The World Bulletin of Public Health (WBPH) is a double-blind peer reviewed, open access journal that publishes original research, review articles, case studies and commentaries on all aspects of public health. The journal publishes papers that can be applied to public health practices, programs and policies. The WBPH is passionate about high quality papers that significantly contribute to both local and international efforts to improve the health of populations and ultimately save lives around the globe. ISSN (E): 2749-3644 Journal Impact Factor : 10.355 SJIF 2026 : 9.682 WBPH considers unpublished, original manuscripts in, but not limited to, the following fields: Public Health, Epidemiology, Occupational Health, Environmental Health, Nursing Research, Global Health, etc.
NEUROINFLAMMATION AND NEURODEGENERATIVE DISEASES:THEIR ROLE IN PATHOGENESIS AND CONTEMPORARYPERSPECTIVES
This article analyzes the role of neuroinflammation in the pathogenesis of neurodegenerative diseases and reviews contemporary scientific perspectives on the subject. Neuroinflammation is a complex immune-inflammatory process that occurs within the central nervous system and develops through the involvement of microglial cells, astrocytes, and pro-inflammatory cytokines. Neurodegenerative diseases are currently among the most pressing challenges facing global healthcare systems. As the world's population continues to age, the prevalence of these disorders is increasing each year. At present, more than 55 million people worldwide are living with dementia, with approximately 10 million new cases diagnosed annually. In most of these disorders, neuroinflammation represents one of the principal pathogenic mechanisms. Recent studies have demonstrated that chronic neuroinflammation contributes to neuronal degeneration in diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and multiple sclerosis. This article highlights the significance of microglial activation, oxidative stress, inflammasome activation, disruption of the blood–brain barrier, and genetic factors in the development of these conditions. In addition, it provides an overview of contemporary therapeutic approaches, including anti-inflammatory therapy, immunotherapy, antioxidant agents, and gene therapy. A deeper understanding of neuroinflammation may enhance opportunities for the early diagnosis and effective treatment of neurodegenerative diseases
Copyright (c) 2026 Oxnorova Sabrina Qaxxor qizi, Ochilova Durdona Obidjonovna, Xamidova Muxlisa Alisher qizi, PhD Ra'nogul Hoji qizi Fayziyeva https://creativecommons.org/licenses/by-nc-nd/4.0
PERIOPERATIVE POLYCHEMOTHERAPY FOR GASTRIC CANCER
Gastric cancer remains one of the leading causes of cancer-related mortality worldwide. Despite advances in surgical techniques, treatment outcomes remain unsatisfactory due to the high rate of recurrence and metastasis. In recent decades, perioperative polychemotherapy, including neoadjuvant and adjuvant treatment, has become increasingly important. The aim of this work is to analyze the effectiveness, safety, and modern approaches to perioperative polychemotherapy in gastric cancer. Clinical trial data and meta-analyses demonstrating improvements in overall and disease-free survival with this approach are reviewed. Special attention is given to modern treatment regimens and the prospects of combination therapy with immunotherapy.
