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1.
Br J Gen Pract ; 2022 Mar 23.
Article in English | MEDLINE | ID: covidwho-1810376

ABSTRACT

BACKGROUND: Colchicine has been proposed as a COVID-19 treatment. AIM: To determine whether colchicine reduces time to recovery and COVID-19-related admissions to hospital and/or deaths among people in the community. DESIGN AND SETTING: Prospective, multicentre, open-label, multi-arm, randomised, controlled, adaptive platform trial (PRINCIPLE). METHOD: Adults aged ≥65 years or ≥18 years with comorbidities or shortness of breath, and unwell for ≤14 days with suspected COVID-19 in the community, were randomised to usual care, usual care plus colchicine (500 µg daily for 14 days), or usual care plus other interventions. The co-primary endpoints were time to first self-reported recovery and admission to hospital/death related to COVID-19, within 28 days, analysed using Bayesian models. RESULTS: The trial opened on 2 April 2020. Randomisation to colchicine started on 4 March 2021 and stopped on 26 May 2021 because the prespecified time to recovery futility criterion was met. The primary analysis model included 2755 participants who were SARS-CoV-2 positive, randomised to colchicine (n = 156), usual care (n = 1145), and other treatments (n = 1454). Time to first self-reported recovery was similar in the colchicine group compared with usual care with an estimated hazard ratio of 0.92 (95% credible interval (CrI) = 0.72 to 1.16) and an estimated increase of 1.4 days in median time to self-reported recovery for colchicine versus usual care. The probability of meaningful benefit in time to recovery was very low at 1.8%. COVID-19-related admissions to hospital/deaths were similar in the colchicine group versus usual care, with an estimated odds ratio of 0.76 (95% CrI = 0.28 to 1.89) and an estimated difference of -0.4% (95% CrI = -2.7 to 2.4). CONCLUSION: Colchicine did not improve time to recovery in people at higher risk of complications with COVID-19 in the community.

2.
Sex Reprod Healthc ; 32: 100731, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1805199

ABSTRACT

OBJECTIVE: To evaluate if a birthing room designed with person-centred considerations improves labour and birth outcomes for nulliparous women when compared to regular birthing rooms. METHODS: A randomised controlled trial was conducted at a Swedish labour ward between January 2019 and October 2020. Nulliparous women in spontaneous labour were randomised either to a birthing room designed with person-centred considerations (New room) or a Regular room. The primary outcome was a composite of four variables: vaginal non-instrumental birth; no oxytocin augmentation; postpartum blood loss < 1000 ml; and a positive childbirth experience. To detect a difference of 8% between the groups, 1274 study participants were needed, but the trial was terminated early due to consequences of the Covid-19 pandemic. RESULTS: A total of 406 women were randomised; 204 to the New room and 202 to the Regular room. There was no significant difference in the primary outcome between the groups (42.2% versus 35.1%; odds ratio: 1.35, 95% Confidence Interval 0.90-2.01; p = 0.18). Participants in the New room used epidural analgesia to a lower extent (54.4% versus 65.3%, relative risk: 0.83, 95% Confidence Interval 0.71-0.98; p = 0.03) and reported to a higher degree that the room contributed to a sense of safety, control, and integrity (p=<0.001). CONCLUSIONS: The hypothesis that the New room would improve the primary outcome could not be verified. Considering the early discontinuation of the study, results should be interpreted with caution. Nevertheless, analyses of our secondary outcomes emphasise the experiential value of the built birth environment in improving care for labouring women.


Subject(s)
COVID-19 , Pandemics , Female , Hospitals , Humans , Parturition , Pregnancy , Sweden
3.
EClinicalMedicine ; 47: 101409, 2022 May.
Article in English | MEDLINE | ID: covidwho-1800090

ABSTRACT

Background: In COVACTA, a randomised, placebo-controlled trial in patients hospitalised with coronavirus disease-19 (COVID-19), tocilizumab did not improve 28-day mortality, but shortened hospital and intensive care unit stay. Longer-term effects of tocilizumab in patients with COVID-19 are unknown. Therefore, the efficacy and safety of tocilizumab in COVID-19 beyond day 28 and its impact on Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) clearance and antibody response in COVACTA were investigated. Methods: Adults in Europe and North America hospitalised with COVID-19 (N = 452) between April 3, 2020 and May 28, 2020 were randomly assigned (2:1) to double-blind intravenous tocilizumab or placebo and assessed for efficacy and safety through day 60. Assessments included mortality, time to hospital discharge, SARS-CoV-2 viral load in nasopharyngeal swab and serum samples, and neutralising anti-SARS-CoV-2 antibodies in serum. ClinicalTrials.gov registration: NCT04320615. Findings: By day 60, 24·5% (72/294) of patients in the tocilizumab arm and 25·0% (36/144) in the placebo arm died (weighted difference -0·5% [95% CI -9·1 to 8·0]), and 67·0% (197/294) in the tocilizumab arm and 63·9% (92/144) in the placebo arm were discharged from the hospital. Serious infections occurred in 24·1% (71/295) of patients in the tocilizumab arm and 29·4% (42/143) in the placebo arm. Median time to negative reverse transcriptase-quantitative polymerase chain reaction result in nasopharyngeal/oropharyngeal samples was 15·0 days (95% CI 14·0 to 21·0) in the tocilizumab arm and 21·0 days (95% CI 14·0 to 28·0) in the placebo arm. All tested patients had positive test results for neutralising anti-SARS-CoV-2 antibodies at day 60. Interpretation: There was no mortality benefit with tocilizumab through day 60. Tocilizumab did not impair viral clearance or host immune response, and no new safety signals were observed. Future investigations may explore potential biomarkers to optimize patient selection for tocilizumab treatment and combination therapy with other treatments. Funding: F. Hoffmann-La Roche Ltd and the US Department of Health and Human Services, Office of the Assistant Secretary for Preparedness and Response, Biomedical Advanced Research and Development Authority, under OT number HHSO100201800036C.

