Medical Drug Use Research Articles

Epidemiology, virology, clinical features, diagnosis, and treatment of SARS-CoV-2 infection

Since December 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged and spread quickly worldwide. The disease is generally mild in adult people but in any with comorbidities may proceed to acute respiratory distress syndrome (ARDS), pneumonia, and multi-organ dysfunction. By performing molecular tests on respiratory secretions can diagnose the virus. Elevated C-reactive protein (CRP) and normal/low white cell counts are common laboratory diagnoses of COVID-19 while the tomographic chest scan is usually irregular for many infected people. Some patients progress to respiratory failure, pneumonia, and finally death by the end of the first week of illness because of the sharp rise in inflammatory cytokines such as IL7, IL2, GCSF, IL10, MIP1A, MCP1, IP10, and TNFα. Various approaches to the COVID- 19 are being performed by scientists. Use of chemical medical drugs that are effective for other viral infections. Among them, remdesivir was approved by FDA on 1th May 2020 because of its impact to treat patients. Also, several studies have revealed that many Chinese herbal remedies have a remarkable impact on the healing process when simultaneously were used along with pharmacological drugs. In the meantime, many efforts have been made to produce an effective vaccine, and so far, the Ad5-vectored COVID-19 vaccine has been successful and has entered phase 2 in the human trial. The current review focus on epidemiology, virology, clinical features, diagnosis, and available treatment of coronavirus that might assist researchers and clinicians in establishing action options for timely against this infection.

Labeling of Immunobiological Drugs, Produced by the Russian Research An-ti-Plague Institution "Microbe" of the Rospotrebnadzor (Review)

Introduction. This publication describes the design and implementation sequence of technological procedures for labeling immunobiological medicinal products produced by the FGHI RusRAPI "Microbe" of the Rospotrebnadzor. In light of meeting the requirements of the Federal Act "On the Circulation of Pharmaceutical Products", the materials of this study are undoubtedly relevant.Text. The paper presents a step-by-step sequence of introducing technological procedures for labeling and interaction with the system for monitoring the movement of pharmaceutical products (MMPP) into the production process of medicines. At the preparatory stage, the following main issues were addressed: verification of the identity of information about medicinal products in the State Register of Medicines and in the automatic identification system "UNISCAN/GS1 RUS"; determination of the method and possibility of applying the identification means onto the secondary packaging; amendments to the pharma-copoeial monographs of the enterprise for each type of drug. Stage 2 [development of requirements for the system of labeling, serialization, verification and aggregation (LSVAS)] included the following activities: development of a functional model of the labeling process in the FGHI RusRAPI "Microbe" and determination of the responsible for the implementation of this scheme units; determination of the method of secondary packaging (manual or automatic), as well as the required degree of aggregation and the required automation of the process, based on the analysis of the functional model and the technological process of labeling; analysis of the experience of introducing drug labeling systems; analysis of the existing IT-structure of the FGHI RusRAPI "Microbe"; monitoring of the market of hardware and software manufacturers; development of technical requirements for the created system of marking, serialization, verification and aggregation. Stage 3 (implementation of the labeling, serialization, verification and aggregation system at the production sites) included the following activities: equipment supply and commissioning; equipment qualification (IQ/OQ); training of the personnel; amendments to regulatory documents. In the materials devoted to the implementation of the final stage, the issues of validation of technological procedures for drug labeling and interaction with the system of labeling, serialization, verification and aggregation are considered.Conclusion. The works performed made it possible to produce medicines in accordance with the requirements of the Federal Act "On the Circulation of Pharmaceutical Products" and the Decree of the Government of the Russian Federation dated December 14, 2018 № 1556 "On Approval of the Regulation on the System for Monitoring the Movement of Drugs for Medical Use". The material presented may be of interest to manufacturers who produce medicines in small amounts.

