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1.
Medicine (Baltimore) ; 101(41): e30998, 2022 Oct 14.
Article in English | MEDLINE | ID: covidwho-2077958

ABSTRACT

BACKGROUND: To date, there has been little agreement on what drug is the "best" drug for treating severe COVID-19 patients. This study aimed to assess the efficacy and safety of different medications available at present for severe COVID-19. METHODS: We searched databases for randomized controlled trials (RCTs) published up to February 28, 2022, with no language restrictions, of medications recommended for patients (aged 16 years or older) with severe COVID-19 infection. We extracted data on trials and patient characteristics, and the following primary outcomes: all-cause mortality (ACM), and treatment-emergent adverse events (TEAEs). RESULTS: We identified 4021 abstracts and of these included 48 RCTs comprising 9147 participants through database searches and other sources. For decrease in ACM, we found that ivermectin/doxycycline, C-IVIG (i.e., a hyperimmune anti-COVID-19 intravenous immunoglobulin), methylprednisolone, interferon-beta/standard-of-care (SOC), interferon-beta-1b, convalescent plasma, remdesivir, lopinavir/ritonavir, immunoglobulin gamma, high dosage sarilumab (HS), auxora, and imatinib were effective when compared with placebo or SOC group. We found that colchicine and interferon-beta/SOC were only associated with the TEAEs of severe COVID-19 patients. CONCLUSION: This study suggested that ivermectin/doxycycline, C-IVIG, methylprednisolone, interferon-beta/SOC, interferon-beta-1b, convalescent plasma (CP), remdesivir, lopinavir/ritonavir, immunoglobulin gamma, HS, auxora, and imatinib were efficacious for treating severe COVID-19 patients. We found that most medications were safe in treating severe COVID-19. More large-scale RCTs are still needed to confirm the results of this study.


Subject(s)
COVID-19 , Coronavirus Infections , Pneumonia, Viral , COVID-19/drug therapy , COVID-19/therapy , Colchicine/therapeutic use , Coronavirus Infections/therapy , Doxycycline/therapeutic use , Humans , Imatinib Mesylate/therapeutic use , Immunization, Passive , Immunoglobulins, Intravenous/therapeutic use , Interferon beta-1b/therapeutic use , Ivermectin/adverse effects , Lopinavir/therapeutic use , Methylprednisolone/therapeutic use , Network Meta-Analysis , Pandemics , Pneumonia, Viral/therapy , Randomized Controlled Trials as Topic , Ritonavir/therapeutic use
2.
Sci Rep ; 12(1): 17561, 2022 Oct 20.
Article in English | MEDLINE | ID: covidwho-2077116

ABSTRACT

The purpose of this work was to review and synthesise the evidence on the comparative effectiveness of neutralising monoclonal antibody (nMAB) therapies in individuals exposed to or infected with SARS-CoV-2 and at high risk of developing severe COVID-19. Outcomes of interest were mortality, healthcare utilisation, and safety. A rapid systematic review was undertaken to identify and synthesise relevant RCT evidence using a Bayesian Network Meta-Analysis. Relative treatment effects for individual nMABs (compared with placebo and one another) were estimated. Pooled effects for the nMAB class compared with placebo were estimated. Relative effects were combined with baseline natural history models to predict the expected risk reductions per 1000 patients treated. Eight articles investigating four nMABs (bamlanivimab, bamlanivimab/etesevimab, casirivimab/imdevimab, sotrovimab) were identified. All four therapies were associated with a statistically significant reduction in hospitalisation (70-80% reduction in relative risk; absolute reduction of 35-40 hospitalisations per 1000 patients). For mortality, ICU admission, and invasive ventilation, the risk was lower for all nMABs compared with placebo with moderate to high uncertainty due to small event numbers. Rates of serious AEs and infusion reactions were comparable between nMABs and placebo. Pairwise comparisons between nMABs were typically uncertain, with broadly comparable efficacy. In conclusion, nMABs are effective at reducing hospitalisation among infected individuals at high-risk of severe COVID-19, and are likely to reduce mortality, ICU admission, and invasive ventilation rates; the effect on these latter outcomes is more uncertain. Widespread vaccination and the emergence of nMAB-resistant variants make the generalisability of these results to current patient populations difficult.


Subject(s)
Antineoplastic Agents, Immunological , COVID-19 , Humans , SARS-CoV-2 , Network Meta-Analysis , Bayes Theorem , Antibodies, Monoclonal/therapeutic use , Antibodies, Neutralizing
3.
J Infect Dev Ctries ; 16(9): 1406-1412, 2022 09 30.
Article in English | MEDLINE | ID: covidwho-2066665

