Administration Scheme Research Articles

First-Line Biologic Therapy and Obesity in Moderate-to-Severe Psoriasis: Results from the Prospective Multicenter Cohort Psobioteq

Background: Obesity is associated with an increased risk of psoriasis. Objective: In this study, we examined whether body mass index (BMI) is taken into account when choosing first-line biologic therapy for psoriasis. Methods: In this cohort study, we compared obese (BMI ≥30 kg/m²) and non-obese patients for the first-line biologic therapy prescribed, its survival, reasons for discontinuation, therapy optimization, co-prescription of methotrexate and factors associated with long drug survival. Results: A total of 931 patients were included: 594 (64%) were male, median age was 46 years (interquartile range 36–56). The most-prescribed biologic agents as first-line treatment were adalimumab (ADA; 42.7%), ustekinumab (UST; 29.9%) and etanercept (ETA; 22.9%); only frequency of infliximab (IFX) prescription differed between groups. Drug survival was significantly shorter for obese than non-obese patients (p < 2.10^–4) and was worse for obese than non-obese patients for UST (p = 0.009) and ETA (p = 0.02), with no difference for ADA (p = 0.11). The main reason for discontinuation was primary inefficacy (62%), which was more frequent in obese than non-obese patients. The cumulative incidence of optimization did not significantly differ between the groups, except for ADA (SHR 1.91, 95% CI [1.23–2.96], p = 0.005). On multivariate analysis, risk of discontinuation was associated with only ETA as first-line biologic therapy (HR 1.51, 95% CI 1.04–2.19). Conclusion: This study highlighted the lack of difference in prescription of first-line biologic treatment, except for IFX, between obese and non-obese patients presenting moderate-to-severe psoriasis. Drug survival in obese patients is shorter, mainly because of inefficacy, than in non-obese patients. This highlights the need for targeted pharmacological studies in obese individuals to find optimal administration schemes.

Clinical Efficacy Analysis of Conbercept Intravitreal Injection for Fundus Diseases Based on Computer Simulation

Fundus diseases can seriously damage the visual acuity of patients, including age-related macular degeneration (ARMD), retinal choroidal neovascularization (CNV), retinal vein occlusion (RVO), central serous chorioretinopathy (CSC), diabetic retinopathy (DR), etc. At the same time, fundus disease generally has a long course, high severity, long-term delay, high recurrence rate, and as long as the patients do not receive timely treatment or do not receive the correct treatment, there will be a variety of complications, causing serious damage to the structure of the patient’s eyes and the patient’s visual function. Clinical trial simulation (CTS) is a newly emerging interdisciplinary subject in recent years. With the increasing cost in the process of new drug development, computer simulation technology has attracted extensive attention of pharmaceutical enterprises. Clinical treatment of fundus diseases includes hormone therapy, etiological treatment, vitrectomy, laser treatment, etc, But the effect is different. This study mainly analyzes the effect of intravitreal injection of conbercept in the treatment of fundus diseases. Based on the analysis and research of CTS research at home and abroad, aiming at the relationship between dosage, blood concentration and efficacy, the change of blood concentration under different dosage was analyzed, and the influence on drug effect under different administration scheme was predicted. Main work: establishment of simulation model (including proportional advantage model, pharmacokinetics / pharmacodynamics model), simulation calculation, model simulation and result analysis.

Replication‐aware secure resource administration scheme for Internet of Things‐smart city applications

AbstractThe distributed and heterogeneous nature of the Internet of Things (IoT) paradigm provides backhauled support for different smart‐city applications. As it provides ubiquitous access to resources and replicated services, the threat for security remains firm for different applications. The concept of cybersecurity in the IoT‐smart‐city combination grants promising outcomes in securing the physical and service‐centric resources from external threats. This article proposes to improve the protection of the IoT services in smart‐city applications using replication‐aware secure resource administration scheme framework. In a smart city application, which involves a cloud, based network, IoT platform, and distributed sensor networks guarantees differentiated protection mechanisms for replicated and non‐replicated infrastructure. Instantly revocable security activities are used to prevent unintended attacks to the original resource supplier from monitoring non‐replicated services. For this purpose, Naïve Bayes' diffusion approach is used to continuously evaluate the likelihood of disclosure of the repeated and unreplicated properties. The hazard and level of exposure for which prompted protection is assessed using the recommendations of the delivery system. The promptness of the security outcome is based on re‐formulating permission delegations, security checks, and so on. This helps to leverage the security level of the available resources irrespective of the impact of the external threats. Besides, the proposed scheme improves the lifetime of the services with controlled overhead and service failures.

