137 research outputs found

    Динамика органной дисфункции и маркеров воспаления у пациентов с септическим шоком при мультимодальной гемокоррекции: мультицентровое, рандомизированное, контролируемое исследование

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    АКТУАЛЬНОСТЬ: Септический шок считается наиболее серьезным осложнением в интенсивной медицине и сопровождается значительной летальностью. Экстракорпоральная гемокоррекция может улучшить результаты лечения пациентов с септическим шоком. ЦЕЛЬ ИССЛЕДОВАНИЯ: оценка влияния гемокоррекции с помощью мультимодального адсорбента «Эфферон ЛПС» на динамику органной дисфункции и маркеры воспаления у пациентов с септическим шоком. МАТЕРИАЛЫ И МЕТОДЫ: Мультицентровое рандомизированное контролируемое исследование проведено в четырех медицинских организациях города Москвы (НИИ СП им. Н.Ф. Склифосовского ДЗМ, ГКБ № 1 им. Н.И. Пирогова ДЗМ, ГКБ им. С.С. Юдина ДЗМ, ГКБ № 68 им. В.П. Демихова ДЗМ) с марта 2021 г. по май 2022 г. В исследование включены 58 пациентов (29 мужчин и 29 женщин) с септическим шоком. Рандомизацию проводили в соотношении 2:1 (гемоперфузия: контроль). Не позднее 24 ч после включения пациента в исследование выполняли процедуры селективной гемоперфузии или использовали стандартную терапию. Гемосорбцию с использованием «Эфферон ЛПС» проводили двукратно, с интервалом 24,5 (23,3–26,0) ч. РЕЗУЛЬТАТЫ: Применение селективного гемосорбента «Эфферон ЛПС» позволило уже через 72 ч снизить тяжесть органной дисфункции у пациентов с септическим шоком с 7 до 3 баллов по шкале SOFA (Sequential Organ Failure Assessment) за счет улучшения гемодинамики, респираторной и почечной функции. В отличие от контрольной группы, в группе «Эфферон ЛПС» уже через 72 ч значимо снижался уровень С-реактивного белка (СРБ) в 1,5 раза, прокальцитонина (ПКТ) — в 2,7 раза, интерлейкина-6 — в 2,3 раза. Тяжесть органной дисфункции значимо коррелировала с уровнем СРБ (r = 0,346) и ПКТ (r = 0,444). Длительность госпитализации выживших пациентов составила 16,1 и 30,1 дня в группе «Эфферон ЛПС» и контрольной группе соответственно (p = 0,032). Потребность в проведении заместительной почечной терапии у выживших к 3-м суткам значимо снижалась с 73,7 до 33,3 % только в группе «Эфферон ЛПС», но не в контрольной группе. ВЫВОДЫ: Применение селективного гемосорбента «Эфферон ЛПС» позволило уменьшить выраженность системного воспаления и значимо снизить тяжесть органной дисфункции у пациентов с септическим шоком за счет улучшения показателей гемодинамики, газообмена и почечной функции

    Protocol for the safety and efficacy of fecal microbiota transplantation liquid in children with autism spectrum disorder: a randomized controlled study

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    BackgroundAutism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social interaction, repetitive behavior and language impairment, and its worldwide prevalence has been found to be increasing annually in recent years. Till now, ASD is uncurable as its pathogenesis remains unknown. However, studies on both animals and humans have demonstrated that fecal microbiota transplantation (FMT) may ameliorate the symptoms of ASD, as well as gastrointestinal symptoms. Nonetheless, there is still no agreement regarding the optimal dosage or duration of FMT treatment for individuals with ASD.MethodsThis clinical study is a double-blind, randomized, interventional trial conducted at a single center. The aim is to investigate the safety and efficacy of a pediatric formulation of FMT for ASD. A total of 42 children between the ages of 3–9 with ASD will be randomly assigned in a 2:1 ratio to either an FMT treatment group (n = 28) or a placebo group (n = 14), forming cohort 1. Additionally, 30 healthy children of similar age and gender will be recruited as the control group (cohort 2). Cohort 1 will be assessed using a variety of scales, including the Autism Behavior Checklist, Childhood Autism Rating Scale, Social Responsiveness Scale, Gastrointestinal Symptom Rating Scale, Children’s Sleep Habits Questionnaire, and Psychoeducational Profile (Third Edition). These assessments will evaluate the effectiveness of FMT in reducing core symptoms and comorbidities (such as gastrointestinal symptoms and sleep disturbances) in children with ASD. The study will use metagenomic and metabolomic sequencing to assess changes in the composition and structure of the intestinal flora and its metabolites in blood, urine, and feces following treatment. Furthermore, the study will evaluate the acceptability of the FMT formulation by participants’ legal guardians and investigate differences in the intestinal flora and metabolism in the FMT group before and after treatment compared to 30 healthy children.Clinical trial registrationhttps://www.chictr.org.cn/, identifier ChiCTR2200058459

