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Harm Reduction Journal Oct 2023E-cigarettes (electronic nicotine delivery system, ENDS) have been presented as a harm reduction strategy for people who smoke tobacco cigarettes but who cannot achieve...
BACKGROUND
E-cigarettes (electronic nicotine delivery system, ENDS) have been presented as a harm reduction strategy for people who smoke tobacco cigarettes but who cannot achieve abstinence, or for those who wish to continue to enjoy nicotine and the habit of smoking. What are the health effects of the substitution of ENDS for tobacco cigarettes? This systematic review evaluates the evidence of human clinical tests on the respiratory effects of ENDS use in participants who smoke tobacco cigarettes.
METHODS
A registered and published protocol was developed conforming to PRISMA 2020 and AMSTAR2 standards. The literature search was conducted in PubMed, Scopus, and the CENTRAL Cochrane Library and updated to May 2022. Three supplementary searches and a grey literature search were performed. Studies were evaluated with the JBI quality tools and the Oxford Catalogue of Bias. Due to the heterogeneity (diversity) of the studies, a narrative data synthesis was performed on the test findings plus three sub-group analyses.
RESULTS
The review consists of sixteen studies and twenty publications. Spirometry tests comprised the majority of the data. In total, 66 respiratory test measurements were reported, out of which 43 (65%) were not significant. Statistically significant findings were mixed, with 9 tests showing improvements and 14 measuring declines, none of which was clinically relevant. Ten studies were rated at a high risk of bias, and six had some concerns primarily due to inadequate research designs and the conduct of the studies. Reporting bias was documented in thirteen studies.
CONCLUSIONS
Most of the studies showed no difference in respiratory parameters. This indicates that ENDS substitution for smoking likely does not result in additional harm to respiratory health. Due to the low quality of the studies, confidence in the conclusions is rated as low. Robust studies with a longer duration and sufficient power are required to validate any potential benefits or possible harms of ENDS substitution. Registration PROSPERO #CRD42021239094, International Registered Report Identifier (IRRID): DERR1-10.2196/29084.
Topics: Humans; Electronic Nicotine Delivery Systems; Smoking Cessation; Nicotine; Tobacco Products
PubMed: 37794458
DOI: 10.1186/s12954-023-00877-9 -
Cardiovascular Therapeutics 2023Optimal antithrombotic therapy during the chronic maintenance period in patients with coronary artery disease (CAD) is unknown. We compared five kinds of mainstream... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Optimal antithrombotic therapy during the chronic maintenance period in patients with coronary artery disease (CAD) is unknown. We compared five kinds of mainstream chronic maintenance antithrombotic strategies at least one year after the acute phase: aspirin alone, clopidogrel alone, ticagrelor alone, continued dual antiplatelet therapy (DAPT) for a period of time, and maintenance with aspirin combined with a low-dose anticoagulant such as rivaroxaban.
METHODS
Ten randomized, controlled trials were selected using PubMed, Ovid MEDLINE, Embase, and Cochrane library through February 2023. The primary outcome was main adverse cardiac events (MACEs), and secondary outcomes include net adverse clinical events (NACEs), cardiac death, all-cause death, ischemic stroke, stent thrombosis, total bleeding, and major bleeding. A network meta-analysis was conducted with a random-effects model. Data extraction was performed by three independent reviewers.
RESULTS
Our search identified ten eligible randomized controlled trials enrolling a total of 82,084 patients comparing different chronic maintenance antithrombotic strategies. As for the primary endpoint, there was no statistical difference in MACE outcomes between any two of the five methods. As for the secondary endpoint, there was no statistical difference in NACE, major bleeding, all-cause death, cardiac death, and stent thrombosis between any two methods. The aspirin plus low-dose rivaroxaban group had a lower incidence of ischemic stroke compared to the aspirin group (OR = 0.49, 95% CrI 0.26-0.91). And the prolonged DAPT group had a higher total bleeding rate compared to aspirin group (OR = 2.4, 95% CrI 1.1-5.9).
