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BMC Cancer Feb 2024To compare the efficacy, safety and effects on quality of life of different ALK-inhibitors for global and Asian patients with advanced ALK-positive non-small-cell lung... (Meta-Analysis)
Meta-Analysis
Identifying optimal ALK inhibitors in first- and second-line treatment of patients with advanced ALK-positive non-small-cell lung cancer: a systematic review and network meta-analysis.
OBJECTIVES
To compare the efficacy, safety and effects on quality of life of different ALK-inhibitors for global and Asian patients with advanced ALK-positive non-small-cell lung cancer (NSCLC).
METHODS
The included RCTs were identified through a systematic search of PubMed, EMBASE, Cochrane Library, Clinical Trials.gov, and major cancer conferences. The assessment of progression-free survival (PFS), intracranial PFS, overall survival (OS), and patient-reported outcomes (PROs) was carried out using restricted mean survival time (RMST) model, fractional polynomial model and Royston-Parmar model. Time-invariant hazard ratio (HR) models were also used to validate and supplement the primary analysis. Objective response rate (ORR) and adverse events with any grade, grade 3-5 were assessed through a Bayesian network meta-analysis. The primary measures for OS, PFS, and PROs were HR and RMST. The odds ratio was the metric for evaluating safety, ORR, 12-month PFS rate, 24-month OS rate, and the 12-month non-deterioration rate of PROs. Subgroup analyses based on patient characteristics were performed.
RESULTS
A total of fourteen studies (ten for first-line, four for second-line) consisting of nine treatments (chemotherapy, crizotinib, alectinib [600mg BID], low-dose alectinib [300mg BID], brigatinib, ceritinib, ensartinib, envonalkib, and lorlatinib) were included. In the first-line setting, alectinib showed a significant advantage over crizotinib and had the longest OS among all ALK-inhibitors. Compared to crizotinib, lorlatinib had the best efficacy regarding PFS for global patients, followed closely by alectinib and brigatinib. For Asian patients, alectinib significantly improved PFS compared to other treatments. In second-line, alectinib had the highest PFS for patients pretreated with crizotinib, followed by brigatinib, ceritinib and chemotherapy. Alectinib, irrespective of the dose, was the safest first-line option, whereas lorlatinib, brigatinib, and ceritinib showed poorer safety profiles. Alectinib was also the safest ALK-inhibitor for crizotinib-resistant patients. Brigatinib had the best performance in terms of PROs.
CONCLUSIONS
Considering both efficacy and safety, alectinib appears to be the preferable treatment in first-line and second-line, particularly for Asian patients.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Crizotinib; Lung Neoplasms; Network Meta-Analysis; Bayes Theorem; Quality of Life; Anaplastic Lymphoma Kinase; Protein Kinase Inhibitors; Carbazoles; Sulfones; Aminopyridines; Lactams; Pyrimidines; Pyrazoles; Organophosphorus Compounds
PubMed: 38331773
DOI: 10.1186/s12885-024-11916-4 -
Food and Chemical Toxicology : An... Mar 2024This systematic review evaluated the health risks of electronic cigarettes (e-cigarettes) compared to traditional cigarettes. It examines various studies and research on... (Review)
Review
BACKGROUND
This systematic review evaluated the health risks of electronic cigarettes (e-cigarettes) compared to traditional cigarettes. It examines various studies and research on the subject to provide a comprehensive analysis of potential health risks associated with both smoking methods.
METHODS
The systematic review, incorporating searches in PubMed, Scopus, Web of Science, and the Cochrane Library up to July 2023, examines the results obtained in relevant studies, and provides a critical discussion of the results.
RESULTS
E-cigarettes exhibit reduced exposure to harmful toxins compared to traditional cigarettes.
CONCLUSION
However, concerns persist regarding respiratory irritation and potential health risks, especially among youth, emphasizing the need for comprehensive, long-term research and protective legislation.
