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Cytotherapy Sep 2023The advanced therapy product tisagenlecleucel is a CD19-directed genetically modified autologous T-cell immunotherapy that has brought hope for children and young adults...
A systematic review on the cost-effectiveness assessment of tisagenlecleucel for refractory or relapsing B-cell acute lymphoblastic leukemia (R/R B-ALL) treatment in children and young adults.
BACKGROUND AIMS
The advanced therapy product tisagenlecleucel is a CD19-directed genetically modified autologous T-cell immunotherapy that has brought hope for children and young adults with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). We sought to evaluate the cost-effectiveness of tisagenlecleucel compared with conventional salvage therapies in pediatric and young adult patients with R/R B-ALL.
METHODS
This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses parameters as registered in International Prospective Register of Systematic Reviews (CRD42021266998). Literature was searched using the MEDLINE databases via PubMed, EMBASE, Lilacs, the Cochrane Central Register of Controlled Trials and Web of Science in January 2022. Titles were screened independently by two reviewers. Articles deemed to meet the inclusion criteria were screened independently on abstract, and full texts were reviewed.
RESULTS
In total, 5627 publications were identified, from which six eligible studies were selected. The conventional therapies identified were blinatumomab (Blina), clofarabine monotherapy (Clo-M), clofarabine combined with cyclophosphamide and etoposide (Clo-C) and the combination of fludarabine, cytarabine and idarubicin (FLA-IDA). The discounted incremental cost-effectiveness ratio (ICER) per quality-adjusted life year (QALY) gained for tisagenlecleucel compared with Clo-C and Blina averages was $38 837 and $25 569, respectively. In relation to the cost of the drug, the average of tisagenlecleucel was approximately 4.3 times, 10.8 times or 4.7 times greater than the Clo-M, Clo-C and Blina, respectively.
CONCLUSIONS
This systematic review highlighted that tisagenlecleucel is a much more expensive therapy than conventional alternatives. However, tisagenlecleucel performed well on the ICER, not exceeding $100 000/QALY. It was also found that the advanced therapy product was more effective than the conventional small molecule and biological drugs, in terms of life years and QALY gained.
Topics: Humans; Young Adult; Child; Clofarabine; Cost-Benefit Analysis; Receptors, Antigen, T-Cell; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Recurrence
PubMed: 37341664
DOI: 10.1016/j.jcyt.2023.05.011 -
Expert Review of Anticancer Therapy 2024Poly(adenosine diphosphate [ADP]-ribose) polymerase inhibitors (PARPi) treatment for ovarian cancer (OC) are ever-changing. This study aimed to compare the efficacy and... (Comparative Study)
Comparative Study Meta-Analysis Review
Comparison of poly (ADP-ribose) polymerase inhibitors (PARPis) as maintenance therapy for newly-diagnosed and platinum-sensitive recurrent ovarian cancer with mutational status: a systematic review and network meta-analysis.
BACKGROUND
Poly(adenosine diphosphate [ADP]-ribose) polymerase inhibitors (PARPi) treatment for ovarian cancer (OC) are ever-changing. This study aimed to compare the efficacy and overall safety of available PARPi as maintenance therapy for BRCA mutation status in patients with newly diagnosed and platinum-sensitive recurrent (PSR) OC patients.
RESEARCH DESIGN AND METHODS
Relevant RCTs were systematically retrieved from PubMed and Embase until 31 May 2022. Progression-free survival (PFS) and overall survival (OS) based on mutation status and adverse events (AEs) regardless of mutation were efficacy and safety endpoints.
RESULTS
In newly diagnosed BRCAm-OC patients, olaparib (HR: 0.33; 95% confidence interval [CI]: 0.25, 0.43) and other PARPis [niraparib (HR: 0.40; 95% CI: 0.29, 0.55), rucaparib (HR: 0.40; 95% CI: 0.21, 0.76) and veliparib (HR: 0.44; 95% CI: 0.28, 0.69)] had a statistically significant effect on PFS versus placebo. In BRCAm-PSROC patients, Olaparib exhibited significant benefit (HR: 0.69; 95% CI: 0.54, 0.88) for OS compared to other PARPis. In BRCAwt-PSR OC patients, Olaparib showed a favorable OS benefit than other PARPis (HR: 0.84; 95% CI: 0.57,1.22). Overall, safety profile of all PARPis was acceptable.
CONCLUSION
All PARPis showed significant benefit, with olaparib showing greater benefit in newly diagnosed and PSR OC women.