Copyright (c) 2026 https://creativecommons.org/licenses/by-nc-nd/4.0
COMPREHENSIVE ASSESSMENT OF PHYSIOLOGICAL AND PSYCHOEMOTIONAL INDICATORS OF CHRONIC STRESS AMONG SPECIALISTS OF DIFFERENT PROFESSIONAL GROUPS IN THE REPUBLIC OF KARAKALPAKSTAN
Chronic stress has become one of the most significant health challenges affecting the psychological and physiological well-being of working populations worldwide. The present study aimed to assess the physiological and psychoemotional manifestations of chronic stress among specialists from different professional groups in the Republic of Karakalpakstan. A comparative analysis was conducted among medical workers, teachers, and civil servants. The results demonstrated that medical workers and teachers experienced higher levels of chronic stress, emotional exhaustion, anxiety, sleep disturbances, and physiological symptoms compared to civil servants. The findings emphasize the necessity of developing preventive strategies and stress-management programs to improve occupational health and wellbeing
OPTIMIZATION OF PARENTERAL NUTRITION AS A FACTOR IN REDUCING COMPLICATIONS IN NECROTIZING ENTEROCOLITIS IN NEWBORNS
Necrotizing enterocolitis (NEC) is one of the most severe diseases of the neonatal period, characterized by high mortality and a significant risk of long-term complications. In conditions where enteral feeding is limited in newborns with NEC, adequate nutritional support becomes especially important. The aim of this review is to analyze current data on the role of optimizing parenteral nutrition in the prevention of metabolic disorders, infectious complications, and in improving clinical outcomes in newborns with necrotizing enterocolitis. The review discusses the features of providing requirements in proteins, lipids, carbohydrates, trace elements, and vitamins, as well as modern strategies for individualizing nutritional support. Data on the impact of balanced parenteral nutrition on reducing the incidence of sepsis, cholestasis, growth retardation, and short bowel syndrome are presented
FEATURES OF PANCREATIC AND ENZYME HOMEOSTASIS UNDER THE COMBINED IMPACT OF HYPOKINESIA, HYPERTHERMIA, AND INSOLATION
These changes are driven by a disruption of water-salt metabolism and c omplex physiological realignments caused by heat stress. The body differentially regulates the protein synthesis of various pancreatic enzymes in response to heat shock. The combination of multiple stressors (hyperthermia, sun exposure, and lack of movement) leads to a more pronounced decrease in exocrine secretion (release into the intestine) and endocrine secretion of enzymes compared to the effect of a single factor. This must be taken into account when designing dietary regimens and assessing the health status of individuals exposed to such conditions
THE ROLE OF THE AZF GENETIC MARKER AS A FACTOR OF CIGARETTE SMOKING AND ALCOHOL CONSUMPTION AFFECTING CHILDREN'S HEALTH
This study investigates the impact of the AZF genetic marker on children's health. The relationship between parental smoking and alcohol consumption habits and the physical development of their children was analyzed. The results showed that parents of children in the AZF+ group had significantly higher smoking rates, which may negatively affect the health of their children. However, no statistically significant differences were observed in the combined effect of smoking and alcohol consumption
MODERN PERSPECTIVES ON THE ETIOLOGY AND PATHOGENESIS OF HEMORRHAGIC VASCULITIS
Hemorrhagic vasculitis, also known as IgA vasculitis, is a systemic smallvessel inflammatory disease characterized by the deposition of immunoglobulin A (IgA)-containing immune complexes in the vascular walls. Despite significant advances in medical science, the exact etiology of the disease remains incompletely understood. Current evidence suggests that genetic predisposition, infectious agents, environmental triggers, and immune dysregulation play crucial roles in the development of the disease. This article reviews contemporary concepts regarding the etiology and pathogenesis of hemorrhagic vasculitis, focusing on the mechanisms of IgA immune complex formation, endothelial injury, inflammatory responses, and the involvement of cytokines and complement pathways. Understanding these pathogenic mechanisms is essential for improving diagnostic approaches and developing targeted therapeutic strategies for patients with hemorrhagic vasculitis.
THE IMPACT OF THE AZF GENE DEFECT ON SPERMATOGENESIS PARAMETERS IN INFERTILITY MEN
This study investigates the impact of AZF gene defects on spermatogenesis parameters in men with fertility disorders. A comparative analysis was conducted between two groups of men: AZF– (n = 150) and AZF+ (n = 69). The results revealed that the presence of AZF gene defects significantly impaired spermatogenesis parameters such as sperm concentration, motility, viability, and morphology. In the AZF+ group, a high frequency of azoospermia (79.7%) was observed, with significantly lower sperm viability. Our findings emphasize the importance of genetic testing for diagnosing male infertility and highlight the need for considering AZF gene defects when developing treatment methods
MORPHOLOGICAL CHANGES IN THE GASTRIC MUCOSA IN CHRONIC KIDNEY DISEASE IN CHILDREN
This article discusses changes in the mucous membranes of the stomach and duodenum observed by esophagogastroduodenoscopy in children aged 7–17 years with chronic kidney disease that were treated with glucocorticosteroids for six months or longer. As a result of the analysis, chronic gastroduodenitis was detected in 65 (55.1%) cases and gastrobioptates were obtained. Morphological alterations in the cellular composition of the gastric mucosal glands were analyzed in relation to the severity of gastric mucosa inflammation, with morphometric evaluation of the cellular composition conducted to characterize these alterations. Morphometric analysis of the samples taken from 26 healthy children was performed to define reference values to characterize the cellular composition of the gastric mucosal glands as myometria measures
EXPERIMENTAL ASSESSMENT OF ENTEROCYTE APICAL SURFACE REMODELING IN COMBINED TOXIC AND METABOLIC DAMAGE
Long-term exposure to toxic compounds together with metabolic imbalance exerts a substantial damaging influence on the gastrointestinal system. The small intestine is among the most vulnerable organs because its epithelial lining simultaneously performs absorptive, enzymatic, and barrier functions. Any disturbance of the enterocyte apical surface may therefore lead to a decline in digestive efficiency and nutrient transport.
