Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 14.198
Filter
Add filters

Year range
1.
Eur J Endocrinol ; 186(1): 9-23, 2021 Nov 30.
Article in English | MEDLINE | ID: covidwho-2325951

ABSTRACT

OBJECTIVE: Indirect evidence suggests that the effects of testosterone on fat mass in men are dependent on aromatization to estradiol (E2). However, no controlled study has assessed the effects of E2 in the absence of testosterone. DESIGN: Six-month randomized, placebo-controlled trial with the hypothesis that men randomized to E2 would reduce their fat mass. METHODS: Seventy-eight participants receiving androgen deprivation therapy for prostate cancer were randomized to 0.9 mg of 0.1% E2 gel per day, or matched placebo. Dual x-ray absorptiometry body composition was measured at baseline, month 3, and month 6. The primary outcome was total fat mass. RESULTS: Serum E2 increased in the estradiol group over 6 months compared to placebo, and mean-adjusted difference (MAD) was 207 pmol/L (95% CI: 123-292), P < 0.001. E2 treatment changed total fat mass, MAD 1007 g (95% CI: 124-1891), but not significantly, so P = 0.09. There were other consistent non-significant trends toward increased proportional fat mass, MAD 0.8% (95% CI: 0.0-1.6), P= 0.15; gynoid fat, MAD 147 g (95% CI: 2-293), P = 0.08; visceral fat, 53 g (95% CI: 1-105) P = 0.13; and subcutaneous fat, MAD 65 g (95% CI: 5-125), P = 0.11. Android fat increased, MAD 164 g (95% CI: 41-286), P = 0.04. CONCLUSION: Contrary to our hypothesis, we provide suggestive evidence that E2 acting in the absence of testosterone, may increase total and regional fat mass in men. Given the premature closure of clinical trials due to the COVID pandemic, this potentially important observation should encourage additional studies to confirm or refute whether E2 promotes fat expansion in the absence of testosterone.


Subject(s)
Adipose Tissue/drug effects , Androgen Antagonists/therapeutic use , Estradiol/pharmacology , Absorptiometry, Photon , Aged , Androgen Antagonists/adverse effects , Australia , Body Composition/drug effects , Double-Blind Method , Humans , Male , Middle Aged , Obesity/complications , Obesity/drug therapy , Prostatic Neoplasms/complications , Prostatic Neoplasms/drug therapy
2.
Radiat Med Prot ; 2(4): 139-145, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-2322869

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative pathogen of the coronavirus disease 2019 (COVID-19), has caused more than 179 million infections and 3.8 million deaths worldwide. Global health authorities working on the COVID-19 outbreak continue to explore methods to reduce the rate of its transmission to healthy individuals. Treatment protocols thus far have focused on social distancing and masking, treatment with antivirals early in infection, and steroids to reduce the inflammatory response. An alternative approach is therapy with low dose radiation (LDR), which has several advantages compared to the current drugs and medicines. To date more than 10 case reports and pilot clinical trial preliminary outcome are available from different countries. These reports cover a wide range of patient conditions and LDR treatment strategies. Although one report showed the failure to observe the improvement of COVID-19 patients after LDR therapy, the majority showed some clinical improvement, and demonstrated the safety of LDR for COVID-19 patients, particularly with 0.5 â€‹Gy. This review aims to summarize the potential rationales and mechanisms of LDR therapy for COVID-19 patients, and its current clinical status and potential use.

3.
Archives of Disease in Childhood ; 108(6):A4, 2023.
Article in English | ProQuest Central | ID: covidwho-2322714

ABSTRACT

IntroductionIn recent years, substantial improvements in clinical trial facilitation have been made through a pan-European network conect4children (c4c), funded by the Innovative Medicines Initiative 2. Within c4c, collaboration and experience-based teaching were attainable due to live meetings and structured social interactions. Since the COVID-19 pandemic, meeting platforms were limited and strictly virtual, creating an artificial communication environment and a gap for young talent to interact and learn.MethodsIn light of c4c's main objective to build strong collaborations and connections between different national clinical trial networks, the younger generation was in need of support. In May 2021, the young investigators community (YIC) platform was launched to facilitate an informal teaching and connecting vehicle. However, interaction with the experienced and leading generation was lacking, in order to mentor the ‘starters' for a durable network.ResultsWithin the first year, the YIC created an open platform in which the 32 members could interact on a regular basis. Topics included involving medical students, how to build and prepare sustainable business plans and working and interacting with industry partners. Inspired by Erasmus+ funded Pathway project and McBride at al (2017) Mentorship profiling, a 4-page intake questionnaire for both mentor and mentee has been designed, that focuses on specific skills and a plan-of-action for the mentorship session, maximizing efficiency of the interaction.ConclusionWithin YIC, a questionnaire was designed to approach mentor and mentee selection, to be used to minimize the gap between young talent and the established community. The method could be beneficial to other national and international network

