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1.
Ann Clin Microbiol Antimicrob ; 21(1): 32, 2022 Jul 03.
Article in English | MEDLINE | ID: covidwho-2196304

ABSTRACT

BACKGROUND: New vaccines are being developed to fight the ongoing COVID-19 pandemic. In our study we compared the efficacy of COVID-19 vaccines to prevent COVID-19-related infections and mortality. METHODS: 17 randomized clinical trials of COVID-19 vaccines were included after search in databases. We compared COVID-19 vaccines based on symptomatic and severe infections, number of deaths and hospitalizations related to COVID-19. Also, we analyzed the efficacy of COVID-19 against different variants of SARS-CoV-2 as well as according to different age groups. Random effects model using Mantel-Haenzeal method was used to pool relative risk (RR). RESULTS: Our meta-analysis shows that full vaccination could decrease not only the risk of symptomatic or severe COVID-19, the risk of hospitalization and death caused by COVID-19. COVID-19 vaccines were also effective against variants of SARS-CoV-2 (RR = 0.36; 95% CI [0.25; 0.53], p < 0.0001). However, efficacy of vaccination varied in COVID-19 variant-dependent manner. Moreover, the analysis in different age groups showed that COVID-19 vaccines had the similar results: the risk was slightly lower in adults compared to elderly cohort [Formula: see text] 65 years): (RR = 0.16, 95% CI [0.11; 0.23]) and (RR = 0.19, 95% CI [0.12; 0.30]), respectively. CONCLUSIONS: Data obtained from clinical trials of COVID-19 vaccines looks promising, in order to fully investigate efficacy of the vaccines further clinical examination is required especially considering new SARS-CoV-2 variants.


Subject(s)
COVID-19 , Viral Vaccines , Adult , Aged , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Pandemics , Randomized Controlled Trials as Topic , SARS-CoV-2/genetics , Vaccination
2.
Medicine (Baltimore) ; 100(40): e27372, 2021 Oct 08.
Article in English | MEDLINE | ID: covidwho-2191071

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) in many countries is still very serious. At present, there is no specific and effective drug for this disease. Traditional Chinese medicine (TCM) has played a great role in fighting against COVID-19. However, their effectiveness and safety are still obscure and deserve further investigation. The aim of the study was to evaluate the efficacy and safety of TCM assisted in conventional treatment in the treatment of mild and common COVID-19. METHODS: PubMed, EMbase, MEDLINE, China National Knowledge Infrastructure Database, WANFANG DATA, and VIP Chinese Science and Technology Periodical Database were searched for randomized controlled trials (RCTs) and non-randomized controlled trials of TCM assisted in conventional treatment. The RCT research quality was evaluated by Cochrane 5.1.0 bias risk scale and the non-randomized controlled trial research quality was evaluated by Newcastle Ottawa scale, and the statistical analysis was conducted by Revman 5.3 and R software. The bias and sensitivity of the statistical results were analyzed by STATA 14.0. Registration number: CRD42020210619. RESULTS: Fifteen studies were included with 7 RCT studies and 8 retrospective cohort studies, involving a total of 1623 patients. Compared with the control group, TCM can improve the main index clinical effective rate (odds ratio [OR] = 2.64, 95% Confidence interval (CI) [1.94,3.59], P < .00001). The results of Begg test (Pr > z = 0.266) and sensitivity analysis showed that the results were relatively stable. Toujie Quwen (OR = 4.9, 95%CI [1.9,14.0]), Shufeng Jiedu (OR = 2.9, 95%CI [1.5,5.7]), and Lianhua Qingwen (OR = 2.4, 95%CI [1.6,3.6]) were with the best. It can also improve the main clinical symptoms (fever, cough, fatigue, and the regression time of the 3 symptoms), severe conversion rate, and computed tomography improvement rate. Its safety was not significantly compared with conventional treatment. However, in terms of safety of a single TCM, Shufeng Jiedu (OR = -0.86, 95%CI [-1.89,0.09]) and Lianhua Qingwen (OR = -0.49, 95%CI[-0.94,-0.05]) were lower than those of conventional treatment. CONCLUSION: TCM as an adjuvant therapy combined with conventional treatment has good curative effect on mild and common type of COVID-19 patients. Its advantages lie in clinical efficacy and improvement of symptom group, and can prevent patients from transforming to severe disease. In terms of clinical efficacy and safety, Shufeng Jiedu and Lianhua Qingwen have obvious advantages, which are worthy of clinical promotion.


Subject(s)
COVID-19/therapy , Drugs, Chinese Herbal/therapeutic use , Combined Modality Therapy , Drugs, Chinese Herbal/administration & dosage , Drugs, Chinese Herbal/adverse effects , Humans , Randomized Controlled Trials as Topic , SARS-CoV-2 , Severity of Illness Index
4.
Cochrane Database Syst Rev ; 6: CD015209, 2022 06 13.
Article in English | MEDLINE | ID: covidwho-2172307

