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1.
BMJ Open ; 12(11): e061360, 2022 11 14.
Article in English | MEDLINE | ID: covidwho-2119452

ABSTRACT

INTRODUCTION: This study will compare the lowering effects of pemafibrate and omega-3 fatty acid ethyl esters on fasting apolipoprotein B-48 (apoB-48), a surrogate marker reflecting postprandial hypertriglyceridaemia, which is a residual risk for atherosclerotic cardiovascular disease with statin treatment. METHODS AND ANALYSIS: This is a prospective, multicentre, open-label, randomised, parallel group, comparative trial. Adult Japanese patients with dyslipidaemia receiving statin treatment for more than 4 weeks with a fasting triglyceride level ≥177 mg/dL will be randomly assigned in a 1:1 ratio to receive pemafibrate (0.4 mg orally per day) or omega-3 fatty acid ethyl esters (4 g orally per day) for 16 weeks. The primary endpoint is the percentage change in fasting apoB-48 from baseline to 16 weeks. The key secondary endpoints include the change in fasting apoB-48 from baseline to 16 weeks, the percentage changes in clinical variables from baseline to 16 weeks and the incidence of adverse events. A total sample size of 128 was set by considering the increased drop-out rate due to the COVID-19 pandemic, in addition to estimation based on a two-sided alpha of 0.05 and a power of 0.8 for apoB-48. ETHICS AND DISSEMINATION: The study protocol has been approved by the Certified Review Board of the University of the Ryukyus for Clinical Research Ethics (No. CRB7200001) and will be performed in accordance with the Declaration of Helsinki. Written informed consent will be obtained from all participants. The results of the study will be disseminated through publications and conference presentations to participants, healthcare professionals and the public. TRIAL REGISTRATION NUMBER: jRCTs071200011.


Subject(s)
COVID-19 , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Hyperlipidemias , Humans , Adult , Apolipoprotein B-48 , Pandemics , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Japan , Prospective Studies , Eicosapentaenoic Acid , Treatment Outcome , Esters , Randomized Controlled Trials as Topic , Multicenter Studies as Topic
2.
Trials ; 23(1): 932, 2022 Nov 08.
Article in English | MEDLINE | ID: covidwho-2108882

ABSTRACT

BACKGROUND: COVID-19 poses a global health challenge with more than 325 million cumulative cases and above 5 million cumulative deaths reported till January 17, 2022, by the World Health Organization. Several potential treatments to treat COVID-19 are under clinical trials including antivirals, steroids, immunomodulators, non-specific IVIG, monoclonal antibodies, and passive immunization through convalescent plasma. The need to produce anti-COVID-19 IVIG therapy must be continued, alongside the current treatment modalities, considering the virus is still mutating into variants of concern. In this context, as the present study will exploit pooled diversified convalescent plasma collected from recovered COVID-19 patients, the proposed hyperimmune Anti-COVID-19 intravenous immunoglobulin (C-IVIG) therapy would be able to counter new infectious COVID-19 variants by neutralizing the virus particles. After the successful outcome of the phase I/II clinical trial of C-IVIG, the current study aims to further evaluate the safety and efficacy of single low dose C-IVIG in severe COVID-19 patients for its phase II/III clinical trial. METHODS: This is a phase II/III, adaptive, multi-center, single-blinded, randomized controlled superiority trial of SARS-CoV-2 specific polyclonal IVIG (C-IVIG). Patients fulfilling the eligibility criteria will be block-randomized using a sealed envelope system to receive either 0.15 g/Kg C-IVIG with standard of care (SOC) or standard of care alone in 2:1 ratio. The patients will be followed-up for 28 days to assess the primary and secondary outcomes. DISCUSSION: This is a phase II/III clinical trial evaluating safety and efficacy of hyperimmune anti-COVID-19 intravenous immunoglobulin (C-IVIG) in severe COVID-19 patients. This study will provide clinical evidence to use C-IVIG as one of the first-line therapeutic options for severe COVID-19 patients. TRIAL REGISTRATION: Registered at clinicaltrial.gov with NCT number NCT04891172 on May 18, 2021.


Subject(s)
COVID-19 , Coronavirus Infections , Pneumonia, Viral , Humans , SARS-CoV-2 , COVID-19/drug therapy , Betacoronavirus , Pneumonia, Viral/drug therapy , Immunoglobulins, Intravenous/adverse effects , Coronavirus Infections/drug therapy , Pandemics , Treatment Outcome , Randomized Controlled Trials as Topic , Multicenter Studies as Topic , Clinical Trials, Phase II as Topic , Clinical Trials, Phase III as Topic
3.
BMJ Open ; 12(11): e063856, 2022 11 04.
Article in English | MEDLINE | ID: covidwho-2108284

ABSTRACT

INTRODUCTION: Hypercoagulation is one the main features of COVID-19. It is induced by the hyperinflammatory response that shifts the balance of haemostasis towards pro-coagulation. Interleukin-6 (IL-6) antagonist therapy has been recommended in certain subgroups of critically ill patients with COVID-19 to modulate inflammatory response. The interaction between immune response and haemostasis is well recognised. Therefore, our objective is to evaluate whether the modulation of the inflammatory response by IL-6 antagonist inflicts any changes in whole blood coagulation as assessed by viscoelastic methods in critically ill patients with COVID-19. METHODS AND ANALYSIS: In this prospective observational study, we are going to collect data on inflammatory parameters and blood coagulation using the ClotPro® device. The primary outcome is the change of the fibrinolytic system measured by the Lysis Time and Lysis onset time before and after immunomodulation therapy. Data will be collected before the IL-6 antagonist administration at baseline (T0) then after 24, 48 hours, then on day 5 and 7 (T1-4, respectively). Secondary outcomes include changes in other parameters related to inflammation, blood coagulation and biomarkers of endothelial injury. ETHICS AND DISSEMINATION: Ethical approval was given by the Medical Research Council of Hungary (1405-3/2022/EÜG). All participants provided written consent. The results of the study will be disseminated through peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05218369; Clinicaltrials.gov.