GASTROESOPHAGEAL REFLUX DISEASE (GERD): A DIAGNOSTIC ALGORITHMS, PATHOPHYSIOLOGY MODELS, AND THERAPEUTIC STRATEGIES
Gastroesophageal reflux disease (GERD) is a chronic, relapsing, and heterogeneous gastrointestinal disorder characterized by retrograde flow of gastric contents into the esophagus, leading to typical symptoms (heartburn, regurgitation) and/or mucosal and extra-esophageal complications. Its global prevalence is steadily increasing due to rising obesity rates, dietary pattern changes, sedentary lifestyle, aging populations, and increasing prevalence of hiatal hernia and metabolic syndrome. GERD represents a major burden on healthcare systems due to reduced quality of life, chronic medication use, and risk of complications such as erosive esophagitis and Barrett’s esophagus. To provide a comprehensive, structured, evidence-based synthesis of GERD, including its pathophysiology, clinical phenotypes, diagnostic algorithms, therapeutic strategies, long-term management outcomes, and regionally adapted considerations with emphasis on resource-limited settings such as Uzbekistan (Andijan region).
FUNDAMENTALS OF EARLY FETAL ULTRASOUND SCREENING
Ultrasound examination of the fetus in the first trimester of pregnancy. In 95% of cases, measurements can be performed using transabdominal scanning; in other cases, transvaginal ultrasound may be required. Equipment should be at least mid-range, preferably with a cineloop mode and the ability to measure tenths of a millimeter. An average examination time of at least 10 minutes allows for confirmation of fetal viability, determination of the number of fetuses, accurate gestational age, detection of gross developmental anomalies, and allows for measurement of the nuchal fold, which, in combination with maternal age, is an important component of screening, allowing for the detection of certain chromosomal abnormalities in early pregnancy with up to 75% accuracy
RELATIONSHIP BETWEEN ATHEROGENIC IMBALANCE (APOB/APOA) AND MARKERS OF OXIDATIVE STRESS IN THE DEVELOPMENT OF ARTERIAL HYPERTENSION
This article explores the relationship between atherogenic imbalance, assessed through the ApoB/ApoA ratio, and markers of oxidative stress in the pathogenesis of arterial hypertension. The ApoB/ApoA ratio reflects the balance between atherogenic and anti-atherogenic lipoproteins and is considered a more precise predictor of cardiovascular risk than traditional lipid parameters. Oxidative stress, characterized by excessive production of reactive oxygen species and insufficient antioxidant defense, plays a central role in endothelial dysfunction and vascular remodeling. The review analyzes current evidence linking elevated ApoB/ApoA ratios with increased oxidative stress biomarkers and discusses their combined contribution to the initiation and progression of arterial hypertension. Particular attention is given to mechanisms involving endothelial injury, inflammation, lipid peroxidation, and impaired nitric oxide bioavailability. Understanding this interaction may improve early risk stratification and open new perspectives for targeted therapeutic strategies in hypertensive patients
EFFECTIVENESS OF SPLINTING STRUCTURES MADE OF THERMOPLASTIC POLYMERS AND COBALT-CHROMIUM ALLOY IN THE TREATMENT OF PERIODONTAL DISEASES
The article is devoted to the study of the mechanical properties and effectiveness of splinting structures made of the thermoplastic polymer Vitacryl and cobalt-chromium alloy in the treatment of periodontitis
Congenital craniofacial bone deformities require reconstruction strategies that respect growth restore symmetry and minimize donor site morbidity
MENOPAUSAL TRANSITION AS A CRITICAL STAGE OF REPRODUCTIVE AGING: NEUROENDOCRINE AND CARDIOMETABOLIC IMPLICATIONS
The menopausal transition is a critical stage of reproductive aging characterized by declining ovarian function, hormonal fluctuations, and systemic neuroendocrine remodeling. Alterations in central neurotransmitter systems, including serotonergic, noradrenergic, dopaminergic, and KNDy pathways, contribute to vasomotor symptoms, which reflect underlying autonomic and vascular dysregulation. Estrogen deficiency is associated with increased sympathetic activity, activation of the hypothalamic–pituitary– adrenal axis, insulin resistance, dyslipidemia, abdominal obesity, and lowgrade inflammation, leading to elevated cardiometabolic risk. Psychoemotional disturbances and sleep disorders further exacerbate these processes through stress-related mechanisms. The menopausal transition should therefore be considered a systemic condition with potential long-term health implications, while vasomotor symptoms may serve as clinical markers of adverse cardiometabolic changes.
