Diagnosis and Treatment Patterns of Chronic Thromboembolic Pulmonary Hypertension in Russia, Kazakhstan, Turkey, Lebanon, and Saudi Arabia: A Registry Study.

BACKGROUND: Patients with chronic thromboembolic pulmonary hypertension (CTEPH) in countries with limited resources have, to date, been poorly represented in registries. OBJECTIVE: This work assesses the epidemiology, diagnosis, hemodynamic and functional parameters, and treatment of CTEPH in Russia, Kazakhstan, Turkey, Lebanon, and Saudi Arabia. METHODS: A prospective, cohort, phase IV, observational registry with 3-year follow-up (n = 212) in patients aged ≥ 18 years diagnosed with CTEPH was created. Clinical, hemodynamic, and functional parameters were obtained at an initial visit, follow-up visits, and a final visit at the end of 3 years' observation or end of follow-up. Data were recorded on electronic case report forms. Parameters evaluated included 6-minute walking distance (6MWD), use of pulmonary endarterectomy (PEA), balloon pulmonary angioplasty (BPA), pulmonary hypertension (PH)-targeted therapy, and survival. All statistical analyses were exploratory and descriptive, and were performed in the overall population. RESULTS: The most common symptoms were typical of those expected for CTEPH. Almost 90% of patients underwent right heart catheterization at diagnosis or initial study visit. In total, 66 patients (31%) underwent PEA before the initial visit; 95 patients (45%) were considered operable, 115 (54%) were inoperable, and two (1%) had no operability data. Only 26 patients (12%) had been assessed for BPA at their initial visit. PH-targeted therapy was documented at diagnosis for 77 patients (36%), most commonly a phosphodiesterase type 5 inhibitor (23%). Use of PH-targeted therapy increased to 142 patients (67%) at the initial visit, remaining similar after 3 years. Use of riociguat increased from 6% of patients at diagnosis to 38% at 3 years. Between baseline and end of observation, results for patients with paired data showed an increase in 6MWD. Survival at the end of observation was 88%. CONCLUSIONS: These data highlight the current diagnosis and management of CTEPH in the participating countries. They show that early CTEPH diagnosis remains challenging, and use of off-label PH-targeted therapy is common. CLINICALTRIALS: gov: NCT02637050; registered December 2015.

Prototype Expert System for Gout Diagnosis on an Outpatient Basis.

Gout is a systemic disease that is caused by the deposition of monosodium urate crystals in various tissues which leads to inflammation in them. This disease is often misdiagnosed. It leads to the lack of adequate medical care and development of serious complications, such as urate nephropathy and disability. The current situation can be improved by optimizing the medical care provided to patients, which requires searching for new strategies in terms of diagnosis. One of these strategies is the development of an expert system for providing information assistance to medical specialists which was a purpose of this study. The developed prototype expert system for gout diagnosis has knowledge base including 1144 medical concepts and 5 640 522 links, intelligent knowledge base editor and software which helps practitioner make the final decision. It has sensitivity of 91,3% [95% CI, 89,1%-93,1%], specificity of 85,4% [95% CI, 82,9%-87,6%] and AUROC 0,954 [95% CI, 0,944-0,963].

Immunomorphogenesis in Degenerative Disc Disease: The Role of Proinflammatory Cytokines and Angiogenesis Factors.

Back pain (BP) due to degenerative disc disease (DDD) is a severe, often disabling condition. The aim of this study was to determine the association between the expression level of proinflammatory cytokines (IL-1ß, IL-6, and IL-17), angiogenesis markers (VEGF-A and CD31) in intervertebral disc (IVD) tissue and IVD degeneration in young people with discogenic BP. In patients who underwent discectomy for a disc herniation, a clinical examination, magnetic resonance imaging of the lumbar spine, histological and immunohistochemical analyses of these factors in IVD were performed in comparison with the parameters of healthy group samples (controls). Histology image analysis of IVD fragments of the DDD group detected zones of inflammatory infiltration, combined with vascularization, the presence of granulation tissue and clusters of chondrocytes in the tissue of nucleus pulposus (NP). Statistically significant increased expression of IL-1ß, IL-6, IL-17, VEGF-A and CD31 was evident in the samples of the DDD group compared with the controls, that showed a strong correlation with the histological disc degeneration stage. Our results denote an immunoinflammatory potential of chondrocytes and demonstrates their altered morphogenetic properties, also NP cells may trigger the angiogenesis.

Comparison of rilmenidine and lisinopril on ambulatory blood pressure and plasma lipid and glucose levels in hypertensive women with metabolic syndrome.