REGISTRATION
CRD42021288932.
Topics: Female; Humans; Adenosine Diphosphate; Carcinoma, Ovarian Epithelial; Neoplasm Recurrence, Local; Network Meta-Analysis; Ovarian Neoplasms; Poly(ADP-ribose) Polymerase Inhibitors; Poly(ADP-ribose) Polymerases; Ribose
PubMed: 38174379
DOI: 10.1080/14737140.2023.2298832 -
Progress in Neuro-psychopharmacology &... Mar 2015Uric acid and purines (such as adenosine) regulate mood, sleep, activity, appetite, cognition, memory, convulsive threshold, social interaction, drive, and impulsivity.... (Review)
Review
Uric acid and purines (such as adenosine) regulate mood, sleep, activity, appetite, cognition, memory, convulsive threshold, social interaction, drive, and impulsivity. A link between purinergic dysfunction and mood disorders was first proposed a century ago. Interestingly, a recent nationwide population-based study showed elevated risk of gout in subjects with bipolar disorder (BD), and a recent meta-analysis and systematic review of placebo-controlled trials of adjuvant purinergic modulators confirmed their benefits in bipolar mania. Uric acid may modulate energy and activity levels, with higher levels associated with higher energy and BD spectrum. Several recent genetic studies suggest that the purinergic system - particularly the modulation of P1 and P2 receptor subtypes - plays a role in mood disorders, lending credence to this model. Nucleotide concentrations can be measured using brain spectroscopy, and ligands for in vivo positron emission tomography (PET) imaging of adenosine (P1) receptors have been developed, thus allowing potential target engagement studies. This review discusses the key role of the purinergic system in the pathophysiology of mood disorders. Focusing on this promising therapeutic target may lead to the development of therapies with antidepressant, mood stabilization, and cognitive effects.
Topics: Adenosine; Adenosine Triphosphate; Animals; Biomarkers; Guanosine; Humans; Models, Neurological; Molecular Targeted Therapy; Mood Disorders; Neuroimaging; Psychotropic Drugs; Receptors, Purinergic
PubMed: 25445063
DOI: 10.1016/j.pnpbp.2014.10.016 -
BMJ Open Mar 2022To summarise specific adverse effects of remdesivir, hydroxychloroquine and lopinavir/ritonavir in patients with COVID-19. (Meta-Analysis)
Meta-Analysis
BACKGROUND
To summarise specific adverse effects of remdesivir, hydroxychloroquine and lopinavir/ritonavir in patients with COVID-19.
METHODS
We searched 32 databases through 27 October 2020. We included randomised trials comparing any of the drugs of interest to placebo or standard care, or against each other. We conducted fixed-effects pairwise meta-analysis and assessed the certainty of evidence using the grading of recommendations assessment, development and evaluation approach.
RESULTS
We included 16 randomised trials which enrolled 8152 patients. For most interventions and outcomes the certainty of the evidence was very low to low except for gastrointestinal adverse effects from hydroxychloroquine, which was moderate certainty. Compared with standard care or placebo, low certainty evidence suggests that remdesivir may not have an important effect on acute kidney injury (risk difference (RD) 8 fewer per 1000, 95% CI 27 fewer to 21 more) or cognitive dysfunction/delirium (RD 3 more per 1000, 95% CI 12 fewer to 19 more). Low certainty evidence suggests that hydroxychloroquine may increase the risk of cardiac toxicity (RD 10 more per 1000, 95% CI 0 more to 30 more) and cognitive dysfunction/delirium (RD 33 more per 1000, 95% CI 18 fewer to 84 more), whereas moderate certainty evidence suggests hydroxychloroquine probably increases the risk of diarrhoea (RD 106 more per 1000, 95% CI 48 more to 175 more) and nausea and/or vomiting (RD 62 more per 1000, 95% CI 23 more to 110 more) compared with standard care or placebo. Low certainty evidence suggests lopinavir/ritonavir may increase the risk of diarrhoea (RD 168 more per 1000, 95% CI 58 more to 330 more) and nausea and/or vomiting (RD 160 more per 1000, 95% CI 100 more to 210 more) compared with standard care or placebo.
DISCUSSION
Hydroxychloroquine probably increases the risk of diarrhoea and nausea and/or vomiting and may increase the risk of cardiac toxicity and cognitive dysfunction/delirium. Lopinavir/ritonavir may increase the risk of diarrhoea and nausea and/or vomiting. Remdesivir may have no important effect on risk of acute kidney injury or cognitive dysfunction/delirium. These findings provide important information to support the development of evidence-based management strategies for patients with COVID-19.
