concurrently detected alongside INH/AcINH and were used to determine whether the fingerprint sample was sufficient for testing. Given a sufficient sample volume, the fingerprint test for INH use has sensitivity, specificity, and accuracy of 100%. Normalization to taurine was found to reduce intradonor variability. Fingerprints are a novel and noninvasive approach to monitor INH therapy. Metabolites can be used as internal markers to demonstrate a sufficient sample volume for testing and reduce intradonor variability.

Current Understanding of Alzheimer's Disease on Biomarkers, Magnetic Resonance Imaging Modalities, and Diagnosis, Prevention, and Treatment Approach

Alzheimer's disease (AD), a neurodegenerative disorder in which Activities of Daily Living (ADL) are hampered and steep decline in gross cognitive function is observed, in the early stage of life. AD is characterized by progressive loss and damage to the structure and/or function of neuronal cell, resulting in death of neurons, however, etiology and pathophysiology of the disease are not known in its entirety. The purpose of this article is to understand, analyze, evaluate, and synthesize information in order to provide conclusive, decisive, and actionable information on (1) microscopic features and known etiology, pathophysiology, genes involved, and protein misfolding observed in AD; (2) selection and use of prominent magnetic resonance imaging (MRI) modalities and allied biomarkers to detect and diagnose AD by application of AI techniques; (3) role of preventive intervention (diet and lifestyle) in reducing risk of developing AD, to act on modifiable and correctable risk factors of AD, to manage AD and treatment strategies of AD through the use of pharmacology and therapeutic drugs. Deep learning-based techniques have proven capabilities to learn features automatically to discriminate class effectively. We proposed a method that incorporates features (biomarkers) derived from the structural MRI modality, clinical assessment tools, and personal and demographic quantifiable parameters into a convolution neural network. and further boosted the ensemble-based learning algorithm to improve prediction accuracy. An ensemble-based learning algorithm is then used to integrate weights to improve prediction accuracy.

Анаплеротичні принципи нутритивної терапії в клініці критичних станів

У статті надані сучасні анаплеротичні концепції нутритивної терапії для модуляції метаболічної відповіді в клініці критичних станів. Метаболічний стрес — універсальна гіперметаболічна гіперкатаболічна відповідь на захворювання, травму з активацією гіпоталамо-гіпофізарно-адреналової системи; виділенням гормонів стресу; катехоламінів; нейропептиду S; фактора, індукованого гіпоксією HIF-1α; експресією генів, що контролюють механізми адаптації до гіпоксії, у тому числі гліколіз і цикл трикарбонових кислот. У статті наведена розроблена нами модель визначення метаболічного стресу і мітохондріальної дисфункції. Анаплеротична терапія базується на концепції використання альтернативних субстратів як для циклу трикарбонових кислот, так і для транспорту електронів у дихальному ланцюзі з метою посилення продукції аденозинтрифосфату. Багато патологічних станів вимагають проведення анаплеротичної терапії або шляхом поповнення пулу анаплеротичних субстратів (піруват, аспартат, аспарагінат та інші джерела, поповнюючи оксалоацетат, глутамін та інші кислоти), або видаленням з тканин продуктів катаплеротичних реакцій — інтермедіатів циклу трикарбонових кислот. Катаплероз врівноважує анаплероз шляхом переміщення надлишку інтермедіаторів циклу трикарбонових кислот з мітохондріального матриксу в цитоплазму, в екстрамітохондріальний простір. Сучасні анаплеротичні концепції для модуляції метаболічної відповіді при критичних станах включають в себе такі позиції: I. Раннє використання розчинів глюкози та інтенсивна інсулінотерапія: мінімальна кількість вуглеводів близько 2 г/кг глюкози/добу; введення інсуліну, якщо два послідовних аналізи показали рівень глюкози &gt; 10 ммоль/л; уникати обов’язкового повноцінного калорійного харчування в перший тиждень, починати з 500 ккал/добу. II. Попередження гіперглікемічного метаболічного стресу — метаболічне прекондиціювання: вживання прозорих рідин припиняється за 2 години до індукції в анестезію, споживання щільної їжі — за 6 годин. Передопераційне призначення вуглеводів застосовується у всіх пацієнтів без цукрового діабету за 2 години до індукції; при наявності протипоказань — в/в інфузія глюкози за 2 години до операції. III. Використання енергосубстратів, що не потребують інсулінової стимуляції для їх входження до клітини: виявлено, що особи, які одержували &lt; 60 г фруктози на добу, мали кращі показники здоров’я, ніж ті, які споживали &gt; 100 г/добу. IV. Амінокислотні суміші: якщо парентеральне харчування показано, доцільно призначати збалансовані амінокислотні суміші, з розрахунку 1,3–1,5 г/кг/добу білка; 0,2–0,4 г/кг/добу L-глутаміну. При тяжких опіках режим введення білка в амінокислотних сумішах зростає до 1,5–2 г/кг/добу. V. Поповнення пулу анаплеротичних жирних кислот: жирові емульсії (LCT, MCT) повинні призначатися в кількості 0,7–1,5 г/кг/добу; ентерально призначається суміш соєвої і оливкової олій, риб’ячий жир, що містять омега-3, -6, -9 жирні кислоти; дієтична анаплеротична терапія з тригептаноїном підвищує виживаність пацієнтів у критичних станах. VI. Використання інтермедіатів циклу Кребса: превентивне або терапевтичне використання сукцинатвмісних препаратів може бути ефективним для активації ургентних адаптивних механізмів. Тіамін є найважливішим вітаміном для підтримки аеробного метаболізму й активності ключових ферментів циклу Кребса, а також чолночного механізму пентозофосфатного циклу.

