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Abstract Background Israel is unique in offering a formal subspecialty in Medical Administration and mandating it for physicians applying for senior roles. Data on the prevalence and characteristics of these specialists are limited. Methods The national registry of licensed physicians was used to identify all living physicians who completed the Medical Administration subspecialty by December 31, 2022. Data on year of medical licensing, city of residence, and list of additional recognized specialties along with their respective date of completion were extracted. Websites of key public health organizations were sampled to identify qualifications of persons in senior leadership positions. Results Since 1987, 277 physicians have completed the Medical Administration subspecialty, with a significant increase in annual certifications from 4.5 in 2015 (interquartile range [IQR] 4–6) to 13 (IQR 10.5–15) in 2022 (p

Abstract Background and objectives Public healthcare systems face constraints in financial and professional resources. The Mandatory Tenders Law 5752 − 1992 stipulates that before entering into a contract for the supply of a service or product, public authorities and government corporations must undergo a public tender process. The authors sought to identify and contextualize the trends observed in tenders for healthcare services over the past decade amid increasingly stringent resource constraints. What prevails over what: quality or price? Methods All tenders for services provided by health professionals published by the Ministry of Health and health maintenance organizations between 2013 and 2023 were collected. Each tender was assessed for the quality and price components. Trends in the quality and price percentage were evaluated. Results A total of 224 tenders were analyzed. A statistically significant weak negative correlation was found between the quality percentage and years (r=-0.185, p

In most cases, portal vein thrombosis progresses without treatment; spontaneous recanalization of portal vein develops in 42 % of patients with liver cirrhosis. Effective treatment strategies include administration of anticoagulants, interventional procedures such as transjugular intrahepatic porto-systemic shunt or endovascular fibrinolysis. Anticoagulant therapy has certain difficulties in patients with liver cirrhosis due to the complex profile of hemostasis, a tendency to both hemorrhages and hypercoagulation. In addition to traditional anticoagulants (heparin preparations, fondaparinux, vitamin K antagonists), direct oral anticoagulants have been widely used in recent years for portal vein thrombosis. Previously, portal vein thrombosis was considered a contraindication to performing transjugular intrahepatic porto-systemic shunt, currently the method is often used to restore portal blood flow through the shunt and prevent repeated thrombosis. Endovascular fibrinolysis is still an option for specialized centers for «difficult» patients. In cases of increased risk of venous thromboembolism, patients with liver cirrhosis are recommended to be prevented with low-molecular-weight heparin or direct oral anticoagulants, but further studies should clarify their effectiveness in this aspect. The review highlights data on the features of therapy, primary and secondary prevention of portal vein thrombosis in patients with liver cirrhosis. Despite the existing clinical recommendations for management of patients with cirrhotic portal vein thrombosis, the choice of a particular strategy primarily depends on an individualized assessment of risks and benefits of each treatment method.

Portal vein thrombosis is the most common thrombotic complication in patients with liver cirrhosis, especially in cases of severe forms. The pathogenesis is multifactorial in nature, it determined by a change in the balance between the coagulation and anticoagulation systems. Thrombosis is often asymptomatic and is accidentally detected, although it can be complicated by varicose bleeding, intestinal ischemia, and portal biliopathy. Ultrasound Doppler examination is a screening method, as an alternative, computed tomography and magnetic resonance imaging are used. The review highlights data on epidemiology, risk factors, clinical features, and diagnosis of portal vein thrombosis in patients with liver cirrhosis. The data on the effect of portal vein thrombosis on the progression of liver cirrhosis and the survival of patients, including after liver transplantation, are presented.

Handwriting kinematics (HWKs) were assessed in the randomized controlled ALPINE study of 2 long-acting injectable antipsychotics started during an acute exacerbation of schizophrenia. This exploratory analysis examined the relationship between baseline HWKs and response to acute antipsychotic treatment. Adults with acute schizophrenia were assigned to aripiprazole lauroxil or paliperidone palmitate (groups combined for this analysis). Treatment response was defined as ≥20% reduction from baseline in Positive and Negative Syndrome Scale (PANSS) total score at week 4. Two HWK measures, peak velocity (decreases with greater dysfunction) and percentage of nonballistic movements (%NBM; increases with greater dysfunction), were captured in 4 handwriting tasks (complex loops, maximum speed circles, overlay circles, and left-right loops). Peak velocity and %NBM at baseline were compared between responders and nonresponders. The analysis included 143 patients (mean baseline PANSS total score, 94.5). PANSS responders (n = 67 [46.9%]) had a lower mean peak velocity (i.e., slower pen movements) on all HWK tasks at baseline compared with nonresponders (n = 76): complex loops, 8.8 versus 12.1 cm/s; maximum speed circles, 18.0 versus 23.7 cm/s; overlay circles, 12.6 versus 17.2 cm/s; and left-right loops, 11.2 versus 14.6 cm/s. PANSS responders had a greater %NBM on 3 tasks compared with nonresponders: complex loops, 57.1% versus 47.4%; overlay circles, 30.6% versus 24.3%; and left-right loops, 58.7% versus 47.0%. In this exploratory analysis, PANSS responders to aripiprazole lauroxil or paliperidone palmitate treatment at week 4 had lower baseline HWK movement velocities and greater baseline %NBM versus nonresponders, suggesting that baseline HWKs might predict response to these antipsychotic drugs.

The article presents an observation of a rare benign lymphoproliferative disease — Castleman’s disease, with pronounced systemic symptoms. The clinical case is of interest not only for the rarity of pathology, but also for the peculiarities of clinical manifestations, including paraneoplastic pseudosclerodermic clinical and immunological syndrome, which was not previously described in the context of Castleman’s disease, Raynaud’s syndrome, severe pulmonary hypertension and a suspected (not proven morphologically) variant of extranodal lesion with its previously also notobserved localization in the sigmoid colon wall.