INTEGRATION OF ARTIFICIAL INTELLIGENCE AND OMICS DATA FOR PREDICTING THE COURSE OF CHRONIC PERIODONTITIS
Chronic periodontitis remains one of the most prevalent inflammatory pathologies of the oral cavity; however, its clinical course is characterized by significant inter-individual variability. Traditional diagnostics—based on assessing periodontal pocket depth, bleeding, and attachment loss— effectively reflect established pathological changes but are less effective at predicting the future progression of the disease process. Consequently, the integration of artificial intelligence and omics data—particularly microbiomics and proteomics—is of particular interest. Microbiome profiles enable the assessment of the degree of dysbiosis and the identification of taxa associated with inflammation, whereas proteomics reflects the functional state of tissues as well as the intensity of the inflammatory response and tissue destruction. Modern machine learning algorithms are capable of integrating these layers of information with clinical parameters to construct models aimed not only at diagnosis but also at predicting therapeutic response and the likelihood of disease progression. Nevertheless, the clinical implementation of such solutions remains limited due to study heterogeneity, a lack of standardized protocols, and insufficient external validation of the models. Frontiers PMC PMC
RESTORATION OF THE ANATOMICAL SHAPE OF TEETH IN CARIOUS LESIONS: MODERN SOLUTIONS
The precise morphological reconstruction of dental tissues following carious degradation is a fundamental prerequisite for maintaining biomechanical equilibrium within the stomatognathic system. This empirical clinical investigation evaluates the morphological retention and marginal integrity of modern restorative interventions, specifically comparing incrementally layered nanohybrid composites against sonic-activated bulk-fill resin systems in complex posterior cavities. Utilizing a split-mouth, randomized clinical design, the study monitored 170 Class II (mesio-occluso-distal) restorations across 85 adult patients over a 12-month functional period. Clinical evaluations were conducted using modified United States Public Health Service (USPHS) criteria, alongside digital volumetric wear analysis. Quantitative diagnostics revealed a pronounced biomechanical advantage for the incremental nanohybrid technique. At the 12-month recall, incrementally layered restorations demonstrated a 94.1% anatomical form retention rate, compared to a rapidly degrading 82.3% within the bulk-fill cohort. Multivariate analysis indicated that managing the cavity configuration factor (C-factor) through stratified application radically minimizes polymerization shrinkage stress, thereby preventing microscopic marginal gap formation. The data dictates a mandatory adherence to biomimetic stratification protocols in advanced restorative dentistry, prioritizing long-term structural integrity and occlusal stability over operational speed
DEVELOPMENT OF DIAGNOSTIC CRITERIA AND CONSTRUCTION OF A PROGNOSTIC MODEL FOR THE COURSE OF THE PANCREATIC NECROBIOTIC PROCESS IN INFECTED PANCREATIC NECROSIS AGAINST THE BACKGROUND OF DIABETES MELLITUS USING ARTIFICIAL INTELLIGENCE TECHNOLOGIES
The scientific article presents the development of diagnostic criteria for predicting the severity of infected pancreatic necrosis (IPN) in 64 patients with diabetes mellitus (DM) and evaluates their effectiveness. It analyzes the scale proposed by the authors for assessing the intensity of pancreatic necrosis (PN) in IPN against the background of DM, as well as a predictive program based on the PN AI scale. The study reports on the results of applying digital and artificial intelligence (AI) technologies in implementing a therapeutic-diagnostic algorithm. Based on the conducted research, the authors concluded that the developed scale allows for the assessment of necrobiosis intensity, while the predictive program complements its capabilities by forecasting the dynamics of the process, significantly increasing the practical value of the proposed model. The developed NP AI scale criteria demonstrate high diagnostic and prognostic efficacy, with a sensitivity of 88.7% and a specificity of 85.3%.