Subject(s)
COVID-19 , Humans , Blood Coagulation , COVID-19/drug therapy , Critical Illness/therapy , Interleukin-6 , Multicenter Studies as Topic , Observational Studies as Topic , Prospective Studies
4.
Gastroenterol Hepatol ; 43(8): 464-471, 2020 Oct.
Article in English, Spanish | MEDLINE | ID: covidwho-2095369

ABSTRACT

The SARS-CoV-2 pandemic is leading to high mortality and a global health crisis. The primary involvement is respiratory; however, the virus can also affect other organs, such as the gastrointestinal tract and liver. The most common symptoms are anorexia and diarrhea. In about half of the cases, viral RNA could be detected in the stool, which is another line of transmission and diagnosis. covid19 has a worse prognosis in patients with comorbidities, although there is not enough evidence in case of previous digestive diseases. Digestive endoscopies may give rise to aerosols, which make them techniques with a high risk of infection. Experts and scientific organizations worldwide have developed guidelines for preventive measures. The available evidence on gastrointestinal and hepatic involvement, the impact on patients with previous digestive diseases and operating guidelines for Endoscopy Units during the pandemic are reviewed.


Subject(s)
Betacoronavirus/pathogenicity , Coronavirus Infections/complications , Digestive System Diseases/etiology , Digestive System/virology , Pandemics , Pneumonia, Viral/complications , Aerosols , Angiotensin-Converting Enzyme 2 , Anorexia/etiology , Antiviral Agents/adverse effects , Betacoronavirus/isolation & purification , Betacoronavirus/physiology , COVID-19 , Cohort Studies , Coronavirus Infections/drug therapy , Coronavirus Infections/prevention & control , Coronavirus Infections/transmission , Diarrhea/etiology , Digestive System Diseases/virology , Endoscopy, Digestive System/adverse effects , Feces/virology , Humans , Immunosuppressive Agents/adverse effects , Intestines/chemistry , Intestines/virology , Liver Diseases/etiology , Multicenter Studies as Topic , Pandemics/prevention & control , Peptidyl-Dipeptidase A/analysis , Peptidyl-Dipeptidase A/physiology , Personal Protective Equipment , Pneumonia, Viral/drug therapy , Pneumonia, Viral/prevention & control , Pneumonia, Viral/transmission , Receptors, Virus/analysis , Receptors, Virus/physiology , Risk , SARS-CoV-2 , Universal Precautions
5.
J Neurol Sci ; 443: 120463, 2022 Dec 15.
Article in English | MEDLINE | ID: covidwho-2086469

ABSTRACT

INTRODUCTION: We aimed to provide insights into transverse myelitis (TM) following COVID-19 by analyzing cases treated at tertiary care neurology centers and a systemic review of the literature. METHODS: The retrospective observational multi-center study was conducted at the four university neurology departments in Croatia, Slovenia, Serbia, and Austria. We searched for acute myelitis cases that occurred during or after COVID-19. A systemic review of the literature on COVID-19 and transverse myelitis was performed. RESULTS: We identified 76 persons with TM associated with COVID-19, 13 from the multi-center study and 63 from the literature review. Most of the participants (55.6%) had an intermediate latency, 25.4% had short and 19% long latency from COVID-19 symptoms to TM. The clinical presentation consisted of the typical TM signs. More than half of the participants had inflammatory changes in the CSF, with rare patients having intrathecal OCB synthesis and positive serology for anti-MOG or anti-AQP4 antibodies. Persons with autonomic symptoms and CSF pleocytosis were significantly more common to have an intermediate latency of 8 to 21 days from COVID-19 to TM (p = 0.005 and p = 0.003; respectively). According to logistic regression analysis, only participants with lesions evident on spinal cord MRI compared to normal spinal cord MRI had reduced risks for poor recovery. >80% of participants were treated with a combination of corticosteroids and intravenous immunoglobulins or plasma exchange with 73% having incomplete recovery. CONCLUSION: Our study further characterizes clinical, laboratory, and MRI features, as well as treatment of TM associated with COVID-19.


Subject(s)
COVID-19 , Myelitis, Transverse , Humans , Myelitis, Transverse/diagnostic imaging , Myelitis, Transverse/etiology , Retrospective Studies , COVID-19/complications , Magnetic Resonance Imaging , Multicenter Studies as Topic
6.
Med Sci Sports Exerc ; 54(7): 1051-1057, 2022 07 01.
Article in English | MEDLINE | ID: covidwho-2079613

