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1.
Trials ; 23(1): 4, 2022 Jan 03.
Article in English | MEDLINE | ID: covidwho-1606541

ABSTRACT

BACKGROUND: Cardiogenic shock (CS) is a life-threatening condition characterized by circulatory insufficiency caused by an acute dysfunction of the heart pump. The pathophysiological approach to CS has recently been enriched by the tissue consequences of low flow, including inflammation, endothelial dysfunction, and alteration of the hypothalamic-pituitary-adrenal axis. The aim of the present trial is to evaluate the impact of early low-dose corticosteroid therapy on shock reversal in adults with CS. METHOD/DESIGN: This is a multicentered randomized, double-blind, placebo-controlled trial with two parallel arms in adult patients with CS recruited from medical, cardiac, and polyvalent intensive care units (ICU) in France. Patients will be randomly allocated into the treatment or control group (1:1 ratio), and we will recruit 380 patients (190 per group). For the treatment group, hydrocortisone (50 mg intravenous bolus every 6 h) and fludrocortisone (50 µg once a day enterally) will be administered for 7 days or until discharge from the ICU. The primary endpoint is catecholamine-free days at day 7. Secondary endpoints include morbidity and all-cause mortality at 28 and 90 days post-randomization. Pre-defined subgroups analyses are planned, including: postcardiotomy, myocardial infarction, etomidate use, vasopressor use, and adrenal profiles according the short corticotropin stimulation test. Each patient will be followed for 90 days. All analyses will be conducted on an intention-to-treat basis. DISCUSSION: This trial will provide valuable evidence about the effectiveness of low dose of corticosteroid therapy for CS. If effective, this therapy might improve outcome and become a therapeutic adjunct for patients with CS. TRIAL REGISTRATION: ClinicalTrials.gov , NCT03773822 . Registered on 12 December 2018.


Subject(s)
COVID-19 , Shock, Cardiogenic , Adult , Humans , Hypothalamo-Hypophyseal System , Multicenter Studies as Topic , Pituitary-Adrenal System , Randomized Controlled Trials as Topic , SARS-CoV-2 , Shock, Cardiogenic/diagnosis , Shock, Cardiogenic/drug therapy , Treatment Outcome
2.
Curr Opin Infect Dis ; 34(6): 654-662, 2021 12 01.
Article in English | MEDLINE | ID: covidwho-1593269

ABSTRACT

PURPOSE OF REVIEW: Focusing on large multicenter cohorts reported over the last months, this review aims at summarizing the available evidence by July 2021 on the impact of coronavirus disease 2019 (COVID-19) on hematopoietic stem cell transplant (HSCT) recipients in terms of epidemiology, clinical features, and outcome. RECENT FINDINGS: The incidence of COVID-19 in institutional cohorts varied according to different regions and study periods from 0.4% to 8.3%. Clinical presentation was overall comparable to other immunocompromised hosts and the general population. Microbiologically confirmed superinfection occurred in 13-25% of recipients, with most episodes due to hospital-acquired bacteria and few reported cases of COVID-19-associated aspergillosis. Prolonged nasopharyngeal severe acute respiratory syndrome coronavirus 2 shedding has been demonstrated for as long as 210 days. Mortality rates were similar across studies (14.8-28.4%) and did not markedly differ from those observed in nontransplant hematological patients during the first wave. Older age and shorter time from transplantation were associated with mortality, as well as underlying disease status and amount of immunosuppression. No outcome differences were found in most studies between allogeneic and autologous procedures. SUMMARY: Considerable advances have been achieved in the characterization of COVID-19 in the HSCT population, although uncertainties remain in the optimal therapeutic management.


Subject(s)
COVID-19 , Hematopoietic Stem Cell Transplantation , Aged , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Immunocompromised Host , Multicenter Studies as Topic , SARS-CoV-2 , Transplant Recipients
3.
In Vivo ; 36(1): 361-370, 2022.
Article in English | MEDLINE | ID: covidwho-1594956

ABSTRACT

BACKGROUND/AIM: Evidence suggests a beneficial effect of prone positioning (PP) in COVID-19. MATERIALS AND METHODS: Meta-analysis of individual (7 investigators' groups) and aggregate data (PubMed/EMBASE) regarding the impact of PP on the ratio of arterial partial pressure of oxygen to fraction of inspired oxygen (PO2/FiO2) in patients with COVID-19. RESULTS: Among 121 patients (mean age±SD 59.1±10.7 years, 55% males, 57% intubated) the mean post-versus pre- PP PO2/FiO2 difference was: (i) 50.4±64.3 mmHg, p<0.01, (ii) similar in awake (58.7±72.1 mmHg) versus intubated patients (44.1±57.5 mmHg, p=NS), (iii) inversely correlated with body mass index (r=-0.43, p<0.01). Meta-analysis of 23 studies (n=547, weighted age 58.3±4.1, 73% males, 59% intubated) showed a pooled PO2/FiO2 difference of 61.8 [95% confidence intervals=49.9-73.6] mmHg. Meta-regression analysis revealed no associations with baseline demographics, the time in PP before assessment, and the risk of bias of the studies. CONCLUSION: PP seems to improve oxygenation of patients with COVID-19.