Effects of different doses of levosimendan combined with Shenmai injection on immune function and galectin-3 and HSP70 levels in rats with acute heart failure

To investigate the effects of different doses of levosimendan combined with Shenmai injection on immune function and galectin-3 and heat shock protein 70 (HSP70) levels in rats with acute heart failure. Forty eight specific-pathogen free Sprague Dawley male rats were selected and divided into 6 groups according to different administration schemes after the heart failure model was established. The left ventricular end diastolic diameter (LVEDD) and left ventricular ejection fraction (LVEF) of rats in each group were observed before and after treatment. After treatment, rats in groups A–D and the model group (MG) showed decreased LVEDDs compared with the control group (CG), and group D showed the highest reduction. In contrast, rats in groups A–D and the MG showed increased LVEFs compared with the CG, and group D showed the highest increase. The MG and groups A–D rats showed an increased percent of CD3+ T cells and CD4+/CD8+ T cell ratio compared with the CG. Levosimendan combined with Shenmai injection optimized the maintenance of immune and cardiac function in rats with acute heart failure compared with Shenmai injection alone. The higher dose of levosimendan combined with Shenmai injection improved the inflammatory reaction and levels of galectin-3 and HSP70.

Optimal treatment strategies to control acute HIV infection.

Various antiretroviral therapies (ART) are administered to symptomatic human immunodeficiency virus (HIV) infected individuals to improve their health. The treatment effectiveness may depend on suppressing development of drug resistance, reduce evolution of new viral strains, minimize serious side effects and the costs of drugs. This paper deals with some results concerning optimal drug administration scheme successful in improving patients' health especially in poorly resourced settings. The model under consideration describes the interaction between the uninfected cells, the latently infected cells, the productively infected cells, and the free viruses. Generally, in viral infection, the drug strategy aspects either the virus infectivity or reduce the virion production. The mathematical model proposed here, deals with both situations with the objective function based on a combination of maximizing benefit relied on T cells count (the white cells that coordinate activities of the immune system) and minimizing the systemic cost. The existence of the optimal control pair is established and the Pontryagin's minimum principle is used to characterize these two optimal controls. The optimality system is derived and solved numerically using the forward and backward sweep method (FBSM). Our results indicate that early initiation of treatment makes a profound impact in both improving the quality of life and reducing the economic costs of therapy.

Stimuli-responsive nanocarriers for therapeutic applications in cancer.

Cancer has become a very serious challenge with aging of the human population. Advances in nanotechnology have provided new perspectives in the treatment of cancer. Through the combination of nanotechnology and therapeutics, nanomedicine has been successfully used to treat cancer in recent years. In terms of nanomedicine, nanocarriers play a key role in delivering therapeutic agents, reducing severe side effects, simplifying the administration scheme, and improving therapeutic efficacies. Modulations of the structure and function of nanocarriers for improved therapeutic efficacy in cancer have attracted increasing attention in recent years. Stimuli-responsive nanocarriers penetrate deeply into tissues and respond to external or internal stimuli by releasing the therapeutic agent for cancer therapy. Notably, stimuli-responsive nanocarriers reduce the severe side effects of therapeutic agents, when compared with systemic chemotherapy, and achieve controlled drug release at tumor sites. Therefore, the development of stimuli-responsive nanocarriers plays a crucial role in drug delivery for cancer therapy. This article focuses on the development of nanomaterials with stimuli-responsive properties for use as nanocarriers, in the last few decades. These nanocarriers are more effective at delivering the therapeutic agent under the control of external or internal stimuli. Furthermore, nanocarriers with theranostic features have been designed and fabricated to confirm their great potential in achieving effective treatment of cancer, which will provide us with better choices for cancer therapy.