ABSTRACT

BACKGROUND: With potential antiviral and anti-inflammatory properties, Janus kinase (JAK) inhibitors represent a potential treatment for symptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. They may modulate the exuberant immune response to SARS-CoV-2 infection. Furthermore, a direct antiviral effect has been described. An understanding of the current evidence regarding the efficacy and safety of JAK inhibitors as a treatment for coronavirus disease 2019 (COVID-19) is required. OBJECTIVES: To assess the effects of systemic JAK inhibitors plus standard of care compared to standard of care alone (plus/minus placebo) on clinical outcomes in individuals (outpatient or in-hospital) with any severity of COVID-19, and to maintain the currency of the evidence using a living systematic review approach. SEARCH METHODS: We searched the Cochrane COVID-19 Study Register (comprising MEDLINE, Embase, ClinicalTrials.gov, World Health Organization (WHO) International Clinical Trials Registry Platform, medRxiv, and Cochrane Central Register of Controlled Trials), Web of Science, WHO COVID-19 Global literature on coronavirus disease, and the US Department of Veterans Affairs Evidence Synthesis Program (VA ESP) Covid-19 Evidence Reviews to identify studies up to February 2022. We monitor newly published randomised controlled trials (RCTs) weekly using the Cochrane COVID-19 Study Register, and have incorporated all new trials from this source until the first week of April 2022. SELECTION CRITERIA: We included RCTs that compared systemic JAK inhibitors plus standard of care to standard of care alone (plus/minus placebo) for the treatment of individuals with COVID-19. We used the WHO definitions of illness severity for COVID-19. DATA COLLECTION AND ANALYSIS: We assessed risk of bias of primary outcomes using Cochrane's Risk of Bias 2 (RoB 2) tool. We used GRADE to rate the certainty of evidence for the following primary outcomes: all-cause mortality (up to day 28), all-cause mortality (up to day 60), improvement in clinical status: alive and without need for in-hospital medical care (up to day 28), worsening of clinical status: new need for invasive mechanical ventilation or death (up to day 28), adverse events (any grade), serious adverse events, secondary infections. MAIN RESULTS: We included six RCTs with 11,145 participants investigating systemic JAK inhibitors plus standard of care compared to standard of care alone (plus/minus placebo). Standard of care followed local protocols and included the application of glucocorticoids (five studies reported their use in a range of 70% to 95% of their participants; one study restricted glucocorticoid use to non-COVID-19 specific indications), antibiotic agents, anticoagulants, and antiviral agents, as well as non-pharmaceutical procedures. At study entry, about 65% of participants required low-flow oxygen, about 23% required high-flow oxygen or non-invasive ventilation, about 8% did not need any respiratory support, and only about 4% were intubated. We also identified 13 ongoing studies, and 9 studies that are completed or terminated and where classification is pending. Individuals with moderate to severe disease Four studies investigated the single agent baricitinib (10,815 participants), one tofacitinib (289 participants), and one ruxolitinib (41 participants). Systemic JAK inhibitors probably decrease all-cause mortality at up to day 28 (95 of 1000 participants in the intervention group versus 131 of 1000 participants in the control group; risk ratio (RR) 0.72, 95% confidence interval (CI) 0.57 to 0.91; 6 studies, 11,145 participants; moderate-certainty evidence), and decrease all-cause mortality at up to day 60 (125 of 1000 participants in the intervention group versus 181 of 1000 participants in the control group; RR 0.69, 95% CI 0.56 to 0.86; 2 studies, 1626 participants; high-certainty evidence). Systemic JAK inhibitors probably make little or no difference in improvement in clinical status (discharged alive or hospitalised, but no longer requiring ongoing medical care) (801 of 1000 participants in the intervention group versus 778 of 1000 participants in the control group; RR 1.03, 95% CI 1.00 to 1.06; 4 studies, 10,802 participants; moderate-certainty evidence). They probably decrease the risk of worsening of clinical status (new need for invasive mechanical ventilation or death at day 28) (154 of 1000 participants in the intervention group versus 172 of 1000 participants in the control group; RR 0.90, 95% CI 0.82 to 0.98; 2 studies, 9417 participants; moderate-certainty evidence). Systemic JAK inhibitors probably make little or no difference in the rate of adverse events (any grade) (427 of 1000 participants in the intervention group versus 441 of 1000 participants in the control group; RR 0.97, 95% CI 0.88 to 1.08; 3 studies, 1885 participants; moderate-certainty evidence), and probably decrease the occurrence of serious adverse events (160 of 1000 participants in the intervention group versus 202 of 1000 participants in the control group; RR 0.79, 95% CI 0.68 to 0.92; 4 studies, 2901 participants; moderate-certainty evidence). JAK inhibitors may make little or no difference to the rate of secondary infection (111 of 1000 participants in the intervention group versus 113 of 1000 participants in the control group; RR 0.98, 95% CI 0.89 to 1.09; 4 studies, 10,041 participants; low-certainty evidence). Subgroup analysis by severity of COVID-19 disease or type of JAK inhibitor did not identify specific subgroups which benefit more or less from systemic JAK inhibitors. Individuals with asymptomatic or mild disease We did not identify any trial for this population. AUTHORS' CONCLUSIONS: In hospitalised individuals with moderate to severe COVID-19, moderate-certainty evidence shows that systemic JAK inhibitors probably decrease all-cause mortality. Baricitinib was the most often evaluated JAK inhibitor. Moderate-certainty evidence suggests that they probably make little or no difference in improvement in clinical status. Moderate-certainty evidence indicates that systemic JAK inhibitors probably decrease the risk of worsening of clinical status and make little or no difference in the rate of adverse events of any grade, whilst they probably decrease the occurrence of serious adverse events. Based on low-certainty evidence, JAK inhibitors may make little or no difference in the rate of secondary infection. Subgroup analysis by severity of COVID-19 or type of agent failed to identify specific subgroups which benefit more or less from systemic JAK inhibitors. Currently, there is no evidence on the efficacy and safety of systemic JAK inhibitors for individuals with asymptomatic or mild disease (non-hospitalised individuals).