4.
Razi Journal of Medical Sciences ; 29(10), 2022.
Article in Persian | CAB Abstracts | ID: covidwho-2322625

ABSTRACT

Background & Aims: In early January 2020, a new corona virus called corona was identified as an infectious agent by the World Health Organization and caused a viral pneumonia outbreak, the first of which was reported in Wuhan, China in December 2019. The virus has so far infected most countries in the world and has become a global problem. By this time in December 2021, about 265 million people in the world have been infected with this virus and 5 million 270 thousand people have died from this disease. According to the World Health Organization, the incidence of this disease is still increasing and will become the third leading cause of death in the world by 2030. This disease has a special complexity and has multiple dimensions and consequences that have caused many problems in the field of health, social and economic as well as psychological for people. The emergence of this disease is now a public health crisis. According to this research, exposure to news and restrictions caused by this disease can lead to many mental health problems. In fact, one of the situations that puts a lot of stress on people during the outbreak of covid 19 disease is the inability to predict and uncertainty about the control and end of the disease. Mental health is defined as a harmonious and harmonious behavior with society, recognizing and accepting social realities, the power to adapt to them and meeting one's balanced needs and is an important factor for the health of society. The prevalence of the disease can also increase feelings of loneliness, decrease social support, feelings of fear and anxiety to clinical stress and anxiety, obsessive-compulsive disorder associated with the disease, and decreased life expectancy. One of the hopeful factors is health and the disease can cause despair, fear and even despair of the patient. The outbreak of a disease has a much deeper and wider impact and affects not only the affected community and relatives, but the entire community. Because everyone finds themselves at risk, and therefore people's feel of safe and healthy changes, and this situation causes people to despair. Hope is the capacity to imagine the ability to create paths to desirable goals and to imagine the motivation to move in those paths. Hope predicts physical and mental health such as positive response to medical interventions, mental health, effective getting along, and health-promoting behaviors. Covid 19 disease can also lead to psychological problems due to its infectious nature and unpredictable nature. In this regard, various researchers consider the implementation of public health policies, including areas related to individual and collective mental health in accordance with the different stages of the epidemic of this disease is very necessary. Mindfulness can be an effective tool for achieving peace of mind and body that helps people become aware of their current feelings. Mindfulness-based interventions are considered as one of the third generation or third wave cognitive-behavioral therapies. Mindfulness is a form of meditation rooted in Eastern religious teachings and rituals, especially Buddhism. Segal has defined mindfulness as paying attention to specific and purposeful ways, in the present time, without judgment or prejudice. Linhan stressed for the first time the need to pay attention to mindfulness as one of the essential components of psychological therapy. Mindfulness requires the development of three components: judgment avoidance, purposeful awareness, and focus on the present moment. Focusing on the present and processing all aspects of the above experience makes one aware of the daily activities and automatic functioning of the mind in the past and future world and he controls emotions, thoughts, and physical states through moment-to-moment awareness of thoughts. As a result, it is released from the everyday and automatic mind focused on the past and the future. Although general vaccination has reduced the virus in some countries, including Iran, and reduced the number of infected people, a large num

5.
Pulmonologiya ; 33(1):52-63, 2023.
Article in Russian | Scopus | ID: covidwho-2322472

ABSTRACT

Post-COVID syndrome develops after COVID-19 (COronaVIrus Disease 2019) and leads to cumulative effects in the form of shortness of breath and impaired lung function. Notably, patients with airway inflammation and COVID-19 were found to have increased concentrations of hyaluronic acid (HA). Since bovhyaluronidase azoximer (Longidase®) catalyzes the hydrolysis of HA, this drug has the potential to reduce HA levels and improve lung function in patients with post-COVID syndrome. The aim of the DISSOLVE trial, which was conducted early in the pandemic, was to investigate the efficacy and safety of bovhyaluronidase azoximer in patients with symptoms associated with post-COVID syndrome. Methods. An open, prospective, controlled, comparative, multicenter clinical trial (NCT04645368) included adult patients (n = 160) who had post-COVID syndrome. Patients in the treatment group (n = 81) received bovhyaluronidase azoximer, and individuals in the control group (n = 79) were followed up without intervention. The study included physical examination, evaluation of forced vital capacity (FVC), assessment of dyspnea with the Modified Medical Research Council Dyspnea Scale (mMRC), 6-minute walking test, and pulse oximetry. These indicators were measured on 3 visits, at days 1 (baseline), 75, and 180. In addition, the number of patients who experienced adverse events and serious adverse events were recorded. Results. Baseline patient characteristics in the treatment group and the control group were similar. In the treatment group, there was a statistically significant reduction in residual pulmonary abnormalities after visit 2 (day 75) and visit 3 (day 180). In addition, FVC, pulse oximetry values, and functional exercise tolerance increased statistically significantly at days 75 and 180 compared to baseline. The mMRC scores for dyspnea decreased statistically significantly in the treatment group over 75 days. The safety profile of the drug was reported to be favorable throughout the study. Conclusion. Treatment with bovhyaluronidase azoximer in patients with post-COVID syndrome showed improvement in FVC, pulse oximetry, functional exercise tolerance, and mMRC dyspnea. © Chuchalin A.G. et al., 2023.