Subject(s)
COVID-19 , Female , Humans , Male , Middle Aged , Multicenter Studies as Topic , Oxygen , Prone Position , Registries , SARS-CoV-2
4.
Int J Environ Res Public Health ; 18(24)2021 12 08.
Article in English | MEDLINE | ID: covidwho-1593482

ABSTRACT

BACKGROUND: As the effectiveness on stress urinary incontinence (SUI) prevention of pelvic floor muscle training (PFMT) for pregnant women has been inconclusive, we are planning to conduct a trial to evaluate a video program designed for prevention of SUI developed through combining PFMT with global postural reeducation (GPR). METHODS: As a randomized controlled trial, eligible participants will be randomized (1:1) into an exercise group and a control group to perform PFMT regularly following video guidance or with no intervention, respectively. The experimental stage will be from the 16th gestation week (GW) to the 12th month postpartum, with eight appointments at the 16th, 28th, 37th GW, delivery, the 6th week and the 3rd, 6th, and 12th month postpartum. Data will be collected regarding urinary leakage symptoms, the stress test, the modified Oxford Scale, pelvic floor ultrasound, perineal laceration classification at delivery, neonatal Apgar score, and questionnaires (PISQ-12, ICIQ-UI SF, I-QOL, OABSS). The primary outcome is the occurrence of the symptomatic SUI and positive stress test at the 6th week postpartum. DISCUSSION: This protocol is anticipated to evaluate the efficacy of the intervention via video app for the design of a future randomized control trial (RCT). TRIAL REGISTRATION: The trial has been registered at Chinese Clinical Trial Registry (registration number: ChiCTR2000029618).


Subject(s)
Mobile Applications , Urinary Incontinence, Stress , Exercise Therapy , Female , Humans , Multicenter Studies as Topic , Pelvic Floor , Pregnancy , Randomized Controlled Trials as Topic , Treatment Outcome , Urinary Incontinence, Stress/prevention & control
5.
BMJ Open ; 11(12): e051284, 2021 12 17.
Article in English | MEDLINE | ID: covidwho-1583104

ABSTRACT

INTRODUCTION: The aim of this study was to evaluate the clinical, epidemiological and laboratory aspects of SARS-CoV-2 infection during pregnancy and postpartum in 16 maternity hospitals. METHODS AND ANALYSIS: A prospective multicentre study, with five axes. First, the prevalence of SARS-CoV-2 infection among women admitted for childbirth will be described in a cross-sectional study. Second, maternal and perinatal outcomes will be assessed in a prospective cohort study including pregnant or postpartum women with suspected COVID-19. Third, a cohort of positive COVID-19 cases with sampling of a variety of biological material. Histopathological and viral analysis of biological maternal and neonatal samples will be performed, and the assessment of nutritional variables to evaluate the association between vitamin D and severity of infection. Fourth, a monitoring and evaluation committee to collect relevant healthcare information and plan actions in centres facing the pandemic. Furthermore, qualitative studies will be performed to study pregnant women, their families and health professionals. Fifth, an ecological study will monitor the number of live births, stillbirths and other outcomes to explore any trend among the periods before, during and after the pandemic. Data will systematically be collected in an electronic platform following standardised operational procedures. For quantitative study components, an appropriate statistical approach will be used for each analysis. For qualitative data, in-depth interviews recorded in audio will be transcribed, checking the text obtained with the recording. Subsequently, thematic analysis with the aid of the NVivo programme will be performed. ETHICS AND DISSEMINATION: Ethical approval was obtained (letters of approval numbers 4.047.168, 4.179.679 and 4.083.988). All women will be fully informed to sign the consent form before enrolment in the study. Findings will be disseminated through peer-reviewed journals and scientific conferences.