ABSTRACT

INTRODUCTION/PURPOSE: SARS-CoV-2 infection (COVID-19) can result in myocarditis. Protocols were developed to allow competitive athletes to safely return to play (RTP) after a COVID-19 infection, but the financial impact of these protocols is unknown. Our objective was to determine the differential cost of post-COVID-19 RTP protocols for competitive collegiate athletes. METHODS: This multicenter retrospective cohort study of clinical evaluation of 295 athletes after COVID-19 infection was performed at four institutions with three RTP protocols. Costs were calculated using adjusted Center for Medicare and Medicaid Services pricing. All athletes underwent electrocardiogram and clinical evaluation. A tiered approach performed cardiac imaging and biomarker analysis for major symptoms. A universal transthoracic echocardiogram (TTE) approach performed TTE and biomarkers for all athletes. A universal exercise stress echocardiogram (ESE) approach performed ESE and biomarkers for all athletes. RESULTS: The cost per athlete was $632.51 ± 651.80 ($44,908 total) in tiered group (n = 71), $1,072.30 ± 517.93 ($87,928 total) in the universal TTE group (n = 82), and $1357.38 ± 757.05 ($192,748 total) in the universal ESE group (n = 142) (P < 0.001). Extrapolated national costs for collegiate athletes would be $39 to 64 million higher for universal imaging approaches versus a tiered approach. Only seven athletes had probable/possible myocarditis with no significant difference between approaches. CONCLUSIONS: Cardiac screening in collegiate athletes after COVID-19 infection resulted in significant cost to the health care system. A tiered-based approach was more economical, and a universal exercise echocardiogram group detected slightly more myocardial abnormalities by cardiac magnetic resonance imaging. The clinical consequences of these approaches are unknown.


Subject(s)
COVID-19 , Myocarditis , Aged , Athletes , Biomarkers , Humans , Medicare , Multicenter Studies as Topic , Retrospective Studies , Return to Sport , SARS-CoV-2 , United States
7.
Trials ; 23(1): 242, 2022 Mar 29.
Article in English | MEDLINE | ID: covidwho-2079532

ABSTRACT

BACKGROUND: The rapidly increasing number of elderly (≥ 65 years old) with TBI is accompanied by substantial medical and economic consequences. An ASDH is the most common injury in elderly with TBI and the surgical versus conservative treatment of this patient group remains an important clinical dilemma. Current BTF guidelines are not based on high-quality evidence and compliance is low, allowing for large international treatment variation. The RESET-ASDH trial is an international multicenter RCT on the (cost-)effectiveness of early neurosurgical hematoma evacuation versus initial conservative treatment in elderly with a t-ASDH METHODS: In total, 300 patients will be recruited from 17 Belgian and Dutch trauma centers. Patients ≥ 65 years with at first presentation a GCS ≥ 9 and a t-ASDH > 10 mm or a t-ASDH < 10 mm and a midline shift > 5 mm, or a GCS < 9 with a traumatic ASDH < 10 mm and a midline shift < 5 mm without extracranial explanation for the comatose state, for whom clinical equipoise exists will be randomized to early surgical hematoma evacuation or initial conservative management with the possibility of delayed secondary surgery. When possible, patients or their legal representatives will be asked for consent before inclusion. When obtaining patient or proxy consent is impossible within the therapeutic time window, patients are enrolled using the deferred consent procedure. Medical-ethical approval was obtained in the Netherlands and Belgium. The choice of neurosurgical techniques will be left to the discretion of the neurosurgeon. Patients will be analyzed according to an intention-to-treat design. The primary endpoint will be functional outcome on the GOS-E after 1 year. Patient recruitment starts in 2022 with the exact timing depending on the current COVID-19 crisis and is expected to end in 2024. DISCUSSION: The study results will be implemented after publication and presented on international conferences. Depending on the trial results, the current Brain Trauma Foundation guidelines will either be substantiated by high-quality evidence or will have to be altered. TRIAL REGISTRATION: Nederlands Trial Register (NTR), Trial NL9012 . CLINICALTRIALS: gov, Trial NCT04648436 .


Subject(s)
Brain Injuries, Traumatic , COVID-19 , Hematoma, Subdural, Acute , Aged , Hematoma, Subdural, Acute/diagnosis , Hematoma, Subdural, Acute/surgery , Humans , Multicenter Studies as Topic , Neurosurgical Procedures , Randomized Controlled Trials as Topic , Trauma Centers
8.
Int J Environ Res Public Health ; 19(19)2022 Oct 07.
Article in English | MEDLINE | ID: covidwho-2066069

ABSTRACT

The COVID-19 pandemic is a major public health problem with millions of confirmed cases and deaths described. Nurses are among the health care professionals most involved at the front line, caring for those affected by COVID-19. Patients and families have been subjected to a high emotional burden of fear, anxiety, and uncertainty. The COVID-19 pandemic has had a significant impact on the approach to patients, the organisation of care, and communication with patients and their families, all requiring considerable adaptation on the part of nurses and health care professionals. The overall aim of this research was to find out the needs of patients with COVID-19, the nursing interventions provided and their outcomes, and to explore the experiences of the nurses, patients, and caregivers. A mixed method study will be performed with a convergent design. The study was divided into three phases. Quantitative methods involved nurses and patients affected by COVID-19 with a questionnaire. Qualitative methods involved nurses, patients, and caregivers with interviews and finally a quantitative analysis of the nursing documentation of the interviewed patients. We hope that this study will help us to understand and identify the main nursing and support needs expressed by patients and their families at different stages of their illness.