6.
Rheumatology (United Kingdom) ; 62(Supplement 2):ii102, 2023.
Article in English | EMBASE | ID: covidwho-2322287

ABSTRACT

Background/Aims Advances in rational drug design and recent clinical trials are leading to emergence of a range of novel therapies for SLE and therapeutic options in clinical practice are expected to broaden rapidly. The optimal real-world place of emerging and established agents will be guided by understanding their differential efficacy on specific SLE manifestations as well as efficacy for more resistant disease. Anifrolumab, a type-I interferon receptor blocking monoclonal antibody, showed efficacy in SLE in phase III trials with a notable effect on mucocutaneous disease although specific lesion subtypes and chroncicity were not explored. Severe refractory mucocutaneous SLE such as scarring discoid lesions are an important and common clinical challenge in current practice. We therefore prospectively evaluated the real-world efficacy and quality of life impact of anifolumab for active mucocutaneous SLE, recalcitrant to multiple biologic and immunosuppressant therapies. Methods Seven patients commenced anifrolumab (300mg by monthly iv infusion) following application to the manufacturer's early access programme (NCT 04750057). Prior biologic therapies were discontinued at least 5 half-lives in advance. Mucocutaneous disease activity was captured by Cutaneous Lupus Disease Area and Severity Index (CLASI) activity score and medical photography. Patient reported health-related quality of life comprising the Dermatology Life Quality Index (DLQI);Lupus-QoL and EQ5D-5L were evaluated at baseline, three and six months. Results Seven female patients with active mucocutaneous SLE (Discoid LE n=5, chilblain LE n=1, subacute cutaneous LE n=1) and median disease duration of 17 years were evaluated. Median baseline CLASI activity score was 17 (range 10-26;higher scores indicating severe disease). Median number of previously failed therapies was 7 and included rituximab in 6/7, belimumab in 2/7 and thalidomide in 4/7. Rapid resolution of scale and erythema in DLE was established within 1 month of anifrolumab treatment. Improvements to chilblain lupus were evident by three months. CLASI activity score was improved >=75% in all patients at 3 months. Clinical responses were associated with significant improvements in DLQI (p<0.001) and EQ5D-VAS (p=0.002) by three months. Lupus-QoL trended toward improvement across all domains but most strongly for fatigue (p=0.01) and pain (p=0.002) by 6 months. One patient discontinued treatment after 4 months due to polydermatomal shingles complicated by sensorineural hearing loss. Infection coincided with background prednisolone dose >15mg daily, recent COVID-19 infection and new on-treatment hypogammaglobulinaemia (IgG <5g/L). Prolonged aciclovir treatment was required for lesion resolution. Conclusion We report rapid real-world efficacy and quality of life impact of anifrolumab on highly refractory mucocutaneous SLE, which exceeded that anticipated from existing clinical trial data. Findings suggest a unique role for emerging interferon targeting therapies in management of mucocutaneous SLE but emphasize need for enhanced VZV precautions among higher risk patients.

7.
Modern Gastroenterology ; 2021(4):21-31, 2021.
Article in Ukrainian | Scopus | ID: covidwho-2322067

ABSTRACT

Objective — Using mFSSG questionnaire, to define the presences of gastrointestinal disturbances, associated with the intake of nonsteroidal anti-inflammatory drugs (NSAIDs) in patients with moderate course of SARS-CoV-2 infection and to investigate ability of esomeprazole (Ezonexa, Farmak) to preventing the development of dyspeptic and reflux symptoms in these patients. Materials and methods. All patients with the established diagnosis of coronaviral disease (n = 85), hospitalized for treatment in the Centre of Therapy of Clinical Emergency Hospital in Lviv, who signed the informed consent, became the participants of an open controlled trial of Ezonexa efficacy at this pathology. The medication was administered in a dose of 20 mg/day in the morning, 30 mins before meals, used to prevent NSAID-induces gas-tropathies for 28 days. Simple blinded method was used to randomize patients into two groups. Subjects of the first group (n = 45) took esomeprazole, second group included controls (n = 40) without active prophylaxis of NSAID-induces gastropathies. The mean patients' age was 69.4 ± 2.6 years. The men age of male subjects was 66.4 ± 2.4 years, of females 72.3 ± 2.7 years. The follow up period lasted 4 weeks. All patients underwent standard examinations and survey to assess the dynamics of clinical manifestations of the disease against the background of the treatment of coronaviral infection. Besides, patients used mFSSG questionnaire to evaluate the intensity of dyspeptic and reflux symptoms. Examinations and survey were performed on the 1st, 10 — 14th and 28th days of follow up. The quality of life indices were assessed with the use of SF-36 questionnaire in all patients at baseline and 4 weeks after the study start. Results. No significant difference in mFSSG scores was reveled in the patients of both groups on the 1st day in terms of clinical manifestations of dyspepsia and reflux. At the second testing on 10 — 14th days, the assessment of dyspeptic and reflux symptoms didn't change in patients of the 1st group, whereas in 49.6 % subjects of the control group presence of the signs of NSAID-induced gastropathy with a pronounced dyspeptic and moderate reflux syndrome was registered. At 28th day, symptoms of both dyspepsia and reflux developed in 11.3 % of patients in the first group, and 78.6 % in the second group. No differences in age and gender ratio were reveled after comparative analysis. However, comorbid pathology, for which patients constantly took low doses of ace-tylsalicylic acid, was an additional aggravating risk factor of the development of NSAID-induced gastropathy. Analysis of the baseline indices of quality of life in both groups showed the significant (р < 0.05) decrease in the majority of scores, except for the scales of physical functions and pain. Positive dynamics against the background of esomeprazole treatment was defined in all indices of the quality of life, in the most extent in the scores of pain, vitality, social and role emotional functions. Conclusions. Esomeprazole in a dose of 20 mg demonstrated excellent protective effects in regard to the gastrointestinal mucosa in elderly patients from the high-risk group, who are particularly sensitive to the gastroduo-denal NSAID-induced toxicity even at short therapeutic course for coronaviral infection. Ezonexa may be considered as a drug of choice to treat NSAID-induced gastropathy;due to its prolonged and stable acid-inhibiting ability, Ezonexa promotes prompt symptoms' relief. Owing to the phenomenon of stereoselectivity, the drug has pharmacokinetic properties that ensure its high clinical efficacy in acid-dependent diseases. © 2021, Publishing Company VIT-A-POL. All rights reserved.