Subject(s)
COVID-19 , Cross-Sectional Studies , Female , Humans , Infant, Newborn , Multicenter Studies as Topic , Parturition , Pregnancy , Prospective Studies , SARS-CoV-2
6.
BMJ Open ; 11(12): e054208, 2021 12 16.
Article in English | MEDLINE | ID: covidwho-1583097

ABSTRACT

INTRODUCTION: Most existing vaccines require higher or additional doses or adjuvants to provide similar protection for people living with HIV (PLWH) compared with HIV-uninfected individuals. Additional research is necessary to inform COVID-19 vaccine use in PLWH. METHODS AND ANALYSIS: This multicentred observational Canadian cohort study will enrol 400 PLWH aged >16 years from Montreal, Ottawa, Toronto and Vancouver. Subpopulations of PLWH of interest will include individuals: (1) >55 years of age; (2) with CD4 counts <350 cells/mm3; (3) with multimorbidity (>2 comorbidities) and (4) 'stable' or 'reference' PLWH (CD4 T cells >350 cells/mm3, suppressed viral load for >6 months and <1 comorbidity). Data for 1000 HIV-negative controls will be obtained via a parallel cohort study (Stop the Spread Ottawa), using similar time points and methods. Participants receiving >1 COVID-19 vaccine will attend five visits: prevaccination; 1 month following the first vaccine dose; and at 3, 6 and 12 months following the second vaccine dose. The primary end point will be the percentage of PLWH with COVID-19-specific antibodies at 6 months following the second vaccine dose. Humoral and cell-mediated immune responses, and the interplay between T cell phenotypes and inflammatory markers, will be described. Regression techniques will be used to compare COVID-19-specific immune responses to determine whether there are differences between the 'unstable' PLWH group (CD4 <350 cells/mm3), the stable PLWH cohort and the HIV-negative controls, adjusting for factors believed to be associated with immune response. Unadjusted analyses will reveal whether there are differences in driving factors associated with group membership. ETHICS AND DISSEMINATION: Research ethics boards at all participating institutions have granted ethics approval for this study. Written informed consent will be obtained from all study participants prior to enrolment. The findings will inform the design of future COVID-19 clinical trials, dosing strategies aimed to improve immune responses and guideline development for PLWH. TRIAL REGISTRATION NUMBER: NCT04894448.


Subject(s)
COVID-19 , HIV Infections , COVID-19 Vaccines , Canada , Cohort Studies , Diterpenes , Humans , Multicenter Studies as Topic , Observational Studies as Topic , SARS-CoV-2 , Vaccination
7.
BMJ Open ; 11(12): e054442, 2021 12 15.
Article in English | MEDLINE | ID: covidwho-1583096

ABSTRACT

INTRODUCTION: COVID-19 is a new viral-induced pneumonia caused by infection with a novel coronavirus, SARS-CoV-2. At present, there are few proven effective treatments. This early-phase experimental medicine protocol describes an overarching and adaptive trial designed to provide safety data in patients with COVID-19, pharmacokinetic (PK)/pharmacodynamic (PD) information and exploratory biological surrogates of efficacy, which may support further development and deployment of candidate therapies in larger scale trials of patients positive for COVID-19. METHODS AND ANALYSIS: Define is an ongoing exploratory multicentre-platform, open-label, randomised study. Patients positive for COVID-19 will be recruited from the following cohorts: (a) community cases; (b) hospitalised patients with evidence of COVID-19 pneumonitis; and (c) hospitalised patients requiring assisted ventilation. The cohort recruited from will be dependent on the experimental therapy, its route of administration and mechanism of action. Randomisation will be computer generated in a 1:1:n ratio. Twenty patients will be recruited per arm for the initial two arms. This is permitted to change as per the experimental therapy. The primary statistical analyses are concerned with the safety of candidate agents as add-on therapy to standard of care in patients with COVID-19. Secondary analysis will assess the following variables during treatment period: (1) the response of key exploratory biomarkers; (2) change in WHO ordinal scale and National Early Warning Score 2 (NEWS2) score; (3) oxygen requirements; (4) viral load; (5) duration of hospital stay; (6) PK/PD; and (7) changes in key coagulation pathways. ETHICS AND DISSEMINATION: The Define trial platform and its initial two treatment and standard of care arms have received a favourable ethical opinion from Scotland A Research Ethics Committee (REC) (20/SS/0066), notice of acceptance from The Medicines and Healthcare Products Regulatory Agency (MHRA) (EudraCT 2020-002230-32) and approval from the relevant National Health Service (NHS) Research and Development (R&D) departments (NHS Lothian and NHS Greater Glasgow and Clyde). Appropriate processes are in place in order to be able to consent adults with and without capacity while following the necessary COVID-19 safe procedures. Patients without capacity could be recruited via a legal representative. Witnessed electronic consent of participants or their legal representatives following consent discussions was established. The results of each study arm will be submitted for publication in a peer-reviewed journal as soon as the treatment arm has finished recruitment, data input is complete and any outstanding patient safety follow-ups have been completed. Depending on the results of these or future arms, data will be shared with larger clinical trial networks, including the Randomised Evaluation of COVID-19 Therapy trial (RECOVERY), and to other partners for rapid roll-out in larger patient cohorts. TRIAL REGISTRATION NUMBER: ISRCTN14212905, NCT04473053.