Topics: Adenosine Monophosphate; Alanine; Drug Combinations; Humans; Hydroxychloroquine; Lopinavir; Randomized Controlled Trials as Topic; Ritonavir; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 35236729
DOI: 10.1136/bmjopen-2020-048502 -
Journal of Obesity 2024Type 2 diabetes mellitus and metabolic syndrome represent two closely intertwined public health challenges that have reached alarming epidemic proportions in low- and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Type 2 diabetes mellitus and metabolic syndrome represent two closely intertwined public health challenges that have reached alarming epidemic proportions in low- and middle-income countries, particularly in sub-Saharan Africa. Therefore, the current study aimed to determine the weighted pooled prevalence of metabolic syndrome and its components among individuals with type 2 diabetes mellitus in sub-Saharan Africa as defined by the 2004 National Cholesterol Education Program-Adult Treatment Panel (NCEP-ATP III 2004) and/or the International Diabetes Federation (IDF) criteria.
METHODS
A systematic search was conducted to retrieve studies published in the English language on the prevalence of metabolic syndrome among type 2 diabetic individuals in sub-Saharan Africa. Searches were carried out in PubMed, Embase, Scopus, Google Scholar, African Index Medicus, and African Journal Online from their inception until July 31, 2023. A random-effects model was employed to estimate the weighted pooled prevalence of metabolic syndrome in sub-Saharan Africa. Evidence of between-study variance attributed to heterogeneity was assessed using Cochran's Q statistic and the I2 statistic. The Joanna Briggs Institute quality appraisal criteria were used to evaluate the methodological quality of the included studies. The summary estimates were presented with forest plots and tables. Publication bias was checked with the funnel plot and Egger's regression test.
RESULTS
Overall, 1421 articles were identified and evaluated using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, and 30 studies that met the inclusion criteria were included in the final analysis. The weighted pooled prevalence of metabolic syndrome among individuals with type 2 diabetes mellitus in sub-Saharan Africa was 63.1% (95% CI: 57.9-68.1) when using the NCEP-ATP III 2004 criteria and 60.8% (95% CI: 50.7-70.0) when using the IDF criteria. Subgroup analysis, using NCEP-ATP III 2004 and IDF criteria, revealed higher weighted pooled prevalence among females: 73.5% (95% CI: 67.4-79.5), 71.6% (95% CI: 60.2-82.9), compared to males: 50.5% (95% CI: 43.8-57.2), 44.5% (95% CI: 34.2-54.8), respectively. Central obesity was the most prevalent component of metabolic syndrome, with a pooled prevalence of 55.9% and 61.6% using NCEP-ATP III 2004 and IDF criteria, respectively. There was no statistical evidence of publication bias in both the NCEP-ATP III 2004 and IDF pooled estimates.
CONCLUSIONS
The findings underscore the alarming prevalence of metabolic syndrome among individuals with type 2 diabetes mellitus in sub-Saharan Africa. Therefore, it is essential to promote lifestyle modifications, such as regular exercise and balanced diets, prioritize routine obesity screenings, and implement early interventions and robust public health measures to mitigate the risks associated with central obesity.
Topics: Male; Adult; Female; Humans; Metabolic Syndrome; Diabetes Mellitus, Type 2; Risk Factors; Obesity, Abdominal; Prevalence; Obesity; Africa South of the Sahara; Adenosine Triphosphate
PubMed: 38410415
DOI: 10.1155/2024/1240457 -
Journal of Medical Virology Feb 2021Treatment options for severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) are limited with no clarity on efficacy and safety profiles. We performed a... (Meta-Analysis)
Meta-Analysis
Treatment options for severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) are limited with no clarity on efficacy and safety profiles. We performed a systematic review and meta-analysis of studies on patients ≥18 years reporting data on therapeutic interventions in SARS-CoV-2. Primary outcome was all-cause mortality and secondary outcomes were rates of mechanical ventilation, viral clearance, adverse events, discharge, and progression to severe disease. Pooled rates and odds ratios (OR) were calculated. Twenty-nine studies with 5207 patients were included. Pooled all-cause mortality in intervention arm was 12.8% (95% confidence interval [CI]: 8.1%-17.4%). Mortality was significantly higher for studies using hydroxychloroquine (HCQ) for intervention (OR: 1.36; 95% CI: 0.97-1.89). Adverse events were also higher in HCQ subgroup (OR: 3.88; 95% CI: 1.60-9.45). There was no difference in other secondary outcomes. There is a need for well-designed randomized clinical trials for further investigation of every therapeutic intervention for further insight into different therapeutic options.
