Complete arterial grafting for coronary artery disease?

AbstractJ Thorac Cardiovasc Surg 2003;125:782-

Comparable patencies of the radial artery and right internal thoracic artery or saphenous vein beyond 5 years: Results from the Radial Artery Patency and Clinical Outcomes trial

ObjectiveTo investigate the optimum conduit for coronary targets other than the left anterior descending artery, we evaluated long-term patencies and clinical outcomes of the radial artery, right internal thoracic artery, and saphenous vein through the Radial Artery Patency and Clinical Outcomes trial.MethodsAs part of a 10-year prospective, randomized, single-center trial, patients undergoing primary coronary surgery were allocated to the radial artery (n = 198) or free right internal thoracic artery (n = 196) if aged less than 70 years (group 1), or radial artery (n = 113) or saphenous vein (n = 112) if aged at least 70 years (group 2). All patients received a left internal thoracic artery to the left anterior descending, and the randomized conduit was used to graft the second largest target. Protocol-directed angiography has been performed at randomly assigned intervals, weighted toward the end of the study period. Grafts are defined as failed if there was occlusion, string sign, or greater than 80% stenosis, independently reported by 3 assessors. Analysis is by intention to treat.ResultsAt mean follow up of 5.5 years, protocol angiography has been performed in groups 1 and 2 in 237 and 113 patients, respectively. There are no significant differences within each group in preoperative comorbidity, age, or urgency. Patencies were similar for either of the 2 conduits in each group (log rank analysis, P = .06 and P = .54, respectively). The differences in estimated 5-year patencies were 6.6% (radial minus right internal thoracic artery) in group 1 and 2.9% (radial minus saphenous vein graft) in group 2.ConclusionAt mean 5-year angiography in largely asymptomatic patients, the selection of arterial or venous conduit for the second graft has not significantly affected patency. This finding offers surgeons, for now, enhanced flexibility in planning revascularization

Is Sustained Virological Response a Marker of Treatment Efficacy in Patients with Chronic Hepatitis C Viral Infection with No Response or Relapse to Previous Antiviral Intervention?

Background: Randomised clinical trials (RCTs) of antiviral interventions in patients with chronic hepatitis C virus (HCV) infection use sustained virological response (SVR) as the main outcome. There is sparse information on long-term mortality from RCTs.  Methods: We created a decision tree model based on a Cochrane systematic review on interferon retreatment for patients who did not respond to initial therapy or who relapsed following SVR. Extrapolating data to 20 years, we modelled the outcome from three scenarios: (1) observed medium-term (5 year) annual mortality rates continue to the long term (20 years); (2) long-term annual mortality in retreatment responders falls to that of the general population while retreatment non-responders continue at the medium-term mortality; (3) long-term annual mortality in retreatment non-responders is the same as control group non-responders (i.e., the increased treatment-related medium mortality “wears off”).  Results: The mean differences in life expectancy over 20 years with interferon versus control in the first, second, and third scenarios were -0.34 years (95% confidence interval (CI) -0.71 to 0.03), -0.23 years (95% CI -0.69 to 0.24), and -0.01 (95% CI -0.3 to 0.27), respectively. The life expectancy was always lower in the interferon group than in the control group in scenario 1. In scenario 3, the interferon group had a longer life expectancy than the control group only when more than 7% in the interferon group achieved SVR.  Conclusions: SVR may be a good prognostic marker but does not seem to be a valid surrogate marker for assessing HCV treatment efficacy of interferon retreatment. The SVR threshold at which retreatment increases life expectancy may be different for different drugs depending upon the adverse event profile and treatment efficacy. This has to be determined for each drug by RCTs and appropriate modelling before SVR can be accepted as a surrogate marker

Estimating past hepatitis C infection risk from reported risk factor histories: implications for imputing age of infection and modeling fibrosis progression

BackgroundChronic hepatitis C virus infection is prevalent and often causes hepatic fibrosis, which can progress to cirrhosis and cause liver cancer or liver failure. Study of fibrosis progression often relies on imputing the time of infection, often as the reported age of first injection drug use. We sought to examine the accuracy of such imputation and implications for modeling factors that influence progression rates.MethodsWe analyzed cross-sectional data on hepatitis C antibody status and reported risk factor histories from two large studies, the Women’s Interagency HIV Study and the Urban Health Study, using modern survival analysis methods for current status data to model past infection risk year by year. We compared fitted distributions of past infection risk to reported age of first injection drug use.ResultsAlthough injection drug use appeared to be a very strong risk factor, models for both studies showed that many subjects had considerable probability of having been infected substantially before or after their reported age of first injection drug use. Persons reporting younger age of first injection drug use were more likely to have been infected after, and persons reporting older age of first injection drug use were more likely to have been infected before.ConclusionsIn studies of fibrosis progression, modern methods such as multiple imputation should be used to account for the substantial uncertainty about when infection occurred. The models presented here can provide the inputs needed by such methods. Using reported age of first injection drug use as the time of infection in studies of fibrosis progression is likely to produce a spuriously strong association of younger age of infection with slower rate of progression