Subject(s)
COVID-19 , Nurses , COVID-19/epidemiology , Caregivers/psychology , Communication , Health Personnel/psychology , Humans , Multicenter Studies as Topic , Pandemics , Qualitative Research
9.
BMJ Open Respir Res ; 9(1)2022 09.
Article in English | MEDLINE | ID: covidwho-2064180

ABSTRACT

INTRODUCTION: Cystic fibrosis (CF) is a life-limiting genetic disorder estimated to affect more than 160 000 individuals and their families worldwide. People living with CF commonly experience significant physical and emotional symptom burdens, disruptions to social roles and complex treatment decision making. While palliative care (PC) interventions have been shown to relieve many such burdens in other serious illnesses, no rigorous evidence exists for palliative care in CF. Thus, this study aims to compare the effect of specialist palliative care plus usual CF care vs usual CF care alone on patient quality of life. METHODS AND ANALYSIS: This is a five-site, two-arm, partially masked, randomised superiority clinical trial. 264 adults with CF will be randomly assigned to usual CF care or usual CF care plus a longitudinal palliative care intervention delivered by a palliative care specialist. The trial's primary outcome is patient quality of life (measured with the Functional Assessment of Chronic Illness Therapy-Palliative care instrument). Secondary outcomes include symptom burden, satisfaction with care and healthcare utilisation. Outcomes will be measured at 12 months (primary endpoint) and 15 months (secondary endpoint). In addition, we will conduct qualitative interviews with patient participants, caregivers, and palliative care and CF care team members to explore perceptions of the intervention's impact and barriers and facilitators to dissemination. ETHICS AND DISSEMINATION: Human subjects research ethics approval was obtained from all participating sites, and all study participants gave informed consent. We will publish the results of this trial in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ISRCTN53323164.


Subject(s)
Cystic Fibrosis , Palliative Care , Adult , Caregivers/psychology , Cystic Fibrosis/therapy , Humans , Multicenter Studies as Topic , Palliative Care/methods , Quality of Life , Randomized Controlled Trials as Topic
10.
Trials ; 23(1): 824, 2022 Sep 30.
Article in English | MEDLINE | ID: covidwho-2053955

ABSTRACT

BACKGROUND: This update summarises key changes made to the protocol since the publication of the original protocol for the NAVKIDS2 trial of patient navigators for children with chronic kidney disease (CKD) experiencing social disadvantage and provides the statistical analysis plan (SAP) which has not previously been published. METHODS/DESIGN: The original protocol was published in BMC Nephrology ( https://doi.org/10.1186/s12882-019-1325-y ) prior to the commencement of trial recruitment. During the course of the trial, some key methodological changes needed to be made including changes to eligibility criteria (addition of patients with CKD stages 1-2, broadening of financial status eligibility criterion, addition of patients living in rural/remote areas, modification of age eligibility to 0-16 years, addition of limits related to the language spoken by family, guidance regarding families with multiple eligible children), changes to sites, reduction of sample size, addition of virtual options for consent and study procedures in response to the COVID-19 pandemic, removal of staggered recruitment across sites, addition of outcomes, and changes to the timing and number of assessments. This update summarises the changes made and their rationale and provides the detailed plan for statistical analysis of the trial. These changes have been finalised prior to the completion of study follow-up and the commencement of data analysis. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12618001152213 . Prospectively registered on 12 July 2018.


Subject(s)
COVID-19 , Patient Navigation , Renal Insufficiency, Chronic , Australia , Child , Humans , Multicenter Studies as Topic , Pandemics , Randomized Controlled Trials as Topic , Renal Insufficiency, Chronic/diagnosis , Renal Insufficiency, Chronic/therapy , SARS-CoV-2 , Treatment Outcome
11.
Trials ; 23(1): 798, 2022 Sep 22.
Article in English | MEDLINE | ID: covidwho-2053951

ABSTRACT

BACKGROUND: Fluid overload is associated with worse outcome in critically ill patients requiring continuous renal replacement therapy (CRRT). Net ultrafiltration (UFNET) allows precise control of the fluid removal but is frequently ceased due to hemodynamic instability episodes. However, approximately 50% of the hemodynamic instability episodes in ICU patients treated with CRRT are not associated with preload dependence (i.e., are not related to a decrease in cardiac preload), suggesting that volume removal is not responsible for these episodes of hemodynamic impairment. The use of advanced hemodynamic monitoring, comprising continuous cardiac output monitoring to repeatedly assess preload dependency, could allow securing UFNET to allow fluid balance control and prevent fluid overload. METHODS: The GO NEUTRAL trial is a multicenter, open-labeled, randomized, controlled, superiority trial with parallel groups and balanced randomization with a 1:1 ratio. The trial will enroll adult patients with acute circulatory failure treated with vasopressors and severe acute kidney injury requiring CRRT who already have been equipped with a continuous cardiac output monitoring device. After informed consent, patients will be randomized into two groups. The control group will receive protocolized fluid removal with an UFNET rate set to 0-25 ml h-1 between inclusion and H72 of inclusion. The intervention group will be treated with an UFNET rate set on the CRRT of at least 100 ml h-1 between inclusion and H72 of inclusion if hemodynamically tolerated based on a protocolized hemodynamic protocol aiming to adjust UFNET based on cardiac output, arterial lactate concentration, and preload dependence assessment by postural maneuvers, performed regularly during nursing rounds, and in case of a hemodynamic instability episode. The primary outcome of the study will be the cumulative fluid balance between inclusion and H72 of inclusion. Randomization will be generated using random block sizes and stratified based on fluid overload status at inclusion. The main outcome will be analyzed in the modified intention-to-treat population, defined as all alive patients at H72 of inclusion, based on their initial allocation group. DISCUSSION: We present in the present protocol all study procedures in regard to the achievement of the GO NEUTRAL trial, to prevent biased analysis of trial outcomes and improve the transparency of the trial result report. Enrollment of patients in the GO NEUTRAL trial has started on June 31, 2021, and is ongoing. TRIAL REGISTRATION: ClinicalTrials.gov NCT04801784. Registered on March 12, 2021, before the start of inclusion.


