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Reviews in Medical Virology Nov 2021The current pandemic caused by SARS-CoV-2 virus infection is known as Covid-19 (coronavirus disease 2019). This disease can be asymptomatic or can affect multiple organ...
The current pandemic caused by SARS-CoV-2 virus infection is known as Covid-19 (coronavirus disease 2019). This disease can be asymptomatic or can affect multiple organ systems. Damage induced by the virus is related to dysfunctional activity of the immune system, but the activity of molecules such as C-reactive protein (CRP) as a factor capable of inducing an inflammatory status that may be involved in the severe evolution of the disease, has not been extensively evaluated. A systematic review was performed using the NCBI-PubMed database to find articles related to Covid-19 immunity, inflammatory response, and CRP published from December 2019 to December 2020. High levels of CRP were found in patients with severe evolution of Covid-19 in which several organ systems were affected and in patients who died. CRP activates complement, induces the production of pro-inflammatory cytokines and induces apoptosis which, together with the inflammatory status during the disease, can lead to a severe outcome. Several drugs can decrease the level or block the effect of CRP and might be useful in the treatment of Covid-19. From this review it is reasonable to conclude that CRP is a factor that can contribute to severe evolution of Covid-19 and that the use of drugs able to lower CRP levels or block its activity should be evaluated in randomized controlled clinical trials.
Topics: ADAM17 Protein; Angiotensin-Converting Enzyme 2; Anti-Inflammatory Agents; Biomarkers; C-Reactive Protein; COVID-19; Celecoxib; Complement System Proteins; Cytokine Release Syndrome; Cytokines; Disease Progression; Doxycycline; Gene Expression Regulation; Humans; Randomized Controlled Trials as Topic; SARS-CoV-2; Severity of Illness Index; Survival Analysis; COVID-19 Drug Treatment
PubMed: 34773448
DOI: 10.1002/rmv.2221 -
Cardiovascular Therapeutics 2022Rivaroxaban and apixaban are the most widely used nonvitamin K oral anticoagulants (NOACs) in patients with venous thromboembolism (VTE). This meta-analysis evaluates... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Rivaroxaban and apixaban are the most widely used nonvitamin K oral anticoagulants (NOACs) in patients with venous thromboembolism (VTE). This meta-analysis evaluates the effectiveness and safety of both NOACs versus standard of care (SoC) in real-world practice.
METHODS
Real-world evidence (RWE) studies were identified through a systematic literature review conducted between January 2012 and July 2020, using Embase, MEDLINE, and the websites of cardiological, hematological, and oncological associations. Eligible RWE studies recruited adult patients with deep vein thrombosis and/or pulmonary embolism and presented a comparison between rivaroxaban and apixaban versus SoC, consisting either of vitamin K antagonists, heparins, or combinations thereof. Hazard ratios (HRs) for the comparison between NOACs and SoC were extracted from the relevant studies or estimated based on the reported binary data. The between-treatment contrasts were reported as HRs with associated 95% confidence intervals.
RESULTS
A total of 65 RWE studies were identified and considered relevant for the meta-analysis. Compared with SoC, both rivaroxaban and apixaban were associated with reduced risks of recurrent VTE and a lower rate of major bleeding events. Patients treated with rivaroxaban were at a lower risk of all-cause death compared with those receiving SoC (HR = 0.56 [0.39-0.80]), while evidence for apixaban from the identified studies was insufficient to demonstrate a statistically significant change in mortality (HR = 0.66 [0.30-1.47]).
CONCLUSION
This analysis indicates that in real-world practice, rivaroxaban and apixaban are associated with a lower risk of recurrent VTE and major bleeding events compared with SoC. Survival benefit in patients treated with rivaroxaban was also observed.