ABSTRACT

INTRODUCTION: COVID-19 is a coronavirus-based infectious illness that was first detected at the end of 2019 in Wuhan, China. The novel virus induces severe acute respiratory syndrome (SARS-CoV-2) and has spread globally, resulting in an ongoing pandemic. There is still a lack of evidence for direct comparison of favipiravir therapy. Network meta-analysis (NMA), may incorporate direct and indirect comparisons in a pooled computation while depending on strong assumptions and premises. This study provides evidence-based recommendations on the safety of currently used clinical pharmacological treatments compared to favipiravir for COVID-19 patients. METHODOLOGY: We conducted a systematic review and Bayesian NMA. We searched the primary databases and clinical trials center for reports of short-term, randomized controlled trials (RCTs) of favipiravir for COVID-19 treatment. The primary endpoints here considered were any adverse events observed or reported during the treatment cycle with estimates of odds ratio (OR) and 95% confidence interval (CI), until November 6, 2021. RESULTS: Between January 2020 and July 2021, 908 individuals were randomly assigned to one of the seven active prescription medication regimens or placebo in this study, generating seven direct comparisons on 12 data points. The safety of favipiravir over the four clinically efficacious monotherapies or combinations including tocilizumab, arbidol, lopinavir + ritonavir, and chloroquine remained unknown due to the lack of a significant difference and the limited sample size. CONCLUSIONS: Overall, comparative rankings could assist doctors and guideline developers in decision-making. We have also concluded that the safety of favipiravir requires further attention.


Subject(s)
COVID-19 , Amides , COVID-19/drug therapy , Chloroquine , Humans , Lopinavir/adverse effects , Network Meta-Analysis , Pyrazines , Ritonavir , SARS-CoV-2 , Treatment Outcome
4.
Am J Respir Crit Care Med ; 205(11): 1300-1310, 2022 06 01.
Article in English | MEDLINE | ID: covidwho-2053493

ABSTRACT

Rationale: The most beneficial positive end-expiratory pressure (PEEP) selection strategy in patients with acute respiratory distress syndrome (ARDS) is unknown, and current practice is variable. Objectives: To compare the relative effects of different PEEP selection strategies on mortality in adults with moderate to severe ARDS. Methods: We conducted a network meta-analysis using a Bayesian framework. Certainty of evidence was evaluated using grading of recommendations assessment, development and evaluation methodology. Measurements and Main Results: We included 18 randomized trials (4,646 participants). Compared with a lower PEEP strategy, the posterior probability of mortality benefit from a higher PEEP without lung recruitment maneuver (LRM) strategy was 99% (risk ratio [RR], 0.77; 95% credible interval [CrI], 0.60-0.96, high certainty), the posterior probability of benefit of the esophageal pressure-guided strategy was 87% (RR, 0.77; 95% CrI, 0.48-1.22, moderate certainty), the posterior probability of benefit of a higher PEEP with brief LRM strategy was 96% (RR, 0.83; 95% CrI, 0.67-1.02, moderate certainty), and the posterior probability of increased mortality from a higher PEEP with prolonged LRM strategy was 77% (RR, 1.06; 95% CrI, 0.89-1.22, low certainty). Compared with a higher PEEP without LRM strategy, the posterior probability of increased mortality from a higher PEEP with prolonged LRM strategy was 99% (RR, 1.37; 95% CrI, 1.04-1.81, moderate certainty). Conclusions: In patients with moderate to severe ARDS, higher PEEP without LRM is associated with a lower risk of death than lower PEEP. A higher PEEP with prolonged LRM strategy is associated with increased risk of death when compared with higher PEEP without LRM.


Subject(s)
Positive-Pressure Respiration , Respiratory Distress Syndrome , Adult , Bayes Theorem , Humans , Lung , Network Meta-Analysis , Positive-Pressure Respiration/methods , Respiratory Distress Syndrome/therapy
6.
Front Public Health ; 10: 959073, 2022.
Article in English | MEDLINE | ID: covidwho-2022982

ABSTRACT

Network meta-analysis of deaths from various underlying diseases after COVID-19 infection. This study included more than 10 research centers with the same level of care. In total, 1,676 subjects were included in our study, including 1,122 men and 554 women, patients diagnosed with COVID-19, and combined with underlying diseases; provided data on the number of deaths from related diseases, such as hypertension, diabetes, heart disease, cerebrovascular disease, malignant tumor, chronic kidney disease, chronic liver disease, and respiratory disease. The comparison RR between hypertension and different diseases shows that it is (RR = 2.35, 95% CI: 1.47, 3.98) compared with diabetes, compared with coronary heart disease (RR = 2.57, 95% CI: 1.5, 4.4), compared with cerebrovascular disease (RR = 3.68, 95% CI: 1.87, 7.29), compared with malignant tumor (RR = 6.35, 95% CI: 3.45, 11.97), and compared with chronic kidney disease (RR = 5.53 95% CI: 3.04, 10.34), compared with chronic liver disease (RR = 15.51, 95% CI: 5.26, 50.98), compared with respiratory diseases (RR = 4.35, 95% CI: 2.37, 7.65), RR values are >1, which is statistically significant. The surface under the cumulative ranking curve (SUCRA) showed that the ranking of disease mortality from high to low was hypertension> diabetes> heart disease> cerebrovascular disease> respiratory disease> chronic kidney disease> malignant tumor> chronic liver disease. The study that hypertension, diabetes, and heart disease are the top three risk factors for patients infected with COVID-19, and management of these patients should be strengthened to improve the prognosis of patients. Ethical approval and patient consent are not required as this study is a meta-analysis based on published studies. The results of this network meta-analysis will be submitted to a peer-reviewed journal for the publication.