Randomized Controlled Trial of Solution-Focused Brief Therapy for Substance-Use-Disorder-Affected Parents Involved in the Child Welfare System

Objective: Solution-focused brief therapy (SFBT) has shown promise as an effective intervention with substance-abusing adults. This study expands on a preliminary study by Kim et al. (2018) by examining the results from the complete sample on substance abuse and trauma-related problems. Method: Child-welfare-involved parents were randomly assigned to either the SFBT (N = 90) or treatment-as-usual (N = 89) control group. Mixed linear models tested changes using intent-to-treat analysis, and effect sizes examined the magnitude of treatment effects. Results: Both the SFBT and control groups decreased on most of the Addiction Severity Index-SR (ASI-SR) measures and on all Trauma Symptom Checklist-40 (TSC-40) measures, indicating improvements. Between-group effect sizes favored the control group for two ASI-SR subscales—medical status and drug use—and favored SFBT for the TSC-40 subscale measures, although none was statistically significant except for the TSC-40 depression subscale. Conclusions: Further exploration of SFBT as an intervention to treat substance abuse and trauma among parents involved in the child welfare system is warranted.

Antibiotic treatment failure

This review presents information on cases of antibiotic failure (insufficient effect) in the global population over the past three years. We analyzed scientific papers, clinical trial data, and the WHO Program for International Drug Monitoring (VigiBase) data from 2018 to 2020. The values of global success and safety rates of antibacterial drugs for medical use are presented. The findings may be of practical interest to physicians, researchers, developers, and healthcare regulators.

Assessment of Substance Use Behavior and Effectiveness of Structured Teaching Programme on Prevention and Ill Effects of Substance Abuse among Adolescents

Background: Substance abuse has become a major problem in any growing society, the pattern ofconsumption of medical and non-medical use of drugs, especially by pre adolescents, adolescents and youngadults, is both complex and changing. In 1992, WHO declared June 26 as the International Day againstsubstance abuse and illicit trafficking1.Methods: It was a two-phase study, during phase-I of the study 485 adolescents were assessed for substanceuse behavior. During phase-II 100 adolescents were given structured teaching programme, pre-test and posttestknowledge and attitude were assessed.Results: The study results revealed that out of 485 adolescents only 3.2% (16) of the adolescents hadtried or experimented with substances and 11.1% (54) of the adolescents reported that their friends use thesubstance in the school. The calculated Z score value was found to be 11.316 which was greater than the tablevalue (1.98) indicates the effectiveness of structured teaching programme.There was a moderate positivecorrelation (0.568) between the post-test knowledge scores and post-test attitude scores of adolescents.Conclusion: The incidence of drug abuse among children and adolescents is higher than the generalpopulation. Therefore, keeping in focus, the investigator felt the need to conduct a research study to assessthe knowledge and attitude regarding the ill effects of substance abuse and its prevention among adolescents,and the study was found to be effective in increasing the knowledge and attitude among adolescents.

Are COL4A1 and COL4A2 gene polymorphisms associated with cerebral palsy?

Objectives This study aims to investigate the association of COL4A1 and COL4A2 gene polymorphisms with susceptibility to risk of developing cerebral palsy (CP) and severity of CP. Patients and methods Between December 2016 and June 2017, a total of 176 patients with CP (101 males, 75 females; mean age 71.8±37.9 months; range, 24 to 184 months) and age-, sex-, and ethnically-matched 178 (90 males, 88 females; mean age 69.3±55.2 months; range, 24 to 214 months) controls were included. Two polymorphisms of COL4A1 (rs1961495) and COL4A2 (rs9521733) genes were typed from genomic deoxyribonucleic acid. Genotype distributions and allelic frequencies were compared between the patient and control groups. Gross Motor Function Classification System, the use of medical drugs, type of involvement, number of affected limbs, accompanying conditions, birth weight, gestational age, and magnetic resonance imaging (MRI) findings were used to evaluate the disease severity and their relationships with the COL4A1 and COL4A2 gene polymorphisms. Results There was no statistically significant difference between the groups in terms of genotype distribution and allele frequency of COL4A1 and COL4A2 gene polymorphisms (p>0.05). In addition, there was no relationship between severity of CP and two gene polymorphisms (p>0.05). A significant association was detected between the COL4A2 polymorphism and growth retardation in CP. The TT genotype (57.1%) and T allele (76.2%) were higher, compared to CC (4.8%) and CT genotypes (38.1%) and C allele (23.8%) in patients with CP with growth retardation (p=0.03 for genotype and p=0.01 for allele frequency). Conclusion These findings suggest that COL4A1 and COL4A2 gene polymorphisms are not associated with susceptibility to CP in a group of Turkish populations, although COL4A2 gene polymorphism may be associated with growth retardation in patients with CP.