Subject(s)
COVID-19 , Continuous Renal Replacement Therapy , Hemodynamic Monitoring , Water-Electrolyte Imbalance , Adult , Critical Illness , Humans , Lactates , Multicenter Studies as Topic , Randomized Controlled Trials as Topic , SARS-CoV-2 , Standard of Care , Water-Electrolyte Balance
12.
JAMA Netw Open ; 5(10): e2234425, 2022 10 03.
Article in English | MEDLINE | ID: covidwho-2047378

ABSTRACT

Importance: Communication and adoption of modern study design and analytical techniques is of high importance for the improvement of clinical research from observational data. Objective: To compare a modern method for statistical inference, including a target trial emulation framework and doubly robust estimation, with approaches common in the clinical literature, such as Cox proportional hazards models. Design, Setting, and Participants: This retrospective cohort study used longitudinal electronic health record data for outcomes at 28-days from time of hospitalization within a multicenter New York, New York, hospital system. Participants included adult patients hospitalized between March 1 and May 15, 2020, with COVID-19 and not receiving corticosteroids for chronic use. Data were analyzed from October 2021 to March 2022. Exposures: Corticosteroid exposure was defined as more than 0.5 mg/kg methylprednisolone equivalent in a 24-hour period. For target trial emulation, exposures were corticosteroids for 6 days if and when a patient met criteria for severe hypoxia vs no corticosteroids. For approaches common in clinical literature, treatment definitions used for variables in Cox regression models varied by study design (no time frame, 1 day, and 5 days from time of severe hypoxia). Main Outcomes and Measures: The main outcome was 28-day mortality from time of hospitalization. The association of corticosteroids with mortality for patients with moderate to severe COVID-19 was assessed using the World Health Organization (WHO) meta-analysis of corticosteroid randomized clinical trials as a benchmark. Results: A total of 3298 patients (median [IQR] age, 65 [53-77] years; 1970 [60%] men) were assessed, including 423 patients who received corticosteroids at any point during hospitalization and 699 patients who died within 28 days of hospitalization. Target trial emulation analysis found corticosteroids were associated with a reduced 28-day mortality rate, from 32.2%; (95% CI, 30.9%-33.5%) to 25.7% (95% CI, 24.5%-26.9%). This estimate is qualitatively identical to the WHO meta-analysis odds ratio of 0.66 (95% CI, 0.53-0.82). Hazard ratios using methods comparable with current corticosteroid research range in size and direction, from 0.50 (95% CI, 0.41-0.62) to 1.08 (95% CI, 0.80-1.47). Conclusions and Relevance: These findings suggest that clinical research based on observational data can be used to estimate findings similar to those from randomized clinical trials; however, the correctness of these estimates requires designing the study and analyzing the data based on principles that are different from the current standard in clinical research.


Subject(s)
COVID-19 , Adrenal Cortex Hormones/therapeutic use , Aged , COVID-19/drug therapy , Clinical Trials as Topic , Female , Humans , Hypoxia , Male , Methylprednisolone/therapeutic use , Middle Aged , Multicenter Studies as Topic , Retrospective Studies
13.
Trials ; 23(1): 797, 2022 Sep 21.
Article in English | MEDLINE | ID: covidwho-2038855

ABSTRACT

BACKGROUND: Depression and anxiety are common among pregnant women. Internet-delivered psychological therapies such as cognitive behavioral therapy (iCBT) have been developed to increase accessibility and address common help-seeking barriers, especially during pandemic period. The objective of this trial is to evaluate the short-term and long-term effects of iCBT on reducing depressive symptoms among pregnant women during the COVID-19 pandemic with the overall goal of preventing depression recurrence in the first 12 months postpartum. METHODS: A multi-site randomized controlled trial will be conducted where 300 pregnant women early in their third trimester will be screened for depression symptoms using the Edinburgh Postnatal Depression Scale (EPDS) during a routine obstetrical visit. Eligible and consenting women with a score greater than 9 will be randomly allocated (1:1) to either intervention group or control group. ICBT involving the completion of 7 weekly online modules will be delivered via a well-designed perinatal mental healthcare app. The primary objective is to evaluate the effect of iCBT on reducing depression symptoms among pregnant Chinese women starting from their third trimester. The secondary objectives are to examine the effect of iCBT on anxiety, sleep quality, social support, parenting stress, co-parenting relationship, and infant development. DISCUSSION: This multi-center randomized controlled trial has been planned in accordance with best practices in behavioral trial design. The internet-based intervention addressed the needs of pregnant women during a major pandemic where face-to-face therapy is not preferable. The trial has a relatively large sample size with sufficient power to evaluate the efficacy of iCBT intervention for the primary and secondary outcomes. One year follow-up evaluation in the study is designed to determine the longer-term effect of the intervention on both maternal and infant outcomes. Although a limitation is the assessment of depression and anxiety using self-report measures, these easily incorporated and maternal-preferred assessments allow for real-life scalability if the intervention is proven to be effective. ETHICS AND DISSEMINATION: Ethics was approved by the institutional review board of International Peace Maternity and Child Health Hospital (GKLW2020-25). Dissemination of results will be published in peer-reviewed academic journals and presented at scientific conferences. TRIAL STATUS: The first patient was enrolled on 19 August 2020. To date, 203 participants have met eligibility requirements and been randomized to either the intervention group or control group. Data collection aims to be complete in September 2022. Date and version identifier: 2020715-version1.0. TRIAL REGISTRATION: ChiCTR2000033433. Registered 31 May 2020, http://www.chictr.org.cn/showproj.aspx?proj=54482 .