Subject(s)
COVID-19 , Cerebrovascular Disorders , Diabetes Mellitus , Heart Diseases , Hypertension , Liver Diseases , Neoplasms , Renal Insufficiency, Chronic , Diabetes Mellitus/epidemiology , Female , Humans , Male , Network Meta-Analysis
7.
PLoS One ; 17(8): e0273693, 2022.
Article in English | MEDLINE | ID: covidwho-2021936

ABSTRACT

INTRODUCTION: Several teaching methods have been used in clinical nursing teaching to increase quality and efficiency, but disagreements over their effects persist. This study will evaluate the effects of five teaching methods in clinical nursing on nursing students' knowledge, skill scores, learning satisfaction, and patients' satisfaction. METHODS: We will conduct searches in PubMed, Embase, Web of Science, The Cochrane Library, China National Knowledge Infrastructure Database (CNKI), China Biological literature database (CBM), Wanfang Database, and China Science and Technology Journal Database (CSTJ) up to April 2022. Relevant randomized controlled trials meeting the eligibility criteria will be included. And the study selection and data extraction will be independently screened for eligibility by two authors. The quality of evidence will be evaluated using the Cochrane risk of bias tool. Pairwise meta-analysis and network meta-analysis (NMA) will be conducted using Rev Man, Stata, and R software. Statistical analyses including homogeneity tests, sensitivity analysis, transitivity tests, consistency tests, and publication bias will be completed. ETHICS AND DISSEMINATION: No formal research ethics approval is required. The results will be disseminated to a peer-reviewed journal for publication. PROTOCOL REGISTRATION NUMBER: INPLASY2021120040.


Subject(s)
Research Design , China , Humans , Meta-Analysis as Topic , Network Meta-Analysis
8.
PLoS One ; 17(7): e0270668, 2022.
Article in English | MEDLINE | ID: covidwho-2021849

ABSTRACT

BACKGROUND: A recent prospective meta-analysis demonstrated that interleukin-6 antagonists are associated with lower all-cause mortality in hospitalised patients with COVID-19, compared with usual care or placebo. However, emerging evidence suggests that clinicians are favouring the use of tocilizumab over sarilumab. A new randomised comparison of these agents from the REMAP-CAP trial shows similar effects on in-hospital mortality. Therefore, we initiated a network meta-analysis, to estimate pairwise associations between tocilizumab, sarilumab and usual care or placebo with 28-day mortality, in COVID-19 patients receiving concomitant corticosteroids and ventilation, based on all available direct and indirect evidence. METHODS: Eligible trials randomised hospitalised patients with COVID-19 that compared tocilizumab or sarilumab with usual care or placebo in the prospective meta-analysis or that directly compared tocilizumab with sarilumab. Data were restricted to patients receiving corticosteroids and either non-invasive or invasive ventilation at randomisation. Pairwise associations between tocilizumab, sarilumab and usual care or placebo for all-cause mortality 28 days after randomisation were estimated using a frequentist contrast-based network meta-analysis of odds ratios (ORs), implementing multivariate fixed-effects models that assume consistency between the direct and indirect evidence. FINDINGS: One trial (REMAP-CAP) was identified that directly compared tocilizumab with sarilumab and supplied results on all-cause mortality at 28-days. This network meta-analysis was based on 898 eligible patients (278 deaths) from REMAP-CAP and 3710 eligible patients from 18 trials (1278 deaths) from the prospective meta-analysis. Summary ORs were similar for tocilizumab [0·82 [0·71-0·95, p = 0·008]] and sarilumab [0·80 [0·61-1·04, p = 0·09]] compared with usual care or placebo. The summary OR for 28-day mortality comparing tocilizumab with sarilumab was 1·03 [95%CI 0·81-1·32, p = 0·80]. The p-value for the global test of inconsistency was 0·28. CONCLUSIONS: Administration of either tocilizumab or sarilumab was associated with lower 28-day all-cause mortality compared with usual care or placebo. The association is not dependent on the choice of interleukin-6 receptor antagonist.


Subject(s)
COVID-19 , Adrenal Cortex Hormones/therapeutic use , Antibodies, Monoclonal, Humanized , COVID-19/drug therapy , Humans , Network Meta-Analysis , Prospective Studies , Randomized Controlled Trials as Topic
9.
PLoS One ; 17(9): e0273733, 2022.
Article in English | MEDLINE | ID: covidwho-2009706

ABSTRACT

PURPOSE: During the coronavirus disease 2019 (COVID-19) pandemic, the European Association of Urology (EAU) recommended that courses of intravesical bacillus Calmette-Guérin (BCG) therapy lasting more than 1 year could be safely terminated for patients with high-risk non-muscle-invasive bladder cancer (NMIBC). Thus, we conducted a systematic review and network meta-analysis according to EAU's COVID-19 recommendations. MATERIALS AND METHODS: A systematic review was performed following the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. We conducted a network meta-analysis of recurrence rate in patients with NMIBC receiving induction therapy (M0) and those receiving maintenance therapy lasting 1 year (M1) and more than 1 year (M2). RESULTS: Nineteen studies of 3,957 patients were included for the network meta-analysis. In a node-split forest plot using Bayesian Markov Chain Monte Carlo (MCMC) modeling, there were no differences between the M1 and M2 groups in recurrence rate [odds ratio (OR) 0.95 (0.73-1.2)]. However, recurrence rate in the M0 group was higher than that in the M1 [OR 1.9 (1.5-2.5)] and M2 [OR 2.0 (1.7-2.4)] groups. P-score tests using frequentist inference to rank the treatments in the network demonstrated that the therapy used in the M2 group (P-score 0.8701) was superior to that used in the M1 (P-score 0.6299) and M0 groups (P-score 0). In rank-probability tests using MCMC modeling, the M2 group showed the highest rank, followed by the M1 and M0 groups. CONCLUSION: In the network meta-analysis, there were no differences between those receiving BCG maintenance therapies in terms of recurrence rate. In the rank tests, therapy lasting more than 1-year appears to be most effective. During the COVID-19 pandemic, 1-year maintenance therapy can be used, but after the COVID-19 pandemic, therapy lasting more than 1-year could be beneficial.


