Chronic pain syndromes are an important medical problem generated by various molecular, genetic, and pathophysiologic mechanisms. Back pain, neuropathic pain, and posttraumatic pain are the most important pathological processes associated with chronic pain in adults. Standard approaches to the treatment of them do not solve the problem of pain chronicity. This is the reason for the search for new personalized strategies for the prevention and treatment of chronic pain. The nitric oxide (NO) system can play one of the key roles in the development of peripheral pain and its chronicity. The purpose of the study is to review publications devoted to changes in the NO system in patients with peripheral chronical pain syndromes. We have carried out a search for the articles published in e-Library, PubMed, Oxford Press, Clinical Case, Springer, Elsevier, and Google Scholar databases. The search was carried out using keywords and their combinations. The role of NO and NO synthases (NOS) isoforms in peripheral pain development and chronicity was demonstrated primarily from animal models to humans. The most studied is the neuronal NOS (nNOS). The role of inducible NOS (iNOS) and endothelial NOS (eNOS) is still under investigation. Associative genetic studies have shown that single nucleotide variants (SNVs) of NOS1, NOS2, and NOS3 genes encoding nNOS, iNOS, and eNOS may be associated with acute and chronic peripheral pain. Prospects for the use of NOS inhibitors to modulate the effect of drugs used to treat peripheral pain syndrome are discussed. Associative genetic studies of SNVs NOS1, NOS2, and NOS3 genes are important for understanding genetic predictors of peripheral pain chronicity and development of new personalized pharmacotherapy strategies.

We studied the complex effect of genetic and non-genetic factors on the formation of opioid-associated resistance using machine learning methods in patients with chronic pain syndrome against the background of pancreatic cancer. Fifty-seven factors for predicting the realization of pharmacoresistance were studied in all examined Caucasian patients. The most significant predictive factors were determined and a software-analytical complex "Algorithm for assessing the significance of clinical and pathogenetic factors for predicting the safety of opioid therapy" was developed.

Pancreatic cancer is a leading cause of deaths among the cancers of gastrointestinal tract organs. It ranks fourth in men and fifth in women among all death causes after lung, stomach, colorectal and prostate cancer, with the incidence equal to 4.2% in the world, including that in Russia [1]. Pancreatic cancer is a malignant neoplasm with high mortality, early metastases and the lack of proper efficiency when chemotherapy, radiation therapy and combination therapy are applied [2].

Background — Obligatory use of strong opioids for treating chronic pain syndrome in patients with pancreatic cancer provides the implementation of opioid-associated adverse reactions. Genetic and non-genetic risk factors are predictive of the opioid therapy safety. Contemporary methods of information analysis allow using prognostic risk models for practical application. Objective — Identification of significant risk factors for the development of opioid-associated adverse drug reactions in patients with chronic pain syndrome against the background of pancreatic cancer. Material and Methods — The study included 90 patients with chronic pain against the background of pancreatic cancer, randomized at a ratio of 1: 1. Group 1 received morphine sulfate (MS), group 2 received fentanyl transdermal therapeutic system (FTTS) with standard adjuvant therapy (ketoprofen, diazepam, amitriptyline). To assess pain level, the 10-point Digital Rating Scale, the Visual Analogue Scale and the pain questionnaires were used. The assessment of the treatment safety was conducted by the Naranjo Scale. Assessment of prognostic genetic and non-genetic factors was carried out using ROC analysis with calculation of AUC (the area under the ROC-curve). Results — Prognostic models of good quality were determined with the optimal ratio of sensitivity and specificity for the influence of genetic and non-genetic risk factors on the development of opioid-associated adverse drug reactions (OA-ADRs) in comparison groups. Various prognostic factors, complementing each other, were identified in the comparison groups. Conclusion — The following OA-ADRs predicting factors were identified: for FTTS-associated nausea and vomiting – age and carriage of rs7438135 AG genotype of UGT2B7 gene; for local reactions – the sum of points on the ESAS scale and carriage of rs7438135 AA genotype of UGT2B7 gene; for difficulty urinating – the level of glomerular filtration rate; for neurotoxicity – the level of AST and bilirubin, and the carriage of rs1128503 GG genotype of ABCB1 gene; for pruritus – carriage of rs1045642642 AA genotype of ABCB1 gene. The prognostic factors for the implementation of MS-associated neurotoxicity were age and comorbidity; for dry mouth was predicted best from the sum of points on the MMCE scale; weakness was predicted by the carriage of rs7668258 TT genotype of UGT2B7 gene.

Relevance. Monitoring of antibiotic resistance and the frequency of isolation of microorganisms at the regional level in each medical organization is of paramount importance for the implementation of epidemiological safety.Objective. To identify the main microbiological trends based on the analysis of the microflora of patients in a single — profile hospital in order to implement weaknesses in strategic planning activities.  Materials and methods. A comprehensive analysis of the pharmacoepidemiological results of the consumption of antimicrobial drugs with calculated drug resistance indices and microbiological monitoring data demonstrated the presence of weaknesses and strengths for the strategic development of a multidisciplinary hospital at the regional level in terms of epidemiological safety. Results. Statistically significant differences in the microbiological structure of pathogens are predetermined by the profile of medical care. The main trends in the change in the microflora of a multidisciplinary hospital as a whole are the prevalence of fungal and gram-negative pathogens over gram-positive ones. The presence of a relatively high index of consumpion of cephalosporins of 3–4 generations, fluoroquinolones, carbapenems, protected penicillins determines the high drug resistance index of Klebsiella pneumoniae (0.86) and characterizes the main microbiological trends of a multidisciplinary clinic. Conclusion. Risk stratification by the level of multidrug-resistant pathogens, the use of deterrent strategies for prescribing antimicrobials, the implementation of educational modules, the evaluation of the effectiveness and monitoring of the risk stratification program with in the framework of antimicrobial technologies, the analysis of microbial landscape data using decision support programs are the main tasks of the functioning of a multidisciplinary team of specialists in a multidisciplinary clinic to control antibiotic resistance.