4.
Front Neurol ; 13: 861214, 2022.
Article in English | MEDLINE | ID: covidwho-1785382

ABSTRACT

Background: Since the emergence of the COVID-19 pandemic, there have been lots of published work examining the association between COVID-19 and mental health, particularly, anxiety and depression in the general populations and disease subpopulations globally. Depression is a debilitating disorder affecting individuals' level of bio-psychological-social functioning across different age groups. Since almost all studies were cross-sectional studies, there seems to be a lack of robust, large-scale, and technological-based interventional studies to restore the general public's optimal psychosocial wellbeing amidst the COVID-19 pandemic. Transcranial pulse stimulation (TPS) is a relatively new non-intrusive brain stimulation (NIBS) technology, and only a paucity of studies was conducted related to the TPS treatment on older adults with mild neurocognitive disorders. However, there is by far no study conducted on young adults with major depressive disorder nationwide. This gives us the impetus to execute the first nationwide study evaluating the efficacy of TPS on the treatment of depression among young adults in Hong Kong. Methods: This study proposes a two-armed single-blinded randomised controlled trial including TPS as an intervention group and a waitlist control group. Both groups will be measured at baseline (T1), immediately after the intervention (T2), and at the 3- month follow-up (T3). Recruitment: A total of 30 community-dwelling subjects who are aged 18 and above and diagnosed with major depressive disorder (MDD) will be recruited in this study. All subjects will be computer randomised into either the intervention group or the waitlist control group, balanced by gender and age on a 1:1 ratio. Intervention: All subjects in each group will have to undertake functional MRI (fMRI) before and after six 30-min TPS sessions, which will be completed in 2 weeks' time. Outcomes: Baseline measurements and post-TPS evaluation of the psychological outcomes (i.e., depression, cognition, anhedonia, and instrumental activities of daily living) will also be conducted on all participants. A 3-month follow-up period will be usedto assess the long-term sustainability of the TPS intervention. For statistical analysis, ANOVA with repeated measures will be used to analyse data. Missing data were managed by multiple mutations. The level of significance will be set to p < 0.05. Significance of the Study: Results of this study will be used to inform health policy to determine whether TPS could be considered as a top treatment option for MDD. Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT05006365.

5.
BMC Pregnancy Childbirth ; 22(1): 309, 2022 Apr 11.
Article in English | MEDLINE | ID: covidwho-1785146

ABSTRACT

BACKGROUND: There are major shortfalls in the midwifery workforce which has been exacerbated by the COVID 19 pandemic. Midwives have high levels of burnout and many, often early career midwives, are planning to leave the profession. There are reports of a poor workplace culture in maternity units, including bullying. Support is essential for the welfare of the workforce to be able to cope with the demands of their jobs. Supportive strategies, such as Clinical Supervision, a recognised approach in healthcare, enable reflection in a facilitated, structured way, and can enhance professional standards. The purpose of this research is to study burnout levels in midwives, those exiting their workplace and perceptions of workplace culture in relation to access to, and attendance of, monthly Clinical Supervision. METHODS: This study will be a cluster randomised controlled trial of maternity sites within Sydney and the surrounding districts. Twelve sites will be recruited and half will receive monthly Clinical Supervision for up to two years. Midwives from all sites will be requested to complete 6-monthly surveys comprising validated measurement tools: the Copenhagen Burnout Inventory (CBI), the Australian Midwifery Workplace Culture (AMWoC) tool and the Clinical Supervision Evaluation Questionnaire (CSEQ) (the latter for intervention sites only). Primary outcomes are the levels of burnout in midwives (using the CBI). Secondary outcomes will be the quality of the intervention (using the CSEQ), perceptions of workplace culture (using the AMWoC tool) and midwives' intention to stay in their role/profession, as well as sick leave rates and numbers of exiting staff. We will also determine the dose effect - ie the impact in relation to how many Clinical Supervision sessions the midwives have attended, as well as other supportive workplace strategies such as mentoring/coaching on outcomes. DISCUSSION: Through attending monthly Clinical Supervision we hypothesise that midwives will report less burnout and more positive perceptions of workplace culture than those in the control sites. The potential implications of which are a productive workforce giving high quality care with the flow-on effect of having physically and psychologically well women and their babies. TRIAL REGISTRATION: The ACTRN Registration number is ACTRN12621000545864p , dated 10/05/2021,.


Subject(s)
Burnout, Professional , COVID-19 , Midwifery , Nurse Midwives , Australia , Burnout, Professional/prevention & control , Female , Humans , Preceptorship , Pregnancy
6.
BMJ Open ; 12(4): e058150, 2022 04 11.
Article in English | MEDLINE | ID: covidwho-1784834

ABSTRACT

INTRODUCTION: General practitioners (GP) report increasing difficulties in referring patients with somatic symptom disorder (SSD) in specialised psychosocial care. Barriers are structural conditions of the respective healthcare system and patients' reservations against receiving specialised psychosocial care. As patients with SSD often predominantly assume somatic influencing factors for the development and maintenance of their somatic complaints, close collaboration between the GP and mental health specialist (MHS) seems particularly important. Integrating internet-based video consultations by remotely located MHS and primary care can improve effective treatment of patients with SSD by overcoming structural barriers and provide low-threshold and timely care. The aim of this randomised controlled feasibility trial is to investigate the feasibility of implementing MHS video consultations in primary care practices. METHODS AND ANALYSIS: Fifty primary care patients with SSD will be individually randomised in two groups receiving either enhanced treatment as usual as provided by their GP (control group) or two versus five video consultations conducted by an MHS additionally to enhanced treatment as usual. The video consultations focus on (a) diagnostic clarification, (b) the development of a biopsychosocial disorder model, and (c) development of a treatment plan against the background of a stepped-care algorithm based on clinical outcomes. We will investigate the following outcomes: effectiveness of the recruitment strategies, patient acceptance of randomisation, practicability of the technical and logistical processes related to implementing video consultations in the practices' workflows, feasibility of the data collection and clinical parameters. ETHICS AND DISSEMINATION: This trial has undergone ethical scrutiny and has been approved by the Medical Faculty of the University of Heidelberg Ethics Committee (S-620/2021). The findings will be disseminated to the research community through presentations at conferences and publications in scientific journals. This feasibility trial will prepare the ground for a large-scale, fully powered randomised controlled trial. TRIAL REGISTRATION NUMBER: DRKS00026075.