Background: Israel is unique in offering a formal subspecialty in Medical Administration and mandating it for physicians applying for senior roles. Data on the prevalence and characteristics of these specialists are limited. Methods: The national registry of licensed physicians was used to identify all living physicians who completed the Medical Administration subspecialty by December 31, 2022. Data on year of medical licensing, city of residence, and list of additional recognized specialties along with their respective date of completion were extracted. Websites of key public health organizations were sampled to identify qualifications of persons in senior leadership positions. Results: Since 1987, 277 physicians have completed the Medical Administration subspecialty, with a significant increase in annual certifications from 4.5 in 2015 (interquartile range [IQR] 4–6) to 13 (IQR 10.5–15) in 2022 (p < 0.001). Specialists completed the subspecialty a median of 18 years (IQR 13–21) post-licensing, with 269 physicians (97.1%) holding additional specialties, primarily in Internal Medicine, Pediatrics, Family Medicine, or Public Health. Compared to the general physician population, some base specialties like Public Health are over-represented while others, like Anesthesiology, are under-represented. Only 40 (14.4%) specialists reside outside major metropolitan areas. Nineteen (61.3%) general hospital CEOs, 2 (20%) psychiatric hospital CEOs, 13 (35.1%) Ministry of Health and 4 (7.8%) Sick Fund executives are specialists in Medical Administration (p < 0.005). Conclusions: The steady growth in the number of specialists in Medical Administration demonstrates the sustainability and scalability of this model, which may serve as a template for other healthcare systems. However, the limited representation of these specialists in senior roles of some organizations, and their concentration within certain specialties and regions, indicates areas for policy attention to enhance leadership diversity and reduce healthcare disparities. [ABSTRACT FROM AUTHOR]

Abstract Background A randomized, controlled, phase 3b study (ALPINE) evaluated efficacy and safety of a 2-month formulation of aripiprazole lauroxil (AL) using a 1-day initiation regimen in patients hospitalized for an acute exacerbation of schizophrenia. Paliperidone palmitate (PP) was used as an active control. Exploratory endpoint assessments included severity of illness, positive and negative symptoms, quality of life, caregiver burden, and satisfaction with medication. Methods Adults were randomly assigned to AL 1064 mg q8wk or PP 156 mg q4wk as inpatients, discharged after 2 weeks, and followed through week 25. Exploratory efficacy measures included the 3 original PANSS subscales, Clinical Global Impression−Severity (CGI-S) subscale, and caregiver Burden Assessment Scale. Exploratory patient-reported outcomes (PROs) included the Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF) and the Medication Satisfaction Questionnaire. Within-group changes from baseline through week 25 were analyzed for AL and PP separately. PROs were summarized based on observed data. Results Of 200 patients randomized (AL, n = 99; PP, n = 101), 99 completed the study (AL, n = 56; PP, n = 43). For AL, PANSS subscale and CGI-S scores improved from baseline through week 25 (mean [SE] change from baseline at week 25: Positive, −7.5 [0.70]; Negative, −3.9 [0.46]; General, −11.8 [0.83]; CGI-S, −1.3 [0.12]). Caregiver burden also improved (mean [SD] changes from baseline at week 9: −8.4 [10.15]; week 25: −8.9 [12.36]). Most AL patients were somewhat/very satisfied with treatment at each timepoint (70.8%–74.7%); mean Q-LES-Q-SF total scores were stable in the outpatient period. For PP, results were similar: PANSS Positive, −7.3 (0.67); Negative, −3.6 (0.69); General, −10.9 (1.22); CGI-S, −1.4 (0.16); caregiver burden, week 9: −8.8 (11.89) and week 25: −9.2 (14.55); satisfaction with treatment, 64.7%–69.3%; and stable Q-LES-Q-SF scores. Conclusions ALPINE patients initiating the 2-month AL formulation using the 1-day initiation regimen as inpatients and continuing outpatient care experienced schizophrenia symptom improvement, sustained patient satisfaction with medication, stable quality of life, and reduced caregiver burden. A similar benefit pattern was observed for PP. These results support the feasibility of starting either long-acting injectable in the hospital and transitioning to outpatient treatment. Trial registration ClinicalTrials.gov identifier: NCT03345979 [trial registration date: 15/11/2017].

Reference scenarios based on mathematical models are used by public health experts to study infectious diseases. To gain insight into modeling assumptions, we analyzed the three major models that served as the basis for policy making in Israel during the COVID-19 pandemic and compared them to independently collected data. The number of confirmed patients, the number of patients in critical condition and the number of COVID-19 deaths predicted by the models were compared to actual data collected and published in the Israeli Ministry of Health's dashboard. Our analysis showed that the models succeeded in predicting the number of COVID-19 cases but failed to deliver an appropriate prediction of the number of critically ill and deceased persons. Inherent uncertainty and a multiplicity of assumptions that were not based on reliable information have led to significant variability among models, and between the models and real-world data. Although models improve policy leaders' ability to act rationally despite great uncertainty, there is an inherent difficulty in relying on mathematical models as reliable tools for predicting and formulating a strategy for dealing with the spread of an unknown disease.

Debatable data on prevalence of coronary artery disease in liver cirrhosis are presented in the review. Influence of etiology of liver cirrhosis, of other risk factors on possibility of development of coronary atherosclerosis in terminal stages of liver pathology is considered. Necessity of conducting researches for purpose of specification of frequency of development of coronary artery disease in liver cirrhosis, of its interrelation with features of hepatic pathology, of possibilities of improvement of risk stratification and working out of treatment strategy of patients, including those expecting liver transplantation is noted.

