Drug Contraindications in Comorbid Diseases: a Protein Interactome Perspective

Adverse drug reactions (ADRs) are leading causes of death and drug withdrawals and frequently co-occur with comorbidities. However, systematic studies on the effects of drugs in comorbidities are lacking. Drug interactions with the cellular protein-protein interaction (PPI) network give rise to ADRs. We selected 6 comorbid disease pairs, identified the drugs used in the treatment of the individual diseases A and B — 44 drugs in anxiety and depression, 128 in asthma and hypertension, 48 in chronic obstructive pulmonary disease and heart failure, 58 in type 2 diabetes and obesity, 58 in Parkinson′s disease and schizophrenia, and 84 in rheumatoid arthritis and osteoporosis — and categorized them based on whether they aggravate the comorbid condition. We constructed drug target networks (DTNs) and examined their enrichment among genes in disease A/B PPI networks, expressed across 53 tissues and involved in ≈1000 pathways. To pinpoint the biological features characterizing the DTNs, we performed principal component analysis and computed the Euclidean distance between DTN component scores and feature loading values. DTNs of disease A drugs not contraindicated in B were affiliated with proteins common to A/B networks or uniquely found in the B network, similarly regulated common pathways, and disease-B specific pathways and tissues. DTNs of disease A drugs contraindicated in B were affiliated with common proteins or those uniquely found in the A network, differentially regulated common pathways, and disease A-specific pathways and tissues. Hence, DTN enrichment in pathways, tissues, and PPI networks of comorbid diseases will help identify drugs contraindications in comorbidities.

Meloxicam in pain syndrome treatment of comorbid diseases patients

The issue nonsteroidal anti-inflammatory drugs (NSAIDs) use safety is associated with a high frequency of adverse events (AEs) from the gastrointestinal tract and cardiovascular risks. Patients with lower back pain (LBP) and osteoarthritis (OA), as a rule, have comorbid diseases, such as arterial hypertension (AH), coronary heart disease (CHD), gastrointestinal tract (GIT) diseases, which significantly complicates the appointment of NSAIDs. The main guideline in NSAIDs appointment is the selective ability to inhibit cyclooxygenase-1 and -2 (COX). The ratio of the activity of NSAIDs when blocking COX-1/COX-2 allows us to judge their potential toxicity. And, then higher the selectivity of NSAIDs, then lower its toxicity. For example, the ratio of COX-1/COX-2 in meloxicam is 0.33, diclofenac – 2.2, tenoxicam – 15, piroxicam – 33, indomethacin – 107. To the predominantly selective COX-2 NSAIDs include meloxicam, which has little effect on the GIT, the lowest relative risk (RR) of complications from the cardiovascular system (CVS). The therapeutic efficacy of meloxicam is comparable to piroxicam and diclofenac. A number of studies have shown the high efficacy of meloxicam, both with per oral (p/o) administration (7.5–15 mg/d), and with intramuscular (i/m) administration (1.5 ml), and when injected into trigger zones. Both with p/o and the injectable form of meloxicam has minimal GIT AEs and absence local reaction in the injection area. The drug can be recommended both as a combination therapy and prescribed in monotherapy.

Assessment of physical function, quality of life, and medication adherence in elderly patients with rheumatic diseases

Background The proportion of older people in the total population has increased in Turkey as well as worldwide. As life expectancy rises, the increasing prevalence of rheumatic diseases poses major problems in the elderly. Comorbid diseases and the aging-induced changes in the endogenous immune response and the pharmacokinetic properties of therapeutic agents may complicate the decision to use a particular drug and result in a different clinical picture and treatment response. We, therefore, aimed to investigate the characteristics of chronic inflammatory diseases, their impact on physical function and quality of life, the prevalence of comorbid diseases that may complicate treatment planning, and treatment adherence in patients aged 65 years or older. Results One hundred seventy-four patients were included and divided into two age groups: 18–64 years (group 1, n = 85) and 65 years or older (group 2, n = 89). The mean age of all recruited patients was 57.55 ± 16.98 years. Of 174, 99 (56.9%) were female and 75 (43.1%) were male. The mean duration of rheumatic disease was 7 ± 4.8 years and age at onset was 51.46 ± 14.78 years. Gender distribution differed significantly by age group (P = 0.024). The percentage of females in group 1 was 48.2% and 65.2% in group 2. The occupational status also differed significantly by age group (P < 0.001). 48.2% of group 1 were employed and 57.3% of group 2 were housewives. Marital status varied significantly by age (P < 0.001). The percentage of married was 74.1% in group 1 and the percentage of separated/divorced/widowed in group 2 was 28.1%. There was no difference between groups 1 and 2 in terms of place of residence (P = 0.459). The prevalence of comorbid diseases and the rate of use of medications for comorbid diseases (non-rheumatic treatments) were higher in elderly patients. The rate of use of disease-modifying anti-rheumatic drugs (DMARDs) was 30.3% and biological agents 61.8% in the elderly group (≥ 65 years) (group 2) (P < 0.001). There were positive correlations between, Health Assessment Questionnaire (HAQ), Bath Ankylosing Spondylitis Functional Index (BASFI) and Nottingham Health Profile (NHP) domains in both groups. There was also a significant negative correlation between Medication Adherence Rating Scale (MARS) and all dimensions. Conclusions Elderly and younger patients with rheumatic diseases have different demographic and clinical characteristics. Physical function and quality of life are more affected by rheumatic diseases and treatment adherence is poorer in the elderly. Our study found a positive correlation between physical function and quality of life in both age groups. The treatment adherence rating scale showed a negative correlation with physical function and quality of life scores, with individuals with poor treatment adherence having worse physical function and quality of life.

