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Frontiers in Endocrinology 2023This study aimed to perform a network meta-analysis to objectively evaluate the efficacy and safety of 10 Glucagon-like peptide-1 receptor agonists (GLP-1RAs) in... (Comparative Study)
Comparative Study Meta-Analysis Review
PURPOSE
This study aimed to perform a network meta-analysis to objectively evaluate the efficacy and safety of 10 Glucagon-like peptide-1 receptor agonists (GLP-1RAs) in combination with metformin that is approved for use worldwide in patients with type 2 diabetes and to provide evidence-based support and reference for the selection of clinical treatment.
METHODS
Three databases (PubMed, Embase, and Cochrane Library) were searched from their respective inception until September 30, 2022. Only randomized controlled trials comparing the efficacy and safety of GLP-1RAs for treating type 2 diabetes (T2D) were included. The 10 GLP-1RAs are exenatide (including exenatide twice daily and once weekly), liraglutide, lixisenatide, dulaglutide, PEX168, semaglutide (subcutaneous and oral semaglutide), tirzepatide and albiglutide.
RESULTS
34 RCTs with 10 GLP-1RAs and 12993 patients were included in the Network Meta-Analysis (NMA). According to the NMA, tirzepatide 15 mg, semaglutide 1.0 mg, PEX168-200μg, oral semaglutide 14 and dulaglutide 1.5 mg reduced HbA1c by -2.23%, -1.57%, -1.12%, -1.10%, -1.09% and body weight by -11.33 kg, -5.99 kg, +0.40 kg, -3.95 kg, -1.87 kg, respectively. There was no significant difference in the rate of adverse events for tirzepatide 15 mg, oral-semaglutide 14 mg, and semaglutide 1.0 mg. PEX168-200μg, tirzepatide 15mg, and oral semaglutide 14mg had Surface Under the Cumulative Ranking (SUCRA) values greater than placebo, and only tirzepatide 15mg and oral semaglutide 14mg were significantly different from placebo in the rate of serious adverse events. All GLP-1RA did not lead to increased incidence of hypoglycemia. Albiglutide 30mg and semaglutide 1.0mg significantly differed from placebo in Adverse Event (AE) withdrawal. Finally, the sensitivity analysis and publication bias analysis results indicate that the study results are reliable.
CONCLUSION
This study's results showed that GLP-1RAs were effective in lowering HbA1c and reducing body weight without increased incidence of hypoglycemic reactions. In addition, this study may provide reference and evidence-based medical evidence for clinicians to select GLP-1RAs in patients with T2D and high body mass index (BMI). Based on the NMA results, tirzepatide 15mg and semaglutide 1.0mg may be preferred.
Topics: Humans; Body Weight; Diabetes Mellitus, Type 2; Exenatide; Glucagon-Like Peptide-1 Receptor; Glycated Hemoglobin; Metformin
PubMed: 37701904
DOI: 10.3389/fendo.2023.1244432 -
Frontiers in Immunology 2023Cytokines are pivotal mediators of cell communication in the tumor microenvironment. Multiple cytokines are involved in the host antitumor response, but the production... (Review)
Review
Cytokines are pivotal mediators of cell communication in the tumor microenvironment. Multiple cytokines are involved in the host antitumor response, but the production and function of these cytokines are usually dysregulated during malignant tumor progression. Considering their clinical potential and the early successful use of cytokines in cancer immunotherapy, such as interferon alpha-2b (IFNα-2b; IntronA) and IL-2 (Proleukin), cytokine-based therapeutics have been extensively evaluated in many follow-up clinical trials. Following these initial breakthroughs, however, clinical translation of these natural messenger molecules has been greatly limited owing to their high-degree pleiotropic features and complex biological properties in many cell types. These characteristics, coupled with poor pharmacokinetics (a short half-life), have hampered the delivery of cytokines via systemic administration, particularly because of severe dose-limiting toxicities. New engineering approaches have been developed to widen the therapeutic window, prolong pharmacokinetic effects, enhance tumor targeting and reduce adverse effects, thereby improving therapeutic efficacy. In this review, we focus on the recent progress and competitive landscape in cytokine engineering strategies and preclinical/clinical therapeutics for cancer. In addition, aiming to promote engineered cytokine-based cancer immunotherapy, we present a profound discussion about the feasibility of recently developed methods in clinical medicine translation.