Topics: Adolescent; Humans; Nicotine; Electronic Nicotine Delivery Systems; Tobacco Products; Smoking
PubMed: 38331086
DOI: 10.1016/j.fct.2024.114507 -
Scientific Reports Feb 2024Individual trials of abemaciclib, palbociclib, and ribociclib show a similar impact on progression-free survival yet differing statistical significance for overall... (Meta-Analysis)
Meta-Analysis
Individual trials of abemaciclib, palbociclib, and ribociclib show a similar impact on progression-free survival yet differing statistical significance for overall survival (OS). A robust comparative evaluation of OS, safety, and tolerability of the three drugs is warranted. A systematic literature search identified phase 3 randomized clinical trials reporting OS of CDK4/6 inhibitors (CDK4/6i) in combination with endocrine therapy in ER-positive/HER2-negative advanced breast cancer. Trial-level data on OS and common and serious adverse events (AE) were extracted for each drug. In the absence of direct comparisons, a network meta-analysis was performed to evaluate pairwise comparative efficacy, safety, and tolerability of each of the CDK4/6i. Seven studies comprising of 4415 patients met the inclusion criteria. Median follow-up was 73.3 months (range: 48.7-97.2 months). There were no statistically significant differences in OS between any of the CDK4/6i. Compared to palbociclib, ribociclib and abemaciclib both showed significantly higher GI toxicity (grade 1-2 vomiting OR 1.87 [95% CI 1.37-2.56] and OR 2.27 [95% CI 1.59-3.23] respectively). Compared to palbociclib, abemaciclib was associated with more grade 3-4 diarrhea OR 118.06 [95% CI 7.28-1915.32]. In contrast, palbociclib was associated with significantly more neutropenia than ribociclib and abemaciclib but significantly lower risk of grade 3-4 infections. Abemaciclib had significantly less grade 3-4 transaminitis and grade 3-4 neutropenia than ribociclib. Treatment discontinuation and death due to AE were significantly higher with abemaciclib than palbociclib and ribociclib. There is no statistically significant difference in OS between CDK4/6i despite differing statistical significance levels of individual trials. Real-world data analyses may help to identify if there is a meaningful inter-drug difference in efficacy. Significant differences between CDK4/6i are observed for safety and tolerability outcomes.
Topics: Female; Humans; Aminopyridines; Antineoplastic Combined Chemotherapy Protocols; Benzimidazoles; Breast Neoplasms; Cyclin-Dependent Kinase 4; Cyclin-Dependent Kinase 6; Cyclin-Dependent Kinase Inhibitor Proteins; Neutropenia; Purines; Clinical Trials, Phase III as Topic; Randomized Controlled Trials as Topic
PubMed: 38326452
DOI: 10.1038/s41598-024-53151-8 -
PloS One 2024To evaluate the efficacy and safety of multi-drug therapy based on eszopiclone in the treatment of insomnia after stroke using a network meta-analysis method and to... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To evaluate the efficacy and safety of multi-drug therapy based on eszopiclone in the treatment of insomnia after stroke using a network meta-analysis method and to provide evidence for clinical practice.
METHOD
Computer searches of PubMed, Excerpt Medica Database (Embase), Cochrane Library Central Register of Controlled Trials, APA PsycInfo, CNKI, WanFang, Sinomed and other databases were performed to search for clinical randomized controlled studies (RCTs) on multi-drug therapy based on eszopiclone in the treatment of insomnia patients after stroke. The search time was from the establishment of each database until July 2023. The bias risk assessment tool recommended by Cochrane was used to evaluate the quality of the included RCTs. Stata 14.0 was applied to perform network meta-analysis using Review Manager 5.3 software for traditional meta-analysis.