Premedication practices for less invasive surfactant administration — results from a nationwide cohort study

Background and aims There are no established premedication schemes for less invasive surfactant administration (LISA) in neonatal RDS. The aim was to describe "real-world" practices and to assess the safety of premedication and its impact on the technical ease of the LISA procedure. Methods Data from the prospective LISA cohort study conducted in 31 tertiary neonatal units were evaluated for premedication practices. Infants who received analgesics and/or sedatives before LISA and those receiving non-pharmacological sedation with sublingual 30% glucose were compared versus nonpremedicated neonates, acting as a reference. Safety of premedication was assessed with the rate of adverse events during LISA, changes in oxygenation status, the need for rescue intubation, and mechanical ventilation in the first 24 h of life. Ease of conducting LISA was an efficacy endpoint. Results Of 500 enrolled newborns, 102 (20.4%) received premedication for LISA; 88 infants were given analgesics/sedatives and 14 sublingual glucose. Pharmacological sedation was most often performed with ketamine (51/88; 57.9%), midazolam (16/88; 18.2%) and propofol (8/88; 1.6%). Compared to non-premedication, the use of analgesics/sedatives was associated with a significant increase in the rate of apnea (9.1 vs 2.6%; p = 0.009) and a significantly higher decrease in SpO2/FiO2 (−55 ± 62 vs −32 ± 50; p < 0.001). However, the rates of rescue intubation and the need for early mechanical ventilation were not significantly different. Sedation with glucose did not affect the frequency of adverse events. LISA procedures had a similar level of ease regardless of the premedication used and were rated as easy or very easy in 69% of non-premedicated infants, 65.9% of the analgesics/sedatives group and 78.5% of the glucose group (p = ns). Conclusion Analgesics/sedatives prior to LISA increased the rate of apnea and decreased blood oxygenation but did not lead to tracheal intubation and early mechanical ventilation. Trials addressing the impact on LISA-related stress are necessary to determine the ultimate usefulness of premedication.

Hair as a matrix in monitoring drug epilepsy therapy.

Hair is considered an efficient tool to investigate drug-related histories; thus, the selection of the method of sample preparation is important to obtain a reliable result. The aim of this study was to compare two methods of hair preparation (cutting and pulverizing) to analyse levetiracetam concentration in hair. An additional aim was to evaluate the potential usefulness of the levetiracetam concentration measured as an index of a dosing schedule. Four groups of 12 rats were included in the experiment. Depending on the group, the rats received 10mg/kg of levetiracetam intraperitoneally every 24, 48 and 72hours for 30days. The control group was not treated. At the end of the drug administration, the rats' hair was shaved, cut or pulverized and analysed by the LC/MS-MS method to determine the concentration of levetiracetam. A stronger correlation between the mean hair levetiracetam concentration in hair and the number of drug doses was found in pulverized hair than in cut hair. A smaller standard deviation between the results was obtained in the case of pulverized hair. The results indicate that pulverization gives a more reliable result of drug concentration in hair than cutting and that drug concentration in hair can reflect the scheme of levetiracetam administration.

PCN145 Economic Effects of Different Administration Scheme of Pembrolizumab in Advanced or Adjuvant Melanoma

This study aimed to evaluate the economic effect of new administration management of pembrolizumab for the treatment of advanced or adjuvant melanoma in Italy. The analysis was developed considering two subsequent methodological steps: a) unit costs estimation for administration of innovative oncological drugs (drug, nurse time, physician time and preparation costs) and b) time consumption for each administration of pembrolizumab, nivolumab or ipilimumab in Italy. These data were derived from a literature review of the Italian legislation and reimbursement scheme for the Italian National Health System (NHS) while the estimated time for each administration were derived from a survey that was sent to the ten main Italian centres for the treatment of metastatic or adjuvant melanoma. Finally, the economic impact was estimated considering a standardized 1,000 patients treated with the new administration scheme with pembrolizumab every six weeks vs standard scheme administration of pembrolizumab, nivolumab and ipilimumab for a time horizon of 6 weeks. the preliminary results demonstrate that the pembrolizumab Q6W scheme could generate a cost savings of € 1.2, € 2.2 and 3.0 million for 1,000 patients if compared with pembrolizumab Q3W, nivolumab and ipilimumab respectively. On average, 40% of these cost reductions were associated with adjuvant treatment patients. The ability to reduce the admissions for drug administration in hospital due to a new therapeutic scheme of pembrolizumab, could generate and efficient management of the oncological ambulatory reducing the number of patients that have to come in hospital.