Topics: Humans; Cytokines; Neoplasms; Immunotherapy; Tumor Microenvironment
PubMed: 37483629
DOI: 10.3389/fimmu.2023.1218082 -
Cancer Treatment Reviews Apr 2024Cancer-related pain often requires opioid treatment with opioid-induced constipation (OIC) as its most frequent gastrointestinal side-effect. Both for prevention and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Cancer-related pain often requires opioid treatment with opioid-induced constipation (OIC) as its most frequent gastrointestinal side-effect. Both for prevention and treatment of OIC osmotic (e.g. polyethylene glycol) and stimulant (e.g. bisacodyl) laxatives are widely used. Newer drugs such as the peripherally acting µ-opioid receptor antagonists (PAMORAs) and naloxone in a fixed combination with oxycodone have become available for the management of OIC. This systematic review and meta-analysis aims to give an overview of the scientific evidence on pharmacological strategies for the prevention and treatment of OIC in cancer patients.
METHODS
A systematic search in PubMed, Embase, Web of Science and the Cochrane Library was completed from inception up to 22 October 2022. Randomized and non-randomized studies were systematically selected. Bowel function and adverse drug events were assessed.
RESULTS
Twenty trials (prevention: five RCTs and three cohort studies; treatment: ten RCTs and two comparative cohort studies) were included in the review. Regarding the prevention of OIC, three RCTs compared laxatives with other laxatives, finding no clear differences in effectivity of the laxatives used. One cohort study showed a significant benefit of magnesium oxide compared with no laxative. One RCT found a significant benefit for the PAMORA naldemedine compared with magnesium oxide. Preventive use of oxycodone/naloxone did not show a significant difference in two out of three other studies compared to oxycodone or fentanyl. A meta-analysis was not possible. Regarding the treatment of OIC, two RCTs compared laxatives, of which one RCT found that polyethylene glycol was significantly more effective than sennosides. Seven studies compared an opioid antagonist (naloxone, methylnaltrexone or naldemedine) with placebo and three studies compared different dosages of opioid antagonists. These studies with opioid antagonists were used for the meta-analysis. Oxycodone/naloxone showed a significant improvement in Bowel Function Index compared to oxycodone with laxatives (MD -13.68; 95 % CI -18.38 to -8.98; I = 58 %). Adverse drug event rates were similar amongst both groups, except for nausea in favour of oxycodone/naloxone (RR 0.51; 95 % CI 0.31-0.83; I = 0 %). Naldemedine (NAL) and methylnaltrexone (MNTX) demonstrated significantly higher response rates compared to placebo (NAL: RR 2.07, 95 % CI 1.64-2.61, I = 0 %; MNTX: RR 3.83, 95 % CI 2.81-5.22, I = 0 %). With regard to adverse events, abdominal pain was more present in treatment with methylnaltrexone and diarrhea was significantly more present in treatment with naldemedine. Different dosages of methylnaltrexone were not significantly different with regard to both efficacy and adverse drug event rates.
CONCLUSIONS
Magnesium oxide and naldemedine are most likely effective for prevention of OIC in cancer patients. Naloxone in a fixed combination with oxycodone, naldemedine and methylnaltrexone effectively treat OIC in cancer patients with acceptable adverse events. However, their effect has not been compared to standard (osmotic and stimulant) laxatives. More studies comparing standard laxatives with each other and with opioid antagonists are necessary before recommendations for clinical practice can be made.