RESULT
Eighteen RCTs and 1646 patients were ultimately included, involving 11 treatment options. The results of the network meta-analysis showed that the ranking of Pittsburgh Sleep Quality Index (PSQI) decline was eszopiclone combined with sweet dream oral liquid (ESZ+SDOL)>eszopiclone combined with a shugan jieyu capsule (ESZ+SGJYC)>eszopiclone combined with agomelatine (ESZ+AGO)>eszopiclone combined with flupentixol and melitracen tablets (ESZ+FMT)>eszopiclone combined with yangxue qingnao granules (ESZ+YXQNG)>eszopiclone combined with mirtazapine (ESZ+MIR)>ESZ>FMT; the modified Edinburgh Scandinavia Stroke Scale (MESSS) decline ranking was ESZ+SDOL>ESZ+AGO>ESZ; and the clinical total effective rate ranking was eszopiclone combined with a xuefu zhuyu capsule (ESZ+XFZYC)>ESZ+MIR>ESZ+SGJYC>ESZ+SDOL> ESZ+FMT>ESZ+YXQNG>ESZ>FMT. In terms of clinical adverse reactions, in addition to ESZ therapy, ESZ+ESC had the highest number of adverse reactions, with abdominal pain being the most common. ESZ+YXQNG had the most types of adverse reactions, with 8 types.
CONCLUSION
Multi-drug therapy based on eszopiclone can effectively improve the sleep quality of patients with insomnia after stroke, and ESZ+SDOL has significant efficacy and safety. However, due to the limitations of this study, efficacy ranking cannot fully explain the superiority or inferiority of clinical efficacy. In the future, more multicentre, large sample, double-blind randomized controlled trials are needed to supplement and demonstrate the results of this study.
Topics: Humans; Eszopiclone; Sleep Initiation and Maintenance Disorders; Network Meta-Analysis; Stroke; Double-Blind Method; Randomized Controlled Trials as Topic
PubMed: 38315683
DOI: 10.1371/journal.pone.0297064 -
The Journal of Headache and Pain Feb 2024To compare the outcomes associated with the use of lasmiditan, rimegepant, ubrogepant, and zavegepant for the acute management of migraine headaches. (Meta-Analysis)
Meta-Analysis Review
Comparison of effectiveness and safety of lasmiditan and CGRP-antagonists for the acute treatment of migraine in adults: systematic review and network meta-analysis of randomised trials.
OBJECTIVE
To compare the outcomes associated with the use of lasmiditan, rimegepant, ubrogepant, and zavegepant for the acute management of migraine headaches.
METHODS
We searched four electronic databases from database inception to August 31, 2023, to identify randomized controlled trials (RCTs) that report efficacy and safety for the acute treatment of migraine. The risk of bias in the included RCTs was evaluated according to the Cochrane tool, and the certainty of evidence using the CINeMA approach. We conducted frequentist network meta-analyses (NMA) to summarise the evidence. Data were analyzed using R-4.3.1.
RESULTS
A total of 18 eligible studies including 10 different types of interventions with 22,429 migraine patients were included. NMA results showed that compared to ubrogepant (25 mg and 50 mg) and zavegepant, lasmiditan (100 mg and 200 mg) exhibits an elevated probability of achieving pain relief within a 2-hour interval. Similarly, relative to zavegepant, rimegepant (75 mg) and ubrogepant (50 mg and 100 mg) demonstrate an enhanced likelihood of sustaining pain relief over a 24-hour period. Furthermore, in contrast to ubrogepant (25 mg) and lasmiditan (50 mg), rimegepant (75 mg) presents a heightened probability of achieving freedom from photophobia within 2 h. Regarding safety, lasmiditan carries the highest risk of adverse events, which are associated with an increased incidence of adverse effects, including dizziness, somnolence, asthenia, paresthesia, and fatigue.
CONCLUSIONS
In this NMA, a spectrum of evidence ranging from very low to high levels underscores the favorable efficacy and tolerability of rimegepant 75 mg and ubrogepant 100 mg, positioning them as potential candidates for the acute management of migraine. Concurrently, lasmiditan (100 mg and 200 mg) exhibits notable efficacy, albeit accompanied by an increased susceptibility to adverse events. These findings should still be approached with caution, primarily due to the intrinsic limitations associated with indirect comparisons.