Subject(s)
Biomedical Research , COVID-19 , Clinical Trials, Phase I as Topic , Clinical Trials, Phase II as Topic , Electronics , Humans , Multicenter Studies as Topic , Randomized Controlled Trials as Topic , State Medicine
8.
Glob Heart ; 16(1): 22, 2021 04 19.
Article in English | MEDLINE | ID: covidwho-1557646

ABSTRACT

Background: The emergence of novel coronavirus disease 2019 (COVID-19), caused by the Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2), has presented an unprecedented global challenge for the healthcare community. The ability of SARS-CoV-2 to get transmitted during the asymptomatic phase, and its high infectivity have led to the rapid transmission of COVID-19 beyond geographic regions facilitated by international travel, leading to a pandemic. To guide effective control and interventions, primary data is required urgently, globally, including from low- and middle-income countries where documentation of cardiovascular manifestations and risk factors in people hospitalized with COVID-19 is limited. Objectives: This study aims to describe the cardiovascular manifestations and cardiovascular risk factors in patients hospitalized with COVID-19. Methods: We propose to conduct an observational cohort study involving 5000 patients recruited from hospitals in low-, middle- and high-income countries. Eligible adult COVID-19 patients will be recruited from the participating hospitals and followed-up until 30 days post admission. The outcomes will be reported at discharge and includes the need of ICU admission, need of ventilator, death (with cause), major adverse cardiovascular events, neurological outcomes, acute renal failure, and pulmonary outcomes. Conclusion: Given the enormous burden posed by COVID-19 and the associated severe prognostic implication of CVD involvement, this study will provide useful insights on the risk factors for severe disease, clinical presentation, and outcomes of various cardiovascular manifestations in COVID-19 patients particularly from low and middle income countries from where the data remain scant.


Subject(s)
COVID-19/epidemiology , Cardiovascular Diseases/virology , Global Health , Observational Studies as Topic/methods , Cohort Studies , Hospitalization , Humans , Multicenter Studies as Topic , Pandemics , Prognosis , Risk Factors
9.
Curr Opin Pediatr ; 33(6): 580-590, 2021 12 01.
Article in English | MEDLINE | ID: covidwho-1546081

ABSTRACT

PURPOSE OF REVIEW: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic has overwhelmed the global community, negatively impacting patient health and research efforts; associated neurological manifestations are a significant cause of morbidity. This review outlines the worldwide epidemiology of neurologic manifestations of different SARS-CoV-2 clinical pediatric phenotypes, including acute coronavirus disease 2019 (COVID-19), multisystem inflammatory syndrome in children (MIS-C) and postacute sequelae of COVID-19 (PASC). We discuss strategies to develop adaptive global research platforms for future investigation into emerging pediatric neurologic conditions. RECENT FINDINGS: Multicenter, multinational studies show that neurological manifestations of acute COVID-19, such as smell/taste disorders, headache, and stroke, are common in hospitalized adults (82%) and children (22%), associated with increased mortality in adults. Neurological manifestations of MIS-C are reported in up to 20% of children, including headache, irritability, and encephalopathy. Data on PASC are emerging and include fatigue, cognitive changes, and headache. Reports of neurological manifestations in each phenotype are limited by lack of pediatric-informed case definitions, common data elements, and resources. SUMMARY: Coordinated, well resourced, multinational investigation into SARS-CoV-2-related neurological manifestations in children is critical to rapid identification of global and region-specific risk factors, and developing treatment and mitigation strategies for the current pandemic and future health neurologic emergencies.


Subject(s)
COVID-19 , Nervous System Diseases/virology , Systemic Inflammatory Response Syndrome , COVID-19/complications , Child , Humans , Multicenter Studies as Topic , Pandemics
10.
Trials ; 22(1): 857, 2021 Nov 27.
Article in English | MEDLINE | ID: covidwho-1538084