Subject(s)
COVID-19 , Mycobacterium bovis , Urinary Bladder Neoplasms , Urology , Adjuvants, Immunologic , Administration, Intravesical , BCG Vaccine/therapeutic use , Bayes Theorem , Duration of Therapy , Humans , Neoplasm Invasiveness , Neoplasm Recurrence, Local/drug therapy , Network Meta-Analysis , Pandemics , Urinary Bladder Neoplasms/drug therapy
10.
J Evid Based Med ; 15(3): 245-262, 2022 Sep.
Article in English | MEDLINE | ID: covidwho-2001688

ABSTRACT

OBJECTIVE: Several vaccines showed a good safety profile and significant efficacy against COVID-19. Moreover, in the absence of direct head to head comparison between COVID-19 vaccines, a network meta-analysis that indirectly compares between them is needed. METHODS: Databases PubMed, CENTRAL, medRxiv, and clinicaltrials.gov were searched. Studies were included if they were placebo-controlled clinical trials and reported the safety profile and/or effectiveness of COVID-19 vaccines. The quality of the included studies was assessed using the Revised Cochrane risk-of-bias tool for randomized trials and the Revised Cochrane risk-of-bias tool for nonrandomized trials. RESULTS: Forty-nine clinical trials that included 421,173 participants and assessed 28 vaccines were included in this network meta-analysis. The network meta-analysis showed that Pfizer is the most effective in preventing COVID-19 infection whereas the Sputnik Vaccine was the most effective in preventing severe COVID-19 infection. In terms of the local and systemic side, the Sinopharm and V-01 vaccines were the safest. CONCLUSION: We found that almost all of the vaccines included in this study crossed the threshold of 50% efficacy. However, some of them did not reach the previously mentioned threshold against the B.1.351 variant while the remainder have not yet investigated vaccine efficacy against this variant. Since each vaccine has its own strong and weak points, we strongly advocate continued vaccination efforts in individualized manner that recommend the best vaccine for each group in the community which is abundantly required to save lives and to avert the emergence of future variants.


Subject(s)
COVID-19 , Vaccines , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Humans , Network Meta-Analysis , SARS-CoV-2
11.
Am J Chin Med ; 50(4): 883-925, 2022.
Article in English | MEDLINE | ID: covidwho-1973868

ABSTRACT

To compare the efficacy of different traditional Chinese medicine (TCM) therapies for the treatment of coronavirus disease 2019 (COVID-19) and provide a higher level of evidence in the form of network meta-analysis (NMA) and systematic review. We searched the studies from the following databases: CNKI, VIP, WanFang, SinoMed, PubMed, Embase, and Web of Science from the establishment of the respective database until December 2021. Relevant studies were screened according to the pre-established inclusion criteria. The quality of the included randomized controlled trials (RCTs) and controlled clinical trials (CCTs) were assessed using the risk of bias (ROB) tool and the Methodological Index for Non-Randomized Studies (MINORS), respectively. R software 4.1.1 and Stata 13.1 were used for data analysis and mapping. A total of 34 studies were included in this network meta-analysis that tested 24 TCM interventions and included 3443 patients. Using cluster analysis of time to negative SARS-CoV-2 reverse transcription-polymerase chain reaction (RT-PCR), the length of hospital stay and composite events, we found that Jinyinhua oral liquid (JYH, 120 mL) + conventional Western medicine (CWM) has the highest SUCRA value at 88.64%, 85.61% and 84.24%. The traditional meta-analysis results revealed that Qingfei Paidu decoction + CWM were significantly different compared with CWM alone for the score of clinical symptoms (MD =-0.75, 95% CI [-1.04, -0.47]). Nine studies reported 57 adverse reactions (ADRs) and 3 adverse events (ADEs) in TCM + CWM groups, and eight studies reported 33 ADRs and 8 ADEs in CWM groups. In conclusion, the combination of TCM and CWM approaches may enhance the efficacy of CWM in COVID-19 patients. Based on the NMA result, JYH (120 mL) + CWM may be a more effective treatment and deserves further investigation. However, the differences in many comparisons between TCM interventions did not reach statistical significance; therefore, further high-quality studies are required to validate these findings.