&lt;i&gt;In vitro&lt;/i&gt; antiviral activity of VIFERON® rectal suppositories against SARS-CoV-2

In 2020–2021, the world was engulfed by the pandemic of a new coronavirus infection (COVID-19) caused by the SARS-CoV-2 virus. The low population coverage with vaccination against COVID-19 and the lack of herd immunity result in the need to find an effective and safe etiotropic treatment. Medicinal agents for treatment of COVID-19, approved while preparing this publication, have several limitations related to the conditions of their use and/or population category. In this situation, interferon-containing drugs widely used in Russia and the CIS for prevention and treatment of viral infectious diseases, i.e. ARVI and influenza, may hold promise. This study aims to confirm in vitro antiviral activity against SARS-CoV-2 for the preparation VIFERON® containing recombinant human interferon alpha-2b (IFNα-2b). Materials and methods. Vero CCL-81 cells were infected with hCoV-19/StPetersburg-RII3524VR4/2020 strain of SARS-CoV-2 at doses of 10 TCID50 or 100 TCID50 per well. The suppressive effect of IFN-2b, extracted from VIFERON® in dosage form of rectal suppositories, was evaluated by qRT-PCR at 24 h and 48 h after the infection of cells in two schemes, simulating preventive (24 h before infection) and therapeutic (2 h after infection) use of drugs. Results. IFNα-2b at concentrations of 800, 400, 200, 100 and 50 IU/ml, extracted from rectal suppositories of VIFERON®, showed high biological activity, displayed as inhibition of SARS-CoV-2 strain replication in both infectious doses evaluated either at 24 h or at 48 h after cell infection. The “preventive” vs. “therapeutic” scheme was found to be more effective. In the “preventive” scheme the virus titre decreased by more than 3 lg TCID50 at 24 hours post-infection and by 5–6 lg TCID50 at 48 hours post-infection after administration of 800 IU/ml IFNα-2b. Conclusion. The study results evidence that VIFERON® in dosage form of rectal suppositories may be promising for prevention and treatment of new coronavirus infection in clinical practice.

New Insights and Potential Therapeutic Targeting of CB2 Cannabinoid Receptors in CNS Disorders.

The endocannabinoid system (ECS) is ubiquitous in most human tissues, and involved in the regulation of mental health. Consequently, its dysregulation is associated with neuropsychiatric and neurodegenerative disorders. Together, the ECS and the expanded endocannabinoidome (eCBome) are composed of genes coding for CB1 and CB2 cannabinoid receptors (CB1R, CB2R), endocannabinoids (eCBs), and the metabolic enzyme machinery for their synthesis and catabolism. The activation of CB1R is associated with adverse effects on the central nervous system (CNS), which has limited the therapeutic use of drugs that bind this receptor. The discovery of the functional neuronal CB2R raised new possibilities for the potential and safe targeting of the ECS for the treatment of CNS disorders. Previous studies were not able to detect CB2R mRNA transcripts in brain tissue and suggested that CB2Rs were absent in the brain and were considered peripheral receptors. Studies done on the role of CB2Rs as a potential therapeutic target for treating different disorders revealed the important putative role of CB2Rs in certain CNS disorders, which requires further clinical validation. This review addresses recent advances on the role of CB2Rs in neuropsychiatric and neurodegenerative disorders, including, but not limited to, anxiety, depression, schizophrenia, Parkinson’s disease (PD), Alzheimer’s disease (AD), Huntington’s disease (HD) and addiction.

Drug utilization study in patients affected with COVID-19 in a dedicated COVID hospital