CONCLUSIONS
In terms of MACE, NACE, all-cause death, cardiac death, stent thrombosis, and major bleeding, there were no significant differences between using aspirin alone, clopidogrel alone, and ticagrelor alone; extending DAPT duration; and using aspirin combined with low-dose rivaroxaban for chronic maintenance antithrombotic regimens. However, choosing aspirin combined with low-dose rivaroxaban can reduce the incidence of ischemic stroke, and prolonged DAPT may have a higher rate of total bleeding. However, it is important to note that this study is based on indirect comparisons, and there is currently a lack of direct evidence comparing various maintenance antiplatelet therapy regimens. Further high-quality studies are needed to address this gap and provide more conclusive evidence on the comparative effectiveness of different maintenance antiplatelet strategies.
Topics: Humans; Coronary Artery Disease; Network Meta-Analysis; Rivaroxaban; Clopidogrel; Fibrinolytic Agents; Platelet Aggregation Inhibitors; Ticagrelor; Ischemic Stroke; Aspirin
PubMed: 37636560
DOI: 10.1155/2023/5446271 -
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 -
Antibiotics (Basel, Switzerland) Jul 2023Bacterial infections have attracted the attention of researchers in recent decades, especially due to the special problems they have faced, such as their increasing... (Review)
Review
Bacterial infections have attracted the attention of researchers in recent decades, especially due to the special problems they have faced, such as their increasing diversity and resistance to antibiotic treatment. The emergence and development of the SARS-CoV-2 infection stimulated even more research to find new structures with antimicrobial and antiviral properties. Among the heterocyclic compounds with remarkable therapeutic properties, benzimidazoles, and triazoles stand out, possessing antimicrobial, antiviral, antitumor, anti-Alzheimer, anti-inflammatory, analgesic, antidiabetic, or anti-ulcer activities. In addition, the literature of the last decade reports benzimidazole-triazole hybrids with improved biological properties compared to the properties of simple mono-heterocyclic compounds. This review aims to provide an update on the synthesis methods of these hybrids, along with their antimicrobial and antiviral activities, as well as the structure-activity relationship reported in the literature. It was found that the presence of certain groups grafted onto the benzimidazole and/or triazole nuclei (-F, -Cl, -Br, -CF, -NO, -CN, -CHO, -OH, OCH, COOCH), as well as the presence of some heterocycles (pyridine, pyrimidine, thiazole, indole, isoxazole, thiadiazole, coumarin) increases the antimicrobial activity of benzimidazole-triazole hybrids. Also, the presence of the oxygen or sulfur atom in the bridge connecting the benzimidazole and triazole rings generally increases the antimicrobial activity of the hybrids. The literature mentions only benzimidazole-1,2,3-triazole hybrids with antiviral properties. Both for antimicrobial and antiviral hybrids, the presence of an additional triazole ring increases their biological activity, which is in agreement with the three-dimensional binding mode of compounds. This review summarizes the advances of benzimidazole triazole derivatives as potential antimicrobial and antiviral agents covering articles published from 2000 to 2023.
PubMed: 37508316
DOI: 10.3390/antibiotics12071220 -
Hypertension in Pregnancy Dec 2024Preeclampsia (PE) is a pregnancy disorder that represents a major cause of maternal and perinatal morbidity and mortality. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Preeclampsia (PE) is a pregnancy disorder that represents a major cause of maternal and perinatal morbidity and mortality.
METHODS
This network meta-analysis was registered with PROSPERO. We searched the PubMed, ClinicalTrials.gov. and Embase databases for studies published from inception to the 31 of March 2023. RevMan5.3 software provided by the Cochrane Collaboration was used for direct meta-analysis (DMA) statistical analysis. Funnel maps, network meta-analysis (NMA), the surface under the cumulative ranking curve (SUCRA) to rank the different interventions and publication bias were generated by STATA 17.0 software.
RESULTS
We included eight randomized controlled trials (RCTs) involving a total of 1192 women with PE; two studies were of high quality and six were of moderate quality. Eight interventions were addressed in the NMA. In the DMA, we found that blood pressure in the Ketanserin group were significantly higher than those in the Nicardipine group. NMA showed that blood pressure in the Dihydralazine group was significantly higher than that in the Methyldopa, Labetalol, Nicardipine and Diltiazem groups. And the blood pressure in the Labetalol group was significantly lower than that in the Nicardipine group. SUCRA values showed that Diltiazem was more effective in lowering blood pressure than other drugs looked at in this study.
