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BMJ (Clinical Research Ed.) Jul 2020To compare the effects of treatments for coronavirus disease 2019 (covid-19). (Comparative Study)
Comparative Study
OBJECTIVE
To compare the effects of treatments for coronavirus disease 2019 (covid-19).
DESIGN
Living systematic review and network meta-analysis.
DATA SOURCES
WHO covid-19 database, a comprehensive multilingual source of global covid-19 literature, up to 3 December 2021 and six additional Chinese databases up to 20 February 2021. Studies identified as of 1 December 2021 were included in the analysis.
STUDY SELECTION
Randomised clinical trials in which people with suspected, probable, or confirmed covid-19 were randomised to drug treatment or to standard care or placebo. Pairs of reviewers independently screened potentially eligible articles.
METHODS
After duplicate data abstraction, a bayesian network meta-analysis was conducted. Risk of bias of the included studies was assessed using a modification of the Cochrane risk of bias 2.0 tool, and the certainty of the evidence using the grading of recommendations assessment, development, and evaluation (GRADE) approach. For each outcome, interventions were classified in groups from the most to the least beneficial or harmful following GRADE guidance.
RESULTS
463 trials enrolling 166 581 patients were included; 267 (57.7%) trials and 89 814 (53.9%) patients are new from the previous iteration; 265 (57.2%) trials evaluating treatments with at least 100 patients or 20 events met the threshold for inclusion in the analyses. Compared with standard care, three drugs reduced mortality in patients with mostly severe disease with at least moderate certainty: systemic corticosteroids (risk difference 23 fewer per 1000 patients, 95% credible interval 40 fewer to 7 fewer, moderate certainty), interleukin-6 receptor antagonists when given with corticosteroids (23 fewer per 1000, 36 fewer to 7 fewer, moderate certainty), and Janus kinase inhibitors (44 fewer per 1000, 64 fewer to 20 fewer, high certainty). Compared with standard care, two drugs probably reduce hospital admission in patients with non-severe disease: nirmatrelvir/ritonavir (36 fewer per 1000, 41 fewer to 26 fewer, moderate certainty) and molnupiravir (19 fewer per 1000, 29 fewer to 5 fewer, moderate certainty). Remdesivir may reduce hospital admission (29 fewer per 1000, 40 fewer to 6 fewer, low certainty). Only molnupiravir had at least moderate quality evidence of a reduction in time to symptom resolution (3.3 days fewer, 4.8 fewer to 1.6 fewer, moderate certainty); several others showed a possible benefit. Several drugs may increase the risk of adverse effects leading to drug discontinuation; hydroxychloroquine probably increases the risk of mechanical ventilation (moderate certainty).
CONCLUSION
Corticosteroids, interleukin-6 receptor antagonists, and Janus kinase inhibitors probably reduce mortality and confer other important benefits in patients with severe covid-19. Molnupiravir and nirmatrelvir/ritonavir probably reduce admission to hospital in patients with non-severe covid-19.
SYSTEMATIC REVIEW REGISTRATION
This review was not registered. The protocol is publicly available in the supplementary material.
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. This is the fifth version of the original article published on 30 July 2020 (BMJ 2020;370:m2980), and previous versions can be found as data supplements. When citing this paper please consider adding the version number and date of access for clarity.
Topics: Adenosine Monophosphate; Alanine; Antiviral Agents; Betacoronavirus; COVID-19; Centers for Disease Control and Prevention, U.S.; China; Coronavirus Infections; Databases, Factual; Drug Combinations; Evidence-Based Medicine; Glucocorticoids; Humans; Hydroxychloroquine; Lopinavir; Network Meta-Analysis; Pandemics; Pneumonia, Viral; Randomized Controlled Trials as Topic; Respiration, Artificial; Ritonavir; SARS-CoV-2; Severity of Illness Index; Standard of Care; Treatment Outcome; United States; COVID-19 Drug Treatment
PubMed: 32732190
DOI: 10.1136/bmj.m2980 -
Journal of Cancer Research and Clinical... Oct 2020Limited treatment options are available in chemotherapy-refractory metastatic colorectal cancer (mCRC). The objective was to conduct a systematic literature review (SLR)... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Limited treatment options are available in chemotherapy-refractory metastatic colorectal cancer (mCRC). The objective was to conduct a systematic literature review (SLR) and exploratory network meta-analysis (NMA) to compare the tolerability and effectiveness of SIRT with Y-90 resin microspheres, regorafenib, TAS-102 (trifluridine/tipiracil), and best supportive care (BSC) as third-line treatment in patients with mCRC.