Subject(s)
COVID-19 , Coinfection , Janus Kinase Inhibitors , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Humans , Janus Kinase Inhibitors/therapeutic use , Oxygen , Randomized Controlled Trials as Topic , SARS-CoV-2 , United States
5.
Lancet ; 399(10339): 1941-1953, 2022 05 21.
Article in English | MEDLINE | ID: covidwho-2159958

ABSTRACT

BACKGROUND: The Solidarity trial among COVID-19 inpatients has previously reported interim mortality analyses for four repurposed antiviral drugs. Lopinavir, hydroxychloroquine, and interferon (IFN)-ß1a were discontinued for futility but randomisation to remdesivir continued. Here, we report the final results of Solidarity and meta-analyses of mortality in all relevant trials to date. METHODS: Solidarity enrolled consenting adults (aged ≥18 years) recently hospitalised with, in the view of their doctor, definite COVID-19 and no contraindication to any of the study drugs, regardless of any other patient characteristics. Participants were randomly allocated, in equal proportions between the locally available options, to receive whichever of the four study drugs (lopinavir, hydroxychloroquine, IFN-ß1a, or remdesivir) were locally available at that time or no study drug (controls). All patients also received the local standard of care. No placebos were given. The protocol-specified primary endpoint was in-hospital mortality, subdivided by disease severity. Secondary endpoints were progression to ventilation if not already ventilated, and time-to-discharge from hospital. Final log-rank and Kaplan-Meier analyses are presented for remdesivir, and are appended for all four study drugs. Meta-analyses give weighted averages of the mortality findings in this and all other randomised trials of these drugs among hospital inpatients. Solidarity is registered with ISRCTN, ISRCTN83971151, and ClinicalTrials.gov, NCT04315948. FINDINGS: Between March 22, 2020, and Jan 29, 2021, 14 304 potentially eligible patients were recruited from 454 hospitals in 35 countries in all six WHO regions. After the exclusion of 83 (0·6%) patients with a refuted COVID-19 diagnosis or encrypted consent not entered into the database, Solidarity enrolled 14 221 patients, including 8275 randomly allocated (1:1) either to remdesivir (ten daily infusions, unless discharged earlier) or to its control (allocated no study drug although remdesivir was locally available). Compliance was high in both groups. Overall, 602 (14·5%) of 4146 patients assigned to remdesivir died versus 643 (15·6%) of 4129 assigned to control (mortality rate ratio [RR] 0·91 [95% CI 0·82-1·02], p=0·12). Of those already ventilated, 151 (42·1%) of 359 assigned to remdesivir died versus 134 (38·6%) of 347 assigned to control (RR 1·13 [0·89-1·42], p=0·32). Of those not ventilated but on oxygen, 14·6% assigned to remdesivir died versus 16·3% assigned to control (RR 0·87 [0·76-0·99], p=0·03). Of 1730 not on oxygen initially, 2·9% assigned to remdesivir died versus 3·8% assigned to control (RR 0·76 [0·46-1·28], p=0·30). Combining all those not ventilated initially, 11·9% assigned to remdesivir died versus 13·5% assigned to control (RR 0·86 [0·76-0·98], p=0·02) and 14·1% versus 15·7% progressed to ventilation (RR 0·88 [0·77-1·00], p=0·04). The non-prespecified composite outcome of death or progression to ventilation occurred in 19·6% assigned to remdesivir versus 22·5% assigned to control (RR 0·84 [0·75-0·93], p=0·001). Allocation to daily remdesivir infusions (vs open-label control) delayed discharge by about 1 day during the 10-day treatment period. A meta-analysis of mortality in all randomised trials of remdesivir versus no remdesivir yielded similar findings. INTERPRETATION: Remdesivir has no significant effect on patients with COVID-19 who are already being ventilated. Among other hospitalised patients, it has a small effect against death or progression to ventilation (or both). FUNDING: WHO.


Subject(s)
Antiviral Agents , COVID-19 , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/therapeutic use , Adult , Alanine/analogs & derivatives , Alanine/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Humans , Hydroxychloroquine/therapeutic use , Interferon beta-1a/therapeutic use , Lopinavir/therapeutic use , Oxygen/administration & dosage , Randomized Controlled Trials as Topic , Treatment Outcome , World Health Organization
6.
Front Public Health ; 10: 917732, 2022.
Article in English | MEDLINE | ID: covidwho-2154833