CONCLUSION
According to the eight RCTs included in this study, Diltiazem was the most effective in reducing blood pressure in PE patients; Labetalol and Nicardipine also had good effects. Diltiazem is preferred for the treatment of patients with severe PE and high blood pressure.
Topics: Pregnancy; Female; Humans; Antihypertensive Agents; Labetalol; Pre-Eclampsia; Diltiazem; Nicardipine; Network Meta-Analysis
PubMed: 38488570
DOI: 10.1080/10641955.2024.2329068 -
PloS One 2023To date, isoniazid mono-resistant tuberculosis (TB) is becoming an emerging global public health problem. It is associated with poor treatment outcome. Different studies... (Meta-Analysis)
Meta-Analysis
BACKGROUND
To date, isoniazid mono-resistant tuberculosis (TB) is becoming an emerging global public health problem. It is associated with poor treatment outcome. Different studies have assessed the treatment outcome of isoniazid mono-resistant TB cases, however, the findings are inconsistent and there is limited global comprehensive report. Thus, this study aimed to assess the poor treatment outcome and its associated risk factors among patients with isoniazid mono-resistant TB.
METHODS
Studies that reported the treatment outcomes and associated factors among isoniazid mono-resistant TB were searched from electronic databases and other sources. We used Joana Briggs Institute critical appraisal tool to assess the study's quality. We assessed publication bias through visual inspection of the funnel plot and confirmed by Egger's regression test. We used STATA version 17 for statistical analysis.
RESULTS
Among 347 studies identified from the whole search, data were extracted from 25 studies reported from 47 countries. The pooled successful and poor treatment outcomes were 78% (95%CI; 74%-83%) and 22% (95%CI; 17%-26%), respectively. Specifically, complete, cure, treatment failure, mortality, loss to follow-up and relapse rates were 34%(95%CI; 17%-52%), 62% (95%CI; 50%-73%), 5% (95%CI; 3%-7%), 6% (95%CI; 4%-8%), 12% (95%CI; 8%-17%), and 1.7% (95%CI; 0.4%-3.1%), respectively. Higher prevalence of pooled poor treatment outcome was found in the South East Asian Region (estimate; 40%, 95%C; 34%-45%), and African Region (estimate; 33%, 95%CI; 24%-42%). Previous TB treatment (OR; 1.74, 95%CI; 1.15-2.33), having cancer (OR; 3.53, 95%CI; 1.43-5.62), and being initially smear positive (OR; 1.26, 95%CI; 1.08-1.43) were associated with poor treatment outcome. While those patients who took rifampicin in the continuation phase (OR; 0.22, 95%CI; 0.04-0.41), had extrapulmonary TB (OR; 0.70, 95%CI; 0.55-0.85), and took second-line injectable drugs (OR; 0.54, 95%CI; 0.33-0.75) had reduced risk of poor treatment outcome.
CONCLUSION
Isoniazid mono-resistant TB patients had high poor treatment outcome. Thus, determination of isoniazid resistance pattern for all bacteriologically confirmed TB cases is critical for successful treatment outcome. PROSPERO registration number: CRD42022372367.
Topics: Humans; Isoniazid; Antitubercular Agents; Tuberculosis, Multidrug-Resistant; Risk Factors; Treatment Outcome
PubMed: 37467275
DOI: 10.1371/journal.pone.0286194 -
Saudi Journal of Gastroenterology :... 2023Vonoprazan-amoxicillin (VA) dual therapy has recently been proposed to eradicate Helicobacter pylori (H. pylori) with controversial results. We, therefore, conducted a... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Vonoprazan-amoxicillin (VA) dual therapy has recently been proposed to eradicate Helicobacter pylori (H. pylori) with controversial results. We, therefore, conducted a meta-analysis to assess the effect of this therapy for H. pylori eradication.
METHODS
We searched PubMed, Embase, Cochrane Library, and Web of Science database from inception until November 2022, collecting randomized controlled trials (RCTs) comparing VA dual therapy with other regimens for H. pylori eradication. Pooled relative risks (RRs) were calculated using random effects model.