Topics: Adenosine Monophosphate; Adrenal Cortex Hormones; Alanine; Antibodies, Monoclonal, Humanized; Antiviral Agents; COVID-19; Drug Administration Schedule; Drug Combinations; Female; Humans; Hydroxychloroquine; Immunization, Passive; Lopinavir; Male; Middle Aged; Odds Ratio; Ritonavir; SARS-CoV-2; Survival Analysis; Treatment Outcome; COVID-19 Serotherapy
PubMed: 32667699
DOI: 10.1002/jmv.26302 -
Journal of Food Protection Dec 2022Adherence to proper environmental cleaning practices is critical in food establishments. To validate cleanliness, cleaning practices should be routinely monitored,... (Meta-Analysis)
Meta-Analysis
Relationship between ATP Bioluminescence Measurements and Microbial Assessments in Studies Conducted in Food Establishments: A Systematic Literature Review and Meta-Analysis.
ABSTRACT
Adherence to proper environmental cleaning practices is critical in food establishments. To validate cleanliness, cleaning practices should be routinely monitored, preferably by a rapid, reliable, and cost-effective method. The aim of this study was to determine whether a correlation exists between ATP bioluminescence measurements and selected microbial assessments in studies conducted in food establishments. A systematic literature review and meta-analysis was conducted using the principles of preferred reporting items for systematic reviews and meta-analyses. Twelve online databases and search engines were selected for the review. Peer-reviewed articles published in English between January 2000 and July 2020 were included in the search. From a total of 19 eligible studies, 3 that included Pearson correlation coefficients (r) between ATP bioluminescence measurements and microbial assessments were used for the meta-analysis calculations. Only the fixed-effect model produced a strong correlation because one value dominated the estimates: r = 0.9339 (0.9278, 0.9399). In contrast, both the random effects model, 0.2978 (0.24, 0.3471), and the mixed effects model, r = 0.3162 (-0.0387, 0.6711), indicated a weak relationship between ATP bioluminescence and microbial assessments, with no evidence of a strong correlation. The meta-analysis results indicated no sufficient evidence of a strong correlation between ATP bioluminescence measurements and microbial assessments when applied within food establishments. This lack of evidence for a strong correlation between the results of these two monitoring tools suggests that food establishments cannot depend on only one method. Yet, with immediate feedback and quantification of organic soiling, ATP bioluminescence could be an effective monitoring tool to use in food establishments.
Topics: Colony Count, Microbial; Adenosine Triphosphate; Luminescent Measurements; Food
PubMed: 36173898
DOI: 10.4315/JFP-22-187 -
Environmental Pollution (Barking, Essex... Nov 2022This systematic review aims to discover the plausible mechanism of Ozone in A.D., to boost translational research. The main focus of our review lies in understanding the... (Review)
Review
This systematic review aims to discover the plausible mechanism of Ozone in A.D., to boost translational research. The main focus of our review lies in understanding the effects of ozone pollution on the human brain and causing degenerative disease. Owing to the number of works carried out as preclinical evidence in association with oxidative stress and Alzheimer's disease and the lack of systematic review or meta-analysis prompted us to initiate a study on Alzheimer's risk due to ground-level ozone. We found relevant studies from PubMed, ScienceDirect, Proquest, DOAJ, and Scopus, narrowing to animal studies and the English language without any time limit. The searches will be re-run before the final analysis. This work was registered in Prospero with Reg ID CRD42022319360, followed the PRISMA-P framework, and followed the PICO approach involving Population, Intervention/Exposure, Comparison, and Outcomes data. Bibliographic details of 16 included studies were studied for Exposure dose of ozone, duration, exposure, and frequency with control and exposure groups. Primary and secondary outcomes were assessed based on pathology significance, and results were significant in inducing Alzheimer-like pathology by ozone. In conclusion, ozone altered oxidative stress, metabolic pathway, and amyloid plaque accumulation besides endothelial stress response involving mitochondria as the critical factor in ATP degeneration, caspase pathway, and neuronal damage. Thus, ozone is a criteria pollutant to be focused on in mitigating Alzheimer's Disease pathology.