Topics: Adult; Humans; Benzamides; Calcitonin Gene-Related Peptide; Migraine Disorders; Network Meta-Analysis; Pain; Piperidines; Pyridines; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 38311738
DOI: 10.1186/s10194-024-01723-4 -
Health and Quality of Life Outcomes Feb 2024Understanding consequences of poor chelation compliance is crucial given the enormous burden of post-transfusional iron overload complications. We systematically... (Review)
Review
Understanding consequences of poor chelation compliance is crucial given the enormous burden of post-transfusional iron overload complications. We systematically reviewed iron-chelation therapy (ICT) compliance, and the relationship between compliance with health outcome and health-related quality of life (HRQoL) in thalassaemia patients. Several reviewers performed systematic search strategy of literature through PubMed, Scopus, and EBSCOhost. The preferred reporting items of systematic reviews and meta-analyses (PRISMA) guidelines were followed. Of 4917 studies, 20 publications were included. The ICT compliance rate ranges from 20.93 to 75.3%. It also varied per agent, ranging from 48.84 to 85.1% for desferioxamine, 87.2-92.2% for deferiprone and 90-100% for deferasirox. Majority of studies (N = 10/11, 90.91%) demonstrated significantly negative correlation between compliance and serum ferritin, while numerous studies revealed poor ICT compliance linked with increased risk of liver disease (N = 4/7, 57.14%) and cardiac disease (N = 6/8, 75%), endocrinologic morbidity (N = 4/5, 90%), and lower HRQoL (N = 4/6, 66.67%). Inadequate compliance to ICT therapy is common. Higher compliance is correlated with lower serum ferritin, lower risk of complications, and higher HRQoL. These findings should be interpreted with caution given the few numbers of evidence.
Topics: Humans; Iron Chelating Agents; Deferasirox; Deferiprone; Deferoxamine; Quality of Life; Pyridones; Benzoates; Triazoles; Thalassemia; Chelation Therapy; Ferritins; Outcome Assessment, Health Care
PubMed: 38302961
DOI: 10.1186/s12955-023-02221-y -
BMC Gastroenterology Jan 2024To evaluate the efficacy and safety of the combination of camrelizumab and apatinib in the treatment of liver cancer and to furnish clinical recommendations for... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To evaluate the efficacy and safety of the combination of camrelizumab and apatinib in the treatment of liver cancer and to furnish clinical recommendations for pharmacological interventions.
METHODS
PubMed, Embase, Web of Science and the Cochrane Library were scrutinized for research publications from their inception to 22 December 2023. Bibliographic perusal and data procurement were executed. The quality of the included studies was evaluated employing the MINORS tool. Meta-analysis was conducted utilizing Stata 15.0 software.
RESULTS
A total of 10 studies involving 849 patients were included in the meta-analysis. The study revealed that the objective response rate (ORR) of the combined therapy was 28% (95% CI: 23%-34%), the disease control rate (DCR) was 69% (95% CI: 64%-73%), the median progression-free survival (mPFS) was 5.87 months (95% CI: 4.96-6.78), the median overall survival (mOS) was 19.35 months (95% CI: 17.53-21.17), the incidence of any grade adverse events was 90% (95% CI: 85%-95%), and the occurrence of grade 3 or higher adverse events was 49% (95% CI: 27%-71%).
CONCLUSION
The combination of camrelizumab and apatinib exhibits commendable effectiveness in the management of liver cancer; nevertheless, vigilance should be exercised concerning potential adverse reactions in clinical applications to enhance the safety of pharmacological interventions.
