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PloS One 2024This study aims to evaluate the efficacy and safety of JAK inhibitors in the treatment of patients with RA. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
This study aims to evaluate the efficacy and safety of JAK inhibitors in the treatment of patients with RA.
METHODS
The databases CNKI, VIP, Wanfang, CBM, and PubMed, Embase, Cochrane Library and Web of Science were searched to identify relevant randomized controlled trials (RCTs), all from the time of database creation to April 2024. Screening, data extraction, and risk of bias assessment (using Review Manager-5.3 software) were independently performed by at least two authors. The network meta-analysis was conducted using R 4.1.3 software. PROSPERO registration number: CRD42022370444.
RESULTS
Thirty-three RCTs included 15,961 patients The experimental groups involved six JAK inhibitors (filgotinib, tofacitinib, decernotinib, baricitinib, upadacitinib and peficitinib) and 12 interventions (different doses of the six JAK inhibitors), and the control group involved adalimumab (ADA) and placebo. Compared with placebo, all JAK inhibitors showed a significant increase in efficacy measures (ACR20/50/70). Compared with ADA, only tofacitinib, low-dose decernotinib, and high-dose peficitinib showed a significant increase in ACR20/50/70. Decernotinib ranked first in the SUCRA ranking of ACR20/50/70. In terms of safety indicators, only those differences between low-dose filgotinib and high-dose upadacitinib, low-dose tofacitinib and high-dose upadacitinib were statistically significant. Low-dose filgotinib ranked first in the SUCRA ranking with adverse events as safety indicators. Only the efficacy and safety of tofacitinib ranked higher among different SUCRA rankings.
CONCLUSION
Six JAK inhibitors have better efficacy than placebo. The superior efficacy of decernotinib and safety of low-dose filgotinib can be found in the SUCRA. However, there are no significant differences in safety between the different JAK inhibitors. Head-to-head trials, directly comparing one against each other, are required to provide more certain evidence.
Topics: Humans; Arthritis, Rheumatoid; Janus Kinase Inhibitors; Bayes Theorem; Pyrimidines; Piperidines; Network Meta-Analysis; Azetidines; Purines; Pyrroles; Pyrazoles; Sulfonamides; Randomized Controlled Trials as Topic; Treatment Outcome; Heterocyclic Compounds, 2-Ring; Niacinamide; Benzamides; Heterocyclic Compounds, 3-Ring; Antirheumatic Agents; Triazoles; Adamantane; Pyridines; Valine
PubMed: 38905267
DOI: 10.1371/journal.pone.0305621 -
BJS Open May 2024Pancreatoduodenectomy is associated with an increased incidence of surgical-site infections, often leading to a significant rise in morbidity and mortality. This trend... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Pancreatoduodenectomy is associated with an increased incidence of surgical-site infections, often leading to a significant rise in morbidity and mortality. This trend underlines the inadequacy of traditional antibiotic prophylaxis strategies. Hence, the aim of this meta-analysis was to assess the outcomes of antimicrobial prophylaxis, comparing piperacillin/tazobactam with traditional antibiotics.
METHODS
Upon registering in PROSPERO, the international prospective register of systematic reviews (CRD42023479100), a systematic search of various databases was conducted over the interval 2000-2023. This inclusive search encompassed a wide range of study types, including prospective and retrospective cohorts and RCTs. The subsequent data analysis was carried out utilizing RevMan 5.4.
RESULTS
A total of eight studies involving 2382 patients who underwent pancreatoduodenectomy and received either piperacillin/tazobactam (1196 patients) or traditional antibiotics (1186 patients) as antibiotic prophylaxis during surgery were included in the meta-analysis. Patients in the piperacillin/tazobactam group had significantly reduced incidences of surgical-site infections (OR 0.43 (95% c.i. 0.30 to 0.62); P < 0.00001) and major surgical complications (Clavien-Dindo grade greater than or equal to III) (OR 0.61 (95% c.i. 0.45 to 0.81); P = 0.0008). Subgroup analysis of surgical-site infections highlighted significantly reduced incidences of superficial surgical-site infections (OR 0.34 (95% c.i. 0.14 to 0.84); P = 0.02) and organ/space surgical-site infections (OR 0.47 (95% c.i. 0.28 to 0.78); P = 0.004) in the piperacillin/tazobactam group. Further, the analysis demonstrated significantly lower incidences of clinically relevant postoperative pancreatic fistulas (grades B and C) (OR 0.67 (95% c.i. 0.53 to 0.83); P = 0.0003) and mortality (OR 0.51 (95% c.i. 0.28 to 0.91); P = 0.02) in the piperacillin/tazobactam group.
CONCLUSION
Piperacillin/tazobactam as antimicrobial prophylaxis significantly lowers the risk of postoperative surgical-site infections, major surgical complications (complications classified as Clavien-Dindo grade greater than or equal to III), clinically relevant postoperative pancreatic fistulas (grades B and C), and mortality, hence supporting the implementation of piperacillin/tazobactam for surgical prophylaxis in current practice.
