Lipid-lowering therapy with PCSK9-inhibitors in the management of cardiovascular high-risk patients: Effectiveness, therapy adherence and safety in a real world cohort

  Background: Proprotein convertase subtilisin/kexin type 9 (PCSK9)-inhibitors have shown great po­tential in efficient lipid lowering to achieve low-density lipoprotein-cholesterol (LDL-C) treatment goals. The aim of the study was too describe the clinical use of PCSK9-inhibitors and to investigate therapy adherence and safety outside of clinical trials. Methods: Thirty-eight patients were treated with PSCK9-inhibitors. Patients were eligible for this therapy based on their individual cardiovascular risk and when all other available lipid-lowering regi­men had failed. Every patient answered a questionnaire concerning medical history and relevant side effects and therapy adherence. Results: Conventional therapy reduced patient LDL-C levels by about 38%. However, in 26 of the 38 patients, LDL-C treatment goals were not fulfilled because patients did not tolerate further dose es­calation due to side effects. Using a PCSK9 inhibitor, LDL-C levels were reduced by another 54% and 42% of patients reaching treatment goals. The results show that most patients still require concomitant therapy to reach LDL-C target levels. Three patients required dose reduction or change of the PCSK9 inhibitor. 16% did not inject the PCSK9 inhibitor regularly. Conclusions: Only a minority of patients reached the recommended LDL-C goals. PCSK9-inhibitors were generally well tolerated. Despite low rates of reported side effects, therapy adherence was incom­plete, with 6 patients not injecting PCSK9-inhibitors on a regular basis. In-depth information about the medication and close supervision is advisable. PCSK9 inhibitors have shown great potential in aggressive lipid lowering therapy, but basic therapy is still required in most cases. Close supervision is recommended to improve therapy adherence. (Cardiol J 2018; 25, 1: 32–41

Style and Intersubjectivity in Youth Interaction

This book examines how style and intersubjective meanings emerge through language use. While numerous studies on youth language focus on face-to-face interaction, this book draws data from conversation, e-forums, teen fiction, and comics to offer an integrated account of language change in a community in flux

"Зелена" покрівля, як елемент захисту будинків

Розвиток міст на сучасному етапі потребує рішення низки проблем, пов'язаних з необхідністю будівництва обєктів у складних геомеханічних умовах [1], зсувонебезпечних територіях [2], реконструкцією житла, забезпечення енерго та ресурсоефективності будівель та споруд, тощо

The effects of nocturnal hemodialysis compared to conventional hemodialysis on change in left ventricular mass: Rationale and study design of a randomized controlled pilot study

BACKGROUND: Nocturnal hemodialysis (NHD) is an alternative to conventional three times per week hemodialysis (CvHD) and has been reported to improve several health outcomes. To date, no randomized controlled trial (RCT) has compared NHD and CvHD. We have undertaken a multi-center RCT in hemodialysis patients comparing the effect of NHD to CvHD on left ventricular (LV) mass, as measured by cardiac magnetic resonance imaging (cMR). METHODOLOGY/DESIGN: All patients in Alberta, Canada, expressing an interest in performing NHD are eligible for the study. Patients enrolled in the study will be randomized to either NHD or CvHD for a six month period. All patients will have a full clinical assessment, including collection of biochemical and cMR data at baseline and at 6 months. Both groups of patients will be monitored biweekly to optimize blood pressure (BP) to a goal of <130/80 mmHg post-dialysis using a predefined BP management protocol. The primary outcome is change in LV mass, a surrogate marker for cardiac mortality, measured at baseline and 6 months. The high sensitivity and reproducibility of cMR facilitates reduction of the required sample size and the time needed between measures compared with echocardiography. Secondary outcomes include BP control, anemia, mineral metabolism, health-related quality of life, and costs. DISCUSSION: To our knowledge, this study will be the first RCT evaluating health outcomes in NHD. The impact of NHD on LV mass represents a clinically important outcome which will further elucidate the potential benefits of NHD and guide future clinical endpoint studies

cAMP-dependent and cholinergic regulation of the electrogenic intestinal/pancreatic Na+/HCO3- cotransporter pNBC1 in human embryonic kidney (HEK293) cells