Subject(s)
COVID-19 , Cognitive Behavioral Therapy , Child , Cognitive Behavioral Therapy/methods , Depression/diagnosis , Depression/therapy , Female , Humans , Internet , Multicenter Studies as Topic , Pandemics , Pregnancy , Randomized Controlled Trials as Topic , Treatment Outcome
14.
Trials ; 23(1): 790, 2022 Sep 20.
Article in English | MEDLINE | ID: covidwho-2038854

ABSTRACT

BACKGROUND: Despite the fast establishment of new therapeutic agents in the management of COVID-19 and large-scale vaccination campaigns since the beginning of the SARS-CoV-2 pandemic in early 2020, severe disease courses still represent a threat, especially to patients with risk factors. This indicates the need for alternative strategies to prevent respiratory complications like acute respiratory distress syndrome (ARDS) associated with COVID-19. Aviptadil, a synthetic form of human vasoactive intestinal peptide, might be beneficial for COVID-19 patients at high risk of developing ARDS because of its ability to influence the regulation of exaggerated pro-inflammatory proteins and orchestrate the lung homeostasis. Aviptadil has recently been shown to considerably improve the prognosis of ARDS in COVID-19 when applied intravenously. An inhaled application of aviptadil has the advantages of achieving a higher concentration in the lung tissue, fast onset of activity, avoiding the hepatic first-pass metabolism, and the reduction of adverse effects. The overall objective of this project is to assess the efficacy and safety of inhaled aviptadil in patients hospitalized for COVID-19 at high risk of developing ARDS. METHODS: This multicenter, placebo-controlled, double-blinded, randomized trial with 132 adult patients hospitalized for COVID-19 and at high risk for ARDS (adapted early acute lung injury score ≥ 2 points) is conducted in five public hospitals in Europe. Key exclusion criteria are mechanical ventilation at baseline, need for intensive care at baseline, and severe hemodynamic instability. Patients are randomly allocated to either inhale 67 µg aviptadil or normal saline (three times a day for 10 days), in addition to standard care, stratified by center. The primary endpoint is time from hospitalization to clinical improvement, defined as either hospital discharge, or improvement of at least two levels on the nine-level scale for clinical status suggested by the World Health Organization. DISCUSSION: Treatment strategies for COVID-19 are still limited. In the context of upcoming new variants of SARS-CoV-2 and possible inefficacy of the available vaccines and antibody therapies, the investigation of alternative therapy options plays a crucial role in decreasing associated mortality and improving prognosis. Due to its unique immunomodulating properties also targeting the SARS-CoV-2 pathways, inhaled aviptadil may have the potential to prevent ARDS in COVID-19. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04536350 . Registered 02 September 2020.


Subject(s)
COVID-19 , Respiratory Distress Syndrome , Adult , Drug Combinations , Humans , Multicenter Studies as Topic , Phentolamine , Randomized Controlled Trials as Topic , Respiratory Distress Syndrome/diagnosis , Respiratory Distress Syndrome/drug therapy , SARS-CoV-2 , Saline Solution , Vasoactive Intestinal Peptide
15.
World J Emerg Surg ; 17(1): 46, 2022 08 29.
Article in English | MEDLINE | ID: covidwho-2038830

ABSTRACT

BACKGROUND: Pleural empyema (PE) is a frequent disease, associated with a high morbidity and mortality. Surgical approach is the standard of care for most patients with II-III stage PE. In the last years, the minimally invasive surgical revolution involved also thoracic surgery allowing the same outcomes in terms of safety and effectiveness combined to better pain management and early discharge. The aim of this study is to demonstrate through our experience on uniportal-video-assisted thoracoscopy (u-VATS) the effectiveness and safety of its approach in treatment of stage II PE. As secondary endpoint, we will evaluate the different pattern of indication of u-VATS in adult and elderly patients with literature review. METHODS: We retrospectively reviewed our prospectively collected database of u-VATS procedures from November 2018 to February 2022, in our regional referral center for Thoracic Surgery of Regione Molise General Surgery Unit of "A. Cardarelli" Hospital, in Campobasso, Molise, Italy. RESULTS: A total of 29 patients underwent u-VATS for II stage PE. Fifteen (51.72%) patients were younger than 70 years old, identified as "adults," 14 (48.28%) patients were older than 70 years old, identified as "elderly." No mortality was found. Mean operative time was 104.68 ± 39.01 min in the total population. The elderly group showed a longer operative time (115 ± 53.15 min) (p = 0.369). Chest tube was removed earlier in adults than in elderly group (5.56 ± 2.06 vs. 10.14 ± 5.58 p = 0.038). The Length of Stay (LOS) was shorter in the adults group (6.44 ± 2.35 vs. 12.29 ± 6.96 p = 0.033). Patients evaluated through Instrumental Activities of Daily Living (IADL) scale returned to normal activities of daily living after surgery. CONCLUSION: In addition, the u-VATS approach seems to be safe and effective ensuring a risk reduction of progression to stage III PE with a lower recurrence risk and septic complications also in elderly patients. Further comparative multicenter analysis are advocated to set the role of u-VATS approach in the treatment of PE in adults and elderly patients.