Використання персоналізованої схеми введення фентанілу під час стентування коронарних артерій

The aim – to develop a personalized scheme of fentanyl administrationfor coronary artery stenting. Materials and methods. Ninety patients with ischemic heart disease who underwent planned stenting of the coronary arteries were studied. The patients who underwent surgery were evenly divided into three study groups, depending on mode of the intraoperative analgesic sedation and the approaches to anesthesia. The first comparison group consisted of patients who received slow intravenous administration of diazepam and fentanyl solutions. The second comparison group consisted of patients with balanced administration of fentanyl and propofol solutions to provide analgesic sedation at the level of conscious anesthesia. The study group consisted of patients with a personalized approach to the administration of opiates, namely, we used the original fentanyl test described in the article. Analgesic sedation at the level of conscious anesthesia (ІІІ by Ramsey) was maintained by propofol infusion. Results. The usage of a personalized scheme of fentanyl administration for stenting of the coronary arteries, compared to the standard sedation using combination of diazepam and fentanyl, was accompanied by better indicators of intraoperative blood saturation with oxygen and carbon dioxide (respectively (103.67 ± 22.05) and (39.64 ± 6.85) mm Hg in group 1, (105.70 ± 31.64) and (37.68 ± 7.11) in group 2 and (109.42 ± 34.36) and (36.25 ± 6.52) mm Hg in patients of the 3rd group), lower blood pressure after surgery ((127.85 ± 9.87)/(79.64 ± 8.62) mm Hg in patients of group 1, (129.48 ± 8.73)/(81.05 ± 7.92) mm Hg in group 2 and (131.15 ± 10.64)/(82.68 ± 9.72) mm Hg in group 3), lower level of stress markers (blood cortisol during surgery in patients of the 1st group (8.83 ± 4.58) mmol/L, in patients of the 2nd group – (7.73 ± 2.79) mmol/L, in patients of the 3rd group – (7.55 ± 4.35) mmol/L), as well as lower frequency of detecting episodes of perioperative pain of various origins. Conclusions. A method of personalized anesthesia was elaborated, based on individual scheme of fentanyl administration («fentanyl test») during coronary artery stenting. Its usage is safe (due to the optimal parameters of gas exchange and hemodynamics and fewer side effects, such as nausea and residual sedation) and effective (due to the lower level of stress markers and less frequent complaints of pain of various origins) than when the routine technique was used. Key words: analgesic sedation, individual sensitivity, fentanyl, diazepam, propofol.

Effect of a complex prebiotic preparation on the preservation, growth intensity and microflora in rabbits intestine

We presented the effect of prebiotic "Bio-active" on preservation, increase of the body weight, the microflora composition in the distal small intestine, histological examination of the intestinal wall and liver of rabbits gray giant breed 45 days aged. Prebiotic "Bio-active" contains products of metabolism of lactic acid bacteria Lactobacillus bulgaricus delbrueckii adsorbed on zeolite. Our results proved the safety of this prebiotic for the rabbits. Optimal scheme for oral administration of the prebiotic was 2.0 g per 1 kg of body weight for 30 days. Such a course provided 95% of animal preservation and increase in the weight gain of the experimental animals, an average of 43.1% compared with the non-treated rabbits. In scarifies of distal intestine in 20% of animals that received the prebiotic and in 100% of those who did not receive it, Bacteria of Proteus genus have been detected. After the course of prebiotic we registered an increased number of Enterobacteriaceae (4.5–6.0 × 108 CFU) and Bifidobacteria (8 × 107–108 CFU) in rabbits’ intestines. We also mentioned the enhanced gram-positive/gram-negative ratio with a predominance of gram-positive (1:1.17 against 1:2.9 in control group). In case of prebiotic usage, the stimulation of goblet cells’ development was determined in the small intestine walls. Almost 100% of rabbits, who did not receive the prebiotic, had dystrophic changes in hepatocytes (74.5 % of the animals had fatty hepato-dystrophy and 25 % had protein granular dystrophy). We registered that only 25% of the animals had fatty hepato-dystrophy and 15% had protein granular dystrophy among those, which received the preparation.