Understanding the Effects of Long-duration Space Flight on Astronant Functional Task Performance

Space flight is known to cause alterations in multiple physiological systems including changes in sensorimotor, cardiovascular, and neuromuscular systems. These physiological changes cause balance, gait and visual disturbances, cardiovascular deconditioning, and loss of muscle mass and strength. These changes may affect a crewmember's ability to perform critical mission tasks immediately after landing on a planetary surface. To understand how changes in physiological function affect functional performance, an interdisciplinary pre- and postflight testing regimen, Functional Task Test (FTT), was developed to systematically evaluate both astronaut functional performance and related physiological changes. Ultimately this information will be used to assess performance risks and inform the design of countermeasures for exploration class missions. We are currently conducting the FTT study on International Space Station (ISS) crewmembers before and after 6-month expeditions. Additionally, in a corresponding study we are using the FTT protocol on subjects before and after 70 days of 6deg head-down bed-rest as an analog for space flight. Bed-rest provides the opportunity for us to investigate the role of prolonged axial body unloading in isolation from the other physiological effects produced by exposure to the microgravity environment of space flight. Therefore, the bed rest analog allows us to investigate the impact of body unloading on both functional tasks and on the underlying physiological factors that lead to decrement in performance and then compare them with the results obtained in our space flight study. Functional tests included ladder climbing, hatch opening, jump down, manual manipulation of objects and tool use, seat egress and obstacle avoidance, recovery from a fall and object translation tasks. Physiological measures included assessments of postural and gait control, dynamic visual acuity, fine motor control, plasma volume, heart rate, blood pressure, orthostatic intolerance, upper- and lower-body muscle strength, power, endurance, control, and neuromuscular drive. ISS crewmembers were tested three times before flight, and on 1, 6, and 30 days after landing. Bed-rest subjects were tested three times before bed-rest and immediately after getting up from bed-rest as well as 1, 6, and 12 days after reambulation

New loci associated with birth weight identify genetic links between intrauterine growth and adult height and metabolism.

Birth weight within the normal range is associated with a variety of adult-onset diseases, but the mechanisms behind these associations are poorly understood. Previous genome-wide association studies of birth weight identified a variant in the ADCY5 gene associated both with birth weight and type 2 diabetes and a second variant, near CCNL1, with no obvious link to adult traits. In an expanded genome-wide association meta-analysis and follow-up study of birth weight (of up to 69,308 individuals of European descent from 43 studies), we have now extended the number of loci associated at genome-wide significance to 7, accounting for a similar proportion of variance as maternal smoking. Five of the loci are known to be associated with other phenotypes: ADCY5 and CDKAL1 with type 2 diabetes, ADRB1 with adult blood pressure and HMGA2 and LCORL with adult height. Our findings highlight genetic links between fetal growth and postnatal growth and metabolism

Impact of Common Diabetes Risk Variant in MTNR1B

The risk of type 2 diabetes (T2D) is increased by abnormalities in sleep quantity and quality, circadian alignment, and melatonin regulation. A common genetic variant in a receptor for the circadian-regulated hormone melatonin (MTNR1B) is associated with increased fasting blood glucose and risk of T2D, but whether sleep or circadian disruption mediates this risk is unknown. We aimed to test if MTNR1B diabetes risk variant rs10830963 associates with measures of sleep or circadian physiology in intensive in-laboratory protocols (n = 58–96) or cross-sectional studies with sleep quantity and quality and timing measures from self-report (n = 4,307–10,332), actigraphy (n = 1,513), or polysomnography (n = 3,021). In the in-laboratory studies, we found a significant association with a substantially longer duration of elevated melatonin levels (41 min) and delayed circadian phase of dim-light melatonin offset (1.37 h), partially mediated through delayed offset of melatonin synthesis. Furthermore, increased T2D risk in MTNR1B risk allele carriers was more pronounced in early risers versus late risers as determined by 7 days of actigraphy. Our results provide the surprising insight that the MTNR1B risk allele influences dynamics of melatonin secretion, generating a novel hypothesis that the MTNR1B risk allele may extend the duration of endogenous melatonin production later into the morning and that early waking may magnify the diabetes risk conferred by the risk allele

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Международный музыкальный конкурс в формировании имиджа страны проведения (на примере Евровидения 2017)