    Comparative safety evaluation of intranasal and intramuscular immunisation with Ad26 and Ad5-vectored vaccines to prevent coronavirus infection

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    Scientific relevance. Intranasal vaccination may dramatically change current approaches to mass immunisation against various infections, shifting the focus from inducing systemic humoral and cellular immune responses to developing mucosal immunity and protective barriers on the mucous membranes, which are entry points for pathogens. Therefore, the safety of switching from intramuscular to intranasal vaccination should be evaluated.Aim. This study aimed to compare the safety of intranasal and intramuscular vaccination using the intermediate results of the phase III VCI-COV-III clinical trial in healthy volunteers.Materials and methods. The evaluation of the safety profile was based on the adverse events and adverse drug reactions (ADRs) documented by investigators in the interim report on the randomised, double-blind clinical trial of the Salnavac intranasal vaccine (InV) and the Gam-COVID-Vac intramuscular vaccine (ImV) against coronavirus infection. The report covered 42 days of observation in 137 healthy volunteers.Results. ADRs were reported for 17/68 (25%) and 30/69 (43.5%) volunteers in the InV group and the ImV group, respectively (p=0.036). The ADRs reported for the InV group were systemic and local, short-term, mostly mild, and generally consistent in incidence and nature with the ADRs typically observed with other nasal products.Conclusions. According to the preliminary data obtained in the clinical trial, the InV demonstrates a high level of safety. Its safety profile is comparable with those of other intranasal and intramuscular vaccines for the prevention of coronavirus infection

    Сравнительная оценка безопасности интраназальной и внутримышечной иммунизации вакцинами для профилактики коронавирусной инфекции на основе аденовирусов Ad26 и Ad5

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    Scientific relevance. Intranasal vaccination may dramatically change current approaches to mass immunisation against various infections, shifting the focus from inducing systemic humoral and cellular immune responses to developing mucosal immunity and protective barriers on the mucous membranes, which are entry points for pathogens. Therefore, the safety of switching from intramuscular to intranasal vaccination should be evaluated.Aim. This study aimed to compare the safety of intranasal and intramuscular vaccination using the intermediate results of the phase III VCI-COV-III clinical trial in healthy volunteers.Materials and methods. The evaluation of the safety profile was based on the adverse events and adverse drug reactions (ADRs) documented by investigators in the interim report on the randomised, double-blind clinical trial of the Salnavac intranasal vaccine (InV) and the Gam-COVID-Vac intramuscular vaccine (ImV) against coronavirus infection. The report covered 42 days of observation in 137 healthy volunteers.Results. ADRs were reported for 17/68 (25%) and 30/69 (43.5%) volunteers in the InV group and the ImV group, respectively (p=0.036). The ADRs reported for the InV group were systemic and local, short-term, mostly mild, and generally consistent in incidence and nature with the ADRs typically observed with other nasal products.Conclusions. According to the preliminary data obtained in the clinical trial, the InV demonstrates a high level of safety. Its safety profile is comparable with those of other intranasal and intramuscular vaccines for the prevention of coronavirus infection.Актуальность. Интраназальная вакцинация может в значительной мере изменить подходы к массовой иммунизации населения для профилактики различных инфекций, меняя акцент с формирования системного гуморального и клеточного ответа на создание барьерной защиты слизистых оболочек – входных ворот возбудителя, и развитие мукозального иммунного ответа. В связи с этим актуальной представляется оценка безопасности применения вакцин для профилактики коронавирусной инфекции при изменении способа введения – с внутримышечного на интраназальный.Цель. Сравнительная оценка безопасности интраназальной и внутримышечной вакцинации на основании промежуточных результатов клинического исследования III фазы VCI-COV-III с участием здоровых добровольцев.Материалы и методы. Оценка безопасности проводилась на основании зарегистрированных исследователями нежелательных явлений и реакций на момент составления промежуточного отчета по данным 42 дней наблюдения за 137 добровольцами в рамках рандомизированного двойного слепого клинического исследования интраназальной вакцины (ИнВ) Салнавак и внутримышечной вакцины (ВмВ) Гам-КОВИД-Вак для профилактики коронавирусной инфекции.Результаты. Число добровольцев с зарегистрированными нежелательными реакциями в исследовании составило 17 из 68 (25%) и 30 из 69 (43,5%) человек в группах с введением ИнВ и ВмВ соответственно (p=0,036). В группе добровольцев, получавших ИнВ, были зарегистрированы кратковременные общие и местные нежелательные реакции в основном легкой степени тяжести. Частота и характер отмечаемых реакций в целом соответствуют таковым при применении иных продуктов с интраназальным путем введения.Выводы. Предварительные данные клинического исследования показали высокий уровень безопасности исследуемой интраназальной вакцины. Профиль безопасности ИнВ сопоставим с иными интраназальными или внутримышечными вакцинами для профилактики коронавирусной инфекции