Topics: Administration, Oral; Anticoagulants; Hemorrhage; Humans; Pyrazoles; Pyridones; Rivaroxaban; Treatment Outcome; Venous Thromboembolism
PubMed: 35801133
DOI: 10.1155/2022/2756682 -
American Journal of Clinical Oncology Jun 2023Patients with recurrent or persistent ovarian cancer often have poor prognoses, and their optimal treatment regimen remains unclear. Inhibition of angiogenesis is a... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Patients with recurrent or persistent ovarian cancer often have poor prognoses, and their optimal treatment regimen remains unclear. Inhibition of angiogenesis is a valuable strategy for treating ovarian cancer, and the drug pazopanib is a potent, multitarget tyrosine kinase inhibitor. However, treatment with pazopanib in combination with chemotherapy remains controversial. We performed a systematic review and meta-analysis to clarify the efficacy and side effects of pazopanib combined with chemotherapy in the treatment of advanced ovarian cancer.
METHODS
The PubMed, Embase, and Cochrane databases were systematically searched for relevant randomized controlled trials published up to September 2, 2022. The primary outcomes of eligible studies included overall response rate (ORR), disease control rate, 1-year progression-free survival (PFS) rate, 2-year PFS rate, 1-year overall survival (OS) rate, 2-year OS rate, and adverse events.
RESULT
Outcomes from a total of 518 recurrent or persistent ovarian cancer patients from 5 studies were analyzed in this systematic review. Pooled results showed that pazopanib plus chemotherapy, when compared with chemotherapy alone, significantly improved the ORR (pooled risk ratio=1.400; 95% CI, 1.062-1.846; P = 0.017) but not the disease control rate, 1-year PFS, 2-year PFS, 1-year OS, or 2-year OS. Moreover, pazopanib increased the risk of neutropenia, hypertension, fatigue, and liver dysfunction.
CONCLUSION
Pazopanib plus chemotherapy improved patient ORR but did not improve survival; it also increased the occurrence of several adverse events. Further large-sample clinical trials are needed to verify these results to guide pazopanib use in patients with ovarian cancer.
Topics: Humans; Female; Ovarian Neoplasms; Pyrimidines; Sulfonamides; Indazoles; Antineoplastic Combined Chemotherapy Protocols
PubMed: 36877187
DOI: 10.1097/COC.0000000000000999 -
PloS One 2021To assess the cardiovascular safety of celecoxib compared to non-selective non-steroid anti-inflammatory drugs or placebo. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To assess the cardiovascular safety of celecoxib compared to non-selective non-steroid anti-inflammatory drugs or placebo.
METHODS
We included randomized controlled trials of oral celecoxib compared with a non-selective NSAID or placebo in rheumatoid arthritis and osteoarthritis patients. We conducted searches in EMBASE, Cochrane CENTRAL, MEDLINE, China National Knowledge Infrastructure, VIP, Wanfang, and Chinese Biomedical Literature Database. Study selection and data extraction were done by two authors independently. The risk of bias was assessed using Cochrane's risk-of-bias Tool for Randomized Trials. The effect size was presented as a risk ratio with their 95% confidence interval.
RESULTS
Until July 22nd, 2021, our search identified 6279 records from which, after exclusions, 21 trials were included in the meta-analysis. The overall pooled risk ratio for Antiplatelet Trialists Collaboration cardiovascular events for celecoxib compared with any non-selective non-steroid anti-inflammatory drugs was 0.89 (95% confidence interval: 0.80-1.00). The pooled risk ratio for all-cause mortality for celecoxib compared with non-selective non-steroid anti-inflammatory drugs was 0.81 (95% confidence interval: 0.66-0.98). The cardiovascular mortality rate of celecoxib was lower than non-selective non-steroid anti-inflammatory drugs (risk ratio: 0.75, 95% confidence interval: 0.57-0.99). There was no significant difference between celecoxib and non-selective non-steroid anti-inflammatory drugs or placebo in the risk of other cardiovascular events.
CONCLUSION
Celecoxib is relatively safe in rheumatoid arthritis and osteoarthritis patients, independent of dose or duration. But it remains uncertain whether this would remain the same in patients treated with aspirin and patients with established cardiovascular diseases.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Cardiovascular System; Celecoxib; Humans; Osteoarthritis; Patient Safety
PubMed: 34932581
DOI: 10.1371/journal.pone.0261239 -
International Immunopharmacology Oct 2021This systematic review and meta-analysis of randomized controlled trials (RCTs) aimed to investigate the clinical efficacy and safety of Janus kinase (JAK) inhibitors... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
This systematic review and meta-analysis of randomized controlled trials (RCTs) aimed to investigate the clinical efficacy and safety of Janus kinase (JAK) inhibitors for COVID-19 patients.