OBJECTIVE: In previous studies, the I1 imidazoline specific agonist rilmenidine effectively lowered office blood pressure (BP) in patients with metabolic syndrome, improved glucose metabolism and did not demonstrate unfavourable effects on plasma lipids. The aim of the present study was to investigate the effects of 12weeks therapy with rilmenidine compared with the ACE inhibitor lisinopril on ambulatory BP, plasma lipid and fasting glucose levels in women with metabolic syndrome. RESEARCH DESIGN: Prospective randomised open-label, blinded end-points study. METHODS: Female patients (n = 51) with hypertension and other components of metabolic syndrome were treated with 1 mg rilmenidine (n = 24) or 10 mg lisinopril (n = 27), once- or twice-daily. Anthropometric measurements, office BP and heart rate (HR) measurements, ambulatory BP monitoring, lipid and fasting glucose assessment were performed before and after 12weeks of treatment MAIN OUTCOME MEASURES: Changes in ambulatory BP and HR, including 24-h, daytime and night-time values, and in lipids and glucose levels. All changes were adjusted for baseline values using the analysis of covariance method. RESULTS: Ambulatory 24-h systolic BP and diastolic BP were decreased significantly in the rilmenidine group (-11.9 +/- 1.9 and -7.7 +/- 0.8 mm Hg, p < 0.001) respectively and the lisinopril group (-11.0 +/- 1.8 and -6.7 +/- 0.7 mm Hg respectively, p < 0.001). There were no significant differences between the two groups. Rilmenidine reduced 24-h ambulatory HR (-3.6 +/- 0.8 bpm versus 0.3 +/- 0.8 bpm with lisinopril; p = 0.002). The reductions of day-time and night-time BP were also significant for both treatment groups, but the rilmenidine group demonstrated a greater decrease in night-time diastolic BP (p = 0.046). Rilmenidine significantly increased HDL cholesterol and decreased fasting glucose levels (p = 0.009 and p = 0.012, respectively). HDL cholesterol tended to increase and fasting glucose tended to decrease in the lisinopril group. However, differences between groups were not significant. CONCLUSION: Rilmenidine has similar effects on ambulatory BP patterns in hypertensive women with metabolic syndrome as lisinopril. Rilmenidine compared with lisinopril significantly reduces ambulatory HR. In this study, rilmenidine and lisinopril demonstrate similar effects on plasma lipid and fasting glucose levels.

Efficacy and Safety Assessment of a Novel Once-Daily Tablet Formulation of Tramadol : A Randomised, Controlled Study versus Twice-Daily Tramadol in Patients with Osteoarthritis of the Knee.

OBJECTIVE: To compare the 24-hour sustained efficacy and safety of a new tramadol once-daily formulation (tramadol OAD) using Contramid((R)) controlled-release technology with a marketed twice-daily formulation (tramadol BID). PATIENTS, DESIGN AND SETTING: 431 patients with osteoarthritis of the knee were enrolled in this randomised, double-blind, multicentre, parallel study. After titration to optimum dose (range 100-400mg), patients received medication for 12 weeks. MAIN OUTCOME MEASURES AND RESULTS: Efficacy evaluations included: Western Ontario and McMaster University Osteoarthritis Index (WOMAC) scores (pain, stiffness, physical function and global), daily efficacy ratings (post-dose: tramadol OAD 24 hours; tramadol BID 12 hours), pain ratings over 24 hours, and patient and investigator overall ratings. Non-inferiority was demonstrated for the primary endpoint, mean percentage change in WOMAC pain score from baseline to week 12 (tramadol OAD 58%; tramadol BID 59%) [95% CI -7.67, 3.82]. The median optimum dose received was 200mg (both treatments). In 73% of patients, pain was mild to absent at the end of the dosing interval for both treatments (tramadol OAD 24 hours; tramadol BID 12 hours). Pain ratings over 24 hours were similar between groups, indicating 24-hour sustained efficacy for tramadol OAD. More tramadol BID patients reported dizziness/vertigo (37% vs 26%), vomiting (14% vs 8%) and headache (18% vs 13%) while tramadol OAD patients reported more somnolence (30% vs 21%). CONCLUSIONS: This study demonstrated that this novel tramadol OAD formulation provides sustained analgesic efficacy over the entire 24-hour dosing interval and a clinically favourable safety profile, both of which will provide a clear clinical benefit.

Relationships between erythrocyte membrane properties and components of metabolic syndrome in women.

BACKGROUND: Membrane structure in metabolic syndrome has not been fully investigated. The aim of our study was to determine the relationship between structural parameters of the erythrocyte membrane and blood pressure, indices of obesity, plasma lipids, and glucose levels in female patients with metabolic syndrome. MATERIAL/METHODS: In 23 women with metabolic syndrome and 12 control normotensive women, anthropometric indices, blood pressure, and serum lipids were evaluated and an oral glucose tolerance test was performed. Erythrocyte membranes obtained from these patients were investigated by electron spin resonance spectroscopy and the spin-labeling method. The order parameter S (membrane microviscosity), parameter h (index of membrane hydrophobicity), and the a/b ratio (index of the membrane surface configuration) were calculated. Data were analyzed using univariate correlation and stepwise multiple regression analysis. RESULTS: All membrane parameters differed significantly in women with metabolic syndrome from controls (P<0.001). The order parameter S was negatively related to waist circumference (R=-0.59, P<0.01) and positively to systolic blood pressure (R=0.44, P<0.05). Negative correlations of parameter h and the a/b ratio with postload plasma glucose level (R=-0.60 and -0.63, respectively, P<0.01) were observed. In stepwise multiple regression analysis the variation in the order parameter S was mainly explained by waist circumference and systolic BP (52%), and in parameter h and a/b ratio by postload glucose level (35% and 34%, respectively). CONCLUSIONS: Erythrocyte membrane structural changes in women are associated with features of metabolic syndrome, especially with abdominal obesity, high systolic blood pressure, and postload glucose level.