Abstract Background The Israeli National Health Insurance Law provides permanent residents with a basket of healthcare services through non-profit public health insurance plans, independently of the individual’s ability to pay. Since 2015, several reforms and programs have been initiated that were aimed at reinforcing public healthcare and redressing negative aspects of the health system, and specifically the constant rise in private health expenditure. These include the “From Reimbursement-to-Networks Arrangement”, the “Cooling-off Period” program and the program to shorten waiting times. The objectives of this study were to identify, describe, and analyze changes in private hospitals in 1) the volume of publicly and privately funded elective surgical procedures; and 2) private health expenditure on surgical procedures. Methods Data on the volume and funding of surgical procedures during 2013–2018 were obtained from Assuta Medical Center, Hertzelia Medical Center, the Israeli Ministry of Health and the Central Bureau of Statistics. The changes in the volume and financing sources of surgical activities in private hospitals, in the wake of the reforms were analyzed using aggregate descriptive statistics. Results Between 2013 and 2018 the volume of surgical activities in private for-profit hospitals increased by 7%. Between 2013 and 2017, the distribution of financing sources of surgical procedures in private hospitals remained stable, with most surgical procedures (75–77%) financed by the voluntary health insurance programs of the health plans (HP-VHI). In 2018, following the regulatory reforms, a significant change in the distribution of financing sources was observed: there was a sharp decline in the volume of HP-VHI-funded surgical procedures to 26%. Concurrently, the share of publicly-funded surgical procedures performed in private hospitals increased to 56% in 2018.,. During the study period, private spending on elective surgical procedures in private hospitals declined by 53% while public funding for them increased by 51%. Conclusions and policy implications In the wake of the reforms, there was a substantial shift from private to public financing of elective surgical activity in private hospitals. Private for-profit hospitals have become important providers of publicly-funded procedures. It is likely that the reforms affected the public-private mix in the financing of elective surgical procedures in those hospitals, but due to the absence of a control group, causality cannot be proven. It is also unclear whether waiting times were shortened. Health reforms must be accompanied by a clear and comprehensive set of indicators for measuring their success.

Abstract Passage of the National Health Insurance Law (NHIL) in 1995 marked a turning point in the history of the Israeli healthcare system, ensuring sustainable, high-quality medical care to all eligible Israeli residents. Over 100 amendments have been made to the law over the years, yet additional adaptations are required to ensure the law’s relevance in years to come. In honor of the 25th anniversary of the passage of the law, the 19th annual Dead Sea Conference brought together prominent figures in the Israeli healthcare system for a discussion on “25 Years to the NHIL: Suggested Changes and Adaptations”. Key topics discussed in the conference were regulatory aspects related to the healthcare system, administration of medical services, and financial aspects pertinent to the NHIL. The following meeting report summarizes the insights and recommendations from this conference.

Clinical case of paraneoplastic vasculitis аssociated a brain tumor was presented. Paraneoplastic vasculitis is a rare type of paraneoplastic syndrome. The frequency of detection of paraneoplastic vasculitis in cancer patients is 0.01-5%. In 70% of cases, the manifestation of vasculitis is observed long before the clinical manifestations of the tumor. Most studies report so-called leukocytoclastic vasculitis (allergic) or allergic angiitis. Vasculitis is usually accompanied by slowly progressing tumors such as breast and prostate cancer. It also develops with of stomach cancer, lung cancer, kidney adenocarcinoma, epithelioma, sarcoma, cholangiocarcinoma, other solid tumors, multiple myeloma, non-Hodgkin’s lymphoma. The nosological forms of paraneoplastic vasculitis include called polyarteritis nodosa, hemorrhagic vasculitis, Wegener’s granulomatosis, non-specific aortoarteritis, idiopathic pulmonary hypertension syndrome, thrombovasculitis, allergic hemorrhagic vasculitis, cutaneous vasculitis, systemic necrotizing vasculitis with increased ANCA titer. The patient suffered from paraneoplastic vasculitis with the development of amyloidosis of vascular tissues and arterial hypertension. The progression of the vascular process led to damage of the arteries of the brain and heart, the development of ischemic stroke and hemodynamically significant stenosis of the coronary arteries, the development of acute myocardial infarction complicated by acute heart failure, which caused death. The clinical significance of the case lies in the fact that paraneoplastic vasculitis, which was developed due to a brain astrocytoma with the formation of amyloidosis was firstly described.

Presenters Kailey Love, MBA, MS, Jaeson Fournier, MPH, D.C, Nicholas Yagoda, MD, George Runger, William Riley, [...], Context: An effective clinic-based population care management program requires an accurate understanding of the complexity and care needs of the patient population. Patient empanelment is the assignment of patients to a provider and/or provider team. However, many patient empanelment methodologies are unidimensional, focusing solely on clinic use or disease state or severity, and do not address the wholistic care needs of the patient. Objective: This study develops a Patient Resource Intensity Scale (PRIS) that includes three dimensions based on resource use, severity, and social determinants of health. The goal is to accurately categorize patients according to their care needs and develop care teams who can meet these needs. Study Design and Analysis: Create and validate a patient stratification scale using a retrospective longitudinal analysis. Setting, Dataset, and Population Studied: The study setting is a large primary care safety net system with 32 sites and over 100,000 patients. The dataset consists of all patients seen by the clinic over a 3-year period (2019-2021). Data were extracted from the electronic health record and the billing system. Instrument: We developed the PRIS scale which incorporates three dimensions: 1) Chronicity/Severity; 2) Resource Intensity/Utilization; and 3) Social Determinants of Health. Outcome Measures and Results: The PRIS scale was used to assign patients to four quadrants based on chronicity and resource use. Patients in each quadrant were then classified according to social determinants of health (SDoH) risk. The findings indicate that approximately 83% of the patients were categorized into Quadrant 1 (low resource, low chronicity); approximately 16% in Quadrant 2 (high resource, low chronicity), and less than 0.7% are categorized in Quadrants 3 (high resource, low chronicity) and 4 (high resource, high chronicity) respectively. Conclusions: Many population care management strategies rely on one dimension, such as total resource use or diagnosis, which often fail to address the complexity of the patient care needs. The PRIS scale developed in this study can be used to better serves the needs of the patient population. The study findings are used to develop interdisciplinary care team models based on patient needs.