METHODS
PubMed, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched from inception to July 12, 2021. RCTs comparing the clinical efficacy and safety of JAK inhibitors with a placebo or standard care in treating COVID-19 patients were included. The primary outcome was all-cause mortality rate at day 28.
RESULTS
Three RCTs were included in this meta-analysis. The all-cause mortality rate at day 28 was lower among the patients receiving JAK inhibitors than among the controls (4.1% [28/647] versus 7.0% [48/684], OR, 0.57; 95% CI, 0.36-0.92, I = 0). The clinical recovery rate was higher among the patients receiving JAK inhibitors than among the controls (85.1% (579/680) versus 80.0% [547/684], OR, 1.45; 95% CI, 1.09-1.93, I = 0). Additionally, the use of JAK inhibitors was associated with a shorter time to recovery than among the controls (MD, -2.84; 95% CI, -5.56 to -0.12; I = 50%). The rate of invasive mechanical ventilation (MV) was lower in the patients who used JAK inhibitors than among the controls. Finally, no significant difference was observed between the patients who used JAK inhibitors and the controls in the risk of any adverse events (OR, 0.92; 95% CI, 0.64-1.34; I = 33%) and serious adverse events (OR, 0.80; 95% CI, 0.45-1.44; I = 46%).
CONCLUSIONS
JAK inhibitors can lead to a better clinical outcome of hospitalized COVID-19 patients, and they are a safe agent in the treatment of COVID-19.
Topics: Azetidines; Humans; Janus Kinase Inhibitors; Nitriles; Piperidines; Purines; Pyrazoles; Pyrimidines; Randomized Controlled Trials as Topic; SARS-CoV-2; Sulfonamides; Treatment Outcome; COVID-19 Drug Treatment
PubMed: 34343937
DOI: 10.1016/j.intimp.2021.108027 -
Brazilian Journal of Otorhinolaryngology 2021Tonsillectomy is the 2nd most common outpatient surgery performed on children in the United States of America. Its main complication is pain, which varies in intensity... (Review)
Review
INTRODUCTION
Tonsillectomy is the 2nd most common outpatient surgery performed on children in the United States of America. Its main complication is pain, which varies in intensity from moderate to severe. Dipyrone is one of the most widely used painkillers in the postoperative period in children. Its use, however, is controversial in the literature, to the point that it is banned in many countries due to its potential severe adverse effects. Because of this controversy, reviewing the analgesic use of dipyrone in the postoperative period of tonsillectomy in children is essential.
OBJECTIVE
The aim of this study was to review the analgesic use of dipyrone in the postoperative period of tonsillectomy in children.
METHODS
Systematic review of the literature, involving an evaluation of the quality of articles in the databases MEDLINE/Pubmed, EMBASE and Virtual Health Library, selected with a preestablished search strategy. Only studies with a randomised clinical trial design evaluating the use of dipyrone in the postoperative period of tonsillectomy in children were included.
RESULTS AND CONCLUSION
Only 2 randomised clinical trials were found. Both compared dipyrone, paracetamol, and placebo. We were unable to carry out a metanalysis because the studies were too heterogenous (dipyrone was used as pre-emptive analgesic in one and only postoperatively in another). The analgesic effect of dipyrone, measured by validated pain scales in childhood, was shown to be superior to placebo and similar to paracetamol. It appears that dipyrone exhibits a profile suitable for use in children. However, the scarcity of randomised clinical trials evaluating its analgesic effect in this age group leads to the conclusion that more well-designed studies are still needed to establish the role of dipyrone in the postoperative period of tonsillectomy in children.