Subject(s)
Medically Unexplained Symptoms , Telemedicine , Feasibility Studies , Humans , Mental Health , Primary Health Care , Randomized Controlled Trials as Topic , Telemedicine/methods
7.
Trials ; 23(1): 250, 2022 Apr 04.
Article in English | MEDLINE | ID: covidwho-1775330

ABSTRACT

BACKGROUND: Major depression is the second leading cause of years lost to disability worldwide and is a leading contributor to suicide. However, first-line antidepressants are only fully effective for 33%, and only 40% of those offered psychological treatment attend for two sessions or more. Views gained from patients and primary care professionals are that greater treatment uptake might be achieved if people with depression could be offered alternative and more accessible treatment options. Although there is evidence that the Alpha-Stim Anxiety Insomnia and Depression (AID) device is safe and effective for anxiety and depression symptoms in people with anxiety disorders, there is much less evidence of efficacy in major depression without anxiety. This study investigates the effectiveness of the Alpha-Stim AID device, a cranial electrotherapy stimulation (CES) treatment that people can safely use independently at home. The device provides CES which has been shown to increase alpha oscillatory brain activity, associated with relaxation. METHODS: The aim of this study is to investigate the clinical and cost-effectiveness of Alpha-Stim AID in treatment-seeking patients (aged 16 years upwards) with moderate to moderately severe depressive symptoms in primary care. The study is a multi-centre parallel-group, double-blind, non-commercial, randomised controlled superiority trial. The primary objective of the study is to examine the clinical efficacy of active daily use of 8 weeks of Alpha-Stim AID versus sham Alpha-Stim AID on depression symptoms at 16 weeks (8 weeks after the end of treatment) in people with moderate severity depression. The primary outcome is the 17-item Hamilton Depression Rating Scale at 16 weeks. All trial and treatment procedures are carried out remotely using videoconferencing, telephone and postal delivery considering the COVID-19 pandemic restrictions. DISCUSSION: This study is investigating whether participants using the Alpha-Stim AID device display a reduction in depressive symptoms that can be maintained over 8 weeks post-treatment. The findings will help to determine whether Alpha-Stim AID should be recommended, including being made available in the NHS for patients with depressive symptoms. TRIAL REGISTRATION: ISRTCN ISRCTN11853110 . Registered on 14 August 2020.


Subject(s)
COVID-19 , Depressive Disorder, Major , Electric Stimulation Therapy , Adolescent , COVID-19/therapy , Cost-Benefit Analysis , Depression/drug therapy , Depression/therapy , Depressive Disorder, Major/therapy , Humans , Pandemics , Primary Health Care
8.
Int J Environ Res Public Health ; 19(6)2022 03 16.
Article in English | MEDLINE | ID: covidwho-1742476

ABSTRACT

Dietary quality and sustainability are central matters to the international community, emphasised by the burden of the COVID-19 pandemic. To promote healthier and more sustainable food-related practices, the protocol of a web-based intervention to enhance adults' food literacy is presented. The FOODLIT-Trial is a two-arm, parallel, experimental, and single-blinded randomised controlled trial delivered over 11 weeks. Based on the Food Literacy Wheel framework and supported by the Health Action Process Approach (HAPA) and the Behaviour Change Techniques Taxonomy, weekly content with customised behaviour change techniques (experimental group) is hypothesised to be more effective to promote food behaviour change when compared to a single-time and non-customised delivery of food-related international guidelines, with no theoretically informed approaches (comparison group). Primary outcome is food literacy, including food-related knowledge, skills, and behaviours, assessed with the FOODLIT-Tool; a secondary outcome includes psychological mechanisms that efficaciously predict change in participants' food literacy, measured with HAPA-driven items. Enlisted through online sources, participants will be assessed across five time points (baseline, post-intervention, and 3-, 6-, and 9-month follow-ups, i.e., T0-T4). A randomisation check will be conducted, analyses will follow an intention-to-treat approach, and linear two-level models within- (T0-T4) and between-level (nested in participants) will be computed, together with a longitudinal mediation analysis. If effective, the FOODLIT-Trial will provide for a multidimensional and cost-effective intervention to enable healthier and more sustainable food practices over the long term.


Subject(s)
COVID-19 , Health Literacy , Adult , Behavior Therapy , COVID-19/epidemiology , COVID-19/prevention & control , Food , Health Literacy/methods , Humans , Pandemics/prevention & control , Randomized Controlled Trials as Topic
9.
Pilot Feasibility Stud ; 8(1): 23, 2022 Feb 01.
Article in English | MEDLINE | ID: covidwho-1736441

ABSTRACT

BACKGROUND: It is estimated that around 160,000 households in Britain experience homelessness each year, although no definitive statistics exist. Between March and September 2020, as part of the initial 'Everyone In' government response to COVID-19 in England, 10,566 people were living in emergency accommodation and nearly 18,911 people had been moved into settled accommodation. However, some forms of temporary accommodation may not be suitable as shared facilities make it impossible for people to adhere to government guidelines to reduce the spread of COVID-19. METHODS: This is parallel group, pilot randomised controlled trial. The target is to recruit three local authorities, each of which will recruit 50 participants (thus a total of approximately 150 participants). Individuals are eligible if they are aged 18 and over, in a single-person homeless household, temporarily accommodated by the LA with recourse to public funds. Participants will be randomised to receive settled accommodation (intervention group) or temporary accommodation (control group). The intervention group includes settled housing such as Private Rented Sector (low and medium support), Social Housing (low and medium support), and Housing First (High support). The control group will maintain treatment as usual. The follow-up period will last 6 months. The primary outcome is to assess the feasibility of recruitment, retention, and acceptability of trial processes against progression criteria laid out in a traffic light system (green: all criteria are met, the trial should progress as designed in this pilot; amber: the majority of criteria are met and with adaptations to methods all criteria could be met; red: the minority of criteria are met and the pilot RCT should not proceed). Secondary outcomes include assessment of completeness of data collection at 3 and 6 months and percentage of participants consenting to data linkage, as well as a process evaluation and economic evaluation. DISCUSSION: This trial will address feasibility questions associated with progression to a fully powered effectiveness trial of models of housing to reduce risk of COVID-19 infection and homelessness. TRIAL REGISTRATION: ISRCTN69564614 . Registered on December 16, 2020.