ABSTRACT

BACKGROUND: Some pain, fatigue, and gastrointestinal adverse events were observed in potential association with injection of COVID-19 vaccines, while there was no preventive intervention for it. We aim to investigate the efficacy of auricular acupressure (AA) therapy in preventing and relieving AEFI after injection of COVID-19 vaccine. METHODS: The study design is a randomized, multicentre, three-arm controlled, single-blind trial. Participants meeting the inclusion criteria will be advertised and enrolled and assigned in the medical institutions randomly for post-injection observation. No less than 360 participants will be randomized into one of three groups: auricular acupressure group, sham auricular acupressure group, and wait-list group. Interventions will be performed immediately and will happen 4 to 5 times per day for 5 days. The primary clinical outcomes will be quality and quantity evaluation among participants who reported any AEFI and who reported local pain at injection site. Secondary outcomes will concern headache, muscle and (or) joint pain, fatigue, nausea, vomiting, diarrhoea, and other potential events. All the outcomes will be assessed at baseline and 1, 3, 5, 7, and 14 days after the injection. Both intention-to-treat and per-protocol analyses will be performed, with significance level determined as 5%. DISCUSSION: Results of this trial will help to clarify the value of auricular acupressure therapy in preventing and relieving overall and certain adverse events following immunization after injection of COVID-19 vaccine. TRIAL REGISTRATION: China Clinical Trial Registry (ChiCTR) ( ChiCTR2100043210 ). Registered on 8 February, 2021.


Subject(s)
Acupressure , COVID-19 , COVID-19 Vaccines , Humans , Multicenter Studies as Topic , Randomized Controlled Trials as Topic , SARS-CoV-2 , Single-Blind Method , Treatment Outcome , Vaccination
11.
BMC Musculoskelet Disord ; 22(1): 953, 2021 Nov 15.
Article in English | MEDLINE | ID: covidwho-1526624

ABSTRACT

BACKGROUND: Hand osteoarthritis is a common and disabling problem without effective therapies. Accumulating evidence suggests the role of local inflammation in causing pain and structural progression in hand osteoarthritis, and hand osteoarthritis with synovitis is a commonly encountered clinical phenotype. Methotrexate is a well-established, low-cost, and effective treatment for inflammatory arthritis with a well-described safety profile. The aim of this multicentre, randomised, double-blind, placebo-controlled trial is to determine whether methotrexate reduces pain over 6 months in patients with hand osteoarthritis and synovitis. METHODS: Ninety-six participants with hand osteoarthritis and synovitis will be recruited through the Osteoarthritis Clinical Trial Network (Melbourne, Hobart, Adelaide, and Perth), and randomly allocated in a 1:1 ratio to receive either methotrexate 20 mg or identical placebo once weekly for 6 months. The primary outcome is pain reduction (assessed by 100 mm visual analogue scale) at 6 months. The secondary outcomes include changes in physical function and quality of life assessed using Functional Index for Hand Osteoarthritis, Australian Canadian Osteoarthritis Hand Index, Health Assessment Questionnaire, Michigan Hand Outcomes Questionnaire, Short-Form-36, tender and swollen joint count, and grip strength, and structural progression assessed using progression of synovitis and bone marrow lesions from magnetic resonance imaging and radiographic progression at 6 months. Adverse events will be recorded. The primary analysis will be by intention to treat, including all participants in their randomised groups. DISCUSSION: This study will provide high-quality evidence to address whether methotrexate has an effect on reducing pain over 6 months in patients with hand osteoarthritis and synovitis, with major clinical and public health importance. While a positive trial will inform international clinical practice guidelines for the management of hand osteoarthritis, a negative trial would be highly topical and change current trends in clinical practice. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR), ACTRN12617000877381. Registered 15 June 2017, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=373124.


Subject(s)
Osteoarthritis , Synovitis , Australia , Canada , Double-Blind Method , Humans , Methotrexate/therapeutic use , Multicenter Studies as Topic , Osteoarthritis/diagnostic imaging , Osteoarthritis/drug therapy , Quality of Life , Randomized Controlled Trials as Topic , Synovitis/diagnostic imaging , Synovitis/drug therapy , Treatment Outcome
13.
Am J Obstet Gynecol MFM ; 3(6): 100468, 2021 11.
Article in English | MEDLINE | ID: covidwho-1525659