ABSTRACT

Objective: This study aimed to determine the efficacy, effectiveness, and cost-effectiveness of inactivated COVID-19 vaccines (CoronaVac and BBIBP-CorV) in China using existing international clinical trials and real-world evidence. Methods: Through a search of PubMed, Embase, Web of Science, and CNKI, studies investigating the effectiveness of inactivated COVID-19 vaccines were identified, and a meta-analysis was undertaken to synthesize the vaccine efficacy and effectiveness data. Moreover, a decision-analytic model was developed to estimate the cost-effectiveness of inactivated vaccines for combating the COVID-19 pandemic in the Chinese context from a societal perspective. Results of the meta-analysis, along with cost data from official websites and works of literature were used to populate the model. Sensitivity analysis was performed to test the robustness of the model results. Results: A total of 24 studies were included in the meta-analysis. In comparison to no immunization, the effectiveness of inactivated vaccine against COVID-19 infection, hospitalization, ICU admission and death were 65.18% (95% CI 62.62, 67.75), 79.10% (95% CI 71.69, 86.51), 90.46% (95% CI 89.42, 91.50), and 86.69% (95% CI 85.68, 87.70); and the efficacy against COVID-19 infection and hospitalization were 70.56% (95% CI 57.87, 83.24) and 100% (95% CI 61.72, 100). Inactivated vaccine vaccination prevented more infections, hospitalizations, ICU admissions, and deaths with lower total costs, thus was cost-saving from a societal perspective in China. Base-case analysis results were robust in the one-way sensitivity analysis, and the percentage of ICU admission or death and direct medical cost ranked the top influential factors in our models. In the probabilistic sensitivity analysis, vaccination had a 100% probability of being cost-effective. Conclusion: Inactivated vaccine is effective in preventing COVID-19 infection, hospitalization, ICU admission and avoiding COVID-19 related death, and COVID-19 vaccination program is cost-saving from societal perspective in China.


Subject(s)
COVID-19 Vaccines , COVID-19 , Cost-Benefit Analysis , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines/therapeutic use , China/epidemiology , Humans , Pandemics/prevention & control , Randomized Controlled Trials as Topic , Vaccines, Inactivated/therapeutic use
7.
BMJ Open ; 12(11): e063895, 2022 11 17.
Article in English | MEDLINE | ID: covidwho-2152994

ABSTRACT

INTRODUCTION: Socioeconomic disparities for breast cancer surgical care exist. Although the aetiology of the observed socioeconomic disparities is likely multifactorial, patient engagement during the surgical consult is critical. Shared decision-making may reduce health disparities by addressing barriers to patient engagement in decision-making that disproportionately impact socioeconomically disadvantaged patients. In this trial, we test the impact of a decision aid on increasing socioeconomically disadvantaged patients' engagement in breast cancer surgery decision-making. METHODS AND ANALYSIS: This multisite randomised trial is conducted through 10 surgical clinics within the National Cancer Institute Community Oncology Research Program (NCORP). We plan a stepped-wedge design with clinics randomised to the time of transition from usual care to the decision aid arm. Study participants are female patients, aged ≥18 years, with newly diagnosed stage 0-III breast cancer who are planning breast surgery. Data collection includes a baseline surgeon survey, baseline patient survey, audio-recording of the surgeon-patient consultation, a follow-up patient survey and medical record data review. Interviews and focus groups are conducted with a subset of patients, surgeons and clinic stakeholders. The effectiveness of the decision aid at increasing patient engagement (primary outcome) is evaluated using generalised linear mixed-effects models. The extent to which the effect of the decision aid intervention on patient engagement is mediated through the mitigation of barriers is tested in joint linear structural equation models. Qualitative interviews explore how barriers impact engagement, especially for socioeconomically disadvantaged women. ETHICS AND DISSEMINATION: This protocol has been approved by the National Cancer Institute Central Institutional Review Board, and Certificate of Confidentiality has been obtained. We plan to disseminate the findings through journal publications and national meetings, including the NCORP network. Our findings will advance the science of medical decision-making with the potential to reduce socioeconomic health disparities. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT03766009).


Subject(s)
Breast Carcinoma In Situ , Breast Neoplasms , Humans , Female , Adolescent , Adult , Male , Patient Participation , Breast Neoplasms/surgery , Decision Making , Mastectomy , Decision Making, Shared , Randomized Controlled Trials as Topic
8.
Curr Opin Crit Care ; 28(6): 660-666, 2022 Dec 01.
Article in English | MEDLINE | ID: covidwho-2152245

ABSTRACT

PURPOSE OF REVIEW: To review the clinical problem and noninvasive treatments of hypoxemia in critically-ill patients with coronavirus disease 2019 pneumonia and describe recent advances in evidence supporting bedside decision making. RECENT FINDINGS: High-flow nasal oxygen and noninvasive ventilation, along with awake prone positioning are potentially helpful therapies for acute hypoxemic respiratory failure. High-flow nasal oxygen therapy has been widely implemented as a form of oxygen support supported by prepandemic randomized controlled trials showing possible benefit over noninvasive ventilation. Given the sheer volume of patients, noninvasive ventilation was often required, and based on a well conducted randomized controlled trial there was a developing role for helmet-interface noninvasive. Coupled with noninvasive supports, the use of awake prone positioning demonstrated physiological benefits, but randomized controlled trial data did not demonstrate clear outcome superiority. SUMMARY: The use of noninvasive oxygen strategies and our understanding of the proposed mechanisms are evolving. Variability in patient severity and physiology may dictate a personalized approach to care. High-flow nasal oxygen may be paired with awake and spontaneously breathing prone-positioning to optimize oxygen and lung mechanics but requires further insight before widely applying to clinical practice.