Abstract Background The Israeli public health system has seen a steady decline in public trust and confidence, which has resulted in an increased rate of individuals holding private and commercial health insurance policies that allow more choice of various services (especially choose the surgeon’s). This study evaluated the attitudes and beliefs of Israeli adults regarding public trust, equitability and choice within the public health system. Methods A cross-sectional telephone survey conducted among a representative random sample of Israeli adults (> 25 years). Participants responded to a 27-item questionnaire. Multivariate regression analyses were performed to determine the contribution of various socio-demographic variables to the perceptions of trust and equitability in the health system and the ability to choose a surgeon, As well as a possible links among these parameters. Results Of 865 adults that responded to the survey, most were women (51.8%), Jewish (68.6%), and married (73.0%). Trust in the public health system, the perception of the system’s equitability and the public’s perception of the importance of selecting a surgeon were inter-related. The results emphasize a possible association between three meaningful factors: the trust in the public health system, the perception of the system’s equitability and the public’s perception regarding the importance of selecting a surgeon. Conclusions Public trust in the public health system is a fundamental condition for maintaining an efficient and equitable health system in Israel. The survey suggests that uncertainty regarding the identity of the surgeon who will perform a procedure in a public hospital may be linked to a sense of insecurity and distrust of the public in the public health system. This study did not examine the causal relationship between the various factors, but the study data suggests a possible link between lower trust in the system and a lower perception of its equitability, and a subsequent associated increase in the public’s desire to select a surgeon. This study suggests to recognize public trust as a central and significant tool to strengthen public health system. One of the ways to strengthen the public’s confidence in the public health system could be to provide the patient with reliable information regarding parameters such as the identity of the senior surgeon in the operating room or the surgeon’s suitability for the patient’s medical condition.

Introduction: Liver plays an essential role in the metabolism, synthesis, transport and clearance of lipids and lipoproteins, therefore, changes in the lipid profile in liver pathology reflects the degree of its dysfunction. Leading role in the development of atherosclerosis belongs to lipid spectrum disorders in the form of hyperlipidaemia and dyslipidaemia, associated with an increased cardiovascular risk in liver cirrhosis. Aim: To study the relationship between violations of lipid profile of blood with the features and the clinical picture of Liver Cirrhosis (LC). Materials and Methods: The study was an open prospective and comparative analysis of patients with LC, conducted at Stavropol State Medical University (Stavropol State, Russia). Research was conducted from June till August 2020. In 108 patients with LC, blood concentration of total cholesterol, triglycerides, High Density Lipoproteins (HDL) and Low Density Lipoproteins (LDL) were studied in association with manifestations of the disease. Control group constituted of 45 healthy individuals, comparable in sex, age and ethnicity. Two sample student’s t-test, Newman Keuls test, chi-square test with Yates’s correction and Pearson’s linear correlation coefficient (r) were calculated. Receiver Operating Characteristic (ROC) analysis was used, the Odds Ratio (OR) and its 95% Confidence Interval (CI), sensitivity, specificity, positive and negative predictive value and accuracy were determined. Differences were considered statistically significant at p≤0.05. Results: Regardless of gender and age of patients, decrease of serum levels of total cholesterol (p

Lei Sun,1 Sergey Yagoda,2 Yangchun Du,3 Lisa von Moltke21Department of Clinical Pharmacology and Translational Medicine, Alkermes, Inc., Waltham, MA, USA; 2Department of Clinical Research, Alkermes, Inc., Waltham, MA, USA; 3Department of Biostatistics, Alkermes, Inc., Waltham, MA, USACorrespondence: Lei SunClinical Pharmacology and Translational Medicine, Alkermes, Inc., 852 Winter Street, Waltham, MA 02451, USATel +1 781 609 6151Fax +1 781 609 5851Email lei.sun@alkermes.comBackground: A combination of olanzapine and samidorphan (OLZ/SAM) is in development to provide the established antipsychotic efficacy of olanzapine while mitigating olanzapine-induced weight gain.Methods: Two multicenter, open-label, parallel-cohort studies were performed to evaluate the effect of moderate hepatic impairment (Child-Pugh score 7–9 [class B]; study 1) and severe renal impairment (estimated glomerular filtration rate: 15–29 mL/min/1.73 m2,; study 2) on the pharmacokinetics, safety, and tolerability of a single dose of OLZ/SAM 5/10 mg.Results: There was a 1.67-fold increase in area under the plasma concentration-time curve from time 0 to infinity (AUC0-∞) and a 2.17-fold increase in maximum plasma concentration (Cmax) of olanzapine, and a 1.52-fold increase in AUC0-∞ and a 1.63-fold increase in Cmax of samidorphan, in subjects with moderate hepatic impairment compared with healthy control subjects. Compared with healthy control subjects, subjects with severe renal impairment had a 33% and 56% reduction in clearance, a 1.51- and 2.31-fold increase in AUC0-∞, and a 1.32- and 1.37-fold increase in Cmax of olanzapine and samidorphan, respectively.Conclusion: OLZ/SAM 5/10 mg was generally well tolerated under the conditions of the studies, with a safety profile consistent with that observed in other clinical studies of OLZ/SAM.Keywords: olanzapine, samidorphan, renal impairment, hepatic impairment, pharmacokinetics