8.
Rheumatology ; 62(Supplement 2), 2023.
Article in English | EMBASE | ID: covidwho-2321647

ABSTRACT

The proceedings contain 343 papers. The topics discussed include: implementation of a disease modifying anti-rheumatic drug blood monitoring software: 8 years of experience in a single center;effectiveness of colchicine among patients with COVID-19 infection: a randomized, open labelled, clinical trial;rheumatic autoimmune diseases following COVID-19 infection: an observational study in Iraqi Kurdistan region;COVID-19 in male elite Irish-based athletes at a national sports institute;the effects of a pain management program for patients with an inflammatory arthritis;a retrospective analysis of the effectiveness safety of platelet rich plasma injections in primary osteoarthritis in knee joint, in patients attending a tertiary care hospital, Sri Lanka;a cohort study;do proformas used in fracture liaison service appointments reflect national osteoporosis clinical standards? a content analysis;calcium pyrophosphate dihydrate crystal in operated rheumatoid arthritis of the knee;cardiac amyloidosis: a case series of 31 patients with a comprehensive literature review;scoping review for the application of center of pressure for patient or intervention assessment in rheumatoid conditions;and four SNPs associated with monocyte/macrophage cell lineage uniquely associated with CRPS-1 in discovery and replication cohorts and suggest predisposition to regional osteopenia and digit misperception.

10.
Int. j. cardiovasc. sci. (Impr.) ; 35(5): 635-642, Sept.-Oct. 2022. tab, graf
Article in English | WHO COVID, LILACS (Americas) | ID: covidwho-2325830

ABSTRACT

Abstract Fundament: Telemedicine for follow-up in heart failure (HF) patients is effective in reducing hospitalizations, total and cardiovascular mortality. However, few studies were conducted in low and middle income, where lower access to technology and illiteracy could impact the results. Objective: To assess the effectiveness of associating telemedicine strategies, when compared to usual care, in reducing hospitalizations related to HF in patients discharged from the hospital due to HF. Methods: Controlled, randomized, multicenter, parallel-arm clinical trial, with an allocation ratio of 1:1, blinded to outcome evaluation, in which 340 patients who were discharged from public hospitals in Belo Horizonte due to HF will be randomized. Patients will be followed for 6 months and the intervention group will receive, in addition to the usual care, Structured Telephone Support (STS) from a nurse, a doctor, and an educational program. Counseling will be according to a clinical decision tree. The level of significance in the statistical analysis will be 5%. Expected results: Reduction in the number of hospital readmissions and/or in hospitalization time, in addition to developing a software with a clinical decision tree for remote follow-up and patient education about HF adapted to local culture. Conclusions: The intention of this study is to develop a telemedicine strategy and assess whether or not, in addition to the usual care, it is effective in reducing hospitalizations and mortality from HF. If effective, the aforementioned strategy could reduce costs and hospital needs in the Unified Health System (SUS, in Portuguese) for patients with HF. These results will be even more relevant considering the pandemic of COVID-19.

11.
American Journal of Gastroenterology ; 117(10 Supplement 2):S191-S192, 2022.
Article in English | EMBASE | ID: covidwho-2327147

ABSTRACT

Introduction: Traditional clinical trials that utilize fixed sites often fail to recruit participants that are representative of the intended use population. Participants, particularly those from minority groups, cite geographical constraints, mistrust, miscommunication, and discrimination as barriers to successful recruitment. A decentralized clinical trial enrollment strategy offers reduced cost, reduced time requirements, and circumvents barriers associated with the recent pandemic outbreak. Method(s): After the mt-sRNA test system entered design-lock, a decentralized clinical trial (CRC-PREVENT) was launched through a digital campaign (https://www.colonscreeningstudy.com/;NCT04739722). Online advertisements were published on multiple social media sites, and engagement with materials directed patients to an online screener. Participants who completed the screener were eligible for enrollment if they met CRC-PREVENT inclusion and exclusion criteria and were willing to complete all clinical trial components, including providing a stool sample before an optical colonoscopy. Result(s): After 12 months of active enrollment, 276,400 individuals engaged with digital advertisements and completed pre-screener surveys to determine eligibility for the clinical trial. In total, 14,264 individuals consented to participate in the CRC-PREVENT clinical trial. Of these individuals, 58% were female (42% were male), and 65% were over 50. Regarding race and ethnicity, eligible individuals directly represented the intended use population: 16% were Black or African American, 0.2% were Native Hawaiian, Pacific Islander, American Indian, or Alaskan Native, and 7% were Hispanic or Latinx. Regarding socioeconomic status, the decentralized approach permitted access to individuals with healthcare inequities: 25% of participants had income under $29,999, 5% of participants were from rural areas (defined as a city center , 10,000 people), and 36.7% of participants were on public insurance. Individuals were derived from 7,644 unique zip codes across all 48 continental United States. (Table) Conclusion(s): A decentralized recruitment strategy permits highly successful enrollment in the face of screening burdens heightened by COVID-19 pandemic. This approach also offered a significantly more diverse population and could mitigate selection bias and attrition bias associated with the cohorts observed in traditional clinical studies.