Subject(s)
COVID-19 , Drugs, Chinese Herbal , COVID-19/drug therapy , Drugs, Chinese Herbal/therapeutic use , Humans , Medicine, Chinese Traditional/methods , Network Meta-Analysis , SARS-CoV-2 , Treatment Outcome
12.
Viruses ; 14(8)2022 08 02.
Article in English | MEDLINE | ID: covidwho-1969513

ABSTRACT

This network meta-analysis compared the clinical efficacy and safety of anti-viral agents for the prevention of disease progression among non-hospitalized patients with COVID-19. PubMed, Embase, Web of Science, Cochrane Library, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform were searched from their inception to 28 May 2022. Only randomized controlled trials (RCTs) that investigated the clinical efficacy of anti-viral agents for non-hospitalized patients with COVID-19 were included. Three RCTs involving 4241 patients were included. Overall, anti-viral agents were associated with a significantly lower risk of COVID-19 related hospitalization or death compared with the placebo (OR, 0.23; 95% CI: 0.06-0.96; p = 0.04). Compared with the placebo, patients receiving nirmatrelvir plus ritonavir had the lowest risk of hospitalization or death (OR, 0.12; 95% CI: 0.06-0.24), followed by remdesivir (OR, 0.13; 95% CI: 0.03-0.57) and then molnupiravir (OR, 0.67; 95% CI: 0.46-0.99). The rank probability for each treatment calculated using the P-score revealed that nirmatrelvir plus ritonavir was the best anti-viral treatment, followed by remdesivir and then molnupiravir. Finally, anti-viral agents were not associated with an increased risk of adverse events compared with the placebo. For non-hospitalized patients with COVID-19 who are at risk of disease progression, the currently recommended three anti-viral agents, nirmatrelvir plus ritonavir, molnupiravir and remdesivir, should continue to be recommended for the prevention of disease progression. Among them, oral nirmatrelvir plus ritonavir and intravenous remdesivir seem to be the better choice, followed by molnupiravir, as determined by this network meta-analysis. Additionally, these three anti-viral agents were shown to be as tolerable as the placebo in this clinical setting.


Subject(s)
COVID-19 , Antiviral Agents/adverse effects , COVID-19/drug therapy , Disease Progression , Humans , Network Meta-Analysis , Randomized Controlled Trials as Topic , Ritonavir/adverse effects , Treatment Outcome
13.
Front Endocrinol (Lausanne) ; 13: 895458, 2022.
Article in English | MEDLINE | ID: covidwho-1963429

ABSTRACT

Aims: This study aimed to assess the impact of different antidiabetic agents on individuals with diabetes and COVID-19. Methods: We searched PubMed, Web of Science, Embase, and Cochrane Library databases from inception to October 31, 2021 and included seven antidiabetic agents. The data were pooled via traditional pairwise meta-analysis and Bayesian network meta-analysis. Results: The pairwise meta-analysis included 35 studies. Metformin (odds ratio (OR), 0.74; P=0.001), dipeptidyl peptidase-4 inhibitors (DPP4i) (OR, 0.88; P=0.04), sodium-glucose cotransporter-2 inhibitors (SGLT2i) (OR, 0.82; P=0.001), and glucagon-like peptide-1 receptor agonists (GLP1RA) (OR, 0.91; P=0.02) treatment were associated with lower COVID-19 mortality in individuals with diabetes compared to respective non-users. However, insulin treatment resulted in higher mortality (OR, 1.8; P=0.001). Mortality did not significantly differ in sulfonylurea (OR, 0.97; P=0.56) and thiazolidinediones (TZDs) (OR, 1.00; P=0.96) users. Furthermore, due to limited data, we analyzed five antidiabetic agents (metformin, DPP4i, sulfonylurea, insulin, and SGLT2i) and found no association between them and severe disease risk (all P>0.05). The Bayesian network meta-analysis included 18 studies. GLP1RA and SGLT2i had the highest first and second rank probability (67.3% and 62.5%, respectively). Insulin showed the maximum probability of ranking seventh (97.0%). Metformin had the third and fourth highest rank probability of 44.8% and 38.9%, respectively. Meanwhile, DPP4i had the fifth-highest rank probability of 42.4%, followed by sulfonylurea at 45.1%. Conclusion: Metformin, DPP4i, SGLT2i, and GLP1RA treatments were highly possible to reduced COVID-19 mortality risk in individuals with diabetes, while insulin might be related to increased mortality risk. Sulfonylurea and TZDs treatments were not associated with mortality. None of the antidiabetic agents studied were associated with the risk of severe disease. Additionally, GLP1RA probably had the most significant protective effect against death, followed by SGLT2i and metformin. Systematic Review Registration: PROSPERO (CRD42021288200).


Subject(s)
COVID-19 , Diabetes Mellitus, Type 2 , Dipeptidyl-Peptidase IV Inhibitors , Metformin , Sodium-Glucose Transporter 2 Inhibitors , Thiazolidinediones , Bayes Theorem , COVID-19/drug therapy , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Dipeptidyl-Peptidase IV Inhibitors/therapeutic use , Humans , Hypoglycemic Agents/therapeutic use , Insulin/therapeutic use , Metformin/therapeutic use , Network Meta-Analysis , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Thiazolidinediones/therapeutic use , Treatment Outcome
14.
CMAJ ; 194(28): E969-E980, 2022 07 25.
Article in English | MEDLINE | ID: covidwho-1963063