Subject(s)
COVID-19 , Noninvasive Ventilation , Respiratory Insufficiency , Humans , COVID-19/therapy , Respiratory Insufficiency/therapy , Oxygen Inhalation Therapy , Hypoxia/therapy , Oxygen , Critical Care , Lung , Randomized Controlled Trials as Topic
9.
Circ Heart Fail ; 14(3): e007767, 2021 03.
Article in English | MEDLINE | ID: covidwho-2153215

ABSTRACT

BACKGROUND: The expense of clinical trials mandates new strategies to efficiently generate evidence and test novel therapies. In this context, we designed a decentralized, patient-centered randomized clinical trial leveraging mobile technologies, rather than in-person site visits, to test the efficacy of 12 weeks of canagliflozin for the treatment of heart failure, regardless of ejection fraction or diabetes status, on the reduction of heart failure symptoms. METHODS: One thousand nine hundred patients will be enrolled with a medical record-confirmed diagnosis of heart failure, stratified by reduced (≤40%) or preserved (>40%) ejection fraction and randomized 1:1 to 100 mg daily of canagliflozin or matching placebo. The primary outcome will be the 12-week change in the total symptom score of the Kansas City Cardiomyopathy Questionnaire. Secondary outcomes will be daily step count and other scales of the Kansas City Cardiomyopathy Questionnaire. RESULTS: The trial is currently enrolling, even in the era of the coronavirus disease 2019 (COVID-19) pandemic. CONCLUSIONS: CHIEF-HF (Canagliflozin: Impact on Health Status, Quality of Life and Functional Status in Heart Failure) is deploying a novel model of conducting a decentralized, patient-centered, randomized clinical trial for a new indication for canagliflozin to improve the symptoms of patients with heart failure. It can model a new method for more cost-effectively testing the efficacy of treatments using mobile technologies with patient-reported outcomes as the primary clinical end point of the trial. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04252287.


Subject(s)
Canagliflozin/therapeutic use , Heart Failure/drug therapy , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Telemedicine , Actigraphy/instrumentation , Canagliflozin/adverse effects , Double-Blind Method , Exercise Tolerance/drug effects , Fitness Trackers , Heart Failure/diagnosis , Heart Failure/physiopathology , Humans , Mobile Applications , Quality of Life , Randomized Controlled Trials as Topic , Recovery of Function , Sodium-Glucose Transporter 2 Inhibitors/adverse effects , Stroke Volume/drug effects , Telemedicine/instrumentation , Time Factors , Treatment Outcome , United States , Ventricular Function, Left/drug effects
10.
BMJ Open Respir Res ; 9(1)2022 09.
Article in English | MEDLINE | ID: covidwho-2137828

ABSTRACT

INTRODUCTION: Breathing pattern disorder (BPD) is an abnormal breathing pattern associated with biochemical, biomechanical and psychophysiological changes. While physiotherapy is often offered, limited evidence-based therapies for BPD are available. Music therapy-based singing exercises have been shown to improve quality of life for individuals with respiratory conditions and may also be beneficial for individuals living with BPD. No study has previously compared these participatory interventions in the treatment of people living with BPD. METHODS AND ANALYSIS: This is a study protocol for an assessor blinded 1:1 randomised controlled trial and qualitative interview study. Forty participants aged 18-40 years who score at least 19 on the Nijmegen Questionnaire (NQ) and do not have any underlying respiratory conditions will be recruited. Participants will be randomised to receive either physiotherapy-led or music therapy-led breathing exercises for 6 weeks. The primary outcome will be between-group difference in NQ post-intervention. Semistructured interviews with a purposive sample of participants will be performed. Qualitative data will be analysed using thematic analysis to better understand participants' intervention and trial experiences. ETHICS AND DISSEMINATION: This study has received ethical approval by Brunel University London College of Health, Medicine and Life Science's Research Ethics Committee (32483-MHR-Mar/2022-38624-3). The anonymised completed dataset will be made available as an open-access file via Brunel University London Figshare and the manuscript containing anonymised patient data will be published in an open-access journal. TRIAL REGISTRATION NUMBER: This trial is registered on the Open Science Framework Registry (https://osf.io/u3ncw).


Subject(s)
Music , Physical Therapists , Adolescent , Adult , Breathing Exercises/methods , Humans , Pilot Projects , Quality of Life , Randomized Controlled Trials as Topic , Respiration , Young Adult
13.
J Clin Invest ; 132(18)2022 09 15.
Article in English | MEDLINE | ID: covidwho-2123274

ABSTRACT

Global vaccination coverage remains indispensable in combatting the ongoing SARS-CoV-2 pandemic. Safety, efficacy, and durability of immune protection are the key parameters of randomized controlled trials (RCTs) and are essential for vaccine approvals, global distribution, and comprehensive population-vaccination programs. Immune protection from either vaccination or natural infection decreases over time, further challenged by rapid viral evolution. In this issue of the JCI, Sobieszczyk and colleagues report an update on the safety, efficacy, and durability of immune protection of AZD12222 in a large-scale, multinational, Phase III RCT. They report that protection lasted through 6 months, with immunity waning after 180 days. The study also highlights challenges facing vaccine trials, including the need for early unblinding for vulnerable participants, which may affect outcome measurements. Another challenge is to ensure fair representation of marginalized and minority ethnic groups in vaccine safety and efficacy studies worldwide.