The article is devoted to analysis of relationship of left ventricular remodeling, plasma renin level, glomerular filtration rate in patients with arterial hypertension and renal additional arteries. It is shown that hormonal and hemodynamic factors in young patients with arterial hypertension of 1–2 degrees with renal additional arteries create a load on left ventricle, contributing to pathological myocardial remodeling in the form of eccentric hypertrophy and concentric remodeling.

Since the discovery of streptomycin, actinomycetes have been a useful source for new antibiotics, but there have been diminishing rates of new finds since the 1960s. The decreasing probability of identifying new active agents led to reduced interest in soil bacteria as a source for new antibiotics. At the same time, actinomycetes remain a promising reservoir for new active molecules. In this work, we present several reporter plasmids encoding visible fluorescent protein genes. These plasmids provide primary information about the action mechanism of antimicrobial agents at an early stage of screening. The reporters and the pipeline described have been optimized and designed to employ citizen scientists without specialized skills or equipment with the aim of essentially crowdsourcing the search for new antibiotic producers in the vast natural reservoir of soil bacteria. The combination of mechanism-based approaches and citizen science has proved its effectiveness in practice, revealing a significant increase in the screening rate. As a proof of concept, two new strains, Streptomyces sp. KB-1 and BV113, were found to produce the antibiotics pikromycin and chartreusin, respectively, demonstrating the efficiency of the pipeline.

Aim of investigation. Nowadays the question, whether pegylated interferon should be completely abandoned in the treatment of chronic hepatitis C (CHC) is still open. Beneficial interferon properties include: absence of mutagenic capacity for hepatitis C virus and drug interaction, stimulation of host immune response. These qualities formed the basis for development of the Russian pegilated interferon-alpha 2b (Pegaltevir®, LLC «FARMAPARK», Russia) and carrying out doublestaged randomized open clinical trial: study of safety, tolerability and pharmacokinetics of Pegaltevir® at single injection of increasing doses in various groups of healthy volunteers - the I stage; studying of efficacy and safety of Pegaltevir® in comparison to PegIntron® (Schering-Plough, USA) at CHC as a part of double antiviral therapy with ribavirin (Rebetol®, Schering-Plough, USA) - the II stage. This article presents results of the II phase of investigation. Material and methods. Original study included 140 adult antiviral treatment-naive patients with CHC and compensated liver function. Patients (aged 18 to 70 years) were distributed into four groups. Group 1 (main group, Pegaltevir®/Rebetol® treatment) - 55 patients, HCV genotype 1; group 2 (comparison group, PegIntron®/Rebetol® treatment) - 20 patients, HCV genotype 1; group 3 (main group, Pegaltevir®/Rebetol® treatment) - 47 patients, non-genotype 1 (2 and 3); group 4 (comparison group, PegIntron®/ Rebetol ® treatment) with non-genotype 1 (2 and 3). Assessment of Pegaltevir® efficacy was carried out in 4 weeks (rapid virologic response, RVR) and 12 weeks of treatment (early virologic response, EVR) in groups 1 and 3 in comparison to corresponding scores in groups 2 and 4 (primary criteria of efficacy were estimated in all 140 patients enrolled in original study. The response rate at the moment of secession of antiviral therapy, the sustained virologic response (SVR), histologic response (comparison of paired liver biopsies) served as secondary efficacy criteria and were estimated in 129 patients who completed treatment. The safety analysis was carried out for each patients included in the protocol who received at least one Pegaltevir® dose in comparison to patients who received at least one dose of PegIntron®, - respectively 102 and 38 patients. Results. RVR was comparable in the Pegaltevir® and PegIntron® groups: 65,6 and 82,4% respectively (p>0,05). RVR frequency genotype one patients was 45,3% in Pegaltevir® treatment group and 66,7% in PegIntron® treatment group (p>0,1). At patients with non-genotype 1 (2 and 3): 92,5 and 100% respectively (p>0,05). RVO did not significantly differ in the studied groups: 91,6 and 97,1% for all genotypes respectively (р>0,1). RVO rate for genotype 1 patients in Pegaltevir® group was 86,8%, in PegIntron® treatment group - 94,4% (р>0,1), in non-genotype 1 patients (2 and 3) it reached 97,6 and 100% in the specified patient groups (р>0,1). Response rate at the moment of treatment secession for Pegaltevir® and PegIntron® was 87,4 and 97,1% respectively for all genotypes (р>0,05). In patients with HCV genotype 1 this score Pegaltevir® treatment group reached 79,3%, in PegIntron® group - 94,4% (р> 0,05), in non-genotype 1 patients (2 and 3) - 97,6 and 100% respectively (р>0,1). SVR rate at Pegaltevir® treatment was 82,1% (for all genotypes), PegIntron® - 82,4% (for all genotypes, p>0,1). In HCV genotype 1 patients in Pegaltevir® treatment group SVR made 73,6%, in PegIntron® treatment group - 83,3%, p>0,1, for non-genotype 1 (2 and 3) - 92,9 and 81,3%, p>0,1. No significant differences between basic and control groups at analysis of paired liver biopsies for fibrosis stage reduction rate, absence of negative changes for fibrosis severity and proportion of patients with fibrosis progression were found. Pegaltevir® and PegIntron® treatment groups were comparable safety profile, adverse events were expected, mainly of mild and moderate severity. Conclusion. The hypothesis of identical efficacy of the Russian drug Pegaltevir® tested in the protocol in comparison to PegIntron® was correct and proved. Safety of Pegaltevir® was comparable to safety of PegIntron® as well.