12.
Hepatology International ; 17(Supplement 1):S123, 2023.
Article in English | EMBASE | ID: covidwho-2327134

ABSTRACT

Background/Aims: The clinical course of hepatitis B virus (HBV) infection in individuals with HIV-1 coinfection is marked by accelerated disease progression. A tenofovir-containing antiretroviral regimen is recommended in most people with HIV-1/HBV-coinfection, but there have not been randomized studies of tenofovir disoproxil fumarate (TDF) vs tenofovir alafenamide (TAF) in treatment- naive HIV-1/HBV-coinfected individuals. We report primary endpoint results from a Phase 3 study comparing bictegravir/emtricitabine/ TAF (B/F/TAF) vs dolutegravir + emtricitabine/TDF (DTG + F/TDF) at Week (W)48 in participants initiating treatment for both viruses. Method(s): Adults with HIV-1/HBV coinfection were randomized 1:1 to initiate blinded treatment with B/F/TAF or DTG + F/TDF (with placebo). Primary endpoints were the proportion of participants with HIV-1 RNA<50 copies/mL (FDA Snapshot) and plasma HBV DNA<29 IU/mL (missing = failure) at W48. Noninferiority was assessed with 95% CI (12% margin). Secondary and other endpoints included change from baseline cluster of differentiation 4 (CD4) count, proportion with hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) loss/seroconversion, and alanine transaminase (ALT) normalization (AASLD criteria). Result(s): Participants (N = 243) were randomized and treated (B/F/ TAF [n = 121], DTG + F/TDF [n = 122]) from 11 countries in Asia, Europe, North, and Latin America. Baseline characteristics were median age of 32 years, 4.5% female, 88% Asian, 30% HIV-1 RNA>100,000 c/mL, 40% CD4<200 cells/lL, median HBV DNA 8.1 log10 IU/mL, 78% HBeAg+. At W48, B/F/TAF was noninferior to DTG + F/TDF at achieving HIV-1 RNA<50 copies/mL (95% vs 91%, difference 4.1%;95% CI -2.5%-10.8%;P = 0.21), with mean CD4 gains of + 200 and + 175 cells/lL, respectively. B/F/TAF was superior to DTG + F/TDF at achieving HBV DNA<29 IU/mL (63% vs 43%, difference 16.6%;95% CI 5.9%-27.3%;P = 0.0023). Participants treated with B/F/TAF vs DTG + F/TDF had numerically higher HBsAg loss (13% vs 6%;P = 0.059), HBeAg loss (26% vs 14%;P = 0.055), HBeAg seroconversion (23% vs 11%;P = 0.031), and ALT normalization (73% vs 55%;P = 0.066). The most frequent adverse events among participants treated with B/F/TAF vs DTG + F/TDF were upper respiratory tract infection (17% vs 11%), COVID- 19 (13% vs 11%), pyrexia (9% vs 12%), ALT increase (7% vs 11%), and nasopharyngitis (11% vs 4%). ALT flares (elevations at >= 2 consecutive postbaseline visits) occurred in 11 participants (7 B/F/ TAF, 4 DTG + F/TDF), and all resolved. Conclusion(s): Among adults with HIV-1/HBV-coinfection starting antiviral therapy, both B/F/TAF and DTG + F/TDF had high HIV-1 suppression at year 1, with B/F/TAF resulting in superior HBV DNA suppression and significantly more HBeAg seroconversion. Safety findings were similar between groups.

13.
International Journal of Infectious Diseases ; 130(Supplement 2):S25, 2023.
Article in English | EMBASE | ID: covidwho-2327123