Effects of Itraconazole and Micafungin on Aspergillus fumigatus Biofilms.

Aspergillus fumigatus (A. fumigatus) is the most common airborne opportunistic fungal pathogen. Biofilm formation is one of the main pathogenic mechanisms of A. fumigatus. During the past decades, A. fumigatus azole resistance has become prevalent due to the medical and agricultural use of antifungal drugs and fungicides. Until now, the role of fungal biofilms in azole resistance of A. fumigatus remains unclear. In the present study, we compared biofilm drug susceptibility and biofilm formation under itraconazole of azole-resistant strains, sensitive strains, and standard strains, separately. The biofilm viability and matrix thickness at the early and the late stage were measured by XTT assay and Calcofluor white. Our results showed that the sessile minimum inhibitory concentration of itraconazole, which describing the inhibition of drugs on fungi sessile with biofilm, was much higher than the traditional minimal inhibitory concentration of itraconazole. Additionally, low concentrations of itraconazole inhibited biofilm formation of A. fumigatus strains. Notably, biofilm formation by azole-resistant strains could not be inhibited by high concentrations of itraconazole but could be effectively restrained by low concentrations of micafungin, revealing the efficacy of a cell-wall inhibitor to disrupt A. fumigatus biofilm formation. However, late-stage biofilms of both azole-resistant strains and standard strains were hard to disrupt using itraconazole. We found that itraconazole was effective to prevent A. fumigatus biofilm formation at the early stage. For the treatment of A. fumigatus biofilm, our findings suggest that an early-stage preventive strategy is preferred and micafungin is effective to control the azole-resistant strain infection.

Лекарственно-индуцированный острый интерcтициальный нефрит

Among the causes of acute interstitial nephritis, drug-induced acute interstitial nephritis accounts for 50 to 78 % of all cases. Th e review summarizes the literature data on drugs that cause acute interstitial nephritis. Search in eLibrary databases.RU, PubMed®, MEDLINE, EMBASE, manuals and guidelines, materials of adverse drug reactions databases, instructions for the medical use of drugs. it was held until October 2020. Th e most probable mechanisms of its development are considered. Most attention is paid to non-steroidal anti-infl ammatory drugs, anticoagulants, antibiotics, antitumor drugs (immune checkpoint inhibitors), which are widely used in clinical practice. Th e symptoms of drug-induced acute interstitial nephritis are variable and oft en non-specific; therefore, a kidney biopsy is required for an accurate diagnosis. The main direction of treatment of drug-induced acute interstitial nephritis is the cancellation of nephrotoxic drugs, if this condition is not feasible and/or the duration of acute interstitial nephritis is less than 3 weeks, the biopsy has minimal interstitial fibrosis and there are no serious contraindications, then the possibility of using it should be considered.

Лекарственно-индуцированная гипонатриемия

Hyponatremia (HN) is one of the most important water-electrolyte disorders in clinical practice. A decrease in sodium levels leads to various complications, including neurological ones. One of the important etiological factors of HN is the intake of a number of drugs. The purpose of the review was to analyze data on those drugs, the intake of which is associated with the development of DI GN, its pathophysiological mechanisms, risk factors, methods of treatment and prevention. The search for the specified keywords was carried out in the databases eLIBRARY.RU, PubMed®, MEDLINE, EMBASE, manuals and methodological recommendations, materials of databases of adverse reactions, instructions for the medical use of drugs in the period from 1971 to 01.07.2021. According to the results obtained, the main culprit drugs include thiazide diuretics, antipsychotic drugs, antidepressants, antiepileptic drugs, antineoplastic drugs. The incidence of HN during the use of antidepressants reaches 40%, with the use of oxcarbazepine occurs in 73.3% of patients. Most often, these drugs lead to HN by the development of a syndrome of inadequate secretion of antidiuretic hormone. During the review, it was found that drugs from a wide variety of groups lead to the development of HN, the mainstay of treatment is drug withdrawal and restriction of fluid intake, and for prevention, dynamic monitoring of sodium levels is required.