Subject(s)
Empyema, Pleural , Thoracic Surgery, Video-Assisted , Activities of Daily Living , Adult , Aged , Empyema, Pleural/surgery , Humans , Length of Stay , Multicenter Studies as Topic , Retrospective Studies , Thoracic Surgery, Video-Assisted/methods
16.
Neurorehabil Neural Repair ; 36(10-11): 659-665, 2022 11.
Article in English | MEDLINE | ID: covidwho-2038589

ABSTRACT

The record-breaking pace of COVID-19 vaccine development and implementation depended heavily on collaboration among academic, government, and commercial stakeholders, especially through data-sharing and robust multicenter trials. Collaborative efforts have not been as fruitful in fields such as neurorehabilitation, where non-pharmacological interventions play a much larger role. Barriers to translating scientific advancements into clinical practice in neurorehabilitation include pervasively small study sizes, exacerbated by limited funding for non-pharmacological multicenter clinical trials; difficulty standardizing-and adequately describing-non-pharmacological interventions; and a lack of incentives for individual patient-level data-sharing. These barriers prevent reliable meta-analysis of non-pharmacological clinical studies in neurorehabilitation. This point-of-view will highlight these challenges as well as suggest practical steps that may be taken to improve the neurorehabilitation pipeline between evidence and implementation.


Subject(s)
COVID-19 , Neurological Rehabilitation , Humans , COVID-19 Vaccines , Motivation , Multicenter Studies as Topic
17.
Trials ; 23(1): 784, 2022 Sep 15.
Article in English | MEDLINE | ID: covidwho-2029733

ABSTRACT

BACKGROUND: Corticosteroids are one of the few drugs that have shown a reduction in mortality in coronavirus disease 2019 (COVID-19). In the RECOVERY trial, the use of dexamethasone reduced 28-day mortality compared to standard care in hospitalized patients with suspected or confirmed COVID-19 requiring supplemental oxygen or invasive mechanical ventilation. Evidence has shown that 30% of COVID-19 patients with mild symptoms at presentation will progress to acute respiratory distress syndrome (ARDS), particularly patients in whom laboratory inflammatory biomarkers associated with COVID-19 disease progression are detected. We postulated that dexamethasone treatment in hospitalized patients with COVID-19 pneumonia without additional oxygen requirements and at risk of progressing to severe disease might lead to a decrease in the development of ARDS and thereby reduce death. METHODS/DESIGN: This is a multicenter, randomized, controlled, parallel, open-label trial testing dexamethasone in 252 adult patients with COVID-19 pneumonia who do not require supplementary oxygen on admission but are at risk factors for the development of ARDS. Risk for the development of ARDS is defined as levels of lactate dehydrogenase > 245 U/L, C-reactive protein > 100 mg/L, and lymphocyte count of < 0.80 × 109/L. Eligible patients will be randomly assigned to receive either dexamethasone or standard of care. Patients in the dexamethasone group will receive a dose of 6 mg once daily during 7 days. The primary outcome is a composite of the development of moderate or more severe ARDS and all-cause mortality during the 30-day period following enrolment. DISCUSSION: If our hypothesis is correct, the results of this study will provide additional insights into the management and progression of this specific subpopulation of patients with COVID-19 pneumonia without additional oxygen requirements and at risk of progressing to severe disease. TRIAL REGISTRATION: ClinicalTrials.gov NCT04836780. Registered on 8 April 2021 as EARLY-DEX COVID-19.


Subject(s)
COVID-19 , Dexamethasone , Pneumonia , Adrenal Cortex Hormones/adverse effects , Adult , C-Reactive Protein , COVID-19/complications , COVID-19/drug therapy , Dexamethasone/adverse effects , Humans , Lactate Dehydrogenases , Multicenter Studies as Topic , Oxygen , Pneumonia/drug therapy , Randomized Controlled Trials as Topic , Respiratory Distress Syndrome/epidemiology , Respiratory Insufficiency/epidemiology
18.
Trials ; 23(1): 774, 2022 Sep 14.
Article in English | MEDLINE | ID: covidwho-2029729

ABSTRACT

BACKGROUND: COVID-19 pneumonia is associated with the development of acute respiratory distress syndrome (ARDS) displaying some typical histological features. These include diffuse alveolar damage with extensive pulmonary coagulation activation. This results in fibrin deposition in the microvasculature, leading to the formation of hyaline membranes in the air sacs. Well-conducted clinical trials have found that nebulised heparin limits pulmonary fibrin deposition, attenuates progression of ARDS, hastens recovery and is safe in non-COVID ARDS. Unfractionated heparin also inactivates the SARS-CoV-2 virus and prevents entry into mammalian cells. Nebulisation of heparin may therefore limit fibrin-mediated lung injury and inhibit pulmonary infection by SARS-CoV-2. Based on these findings, we designed the CHARTER-Ireland Study, a phase 1b/2a randomised controlled study of nebulised heparin in patients requiring advanced respiratory support for COVID-19 pneumonia. METHODS: This is a multi-centre, phase 1b/IIa, randomised, parallel-group, open-label study. The study will randomise 40 SARs-CoV-2-positive patients receiving advanced respiratory support in a critical care area. Randomisation will be via 1:1 allocation to usual care plus nebulised unfractionated heparin 6 hourly to day 10 while receiving advanced respiratory support or usual care only. The study aims to evaluate whether unfractionated heparin will decrease the procoagulant response associated with ARDS up to day 10. The study will also assess safety and tolerability of nebulised heparin as defined by number of severe adverse events; oxygen index and respiratory oxygenation index of intubated and unintubated, respectively; ventilatory ratio; and plasma concentration of interleukin (IL)-1ß, IL6, IL-8, IL-10 and soluble tumour necrosis factor receptor 1, C-reactive protein, procalcitonin, ferritin, fibrinogen and lactate dehydrogenase as well as the ratios of IL-1ß/IL-10 and IL-6/IL-10. These parameters will be assessed on days 1, 3, 5 and 10; time to separation from advanced respiratory support, time to discharge from the intensive care unit and number tracheostomised to day 28; and survival to days 28 and 60 and to hospital discharge, censored at day 60. Some clinical outcome data from our study will be included in the international meta-trials, CHARTER and INHALE-HEP. DISCUSSION: This trial aims to provide evidence of potential therapeutic benefit while establishing safety of nebulised heparin in the management of ARDS associated with SARs-CoV-2 infection. TRIAL REGISTRATION: ClinicalTrials.gov NCT04511923 . Registered on 13 August 2020. Protocol version 8, 22/12/2021 Protocol identifier: NUIG-2020-003 EudraCT registration number: 2020-003349-12 9 October 2020.