METHODS
An SLR was conducted to identify studies comparing two or more of the treatments and reporting overall survival (OS), progression-free survival, tumor response, or adverse event (AE) incidence. An exploratory NMA was conducted to compare hazard ratios (HRs) for OS using Markov chain Monte Carlo (MCMC) techniques.
RESULTS
Seven studies were identified in the SLR: two double-blind randomized-controlled trials (RCT) for each drug, one open-label RCT, and two non-randomized comparative studies for SIRT. Patient selection criteria differed between studies, with SIRT studies including patients with liver-dominant colorectal metastases. Nausea and vomiting were more frequent with TAS-102 than regorafenib or SIRT; diarrhea was more common with TAS-102 and regorafenib than SIRT. The exploratory NMA suggested that all active treatments improved OS, with HRs of 0.48 (95% CrI 0.30-0.78) for SIRT with Y-90 resin microspheres, 0.63 (0.38-1.03) for TAS-102, and 0.67 (0.40-1.08) for regorafenib each compared to BSC.
CONCLUSIONS
Regorafenib, TAS-102 and SIRT using Y-90 resin microspheres are more effective than BSC in third-line treatment of mCRC; however, study heterogeneity made comparisons between active treatments challenging. SIRT is a viable treatment for third-line mCRC and its favorable AE profile should be considered in the therapeutic decision-making process.
Topics: Antineoplastic Combined Chemotherapy Protocols; Brachytherapy; Colorectal Neoplasms; Double-Blind Method; Drug Combinations; Humans; Microspheres; Neoplasm Metastasis; Network Meta-Analysis; Palliative Care; Phenylurea Compounds; Progression-Free Survival; Pyridines; Pyrrolidines; Randomized Controlled Trials as Topic; Thymine; Trifluridine; Uracil; Yttrium Radioisotopes
PubMed: 32715436
DOI: 10.1007/s00432-020-03315-6 -
An overview of the safety, clinical application and antiviral research of the COVID-19 therapeutics.Journal of Infection and Public Health Oct 2020Since a novel coronavirus pneumonia outbreak in late December 2019, coronavirus disease -19 (COVID-19) epidemic has gradually spread worldwide, becoming a major public...
Since a novel coronavirus pneumonia outbreak in late December 2019, coronavirus disease -19 (COVID-19) epidemic has gradually spread worldwide, becoming a major public health event. No specific antivirals are currently available for COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The treatments for COVID-19 are mainly based on the experiences of similar virus such SARS-CoV, MERS-CoV, HIV and influenza viruses. Scientists have taken great efforts to investigate the effective methods for the treatment of COVID-19. Up to now, there are over 1000 clinical studies for COVID-19 all over the world. In this article, we reviewed the current options for COVID-19 therapy including small molecules such as Remdesivir, Favipiravir, Lopinavir/Ritonavir etc, peptide inhibitors of ACE2, Traditional Chinese Medicines and Biologics such as SARS-CoV-2-specific neutralizing antibodies, mesenchymal stem cells and vaccines etc. Meanwhile, we systematically reviewed their clinical safety, clinical applications and progress of antiviral researches. The therapeutic effect of these antiviral drugs is summarized and compared, hoping to provide some ideas for clinical options of COVID-19 treatment and also provide experiences for the life-threatening virus diseases in the future.
Topics: Adenosine Monophosphate; Alanine; Amides; Angiotensin-Converting Enzyme Inhibitors; Antimalarials; Antiviral Agents; Betacoronavirus; Biomedical Research; COVID-19; Coronavirus Infections; Drug Combinations; Drug Development; Drugs, Chinese Herbal; Humans; Hydroxychloroquine; Immunization, Passive; Indoles; Interferons; Lopinavir; Pandemics; Pneumonia, Viral; Pyrazines; Ribavirin; Ritonavir; SARS-CoV-2; COVID-19 Serotherapy
PubMed: 32684351
DOI: 10.1016/j.jiph.2020.07.004 -
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 -
BMC Urology Jul 2020Mitomycin (MMC) has been frequently used as the compound for intravesical treatment. The relatively new pyrimidine analog gemcitabine (GEM) has exhibited anticancer... (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND
Mitomycin (MMC) has been frequently used as the compound for intravesical treatment. The relatively new pyrimidine analog gemcitabine (GEM) has exhibited anticancer effect on various solid cancers, such as the advanced bladder cancer. In this study, the GEM and MMC in treating non-muscle invasive bladder cancer (NMIBC) cases was compared through systemic review.