10.
Clin Infect Dis ; 2022 Mar 02.
Article in English | MEDLINE | ID: covidwho-1722275

ABSTRACT

BACKGROUND: BNT162b2 by Pfizer-BioNTech and mRNA-1273 by Moderna are the most commonly used vaccines to prevent SARS-CoV-2 infections. Head-to-head comparison of the efficacy of these vaccines in immunocompromised patients is lacking. METHODS: Parallel, two-arm (allocation 1:1), open-label, non-inferiority randomised clinical trial nested into the Swiss HIV Cohort Study and the Swiss Transplant Cohort Study. Patients living with HIV (PLWH) or solid organ transplant recipients (SOTR; i.e. lung and kidney) from these cohorts were randomised to mRNA-1273 or BNT162b2. The primary endpoint was antibody response to SARS-CoV-2 spike (S1) protein receptor binding domain (Elecsys Anti-SARS-CoV-2 immunoassay, Roche; cut-off ≥0.8 units/ml) 8 weeks after second vaccination. In addition, antibody response was measured with the Antibody CORonavirus Assay 2 (ABCORA 2). RESULTS: 430 patients were randomised and 412 were included in the intention-to-treat analysis (341 PLWH and 71 SOTR). The percentage of patients showing an immune response was 92.1% (95% confidence interval [CI] 88.4-95.8%; 186/202) for mRNA-1273 and 94.3% (95% CI 91.2-97.4; 198/210) for BNT162b2 (difference: 2.2%; 95% CI -7.1 to 2.7), fulfilling non-inferiority of mRNA-1273. With the ABCORA 2 test 89.1% had an immune response to mRNA-1273 (95% CI 84.8-93.4%; 180/202) and 89.5% to BNT162b2 (95% CI 85.4-93.7%; 188/210). Based on the Elecsys test, all PLWH had an antibody response (100.0%; 341/341), while for SOTR only 60.6% (95% CI 49.2-71.9%; 43/71) had titres above the cut-off. CONCLUSIONS: In immunocompromised patients the antibody response of mRNA-1273 was non-inferior to BNT162b2. PLWH had in general an antibody response, while a high proportion of SOTR had no antibody response.

11.
Br J Sports Med ; 56(12): 667-675, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1691362

ABSTRACT

OBJECTIVE: Public life restrictions associated with the COVID-19 pandemic caused reductions in physical activity (PA) and decreases in mental and somatic health. Considering the interplay between these factors, we investigated the effects of digital home exercise (DHE) during government-enforced lockdowns. METHODS: A multicentre randomised controlled trial was performed allocating healthy individuals from nine countries (N=763; 523 female) to a DHE or an inactive control group. During the 4-week main intervention, DHE members engaged in live-streamed multicomponent home exercise. Subsequently, both groups had access to prerecorded workouts for an additional 4 weeks. Outcomes, assessed weekly, included PA level (Nordic Physical Activity Questionnaire-Short), anxiety (Generalized Anxiety Disorder Scale-7), mental well-being (WHO-5 Questionnaire), sleep quality (Medical Outcome Study Sleep Scale), pain/disability (Chronic Pain Grade Scale) and exercise motivation (Self-Concordance Scale). Mixed models were used for analysis. RESULTS: Live-streamed DHE consistently increased moderate PA (eg, week 1: 1.65 times more minutes per week, 95% CI 1.40 to 1.94) and vigorous PA (eg, week 1: 1.31 times more minutes per week, 95% CI 1.08 to 1.61), although the effects decreased over time. In addition, exercise motivation, sleep quality and anxiety were slightly improved for DHE in the 4-week live streaming period. The same applied to mental well-being (mean difference at week 4: +0.99, 95% CI 0.13 to 1.86), but an inverted trend was observed after live streaming was substituted by prerecorded exercise. CONCLUSIONS: Live-streamed DHE represents an efficacious method to enhance PA and selected markers of health during pandemic-related public life restrictions. However, research on implementation is warranted to reduce dropout rates. TRIAL REGISTRATION NUMBER: DRKS00021273.


Subject(s)
COVID-19 , COVID-19/epidemiology , COVID-19/prevention & control , Communicable Disease Control , Exercise , Female , Humans , Pandemics/prevention & control , Sedentary Behavior
12.
Trials ; 23(1): 95, 2022 Jan 31.
Article in English | MEDLINE | ID: covidwho-1662421