Topics: Humans; Antibodies, Monoclonal, Humanized; Pyridines; Liver Neoplasms
PubMed: 38297195
DOI: 10.1186/s12876-024-03144-8 -
International Journal of Molecular... Jan 2024This systematic review and meta-analysis evaluated the efficacy of dexlansoprazole (a proton pump inhibitor-PPI) in resolving heartburn, reflux, and other symptoms and... (Meta-Analysis)
Meta-Analysis Review
This systematic review and meta-analysis evaluated the efficacy of dexlansoprazole (a proton pump inhibitor-PPI) in resolving heartburn, reflux, and other symptoms and complications resulting from gastroesophageal reflux disease (GERD). The study followed PRISMA 2020 and was registered in PROSPERO (CRD42020206513). The search strategy used MeSH and free terms appropriately adapted for each database. Only randomized clinical trials (RCTs) were included. The Cochrane tool (RoB 2.0) was used to assess the risk of bias, and the certainty of evidence was rated using GRADE. Ten RCTs were included. Dexlansoprazole outperformed the placebo and other PPIs in the resolution of heartburn and reflux symptoms in patients with GERD, with benefits during and after treatment, especially in those with moderate and severe symptoms. The meta-analyses indicated that dexlansoprazole at doses of 30 and 60 mg had more 24 h heartburn-free days and nights compared to the placebo medications; no difference was reported between dexlansoprazole at doses of 30 and 60 mg in heartburn-free nights. A low bias risk and a moderate certainty of evidence were observed. This review confirms the therapeutic effect of dexlansoprazole (placebo-controlled) and its improvements in GERD symptoms compared to another PPI. However, the interpretation of the results should be carried out cautiously due to the small number of included studies and other reported limitations.
Topics: Humans; Dexlansoprazole; Gastroesophageal Reflux; Heartburn; Proton Pump Inhibitors; Treatment Outcome
PubMed: 38279248
DOI: 10.3390/ijms25021247 -
The Cochrane Database of Systematic... Jan 2024Balancing the risk of bleeding and thrombosis after acute myocardial infarction (AMI) is challenging, and the optimal antithrombotic therapy remains uncertain. The... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Balancing the risk of bleeding and thrombosis after acute myocardial infarction (AMI) is challenging, and the optimal antithrombotic therapy remains uncertain. The potential of non-vitamin K antagonist oral anticoagulants (NOACs) to prevent ischaemic cardiovascular events is promising, but the evidence remains limited.
OBJECTIVES
To evaluate the efficacy and safety of non-vitamin-K-antagonist oral anticoagulants (NOACs) in addition to background antiplatelet therapy, compared with placebo, antiplatelet therapy, or both, after acute myocardial infarction (AMI) in people without an indication for anticoagulation (i.e. atrial fibrillation or venous thromboembolism).
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, the Conference Proceedings Citation Index - Science, and two clinical trial registers in September 2022 with no language restrictions. We checked the reference lists of included studies for any additional trials.
SELECTION CRITERIA
We searched for randomised controlled trials (RCTs) that evaluated NOACs plus antiplatelet therapy versus placebo, antiplatelet therapy, or both, in people without an indication for anticoagulation after an AMI.
DATA COLLECTION AND ANALYSIS
Two review authors independently checked the results of searches to identify relevant studies, assessed each included study, and extracted study data. We conducted random-effects pairwise analyses using Review Manager Web, and network meta-analysis using the R package 'netmeta'. We ranked competing treatments by P scores, which are derived from the P values of all pairwise comparisons and allow ranking of treatments on a continuous 0-to-1 scale.