Aim. To evaluate diagnostic significance of the type A vascular endothelial growth factor (VEGF-A) and its receptors type 1 and 2 (VEGF-R1 and VEGF-R2) in primary mitral valve prolapse (MVP) patients.Material and methods. Totally, 83 MVP patients studied: 61 males, 22 females; mean age 21,93±4,22 y. o. The signs of systemic inflammation were assessed, as the grade of connective tissue involvement. Immune enzyme analysis was done for serum levels of VEGF-А, VEGF-R1 and VEGF-R2 (“Bender MedSystems GmbH”,Austria). Controls included 20 healthy volunteers — 14 males, 6 females, mean age 21,10±0,55 y. o. with no MVP and any other dysplastic features.Results. In the MVP group, the decreased levels of circulating VEGF-R1 were found, as the increase of cases number of high (42,17%) and low (32,53%) concentration of VEGF-А. In low levels of VEGF-A and VEGF-A/ VEGF-R1 prevalence of grade II mitral regurgitation increases 5,1 times comparing to the group of retained balance of VEGF-A and VEGF-R1 — 95% confidence interval (CI) 1,25-20,88, and the prevalence of clinically significant cardiac rhythm and conduction disorders increases 5,25 times in comparison to the cases with elevated VEGF-A and VEGF-R1 — 95% CI 1,33-20,76 and 4,09 times — comparing MVP patients with retained balance of VEGF-A and VEGF-R1 — 95% CI 1,18-14,17.Conclusion. In primary MVP patients, regardless clinical phenotype of monogenic hereditary syndromes, the heterogeneity of deviation and regulation of VEGF has been established. Highest number of II grade mitral regurgitation, significant rhythm disorders was found in the group with low VEGF-A and VEGF-A/VEGF-R1, that might be implemented as optimized risk stratification in heterogenic MVP patients population.

INTRODUCTION In 2016, more than 90 million Americans, nearly 40% of our voting-eligible population, did not vote. (1) Significant gaps in voter participation occurred along racial, educational, and income-level divides, [...], Although the public&apos;s essential capacity for self-rule in the United States lies in the power of the ballot, there exist many barriers to voting, particularly for marginalized communities. These barriers cultivate less representative government and less inclusive public policy. Nonprofit and private health organizations, and in particular community health centers and safety-net hospitals, can help marginalized voting-eligible individuals overcome barriers to the ballot. With augmented, unbiased voter participation, elections would yield government that is more representative and public policy that is more equitable, while reducing costly and preventable health disparities. Health organizations can promote comprehensive, nonpartisan voter engagement through registration, mobilization, education, and protection of all voters. Key words: health; disparities; integrated; equity; voter engagement; voter registration; mobilization; education; voter education; protection

Background: Clinical practice guidelines support efforts to improve functioning in patients with schizophrenia. Discrepancies in the perception of cognitive status between clinicians, patients with schizophrenia, and their caregivers have been associated with impaired functional abilities in patients; medication side effects might worsen both cognition and daily functioning. We assessed daily/social functioning and cognition in stable patients with schizophrenia who switched to the long-acting injectable (LAI) antipsychotic aripiprazole lauroxil (AL). Methods: Clinically stable adults with residual symptoms of schizophrenia or intolerance following three or more doses of paliperidone palmitate or risperidone LAI were switched to flexibly dosed open-label AL treatment (441mg, 662mg, or 882mg every 4 weeks or 882mg every 6 weeks) for six months (ClinicalTrials.gov identifier: NCT02634320). Daily/social functioning was assessed using the Personal and Social Performance Scale (PSP); total and subscale scores were summarized using descriptive statistics. The cognitive status of patients was assessed using the New York Assessment of Adverse Cognitive Effects of Neuropsychiatric Treatment (NY-AACENT) at baseline and Month 6 or early termination, providing patient, caregiver, and clinician perspectives. A post hoc analysis assessed level of agreement in ratings of cognitive status among respondents, evaluated at baseline and last assessment, using weighted kappa coefficients (0.01-0.20, slight agreement; 0.21-0.40, fair agreement; 0.41-0.60, moderate agreement; 0.61-0.80, substantial agreement.). Results: All 51 enrolled patients received one or more AL doses; 35 completed the study, and 45 contributed data at last assessment. Mean age was 40.6 years; 72.5 percent of patients were male. Based on PSP total score, functioning was maintained from baseline (mean [standard deviation (SD)]: 55.1 [10.5]) through six months of AL treatment (mean [SD]: 57.7 [13.2]). Proportions of patients rating personal and social functioning issues as "not present" or "mild" remained stable between baseline and Month 6 for each PSP subscale. At baseline (n=50), cognitive difficulties were most commonly rated "not present" or "mild" in all NY-AACENT domains by patients (58-86% across domains), clinicians (62-94%), and caregivers (50-92%), and these rates were maintained or increased at last assessment for all reporters. Weighted kappa coefficients indicated fair-to-substantial agreement between patients and clinicians across domains at last assessment (0.32-0.64; baseline: 0.14-0.55); patient--caregiver agreement ranged from 0.07 to 0.50 at last assessment (baseline: 0.25-0.60). Conclusion: In clinically stable patients with schizophrenia who initiated AL, self-reported functioning was maintained over six months of treatment. Clinician-, caregiver-, and patient-reported cognitive function was stable at baseline and maintained in all NY-AACENT domains; patient--clinician agreement on level of cognitive impairment increased over six months of treatment with AL. [ABSTRACT FROM AUTHOR]