Subject(s)
Acute Lung Injury , COVID-19 , Respiratory Distress Syndrome , Acute Lung Injury/diagnosis , Acute Lung Injury/etiology , Animals , Fibrin , Heparin/adverse effects , Humans , Interleukin-10 , Ireland , Mammals , Multicenter Studies as Topic , Randomized Controlled Trials as Topic , Respiratory Distress Syndrome/diagnosis , Respiratory Distress Syndrome/drug therapy , SARS-CoV-2
19.
BMJ Open ; 12(9): e061172, 2022 09 14.
Article in English | MEDLINE | ID: covidwho-2029502

ABSTRACT

INTRODUCTION: The COVID-19 pandemic has been a major concern worldwide; however, easily accessible treatment options for patients with mild COVID-19 remain limited. Since the oral intake of Lactococcus lactis strain plasma (LC-Plasma) enhances both the innate and acquired immune systems through the activation of plasmacytoid dendritic cells (pDCs), we hypothesised that the oral intake of LC-Plasma could aid the relief or prevention of symptoms in patients with asymptomatic or mild COVID-19. METHODS AND ANALYSIS: This is an exploratory, multicentre, double-blinded, randomised, placebo-controlled trial. This study was initiated in December 2021 and concludes in April 2023. The planned number of enrolled subjects is 100 (50 subjects×2 groups); subject enrolment will be conducted until October 2022. Patients with asymptomatic or mild COVID-19 will be enrolled and randomly assigned in a 1:1 ratio to group A (oral intake of LC-Plasma-containing capsule, 200 mg/day, for 14 days) or group B (oral intake of placebo capsule, for 14 days). The primary endpoint is the change in subjective symptoms measured by the severity score. Secondary endpoints include SARS-CoV-2 viral loads, biomarkers for pDC activation, serum SARS-CoV-2-specific antibodies, serum cytokines, interferon and interferon-inducible antiviral effectors and the proportion of subjects with emergency room visits to medical institutions or who are hospitalised. ETHICS AND DISSEMINATION: The study protocol was approved by the Clinical Research Review Board of Nagasaki University, in accordance with the Clinical Trials Act of Japan. The study will be conducted in accordance with the Declaration of Helsinki, the Clinical Trials Act, and other current legal regulations in Japan. Written informed consent will be obtained from all the participants. The results of this study will be reported in journal publications. TRIAL REGISTRATION NUMBER: Japan Registry of Clinical Trials (registration number: jRCTs071210097).


Subject(s)
COVID-19 , Lactococcus lactis , Humans , Interferons , Lactococcus lactis/physiology , Multicenter Studies as Topic , Pandemics , Randomized Controlled Trials as Topic , SARS-CoV-2
20.
Contemp Clin Trials ; 121: 106924, 2022 Oct.
Article in English | MEDLINE | ID: covidwho-2027945

ABSTRACT

Efficiency in clinical trial recruitment and enrollment remains a major challenge in many areas of clinical medicine. In particular, despite the prevalence of heart failure with preserved ejection fraction (HFpEF), identifying patients with HFpEF for clinical trials has proven to be especially challenging. In this manuscript, we review strategies for contemporary clinical trial recruitment and present insights from the results of the DELIVER Electronic Health Record (EHR) Screening Initiative. The DELIVER trial was designed to evaluate the effects of dapagliflozin on clinical outcomes in patients with HFpEF. Within this trial, the multicenter DELIVER EHR Screening Initiative utilized EHR-based techniques in order to improve recruitment at selected sites in the United States. For this initiative, we developed and deployed a computable phenotype from the trial's eligibility criteria along with additional EHR tools at interested sites. Sites were then surveyed at the end of the program regarding lessons learned. Six sites were recruited, trained, and supported to utilize the EHR methodology and computable phenotype. Sites found the initiative to be helpful in identifying eligible patients and cited the individualized expert technical support as a critical factor in utilizing the program effectively. We found that the major challenge of implementation was the process of converting traditional inclusion/exclusion criteria into a computable phenotype within an established and ongoing trial. Other significant challenges noted by sites were the following: impact of the COVID-19 pandemic, engagement/support by local institutions, and limited availability of internal EHR experts/resources to execute programming. The study represents a proof-of-concept in the ability to utilize EHR-based tools in clinical trial recruitment for patients with HFpEF and provides important lessons for future initiatives. ClinicalTrials.gov Identifier: NCT03619213.


Subject(s)
COVID-19 , Heart Failure , Clinical Trials as Topic , Electronic Health Records , Heart Failure/diagnosis , Heart Failure/drug therapy , Humans , Multicenter Studies as Topic , Pandemics , Stroke Volume
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