Topics: Analgesia; Child; Dipyrone; Humans; Pain Measurement; Pain, Postoperative; Randomized Controlled Trials as Topic; Tonsillectomy
PubMed: 33485779
DOI: 10.1016/j.bjorl.2020.12.005 -
Clinical and Applied... 2020There is no direct evidence comparing the 2 most commonly prescribed direct oral anticoagulants, apixaban and rivaroxaban, used for stroke prevention in nonvalvular... (Comparative Study)
Comparative Study
There is no direct evidence comparing the 2 most commonly prescribed direct oral anticoagulants, apixaban and rivaroxaban, used for stroke prevention in nonvalvular atrial fibrillation (NVAF). A number of network meta-analyses (NMAs) of randomized control trials and real-world evidence (RWE) studies comparing the efficacy, effectiveness, and safety of apixaban and rivaroxaban have been published; however, a comprehensive evidence review across the available body of evidence is lacking. In this study, we aimed to systematically review and evaluate the clinical outcomes of apixaban and rivaroxaban using a combination of data gleaned from both NMAs and RWE studies. The review identified 21 NMAs and 5 RWE studies. The data demonstrated that apixaban was associated with fewer major bleeding events compared to rivaroxaban. There was no difference in the efficacy/effectiveness profiles between these treatments. Bleeding is a serious complication of anticoagulation therapy for the management of NVAF, and is associated with increased rates of hospitalization, morbidity, mortality, and health-care expenditure. The majority of studies in this comprehensive evidence review suggests that apixaban has a lower risk of major bleeding events compared to rivaroxaban in patients with NVAF.
Topics: Aged; Atrial Fibrillation; Female; Hemorrhage; Humans; Male; Middle Aged; Network Meta-Analysis; Pyrazoles; Pyridones; Rivaroxaban
PubMed: 31918558
DOI: 10.1177/1076029619898764 -
Annals of the Rheumatic Diseases Jan 2022To update the EULAR points to consider (PtCs) on the use of immunomodulatory therapies in COVID-19.
OBJECTIVES
To update the EULAR points to consider (PtCs) on the use of immunomodulatory therapies in COVID-19.
METHODS
According to the EULAR standardised operating procedures, a systematic literature review up to 14 July 2021 was conducted and followed by a consensus meeting of an international multidisciplinary task force. The new statements were consolidated by formal voting.
RESULTS
We updated 2 overarching principles and 12 PtC. Evidence was only available in moderate to severe and critical patients. Glucocorticoids alone or in combination with tocilizumab are beneficial in COVID-19 cases requiring oxygen therapy and in critical COVID-19. Use of Janus kinase inhibitors (baricitinib and tofacitinib) is promising in the same populations of severe and critical COVID-19. Anti-SARS-CoV-2 monoclonal antibodies and convalescent plasma may find application in early phases of the disease and in selected subgroups of immunosuppressed patients. There was insufficient robust evidence for the efficacy of other immunomodulators with further work being needed in relation to biomarker-based stratification for IL-1 therapy CONCLUSIONS: Growing evidence supports incremental efficacy of glucocorticoids alone or combined with tocilizumab/Janus kinase inhibitors in moderate to severe and critical COVID-19. Ongoing studies may unmask the potential application of other therapeutic approaches. Involvement of rheumatologists, as systemic inflammatory diseases experts, should be encouraged in clinical trials of immunomodulatory therapy in COVID-19.
