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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 -
The Cochrane Database of Systematic... Nov 2019Multiple myeloma is a bone marrow-based hematological malignancy accounting for approximately two per cent of cancers. First-line treatment for transplant-ineligible... (Meta-Analysis)
Meta-Analysis
Multiple drug combinations of bortezomib, lenalidomide, and thalidomide for first-line treatment in adults with transplant-ineligible multiple myeloma: a network meta-analysis.
BACKGROUND
Multiple myeloma is a bone marrow-based hematological malignancy accounting for approximately two per cent of cancers. First-line treatment for transplant-ineligible individuals consists of multiple drug combinations of bortezomib (V), lenalidomide (R), or thalidomide (T). However, access to these medicines is restricted in many countries worldwide.
OBJECTIVES
To assess and compare the effectiveness and safety of multiple drug combinations of V, R, and T for adults with newly diagnosed transplant-ineligible multiple myeloma and to inform an application for the inclusion of these medicines into the World Health Organization's (WHO) list of essential medicines.
SEARCH METHODS
We searched CENTRAL and MEDLINE, conference proceedings and study registries on 14 February 2019 for randomised controlled trials (RCTs) comparing multiple drug combinations of V, R and T for adults with newly diagnosed transplant-ineligible multiple myeloma.
SELECTION CRITERIA
We included RCTs comparing combination therapies of V, R, and T, plus melphalan and prednisone (MP) or dexamethasone (D) for first-line treatment of adults with transplant-ineligible multiple myeloma. We excluded trials including adults with relapsed or refractory disease, trials comparing drug therapies to other types of therapy and trials including second-generation novel agents.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data and assessed risk of bias of included trials. As effect measures we used hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) and risk ratios (RRs) for adverse events. An HR or RR < 1 indicates an advantage for the intervention compared to the main comparator MP. Where available, we extracted quality of life (QoL) data (scores of standardised questionnaires). Results quoted are from network meta-analysis (NMA) unless stated.
MAIN RESULTS
We included 25 studies (148 references) comprising 11,403 participants and 21 treatment regimens. Treatments were differentiated between restricted treatment duration (treatment with a pre-specified amount of cycles) and continuous therapy (treatment administered until disease progression, the person becomes intolerant to the drug, or treatment given for a prolonged period). Continuous therapies are indicated with a "c". Risk of bias was generally high across studies due to the open-label study design. Overall survival (OS) Evidence suggests that treatment with RD (HR 0.63 (95% confidence interval (CI) 0.40 to 0.99), median OS 55.2 months (35.2 to 87.0)); TMP (HR 0.75 (95% CI 0.58 to 0.97), median OS: 46.4 months (35.9 to 60.0)); and VRDc (HR 0.49 (95% CI 0.26 to 0.92), median OS 71.0 months (37.8 to 133.8)) probably increases survival compared to median reported OS of 34.8 months with MP (moderate certainty). Treatment with VMP may result in a large increase in OS, compared to MP (HR 0.70 (95% CI 0.45 to 1.07), median OS 49.7 months (32.5 to 77.3)), low certainty). Progression-free survival (PFS) Treatment withRD (HR 0.65 (95% CI0.44 to 0.96), median PFS: 24.9 months (16.9 to 36.8)); TMP (HR 0.63 (95% CI 0.50 to 0.78), median PFS:25.7 months (20.8 to 32.4)); VMP (HR 0.56 (95% CI 0.35 to 0.90), median PFS: 28.9 months (18.0 to 46.3)); and VRDc (HR 0.34 (95% CI 0.20 to 0.58), median PFS: 47.6 months (27.9 to 81.0)) may result in a large increase in PFS (low certainty) compared to MP (median reported PFS: 16.2 months). Adverse events The risk of polyneuropathies may be lower with RD compared to treatment with MP (RR 0.57 (95% CI 0.16 to 1.99), risk for RD: 0.5% (0.1 to 1.8), mean reported risk for MP: 0.9% (10 of 1074 patients affected), low certainty). However, the CIs are also compatible with no difference or an increase in neuropathies. Treatment with TMP (RR 4.44 (95% CI1.77 to 11.11), risk: 4.0% (1.6 to 10.0)) and VMP (RR 88.22 (95% CI 5.36 to 1451.11), risk: 79.4% (4.8 to 1306.0)) probably results in a large increase in polyneuropathies compared to MP (moderate certainty). No study reported the amount of participants with grade ≥ 3 polyneuropathies for treatment with VRDc. VMP probably increases the proportion of participants with serious adverse events (SAEs) compared to MP (RR 1.28 (95% CI 1.06 to 1.54), risk for VMP: 46.2% (38.3 to 55.6), mean risk for MP: 36.1% (177 of 490 patients affected), moderate certainty). RD, TMP, and VRDc were not connected to MP in the network and the risk of SAEs could not be compared. Treatment with RD (RR 4.18 (95% CI 2.13 to 8.20), NMA-risk: 38.5% (19.6 to 75.4)); and TMP (RR 4.10 (95% CI 2.40 to 7.01), risk: 37.7% (22.1 to 64.5)) results in a large increase of withdrawals from the trial due to adverse events (high certainty) compared to MP (mean reported risk: 9.2% (77 of 837 patients withdrew)). The risk is probably slightly increased with VMP (RR 1.06 (95% CI 0.63 to 1.81), risk: 9.75% (5.8 to 16.7), moderate certainty), while it is much increased with VRDc (RR 8.92 (95% CI 3.82 to 20.84), risk: 82.1% (35.1 to 191.7), high certainty) compared to MP. Quality of life QoL was reported in four studies for seven different treatment regimens (MP, MPc, RD, RMP, RMPc, TMP, TMPc) and was measured with four different tools. Assessment and reporting differed between studies and could not be meta-analysed. However, all studies reported an improvement of QoL after initiation of anti-myeloma treatment for all assessed treatment regimens.