ABSTRACT

Intro: VLA2001 is a highly-purified, inactivated whole-virus SARS-CoV-2 vaccine based on a dual-adjuvant system of Alum and CpG1018 for induction of a robust immune response. The vaccine was designed using a well-established technology platform and has received full marketing authorization in Europe. In a pivotal Phase 3 trial, VLA2001 demonstrated superior neutralizing antibody geometric mean titers (GMT) to the comparator, AstraZeneca's AZD1222, as well as non-inferior seroconversion rates two weeks after priming. The extension of the Phase 3 trial evaluated safety and immunogenicity of homologous and heterologous booster vaccinations of VLA2001. Method(s): This is a randomized observer-blind controlled, pivotal trial conducted in the UK in participants aged >=18 years who were randomly assigned 2:1 to receive two doses of VLA2001 or AZD1222, 28 days apart. A booster with VLA2001 was administered to eligible participants at 7 to 8 months after priming. The primary safety outcome was the frequency and severity of any adverse event following the booster vaccination. The primary immunogenicity outcomes were the GMT and fold increase of neutralizing antibodies against SARS-CoV-2 two weeks after the booster vaccination. The study is registered under NCT04864561. Finding(s): A booster dose of VLA2001 is well-tolerated in both AZD1222 and VLA2001 primed participants. High neutralizing antibody titers and fold- increases were generated two weeks following a booster of VLA2001. Cross- neutralizing serological responses against Delta and the Omicron BA.4/BA.5 variants of concern are elicited following a homologous or heterologous booster dose in VLA2001 or AZD1222 primed participants, respectively. Additionally, VLA2001 induced broad T-cell responses with antigen-specific IFN-gamma producing T-cells against the Spike, the Nucleocapsid and the Membrane protein. Conclusion(s): Homologous and heterologous booster doses of VLA2001 demonstrated a favorable tolerability profile irrespective of priming and induced broadly reactive neutralizing antibodies against the ancestral virus and variants of concern, including the currently circulating BA.4/BA.5.Copyright © 2023

14.
Journal of Parenteral and Enteral Nutrition ; 47(Supplement 2):S38-S40, 2023.
Article in English | EMBASE | ID: covidwho-2326824

ABSTRACT

Background: Indirect calorimetry (IC) is the gold-standard procedure for measuring resting energy expenditure (REE) in hospitalized patients. Predictive energy equations commonly use static variables and rarely account for changes in REE throughout hospitalization. We hypothesize that predictive equations are typically inaccurate in surgical intensive care unit (ICU) patients. More specifically, we hypothesize that predictive equations often overpredict measured resting energy expenditure (mREE) in early-stage critical illness and underpredict needs later in surgical ICU stay, leading to over-/under-feeding and associated complications. Method(s): This prospective observational trial enrolled surgical ICU patients who underwent emergent or urgent operations for abdominal trauma, perforated viscus, or ischemic bowel within 72 hours of their surgical procedure. Metabolic assessments were performed using the COSMED Q-NRG + Metabolic Monitor ventilator, mask, and canopy at regular intervals during and post ICU admission until hospital discharge. Measurements were categorized by post-surgical intervention ICU admission days 0-3, 4-7, 8-14, 15-21, and 22-28. Patients with multiple measurements taken during the same time interval were averaged. mREE reported in calories (kcal) per kilogram (kg) of admission body weight per day were compared in obese (BMI > 30 kg/m2) and non-obese (BMI < 30 kg/m2) subgroups. Compared to IC, the Mifflin St Jeor (MSJ) equation determined predicted REE using ICU admission anthropometrics. Data are reported as mean+/-standard error of the mean (SEM) and median (interquartile range), and a two-sided p-value of <0.05 was determined significant. Result(s): In total, 18 surgical ICU patients who contributed 47 IC measurements were included in the analysis (Table 1). Most measures were obtained within the first 7 days of post-surgical ICU admission (72%). mREE peaked between days 8-14 in obese and non-obese subgroups (20.6 vs 28.5 kcal/kg;p = 0.02) and was lowest during 0-3 days of post-surgical ICU admission in both groups. Across all 5-time intervals, average kcal/ kg ranged from 14.7-20.6 among obese patients and from 20.1-28.5 in non-obese counterparts (Table 2). Non-obese patients had higher mREE per kg of body weight than obese patients at all time points (Figure 1). MSJ over-predicted mREE during the first 7 days post ICU admission in non-obese patients and within the first 3 days in obese patients and underpredicted mREE in both groups thereafter. Conclusion(s): Equations such as MSJ over- and under-predict mREE in post-operative surgical ICU patients depending on the days elapsed since post-surgical ICU admission. ASPEN's current guideline recommendation of 12-25 kcal/kg may also underfeed post-surgical populations while 25 kcal/kg may not support hypermetabolism among non-obese patients seen in week 2 following post-surgical ICU admission. Alternatively, MSJ multiplied by a 1.2 activity factor may account for hypermetabolism during this time. Notably, non-obese patients experienced greater hypermetabolism than obese patients during week 2 which is consistent with our previously published data in mechanically ventilated COVID- 19 patients. Additionally, the striking dichotomy between the mREE of obese and non-obese patients at all post-surgical time points should be considered in the clinical care of patients. Ultimately, IC remains the gold-standard means of measuring REE and is a critical tool to capture the dynamic nature of energy requirements in post-surgical populations as weight-based and predictive equations continually fall short. (Table Presented).

15.
Annals of Operations Research ; : 1-25, 2023.
Article in English | EuropePMC | ID: covidwho-2326714

ABSTRACT

During a pandemic, medical specialists have substantial challenges in discovering and validating new disease risk factors and designing effective treatment strategies. Traditionally, this approach entails several clinical studies and trials that might last several years, during which strict preventive measures are enforced to manage the outbreak and limit the death toll. Advanced data analytics technologies, on the other hand, could be utilized to monitor and expedite the procedure. This research integrates evolutionary search algorithms, Bayesian belief networks, and innovative interpretation techniques to provide a comprehensive exploratory–descriptive–explanatory machine learning methodology to assist clinical decision-makers in responding promptly to pandemic scenarios. The proposed approach is illustrated through a case study in which the survival of COVID-19 patients is determined using inpatient and emergency department (ED) encounters from a real-world electronic health record database. Following an exploratory phase in which genetic algorithms are used to identify a set of the most critical chronic risk factors and their validation using descriptive tools based on the concept of Bayesian Belief Nets, the framework develops and trains a probabilistic graphical model to explain and predict patient survival (with an AUC of 0.92). Finally, a publicly available online, probabilistic decision support inference simulator was constructed to facilitate what-if analysis and aid general users and healthcare professionals in interpreting model findings. The results widely corroborate intensive and expensive clinical trial research assessments.