Subject(s)
COVID-19 Vaccines , COVID-19 , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Clinical Trials, Phase III as Topic , Humans , Randomized Controlled Trials as Topic
14.
Ann Intern Med ; 173(3): 204-216, 2020 08 04.
Article in English | MEDLINE | ID: covidwho-2110840

ABSTRACT

BACKGROUND: Mechanical ventilation is used to treat respiratory failure in coronavirus disease 2019 (COVID-19). PURPOSE: To review multiple streams of evidence regarding the benefits and harms of ventilation techniques for coronavirus infections, including that causing COVID-19. DATA SOURCES: 21 standard, World Health Organization-specific and COVID-19-specific databases, without language restrictions, until 1 May 2020. STUDY SELECTION: Studies of any design and language comparing different oxygenation approaches in patients with coronavirus infections, including severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS), or with hypoxemic respiratory failure. Animal, mechanistic, laboratory, and preclinical evidence was gathered regarding aerosol dispersion of coronavirus. Studies evaluating risk for virus transmission to health care workers from aerosol-generating procedures (AGPs) were included. DATA EXTRACTION: Independent and duplicate screening, data abstraction, and risk-of-bias assessment (GRADE for certainty of evidence and AMSTAR 2 for included systematic reviews). DATA SYNTHESIS: 123 studies were eligible (45 on COVID-19, 70 on SARS, 8 on MERS), but only 5 studies (1 on COVID-19, 3 on SARS, 1 on MERS) adjusted for important confounders. A study in hospitalized patients with COVID-19 reported slightly higher mortality with noninvasive ventilation (NIV) than with invasive mechanical ventilation (IMV), but 2 opposing studies, 1 in patients with MERS and 1 in patients with SARS, suggest a reduction in mortality with NIV (very-low-certainty evidence). Two studies in patients with SARS report a reduction in mortality with NIV compared with no mechanical ventilation (low-certainty evidence). Two systematic reviews suggest a large reduction in mortality with NIV compared with conventional oxygen therapy. Other included studies suggest increased odds of transmission from AGPs. LIMITATION: Direct studies in COVID-19 are limited and poorly reported. CONCLUSION: Indirect and low-certainty evidence suggests that use of NIV, similar to IMV, probably reduces mortality but may increase the risk for transmission of COVID-19 to health care workers. PRIMARY FUNDING SOURCE: World Health Organization. (PROSPERO: CRD42020178187).


Subject(s)
Coronavirus Infections/transmission , Pneumonia, Viral/transmission , Respiration, Artificial/adverse effects , Respiration, Artificial/methods , Aerosols , Animals , Betacoronavirus , COVID-19 , Coronavirus Infections/mortality , Humans , Pandemics , Pneumonia, Viral/mortality , Randomized Controlled Trials as Topic , SARS-CoV-2 , Severe Acute Respiratory Syndrome/transmission , Systematic Reviews as Topic , World Health Organization
15.
Rev Bras Ter Intensiva ; 34(3): 335-341, 2022.
Article in Portuguese, English | MEDLINE | ID: covidwho-2110721

ABSTRACT

OBJECTIVE: To compare the lung mechanics and outcomes between COVID-19-associated acute respiratory distress syndrome and non-COVID-19-associated acute respiratory distress syndrome. METHODS: We combined data from two randomized trials in acute respiratory distress syndrome, one including only COVID-19 patients and the other including only patients without COVID-19, to determine whether COVID-19-associated acute respiratory distress syndrome is associated with higher 28-day mortality than non-COVID-19 acute respiratory distress syndrome and to examine the differences in lung mechanics between these two types of acute respiratory distress syndrome. RESULTS: A total of 299 patients with COVID-19-associated acute respiratory distress syndrome and 1,010 patients with non-COVID-19-associated acute respiratory distress syndrome were included in the main analysis. The results showed that non-COVID-19 patients used higher positive end-expiratory pressure (12.5cmH2O; SD 3.2 versus 11.7cmH2O SD 2.8; p < 0.001), were ventilated with lower tidal volumes (5.8mL/kg; SD 1.0 versus 6.5mL/kg; SD 1.2; p < 0.001) and had lower static respiratory compliance adjusted for ideal body weight (0.5mL/cmH2O/kg; SD 0.3 versus 0.6mL/cmH2O/kg; SD 0.3; p = 0.01). There was no difference between groups in 28-day mortality (52.3% versus 58.9%; p = 0.52) or mechanical ventilation duration in the first 28 days among survivors (13 [IQR 5 - 22] versus 12 [IQR 6 - 26], p = 0.46). CONCLUSION: This analysis showed that patients with non-COVID-19-associated acute respiratory distress syndrome have different lung mechanics but similar outcomes to COVID-19-associated acute respiratory distress syndrome patients. After propensity score matching, there was no difference in lung mechanics or outcomes between groups.


OBJETIVO: Comparar a mecânica pulmonar e os desfechos entre a síndrome do desconforto respiratório agudo associada à COVID-19 e a síndrome do desconforto respiratório agudo não associada à COVID-19. MÉTODOS: Combinamos dados de dois ensaios randomizados sobre a síndrome do desconforto respiratório agudo, um incluindo apenas pacientes com COVID-19 e o outro incluindo apenas pacientes sem COVID-19, para determinar se a síndrome do desconforto respiratório agudo associada à COVID-19 está associada à maior mortalidade aos 28 dias do que a síndrome do desconforto respiratório agudo não associada à COVID-19 e também examinar as diferenças na mecânica pulmonar entre esses dois tipos de síndrome do desconforto respiratório agudo. RESULTADOS: Foram incluídos na análise principal 299 pacientes com síndrome do desconforto respiratório agudo associada à COVID-19 e 1.010 pacientes com síndrome do desconforto respiratório agudo não associada à COVID-19. Os resultados mostraram que os pacientes sem COVID-19 utilizaram pressão positiva expiratória final mais alta (12,5cmH2O; DP 3,2 versus 11,7cmH2O; DP 2,8; p < 0,001), foram ventilados com volumes correntes mais baixos (5,8mL/kg; DP 1,0 versus 6,5mL/kg; DP 1,2; p < 0,001) e apresentaram menor complacência respiratória estática ajustada para o peso ideal (0,5mL/cmH2O/kg; DP 0,3 versus 0,6mL/cmH2O/kg; DP 0,3; p = 0,01). Não houve diferença entre os grupos quanto à mortalidade aos 28 dias (52,3% versus 58,9%; p = 0,52) ou à duração da ventilação mecânica nos primeiros 28 dias entre os sobreviventes (13 [IQ 5 - 22] dias versus 12 [IQ 6 - 26] dias; p = 0,46). CONCLUSÃO: Esta análise mostrou que os pacientes com síndrome do desconforto respiratório agudo não associada à COVID-19 têm mecânica pulmonar diferente, mas desfechos semelhantes aos dos pacientes com síndrome do desconforto respiratório agudo associada à COVID-19. Após pareamento por escore de propensão, não houve diferença na mecânica pulmonar e nem nos desfechos entre os grupos.