A study on hospitalized patients of junctional rhythm with reference to the prevalence of different underlying etiologies

Introduction: Junctional rhythm (JR) is a rescue rhythm where the upstream impulse generators fail to pace the heart and atrioventricular (AV) junction takes up that function. The presentation is variable ranging from totally asymptomatic cases, where it is a manifestation of heightened vagal tone, to life-threatening bradycardia, resulting from some serious underlying pathologies. JR results from diverse causes such as sick sinus syndrome, acute myocardial infarction (AMI), dyselectrolytemia, drugs, and toxins. Understanding the etiologic factor has immense implication in the management as the prognosis is related mainly to the primary pathology rather than JR itself. Subjects and Methods: In this observational study, we evaluated 100 hospitalized patients of JR over a period of 1 year regarding their symptoms, signs, and underlying pathology. Results: Among 100 patients, 38 had a history of syncope and 42 had angina. Twenty-four patients had hyperkalemia (22 of them had renal dysfunction). Thirty patients had elevated troponin-T and/or CK-MB. The most common etiology was AMI responsible in 28% patients followed by hyperkalemia (24%), sick sinus syndrome (20%), and medication drug use (16%) as the principal causes of JR. Myocarditis, toxin, and hypothyroidism were uncommon association. Accelerated JR and junctional tachycardia were associated with AV nodal ablation and postsurgical patients, respectively. Conclusion: JR is a manifestation of several diverse etiopathologies, and elucidation of them is extremely important for the patient management. We estimated the prevalence of various underlying etiologies which should be considered during the management of such patients.

Features of Preclinical Studies of Cell Therapy Products

Preclinical studies are one of the most important stages in the development of drugs for medical use, including cell therapy products (in accordance with the legislation of the Russian Federation — biomedical cell products). Regulatory authorities decide on the possibility of conducting clinical trials in order to bring the medications to the market on the basis of the results of the study of their specific activity and safety. Russian requirements for preclinical studies of cell therapy products generally correspond to foreign ones, the main difference is the need for an expanded program of their conduct. The article analyzes the aspects of preclinical studies (scope, justification of the reduced program, design, animal models used) of some cell therapy products approved for use in medical practice in the United States, the European Union, Japan, and South Korea.

Multi-vector analysis of the market for drugs used to treat hepatitis C

The article presents a study on the structural assessment of the range of drugs for the treatment of hepatitis C. Methods of content analysis, data aggregation, grouping, comparative and marketing analysis have been used. The information base of the study was the State Register of Medicines and National Register of Medicines of April 24, 2020, as well as instructions for the medical use of drugs. It was revealed that 52 trade names of medicinal products (23 INN) and 17 substances had been registered in the Russian Federation. The analysis carried out by pharmaceutical producing countries has shown that the leading positions in the supply structure are occupied by Russian manufacturers (73.08%). Structuring by dosage forms enables to isolate tablets, covering 32.69%, as well as solutions and capsules, which are 23.08%, respectively. The largest share in the structure of the assortment of substances is occupied by interferon alpha-2b (20.93%). The results of the analysis has shown that the manufacturer carries out all stages of production for the majority of drugs. The index of renewal of the researched drug market over the past 5 years is 16.27%.