This article comprehensively analyzes the biophysical structure of blood, its components, and its main physicochemical properties. The composition of blood, consisting of plasma and formed elements, as well as important indicators such as viscosity, density, osmotic pressure, and oncotic pressure, are scientifically described. In addition, the rheological properties of blood, namely its behavior as a non-Newtonian fluid, the deformability of erythrocytes, and its role in microcirculation, are examined. The transport, protective, regulatory, and thermoregulatory functions of blood are also analyzed from a physical perspective. The results of the study demonstrate the important role of blood biophysical parameters in maintaining physiological balance, early disease detection, and modern clinical diagnostics
INTENSIVE CARE FOR HEPATOTOXIC AND NEUROTOXIC COMPLICATIONS OF CHEMOTHERAPY IN LUNG CANCER
Chemotherapy remains one of the key methods for treating lung cancer; however, its use is limited by the development of toxic complications. The most clinically significant are hepatotoxic and neurotoxic reactions, which can lead to treatment interruption, reduced efficacy, and worse prognosis. This paper reviews current understanding of the pathogenesis of these complications, their clinical manifestations, and approaches to intensive care based on evidence-based medicine.
THE ROLE OF DIGITAL TECHNOLOGIES IN DEVELOPING THE CREATIVE ABILITIES OF PRIMARY TEACHERS
This article analyzes the role of digital technologies in the formation of creative competence in the process of training primary school teachers and suggests mechanisms for implementing innovative approaches in the pedagogical process. The conditions for the development of the components of creative competence of future primary school teachers are analyzed. Creative competence depends not only on pedagogical knowledge, but also on the ability to think creatively, based on a practical approach.
INTERPRETATION OF CYTOLOGICAL STUDIES ACCORDING TOTHE BETHESDA SYSTEM
This topic provides a comprehensive overview of the interpretation of cytological examination results using the Bethesda System. It highlights the importance of standardized reporting in cytology, particularly in cervical cancer screening programs. The annotation explains how the system classifies cellular findings into categories such as normal, atypical, lowgrade, and high-grade lesions, helping healthcare professionals identify early pathological changes
Copyright (c) 2026 Butayeva Hulkar Shavkatovna https://creativecommons.org/licenses/by-nc-nd/4.0
CLINICAL AND PHARMACOLOGICAL APPROACH TO THE TREATMENT OF CARDIAC ARRHYTHMIA USING ANTIARRHYTHMIC DRUGS
This article provides a comprehensive analysis of cardiac arrhythmias and the clinical and pharmacological characteristics of antiarrhythmic drugs used in their treatment. Arrhythmias arise as a result of disturbances in the heart rhythm and conduction system and manifest with varying degrees of clinical symptoms. In modern medicine, antiarrhythmic agents are considered one of the main tools for normalizing heart rhythm. In particular, the specific features of their use in both children and adults highlight their clinical significance. Therefore, this article discusses the pharmacodynamics, pharmacokinetics, indications for use, adverse effects, and the importance of an individualized approach to therapy. It also substantiates that the patient’s general condition, underlying diseases, and the type of arrhythmia are key factors in selecting appropriate treatment in clinical practice.