Topics: Antibodies, Monoclonal, Humanized; Azetidines; Consensus Development Conferences as Topic; Drug Therapy, Combination; Glucocorticoids; Humans; Immunomodulating Agents; Immunomodulation; Janus Kinase Inhibitors; Piperidines; Purines; Pyrazoles; Pyrimidines; SARS-CoV-2; Sulfonamides; COVID-19 Drug Treatment
PubMed: 34620584
DOI: 10.1136/annrheumdis-2021-221366 -
British Journal of Haematology Feb 2020Persistent immune thrombocytopenia (ITP) patients require second-line treatments, for which information on clinical outcomes are lacking. A systematic review and network... (Meta-Analysis)
Meta-Analysis
Persistent immune thrombocytopenia (ITP) patients require second-line treatments, for which information on clinical outcomes are lacking. A systematic review and network meta-analysis (NMA) were conducted. Only randomised controlled trials (RCT) of second-line drugs in adult persistent ITP patients with platelet response, platelet count, any bleeding or serious adverse events (SAE) outcome were eligible. Twelve RCTs (n = 1313) were included in NMA. For platelet response outcome, eltrombopag and romiplostin were the best relative to placebo; the former had a non-significant advantage [risk ratio (RR) = 1·10 (95% confidence interval: 0·46, 2·67)]. Both treatments were superior to rituximab and recombinant human thrombopoietin (rhTPO)+rituximab, with corresponding RRs of 4·56 (1·89, 10·96) and 4·18 (1·21, 14·49) for eltrombopag; 4·13 (1·56, 10·94) and 3·79 (1·02, 14·09) for romiplostim. For platelet count, romiplostim ranked highest, followed by eltrombopag, rhTPO+rituximab, and rituximab. For bleeding, rituximab had lowest risk, followed by eltrombopag and romiplostim. For SAEs, rhTPO+rituximab had highest risk, followed by rituximab, eltrombopag and romiplostim. From clustered ranking, romiplostim had the best balance between short-term efficacy and SAEs, followed by eltrombopag. In conclusion, romiplostim and eltrombopag may yield high efficacy and safety. Rituximab may not be beneficial due to lower efficacy and higher complications compared with the thrombopoietin receptor agonists. RCTs with long-term clinical outcomes are required.
Topics: Adult; Benzoates; Drug Therapy, Combination; Female; Humans; Hydrazines; Male; Platelet Count; Prospective Studies; Purpura, Thrombocytopenic, Idiopathic; Pyrazoles; Randomized Controlled Trials as Topic; Receptors, Fc; Recombinant Fusion Proteins; Rituximab; Thrombopoietin
PubMed: 31423574
DOI: 10.1111/bjh.16161 -
The Cochrane Database of Systematic... Oct 2020Several comparative randomised controlled trials (RCTs) have been performed including combinations of tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Several comparative randomised controlled trials (RCTs) have been performed including combinations of tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors since the publication of a Cochrane Review on targeted therapy for metastatic renal cell carcinoma (mRCC) in 2008. This review represents an update of that original review.
OBJECTIVES
To assess the effects of targeted therapies for clear cell mRCC in patients naïve to systemic therapy.
SEARCH METHODS
We performed a comprehensive search with no restrictions on language or publication status. The date of the latest search was 18 June 2020.
SELECTION CRITERIA
We included randomised controlled trials, recruiting patients with clear cell mRCC naïve to previous systemic treatment. The index intervention was any TKI-based targeted therapy.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed the included studies and extracted data for the primary outcomes: progression-free survival (PFS), overall survival (OS) and serious adverse events (SAEs); and the secondary outcomes: health-related quality of life (QoL), response rate and minor adverse events (AEs). We performed statistical analyses using a random-effects model and rated the certainty of evidence according to the GRADE approach.
MAIN RESULTS