ABSTRACT

OBJECTIVE: This study aimed to report the spectrum of placental pathology findings in pregnancies complicated by SARS-CoV-2 infection. DATA SOURCES: MEDLINE, Embase, Google Scholar, and the Web of Science databases were searched up to August 11, 2021. STUDY ELIGIBILITY CRITERIA: Histopathologic anomalies included maternal vascular malperfusion, fetal vascular malperfusion, acute inflammatory pathology, chronic inflammatory pathology, increased perivillous fibrin, and intervillous thrombosis. Moreover, subanalyses of symptomatic women only and high-risk pregnancies were performed. METHODS: Histopathologic analysis of the placenta included gross examination, histopathology on hematoxylin and eosin, immunohistochemistry, fluorescence in situ hybridization, quantitative reverse transcription-polymerase chain reaction on placental tissue, and transmission electron microscope. Random-effect meta-analyses were used to analyze the data. RESULTS: A total of 56 studies (1008 pregnancies) were included. Maternal vascular malperfusion was reported in 30.7% of placentas (95% confidence interval, 20.3-42.1), whereas fetal vascular malperfusion was observed in 27.08 % of cases (95% confidence interval, 19.2-35.6). Acute and chronic inflammatory pathologies were reported in 22.68% (95% confidence interval, 16.9-29.0) and 25.65% (95% confidence interval, 18.4-33.6) of cases, respectively. Increased perivillous fibrin was observed in 32.7% (95% confidence interval, 24.1-42.0) of placentas undergoing histopathologic analysis, whereas intervillous thrombosis was observed in 14.6% of cases (95% confidence interval, 9.7-20.2). Other placental findings, including a basal plate with attached myometrial fibers, microscopic accretism, villous edema, increased circulating nucleated red blood cells, or membranes with hemorrhage, were reported in 37.5% of cases (95% confidence interval, 28.0-47.5), whereas only 17.5% of cases (95% confidence interval, 10.9-25.2) did not present any abnormal histologic findings. The subanalyses according to maternal symptoms owing to SARS-CoV-2 infection or the presence of a high-risk pregnancy showed a similar distribution of the different histopathologic anomalies to that reported in the main analysis. Moreover, the risk of placental histopathologic anomalies was higher when considering only case-control studies comparing women with SARS-CoV-2 infection with healthy controls. CONCLUSION: In pregnant women with SARS-CoV-2 infection, a significant proportion of placentas showed histopathologic findings, suggesting placental hypoperfusion and inflammation. Future multicenter prospective blinded studies are needed to correlate these placental lesions with pregnancy outcomes.


Subject(s)
COVID-19 , Pregnancy Complications, Infectious , Female , Humans , In Situ Hybridization, Fluorescence , Multicenter Studies as Topic , Placenta , Pregnancy , Pregnancy Outcome , Prospective Studies , SARS-CoV-2
14.
Ann Intern Med ; 174(1): JC3, 2021 01.
Article in English | MEDLINE | ID: covidwho-1518748

ABSTRACT

SOURCE CITATION: RECOVERY Collaborative Group. Lopinavir-ritonavir in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. Lancet. 2020;396:1345-52. 33031764.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19/drug therapy , Hospitalization , Lopinavir/therapeutic use , Ritonavir/therapeutic use , Administration, Oral , Aged , Antiviral Agents/administration & dosage , COVID-19/mortality , Drug Combinations , Female , Humans , Lopinavir/administration & dosage , Male , Multicenter Studies as Topic , Randomized Controlled Trials as Topic , Ritonavir/administration & dosage , SARS-CoV-2 , United Kingdom
15.
BMJ Open ; 11(11): e050202, 2021 11 11.
Article in English | MEDLINE | ID: covidwho-1515299

ABSTRACT

INTRODUCTION: Severe SARS-CoV-2 infection is associated with a dysregulated immune response. Inflammatory monocytes and macrophages are crucial, promoting injurious, proinflammatory sequelae. Immunomodulation is, therefore, an attractive therapeutic strategy and we sought to test licensed and novel candidate drugs. METHODS AND ANALYSIS: The CATALYST trial is a multiarm, open-label, multicentre, phase II platform trial designed to identify candidate novel treatments to improve outcomes of patients hospitalised with COVID-19 compared with usual care. Treatments with evidence of biomarker improvements will be put forward for larger-scale testing by current national phase III platform trials. Hospitalised patients >16 years with a clinical picture strongly suggestive of SARS-CoV-2 pneumonia (confirmed by chest X-ray or CT scan, with or without a positive reverse transcription PCR assay) and a C reactive protein (CRP) ≥40 mg/L are eligible. The primary outcome measure is CRP, measured serially from admission to day 14, hospital discharge or death. Secondary outcomes include the WHO Clinical Progression Improvement Scale as a principal efficacy assessment. ETHICS AND DISSEMINATION: The protocol was approved by the East Midlands-Nottingham 2 Research Ethics Committee (20/EM/0115) and given urgent public health status; initial approval was received on 5 May 2020, current protocol version (V.6.0) approval on 12 October 2020. The MHRA also approved all protocol versions. The results of this trial will be disseminated through national and international presentations and peer-reviewed publications. TRIAL REGISTRATION NUMBERS: EudraCT2020-001684-89, ISRCTN40580903.