ABSTRACT

BACKGROUND: Randomized trial evidence suggests that some antiviral drugs are effective in patients with COVID-19. However, the comparative effectiveness of antiviral drugs in nonsevere COVID-19 is unclear. METHODS: We searched the Epistemonikos COVID-19 L·OVE (Living Overview of Evidence) database for randomized trials comparing antiviral treatments, standard care or placebo in adult patients with nonsevere COVID-19 up to Apr. 25, 2022. Reviewers extracted data and assessed risk of bias. We performed a frequentist network meta-analysis and assessed the certainty of evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. RESULTS: We identified 41 trials, which included 18 568 patients. Compared with standard care or placebo, molnupiravir and nirmatrelvir-ritonavir each reduced risk of death with moderate certainty (10.9 fewer deaths per 1000, 95% confidence interval [CI] 12.6 to 4.5 fewer for molnupiravir; 11.7 fewer deaths per 1000, 95% CI 13.1 fewer to 2.6 more). Compared with molnupiravir, nirmatrelvir-ritonavir probably reduced risk of hospital admission (27.8 fewer admissions per 1000, 95% CI 32.8 to 18.3 fewer; moderate certainty). Remdesivir probably has no effect on risk of death, but may reduce hospital admissions (39.1 fewer admissions per 1000, 95% CI 48.7 to 13.7 fewer; low certainty). INTERPRETATION: Molnupiravir and nirmatrelvir-ritonavir probably reduce risk of hospital admissions and death among patients with nonsevere COVID-19. Nirmatrelvir-ritonavir is probably more effective than molnupiravir for reducing risk of hospital admissions. Most trials were conducted with unvaccinated patients, before the emergence of the Omicron variant; the effectiveness of these drugs must thus be tested among vaccinated patients and against newer variants.


Subject(s)
COVID-19 , Adult , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Humans , Network Meta-Analysis , Ritonavir/therapeutic use , SARS-CoV-2
15.
PLoS One ; 17(6): e0270196, 2022.
Article in English | MEDLINE | ID: covidwho-1963014

ABSTRACT

BACKGROUND: The ongoing COVID-19 pandemic has claimed >4 million lives globally, and these deaths often occurred in hospitalized patients with comorbidities. Therefore, the proposed review aims to distinguish the inpatient mortality and invasive mechanical ventilation risk in COVID-19 patients treated with the anti-SARS-CoV-2 monoclonal antibodies and/or the antiviral agents. METHODS: A search in PubMed, Embase, and Scopus will ensue for the publications on randomized controlled trials testing the above, irrespective of the publication date or geographic boundary. Risk of bias assessment of the studies included in the review will occur using the Cochrane risk of bias tool for randomized trials (RoB 2). Frequentist method network meta-analyses (NMA) will compare each outcome's risk across both types of anti-SARS-CoV-2 agents in one model and each in separate models. Additional NMA models will compare these in COVID-19 patients who were severely or critically ill, immunocompromised, admitted to the intensive care unit, diagnosed by nucleic acid amplification test, not treated with steroids, <18 years old, and at risk of infection due to variants of concern. The plan of excluding non-hospitalized patients from the proposed review is to minimize intransitivity risk. The acceptance of the network consistency assumption will transpire if the local and overall inconsistency assessment indicates no inconsistency. For each NMA model, the effect sizes (risk ratio) and their 95% confidence intervals will get reported in league tables. The best intervention prediction and quality of evidence grading will happen using the surface under the cumulative ranking curve values and the Grading of Recommendations Assessment, Development and Evaluation-based Confidence in Network Meta-Analysis approach, respectively. Sensitivity analysis will repeat the preliminary NMA while excluding the trials at high risk of bias. The Stata statistical software (v16) will be used for analysis. The statistical significance will get determined at p<0.05 and 95% confidence interval. TRIAL REGISTRATION: PROSPERO Registration No: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021277663.


Subject(s)
COVID-19 , Adolescent , Antibodies, Monoclonal/therapeutic use , Antibodies, Viral , Antiviral Agents/therapeutic use , Humans , Meta-Analysis as Topic , Network Meta-Analysis , Pandemics , Respiration, Artificial , Systematic Reviews as Topic , Treatment Outcome
16.
BMJ ; 378: e070022, 2022 07 04.
Article in English | MEDLINE | ID: covidwho-1932663