The structure and features of the course of chronic kidney disease in patients with coronary heart disease and comorbid diseases

Aim. To investigate the prevalence, structure, and features of the course of chronic kidney disease (CKD) in patients with coronary heart disease (CHD) associated with comorbid diseases. Methods. The observation group consisted of 257 patients of the Interregional Clinical Diagnostic Center (Kazan) with coronary heart disease (20142018): 183 males and 74 females, aged from 38 to 95 years (mean age 61.80.6). Observation program: clinical examination; serum creatinine and lipid profiles, the albumin/creatinine ratio in a single portion of urine, morning urine osmolality, glomerular filtration rate estimated by the CKD-EPI; renal scintigraphy, ultrasonography of the kidneys, renal Doppler ultrasound and angiography. Chronic kidney disease was diagnosed if one of the criteria was met: the glomerular filtration rate 60 ml/min/1.73 m2 or the ratio of albumin to creatinine in urine (ACR) 30 mg/g. Statistical analysis was performed by using the methods of variational statistics: determination of the arithmetic mean (M), standard error of the mean (m) and difference significance according to the Student's test (t). Results. Examination of patients revealed the following comorbid diseases and syndromes: hypertension (90.7%), hyper- and dyslipidemia (96.5%), overweight/obesity (74.3%), diabetes mellitus (17.9%), chronic heart failure stages IIIa according to StrazheskoVasilenko classification (100%). 164 (63.8%) patients were first time diagnosed with chronic kidney disease: hypertensive nephropathy in 66.4%, ischemic renal disease in 21.9%, diabetic nephropathy in 2.4%, a combination of diabetic and hypertensive nephropathy in 9.3%. 51.2% of patients had stage 2 of chronic kidney disease, 42.1% stage 3, 6.7% stage 4 or 5. A feature of chronic kidney disease is its latent course (absence of complaints and clinical manifestations) and, as a consequence, unidentified diagnosis at the prehospital stage, which is generally characteristic of secondary nephropathies in cardiovascular diseases and these comorbid conditions. Conclusion. Chronic kidney disease was first diagnosed in 63.8% of patients with coronary heart disease with 1 to 5 comorbid diseases; a feature of chronic kidney disease is its secondary nature, the course of the disease is hidden by underlying and/or comorbid disease and, as a result, its late diagnosis.

Analytical assessment of hospital management of patients with COVID-19

Objective. To conduct an analytical assessment of the dynamics of the state of patients with COVID-19 in the conditions of a clinical healthcare organization taking into account comorbid diseases.Materials and methods. 96 in-patients` medical records kept in the state healthcare institution “Gomel City Clinical Hospital No.3” have been retrospectively analyzed.Results. The median age for women having undergone hospital treatment for pneumonia associated with COVID-19 was 58 years [45; 66], for men — 58 years [39; 64]. All the patients underwent a clinical examination according to temporary protocols. The most frequent comorbid diseases in the patients with COVID-19 were: arterial hypertension, ischemic heart disease, non-alcoholic liver disease, diabetes mellitus, chronic pyelonephritis, obesity. Polymorbidity was revealed in 49 % of the patients. Most patients had moderately severe pneumonia associated with COVID-19 (75 % of all the surveyed patients). In the patients with a mild course of pneumonia associated with COVID-19, the neutrophil-to-lymphocyte ratioin the peripheral blood was 2.1, whereas in the patients with a severe course — 8.82, which correlated with traditional prognostic indicators — the levels of C-reactive protein, d-dimers, lactate dehydrogenase.Conclusion. The neutrophil-to-lymphocyte ratio in the peripheral blood is a simple and affordable method of COVID-19 course prediction in comorbid patients.