Background: There exists a treatment dilemma regarding the optimal and effective use of therapeutic drugs (hydroxychloroquine/chloroquine/azithromycin) for COVID-19. Furthermore, with changing guidelines, the data on drug utilization patterns across India are limited. Hence, this study was conducted to assess the prescription pattern and drug utilization trends in COVID-19 patients with the aim to study the drug utilization pattern in patients affected with COVID-19 in a dedicated COVID-19 hospital. Aims and Objectives: The objectives of the study are as follows: (1) To study drug utilization patterns according to the severity of the disease. (2) To study the prevalence of adverse drug reactions (ADRs). Materials and Methods: Data were collected retrospectively from 100 medical records of patients ≥18 years irrespective of sex admitted in the COVID ward and ICU of a dedicated COVID hospital from May to August 2020. Pregnant and lactating women were excluded from the study. ADRs reported were also analyzed. Results: About 71% were mild in this study, 18% were moderate, and 11% were severe COVID-19 patients. Overall, the most common drugs prescribed were multivitamins, followed by pantoprazole, paracetamol, and azithromycin. Hydroxychloroquine was prescribed in 22%, favipiravir in 7%, and remdesivir in 3% of cases. The majority of moderate COVID patients received injectables piperacillin-tazobactam, methylprednisolone, and enoxaparin. The mean number of medications, duration of admission, and number of days on oxygen were higher and significant in moderate compared to mild and severe COVID patients. Overall, ADRs were encountered in 9% of cases. Conclusion: The prescribed pattern of drugs was by the national standard guidelines. Multivitamins, followed by pantoprazole, paracetamol, and azithromycin dominated the prescription pattern. Polypharmacy was encountered, which needs to be addressed for the rational use of drugs.

Psychiatric management of Patients in intensive care units.

Psychiatric management of Patients in intensive care units.

Factors affecting the occurrence of gastrointestinal parasites and lungworm in dogs and assessment of antiparasitic drug use patterns

Dogs are hosts of parasites with different pathogenicities and zoonotic risks. The aim of our study was to assess factors that could affect the occurrence of endoparasitic infections in dogs using questionnaires for owners and examining canine faeces. Based on the responses of dog owners, we evaluated ways of the preventive and therapeutic use of antiparasitic drugs. One faecal sample was obtained from each dog (391 samples total), and then examined by flotation, larvoscopic, and polymerase chain reaction (PCR) methods. We focused on zoonotic tapeworms Echinococcus multilocularis and Taenia crassiceps. The answers in the dog owners’ questionnaires showed that owners most often dewormed their dogs irregularly (96.4%), namely, twice a year (24.3%). In coprological examinations the following parasites were detected: Giardia spp., Cystoisospora ohioensis complex, Neospora caninum/Hammondia heydorni, Toxocara canis, Toxascaris leonina, Capillaria spp., Trichuris spp., Angiostrongylus vasorum, Crenosoma vulpis, Ancylostoma spp. and Taenia spp. A total of 4 out of 391 PCR investigated samples of faeces were positive for DNA of Taenia species. Sequences were obtained for 3 of them, confirming 100% identity with T. crassiceps. The zoonotic helminths Toxocara canis were the more prevalent species (9.3%, 4.3%, 1.9% group A, B, C). We consider the presence of T. crassiceps in 3 dog faecal samples to be serious due to its zoonotic potential. Data collected within this study showed that the prevention against endoparasites carried out at the breeders’ discretion is insufficient to ensure the health of their dogs or to cover the risk of zoonotic transmission.

Uncountered Effects of Immunomodulators

Certain shortcomings of clinical immunology at the present time are discussed, which leads to a reduction in the therapeutic use of immunomodulatory drugs, even despite their often high clinical effect and the imperfection of methods for specific target immunodiagnostics. Moreover, it is significant that their effect on the immune system is nonspecific. The non-immune systemic action of immunomodulators on various body systems is not taken into account. New methods for assessing the immune response are considered, which are not detected when using "stencil" methods.

Revisiting the Term "Compassionate Use" and Leadership of the World Health Organization in Resolving Confusion in the Age of COVID-19 and Beyond.

We discuss the term "compassionate use" (CU) as an example of terminology having a huge impact on drug regulation. CU is used in many confusing situations, and its meaning varies significantly. We ethically affirm the necessity of CU. We insist that CU should be properly placed in exceptional status. The regulation of CUs is much more lenient than that of clinical trials because of the difference in the purpose. Whether consciously or unconsciously, abuse results in confusion and is never acceptable. The World Health Organization (WHO) proposed not to use the previous term CU but to replace it with another one. WHO also proposed the term MEURI (monitored emergency use of unregistered and experimental interventions). However, this was extremely incomplete, and WHO used the term CU subsequently. The main purpose of the proposal needs to be thoroughly implemented. In the context of the COVID-19 pandemic and beyond, expectations regarding WHO's role and leadership in global health issues are rising. We hope that WHO will play a major role in promoting research ethics preparedness while discontinuing the use of confusing terms such as CU and will develop alternative terms and their content. We discuss the evaluation of MEURI, the Japanese version of CU, and appropriate and inappropriate terminology related to the therapeutic use of unapproved drugs. We also discuss the expected appearance of CU including its name. It is appropriate to target group/cohort patients and unapproved drugs in the late stage of development. It is also important to solve the problem of incentives for CUs of pharmaceutical companies that are rushing to obtain marketing approval. The UK's Early Access to Medicine Scheme has provided many suggestions. We believe that our opinion can contribute to WHO's efforts to resolve the confusion and promote research ethics preparedness in health emergencies.