ABSTRACT

BACKGROUND: Child mortality remains unacceptably high, with Northern Nigeria reporting some of the highest rates globally (e.g. 192/1000 live births in Jigawa State). Coverage of key protect and prevent interventions, such as vaccination and clean cooking fuel use, is low. Additionally, knowledge, care-seeking and health system factors are poor. Therefore, a whole systems approach is needed for sustainable reductions in child mortality. METHODS: This is a cluster randomised controlled trial, with integrated process and economic evaluations, conducted from January 2021 to September 2022. The trial will be conducted in Kiyawa Local Government Area, Jigawa State, Nigeria, with an estimated population of 230,000. Clusters are defined as primary government health facility catchment areas (n = 33). The 33 clusters will be randomly allocated (1:1) in a public ceremony, and 32 clusters included in the impact evaluation. The trial will evaluate a locally adapted 'whole systems strengthening' package of three evidence-based methods: community men's and women's groups, Partnership Defined Quality Scorecard and healthcare worker training, mentorship and provision of basic essential equipment and commodities. The primary outcome is mortality of children aged 7 days to 59 months. Mortality will be recorded prospectively using a cohort design, and secondary outcomes measured through baseline and endline cross-sectional surveys. Assuming the following, we will have a minimum detectable effect size of 30%: (a) baseline mortality of 100 per 1000 livebirths, (b) 4480 compounds with 3 eligible children per compound, (c) 80% power, (d) 5% significance, (e) intra-cluster correlation of 0.007 and (f) coefficient of variance of cluster size of 0.74. Analysis will be by intention-to-treat, comparing intervention and control clusters, adjusting for compound and trial clustering. DISCUSSION: This study will provide robust evidence of the effectiveness and cost-effectiveness of community-based participatory learning and action, with integrated health system strengthening and accountability mechanisms, to reduce child mortality. The ethnographic process evaluation will allow for a rich understanding of how the intervention works in this context. However, we encountered a key challenge in calculating the sample size, given the lack of timely and reliable mortality data and the uncertain impacts of the COVID-19 pandemic. TRIAL REGISTRATION: ISRCTN 39213655 . Registered on 11 December 2019.


Subject(s)
COVID-19 , Communicable Diseases , Child , Cross-Sectional Studies , Female , Humans , Infant Mortality , Male , Maternal Mortality , Nigeria , Pandemics , Randomized Controlled Trials as Topic , SARS-CoV-2
13.
Trials ; 22(1): 127, 2021 Feb 10.
Article in English | MEDLINE | ID: covidwho-1629960

ABSTRACT

OBJECTIVES: The objective of the study is to measure the efficacy of ionic-iodine polymer complex [1] for clinical and radiological improvement in coronavirus disease 2019 (COVID-19) patients. TRIAL DESIGN: The trial will be closed label, randomized and placebo-controlled with a 1:1:1:1 allocation ratio and superiority framework. PARTICIPANTS: All PCR confirmed COVID-19 adult patients including non-pregnant females, with mild to moderate disease, will be enrolled from Shaikh Zayed Post-Graduate Medical Complex, Ali Clinic and Doctors Lounge in Lahore (Pakistan). Patients with any pre-existing chronic illness will be excluded from the study. INTERVENTION AND COMPARATOR: In this multi-armed study ionic-iodine polymer complex with 200 mg of elemental iodine will be given using three formulations to evaluate efficacy. Patients will be receiving either encapsulated iodine complex of 200 mg (arm A), iodine complex syrup form 40 ml (arm B), iodine complex throat spray of 2 puffs (arm C) or empty capsule (arm D) as placebo; all three times a day. All the 4 arms will be receiving standard care as per version 3.0 of the clinical management guidelines for COVID-19 established by the Ministry of National Health Services of Pakistan. MAIN OUTCOMES: Primary outcomes will be viral clearance with radiological and clinical improvement. SARS-CoV-2 RT-PCR and HRCT chest scans will be done on the admission day and then after every fourth day for 12 days or till the symptoms are resolved. RT-PCR will only be shown as positive or negative while HRCT chest scoring will be done depending on the area and severity of lung involvement [2]. Time taken for the alleviation of symptoms will be calculated by the number of days the patient remained symptomatic. 30-day mortality will be considered as a secondary outcome. RANDOMISATION: Stratification for initial COVID-19 status (or days from initial symptoms as a proxy), age groups, gender, baseline severity of symptoms and co-morbidities will be used to ensure that the study arms remain balanced in size for the 1:1:1:1 allocation ratio. Randomization will be done using the lottery method. As patients are being admitted at different times, they will be recruited after obtaining their voluntary written informed consent following all standard protocols of the infection, control and disinfection. BLINDING (MASKING): This is a quadruple (participants, care providers, investigators and outcomes assessors) blinded study where only the study's Primary Investigator will have information about the arms and their interventions. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): 200 patients will be randomized into four groups with three experimental and one placebo arm. TRIAL STATUS: Protocol Version Number is 2.3 and it is approved from IRB Shaikh Zayed Hospital with ID SZMC/IRB/Internal0056/2020 on July 14th, 2020. The recruitment is in progress. It was started on July 30, 2020, and the estimated end date for the trial is August 15, 2021. TRIAL REGISTRATION: Clinical Trial has been retrospectively registered on www.clinicaltrials.gov with registration ID NCT04473261 dated July 16, 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). With the intention of expediting dissemination of this trial, the conventional formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines.


Subject(s)
COVID-19/drug therapy , Iodine Compounds/administration & dosage , Polymers/administration & dosage , SARS-CoV-2/genetics , Severity of Illness Index , Adult , COVID-19/epidemiology , COVID-19/mortality , Capsules , Female , Humans , Male , Oral Sprays , Pakistan/epidemiology , Patient Admission , Randomized Controlled Trials as Topic , Reverse Transcriptase Polymerase Chain Reaction , Treatment Outcome
14.
Trials ; 23(1): 35, 2022 Jan 15.
Article in English | MEDLINE | ID: covidwho-1635071