Subject(s)
COVID-19 , Respiratory Distress Syndrome , Humans , Propensity Score , COVID-19/complications , Randomized Controlled Trials as Topic , Respiratory Distress Syndrome/therapy , Lung , Respiration, Artificial/methods , Respiratory Mechanics
16.
PLoS One ; 17(5): e0262776, 2022.
Article in English | MEDLINE | ID: covidwho-2121907

ABSTRACT

BACKGROUND: Severe pneumonia (SP) has a high mortality and is responsible for significant healthcare cost. Chinese herbal injections (CHIs) have been widely used in China as a novel and promising treatment option for SP. Therefore, this study will assess and rank the effectiveness of CHIs to provide more sights for the selection of SP treatment. METHOD: Seven databases will be searched, including PubMed, the Cochrane Library, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang Database, and the Chinese Scientific Journal Database (VIP) from their inception up to October, 2021. The literatures screening, data extraction and the quality assessment of included studies will be conducted independently by two reviewers. Then Bayesian network meta-analysis (NMA) will be performed by WinBUGS 14.0 and STATA 14.0 software. Surface under the cumulative ranking curve (SUCRA) probability values will be applied to rank the examined treatments. The risk of bias of each included study will be evaluated using the Revised Cochrane risk-of-bias tool for randomized trials (ROB 2). Publication bias will be reflected by a funnel plot. RESULTS: The results of this NMA will be disseminated through a peer-reviewed journal publication. CONCLUSION: Our study findings maybe reveal which CHI or CHIs will be better in the treatment of SP and provide more therapy strategies for clinical practitioners and patients. PROSPERO REGISTRATION NUMBER: CRD42021244587. STRENGTHS AND LIMITATIONS OF THIS STUDY: Bayesian network meta-analysis (NMA) can integrate direct evidence with indirect evidence of severe pneumonia treated by Chinese herbal injections to generate a clinically useful ranking of these regimens. This NMA will address Chinese herbal injections for SP and its findings may help to provide more sights for selection of SP treatment. Evidence drawn from an NMA is limited and should be interpreted with caution. We only included studies in Chinese and English languages, which may increase the publication bias.


Subject(s)
Drugs, Chinese Herbal , Pneumonia , Bayes Theorem , Drugs, Chinese Herbal/administration & dosage , Drugs, Chinese Herbal/therapeutic use , Humans , Injections , Language , Meta-Analysis as Topic , Network Meta-Analysis , Pneumonia/drug therapy , Randomized Controlled Trials as Topic , Systematic Reviews as Topic , Treatment Outcome
17.
Front Immunol ; 13: 1046352, 2022.
Article in English | MEDLINE | ID: covidwho-2119704

ABSTRACT

Background: Coronavirus disease 2019 (COVID-19) have brought great disaster to mankind, and there is currently no globally recognized specific drug or treatment. Severe COVID-19 may trigger a cytokine storm, manifested by increased levels of cytokines including interleukin-17 (IL-17), so a new strategy to treat COVID-19 may be to use existing IL-17 inhibitors, which have demonstrated efficacy, safety and tolerability in the treatment of psoriasis. However, the use of IL-17 inhibitors in patients with psoriasis during the COVID-19 pandemic remains controversial due to reports that IL-17 inhibitors may increase the risk of respiratory tract infections. Objectives: The systematic review and meta-analysis aimed to evaluate the effect of IL-17 inhibitors on the risk of COVID-19 infection, hospitalization, and mortality in patients with psoriasis. Methods: Databases (including Embase, PubMed, SCI-Web of Science, Scopus, CNKI, and the Cochrane Library) were searched up to August 23, 2022, for studies exploring differences in COVID-19 outcomes between psoriasis patients using IL-17 inhibitors and those using non-biologics. Two authors independently extracted data and assessed the risk of bias in a double-blind manner. The risk ratios (RRs) and 95% confidence intervals (CIs) were calculated and heterogeneities were determined by the Q test and I 2 statistic. And the numbers needed to treat (NNTs) were calculated to assess the clinical value of IL-17 inhibitors in preventing SARS-CoV-2 infection and treating COVID-19. Results: Nine observational studies involving 7,106 participants were included. The pooled effect showed no significant differences in the rates of SARS-CoV-2 infection (P = 0.94; I 2 = 19.5%), COVID-19 hospitalization (P = 0.64; I 2 = 0.0%), and COVID-19 mortality (P = 0.32; I 2 = 0.0%) in psoriasis patients using IL-17 inhibitors compared with using non-biologics. Subgroup analyses grouped by age and COVID-19 cases, respectively, revealed consistent results as above. Meanwhile, the pooled NNTs showed no significant differences between the two groups in the clinical value of preventing SARS-CoV-2 infection and treating COVID-19. Conclusion: The use of IL-17 inhibitors in patients with psoriasis does not increase the risk of SARS-CoV-2 infection or worsen the course of COVID-19. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022335195.