Subject(s)
COVID-19 , Adult , Clinical Trials, Phase II as Topic , Hospitalization , Humans , Multicenter Studies as Topic , Research , SARS-CoV-2
16.
J Clin Microbiol ; 59(9): e0076721, 2021 08 18.
Article in English | MEDLINE | ID: covidwho-1501529

ABSTRACT

In response to the worldwide pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the subsequent antibody tests that flooded the market, a nationwide collaborative approach in the Netherlands was employed. Forty-one Dutch laboratories joined forces and shared their evaluation data to allow for the evaluation of a quantity of serological assays for SARS-CoV-2 that exceeds the capacity of each individual laboratory. As of April 2020, these performance data had been aggregated and shared in regularly updated reports with other laboratories, Dutch government, public health organizations, and the public. This frequently updated overview of assay performance increased the efficiency of our national laboratory response, supporting laboratories in their choice and implementation of assays. Aggregated performance data for 47 immunoassays for SARS-CoV-2 showed that none of the evaluated immunoassays that detect only IgM or IgA met the diagnostic criteria, indicating that they are not suitable for diagnosing acute infections. For the detection of IgG, only the Biozek Corona virus COVID rapid test, Euroimmun SARS-CoV-2 IgG, and Wantai SARS-CoV-2 antibody (Ab) ELISA met predefined performance criteria in hospitalized patients where samples were collected 14 days post-onset of symptoms (DPO), while for patients with mild or asymptomatic infections, only the Wantai SARS-CoV-2 Ab ELISA met the predefined performance criteria if samples were collected 14 days postonset. Here, we describe this unique nationwide collaboration during the onset of the COVID-19 pandemic; the collected data and their results are an example of what can be accomplished when forces are joined during a public health crisis.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Viral , COVID-19 Testing , Humans , Immunoassay , Immunoglobulin M , Laboratories , Multicenter Studies as Topic , Pandemics , Sensitivity and Specificity
17.
Geroscience ; 43(3): 1093-1112, 2021 06.
Article in English | MEDLINE | ID: covidwho-1499503

ABSTRACT

We are in the midst of the global pandemic. Though acute respiratory coronavirus (SARS-COV2) that leads to COVID-19 infects people of all ages, severe symptoms and mortality occur disproportionately in older adults. Geroscience interventions that target biological aging could decrease risk across multiple age-related diseases and improve outcomes in response to infectious disease. This offers hope for a new host-directed therapeutic approach that could (i) improve outcomes following exposure or shorten treatment regimens; (ii) reduce the chronic pathology associated with the infectious disease and subsequent comorbidity, frailty, and disability; and (iii) promote development of immunological memory that protects against relapse or improves response to vaccination. We review the possibility of this approach by examining available evidence in metformin: a generic drug with a proven safety record that will be used in a large-scale multicenter clinical trial. Though rigorous translational research and clinical trials are needed to test this empirically, metformin may improve host immune defenses and confer protection against long-term health consequences of infectious disease, age-related chronic diseases, and geriatric syndromes.


Subject(s)
COVID-19 , Communicable Diseases , Metformin , Aged , Communicable Diseases/drug therapy , Humans , Metformin/therapeutic use , Multicenter Studies as Topic , RNA, Viral , SARS-CoV-2
18.
BMJ Open ; 11(9): e054711, 2021 09 28.
Article in English | MEDLINE | ID: covidwho-1495475

ABSTRACT

INTRODUCTION: The majority of women admitted with threatened preterm labour (PTL) do not delivery prematurely. While those with microbial invasion of the amniotic cavity (MIAC) represent the highest risk group, this is a condition that is not routinely ruled out since it requires amniocentesis. Identification of low-risk or high-risk cases might allow individualisation of care, that is, reducing overtreatment with corticosteroids and shorten hospital stay in low-risk women, while allowing early antibiotic therapy in those with MIAC. Benefits versus risks of amniocentesis-based predictor models of spontaneous delivery within 7 days and/or MIAC have not been evaluated. METHODS AND ANALYSIS: This will be a Spanish randomised, multicentre clinical trial in singleton pregnancies (23.0-34.6 weeks) with PTL, conducted in 13 tertiary centres. The intervention arm will consist in the use of amniocentesis-based predictor models: if low risk, hospital discharge within 24 hours of results with no further medication will be recommended. If high risk, antibiotics will be added to standard management. The control group will be managed according to standard institutional protocols, without performing amniocentesis for this indication. The primary outcome will be total antenatal doses of corticosteroids, and secondary outcomes will be days of maternal stay and the occurrence of clinical chorioamnionitis. A cost analysis will be undertaken. To observe a reduction from 90% to 70% in corticosteroid doses, a reduction in 1 day of hospital stay (SD of 2) and a reduction from 24% to 12% of clinical chorioamnionitis, a total of 340 eligible patients randomised 1 to 1 to each study arm is required (power of 80%, with type I error α=0.05 and two-sided test, considering a dropout rate of 20%). Randomisation will be stratified by gestational age and centre. ETHICS AND DISSEMINATION: Prior to receiving approval from the Ethics Committee (HCB/2020/1356) and the Spanish Agency of Medicines and Medical Devices (AEMPS) (identification number: 2020-005-202-26), the trial was registered in the European Union Drug Regulating Authorities Clinical Trials database (2020-005202-26). AEMPS approved the trial as a low-intervention trial. All participants will be required to provide written informed consent. Findings will be disseminated through workshops, peer-reviewed publications and national/international conferences. PROTOCOL VERSION: V.4 10 May 2021. TRIAL REGISTRATION NUMBERS: NCT04831086 and Eudract number 2020-005202-26.