STATE OF SYSTEMIC AND LOCAL IMMUNE RESPONSE IN PATIENTS WITH OSTEOARTICULAR TUBERCULOSIS IN THE PERIOPERATIVE PERIOD
Bone and joint tuberculosis represents one of the most severe extrapulmonary forms of tuberculosis infection, constituting, according to various data, from 3 to 5% in the structure of all registered cases of tuberculosis. The disease is characterized by steadily progressive destructive damage to bone tissue, which often leads to persistent loss of joint function, disability of patients, and a significant decrease in their quality of life.
METABOLIC CHARACTERISTICS OF CONNECTIVE TISSUE IN THE PATHOGENESIS OF CHRONIC GENERALIZED PERIODONTITIS
The aim of the study was to assess the indicators of acute-phase inflammation and glycosaminoglycan metabolism in patients with chronic generalized periodontitis of various age groups. A total of 60 patients aged 20–55 years with moderate and severe chronic generalized periodontitis (CHP) and 20 healthy individuals were examined. Statistical processing was carried out using the student’s t-test at the significance level
MAIN ASPECTS OF COMPETENCY-BASED EDUCATION
This article provides a comprehensive analysis of the theoretical and practical aspects of education organized on the basis of a competencybased approach. In particular, it examines the types of professional and practical competencies, as well as the mechanisms of their formation and stage-by-stage development on a scientific and methodological basis
ENDOCRINE DYNAMICS AND METABOLIC TOXICITY OF GLUCOCORTICOID PHARMACOTHERAPY: OPTIMIZING TAPERING PROTOCOLS IN SYSTEMIC AUTOIMMUNE EXACERBATIONS
The potent immunosuppressive and anti-inflammatory properties of exogenous glucocorticoids are inextricably linked to severe, dose-dependent systemic toxicity, primarily manifesting as hypothalamic-pituitary-adrenal axis suppression and iatrogenic metabolic syndrome. This study evaluates the precise clinical efficacy, endocrine preservation, and metabolic outcomes of utilizing a rapid-tapering glucocorticoid bridge protocol compared to conventional, prolonged step-down therapy. A prospective observational cohort study was conducted involving 142 adult patients diagnosed with acute exacerbations of severe rheumatoid arthritis requiring immediate systemic corticosteroid intervention. Subjects were stratified into two clinical pathways: a conventional prolonged therapy cohort (n=68) receiving a standard, slow prednisone taper over 24 weeks, and a targeted rapid-taper cohort (n=74) achieving complete glucocorticoid cessation within 8 weeks, heavily bridged with early disease-modifying antirheumatic drugs. Clinical data indicate that extended receptor occupation by synthetic corticosteroids aggressively paralyses endogenous endocrine function while driving massive hepatic gluconeogenesis. The targeted rapid-taper cohort demonstrated an equivalent rate of clinical remission, maintaining a mean Disease Activity Score-28 of 2.9 ± 0.4 by week 24, but successfully preserved intrinsic adrenal function, evidenced by normal morning serum cortisol levels averaging 14.1 ± 2.2 mcg/dL. Conversely, the conventional group exhibited profound endocrine suppression, with morning cortisol plummeting to 5.2 ± 1.6 mcg/dL (p < 0.001), alongside a 28.3% incidence of clinically significant hyperglycemia. The dynamics of the observed results suggest that the historical paradigm of prolonged, cautious steroid weaning induces unacceptable metabolic collateral damage. Comprehensive pharmacotherapy must actively integrate aggressive, rapid dose deescalation protocols matched with potent steroid-sparing agents to halt acute inflammatory cascades without subjecting the patient to irreversible secondary adrenal insufficiency and progressive osteopenia.