    Relatório de estágio de coordenação em investigação clínica em dois hospitais parceiros da Blueclinical CRP

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    Este relatório descreve as atividades realizadas no âmbito do estágio curricular em coordenação de investigação clínica que decorreu através da BlueClinical, nos hospitais Pedro Hispano da Unidade Local de Saúde de Matosinhos e Senhora da Oliveira em Guimarães, no âmbito do Mestrado em Gestão da Investigação Clínica, durante o período de cerca de 8 meses, com início em setembro de 2021. Este estágio teve como objetivos a aquisição de competências para realizar tarefas relacionadas com a atividade de coordenação clínica, de modo a permitir o exercício das atividades desde o início até à conclusão de um ensaio clínico, num ambiente real de trabalho. Neste relatório é também abordado o estado da arte da investigação clínica em Portugal, com especial enfoque nos obstáculos que dificultam a evolução da investigação em Portugal e potenciais iniciativas para os ultrapassar. Adicionalmente, é ainda analisado o futuro da investigação clínica e que possíveis reformulações à forma de implementar ensaios clínicos podem daí advir. As características dos estudos com que foi possível contactar no decorrer do estágio curricular serão descritas, bem como as diferentes atividades que foram desenvolvidas no papel de coordenador de ensaios clínicos. Foi ainda realizada uma análise exploratória dos potenciais riscos na execução do estágio e da própria atividade de coordenação através de um plano de gestão de risco. A avaliação global da experiência no estágio e das competências adquiridas foi positiva e permitiu aplicar na prática todo o conhecimento que foi transmitido ao longo do programa do Mestrado. Os objetivos propostos inicialmente foram atingidos com sucesso, o que permite concluir que toda a experiência foi capaz de habilitar para o exercício das funções de coordenação da investigação clínica no mundo profissional.This report describes the activities carried out within the scope of the curricular internship in clinical research coordination that took place through BlueClinical, in the hospitals of Pedro Hispano of the Local Health Unit in Matosinhos and Senhora da Oliveira in Guimarães, within the scope of the master’s degree in Clinical Research Management, over a period of about 8 months starting in September 2021. This internship aimed to provide the skills to perform tasks related to the clinical coordination activity and to perform these activities from the beginning to the end of a clinical trial, in a real work environment. This report also explores the state of the art of the clinical research in Portugal, with a special focus on the obstacles that hinder the evolution of research in Portugal and potential initiatives to overcome them. In addition, the future of clinical research is also analyzed as well as the possible reformulations in the way of implementing clinical trials that may result from it. The characteristics of the studies that were accompanied during the curricular internship are described, as well as the different activities that were developed in the role of clinical trial coordinator. An exploratory analysis of the potential risks in the execution of the internship and the coordination activity itself was also carried out through a risk management plan. The global assessment of the internship experience and skills acquired was positive and allowed to apply in the practice all the knowledge that was transmitted throughout the Master program. The objectives that were initially proposed were successfully achieved, which allows us to conclude that the whole experience was able to capacitate for the exercise of functions in clinical research coordination in the professional world