Introduction in practice of therapeutic establishments in the RF of antiviral therapy of chronic viral hepatitis in the form of interferon-free schemes led to considerable increase of the frequency of the stable virologic response. Study objective: determination of virologic response predictors in CVHC patients when various therapeutic schemes are used. Materials and methods: Group 1 of CVHC 52 patients with genotype 1 of HCV received standard anti-viral therapy, Group 2 (21 subject) – interferon-free scheme (Viekira Pak+ Ribavirin). Genetic polymorphisms IL-28В rs12979860 (С>Т) and rs8099917 (Т>G) and blood interferon-γ induced protein – IP-10 were determined. Results: standard anti-viral therapy in Group 1 resulted in SVR (sustained viral response) in 29 patients (55.7%). In Group 2 that received Viekira Pak 100% SVR was achieved in spite of more frequent F3 and 4 stage of fibrosis, unsuccessful anti-viral therapy (9 persons), contraindications to IFN-α drugs (6 persons). Unfavorable genotypes IL-28B ТТ (rs12979860) and GG (rs8099917) were associated in Group 1 with lack of SVR, level of IP-10 in patients with SVR was lower than the one in non-respondents. The therapy by Viekira Pak was well tolerated and resulted in SVR despite presence of grave hepatic fibrosis/ cirrhosis, concomitant pathology, unfavourable options of IL-28B, high IP-10 protein levels. Conclusion: choice of optimal anti-viral therapy schemes for each patient with CVHC must be done taken into account all possible predictors, which allows optimizing the therapy and preventing the necessity of repeated therapy.

Introduction: Adhesion molecules play an important role in the migration of leukocytes, process of inflammation and in remodeling of tissue. Intercellular Adhesion Molecule-1 (ICAM-1) is expressed along the luminal, intercellular, and subluminal surface of endothelial cells and their expression increases after stimulation by cytokines and TNF-α in Rheumatoid Arthritis (RA). Aim: To study the serum concentration of ICAM-1 in patients with rheumatoid arthritis. Materials and Methods: Levels of ICAM-1 in 134 patients with rheumatoid arthritis (30 male, 104 female) aged 20 to 66 years were studied. Control group constituted of 70 healthy individuals of age 22 to 55 years. Concentration of ICAM-1 was determined by ELISA. Statistical analysis of the data was performed using two sample Student’s t-criterion, criteria of Newman-Keuls and correlation n analysis with application of Pearson (r) and Spearman (rs) criteria. Results: Index DAS28 scored up to 5.49 (4.88-6.01) in the patients. Most of the patients were diagnosed with III x-ray stage, II and III functional class of the disease. In patients with rheumatoid arthritis significantly increased (p

Aim. To assess the condition of adhesion function of endothelium in various clinical variants of primary mitral valve prolapse (MVP). Material and methods. Totally, 91 patient studied with primary MVP at the age 21 (19-24) y. First grade mitral regurgitation was found in 45,1% and II — in 54,9% patients. MVP was solitary variant (6,6%) and comorbid with 1-3 minor anomalies of the heart (93,4%). Doppler-echocardiography was done on Vivid07 equipment (Israel). The grade of systemic involvement of connective tissue was 2 (1,5-4,0) points. Controls were 10 healthy persons, matched by age, sex, smoking, body mass index. By the immune enzyme method we checked plasmatic concentrations of L-, E-, Р-selectins, ICAM-1, VCAM-1, PECAM-1 (Bender MedSystems GmbH, Austria). Findings are presented as mediana (25-75 percentiles). Results. In MVP patients the levels of Е-selectin — 43,0 (33,7-54,8) ng/ mL, ICAM-1 — 669,9 (546,4-883,3) ng/mL and VCAM-1 — 925,0 (707,5- 1215,0) ng/mL, were significantly higher, and the level of РЕСАМ-1 — 49,8 (40,4-63,2) ng/mL, in opposite, lower than in control group. L- and P-selectins levels in MVP group were measured as relevant to controls values (p>0,05). In regurgitation cases of II degree, the level of E-selectin and ICAM-1 were maximal (p

Aim. To reveal changes in the thromboxane-prostacyclin balance and platelet aggregability in patients with various variants of minor cardiac abnormalities. Subjects and methods: Six-five patients (mean age 23.0±0.7 years) with minor cardiac abnormalities and 10 apparently healthy individuals were examined. Platelet aggregation induced by adrenaline, adenosine diphosphate, collagen) and the plasma levels of thromboxane B2 (TxB2) and 6-keto-prostaglandin F1α (6-keto-PGF1α) were determined. Results. Patients with abnormally located chordae (ALC) were found to have no deviations in the thromboxane-prostacyclin balance and platelet aggregability. Only decreased collagen aggregation was recorded in the groups of first-degree mitral prolapse (MP) and first-degree MP + ALC; in second-degree MP and second-degree MP + ALC, there was a reduction in platelet aggregation on all inductors and an increase in TxB2. Patients with myxomatous degeneration of the mitral valve exhibited reduced collagen-induced platelet aggregation and lower plasma 6-keto-PGF1α levels. Conclusion. The most pronounced changes in the thromboxane-prostacyclin balance and platelet aggregability were found in patients with MP and second-degree regurgitation, three intracardiac microabnomalities, and myxomatous degeneration of the mitral valve.