Leading conduct in renovascular hypertension

Introduction: The Renovascular hypertension (RH) is the leading cause of secondary hypertension. The main cause for RH is renal arterial stenosis and with early treatment is possible to reverse the clinical state. Therefore, the diagnosis and choice of a proper treatment are extremely important, especially in this pathology.Methodology: Thus, this paper aimed to conduct a narrative review, using articles from indexed journals and narrative and systematic reviews of Medline, SciELO and Cochrane CENTRAL databases, comparing comparing the use of stent in cirurgical intervention versus the use of medical drugs in the treatment of RH. Results: In none of the studies (RADAR, RAOOD) or systemic reviews or metaanalysee was observed the restoration of renal function. Discussion: The diseases occur due to decreased blood flow of the renal artery, usually by an atheroma plaque. The physiopathology of RH disease consists in the interaction between the renin-angiotensin-aldosterone system (RAAS), that when activated is responsible for sodium and volume retention, combined with other pressure systems such as Sympathetic Nervous System. RH treatment can be performed through drug therapy, mainly ACE inhibitors or through surgical intervention with stent placement. Conclusion: The conclusion observed was that the efficiency of the stent when combined with the use of pharmacos, obtaining an improvement in the clinical picture.

Female rats self-administer heroin by vapor inhalation

Over the last two decades the United States has experienced a significant increase in the medical and non-medical use of opioid drugs, resulting in record numbers of opioid-related overdoses and deaths. There was an initial increase in non-medical use of prescription opioids around 2002, followed later by increased heroin use and then most recently fentanyl. Inhalation is a common route of administration for opioids, with a documented history spanning back to Mediterranean antiquity and up through modern use with e-cigarette devices. Unfortunately, preclinical studies using inhalation as the route of administration remain relatively few. This study was conducted to determine the efficacy of e-cigarette vapor inhalation of heroin in rats. Non-contingent exposure to heroin or methadone vapor produced anti-nociceptive efficacy in male and female rats. Female rats were trained to self-administer heroin vapor; the most-preferring half of the distribution obtained more vapor reinforcers when the concentration of heroin was reduced in the vapor vehicle and when pre-treated with the opioid receptor antagonist naloxone. The anti-nociceptive effect of heroin self-administered by vapor was identical in magnitude to that produced by intravenous self-administration. Finally, anxiety-like behavior increased 24–48 h after last heroin vapor access, consistent with withdrawal signs observed after intravenous self-administration. In sum, these studies show that rewarding and anti-nociceptive effects of heroin are produced in rats by vapor inhalation using e-cigarette technology. Importantly, self-administration models by this route can be deployed to determine health effects of inhaled heroin or other opioids.

The Ethics of Prenatal Injury

I argue that it is permissible for pregnant women to expose their unborn children to risks and injury. I begin with the premise that abortion is permissible. If so, then just as a pregnant woman may permissibly prevent an unborn child from experiencing any future wellbeing, she also may permissibly provide her child relatively poorer prospects for wellbeing. Therefore, it is permissible for pregnant women to take risks and cause prenatal injury. This argument has revisionary implications for policies that prevent medical research and drug use during pregnancy. It also explains why moralistic criticism of pregnant women is unwarranted.

Improvements to the formation of lists of drugs for medical use: analysis of changes in the Government Decree no. 871

The article presents a description of amendments of the Russian Federation Government Decree No. 871 from August 28, 2014 (with amendments from November 20, 2018). The authors analyzed the historical development of approaches for complex drug assessment in Russia, also criteria for its evaluation were under investigation. The changes affecting both the order and the procedure of forming the lists of medical drugs for medical use are reviewed. The particularities of the current procedure for the formation of lists of drugs for medical use are described in detail. In reliance on the analysis, further direction for improvement/development of the system of formation the lists of medical drugs for medical use are educed (List of Vital and Essential Medicines, List of Medical Drugs for Certain Categories of Citizens, List of High-Cost Medical Drugs).

Fever in children: review of national and international studies and clinical guidelines

Fever in children is one of the most common reasons for seeking medical care and use of antipyretic drugs. The reasons can be various. It is extremely important for the pediatrician to find the cause of the fever and prescribe adequate therapy. Antipyretic drugs are symptomatic, they only relieve the condition of the child and improve the quality of life. The article reviews national and international studies and clinical guidelines of professional communities on fever in children. Currently, only ibuprofen and paracetamol fully meet the safety and efficacy criteria, and they are recommended for use in pediatric practice as antipyretic drugs.