MAIN RESULTS
We identified seven eligible RCTs, including an ongoing trial that we could not include in the analysis. Of the six RCTs involving 33,039 participants, three RCTs compared rivaroxaban with placebo, two RCTs compared apixaban with placebo, and one RCT compared dabigatran with placebo. All participants in the six RCTs received concomitant antiplatelet therapy. The available evidence suggests that rivaroxaban compared with placebo reduces the rate of all-cause mortality (risk ratio (RR) 0.82, 95% confidence interval (CI) 0.69 to 0.98; number needed to treat for an additional beneficial outcome (NNTB) 250; 3 studies, 21,870 participants; high certainty) and probably reduces cardiovascular mortality (RR 0.83, 95% CI 0.69 to 1.01; NNTB 250; 3 studies, 21,870 participants; moderate certainty). There is probably little or no difference between apixaban and placebo in all-cause mortality (RR 1.09, 95% CI 0.88 to 1.35; number needed to treat for an additional harmful outcome (NNTH) 334; 2 studies, 8638 participants; moderate certainty) and cardiovascular mortality (RR 0.99, 95% CI 0.77 to 1.27; number needed to treat not applicable; 2 studies, 8638 participants; moderate certainty). Dabigatran may reduce the rate of all-cause mortality compared with placebo (RR 0.57, 95% CI 0.31 to 1.06; NNTB 63; 1 study, 1861 participants; low certainty). Dabigatran compared with placebo may have little or no effect on cardiovascular mortality, although the point estimate suggests benefit (RR 0.72, 95% CI 0.34 to 1.52; NNTB 143; 1 study, 1861 participants; low certainty). Two of the investigated NOACs were associated with an increased risk of major bleeding compared to placebo: apixaban (RR 2.41, 95% CI 1.44 to 4.06; NNTH 143; 2 studies, 8544 participants; high certainty) and rivaroxaban (RR 3.31, 95% CI 1.12 to 9.77; NNTH 125; 3 studies, 21,870 participants; high certainty). There may be little or no difference between dabigatran and placebo in the risk of major bleeding (RR 1.74, 95% CI 0.22 to 14.12; NNTH 500; 1 study, 1861 participants; low certainty). The results of the network meta-analysis were inconclusive between the different NOACs at all individual doses for all primary outcomes. However, low-certainty evidence suggests that apixaban (combined dose) may be less effective than rivaroxaban and dabigatran for preventing all-cause mortality after AMI in people without an indication for anticoagulation.
AUTHORS' CONCLUSIONS
Compared with placebo, rivaroxaban reduces all-cause mortality and probably reduces cardiovascular mortality after AMI in people without an indication for anticoagulation. Dabigatran may reduce the rate of all-cause mortality and may have little or no effect on cardiovascular mortality. There is probably no meaningful difference in the rate of all-cause mortality and cardiovascular mortality between apixaban and placebo. Moreover, we found no meaningful benefit in efficacy outcomes for specific therapy doses of any investigated NOACs following AMI in people without an indication for anticoagulation. Evidence from the included studies suggests that rivaroxaban and apixaban increase the risk of major bleeding compared with placebo. There may be little or no difference between dabigatran and placebo in the risk of major bleeding. Network meta-analysis did not show any superiority of one NOAC over another for our prespecified primary outcomes. Although the evidence suggests that NOACs reduce mortality, the effect size or impact is small; moreover, NOACs may increase major bleeding. Head-to-head trials, comparing NOACs against each other, are required to provide more solid evidence.
Topics: Humans; Dabigatran; Rivaroxaban; Network Meta-Analysis; Platelet Aggregation Inhibitors; Anticoagulants; Myocardial Infarction; Hemorrhage
PubMed: 38264795
DOI: 10.1002/14651858.CD014678.pub2 -
Biomolecules Dec 2023The purported cognitive benefits associated with nicotine and its metabolites in the brain are a matter of debate. In this review, the impact of the pharmacologically... (Review)
Review
The purported cognitive benefits associated with nicotine and its metabolites in the brain are a matter of debate. In this review, the impact of the pharmacologically active metabolite of a nicotine derivative produced by bacteria named 6-hydroxy-L-nicotine (6HLN) on memory, oxidative stress, and the activity of the cholinergic system in the brain was examined. A search in the PubMed, Science Direct, Web of Science, and Google Scholar databases, limiting entries to those published between 1992 and 2023, was conducted. The search focused specifically on articles about nicotine metabolites, memory, oxidative stress, and cholinergic system activity, as well as enzymes or pathways related to nicotine degradation in bacteria. The preliminary search resulted in 696 articles, and following the application of exclusion criteria, 212 articles were deemed eligible for inclusion. This review focuses on experimental studies supporting nicotine catabolism in bacteria, and the chemical and pharmacological activities of nicotine and its metabolite 6HLN.
Topics: Bacteria; Brain; Cholinergic Agents; Databases, Factual; Nicotine; Humans
PubMed: 38254623
DOI: 10.3390/biom14010023