    Randomized controlled trial to evaluate the efficacy and safety of fexuprazan compared with esomeprazole in erosive esophagitis

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    Background: Fexuprazan, a novel potassium-competitive acid blocker, reversibly suppresses the K+/H+-ATPase enzyme in proton pumps within gastric parietal cells. Fexuprazan's suppression of gastric acid was maintained in healthy individuals for 24 h in a dose-dependent manner. Aim: To compare fexuprazan to esomeprazole and establish its efficacy and safety in patients with erosive esophagitis (EE). Methods: Korean adult patients with endoscopically confirmed EE were randomized 1:1 to receive fexuprazan 40 mg or esomeprazole 40 mg once daily for eight weeks. The primary endpoint was the proportion of patients with healed EE confirmed by endoscopy at week 8. The secondary endpoints included the healing rate of EE at week 4, symptom response, and quality of life assessment. Safety profiles and serum gastrin levels were compared between the groups. Results: Of the 263 randomized, 218 completed the study per protocol (fexuprazan 40 mg, n = 107; esomeprazole 40 mg, n = 111). Fexuprazan was non-inferior to esomeprazole regarding the healing rate at week 8 [99.1% (106/107) vs 99.1% (110/111)]. There were no between-group differences in the EE healing rate at week 4 [90.3% (93/103) vs 88.5% (92/104)], symptom responses, and quality of life assessments. Additionally, serum gastrin levels at weeks 4 and 8 and drug-related side effects did not significantly differ between the groups. Conclusion: Fexuprazan 40 mg is non-inferior to esomeprazole 40 mg in EE healing at week 8. We suggest that fexuprazan is an alternative promising treatment option to PPIs for patients with EE.ope

    Safety and efficacy of ganaxolone in patients with CDKL5 deficiency disorder: results from the double-blind phase of a randomised, placebo-controlled, phase 3 trial

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    BACKGROUND: CDKL5 deficiency disorder (CDD) is a rare, X-linked, developmental and epileptic encephalopathy characterised by severe global developmental impairment and seizures that can begin in the first few months after birth and are often treatment refractory. Ganaxolone, an investigational neuroactive steroid, reduced seizure frequency in an open-label, phase 2 trial that included patients with CDD. We aimed to further assess the efficacy and safety of ganaxolone in patients with CDD-associated refractory epilepsy. METHODS: In the double-blind phase of this randomised, placebo-controlled, phase 3 trial, done at 39 outpatient clinics in eight countries (Australia, France, Israel, Italy, Poland, Russia, the UK, and the USA), patients were eligible if they were aged 2-21 years with a pathogenic or probably pathogenic CDKL5 variant and at least 16 major motor seizures (defined as bilateral tonic, generalised tonic-clonic, bilateral clonic, atonic, or focal to bilateral tonic-clonic) per 28 days in each 4-week period of an 8-week historical period. After a 6-week prospective baseline period, patients were randomly assigned (1:1) via an interactive web response system to receive either enteral adjunctive ganaxolone or matching enteral adjunctive placebo (maximum dose 63 mg/kg per day for patients weighing ≤28 kg or 1800 mg/day for patients weighing >28 kg) for 17 weeks. Patients, caregivers, investigators (including those analysing data), trial staff, and the sponsor (other than the investigational product manager) were masked to treatment allocation. The primary efficacy endpoint was percentage change in median 28-day major motor seizure frequency from the baseline period to the 17-week double-blind phase and was analysed (using a Wilcoxon-rank sum test) in all patients who received at least one dose of trial treatment and for whom baseline data were available. Safety (compared descriptively across groups) was analysed in all patients who received at least one dose of trial treatment. This study is registered with ClinicalTrials.gov, NCT03572933, and the open-label extension phase is ongoing. FINDINGS: Between June 25, 2018, and July 2, 2020, 114 patients were screened for eligibility, of whom 101 (median age 6 years [IQR 3 to 10]) were randomly assigned to receive either ganaxolone (n=50) or placebo (n=51). All patients received at least one dose of a study drug, but seizure frequency for one patient in the ganaxolone group was not recorded at baseline and so the primary endpoint was analysed in a population of 100 patients. There was a median percentage change in 28-day major motor seizure frequency of -30·7% (IQR -49·5 to -1·9) in the ganaxolone group and of -6·9% (-24·1 to 39·7) in the placebo group (p=0·0036). The Hodges-Lehmann estimate of median difference in responses to ganaxolone versus placebo was -27·1% (95% CI -47·9 to - 9·6). Treatment-emergent adverse events occurred in 43 (86%) of 50 patients in the ganaxolone group and in 45 (88%) of 51 patients in the placebo group. Somnolence, pyrexia, and upper respiratory tract infections occurred in at least 10% of patients in the ganaxolone group and more frequently than in the placebo group. Serious adverse events occurred in six (12%) patients in the ganaxolone group and in five (10%) patients in the placebo group. Two (4%) patients in the ganaxolone group and four (8%) patients in the placebo group discontinued the trial. There were no deaths in the double-blind phase. INTERPRETATION: Ganaxolone significantly reduced the frequency of CDD-associated seizures compared with placebo and was generally well tolerated. Results from what is, to our knowledge, the first controlled trial in CDD suggest a potential treatment benefit for ganaxolone. Long-term treatment is being assessed in the ongoing open-label extension phase of this trial. FUNDING: Marinus Pharmaceuticals