HEMODYNAMIC AND GASTROINTESTINAL PHARMACODYNAMICS OF CYCLOOXYGENASE INHIBITORS: OPTIMIZING ANTI-INFLAMMATORY THERAPY IN CHRONIC OSTEOARTHRITIS
The chronic administration of non-steroidal anti-inflammatory drugs dictates a complex physiological compromise between prostaglandin-mediated mucosal defense and endothelial prostacyclin suppression. This study evaluates the precise clinical, gastrointestinal, and renal hemodynamic outcomes of utilizing highly selective cyclooxygenase-2 inhibitors compared to traditional non-selective agents buffered with proton pump inhibitors. A prospective observational cohort study was conducted involving 156 adult patients diagnosed with active, chronic osteoarthritis requiring daily systemic pharmacotherapy. Subjects were stratified into two clinical pathways: a conventional cohort (n=75) receiving continuous diclofenac coupled with omeprazole, and a targeted modern cohort (n=81) receiving isolated celecoxib therapy adjusted for baseline cardiovascular risk. Clinical data indicate that the constitutive suppression of cyclooxygenase-1 generates persistent microvascular ischemia in the gastric mucosa, despite profound acid suppression. The conventional cohort demonstrated a 22.6% incidence of subclinical erosive gastropathy and a mean hemoglobin drop of 1.2 ± 0.3 g/dL by day 90. Conversely, the targeted celecoxib group exhibited an 88.5% reduction in endoscopically confirmed mucosal lesions while maintaining equivalent pain suppression metrics. The selective inhibition of endothelial cyclooxygenase-2 in the targeted group, however, precipitated a subtle but statistically significant elevation in systolic blood pressure by an average of 4.5 ± 1.2 mmHg (p = 0.021), directly correlating with transient sodium retention and mild glomerular filtration rate depression. The dynamics of the observed results suggest that the universal prescription of any single anti-inflammatory class remains physiologically flawed. Comprehensive pharmacotherapy must actively integrate individualized baseline risk stratifications—balancing inherent gastrointestinal vulnerability against silent renovascular rigidity—to achieve sustained musculoskeletal analgesia without inducing iatrogenic organ failure.
PHARMACOKINETIC OPTIMIZATION AND TOXICITY MITIGATION OF CARDIAC GLYCOSIDES: THERAPEUTIC DRUG MONITORING OF DIGOXIN IN CHRONIC HEART FAILURE WITH ATRIAL FIBRILLATION
The integration of cardiac glycosides into contemporary cardiovascular pharmacotherapy demands an extraordinarily precise balance between positive inotropic efficacy and the constant threat of life-threatening proarrhythmic toxicity. This study evaluates the specific clinical, hemodynamic, and electrocardiographic outcomes of utilizing digoxin under strictly controlled pharmacokinetic parameters compared to traditional empirical dosing in a highly vulnerable patient cohort. A prospective clinical analysis was conducted involving 128 adult patients diagnosed with chronic heart failure with reduced ejection fraction and concomitant rapid atrial fibrillation. Subjects were stratified into two clinical pathways: a conventional empirical dosing cohort (n=62) receiving standard maintenance doses based strictly on body weight, and a targeted pharmacokinetic-guided cohort (n=66) where dosing was continuously adjusted via therapeutic drug monitoring and real-time glomerular filtration rate calculations. Clinical data indicate that static, uncalibrated dosing frequently ignores the highly variable volume of distribution and unpredictable renal clearance inherent to this drug class. The targeted cohort demonstrated a 91.0% success rate in achieving optimal serum trough concentrations (0.5–0.9 ng/mL), directly correlating with a rapid reduction in resting ventricular rates from 118 ± 12 bpm to 78 ± 8 bpm without inducing atrioventricular blockade. Conversely, the empirical group exhibited a 24.1% incidence of subclinical and overt digitalis toxicity, driven by unrecognized hypokalemia and transient renal impairment. The dynamics of the observed results suggest that the narrow therapeutic index of digoxin renders historical prescribing habits obsolete. Comprehensive pharmacotherapy must actively integrate rigorous serum concentration tracking, electrolyte stabilization, and continuous dynamic renal assessment to harness the vagomimetic benefits of cardiac glycosides while neutralizing their lethal toxic potential.