Subject(s)
COVID-19 , Obstetric Labor, Premature , Amniocentesis , Female , Hospitalization , Humans , Infant, Newborn , Multicenter Studies as Topic , Obstetric Labor, Premature/prevention & control , Pregnancy , Randomized Controlled Trials as Topic , SARS-CoV-2
19.
BMJ Open ; 11(10): e052101, 2021 10 28.
Article in English | MEDLINE | ID: covidwho-1495466

ABSTRACT

INTRODUCTION: BCG vaccination modulates immune responses to unrelated pathogens. This off-target effect could reduce the impact of emerging pathogens. As a readily available, inexpensive intervention that has a well-established safety profile, BCG is a good candidate for protecting healthcare workers (HCWs) and other vulnerable groups against COVID-19. METHODS AND ANALYSIS: This international multicentre phase III randomised controlled trial aims to determine if BCG vaccination reduces the incidence of symptomatic and severe COVID-19 at 6 months (co-primary outcomes) compared with no BCG vaccination. We plan to randomise 10 078 HCWs from Australia, The Netherlands, Spain, the UK and Brazil in a 1:1 ratio to BCG vaccination or no BCG (control group). The participants will be followed for 1 year with questionnaires and collection of blood samples. For any episode of illness, clinical details will be collected daily, and the participant will be tested for SARS-CoV-2 infection. The secondary objectives are to determine if BCG vaccination reduces the rate, incidence, and severity of any febrile or respiratory illness (including SARS-CoV-2), as well as work absenteeism. The safety of BCG vaccination in HCWs will also be evaluated. Immunological analyses will assess changes in the immune system following vaccination, and identify factors associated with susceptibility to or protection against SARS-CoV-2 and other infections. ETHICS AND DISSEMINATION: Ethical and governance approval will be obtained from participating sites. Results will be published in peer-reviewed open-access journals. The final cleaned and locked database will be deposited in a data sharing repository archiving system. TRIAL REGISTRATION: ClinicalTrials.gov NCT04327206.


Subject(s)
BCG Vaccine , COVID-19 , Health Personnel , Humans , Multicenter Studies as Topic , Randomized Controlled Trials as Topic , SARS-CoV-2 , Treatment Outcome , Vaccination
20.
BMJ Open ; 11(9): e048591, 2021 09 14.
Article in English | MEDLINE | ID: covidwho-1495462

ABSTRACT

INTRODUCTION: Pre-emptive inhaled antibiotics may be effective to reduce the occurrence of ventilator-associated pneumonia among critically ill patients. Meta-analysis of small sample size trials showed a favourable signal. Inhaled antibiotics are associated with a reduced emergence of antibiotic resistant bacteria. The aim of this trial is to evaluate the benefit of a 3-day course of inhaled antibiotics among patients undergoing invasive mechanical ventilation for more than 3 days on the occurrence of ventilator-associated pneumonia. METHODS AND ANALYSIS: Academic, investigator-initiated, parallel two group arms, double-blind, multicentre superiority randomised controlled trial. Patients invasively ventilated more than 3 days will be randomised to receive 20 mg/kg inhaled amikacin daily for 3 days or inhaled placebo (0.9% Sodium Chloride). Occurrence of ventilator-associated pneumonia will be recorded based on a standardised diagnostic framework from randomisation to day 28 and adjudicated by a centralised blinded committee. ETHICS AND DISSEMINATION: The protocol and amendments have been approved by the regional ethics review board and French competent authorities (Comité de protection des personnes Ouest I, No.2016-R29). All patients will be included after informed consent according to French law. Results will be disseminated in international scientific journals. TRIAL REGISTRATION NUMBERS: EudraCT 2016-001054-17 and NCT03149640.


Subject(s)
Amikacin , Pneumonia, Ventilator-Associated , Administration, Inhalation , Amikacin/administration & dosage , Double-Blind Method , Humans , Multicenter Studies as Topic , Pneumonia, Ventilator-Associated/prevention & control , Randomized Controlled Trials as Topic , Respiration, Artificial/adverse effects , Treatment Outcome
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