Topics: Humans; Laxatives; Analgesics, Opioid; Narcotic Antagonists; Constipation; Oxycodone; Opioid-Induced Constipation; Magnesium Oxide; Cohort Studies; Naloxone; Polyethylene Glycols; Neoplasms; Drug-Related Side Effects and Adverse Reactions; Quaternary Ammonium Compounds; Naltrexone
PubMed: 38452708
DOI: 10.1016/j.ctrv.2024.102704 -
Scientific Reports Nov 2023Polyethylene glycol loxenatide (PEX168) is a novel glucagon-like peptide-1 receptor agonist with a longer half-life developed by modifying the chemical structure of... (Meta-Analysis)
Meta-Analysis
Polyethylene glycol loxenatide (PEX168) is a novel glucagon-like peptide-1 receptor agonist with a longer half-life developed by modifying the chemical structure of exenatide. This study aims to assess the efficacy and safety of PEX168 and determine the best dose. We searched PubMed, Scopus, Cochrane Library, and Web of Science databases from inception to April 25, 2023, for randomized controlled trials (RCTs) comparing PEX168 therapy alone or in combination with metformin versus other therapies. We used the risk ratio (RR) for dichotomous outcomes and the mean difference (MD) for continuous outcomes, both with 95% confidence intervals (CI). Six RCTs, including 1248 participants, were included. PEX168 added to metformin was significantly better than metformin alone regarding fasting blood glucose (MD = -1.20, 95% CI (-1.78, - 0.62), p < 0.0001), HbA1c (MD = -1.01, 95% CI (-1.48, - 0.53), p < 0.0001), and postprandial glycemia (MD = -1.94, 95% CI (-2.99, - 0.90), p = 0.0003). Similarly, for glycemic control, PEX168 monotherapy was superior to placebo (P < 0.05). No significant effects were noticed in terms of triglycerides, low-density lipoprotein, or high-density lipoprotein (p > 0.05). Body weight was significantly reduced in obese diabetic patients receiving PEX168 compared to the control group (MD = -5.46, 95% CI (-7.90, - 3.01), p < 0.0001) but not in non-obese patients (MD = 0.06, 95% CI (-0.47, 0.59), p = 0.83). People who received PEX168 alone or with metformin showed more common gastrointestinal adverse effects, especially nausea and vomiting (p < 0.05). PEX168 100, 200, and 300 ug monotherapy demonstrated comparable safety and diabetes control to metformin, but when combined with metformin, PEX168 100 and 200 ug showed significant effects on diabetes control; however, only the latter showed a significantly higher incidence of nausea and vomiting (p < 0.05). PEX168 could be a viable option for treating diabetic patients whose metformin control is inadequate or who cannot tolerate metformin. PEX168 at 100 ug in combination with metformin was found to be safe and more effective compared to metformin; however, due to the small number of trials included, these findings should be interpreted with caution, and additional trials are required.
Topics: Humans; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Metformin; Nausea; Randomized Controlled Trials as Topic; Vomiting
PubMed: 37923756
DOI: 10.1038/s41598-023-46274-x -
Digestive Diseases and Sciences Dec 2023The rate of adequate cleansing (ACR) and complete examinations (CR) are key quality indicators in capsule colonoscopy (CC) and pan-intestinal capsule endoscopy (PCE). (Meta-Analysis)
Meta-Analysis
BACKGROUND
The rate of adequate cleansing (ACR) and complete examinations (CR) are key quality indicators in capsule colonoscopy (CC) and pan-intestinal capsule endoscopy (PCE).
AIMS
To evaluate the efficacy of bowel preparation protocols regarding ACR and CR.
METHODS
We conducted a systematic review and meta-analysis, search terms regarding colon capsule preparation, publication date from 2006/01, and date of search 2021/12, in six bibliographic databases. Multiple steps of the cleansing protocol were assessed: diet, adjunctive laxatives, purgative solution, use of prokinetic agents, and "booster". The meta-analytical frequency of ACR and CR was estimated, and subgroup analyses performed. Strategies associated with higher ACR and CR were explored using meta-analytical univariable and multivariable regression models.
RESULTS
Twenty-six observational studies and five RCTs included (n = 4072 patients). The pooled rate of ACR was 72.5% (95% C.I. 67.8-77.5%; I = 92.4%), and the pooled rate of CR was 83.0% (95% C.I. 78.7-87.7%; I = 96.5%). The highest ACR were obtained using a low-fibre diet [78.5% (95% C.I. 72.0-85.6%); I = 57.0%], adjunctive laxatives [74.7% (95% C.I. 69.8-80.1%); I = 85.3%], and split dose < 4L polyethylene glycol (PEG) as purgative [77.5% (95% C.I. 68.4-87.8%); I = 47.3%]. The highest CR were observed using routine prokinetics prior to capsule ingestion [84.4% (95% C.I. 79.9-89.2%); I = 89.8%], and sodium phosphate (NaP) as "booster" [86.2% (95% C.I. 82.3-90.2%); I = 86.8%]. In univariable models, adjunctive laxatives were associated with higher ACR [OR 1.81 (95% C.I. 1.13; 2.90); p = 0.014]. CR was higher with routine prokinetics [OR 1.86 (95% C.I. 1.13; 3.05); p = 0.015] and split-dose PEG purgative [OR 2.03 (95% C.I. 1.01; 4.09), p = 0.048].
CONCLUSIONS
Main quality outcomes (ACR, CR) remain suboptimal for CC and PCE. Despite considerable heterogeneity, our results support low-fibre diet, use of adjunctive sennosides, split dose < 4L PEG, and routine prokinetics, while NaP remains the most consistent option as booster.