Аннотация выпускной квалификационной работы Орлов Никита Сергеевич «МЕЖДУНАРОДНЫЙ МУЗЫКАЛЬНЫЙ КОНКУРС В ФОРМИРОВАНИИ ИМИДЖА СТРАНЫ ПРОВЕДЕНИЯ (НА ПРИМЕРЕ ЕВРОВИДЕНИЯ-2017)» Н. рук. - Быкова Елена Владимировна, доктор филологических наук, доцент Кафедра связей с общественностью Очная форма обучения Актуальность: международный музыкальный конкурс Евровидение как самое масштабное регулярное высокотехнологичное телевизионное и медиа-событие, которое . Е ежегодно акцентирует внимание аудитории на национально-культурных особенностях страны-организатора конкурса, формирует значительные туристические потоки и тем самым способствует формированию имиджа территории. Более того, победа страны-участницы конкурса Евровидения зачастую отражает идеолого-политический вектор Европы и по сути дела выполняет функцию политического PR страны-победителя и страны-хозяйки мероприятия. Следовательно анализ используемых на мероприятии коммуникативных технологий является актуальным и востребованным для событийного и устроительного PR Объект исследования: коммуникационные активности международного музыкального конкурса (на примере Евровидения в Киеве в 2017 г.). Предмет исследования: функция статусного PR-мероприятия в формировании имиджа страны. Цель исследования: доказать, что международный музыкальный конкурс Евровидение способствует формированию имиджа страны проведения. Задачи исследования: разработать терминологический аппарат исследования на основе научной литературы по имиджмейкингу, брендингу и ивент-менеджменту; определить актуальные коммуникационные технологии, применяемые в рамках специальных событий для формирования имиджа страны; описать роль Европейского Вещательного Союза как организатора Евровидения в формировании имиджа страны проведения конкурса; оценить эффективность реализованных коммуникативных технологий формирования имиджа страны в рамках Евровидения; дать рекомендации по формированию имиджа страны с помощью Евровидения. Теоретическая база: научные труды Е. Быковой, Д. Гавры, А. Панкрухина, Б. Дженеса, Е. Кавериной, У. Хальцбаура, Дж. Голдблатта а также труды Д. Пассмана о музыкальном бизнесе, П. Джордана о продвижении имиджа стран с помощью Евровидения и др. Эмпирическая база: PR-документы, размещенные на сайте Евровидения и Европейского Вещательного Союза; более полутора миллиона статей об Украине в европейских СМИ, размещенные в базе проекта мониторинга международного имиджа Украины «Oko»; данные базы материалов СМИ и социальных медиа Factiva; данные Google.Analytics. Практическая значимость: исследование доказывает, что международный музыкальный конкурс Евровидение формирует имидж страны проведения независимо от успешности использования конкретных технологий формирования имиджа страны. Тезисы исследования были апробированы на международном научном форуме «Медиа в современном мире. 57-е Петербургские чтения», опубликованы в сборнике материалов статей форума и имеют статус научной статьи, размещенной в базе РИНЦ. Структура работы: Работа состоит из введения, 3 глав: «функция специального события в формировании имиджа страны», «Евровидение как специальное событие Европейского Вещательного Союза» и «коммуникационный потенциал Евровидения как площадки для формирования имиджа страны», заключения, списка использованной литературы из 67 позиций и 12 приложений. Общий объем 76 страниц.Abstract of graduating qualification thesis Mikita Arlou INTERNATIONAL MUSIC CONTEST IN HOST COUNTRY IMAGE FORMATION (ON THE EXAMPLE OF EUROVISION 2017) Supervisor associate professor Elena Bykova, doctor of philology Department of PR in business full-time study Relevance: the international music contest Eurovision as the most wide scale regular high tech TV and Media event which annually emphasizes audience attention on national cultural features of the host country, forms tourist flows which have huge influence on territorial image formation. Besides the win of a participating in the Eurovision country often shows the ideological and political European vector and in fact serves as political PR of the winning or host country. Consequently the analysis of applied communication technologies is relevant and in-demand for event PR. Research object: communication activities of international music contest (on the example of Eurovision in Kyiv in 2017). Research subject: function of status PR event in country image formation. The aim of research: to prove that international music contest Eurovision contributes host country image formation. The tasks of research: to develop research terminology based on scientific literature on image making, branding and event management; to define actual communication technologies applied in special PR events on country image formation; to describe European Broadcasting Union role in host country image formation; to appreciate effectiveness of applied communication technologies on host country image formation in Eurovision; to give recommendations for host country image formation with the help of Eurovision. Theoretical base: scientific works written by E. Bykova, D. Gavra, A. Pankrukhin, B. Jenes, E. Kaverina, U. Halcbaur, J. Goldblatt and D. Passman´s works on music business and P. Jordan on county image building with the help of Eurovision, etc. The empirical base: PR documents from official Eurovision and European Broadcasting Union websites; more than 1.5 million articles on Ukraine in European media stored in the base of international Ukrainian image monitoring project Oko; content of the mass media and social media base Factiva; Google.Analytics data. Practical significance: the research proves that international music contest Eurovision is relevant for the host country image formation independently of the success level of applied country image formation communication technologies. Approbation: General positions of current thesis were aprobated on international scientific forum Media in modern world and were published at the collection of articles of the forum and have the status of a scientific article posted in the RINC database. Thesis structure: Research consists of introduction, 3 chapters: Special event function in country image formation, Eurovision as EBU special event and communication potential of Eurovision as a platform for image formation; conclusion, literature list from 67 positions and 12 attachments. The total volume is 76 pages