Aim. To investigate a clinicopathogenetic role of fibrinolysis regulators in chronic viral hepatitis (CVH) and viral cyrrhosis of the liver (CL). Material and methods. Seventy patients entered the study: 10 patients with CVH B, 33 - with CVH C, 6 - with CVH D, 21 - with viral CL (HCV-associated in 14 cases and HBV-associated in 7 cases. A concentration and activity of tissue plasminogen activator (TPA), the level of plasminogen-1 activator inhibitor (PAI-1) in blood plasma were estimated with enzyme immunoassay (Technoclone GmbH, Austria). PAI-1/TPA was estimated. Results. Increased TPA, PAI-1 concentrations and TPA activity in plasma with maximal values in CL were found. Most severe imbalance in the system of fibrinolysis regulators occurs in poor-prognosis cirrhosis and decompensated portal hypertension. High TPA concentration and activity in CL have a positive correlation with the Child-Pugh index, while low PAI-1/TPA correlates negatively with this index. Conclusion. TPA and PAI-1 correlations with hemorrhagic manifestations and prognosis of the disease suggest an essential clinical role of fibrinolysis regulators in chronic viral pathology of the liver.

Purpose. The objective is to determine the stress-strain state of supporting structures of the head car body and the traction transmission unit, which can be created in the operation of emergency situations, and to develop the measures aimed at improving the stress-strain state of these elements. Methodology. In order to achieve this objective, in performing the work an experimental determination of efforts and stress levels in the most loaded elements of supporting structures as well as the traction transmission units was conducted; design models for the theoretical determination of stress and effort levels were developed. Findings. Based on the analysis of the calculation results the best options for the upgrades, which have been put into the basis of proposals aimed at improving the strength indices, were revealed. Originality. Based on the experimental and theoretical studies, scientific monitoring of development works on modernization and improvement of strength indices of supporting structures of head cars of diesel trains DR1A was performed. Practical value. The technical solution to the measures, which are to be carried out beyond the limits of assigned operation lifetime for diesel train of the series specified was developed and transferred to the Ukrzaliznytsia experts to introduce the proposed measures on improving the strength indices.

Aim of investigation. To establish interrelation of intercellular interaction mediators with histological changes at chronic viral liver disease.Material and methods. Blood contents of immunoglobulins superfamily and selectin molecules was investigated in 101 patients with chronic viral liver diseases. Scores of ICAM-1, VCAM-1, Е-selectin, L-selectin and the Р-selectin were determined by enzyme-linked immunoassay method and were compared to values of Knodell histological activity index and Desmet fibrosis score as well as to E.M. Brunt hepatic steatosis levels.Results. At chronic viral hepatitis ICAM-1 and selectins blood contents increase whereas in patients with liver cirrhosis elevation of all adhesin levels was marked. Concentration of ICAM-1, VCAM-1, Е-, L-and Р-selectin at chronic viral liver diseases was increased along with increase of severity of inflammation and severity of hepatic fibrosis and had positive correlation with histological activity indexes (HAI) and liver fibrosis. Positive correlation of ICAM-1, VCAM-1 and Е-selectin with degree of liver steatosis was found. Level of immunoglobulin superfamily and selectin molecules were characterized by sufficient accuracy in detection of HAI over 8 points and detection of moderate/severe degree of fibrosis.Conclusions. Association of morphological signs with mediators of intercellular interactions indicates their important role in development and progression of chronic viral liver disease.

Aim of investigation. Comparative assessment of efficacy and safety of Pegaltevir and PegIntron in within pattern of combined antiviral therapy in previously untreated patients with chronic hepatitis C.Material and methods. Overall 140 patients with chronic hepatitis C, who received no antiviral therapy previously were included in original study. Patients were randomized in 4 groups. Groups differed in relation to received drug and hepatitis C virus genotype. All patients received 1,5 mkg per 1 kg body weight per week of Pegaltevir or PegIntron and 800–1400 mg of ribavirin per day. Preliminary estimation of drug efficacy was based on rates of rapid and early virologic response (RVR and EVR) achievement, dynamics of biochemical tests, dynamics of blood level of peginterferon alpha and neopterin. Safety features were estimated as well.Results. Comparative analysis has demonstrated absence of statistically significant distinctions of RVR and РВО rates at application of two peginterferon alpha-2b drugs. There were no differences in frequency of achievement of serologic response, as well as safety in Pegaltevir and PegIntron groups. Dynamics of blood concentration of peginterferon alpha correlated to neopterin concentration both in Pegaltevir group and in PegIntron group.Conclusions. Study results have shown high rates of RVR and РВО achievement, and acceptable safety profile of Pegaltevir, comparable with that of PegIntron at chronic hepatitis C in previously untreated patients.

Abstract. The levels of autoantibodies to collagen type I, II, III, IV and V were studied in blood plasma of 130 patients (18-32 years old) with undifferentiated connective tissue dysplasia, using immunoenzyme analysis. A correlation was revealed between the levels of autoantibodies to various collagen types, and external and/or heart manifestations of connective tissue dysplasia. Increased levels of autoantibodies to collagen type I and II were shown in patients with chest deformation, scoliosis, pronounced joint hypermobility syndrome, multiple minor intracardial anomalies. Increased antibodies to type I collagen were associated with flat-footedness, whereas levels of antibodies to collagen type I, II, and V correlated with myxomatous degeneration of mitral valve prolapse. Increase in anticollagen antibody levels in cases of pronounced external and cardiac markers of connective tissue dysplasia suggests an impairment of autoimmune regulatory mechanisms of collagen metabolism.