Subject(s)
COVID-19 , Psoriasis , Humans , COVID-19/drug therapy , Interleukin-17 , Interleukin Inhibitors , Pandemics , Antibodies, Monoclonal/therapeutic use , SARS-CoV-2 , Psoriasis/drug therapy , Hospitalization , Randomized Controlled Trials as Topic
18.
Front Immunol ; 13: 1023903, 2022.
Article in English | MEDLINE | ID: covidwho-2119689

ABSTRACT

Vitamin D supplementation and its impact on immunoregulation are widely investigated. We aimed to assess the prevention and treatment efficiency of vitamin D supplementation in the context of coronavirus disease 2019 (COVID-19) and any disease-related complications. For this systematic review and meta-analysis, we searched databases (PubMed, Embase, Scopus, Web of Science, The Cochrane Library, medRxiv, Cochrane COVID-19 Study Register, and ClinicalTrial.gov) for studies published between 1 November 2019 and 17 September 2021. We considered randomized trials (RCTs) as potentially eligible when patients were tested for SARS-CoV-2 infection and received vitamin D supplementation versus a placebo or standard-of-care control. A random-effects model was implemented to obtain pooled odds ratios for the effect of vitamin D supplementation on the main outcome of mortality as well as clinical outcomes. We identified a total of 5,733 articles, of which eight RCTs (657 patients) met the eligibility criteria. Although no statistically significant effects were reached, the use of vitamin D supplementation showed a trend for reduced mortality [odds ratio (OR) 0.74, 95% confidence interval (CI) 0.32-1.71, p = 0.48] compared with the control group, with even stronger effects, when vitamin D was administered repeatedly (OR 0.33, 95% CI 0.1-1.14). The mean difference for the length of hospitalization was -0.28 (95% CI -0.60 to 0.04), and the ORs were 0.41 (95% CI 0.15-1.12) and 0.52 (95% CI 0.27-1.02) for ICU admission and mechanical ventilation, respectively. In conclusion, vitamin D supplementation did not improve the clinical outcomes in COVID-19 patients, but trends of beneficial effects were observed. Further investigations are required, especially studies focusing on the daily administration of vitamin D.


Subject(s)
COVID-19 , Humans , COVID-19/drug therapy , Dietary Supplements , SARS-CoV-2 , Randomized Controlled Trials as Topic , Vitamin D/therapeutic use , Vitamins/therapeutic use
19.
BMJ Open ; 12(11): e063526, 2022 11 10.
Article in English | MEDLINE | ID: covidwho-2119463

ABSTRACT

INTRODUCTION: Basal cell carcinomas (BCCs) represent 70% of all skin cancers. These tumours do not metastasise but are locally invasive if left untreated. There is a high incidence of BCC in the elderly, and clinicians frequently face important treatment dilemmas. The approach to BCC in the elderly should be investigated thoroughly. METHODS AND ANALYSIS: Data on health-related quality of life (HrQoL), survival and complication rate will be examined in a treatment and a non-treatment arm (1:1 allocation). In the non-treatment arm, in vivo biological behaviour of low-risk BCCs in elderly patients will be examined. The main objective is to combine tumour characteristics with demographic data, in order to determine whether treatment will positively affect the patients' HrQoL within a predetermined time frame. A monocentric randomised controlled trial (RCT) was designed at the Ghent University Hospital. The study population consists of patients with the minimum age of 75 years and a new diagnosis of (a) low-risk BCC(s). Patients in the treatment arm will receive standard care. Patients in the non-treatment arm will be closely monitored: the tumour will be intensively evaluated using multispectral dermoscopy, reflectance confocal microscopy and high-definition optical coherence tomography. All patients will be asked to fill in a questionnaire concerning their HrQoL at consecutive time points. Patient-reported side effects will be evaluated via an additional questionnaire.Primary outcomes will include the difference in HrQoL and the difference in complication risks (treatment vs non-treatment) at different time points of the study. Secondary endpoints are the evolution of the BCCs in the non-treatment arm and the long-term survival in both study arms. Tertiary endpoint is the treatment effectiveness in the treatment arm. The sample size calculation was performed and resulted in a target sample size of 272 patients in this study with a 1:1 allocation. ETHICS AND DISSEMINATION: Subjects can withdraw from participating in this study at any time for any reason without any consequences. Approval for this study was received from the Ethics Committee of the Ghent University Hospital on 26 August 2021.The results of this RCT will be submitted for publication in one or more international, peer-reviewed medical journals, regardless of the nature of the study results. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov (NCT05110924).


Subject(s)
COVID-19 , Carcinoma, Basal Cell , Skin Neoplasms , Aged , Aged, 80 and over , Humans , Randomized Controlled Trials as Topic , SARS-CoV-2 , Treatment Outcome , Pragmatic Clinical Trials as Topic
20.
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
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