Topics: Animals; Humans; Adenosine Triphosphate; Alzheimer Disease; Amyloid beta-Peptides; Caspases; Environmental Pollutants; Memory Disorders; Meta-Analysis as Topic; Ozone
PubMed: 36089140
DOI: 10.1016/j.envpol.2022.120136 -
ACS Biomaterials Science & Engineering May 2022Biomaterial-associated infection is difficult to detect and brings consequences that can lead to morbidity and mortality. Bacteria can adhere to the implant surface,... (Meta-Analysis)
Meta-Analysis Review
Biomaterial-associated infection is difficult to detect and brings consequences that can lead to morbidity and mortality. Bacteria can adhere to the implant surface, grow, and form biofilms. Antimicrobial peptides (AMPs) can target and kill bacterial cells using a plethora of mechanisms of action such as rupturing the cell membrane by creating pores via depolarization with their cationic and amphipathic nature. AMPs can thus be coated onto metal implants to prevent microbial cell adhesion and growth. The aim of this systematic review was to determine the potential clinical applications of AMP-modified implants through in vivo induced infection models. Following a database search recently up to 22 January 2022 using PubMed, Web of Science and Cochrane databases, and abstract/title screening using the PRISMA framework, 24 studies remained, of which 18 were used in the random effects meta-analysis of standardized mean differences (SMD) to get effect sizes. Quality of studies was assessed using SYRCLE's risk of bias tool. The data from these 18 studies showed that AMPs carry antibacterial effects, and the meta-analysis confirmed the favorited antibacterial efficacy of AMP-coated groups over controls (SMD -1.74, 95%CI [-2.26, -1.26], < 0.00001). Subgroup analysis showed that the differences in effect size are random, and high heterogeneity values suggested the same. HHC36 and vancomycin were the most common AMPs for surface modification and , the most tested bacterium in vivo. Covalent binding with polymer brush coating and physical layer-by-layer incorporation of AMPs were recognized as key methods of incorporation to achieve desired densities. The use of fusion peptides seemed admirable to incorporate additional benefits such as osteointegration and wound healing and possibly targeting more microbe strains. Further investigation into the incorporation methods, AMP activity against different bacterial strains, and the number of AMPs used for metal implant surface modification is needed to progress toward potential clinical application.
Topics: Adenosine Monophosphate; Anti-Bacterial Agents; Antimicrobial Peptides; Bacteria; Biofilms; Staphylococcus aureus
PubMed: 35412810
DOI: 10.1021/acsbiomaterials.1c01307 -
The Cochrane Database of Systematic... Aug 2021Remdesivir is an antiviral medicine with properties to inhibit viral replication of SARS-CoV-2. Positive results from early studies attracted media attention and led to...
BACKGROUND
Remdesivir is an antiviral medicine with properties to inhibit viral replication of SARS-CoV-2. Positive results from early studies attracted media attention and led to emergency use authorisation of remdesivir in COVID-19. A thorough understanding of the current evidence regarding the effects of remdesivir as a treatment for SARS-CoV-2 infection based on randomised controlled trials (RCTs) is required.
OBJECTIVES
To assess the effects of remdesivir compared to placebo or standard care alone on clinical outcomes in hospitalised patients with SARS-CoV-2 infection, and to maintain the currency of the evidence using a living systematic review approach.
SEARCH METHODS
We searched the Cochrane COVID-19 Study Register (which comprises the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase, ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, and medRxiv) as well as Web of Science (Science Citation Index Expanded and Emerging Sources Citation Index) and WHO COVID-19 Global literature on coronavirus disease to identify completed and ongoing studies without language restrictions. We conducted the searches on 16 April 2021.
SELECTION CRITERIA
We followed standard Cochrane methodology. We included RCTs evaluating remdesivir for the treatment of SARS-CoV-2 infection in hospitalised adults compared to placebo or standard care alone irrespective of disease severity, gender, ethnicity, or setting. We excluded studies that evaluated remdesivir for the treatment of other coronavirus diseases.
DATA COLLECTION AND ANALYSIS
We followed standard Cochrane methodology. To assess risk of bias in included studies, we used the Cochrane RoB 2 tool for RCTs. We rated the certainty of evidence using the GRADE approach for outcomes that were reported according to our prioritised categories: all-cause mortality at up to day 28, duration to liberation from invasive mechanical ventilation, duration to liberation from supplemental oxygen, new need for mechanical ventilation (high-flow oxygen or non-invasive or invasive mechanical ventilation), new need for invasive mechanical ventilation, new need for non-invasive mechanical ventilation or high-flow oxygen, new need for oxygen by mask or nasal prongs, quality of life, adverse events (any grade), and serious adverse events.