METHODS
In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, the electronic databases, including Embase, PubMed, Chinese biomedicine literature database, the Cochrane Library, the National Institute for Health and Clinical Excellence, NHS Evidence, Chinese technological periodical full-text database, and Chinese periodical full-text database, were systemically reviewed from inception to October 2018. Then, the RevMan 5.0 software was applied for data analysis. Five randomized controlled trials (RCTs) involving a total of 335 patients were included.
RESULTS
For MMC group, the recurrence rate in the mitomycin arm increased compared with that in GEM group (OR = 0.44 95% CI [0.24, 0.78]), and the difference was statistically significant between the two groups. GEM was associated with reduced incidence of chemical cystitis compared with that of MMC (OR = 0.23 95% CI [0.12, 0.44]). Differences in hematuria (OR = 0.46 95% CI [0.16, 1.31]), skin reaction (OR = 0.49 95% CI [0.14, 1.70]) and liver and kidney function damage (OR = 0.51 95% CI [0.09, 2.85]) displayed no statistical significance between the two groups.
CONCLUSION
Findings in our study demonstrate the superior efficacy of GEM over MMC in reducing the relapse rate among NMIBC patients following transurethral resection (TUR). In addition, GEM is associated with reduced local toxic effects on the bladder compared with those of MMC. However, more future studies are needed to examine GEM safety when used as the monotherapy or polytherapy for bladder patients. More RCTs with high quality are also required to validate our findings due to the limitations of the current meta-analysis.
Topics: Administration, Intravesical; Antibiotics, Antineoplastic; Antimetabolites, Antineoplastic; Deoxycytidine; Humans; Mitomycin; Neoplasm Invasiveness; Randomized Controlled Trials as Topic; Urinary Bladder Neoplasms; Gemcitabine
PubMed: 32660456
DOI: 10.1186/s12894-020-00610-9 -
BMC Cancer Jul 2020Pancreatic cancer has a poor prognosis and few choices of therapy. For patients with adequate performance status, FOLFIRINOX or gemcitabine plus nab-paclitaxel are... (Comparative Study)
Comparative Study Meta-Analysis
Meta-analysis examining overall survival in patients with pancreatic cancer treated with second-line 5-fluorouracil and oxaliplatin-based therapy after failing first-line gemcitabine-containing therapy: effect of performance status and comparison with other regimens.
BACKGROUND
Pancreatic cancer has a poor prognosis and few choices of therapy. For patients with adequate performance status, FOLFIRINOX or gemcitabine plus nab-paclitaxel are preferred first-line treatment. 5-Fluorouracil (5-FU)-based therapy (e.g. FOLFIRI, OFF, or FOLFOX) are often used in patients who previously received gemcitabine-based regimens. A systematic review was conducted of the safety and efficacy of FOLFOX for metastatic pancreatic cancer following prior gemcitabine-based therapy. A Bayesian fixed-effect meta-analysis with adjustment of patient performance status (PS) was conducted to evaluate overall survival (OS) and compare outcomes with nanoliposomal irinotecan combination therapy.
METHODS
PubMed.gov , FDA.gov , ClinicalTrials.gov , congress abstracts, Cochrane.org library, and EMBASE database searches were conducted to identify randomized controlled trials of advanced/metastatic disease, prior gemcitabine-based therapy, and second-line treatment with 5-FU and oxaliplatin. The database search dates were January 1, 1990-June 30, 2019. Endpoints were OS and severe treatment-related adverse events (TRAEs). Trial-level PS scores were standardized by converting Karnofsky grade scores to Eastern Cooperative Oncology Group (ECOG) Grade, and overall study-weighted PS was calculated based on weighted average of all patients.
RESULTS
Of 282 studies identified, 11 randomized controlled trials (N = 454) were included in the meta-analysis. Baseline weighted PS scores predicted OS in 10 of the 11 studies, and calculated PS scores of 1.0 were associated with a median OS of 6.3 months (95% posterior interval, 5.4-7.4). After adjusting for baseline PS, FOLFOX had a similar treatment effect profile (median OS, range 2.6-6.7 months) as 5-FU/leucovorin plus nanoliposomal irinotecan therapy (median OS, 6.1 months; 95% confidence interval 4.8-8.9). Neutropenia and fatigue were the most commonly reported Grade 3-4 TRAEs associated with FOLFOX.
CONCLUSIONS
Baseline PS is a strong prognostic factor when interpreting the efficacy of 5-FU and oxaliplatin-based therapy of pancreatic cancer after progression on first-line gemcitabine-based regimens. When baseline PS is considered, FOLFOX has a similar treatment effect as 5-FU and nanoliposomal irinotecan therapy and a comparable safety profile. These findings suggest that 5-FU and oxaliplatin-based therapies remain an acceptable and alternative second-line treatment option for patients with pancreatic cancer and adequate PS (e.g. ECOG 0-1) following gemcitabine treatment.