We included 18 RCTs reporting on 11,590 participants randomised across 18 comparisons. This abstract focuses on the primary outcomes of select comparisons. 1. Pazopanib versus sunitinib Pazopanib may result in little to no difference in PFS as compared to sunitinib (hazard ratio (HR) 1.05, 95% confidence interval (CI) 0.90 to 1.23; 1 study, 1110 participants; low-certainty evidence). Based on the control event risk of 420 per 1000 in this trial at 12 months, this corresponds to 18 fewer participants experiencing PFS (95% CI 76 fewer to 38 more) per 1000 participants. Pazopanib may result in little to no difference in OS compared to sunitinib (HR 0.92, 95% CI 0.80 to 1.06; 1 study, 1110 participants; low-certainty evidence). Based on the control event risk of 550 per 1000 in this trial at 12 months, this corresponds to 27 more OSs (95% CI 19 fewer to 70 more) per 1000 participants. Pazopanib may result in little to no difference in SAEs as compared to sunitinib (risk ratio (RR) 1.01, 95% CI 0.94 to 1.09; 1 study, 1102 participants; low-certainty evidence). Based on the control event risk of 734 per 1000 in this trial, this corresponds to 7 more participants experiencing SAEs (95% CI 44 fewer to 66 more) per 1000 participants. 2. Sunitinib versus avelumab and axitinib Sunitinib probably reduces PFS as compared to avelumab plus axitinib (HR 1.45, 95% CI 1.17 to 1.80; 1 study, 886 participants; moderate-certainty evidence). Based on the control event risk of 550 per 1000 in this trial at 12 months, this corresponds to 130 fewer participants experiencing PFS (95% CI 209 fewer to 53 fewer) per 1000 participants. Sunitinib may result in little to no difference in OS (HR 1.28, 95% CI 0.92 to 1.79; 1 study, 886 participants; low-certainty evidence). Based on the control event risk of 890 per 1000 in this trial at 12 months, this would result in 29 fewer OSs (95% CI 78 fewer to 8 more) per 1000 participants. Sunitinib may result in little to no difference in SAEs (RR 1.01, 95% CI 0.93 to 1.10; 1 study, 873 participants; low-certainty evidence). Based on the control event risk of 705 per 1000 in this trial, this corresponds to 7 more SAEs (95% CI 49 fewer to 71 more) per 1000 participants. 3. Sunitinib versus pembrolizumab and axitinib Sunitinib probably reduces PFS as compared to pembrolizumab plus axitinib (HR 1.45, 95% CI 1.19 to 1.76; 1 study, 861 participants; moderate-certainty evidence). Based on the control event risk of 590 per 1000 in this trial at 12 months, this corresponds to 125 fewer participants experiencing PFS (95% CI 195 fewer to 56 fewer) per 1000 participants. Sunitinib probably reduces OS (HR 1.90, 95% CI 1.36 to 2.65; 1 study, 861 participants; moderate-certainty evidence). Based on the control event risk of 880 per 1000 in this trial at 12 months, this would result in 96 fewer OSs (95% CI 167 fewer to 40 fewer) per 1000 participants. Sunitinib may reduce SAEs as compared to pembrolizumab plus axitinib (RR 0.90, 95% CI 0.81 to 1.02; 1 study, 854 participants; low-certainty evidence) although the CI includes the possibility of no effect. Based on the control event risk of 604 per 1000 in this trial, this corresponds to 60 fewer SAEs (95% CI 115 fewer to 12 more) per 1000 participants. 4. Sunitinib versus nivolumab and ipilimumab Sunitinib may reduce PFS as compared to nivolumab plus ipilimumab (HR 1.30, 95% CI 1.11 to 1.52; 1 study, 847 participants; low-certainty evidence). Based on the control event risk of 280 per 1000 in this trial at 30 months' follow-up, this corresponds to 89 fewer PFSs (95% CI 136 fewer to 37 fewer) per 1000 participants. Sunitinib reduces OS (HR 1.52, 95% CI 1.23 to 1.89; 1 study, 847 participants; high-certainty evidence). Based on the control event risk 600 per 1000 in this trial at 30 months, this would result in 140 fewer OSs (95% CI 219 fewer to 67 fewer) per 1000 participants. Sunitinib probably increases SAEs (RR 1.37, 95% CI 1.22 to 1.53; 1 study, 1082 participants; moderate-certainty evidence). Based on the control event risk of 457 per 1000 in this trial, this corresponds to 169 more SAEs (95% CI 101 more to 242 more) per 1000 participants.
AUTHORS' CONCLUSIONS
Based on the low to high certainty of evidence, several combinations of immune checkpoint inhibitors appear to be superior to single-agent targeted therapy in terms of PFS and OS, and with a favourable AE profile. Some single-agent targeted therapies demonstrated a similar or improved oncological outcome compared to others; minor differences were observed for AE within this group. The certainty of evidence was variable ranging from high to very low and all comparisons were based on single trials.
Topics: Adult; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Antineoplastic Agents, Immunological; Axitinib; Bevacizumab; Bias; Carcinoma, Renal Cell; Everolimus; Humans; Indazoles; Ipilimumab; Kidney Neoplasms; Phenylurea Compounds; Progression-Free Survival; Protein Kinase Inhibitors; Pyrimidines; Quality of Life; Quinolines; Randomized Controlled Trials as Topic; Receptors, Vascular Endothelial Growth Factor; Sirolimus; Sorafenib; Sulfonamides; Sunitinib
PubMed: 33058158
DOI: 10.1002/14651858.CD012796.pub2