ABSTRACT

BACKGROUND: Since December 2019, SARS-CoV-2 virus has infected millions of people worldwide. In patients with COVID-19 pneumonia in need of oxygen therapy or mechanical ventilation, dexamethasone 6 mg per day is currently recommended. However, the dose of 6 mg of dexamethasone is currently being reappraised and may miss important therapeutic potential or may prevent potential deleterious effects of higher doses of corticosteroids. METHODS: REMED is a prospective, open-label, randomised controlled trial testing the superiority of dexamethasone 20 mg (dexamethasone 20 mg on days 1-5, followed by dexamethasone 10 mg on days 6-10) vs 6 mg administered once daily intravenously for 10 days in adult patients with moderate or severe ARDS due to confirmed COVID-19. Three hundred participants will be enrolled and followed up for 360 days after randomization. Patients will be randomised in a 1:1 ratio into one of the two treatment arms. The following stratification factors will be applied: age, Charlson Comorbidity Index, CRP levels and trial centre. The primary endpoint is the number of ventilator-free days (VFDs) at 28 days after randomisation. The secondary endpoints are mortality from any cause at 60 days after randomisation; dynamics of the inflammatory marker, change in WHO Clinical Progression Scale at day 14; and adverse events related to corticosteroids and independence at 90 days after randomisation assessed by the Barthel Index. The long-term outcomes of this study are to assess long-term consequences on mortality and quality of life at 180 and 360 days. The study will be conducted in the intensive care units (ICUs) of ten university hospitals in the Czech Republic. DISCUSSION: We aim to compare two different doses of dexamethasone in patients with moderate to severe ARDS undergoing mechanical ventilation regarding efficacy and safety. TRIAL REGISTRATION: EudraCT No. 2020-005887-70. ClinicalTrials.gov NCT04663555. Registered on December 11, 2020.


Subject(s)
COVID-19 , Respiratory Distress Syndrome , Adult , COVID-19/drug therapy , Dexamethasone/adverse effects , Humans , Multicenter Studies as Topic , Prospective Studies , Quality of Life , Randomized Controlled Trials as Topic , Respiratory Distress Syndrome/diagnosis , Respiratory Distress Syndrome/drug therapy , SARS-CoV-2 , Treatment Outcome
15.
Trials ; 22(1): 172, 2021 Mar 01.
Article in English | MEDLINE | ID: covidwho-1622253

ABSTRACT

OBJECTIVES: The primary objective of this study is to test the hypothesis that administration of dexamethasone 20 mg is superior to a 6 mg dose in adult patients with moderate or severe ARDS due to confirmed COVID-19. The secondary objective is to investigate the efficacy and safety of dexamethasone 20 mg versus dexamethasone 6 mg. The exploratory objective of this study is to assess long-term consequences on mortality and quality of life at 180 and 360 days. TRIAL DESIGN: REMED is a prospective, phase II, open-label, randomised controlled trial testing superiority of dexamethasone 20 mg vs 6 mg. The trial aims to be pragmatic, i.e. designed to evaluate the effectiveness of the intervention in conditions that are close to real-life routine clinical practice. PARTICIPANTS: The study is multi-centre and will be conducted in the intensive care units (ICUs) of ten university hospitals in the Czech Republic. INCLUSION CRITERIA: Subjects will be eligible for the trial if they meet all of the following criteria: 1. Adult (≥18 years of age) at time of enrolment; 2. Present COVID-19 (infection confirmed by RT-PCR or antigen testing); 3. Intubation/mechanical ventilation or ongoing high-flow nasal cannula (HFNC) oxygen therapy; 4. Moderate or severe ARDS according to Berlin criteria: • Moderate - PaO2/FiO2 100-200 mmHg; • Severe - PaO2/FiO2 < 100 mmHg; 5. Admission to ICU in the last 24 hours. EXCLUSION CRITERIA: Subjects will not be eligible for the trial if they meet any of the following criteria: 1. Known allergy/hypersensitivity to dexamethasone or excipients of the investigational medicinal product (e.g. parabens, benzyl alcohol); 2. Fulfilled criteria for ARDS for ≥14 days at enrolment; 3. Pregnancy or breastfeeding; 4. Unwillingness to comply with contraception measurements from enrolment until at least 1 week after the last dose of dexamethasone (sexual abstinence is considered an adequate contraception method); 5. End-of-life decision or patient is expected to die within next 24 hours; 6. Decision not to intubate or ceilings of care in place; 7. Immunosuppression and/or immunosuppressive drugs in medical history: a) Systemic immunosuppressive drugs or chemotherapy in the past 30 days; b) Systemic corticosteroid use before hospitalization; c) Any dose of dexamethasone during the present hospital stay for COVID-19 for ≥5 days before enrolment; d) Systemic corticosteroids during present hospital stay for conditions other than COVID-19 (e.g. septic shock); 8. Current haematological or generalized solid malignancy; 9. Any contraindication for corticosteroid administration, e.g. • intractable hyperglycaemia; • active gastrointestinal bleeding; • adrenal gland disorders; • presence of superinfection diagnosed with locally established clinical and laboratory criteria without adequate antimicrobial treatment; 10. Cardiac arrest before ICU admission; 11. Participation in another interventional trial in the last 30 days. INTERVENTION AND COMPARATOR: Dexamethasone solution for injection/infusion is the investigational medicinal product as well as the comparator. The trial will assess two doses, 20 mg (investigational) vs 6 mg (comparator). Patients in the intervention group will receive dexamethasone 20 mg intravenously once daily on day 1-5, followed by dexamethasone 10 mg intravenously once daily on day 6-10. Patients in the control group will receive dexamethasone 6 mg day 1-10. All authorized medicinal products containing dexamethasone in the form of solution for i.v. injection/infusion can be used. MAIN OUTCOMES: Primary endpoint: Number of ventilator-free days (VFDs) at 28 days after randomisation, defined as being alive and free from mechanical ventilation. SECONDARY ENDPOINTS: a) Mortality from any cause at 60 days after randomisation; b) Dynamics of inflammatory marker (C-Reactive Protein, CRP) change from Day 1 to Day 14; c) WHO Clinical Progression Scale at Day 14; d) Adverse events related to corticosteroids (new infections, new thrombotic complications) until Day 28 or hospital discharge; e) Independence at 90 days after randomisation assessed by Barthel Index. The long-term outcomes of this study are to assess long-term consequences on mortality and quality of life at 180 and 360 days through telephone structured interviews using the Barthel Index. RANDOMISATION: Randomisation will be carried out within the electronic case report form (eCRF) by the stratified permuted block randomisation method. Allocation sequences will be prepared by a statistician independent of the study team. Allocation to the treatment arm of an individual patient will not be available to the investigators before completion of the whole randomisation process. The following stratification factors will be applied: • Age <65 and ≥ 65; • Charlson Comorbidity index (CCI) <3 and ≥3; • CRP <150 mg/L and ≥150 mg/L • Trial centre. Patients will be randomised in a 1 : 1 ratio into one of the two treatment arms. Randomisation through the eCRF will be available 24 hours every day. BLINDING (MASKING): This is an open-label trial in which the participants and the study staff will be aware of the allocated intervention. Blinded pre-planned statistical analysis will be performed. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The sample size is calculated to detect the difference of 3 VFDs at 28 days (primary efficacy endpoint) between the two treatment arms with a two-sided type I error of 0.05 and power of 80%. Based on data from a multi-centre randomised controlled trial in COVID-19 ARDS patients in Brazil and a multi-centre observational study from French and Belgian ICUs regarding moderate to severe ARDS related to COVID-19, investigators assumed a standard deviation of VFD at 28 days as 9. Using these assumptions, a total of 142 patients per treatment arm would be needed. After adjustment for a drop-out rate, 150 per treatment arm (300 patients per study) will be enrolled. TRIAL STATUS: This is protocol version 1.1, 15.01.2021. The trial is due to start on 2 February 2021 and recruitment is expected to be completed by December 2021. TRIAL REGISTRATION: The study protocol was registered on EudraCT No.:2020-005887-70, and on December 11, 2020 on ClinicalTrials.gov (Title: Effect of Two Different Doses of Dexamethasone in Patients With ARDS and COVID-19 (REMED)) Identifier: NCT04663555 with a last update posted on February 1, 2021. FULL PROTOCOL: The full protocol (version 1.1) is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting dissemination of this material, the standard formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