AUTHORS' CONCLUSIONS
Based on our four pre-selected comparisons of interest, continuous treatment with VRD had the largest survival benefit compared with MP, while RD and TMP also probably considerably increase survival. However, treatment combinations of V, R, and T also substantially increase the incidence of AEs, and lead to a higher risk of treatment discontinuation. Their effectiveness and safety profiles may best be analysed in further randomised head-to-head trials. Further trials should focus on consistent reporting of safety outcomes and should use a standardised instrument to evaluate QoL to ensure comparability of treatment-combinations.
Topics: Antibodies, Monoclonal; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bortezomib; Humans; Lenalidomide; Multiple Myeloma; Network Meta-Analysis; Randomized Controlled Trials as Topic; Thalidomide
PubMed: 31765002
DOI: 10.1002/14651858.CD013487 -
Medicine Sep 2019The purpose of this study was to assess the efficacy and hypoglycemic risk of sitagliptin versus that of GLP-1 receptor agonists in the management of obese/overweight... (Comparative Study)
Comparative Study Meta-Analysis
OBJECTIVE
The purpose of this study was to assess the efficacy and hypoglycemic risk of sitagliptin versus that of GLP-1 receptor agonists in the management of obese/overweight patients with T2DM.
METHODS
EMBASE, PubMed, Cochrane Library, and ClinicalTrials.gov were searched; randomized controlled trials comparing the efficacy of sitagliptin versus that of GLP-1 receptor agonists in obese/overweight patients with T2DM were included. The mean BMI of participants for each study was ≥30 kg/m. We conducted a meta-analysis according to the methods specified in the Cochrane Handbook for Systematic Reviews of Interventions. RevMan 5.1 software was used to perform the meta-analysis. The Cochrane Q test and I statistics were used to estimate the heterogeneity among studies. The results are expressed as the mean difference (MD) or risk ratio (RR) with 95% confidence intervals.
RESULTS
A total of 8 eligible studies were included in our meta-analysis. Compared with GLP-1 receptor agonists, sitagliptin was less effective at reducing HbA1c (0.42 [0.27, 0.56]), FPG (0.78 [0.36, 1.19]), PPG (2.61 [1.35, 3.87]), and body weight (1.42 [0.71, 2.14]). Conversely, there were no significant differences in SBP reduction (0.38 [-1.14, 1.89]), DBP reduction (-0.30 [-1.00, 0.39]), and hypoglycemic risk (1.09 [0.50, 2.35]).
CONCLUSION
For obese/overweight patients, sitagliptin may exert a less potent effect on HbA1C, FPG, PPG, and weight reduction than GLP-1 receptor agonists, but these drugs had a similar efficacy in reducing blood pressure; furthermore, there was no significant difference in hypoglycemic risk.
Topics: Blood Glucose; Blood Pressure; Body Weight; Diabetes Mellitus, Type 2; Glucagon-Like Peptide-1 Receptor; Humans; Hypoglycemia; Hypoglycemic Agents; Obesity; Sitagliptin Phosphate
PubMed: 31490412
DOI: 10.1097/MD.0000000000017081 -
Journal of Comparative Effectiveness... Sep 2019To assess the cost-effectiveness of lenalidomide plus low dose dexamethasone (Rd) relative to bortezomib-contained therapy (BCT) for newly diagnosed multiple myeloma...
To assess the cost-effectiveness of lenalidomide plus low dose dexamethasone (Rd) relative to bortezomib-contained therapy (BCT) for newly diagnosed multiple myeloma patients ineligible for stem cell transplantation (ndMM) in China. A literature review was conducted to identify appropriate evidence for developing a cost-effectiveness model comparing Rd with BCT for lifetime health outcomes and direct medical costs in Chinese ndMM patients. The estimated incremental cost-effectiveness ratio per gained quality-adjusted life years for Rd versus BCT was ¥49,793. The chance for Rd to be cost effective, under the cost-effectiveness thresholds of three-times the 2018 Chinese gross domestic goods per capita, was 90.8%. The cost-effectiveness of Rd relative to BCT for ndMM in Chinese patients is highly attractive.
Topics: Antineoplastic Combined Chemotherapy Protocols; Bortezomib; China; Combined Modality Therapy; Cost-Benefit Analysis; Dexamethasone; Female; Humans; Lenalidomide; Male; Middle Aged; Multiple Myeloma; Observational Studies as Topic; Quality-Adjusted Life Years; Stem Cell Transplantation; Thalidomide
PubMed: 31232089
DOI: 10.2217/cer-2019-0052