    Olaparib as maintenance treatment in patients with chemosensitive small cell lung cancer (STOMP) : a randomised, double-blind, placebo-controlled phase II trial

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    Objectives Small cell lung cancer (SCLC) responds well to chemoradiotherapy but frequently relapses. Here, we evaluate activity and safety of the poly (adenosine diphosphate (ADP)-ribose) polymerase (PARP) inhibitor olaparib as maintenance treatment for patients with chemoresponsive SCLC. Materials and methods Eligible patients had complete or partial response to first line chemotherapy or chemoradiotherapy for SCLC. Patients were randomised 2:2:1:1 to olaparib 300 mg twice a day (BD), olaparib 200 mg three times a day (TDS), placebo BD or placebo TDS. The primary outcome was progression-free survival time (PFS). The trial design had 80% power to detect a 3-month difference in median PFS based on a one-sided 5% significance level. Secondary outcome measures included overall survival time (OS), adverse events and quality of life. ISRCTN 73164486, EudraCT 2010-021165-76. Results 220 patients were randomised: 74 placebo, 73 olaparib BD, 73 olaparib TDS. Median PFS (90% confidence interval (CI)) was 2·5 (1·8, 3·7), 3·7 (3·1, 4·6) and 3·6 (2·8, 4·7) months in the placebo, olaparib BD and TDS arms, respectively. There was no significant difference in PFS between olaparib and placebo for either BD (Hazard Ratio (HR) (90%CI) 0·76 (0·57, 1·02), P = 0·125 or TDS 0·86, (0·64, 1·15), P = 0·402. Common adverse events on olaparib were fatigue, nausea, anaemia, vomiting and anorexia. Of 214 patients who discontinued treatment before 24 months, toxicity was the reason cited for 66 (18 placebo, 24 olaparib BD, 24 olaparib TDS). Conclusion This trial does not provide sufficient evidence that either the BD or TDS regimen for maintenance olaparib monotherapy improves PFS or OS in an unselected SCLC population to warrant further research. Toxicity for olaparib was similar to other studies

    Protected Areas in Forest Conservation: Challenges and Opportunities

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    Forest ecosystems are important habitats for a vast number of species worldwide. These ecosystems are degrading faster than they are regenerating, due to the increased demand for natural resources. In order to protect these ecosystems, the designation of Protected Areas (PAs) has become the primary policy tool for forest conservation. The articles included in this book explore challenges and opportunities within forest PAs, focusing on four main themes. The first theme refers to current initiatives in forest management across the world, reflecting the efforts of several organizations in halting deforestation. Major challenges are also identified, reflecting the declining rates of forest coverage across the world. A second theme refers to policy planning processes withing existing governance frameworks focusing, in particular, on the level of engagement of local stakeholders. A third theme of the book refers to social equity and how the impacts of forest PAs are distributed among different users. A final theme in the SI refers to potential solutions in order to halt the loss of biodiversity within forest ecosystems. Several directions are proposed by the authors that can be useful for policy makers and practitioners, especially in the context of the 30 by 30 targets
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