16.
Rheumatology (United Kingdom) ; 62(Supplement 2):ii53-ii54, 2023.
Article in English | EMBASE | ID: covidwho-2326530

ABSTRACT

Background/Aims Immunocompromised patients have a reduced ability to generate antibodies after COVID-19 vaccination, and are at a high risk of SARSPOSTERS CoV-2 infection, complications and mortality. Tixagevimab/Cilgavimab (Evusheld) is a combination of two monoclonal antibodies which bind to the SARS-CoV-2 spike protein, preventing the virus entering human cells. Tixagevimab/Cilgavimab has been approved as COVID-19 prophylaxis for immunocompromised individuals, and is being used in over 32 different countries. The phase III PROVENT clinical trial found that high-risk participants prophylactically administered Tixagevimab/Cilgavimab had a significantly reduced risk of COVID- 19 infection after three and six months compared to controls. However, the PROVENT trial was conducted prior to the SARS-CoV- 2 Omicron wave, and did not include participants who had been previously vaccinated or infected. This systematic review provides an updated summary of the real-world clinical evidence of the efficacy of Tixagevimab/Cilgavimab for immunocompromised patients. The review reports breakthrough COVID-19 infections as its primary outcome. COVID-19-related hospitalisations, ITU admissions and mortality were included as secondary outcomes. Methods Two independent reviewers conducted electronic searches of PubMed and Medxriv, on 03/08/22 and 01/10/22. Clinical studies which reported the primary outcome of breakthrough COVID-19 infections after Tixagevimab/Cilgavimab administration were included. Clinical effectiveness was determined using the case-control clinical effectiveness methodology. Odds ratios and 95% confidence intervals (CI) between intervention and control groups were also calculated. The GRADE tool was used to assess the level of certainty for the primary outcome. Results 17 clinical studies were included in the review, with a total of 24,773 immunocompromised participants from across the world, of whom 10,775 received Tixagevimab/Cilgavimab. One randomised controlled trial, ten retrospective cohort studies (two of which were preprints) and six prospective cohort studies (one preprint) were included. The majority of studies reported clinical outcomes during the SARS-CoV-2 Omicron wave. Six studies compared a Tixagevimab/Cilgavimab intervention group to a control group. Reasons for participant immunocompromise included rheumatology patients treated with immunosuppressant drugs, transplant recipients and those with malignancies. Overall, the clinical effectiveness of prophylactic Tixagevimab/Cilgavimab against COVID- 19 breakthrough infection was 40.47% (CI 29.82-49.67;p<0.0001), COVID-19 hospitalisation- 69.23% (CI: 50.78-81.64;p<0.00001), ITU admission- 87.89% (CI: 47.12-98.66;p=0.0008), all-cause mortality- 81.29% (66.93-90.28;p<0.0001 and COVID-19-specifc mortality- 86.36% (CI:-6.21-99.70;p=0.0351). Conclusion There is a growing body of real-world evidence validating the original PROVENT phase III study regarding the clinical effectiveness of Tixagevimab/Cilgavimab as prophylaxis for immunocompromised groups, notably demonstrating effectiveness during the Omicron wave. This systematic review demonstrates the significant clinical effectiveness of prophylactic Tixagevimb/Cilgavimab at reducing COVID-19 infection, hospitalisation, ITU admission and mortality for immunosuppressed individuals. It is critically important that largerscale and better-controlled studies are performed to highlight the significant clinical benefit of prophylactic antibody treatment in immunocompromised groups.

18.
HIV Medicine ; 24(Supplement 3):101, 2023.
Article in English | EMBASE | ID: covidwho-2326437

ABSTRACT

Background: Since COVID there are fewer site investigator meetings for non-CTIMP studies to discuss recruitment barriers. Additionally, literature highlights various research trials that have successfully recruited do not report their strategies, consequently impacting ability to learn from success. The pandemic has had considerable impact on enrolment to clinical research, thus services have needed to revaluate their approach. Following the pandemic, patients report more likely to engage in research if offered remote or combined visits. Method(s): We reviewed recruitment strategies at our clinic for two observational studies with large targets (SCAPE-HIV, Positive Voices). SCAPE-HIV, a prospective study exploring immune responses of PLWH to SARS CoV2 infection and vaccination. Positive Voices, a crosssectional questionnaire study. Minimum recruitment targets, 600 and 262 respectively. SCAPE involves open-offer enrolment, Positive Voices from a defined pre-selected cohort. Initial approaches identified people opportunistically at clinic visits, with research staff offering information. However, reaching our targets through COVID became challenging and a move to virtual appointments condensed our opportunities to approach. To increase recruitment, engagement and training of NHS nursing and clinical staff was undertaken alongside remote patient contact. Result(s): After implementing collaborative methods, Positive Voices recruitment increased to 170 in July/ August 2022 (73 in May/June). SCAPE recruitment also improved. Hybrid nurse practitioners dedicating time to approach people during clinic visits and clinic staff involvement attributed to this rise, representing over half of consents (Table A). The clinic team's substantial knowledge of our cohort, combined with their openness to research, leads to greater understanding of how likely individuals are to accept studies. Conclusion(s): Positive Voices and SCAPE-HIV studies have been successful with recruitment due to a collaborative approach, resulting in our site being the highest current recruiting site involved in Positive Voices. This approach has helped motivate the NHS team to become more involved and has become an exemplar for clinical trial delivery within our Trust. (Table Presented).