Topics: Antineoplastic Combined Chemotherapy Protocols; Deoxycytidine; Drug Resistance, Neoplasm; Drug-Related Side Effects and Adverse Reactions; Fluorouracil; Humans; Karnofsky Performance Status; Leucovorin; Organoplatinum Compounds; Oxaliplatin; Pancreatic Neoplasms; Prognosis; Randomized Controlled Trials as Topic; Risk Factors; Survival Analysis; Treatment Outcome; Gemcitabine
PubMed: 32641104
DOI: 10.1186/s12885-020-07110-x -
Annals of Palliative Medicine Jul 2020Gemcitabine combined the oral fluoropyrimidine capecitabine (GemCap) is an active antitumor therapy in the treatment of advanced or metastatic pancreatic cancer, and has... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Gemcitabine combined the oral fluoropyrimidine capecitabine (GemCap) is an active antitumor therapy in the treatment of advanced or metastatic pancreatic cancer, and has been shown potential synergistic activity in previous clinical trials. In this study, we sought to systematically review and synthesize the efficacy and safety of GemCap in the treatment of advanced or metastatic pancreatic cancer.
METHODS
A systematic review was performed through PubMed, Cochrane Library, EMBASE, and Web of Science databases up to Jul 10, 2019 to identify clinical trials that included advanced or metastatic pancreatic cancer patients treated with GemCap. Data of overall survival (OS), progression-free survival (PFS), 1-year survival rate, objective response rate (ORR), disease control rate (DCR) and adverse events were extracted and meta-analyzed.
RESULTS
Fifteen studies were identified for systematic review, of which 13 were included in the metaanalysis. In comparison with Gem monotherapy, the pooled hazard ratios (HR) of GemCap treatment for OS and PFS were 0.85 (95% CI: 0.75-0.95, P=0.007) and 0.80 (95% CI: 0.72-1.04, P=0.0002). The pooled 1-year survival rate, ORR and DCR of GemCap were, respectively, 33.1% (95% CI: 28.7-37.5), 22.9% (95% CI: 17.6-28.3) and 65.7% (95% CI: 56.7-74.8). GemCap combination therapy showed significantly higher ORR (OR: 1.98, 95% CI: 1.34-2.67, P=0.0003) and DCR (OR: 1.41, 95% CI: 1.05- 1.88, P=0.02) compared to Gem monotherapy. The most common grade ≥3 hematological toxicities in patients treated with GemCap combination therapy were neutropenia (19.7%), leucocytopenia (7.9%) and anemia (4.9%). The most common grade ≥3 non-hematological toxicities were hand-foot syndrome (6.3%), fatigue (5.7%) and nausea (4.8%).
CONCLUSIONS
GemCap combination therapy had an encouraging activity and might be a better treatment strategy compared with Gem alone in the first-line treatment for patients with advanced or metastatic pancreatic cancer.
Topics: Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Deoxycytidine; Humans; Pancreatic Neoplasms; Gemcitabine
PubMed: 32576005
DOI: 10.21037/apm-20-45 -
Urology Oct 2020Chemoablation is an emerging treatment for urothelial carcinomas. This review provides an overview of the evidence for intracavitary chemoablation in the treatment of...
Chemoablation is an emerging treatment for urothelial carcinomas. This review provides an overview of the evidence for intracavitary chemoablation in the treatment of urothelial carcinomas. The benefits of such agents include a reduction in morbidity and diseased organ preservation. While numerous agents have shown promise, research is limited due to small patient cohorts, varying follow-up, and no standardized methodology to assess response. Therefore, to date, chemoablation has not been widely adopted. This may change as a novel mitomycin formulation has recently been approved for treating low-grade upper tract urothelial carcinoma. Future studies are ongoing which evaluate other promising chemoablation options in urothelial carcinoma.
Topics: Administration, Intravesical; Antineoplastic Agents; Aziridines; BCG Vaccine; Carcinoma, Transitional Cell; Clinical Trials as Topic; Cystoscopy; Deoxycytidine; Epirubicin; Ethanol; Forecasting; Humans; Indolequinones; Injections, Intralesional; Interferon-alpha; Interleukin-2; Mitomycin; Urinary Bladder Neoplasms; Urothelium; Gemcitabine
PubMed: 32540302
DOI: 10.1016/j.urology.2020.05.066 -
International Journal of Rheumatic... Jul 2020The relative efficacy and safety of tofacitinib and peficitinib were assessed in patients with rheumatoid arthritis (RA) with an inadequate response to disease-modifying... (Meta-Analysis)
Meta-Analysis
Comparison of the efficacy and safety of tofacitinib and peficitinib in patients with active rheumatoid arthritis: A Bayesian network meta-analysis of randomized controlled trials.