Subject(s)
COVID-19/therapy , Dexamethasone/administration & dosage , Glucocorticoids/administration & dosage , Respiration, Artificial , Respiratory Distress Syndrome/therapy , COVID-19/complications , Clinical Trials, Phase II as Topic , Disease Progression , Dose-Response Relationship, Drug , Equivalence Trials as Topic , Humans , Length of Stay , Multicenter Studies as Topic , Randomized Controlled Trials as Topic , Respiratory Distress Syndrome/etiology , SARS-CoV-2
16.
Contemp Clin Trials Commun ; 26: 100884, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1616437

ABSTRACT

Addressing the mental health needs of healthcare staff exposed to psychologically traumatic events at work during the COVID-19 pandemic is a pressing global priority. We need to swiftly develop interventions to target the psychological consequences (e.g., persistent intrusive memories of trauma). Interventions for healthcare staff must be brief, flexible, fitted around the reality and demands of working life under the pandemic, and repeatable during ongoing/further trauma exposure. Intervention delivery during the pandemic should be remote to mitigate risk of infection; e.g., here using a blend of digitalized self-administered materials (e.g., video instructions) and guided (remote) support from a researcher. This parallel groups, two-arm, randomised controlled trial (RCT) with healthcare staff working during the COVID-19 pandemic is the first evaluation of whether a digitalized form of a brief cognitive task intervention, which is remotely-delivered (guided), reduces intrusive memories. Healthcare staff who experience intrusive memories of work-related traumatic event(s) during the COVID-19 pandemic (≥2 in the week before inclusion) will be randomly allocated (1:1) to receive either the cognitive task intervention or an active (attention placebo) control, and followed up at 1-week, 1-month, 3-months, and 6-months post-intervention. The primary outcome will be the number of intrusive memories reported during Week 5; secondary and other outcomes include the number of intrusive memories reported during Week 1, and other intrusive symptoms. Findings will inform further development and dissemination of a brief cognitive task intervention to target intrusive memories.

17.
Int J Antimicrob Agents ; 59(2): 106516, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1611755

ABSTRACT

High concentrations of ivermectin demonstrated antiviral activity against SARS-CoV-2 in vitro. The aim of this study was to assess the safety and efficacy of high-dose ivermectin in reducing viral load in individuals with early SARS-CoV-2 infection. This was a randomised, double-blind, multicentre, phase II, dose-finding, proof-of-concept clinical trial. Participants were adults recently diagnosed with asymptomatic/oligosymptomatic SARS-CoV-2 infection. Exclusion criteria were: pregnant or lactating women; CNS disease; dialysis; severe medical condition with prognosis <6 months; warfarin treatment; and antiviral/chloroquine phosphate/hydroxychloroquine treatment. Participants were assigned (ratio 1:1:1) according to a randomised permuted block procedure to one of the following arms: placebo (arm A); single-dose ivermectin 600 µg/kg plus placebo for 5 days (arm B); and single-dose ivermectin 1200 µg/kg for 5 days (arm C). Primary outcomes were serious adverse drug reactions (SADRs) and change in viral load at Day 7. From 31 July 2020 to 26 May 2021, 32 participants were randomised to arm A, 29 to arm B and 32 to arm C. Recruitment was stopped on 10 June because of a dramatic drop in cases. The safety analysis included 89 participants and the change in viral load was calculated in 87 participants. No SADRs were registered. Mean (S.D.) log10 viral load reduction was 2.9 (1.6) in arm C, 2.5 (2.2) in arm B and 2.0 (2.1) in arm A, with no significant differences (P = 0.099 and 0.122 for C vs. A and B vs. A, respectively). High-dose ivermectin was safe but did not show efficacy to reduce viral load.