The Analysis of Scientific Data on the Efficacy of Pneumococcal Conjugated Vaccine in the Cohort of Children with Bronchial Asthma

This article refutes one popular-science review that has appeared on the MDedge news site in January 2020. It has stated that there was no effect of vaccination with 7-valent pneumococcal conjugate vaccine (PCV-7) against invasive forms of Streptococcus pneumoniae in children with bronchial asthma. The author of this publication refers to the article «Asthma and the Risk of Invasive Pneumococcal Disease: A Meta-analysis» that described episodes of invasive pneumococcal disease and pneumonia development in children with bronchial asthma and in healthy children who was vaccinated with pneumococcal conjugate vaccine. It was concluded that the PCV-7 provides limited protection against colonization only with vaccine pneumococcus serotypes (according to the obtained data), and, thus, there was high risk of carriage of non-included serotypes in children with bronchial asthma (BA). The analysis of the article mentioned above has revealed that the representativeness of the data is extremely low. For example, the study groups were selected incorrectly, the PCV-7 administration scheme was not analyzed, whereas its violation may cause ineffective immunity development and as result disease development. Another crucial aspect is the lack of any data on the BA severity and inhaled corticosteroid therapy in vaccinated children. Nowadays, there are numerous scientific studies on the clinical efficacy of PCV in the prevention of IPD including the children with BA. Most world-class experts support the necessity of PCV-7 usage in children with BA for the prevention of IPD and suggest their patients over 6 years old on inhaled corticosteroid therapy to perform additional administration of pneumococcal polysaccharide vaccine.

Effects of Artemisinin and Its Derivatives on Oral Microbes

The oral environment provides suitable conditions for the colonization of various microorganisms. However, the oral microbials could be the initial factors of some kinds of oral infectious diseases, therefore the treatment against oral microbial pathogens has become an effective strategy. Artemisinin, a kind of sesquiterpene lactone extracted from Traditional Chinese Medicine Artemisia annua L., is the first-line therapy to treat tertian malaria, subtertian malaria and anti-chloroquine malaria for its high efficiency and low toxicity. In recent years, artemisinin and its derivatives have also been proven to be effective against bacteria, fungi, viruses, parasites, and tumors, some of which are closely related to oral diseases. In this review, we summarize the potential effects of artemisinin and its derivatives on oral microorganism by analyzing previous research and latest progress to provide the evidence for further improvement, and look forward to the new research directions. Further studies are needed to improve existing technologies and standards to clarify the effects of artemisinin and its derivatives on microorganisms with controversial effects, to expand the detection of microorganisms associated with oral infectious diseases, and to clarify the interaction with existing antifungal agents in the field of antifungal diseases. In addition, in the study of anti-oral infectious diseases, artemisinin and its derivatives' administration scheme, potential drug interactions, toxic and side effects and other aspects are necessary conditions for further research, which is also a new direction of research. With the maturity of the production process, the improvement of relevant research and the potential demand for the treatment of oral infectious diseases, artemisinin and its derivatives have a broad prospect in the field of oral microorganisms, and provide a new opportunity for the research and development of oral drugs.

Analysis of visualization index using technique of simultaneous laparoscopic operations

Fatigue is a temporary decrease in the efficiency of an organism or organ due to intensive or long-term work, which is manifested in a decrease in quantitative and qualitative indicators of work and deterioration of coordination of work functions. Groups of simultaneous operations (411 patients) and group of single operations (746 patients) were formed. In both groups these changes were insignificant in most cases (except for marginal values in obese patients III, there were 6 such cases in the first group and8 inthe second), corrections of the port administration scheme were performed when performing vertical gastrectomy in both groups. After the calculation, the average deviations were1.2 cmin the first group and1.4 cmin the second. When using a laparoscope with a viewing angle of 0 o, the approach distance of the laparoscope with its own method of access on average during normal surgery is (6.92 ± 0.306) cm and is slightly smaller than standard methods, the average value of the studied parameter in the control group is - (6.98 ± 0.258) cm (p &lt;0.001). Visualisation during simultaneous laparoscopic operations using our developed technique was on the level with single laparoscopic operation, performed classically.

Elimination profiles of microdosed ostarine mimicking contaminated products ingestion.