<p>Abstract</p> <p>Background</p> <p>The renal (kNBC1) and intestinal (pNBC1) electrogenic Na⁺/HCO₃^-cotransporter variants differ in their primary structure, transport direction, and response to secretagogues. Previous studies have suggested that regulatory differences between the two subtypes can be partially explained by unique consensus phosphorylation sites included in the pNBC1, but not the kNBC1 sequence. After having shown activation of NBC by carbachol and forskolin in murine colon, we now investigated these pathways in HEK293 cells transiently expressing a GFP-tagged pNBC1 construct. </p> <p>Results</p> <p>Na⁺- and HCO₃^--dependent pH_irecovery from an acid load (measured with BCECF) was enhanced by 5-fold in GFP-positive cells compared to the control cells in the presence of CO₂/HCO₃^-. Forskolin (10^-5M) had no effect in untransfected cells, but inhibited the pH_irecovery in cells expressing pNBC1 by 62%. After preincubation with carbachol (10^-4M), the pH_irecovery was enhanced to the same degree both in transfected and untransfected cells, indicating activation of endogenous alkalizing ion transporters. Acid-activated Na⁺/HCO₃^-cotransport via pNBC1 expressed in renal cells is thus inhibited by cAMP and not affected by cholinergic stimulation, as opposed to the findings in native intestinal tissue. </p> <p>Conclusion</p> <p>Regulation of pNBC1 by secretagogues appears to be not solely dependent on its primary structure, but also on properties of the cell type in which it is expressed.</p

Therapy preferences of patients with lung and colon cancer: A discrete choice experiment

Objectives: There is increasing interest in studies that examine patient preferences to measure health-related outcomes. Understanding patients’ preferences can improve the treatment process and is particularly relevant for oncology. In this study, we aimed to identify the subgroup-specific treatment preferences of German patients with lung cancer (LC) or colorectal cancer (CRC). Methods: Six discrete choice experiment (DCE) attributes were established on the basis of a systematic literature review and qualitative interviews. The DCE analyses comprised generalized linear mixed-effects model and latent class mixed logit model. Results: The study cohort comprised 310 patients (194 with LC, 108 with CRC, 8 with both types of cancer) with a median age of 63 (SD =10.66) years. The generalized linear mixed-effects model showed a significant (P<0.05) degree of association for all of the tested attributes. “Strongly increased life expectancy” was the attribute given the greatest weight by all patient groups. Using latent class mixed logit model analysis, we identified three classes of patients. Patients who were better informed tended to prefer a more balanced relationship between length and health-related quality of life (HRQoL) than those who were less informed. Class 2 (LC patients with low HRQoL who had undergone surgery) gave a very strong weighting to increased length of life. We deduced from Class 3 patients that those with a relatively good life expectancy (CRC compared with LC) gave a greater weight to moderate effects on HRQoL than to a longer life. Conclusion: Overall survival was the most important attribute of therapy for patients with LC or CRC. Differences in treatment preferences between subgroups should be considered in regard to treatment and development of guidelines. Patients’ preferences were not affected by sex or age, but were affected by the cancer type, HRQoL, surgery status, and the main source of information on the disease

Технологические решения для строительства разведочной вертикальной скважины глубиной 2800 метров на нефтяном месторождении (Томская область)

Цель работы – проектирование строительства разведочной вертикальной скважины глубиной 2800 метров на Лесмуровском нефтяном месторождении Томской области. В работе содержатся данные о геолого-геофизических данных Лесмуровского месторождения, технологических параметрах сооружения скважины, процессах бурения и заканчивания скважин, выбранном оборудовании, вопросы охраны окружающей среды и оценка экономической эффективности строительства скважины. Дипломная работа выполнена, опираясь на современные достижения техники и технологии в области строительства нефтяных и газовых скважин.The aim of the work is the design of the construction of an exploratory vertical well with a depth of 2,800 meters at the Lesmurovskoye oil field in the Tomsk Region. The work contains data on the geological and geophysical data of the Lesmurovskoye oil field, the technological parameters of the well construction, the drilling and completion processes, the selected equipment, environmental issues and the economic evaluation of well construction. The thesis is executed, relying on modern achievements of technology and technology in the field of oil and gas well construction

Regional differences in health care of patients with inflammatory bowel disease in Germany

Background: The regional availability of specialized physicians is an important aspect in healthcare of patients with IBD. The association between physician density and healthcare is not yet clear. Most studies did not consider district type, which reflects population density. Our research question was, “Do specialist density and district type influence the healthcare of IBD patients in Germany?” Methods: We combined a claims dataset from a German health insurance fund with population and physician data. Four main aspects were investigated: regular specialist visits, drug therapies, surveillance colonoscopy, and IBD-related hospitalizations. Various regression analyses were performed. Results: The study cohort was comprised of 21,771 individuals, including 9282 patients with Crohn disease and 12,489 patients with ulcerative colitis. Patients who were living in districts with higher specialist densities were more likely to attend specialist visits on a regular basis. No difference in the frequencies of TNF-alpha inhibitor therapies was found. However, individuals from urban areas were more likely to receive a permanent immunosuppressive therapy with continuous specialist support. Conclusions: The results revealed that some aspects had positive effects on the probability of implementing healthcare in accordance with pathways and guidelines. No clear evidence of a general healthcare undersupply in rural areas was found.DF