OBJECTIVES
The relative efficacy and safety of tofacitinib and peficitinib were assessed in patients with rheumatoid arthritis (RA) with an inadequate response to disease-modifying antirheumatic drugs (DMARDs).
METHOD
We performed a Bayesian network meta-analysis to combine direct and indirect evidence from randomized controlled trials (RCTs) to examine the efficacy and safety of tofacitinib and peficitinib in combination with DMARDs in patients with an inadequate response to DMARDs.
RESULTS
Nine RCTs, including 3836 patients, met the inclusion criteria. Fifteen pairwise comparisons were performed, including six direct comparisons of seven interventions. Tofacitinib 10 mg+methotrexate (MTX) and peficitinib 150 mg+MTX were among the most effective treatments for patients with active RA with an inadequate DMARD response. The efficacy of tofacitinib 10 mg+MTX, peficitinib 150 mg+MTX or tofacitinib 5 mg+MTX tended to be higher than that of adalimumab+MTX. The ranking probability based on the surface under the cumulative ranking curve indicated that tofacitinib 10 mg+MTX had the greatest probability of being the best treatment to achieve the American College of Rheumatology 20 response rate, followed by peficitinib 150 mg+MTX, tofacitinib 5 mg+MTX, adalimumab+MTX, peficitinib 100 mg+MTX, and placebo+MTX. No significant differences were observed in the incidence of serious adverse events after treatment with tofacitinib+MTX, peficitinib+MTX, adalimumab+MTX, or placebo+MTX.
CONCLUSIONS
In patients with RA with an inadequate response to DMARDs, tofacitinib 10 mg+MTX and peficitinib 150 mg+MTX were the most efficacious interventions and were not associated with a significant risk of serious adverse events.
Topics: Adamantane; Antirheumatic Agents; Arthritis, Rheumatoid; Bayes Theorem; Drug Therapy, Combination; Humans; Network Meta-Analysis; Niacinamide; Piperidines; Protein Kinase Inhibitors; Pyrimidines; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 32483919
DOI: 10.1111/1756-185X.13854 -
Journal of Gynecology Obstetrics and... Jan 2021Our objective was to assess and rank different pharmacological interventions for relieving endometriosis-related pain. We conducted an online bibliographic search in... (Meta-Analysis)
Meta-Analysis
Our objective was to assess and rank different pharmacological interventions for relieving endometriosis-related pain. We conducted an online bibliographic search in different databases from their inception until March 2019. We included randomized controlled trials (RCTs) that assessed different medical therapies in the management of endometriosis-related pain. We applied this network meta-analysis (NMA) based on the frequentist approach using statistical package "netmeta" (version 1.0-1) in R software. Our main outcomes were the change in severity of pelvic pain, dysmenorrhea score, non-menstrual pelvic pain score, and dyspareunia score. Overall, 36 RCTs were included in this study (patients no. = 7942). Dienogest (0.94), combined hormonal contraceptives (CHCs) (0.782), and elagolix (0.38) were the highest-ranked interventions for reducing the severity of pelvic pain at three months, while at six months, gonadotropin-releasing hormone (GnRH) analogues (0.75), levonorgestrel-releasing intrauterine system (LNG-IUS) (0.73), and dienogest (0.65) were linked to more reduction in pelvic pain. The ranking p-score showed that GnRH analogues was the highest-ranked treatment for reducing dysmenorrhea at 3 months (1.00), while CHCs were the highest-ranked treatment at 6 months (0.97), followed by GnRH analogues (0.89). GnRH analogues (0.63) and elagolix (0.54) at three months while desogestrel (0.94) and CHCs (0.91) at six months were the highest-ranked treatment to reduce non-menstrual pelvic pain. GnRH analogues and elagolix were the highest-ranked pharmacologic therapies for reducing dyspareunia. In conclusion, CHCs, GnRH analogues, progesterone, and elagolix were the best approaches in reducing the pain of endometriosis.
Topics: Contraceptive Agents, Hormonal; Contraceptives, Oral, Hormonal; Dysmenorrhea; Endometriosis; Female; Gonadotropin-Releasing Hormone; Humans; Hydrocarbons, Fluorinated; Levonorgestrel; Nandrolone; Network Meta-Analysis; Pelvic Pain; Pyrimidines; Randomized Controlled Trials as Topic; Visual Analog Scale
PubMed: 32479894
DOI: 10.1016/j.jogoh.2020.101798