ABSTRACT

OBJECTIVE: To assess the benefits and harms of different types and doses of anticoagulant drugs for the prevention of venous thromboembolism in patients who are acutely ill and admitted to hospital. DESIGN: Systematic review and network meta-analysis. DATA SOURCES: Cochrane CENTRAL, PubMed/Medline, Embase, Web of Science, clinical trial registries, and national health authority databases. The search was last updated on 16 November 2021. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Published and unpublished randomised controlled trials that evaluated low or intermediate dose low-molecular-weight heparin, low or intermediate dose unfractionated heparin, direct oral anticoagulants, pentasaccharides, placebo, or no intervention for the prevention of venous thromboembolism in acutely ill adult patients in hospital. MAIN OUTCOME MEASURES: Random effects, bayesian network meta-analyses used four co-primary outcomes: all cause mortality, symptomatic venous thromboembolism, major bleeding, and serious adverse events at or closest timing to 90 days. Risk of bias was also assessed using the Cochrane risk-of-bias 2.0 tool. The quality of evidence was graded using the Confidence in Network Meta-Analysis framework. RESULTS: 44 randomised controlled trials that randomly assigned 90 095 participants were included in the main analysis. Evidence of low to moderate quality suggested none of the interventions reduced all cause mortality compared with placebo. Pentasaccharides (odds ratio 0.32, 95% credible interval 0.08 to 1.07), intermediate dose low-molecular-weight heparin (0.66, 0.46 to 0.93), direct oral anticoagulants (0.68, 0.33 to 1.34), and intermediate dose unfractionated heparin (0.71, 0.43 to 1.19) were most likely to reduce symptomatic venous thromboembolism (very low to low quality evidence). Intermediate dose unfractionated heparin (2.63, 1.00 to 6.21) and direct oral anticoagulants (2.31, 0.82 to 6.47) were most likely to increase major bleeding (low to moderate quality evidence). No conclusive differences were noted between interventions regarding serious adverse events (very low to low quality evidence). When compared with no intervention instead of placebo, all active interventions did more favourably with regard to risk of venous thromboembolism and mortality, and less favourably with regard to risk of major bleeding. The results were robust in prespecified sensitivity and subgroup analyses. CONCLUSIONS: Low-molecular-weight heparin in an intermediate dose appears to confer the best balance of benefits and harms for prevention of venous thromboembolism. Unfractionated heparin, in particular the intermediate dose, and direct oral anticoagulants had the least favourable profile. A systematic discrepancy was noted in intervention effects that depended on whether placebo or no intervention was the reference treatment. Main limitations of this study include the quality of the evidence, which was generally low to moderate due to imprecision and within-study bias, and statistical inconsistency, which was addressed post hoc. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020173088.


Subject(s)
Thrombosis , Venous Thromboembolism , Anticoagulants/adverse effects , Bayes Theorem , Hemorrhage/chemically induced , Hemorrhage/drug therapy , Heparin/adverse effects , Heparin, Low-Molecular-Weight/adverse effects , Hospitals , Humans , Network Meta-Analysis , Randomized Controlled Trials as Topic , Thrombosis/drug therapy , Venous Thromboembolism/drug therapy
17.
BMJ ; 377: e069989, 2022 05 31.
Article in English | MEDLINE | ID: covidwho-1874530

ABSTRACT

OBJECTIVE: To evaluate the effectiveness of heterologous and homologous covid-19 vaccine regimens with and without boosting in preventing covid-19 related infection, hospital admission, and death. DESIGN: Living systematic review and network meta-analysis. DATA SOURCES: World Health Organization covid-19 databases, including 38 sources of published studies and preprints. STUDY SELECTION: Randomised controlled trials, cohort studies, and case-control studies. METHODS: 38 WHO covid-19 databases were searched on a weekly basis from 8 March 2022. Studies that assessed the effectiveness of heterologous and homologous covid-19 vaccine regimens with or without a booster were identified. Studies were eligible when they reported the number of documented, symptomatic, severe covid-19 infections, covid-19 related hospital admissions, or covid-19 related deaths among populations that were vaccinated and unvaccinated. The primary measure was vaccine effectiveness calculated as 1-odds ratio. Secondary measures were surface under the cumulative ranking curve (SUCRA) scores and the relative effects for pairwise comparisons. The risk of bias was evaluated by using the risk of bias in non-randomised studies of interventions (ROBINS-I) tool for all cohort and case-control studies. The Cochrane risk of bias tool (version 2; ROB-2) was used to assess randomised controlled trials. RESULTS: The first round of the analysis comprised 53 studies. 24 combinations of covid-19 vaccine regimens were identified, of which a three dose mRNA regimen was found to be the most effective against asymptomatic and symptomatic covid-19 infections (vaccine effectiveness 96%, 95% credible interval 72% to 99%). Heterologous boosting using two dose adenovirus vector vaccines with one mRNA vaccine has a satisfactory vaccine effectiveness of 88% (59% to 97%). A homologous two dose mRNA regimen has a vaccine effectiveness of 99% (79% to 100%) in the prevention of severe covid-19 infections. Three dose mRNA is the most effective in reducing covid-19 related hospital admission (95%, 90% to 97%). The vaccine effectiveness against death in people who received three doses of mRNA vaccine remains uncertain owing to confounders. In the subgroup analyses, a three dose regimen is similarly effective in all age groups, even in the older population (≥65 years). A three dose mRNA regimen works comparably well in patients who are immunocompromised and those who are non-immunocompromised. Homologous and heterologous three dose regimens are effective in preventing infection by covid-19 variants (alpha, delta, and omicron). CONCLUSION: An mRNA booster is recommended to supplement any primary vaccine course. Heterologous and homologous three dose regimens work comparably well in preventing covid-19 infections, even against different variants. The effectiveness of three dose vaccine regimens against covid-19 related death remains uncertain. SYSTEMATIC REVIEW REGISTRATION: This review was not registered. The protocol is included in the supplementary document. READERS' NOTE: This article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication.