Structural analysis of drugs assortment for etiopathogenetic therapy of children with acute viral infections

The purpose evaluated the range of drugs for the etiopathogenetic treatment of children with acute viral infections. The methods of content analysis, data aggregation, comparative analysis are used. The research information base was made up of State Register of Medicines and National Registry of Medicines data as of 26 November 2019, as well as instructions for the medical use of drugs. It is shown that in the Russian Federation 201 trade names of drugs (35 INN) and 57 substances are registered. The leading positions in the structure of the supply of drugs and substances are held by russian manufacturers (76,00% and 70,00%, respectively). At the same time, structuring by dosage forms allows one to isolate tablets and powders (39,00% and 78,00% for finished dosage forms and substances, respectively). Acyclovir prevails in the structure of the range of medicines (25,00% and 19,00% for international non-proprietary and trade names, respectively). The largest share in the structure of the assortment of substances is covered by interferon alfa-2b (17,50%). The results of the analysis demonstrate that for most drugs, the manufacturer carries out all stages of production, including issuing quality control (67,00%). For 2015-2019, the renewal index of the assortment of the study group was 22,38%.
 Given the uncontrolled increase in the incidence rate, the presented assortment of antiviral and immunomodulating agents is sufficient to satisfy the needs of Russian pediatrics. One of the promising vectors for the development of the pharmaceutical industry in terms of providing medicines for children with acute viral infections is the development of drugs in the form of children's corrected forms.

The Role of Past and Current Medical Use on Nonmedical Use of Prescription Drugs among College Students: Exploring Same-Drug and Cross-Drug Class Associations

Background: Understanding the role that medical use of prescription drugs plays in nonmedical use of prescription drugs can inform prevention efforts. In order to understand fully the potential risk that medical use of prescription drugs conveys for nonmedical use of prescription drugs, the current study explored (a) the simultaneous associations between the medical use of several classes of prescription drugs with current nonmedical use of the same and other prescription drug classes, and (b) whether the associations depended upon past or current medical use. Methods: Data came from a cross-sectional survey of 1686 college students, which assessed past and current medical use and current nonmedical use of stimulants, sedatives/anxiolytics, and opioid analgesics. Results: Logistic regression analyses revealed that both past and current medical use of sedatives/anxiolytics and opioid analgesics predicted the current nonmedical use of the same drug class, whereas past medical use of stimulants predicted the current nonmedical use of stimulants. In addition, current medical use of stimulants predicted current nonmedical use of sedatives/anxiolytics and past medical use of sedatives/anxiolytics predicted current nonmedical use of opioid analgesics. Conclusions: This study provides a broader examination than past research of simultaneous same-drug class and cross-drug class associations between medical and nonmedical prescription drug use, as well as the role of past and current medical use in these associations. Overall, the results suggest that efforts to prevent nonmedical use of a prescription drug class should move beyond targeting only those who have or who are using the same drug class medically.

Reporting trigger factors for (hypo)manic episodes in bipolar disorder: association with personality and prognosis.

To investigate external factors that trigger manic and hypomanic relapses and how this is associated with personality and clinical outcome measured as number of affective episodes over a 7-year period. This is a prospective cohort study of 204 meticulously characterized Swedish bipolar disorder patients. Personality was evaluated at baseline using the Swedish universities Scales of Personality in 170 patients, and 90 patients were followed up after approximately 7years in order to evaluate clinical outcomes. We found that 44% of the patients reported trigger factors, including sleep disturbance, work- or family-related issues, medication, and illicit drug use. There were no significant differences in any of the personality traits when comparing the 74 patients that reported triggers with the 90 patients that did not. At 7-year follow-up, there was no difference between the groups in number of affective episodes (depressive, hypomanic, manic, or mixed), involuntary commitments, suicide attempts, or self-harm incidents since baseline. Around 40% of the patients reported external triggers for manic and hypomanic episodes. However, this was neither associated with personality traits nor number of affective episodes at 7-year follow-up.