19.
Hepatology International ; 17(Supplement 1):S25, 2023.
Article in English | EMBASE | ID: covidwho-2326276

ABSTRACT

Ablation includes ethanol injection, radiofrequency ablation (RFA), microwave ablation (MWA), etc. Ablation can be potentially curative, minimally invasive and easily repeatable for recurrence. RFA has been the most widely used ablation technique for liver tumors. The new-generation MWA system incorporating antenna cooling and high-power generation has attracted attention. It can create a more predictable ablation zone and a larger ablation volume in a shorter procedure time. Many high-volume centers have introduced new-generation MWA in Japan. However, many studies failed to show that new-generation MWA is superior to RFA in terms of local control and overall survival. In MWA, clinical data have been insufficient compared with those of RFA. There has been keen competition between surgical resection and ablation for almost 40 years since the era of ethanol injection. In 2021, SURF trial revealed that overall survival and recurrence-free survival were not significantly different between surgical resection and RFA. SURF trial was a multicenter randomized controlled trial in which 49 major centers in Japan enrolled patients with good hepatic function (Child-Pugh scores <= 7) and primary HCC of largest diameter <= 3 cm, and <= 3 nodules during the 6-year period of 2009-2015. The registered patients were followed for at least 5 years. As the result of SURF trial and other comparative studies, the revised Japanese clinical practice guidelines in 2021 treats hepatic resection and ablation equally for patients with <= 3 lesions, <= 3 cm in diameter. Recently, the combination of systemic and locoregional therapies has been attracting much attention. Systemic therapy using molecular targeted agents or immune checkpoint inhibitors is used for advanced HCC which cannot be treated by surgery or ablation. On the other hand, some locoregional therapies, such as hepatectomy and ablation, are potentially curative, but they cannot be indicated for advanced HCC. Combination of both therapies is an approach to improve the prognosis of advanced HCC, which is not indicated for curative treatment. Systemic therapy is used to shrink the tumor, and then locoregional therapies are performed to eradicate it. The combination may build a new strategy for advanced HCC. Ablation is highly operator-dependent. The skills and outcomes are very different from operator to operator. Before the pandemic of COVID-19, we held domestic and international training programs for intermediate and advanced doctors and hands-on seminars for young doctors. These were activities to exchange knowledge and experience and standardize the procedure. During the pandemic, we cannot get together. Since August 2020, we have conducted Japan Ablation Webinar 8 times with a total of 1,566 participants. We have also conducted International Ablation Webinar 4 times with a total of 1,272 participated doctors. Education is important to acquire skills and knowledge for successful ablation. We have established Japan Academy of Tumor Ablation (JATA) this year. There are two triggers. One is that SURF trial revealed that there is no difference between hepatectomy and ablation. The other is that ablation for lung, bone and soft tissue and kidney cancers has become reimbursed with health insurance since this September.

20.
Sleep advances : a journal of the Sleep Research Society ; 2(Suppl 1):A64-A64, 2021.
Article in English | EuropePMC | ID: covidwho-2326257

ABSTRACT

Introduction A pilot randomised controlled trial (RCT) examining the feasibility of a new model of non-invasive ventilation (NIV) implementation was due to commence in early 2020. Based on previous research, it was anticipated that 100% of people with motor neurone disease (MND) would be eligible, 60% would consent to participate and 20 people would be randomised in five months. The aim of this report is to describe the impact of COVID-19 pandemic contingencies on trial recruitment. Methods Report of project progress, participant screening and recruitment. Results First reports of COVID-19 coincided with study commencement and changed usual healthcare delivery. Lockdowns meant telehealth substituted for face-to-face assessment, respiratory function testing was limited and/or patients were reluctant to seek medical treatment. This modified pathway impacted evaluation of diagnosis, timing of need for NIV and procedural safety, with patients then referred specifically for a single-day hospital NIV implementation to enable face-to-face multidisciplinary assessment to aid decisions. Of 81 potential participants screened in an 8-month period, 64% were ineligible for the RCT. Despite this shift in eligibility rate, 16 people with MND have been recruited as of May 2021. Conclusion The current climate has amplified the significance of this research trial;people with MND have had reduced access to face-to-face services globally and clinicians have had to quickly adapt to a changing landscape of telemedicine and remote monitoring of patients. This trial's screening data suggest that COVID-19 hasn't stopped people with MND being implemented on NIV, but it has altered assessment pathways.

SELECTION OF CITATIONS
SEARCH DETAIL