Subject(s)
COVID-19 Vaccines , COVID-19 , Aged , COVID-19/epidemiology , COVID-19/prevention & control , Humans , Network Meta-Analysis , RNA, Messenger , SARS-CoV-2 , Vaccines, Synthetic
18.
Sci Rep ; 12(1): 5823, 2022 04 06.
Article in English | MEDLINE | ID: covidwho-1784020

ABSTRACT

Several concerns regarding the safety of face masks use have been propounded in public opinion. The objective of this review is to examine if these concerns find support in the literature by providing a comprehensive overview of physiological responses to the use of face masks. We have performed a systematic review, pairwise and network meta-analyses to investigate physiological responses to the use of face masks. The study has been registered with PROSPERO (C RD42020224791). Obtained results were screened using our exclusion and inclusion criteria. Meta-analyses were performed using the GeMTC and meta R packages. We have identified 26 studies meeting our inclusion and exclusion criteria, encompassing 751 participants. The use of face masks was not associated with significant changes in pulsoxymetrically measured oxygen saturation, even during maximal-effort exercises. The only significant physiological responses to the use of face masks during low-intensity activities were a slight increase in heart rate, mildly elevated partial pressure of carbon dioxide (not meeting criteria for hypercarbia), increased temperature of facial skin covered by the mask, and subsequent increase of the score in the rating of heat perception, with N95 filtering facepiece respirators having a greater effect than surgical masks. In high-intensity conditions, the use of face masks was associated with decreased oxygen uptake, ventilation, and RR. Face masks are safe to use and do not cause significant alterations in human physiology. The increase in heart rate stems most likely from increased respiratory work required to overcome breathing resistance. The increase in carbon dioxide is too small to be clinically relevant. An increased rating of heat perception when using face masks results from higher temperature of facial skin covered by the mask.


Subject(s)
COVID-19 , Masks , Bayes Theorem , Carbon Dioxide , Humans , Network Meta-Analysis , SARS-CoV-2
19.
Br J Clin Pharmacol ; 88(9): 4080-4091, 2022 09.
Article in English | MEDLINE | ID: covidwho-1769686

ABSTRACT

AIMS: To perform network meta-analysis for a head-to-head comparison of various interventions used in coronavirus disease 2019 (COVID-19) on mortality, clinical recovery, time to clinical improvement and the occurrence of serious adverse events. METHODS: Systematic search was performed using online databases with suitable MeSH terms including coronavirus, COVID-19, randomized controlled trial, hydroxychloroquine, lopinavir/ritonavir, tocilizumab, remdesivir, favipiravir, dexamethasone and interferon-ß. Data were independently extracted by 2 study investigators and analysed. RESULTS: Out of 1225 studies screened, 23 were included for qualitative and quantitative analysis. Among the drugs studied, dexamethasone reduces mortality by 10%, with a relative risk of 0.90 (95% confidence interval [0.82-0.97]) and increases clinical recovery by 6% (relative risk 1.06, 95% confidence interval [1.02-1.10]) compared to standard of care. Similarly, remdesivir administered for 10 days increased clinical recovery by 10%, reduced time to clinical improvement by 4 days and lowered the occurrence of serious adverse events by 27% as compared to standard of care. CONCLUSION: In comparison to standard of care, dexamethasone was found to increase clinical recovery and lower mortality; remdesivir was significantly associated with a lower risk of mortality as compared to tocilizumab and higher clinical recovery and shorter time to clinical improvement as compared to hydroxychloroquine and tocilizumab; remdesivir followed by tocilizumab were found to have lesser occurrence of serious adverse events in patients with moderate to severe COVID-19.


Subject(s)
Antiviral Agents , COVID-19 , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Dexamethasone/therapeutic use , Humans , Hydroxychloroquine/therapeutic use , Lopinavir/therapeutic use , Network Meta-Analysis , Randomized Controlled Trials as Topic , Treatment Outcome
20.
Infection ; 50(6): 1453-1463, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-1767728

ABSTRACT

PURPOSE: As no reported randomized control trials (RCTs) directly compare the three administration doses of anticoagulants (prophylactic dose, treatment dose, and no treatment), the most recommended dose to be administered to patients with coronavirus disease 2019 (COVID-19) remains unclear. The purpose of this study was to examine the effects of anticoagulant doses administered to patients with COVID-19, using a network meta-analysis (NMA) including high-quality studies. METHODS: All eligible trials from the Cochrane Central Register of Controlled Trials, MEDLINE, and Clinicaltrials.gov were included. We included RCTs and observational studies adjusted for covariates for patients aged ≥ 18 years and hospitalized due to objectively confirmed COVID-19. The main study outcome was mortality. RESULTS: In patients with moderate COVID-19, the prophylactic (relative risk (RR) 0.64 [95% confidence interval (CI) 0.52-0.80]) and treatment dose (RR 0.57 [95% CI 0.45-0.72] were associated with a lower risk of short-term mortality than that with no anticoagulant treatment. However, the prophylactic and treatment dose groups were not significantly different. The hierarchy for efficacy in reducing short-term mortality was treatment dose (P score 92.4) > prophylactic dose (57.6) > no treatment (0.0). In patients with severe COVID-19, due to the absence of trials with the no-treatment group, NMA could not be conducted. However, pairwise comparison did not show a significant difference between the prophylactic and treatment dose groups. CONCLUSIONS: Treatment and prophylactic doses of anticoagulants showed similar effects on mortality; however, the treatment dose is preferred over the prophylactic dose for patients with both moderate and severe COVID-19. TRIAL REGISTRATION NUMBER AND REGISTRATION DATES: PROSPERO (registration number: CRD42021245308, 05/21/2021).


Subject(s)
Anticoagulants , COVID-19 , Humans , Anticoagulants/therapeutic use , Network Meta-Analysis , COVID-19/drug therapy
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