Subject(s)
Antiviral Agents/pharmacokinetics , COVID-19/drug therapy , Ivermectin/pharmacokinetics , SARS-CoV-2/drug effects , Adult , Antiparasitic Agents/blood , Antiparasitic Agents/pharmacokinetics , Antiparasitic Agents/pharmacology , Antiviral Agents/blood , Antiviral Agents/pharmacology , COVID-19/blood , COVID-19/virology , Double-Blind Method , Drug Repositioning , Female , Humans , Ivermectin/blood , Ivermectin/pharmacology , Male , Middle Aged , SARS-CoV-2/growth & development , SARS-CoV-2/pathogenicity , Treatment Outcome , Viral Load/drug effects
18.
Br J Gen Pract ; 72(716): e217-e224, 2022 03.
Article in English | MEDLINE | ID: covidwho-1608429

ABSTRACT

BACKGROUND: There is little evidence about the relationship between aetiology, illness severity, and clinical course of respiratory tract infections (RTIs) in primary care. Understanding these associations would aid in the development of effective management strategies for these infections. AIM: To investigate whether clinical presentation and illness course differ between RTIs where a viral pathogen was detected and those where a potential bacterial pathogen was found. DESIGN AND SETTING: Post hoc analysis of data from a pragmatic randomised trial on the effects of oseltamivir in patients with flu-like illness in primary care (n = 3266) in 15 European countries. METHOD: Patient characteristics and their signs and symptoms of disease were registered at baseline. Nasopharyngeal (adults) or nasal and pharyngeal (children) swabs were taken for polymerase chain reaction analysis. Patients were followed up until 28 days after inclusion. Regression models and Kaplan-Meier curves were used to analyse the relationship between aetiology, clinical presentation at baseline, and course of disease including complications. RESULTS: Except for a less prominent congested nose (odds ratio [OR] 0.55, 95% confidence interval [CI] = 0.35 to 0.86) and acute cough (OR 0.42, 95% CI = 0.27 to 0.65) in patients with flu-like illness in whom a possible bacterial pathogen was isolated, there were no clear clinical differences in presentations between those with a possible bacterial aetiology compared with those with a viral aetiology. Also, course of disease and complications were not related to aetiology. CONCLUSION: Given current available microbiological tests and antimicrobial treatments, and outside pandemics such as COVID-19, microbiological testing in primary care patients with flu-like illness seems to have limited value. A wait-and-see policy in most of these patients with flu-like illness seems the best option.


Subject(s)
COVID-19 , Respiratory Tract Infections , Virus Diseases , Adult , Child , Humans , Pandemics , Respiratory Tract Infections/diagnosis , Respiratory Tract Infections/drug therapy , Respiratory Tract Infections/microbiology , SARS-CoV-2 , Virus Diseases/complications , Virus Diseases/diagnosis , Virus Diseases/epidemiology
19.
Psychon Bull Rev ; 28(6): 2085-2093, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1572698

ABSTRACT

Randomised assignment of individuals to treatment and controls groups is often considered the gold standard to draw valid conclusions about the efficacy of an intervention. In practice, randomisation can lead to accidental differences due to chance. Researchers have offered alternatives to reduce such differences, but these methods are not used frequently due to the requirement of advanced statistical methods. Here, we recommend a simple assignment procedure based on variance minimisation (VM), which assigns incoming participants automatically to the condition that minimises differences between groups in relevant measures. As an example of its application in the research context, we simulated an intervention study whereby a researcher used the VM procedure on a covariate to assign participants to a control and intervention group rather than controlling for the covariate at the analysis stage. Among other features of the simulated study, such as effect size and sample size, we manipulated the correlation between the matching covariate and the outcome variable and the presence of imbalance between groups in the covariate. Our results highlighted the advantages of VM over prevalent random assignment procedure in terms of reducing the Type I error rate and providing accurate estimates of the effect of the group on the outcome variable. The VM procedure is valuable in situations whereby the intervention to an individual begins before the recruitment of the entire sample size is completed. We provide an Excel spreadsheet, as well as scripts in R, MATLAB, and Python to ease and foster the implementation of the VM procedure.


Subject(s)
COVID-19 , Humans , Research Design
20.
Trials ; 22(1): 913, 2021 Dec 11.
Article in English | MEDLINE | ID: covidwho-1571922

ABSTRACT

BACKGROUND: Theoretical models of insomnia suggest that stressful life events, such as the COVID-19 pandemic, can cause acute insomnia (short-term disruptions to sleep). Early interventions may prevent short-term sleep problems from progressing to insomnia disorder. Although cognitive behavioural therapy for insomnia (CBT-I) is effective in treating insomnia disorder, this can be time and resource-intensive. Further, online interventions can be used to deliver treatment to a large number of individuals. The objective of this study is to investigate if an online behavioural intervention, in the form of a leaflet, which has been successfully used alongside CBT-I for acute insomnia, can reduce symptoms of acute insomnia in poor sleepers. METHODS: A total of 124 self-reported good and poor sleepers will be enrolled in an online stratified randomised controlled trial. After baseline assessments (T1), participants will complete a 1-week pre-intervention sleep monitoring period (T2) where they will complete daily sleep-diaries. Poor sleepers (n = 62) will be randomly allocated to an invention or wait-list group, where they will receive the intervention (T3), or will do so after a 28-day delay. Good sleepers (n = 62) will be randomly assigned to an intervention or no intervention group. All participants will complete a 1-week post intervention sleep monitoring period using daily sleep diaries (T4). Participants will be followed up at 1 week (T5), 1 month (T6) and 3 months (T7) post intervention. The primary outcome measure will be insomnia severity, measured using the Insomnia Severity Index. Secondary outcome measures will include subjective mood and subjective sleep continuity, measured using sleep diaries. Data will be analysed using an intention-to-treat approach. DISCUSSION: It is expected that this online intervention will reduce symptoms of acute insomnia in self-reported short-term poor sleepers, and will also prevent the transition to poor sleep in good sleepers. We expect that this will demonstrate the feasibility of online interventions for the treatment and prevention of acute insomnia. Specific advantages of online approaches include the low cost, ease of administration and increased availability of treatment, relative to face-to-face therapy. TRIAL REGISTRATION: ISRCTN43900695 (Prospectively registered 8th of April 2020).


Subject(s)
COVID-19 , Internet-Based Intervention , Humans , Pandemics , Randomized Controlled Trials as Topic , SARS-CoV-2 , Self Report , Sleep
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