RESULTS
Five RCTs were ultimately included. Compared with the vonoprazan-amoxicillin-clarithromycin (VAC) triple therapy, the eradication rate of VA dual therapy was lower in intention-to-treat (ITT) analysis (n = 3 RCTs, RR = 0.94, 95% CI: 0.88-0.99, P = 0.03), but there was no significant difference between them in the per-protocol (PP) analysis (RR = 0.96, 95% CI: 0.91-1.01, P = 0.11). For clarithromycin-resistant H. pylori strains, the eradication rate of VA dual therapy was significantly higher than that of the VAC triple therapy (n = 2 RCTs, RR = 1.20, 95% CI: 1.03-1.39, P = 0.02). Compared with the PPI-based triple therapy (PAC), VA dual therapy had a superior eradication rate (n = 2 RCTs, ITT analysis: RR = 1.13, 95% CI: 1.04-1.23, P = 0.003; PP analysis: pooled RR = 1.14, 95% CI: 1.06-1.22, P = 0.0004). Compared with VAC or PAC triple therapy, VA dual therapy has a similar incidence of total adverse events and compliance.
CONCLUSIONS
VA dual therapy had a similar effect compared to VAC triple therapy and was superior to PAC triple therapy. Future RCTs are needed to ascertain the optimal dosage and duration of vonoprazan and amoxicillin, and the effect of VA dual therapy compared with the mainstream regimens recommended by current guidelines.
Topics: Humans; Amoxicillin; Clarithromycin; Anti-Bacterial Agents; Helicobacter pylori; Helicobacter Infections; Proton Pump Inhibitors; Randomized Controlled Trials as Topic; Drug Therapy, Combination; Treatment Outcome
PubMed: 37602635
DOI: 10.4103/sjg.sjg_153_23 -
Immunity, Inflammation and Disease Feb 2024There has been a global increase in the use of electronic cigarettes (EC). However, to our knowledge, no review has summarized or categorized changes in inflammatory... (Meta-Analysis)
Meta-Analysis
CONTEXT
There has been a global increase in the use of electronic cigarettes (EC). However, to our knowledge, no review has summarized or categorized changes in inflammatory biomarkers after EC use in the extant literature.
OBJECTIVE
To evaluate changes in general, cardiopulmonary, and oxidative stress-related inflammatory biomarkers in healthy adults who use ECs.
METHODS
A scoping review was conducted according to the Arksey and O'Malley framework. PubMed and MEDLINE (Ovid) databases were used for our search. After initial pilot searches and discussions, we performed a final search with medical subject headings and plain language terms related to inflammation, biomarkers, ECs, and adult humans. All full-text articles, gray literature, and primary studies dating from the inception of the searched databases to the present were included. Studies of human participants with known confounding medical histories were excluded.
RESULTS
Thirty-seven studies met the inclusion criteria. After short-term (<1 month) use, ECs containing nicotine moderately increased cardiovascular (CV) and oxidative stress markers of inflammation. Of all reported results, 50% of CV biomarkers were increased, and 64% of oxidative stress markers were increased. After long-term (>1 month) use, ECs containing nicotine produced mixed results. Two commonly measured biomarkers in this group, matrix metalloproteinase-9 (MMP-9) and interleukin-6 (IL-6), were elevated in 75% and 60% of measured instances, respectively.
CONCLUSION
The results of studies evaluated in our scoping review suggested that short-term use of nicotine-containing ECs may result in increased CV and oxidative stress inflammation, contributing to potential CV or neurologic disease development. The results of studies evaluated in our scoping review also suggested that long-term use of nicotine-containing ECs resulted in no significant changes in general inflammatory biomarker levels. A rigorous systematic review and meta-analysis is necessary to corroborate our findings and to determine the effect of long-term EC use on MMP-9 and IL-6 levels.