MAIN RESULTS
We included five RCTs with 7452 participants diagnosed with SARS-CoV-2 infection and a mean age of 59 years, of whom 3886 participants were randomised to receive remdesivir. Most participants required low-flow oxygen (n=4409) or mechanical ventilation (n=1025) at baseline. We identified two ongoing studies, one was suspended due to a lack of COVID-19 patients to recruit. Risk of bias was considered to be of some concerns or high risk for clinical status and safety outcomes because participants who had died did not contribute information to these outcomes. Without adjustment, this leads to an uncertain amount of missing values and the potential for bias due to missing data. Effects of remdesivir in hospitalised individuals Remdesivir probably makes little or no difference to all-cause mortality at up to day 28 (risk ratio (RR) 0.93, 95% confidence interval (CI) 0.81 to 1.06; risk difference (RD) 8 fewer per 1000, 95% CI 21 fewer to 7 more; 4 studies, 7142 participants; moderate-certainty evidence). Considering the initial severity of condition, only one study showed a beneficial effect of remdesivir in patients who received low-flow oxygen at baseline (RR 0.32, 95% CI 0.15 to 0.66, 435 participants), but conflicting results exists from another study, and we were unable to validly assess this observations due to limited availability of comparable data. Remdesivir may have little or no effect on the duration to liberation from invasive mechanical ventilation (2 studies, 1298 participants, data not pooled, low-certainty evidence). We are uncertain whether remdesivir increases or decreases the chance of clinical improvement in terms of duration to liberation from supplemental oxygen at up to day 28 (3 studies, 1691 participants, data not pooled, very low-certainty evidence). We are very uncertain whether remdesivir decreases or increases the risk of clinical worsening in terms of new need for mechanical ventilation at up to day 28 (high-flow oxygen or non-invasive ventilation or invasive mechanical ventilation) (RR 0.78, 95% CI 0.48 to 1.24; RD 29 fewer per 1000, 95% CI 68 fewer to 32 more; 3 studies, 6696 participants; very low-certainty evidence); new need for non-invasive mechanical ventilation or high-flow oxygen (RR 0.70, 95% CI 0.51 to 0.98; RD 72 fewer per 1000, 95% CI 118 fewer to 5 fewer; 1 study, 573 participants; very low-certainty evidence); and new need for oxygen by mask or nasal prongs (RR 0.81, 95% CI 0.54 to 1.22; RD 84 fewer per 1000, 95% CI 204 fewer to 98 more; 1 study, 138 participants; very low-certainty evidence). The evidence suggests that remdesivir may decrease the risk of clinical worsening in terms of new need for invasive mechanical ventilation (67 fewer participants amongst 1000 participants; RR 0.56, 95% CI 0.41 to 0.77; 2 studies, 1159 participants; low-certainty evidence). None of the included studies reported quality of life. Remdesivir probably decreases the serious adverse events rate at up to 28 days (RR 0.75, 95% CI 0.63 to 0.90; RD 63 fewer per 1000, 95% CI 94 fewer to 25 fewer; 3 studies, 1674 participants; moderate-certainty evidence). We are very uncertain whether remdesivir increases or decreases adverse events rate (any grade) (RR 1.05, 95% CI 0.86 to 1.27; RD 29 more per 1000, 95% CI 82 fewer to 158 more; 3 studies, 1674 participants; very low-certainty evidence).
AUTHORS' CONCLUSIONS
Based on the currently available evidence, we are moderately certain that remdesivir probably has little or no effect on all-cause mortality at up to day 28 in hospitalised adults with SARS-CoV-2 infection. We are uncertain about the effects of remdesivir on clinical improvement and worsening. There were insufficient data available to validly examine the effect of remdesivir on mortality in subgroups depending on the extent of respiratory support at baseline. Future studies should provide additional data on efficacy and safety of remdesivir for defined core outcomes in COVID-19 research, especially for different population subgroups. This could allow us to draw more reliable conclusions on the potential benefits and harms of remdesivir in future updates of this review. Due to the living approach of this work, we will update the review periodically.
Topics: Adenosine Monophosphate; Alanine; Antiviral Agents; Bias; COVID-19; Cause of Death; Confidence Intervals; Disease Progression; Humans; Middle Aged; Oxygen; Randomized Controlled Trials as Topic; Respiration, Artificial; SARS-CoV-2; Ventilator Weaning; COVID-19 Drug Treatment
PubMed: 34350582
DOI: 10.1002/14651858.CD014962