Topics: Humans; Cathartics; Laxatives; Capsule Endoscopy; Colonoscopy; Polyethylene Glycols
PubMed: 37833441
DOI: 10.1007/s10620-023-08133-7 -
Polymers Sep 2023Composite resin is universally used for posterior teeth restorations. Fibers have been suggested for the mechanical improvement of the restorations. This study assessed... (Review)
Review
Composite resin is universally used for posterior teeth restorations. Fibers have been suggested for the mechanical improvement of the restorations. This study assessed the fracture resistance of class II fiber-reinforced composite restorations and compared it with the fracture resistance of three control groups: (1) healthy teeth, (2) non-fiber-reinforced restorations and (3) unrestored cavities. A search was performed using PubMed, Web of Science and Google Scholar from 15 May to 12 June 2023. Only in vitro studies from the last 10 years were included for this systematic analysis. This study was registered in the PROSPERO database, it followed PRISMA guidelines and the risk of bias was assessed using the QUIN tool. Fracture resistance median values, in Newtons (N), were calculated for the experimental and control groups (95% confidence interval). For pairwise comparison, nonparametric tests ( < 0.05) were applied. Twenty-four in vitro studies met the inclusion criteria. The fracture resistance of the experimental group was 976.0 N and differed ( < 0.05) from all controls. The experimental group showed lower values of fracture resistance than healthy teeth (1459.9 N; = 0.048) but higher values than non-fiber-reinforced restorations (771.0 N; = 0.008) and unrestored cavities (386.6 N; < 0.001). In vitro systematic outcomes evidenced that glass and/or polyethylene fibers improved the fracture resistance of composite restorations.
PubMed: 37765654
DOI: 10.3390/polym15183802 -
Journal of Environmental Health Science... Dec 2023Pollution of the environment with all kinds of plastics has become a growing problem. The problem of microplastics is mainly due to the absorption of stable organic...
PURPOSE
Pollution of the environment with all kinds of plastics has become a growing problem. The problem of microplastics is mainly due to the absorption of stable organic pollutants and metals into them, and as a result, their environmental toxicity increases. The main purpose of this study is to investigate the appropriate and efficient methods of removing microplastics from aqueous environments through a systematic review.
METHODS
Present study designed according to PRISMA guidelines. Two independent researchers followed all process from search to final analysis, for the relevant studies using international databases of PubMed, Scopus and ISI/WOS (Web of Science), without time limit. The search strategy developed based on the main axis of "microplastics", "aqueous environments" and "removal". This research was carried out from 2017 until the March of 2022. All relevant observational, analytical studies, review articles, and a meta-analysis were included.
RESULTS
Through a comprehensive systematic search we found 2974 papers, after running the proses of refining, 80 eligible papers included to the study. According to the results of the review, the methods of removing microplastics from aquatic environments were divided to physical (12), chemical (18), physicochemical (27), biological (12) and integrated (11) methods. In different removal methods, the most dominant group of studied microplastics belonged to the four groups of polyethylene (PE), polystyrene (PS), polypropylene (PP) and polyethylene tetra phthalate (PET). Average removal efficiency of microplastics in different processes in each method was as: physical method (73.76%), chemical method (74.38%), physicochemical method (80.44%), biological method (75.23%) and integrated method (88.63%). The highest removal efficiency occurred in the processes based on the integrated method and the lowest efficiency occurred in the physical method. In total, 80% of the studies were conducted on a laboratory scale, 18.75% on a full scale and 1.25% on a pilot scale.
CONCLUSION
According to the findings; different processes based on physical, chemical, physicochemical, biological and integrated methods are able to remove microplastics with high efficiency from aqueous environments and in order to reduce their hazardous effects on health and environment, these processes can be easily used.
PubMed: 37869596
DOI: 10.1007/s40201-023-00872-z -
Alternative Therapies in Health and... Nov 2023An intertrochanteric fracture can cause ischemic necrosis in the femoral head, leading to negative effects. There are many types of implants for this fracture procedure,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
An intertrochanteric fracture can cause ischemic necrosis in the femoral head, leading to negative effects. There are many types of implants for this fracture procedure, including metal-on-metal, metal-on-polyethylene, ceramic-on-ceramic, and ceramic-on-polyethylene, that are currently in use. The current modification is a hybrid prosthetic implant with high functional capacity compared with predecessors. This study aims to determine the procedure's efficacy in recovery, function restoration, complications, and cost-effectiveness.