Topics: Adult; Humans; Biomarkers; Electronic Nicotine Delivery Systems; Inflammation; Interleukin-6; Matrix Metalloproteinase 9; Nicotine; Vaping
PubMed: 38353387
DOI: 10.1002/iid3.1170 -
Frontiers in Immunology 2024Although immune checkpoint inhibitors (ICIs) show a significant overall survival advantage over standard advanced renal cell carcinoma (aRCC) therapies, tumor response... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Although immune checkpoint inhibitors (ICIs) show a significant overall survival advantage over standard advanced renal cell carcinoma (aRCC) therapies, tumor response to these agents remains poor. Some studies have shown that combination therapy including an ICI appears to be the best treatment; however, the overall benefit in terms of efficacy and toxicity still needs to be assessed. Thus, we performed a network meta-analysis to evaluate the differences in the efficacy of several combinations that include an ICI to provide a basis for clinical treatment selection.
METHODS
We conducted a thorough search of PubMed, EMBASE, and the Cochrane Library for articles from January 2010 to June 2023. R 4.4.2 and STATA 16.0 were used to analyze data; hazard ratio (HR) and odds ratio (OR) with 95% confidence intervals (CI) were used to assess the results.
RESULTS
An indirect comparison showed that nivolumab plus cabozantinib and pembrolizumab plus lenvatinib were the most effective treatments for progression-free survival (PFS), with no significant differences between the two interventions (HR, 1.31; 95% CI, 0.96-1.78; P=0.08); rank probability showed that pembrolizumab plus lenvatinib had a 57.1% chance of being the preferred treatment. In the absence of indirect comparisons between pembrolizumab plus axitinib, nivolumab plus ipilimumab, avelumab plus axitinib, nivolumab plus cabozantinib, and pembrolizumab plus lenvatinib, pembrolizumab plus axitinib (40.2%) was the best treatment option for overall survival (OS). Compared to pembrolizumab plus lenvatinib, nivolumab plus ipilimumab (OR, 0.07; 95% CI, 0.01-0.65; P=0.02) and pembrolizumab plus axitinib (OR, 0.05; 95% CI, 0.00-0.78; P<0.001) had a lower incidence of overall adverse events (AEs).
CONCLUSION
Pembrolizumab plus lenvatinib and pembrolizumab plus axitinib resulted in the highest PFS and OS rates, respectively. Pembrolizumab plus axitinib may be the best option when AEs are a concern.
SYSTEMATIC REVIEW REGISTRATION
https://inplasy.com/, identifier INPLASY202410078.
Topics: Humans; Carcinoma, Renal Cell; Axitinib; Nivolumab; Immune Checkpoint Inhibitors; Ipilimumab; Network Meta-Analysis; Kidney Neoplasms; Anilides; Phenylurea Compounds; Pyridines; Quinolines
PubMed: 38390328
DOI: 10.3389/fimmu.2024.1255577 -
Open Heart Nov 2023Clopidogrel is a P2Y inhibitor that has become a mainstay treatment following percutaneous intervention with drug-eluting stent placement to decrease restenosis and its...
INTRODUCTION
Clopidogrel is a P2Y inhibitor that has become a mainstay treatment following percutaneous intervention with drug-eluting stent placement to decrease restenosis and its potential complications, including sudden cardiac death and ischaemic strokes in patients with significant vascular disease.
AREAS COVERED
As a prodrug, the metabolism and efficacy of clopidogrel are contingent on the presence of wild-type CYP450 (CYP2C19) alleles. Genetic polymorphisms and variants are well known to impair its ability to prevent major adverse cardiovascular events in these patients, with inadequate response rates as high as 30% in previous publications. Patterns of allelic frequencies are expected to exhibit similarities between individuals of the same ancestry, ethnic group or geographic region. Accordingly, we seek to further elucidate worldwide prevalence rates for genetic polymorphisms in the CYP2C19-dependent metabolism of clopidogrel and review the potential of personalised CYP2C19 genotyping in clinical practice to mitigate this high treatment resistance and its associated burden on patients.
EXPERTS' COMMENTARY
Our findings support the consideration of genotyping before initiation of therapy to guide adequate dosage or substitutions of other P2Y inhibitors to promote personalised, precision medicine and to prevent adverse events when these therapies may inevitably fail in patients with variants of the CYP450 (CYP2C19) system.
Topics: Humans; Clopidogrel; Platelet Aggregation Inhibitors; Cytochrome P-450 CYP2C19; Drug-Eluting Stents; Polymorphism, Genetic
PubMed: 37963685
DOI: 10.1136/openhrt-2023-002436