The possibility of nutritional supplement contamination with minute amounts of the selective androgen receptor modulator (SARM) ostarine has become a major concern for athletes and result managing authorities. In case of an adverse analytical finding (AAF), affected athletes need to provide conclusive information, demonstrating that the test result originates from a contamination scenario rather than doping. The aim of this research project was to study the elimination profiles of microdosed ostarine and characterize the time-dependent urinary excretion of the drug and selected metabolites. Single- and multi-dose administration studies with 1, 10, and 50 μg of ostarine were conducted, and collected urine samples were analyzed by LC-MS/MS following solid-phase extraction or enzymatic hydrolysis combined with liquid-liquid extraction. In the post-administration samples, both the maximum urine concentrations/abundance ratios and detection times of ostarine and its phase-I and phase-II metabolites were found to correlate with the administered drug dose. With regard to the observed maximum levels of ostarine, the time points of peak urinary concentrations/abundance ratios, and detection windows, a high inter-individual variation was observed. However, the study demonstrated that a single oral dose of as little as 1 μg can be detected for up to 9 (5) days by monitoring ostarine (glucuronide), and hydroxylated metabolites (especially M1a) appear to offer a considerably shorter detection window. The obtained data on ostarine (metabolite) detection times and urinary concentrations following different administration schemes support the interpretation of AAFs, in particular when scenarios of proven supplement contamination are discussed and supplement administration protocols exist.

An Adaptive Control Scheme for Interleukin-2 Therapy.

SummaryRegulatory T cells (Treg) are suppressor cells that control self-reactive and excessive effector conventional T helper cell (Tconv) responses. Breakdown of the balance between Tregs and Tconvs is a hallmark of autoimmune and inflammatory diseases. Interleukin-2 (IL-2) is a growth factor for both populations and subtle leverage to restore the healthy immune balance in IL-2 therapy. By using a mechanistic mathematical model, we introduced an adaptive control strategy to design the minimal therapeutic IL-2 dosage required to increase and stabilize Treg population and restrict inflammatory response. This adaptive protocol allows for dose adjustments based on the feedback of the immune kinetics of the patient. Our simulation results showed that a minimal Treg population was required to restrict the transient side effect of IL-2 injections on the effector Tconv response. In silico results suggested that a combination of IL-2 and adoptive Treg transfer therapies can limit this side effect.

The challenge to define the optimal prophylactic regimen for vitamin K deficiency bleeding in infants.

Infants are at risk of vitamin K deficiency that may lead to vitamin K deficiency bleeding (VKDB). Although many vitamin K prophylactic regimens have been developed throughout the years, still cases of late form VKBD may occur. The introduction of combined prophylactic strategy with prolonged oral prophylaxes after the intramuscular dose at birth has showed a decrease of the late severe VKDB incidence. Nevertheless, there is still lack of consensus about the administration scheme after the first dose at birth. CONCLUSION: Late form VKBD is not eradicated, and the best prophylactic regimen in term and preterm infants is still an open debate.

La problemática administrativo-fiscal de un país naciente: México, 1821-1824

&lt;p&gt;Este estudio parte de la idea de que no se puede entender la situación financiera de los gobiernos postindependentistas sin tener conocimiento de la administración que se hacía cargo de los recursos públicos. En las siguientes páginas se analizan las oficinas que resguardaban los dineros públicos en una época de guerra interna; concretamente, la que llevó a la consumación de la independencia de Nueva España. Se concluye sobre la razón para el establecimiento del ministerio de hacienda. También se sugiere el motivo por el cual las juntas provinciales procedieron a formar sus propias administraciones financieras y se aporta una razón más para el establecimiento del federalismo en 1824. El estudio explora el destino de los intendentes, cómo paulatinamente fueron perdiendo razón de ser en la administración provincial del México independiente hasta su desaparición por motivo del establecimiento de la nueva administración financiera de la república federal.&lt;/p&gt;

Social Determinants of Health Are Needed in COVID-19 Risk Assessments for the Workforce

Social Determinants of Health Are Needed in COVID-19 Risk Assessments for the Workforce

Паєнок Станіслав Мартинович — доктор біологічних наук, професор (1928–1994)

Stanislav Payenok was doctor of biological sciences, professor. The research conducted by S. Payenok launched a new direction in zootechnical vitaminology. The studies touched upon the problems of vitamin nutrition of different animals, development of new and efficient vitamin preparations, studying their biological impact and establishing optimum amounts, means and schemes of administration.