METHODS
Our study used a total of 200 patients undergoing total hip arthroplasty and 135 patients undergoing semi-hip arthroplasty to determine the effectiveness of total hip arthroplasty and femoral head arthroplasty From May 2022 to May 2023. Using the RAOSOFT sampling technique, 132 and 101 in the observation and control group, respectively, the sample is obtained with a confidence interval of 95%, an error margin of 1%, and response interval confidence of 50%. This is a descriptive type of research that relies on a meta-analysis of the available data from PubMed, scholarly articles, and the Chinese biomedical database to gather the fundamental data needed to conduct the research. Data obtained is analyzed using SSPS and STATA and presented in tables showing a summary of the objective measured value.
RESULT
In this study, the Harris joint score of patients in the total hip arthroplasty group was significantly higher than that of the control group, indicating that total hip arthroplasty can restore femoral head function, but still lacks absolute strength like half hip arthroplasty.
CONCLUSIONS
Femoral head replacement is a complex procedure, but the efficacy in restoring the function is better. In conclusion, despite slow healing and regeneration, the efficacy of complete artificial femoral head replacement is higher in restoring function for various fractures.
Topics: Humans; Hip Prosthesis; Femur Head; Arthroplasty, Replacement, Hip; Hip Fractures; Polyethylene; Treatment Outcome; Retrospective Studies
PubMed: 37820651
DOI: No ID Found -
Journal of Gastrointestinal Oncology Aug 2023Although both high- and low-volume polyethylene glycol (PEG) are widely used in intestinal preparation before colonoscopy, there is still controversy over the...
The safety and effects of high- and low-volume polyethylene glycol bowel preparation methods before colonoscopy on bowel cleanliness: a systematic review and meta-analysis.
BACKGROUND
Although both high- and low-volume polyethylene glycol (PEG) are widely used in intestinal preparation before colonoscopy, there is still controversy over the superiority of their cleaning effects. This meta-analysis sought to explore the safety and effects of high-volume PEG solution and low-volume PEG mixed solution on intestinal cleanliness before colonoscopy.
METHODS
The PubMed, EMBASE, and Cochrane Library databases were searched to retrieve relevant articles on the effects of high- and low-volume PEG mixture solutions on intestinal cleanliness from the inception of the databases to October 15, 2022. Two independent researchers screened the literature according to the predetermined inclusion and exclusion criteria, and extracted the required data separately. A bias risk assessment was conducted for each study using the relevant tools in the Cochrane Handbook. The included data were subjected to a meta-analysis using R 4.2.1 software.
RESULTS
This article includes a total of 15 studies involving a total of 5,847 patients. There was no difference in the cleanliness score, qualified rate of intestinal cleanliness and patient compliance between the high- and low-volume group. The patients in the low-volume PEG mixed solution group had a higher repeat willingness bowel cleansing rate than those in the high-volume PEG group [risk ratio (RR) =0.71, 95% confidence interval (CI): 0.62-0.82, P<0.01]. Compared with the low-volume group, the incidence of adverse reactions such as nausea, vomiting, and abdominal pain increased in the high-volume group (RR =1.38, 95% CI: 1.22-1.56, P<0.01; RR =1.79, 95% CI: 1.41-2.27, P<0.01; RR =1.05, 95% CI: 1.01-1.08, P<0.01).
CONCLUSIONS
In the pre-colonoscopy preparation method for patients, although the high-volume PEG and low-volume PEG mixed regimen have similar effects on intestinal cleanliness, the low-volume mixed regimen has a higher willingness to repeat and a lower incidence of adverse reactions. In clinical practice, considering patient compliance and safety, a low-volume mixed regimen may be a more optimal option.
PubMed: 37720457
DOI: 10.21037/jgo-23-581 -
Sensors (Basel, Switzerland) Sep 2023This research presents a dual-pronged bibliometric and systematic review of the integration of phase change materials (PCM) in asphalt pavements to counteract the urban... (Review)
Review
This research presents a dual-pronged bibliometric and systematic review of the integration of phase change materials (PCM) in asphalt pavements to counteract the urban heat island (UHI) effect. The bibliometric approach discerns the evolution of PCM-inclusion asphalt research, highlighting a marked rise in the number of publications between 2019 and 2022. Notably, Chang'an University in China has emerged as a leading contributor. The systematic review addresses key questions like optimal PCM types for UHI effect mitigation, strategies for PCM leakage prevention in asphalt, and effects on mechanical properties. The findings identify polyethylene glycols (PEGs), especially PEG2000 and PEG4000, as prevailing PCM due to their wide phase-change temperature range and significant enthalpy during phase transitions. While including PCM can modify asphalt's mechanical attributes, such mixtures typically stay within performance norms. This review emphasises the potential of PCM in urban heat management and the need for further research to achieve optimal thermal and mechanical balance.
PubMed: 37765798
DOI: 10.3390/s23187741