Topics: Humans; Pancreaticoduodenectomy; Antibiotic Prophylaxis; Piperacillin, Tazobactam Drug Combination; Surgical Wound Infection; Anti-Bacterial Agents; Piperacillin
PubMed: 38869238
DOI: 10.1093/bjsopen/zrae066 -
Aging Jun 2024This meta-analysis aimed to describe the efficacy of bumetanide in improving infarct volume, brain edema, and behavioral outcomes in animal models of cerebral ischemia.... (Meta-Analysis)
Meta-Analysis
This meta-analysis aimed to describe the efficacy of bumetanide in improving infarct volume, brain edema, and behavioral outcomes in animal models of cerebral ischemia. Embase, PubMed and Web of Science databases were searched from their inception to February 2024 (INPLASY:202430023). Data on the animal species, stroke model, drug dose, time of treatment, method of administration, study quality, and outcomes were extracted and pooled in a meta-analysis. The combined standardized mean difference (SMD) or mean difference (MD) estimates and 95% confidence intervals (CIs) were calculated using random- or fixed-effects models. Thirteen eligible studies involving >200 animals fulfilled the inclusion criteria and were included in this meta-analysis. Meta-analyses demonstrated that bumetanide treatment significantly reduced cerebral infarct volume (SMD: -0.42; 95% CI: -0.75, -0.09; < 0.01; = 186 animals) and consistently relieved brain edema (SMD: -1.39; 95% CI: -2.06, -0.72; < 0.01; = 64 animals). Subgroup analyses demonstrated that bumetanide treatment reduced infarct volume in transient but not permanent cerebral ischemia models. When administered after the stroke, it was more effective than treatment initiation before the stroke. Eight studies assessed the effect of bumetanide on behavioral function and the results showed that bumetanide treatment significantly improved neurobehavioral deficits (SMD: -2.35; 95% CI: -2.72, -1.97; < 0.01; = 250 animals). We conclude that bumetanide appears to be effective in reducing infarct volume and brain edema and improving behavioral recovery in animal models of cerebral ischemia. This mechanism needs to be confirmed through further investigation.
Topics: Bumetanide; Animals; Ischemic Stroke; Disease Models, Animal; Brain Edema; Sodium Potassium Chloride Symporter Inhibitors; Neuroprotective Agents
PubMed: 38850525
DOI: 10.18632/aging.205910 -
Drug Design, Development and Therapy 2024Several population pharmacokinetic (PPK) models of B cell lymphoma-2 (BCL-2) venetoclax (VEN) have been developed and published to characterize the influencing factors... (Review)
Review
Several population pharmacokinetic (PPK) models of B cell lymphoma-2 (BCL-2) venetoclax (VEN) have been developed and published to characterize the influencing factors of pharmacokinetics in hematologic malignancies. This review described PPK models of VEN examining the magnitude and types of covariate effects in PK parameters, as well as identified areas that require further investigation in order to facilitate their use. Currently, there are six analyses on PPK models of VEN summarized in this review. Most analyses described the pharmacokinetics of VEN with a two-compartment model and all covariates are categorical. The median estimated apparent clearance (CL/F) was 446 L/Day and apparent volume of distribution of the central compartment (V/F) was 114.5 L. The median IIV of CL/F reported was 39.5% and V/F was 46.7%. Most commonly, CYP3A inhibitors, OATP1B3 inhibitors and rituximab co-administration were found to be significant covariates on CL/F. In addition, sex and population were influential covariates on V/F. A detailed description of the characteristics of PPK models of VEN is provided in this review, as well as the effects of covariates on the PK parameters. For future development of the VEN PPK model, CYP3A inhibitors, rituximab co-administration, OATP1B1 transporter inhibitors, sex, population, and food might be considered. Further research and comprehensive investigations should be undertaken to explore reference ranges for therapeutic drug monitoring, define the potential role of patients with cerebrospinal fluid complications, and assess new or potential covariates. These endeavors will facilitate the development of personalized VEN therapy.
Topics: Humans; Hematologic Neoplasms; Sulfonamides; Bridged Bicyclo Compounds, Heterocyclic; Antineoplastic Agents; Models, Biological
PubMed: 38828021
DOI: 10.2147/DDDT.S458927 -
Biochemical Pharmacology Jul 2024Epidemiological evidence links chemical exposure with type 2 diabetes (T2DM) risk and prevalence. Chemical exposure may therefore also limit success of weight loss or... (Meta-Analysis)
Meta-Analysis Review
A systematic review and meta-analysis of environmental contaminant exposure impacts on weight loss and glucose regulation during calorie-restricted diets in preclinical studies: Persistent organic pollutants may impede glycemic control.
Epidemiological evidence links chemical exposure with type 2 diabetes (T2DM) risk and prevalence. Chemical exposure may therefore also limit success of weight loss or restoration of glycemic control during calorie restricted diets. Few human studies examine this hypothesis. This systematic review and clustered meta-analysis examines preclinical evidence that exposure to anthropogenic environmental contaminants impedes weight loss and resumption of glycemic control during calorie restriction. Of five eligible papers from 212 unique citations, four used C57BL/6 mice and one used Sprague Dawley rats. In four the animals received high fat diets to induce obesity and impaired glycemic control. All examined persistent organic pollutants (POPs). Polychlorinated biphenyl (PCB) 77 exposure did not affect final mass (standardised mean difference (SMD) = -0.35 [-1.09, 0.39]; n = 5 (experiments); n = 3 (papers)), or response to insulin in insulin tolerance tests (SMD = -1.54 [-3.25, 0.16] n = 3 (experiments); n = 2 (papers)), but impaired glucose control in glucose tolerance tests (SMD = -1.30 [-1.96, -0.63]; n = 6 (experiments); n = 3 (papers)). The impaired glycemic control following perfluoro-octane sulphonic acid (PFOS) exposure and enhanced mass loss following dichlorodiphenyltrichloroethane (DDT) exposure have not been replicated. Animal studies thus suggest some chemical groups, especially PCB and PFOS, could impair glucose control management during calorie restriction, similar to conclusions from limited existing clinical studies. We discuss the research that is urgently required to inform weight management services that are now the mainstay prevention initiative for T2DM.
Topics: Animals; Mice; Blood Glucose; Caloric Restriction; Diabetes Mellitus, Type 2; Environmental Exposure; Environmental Pollutants; Glycemic Control; Persistent Organic Pollutants; Weight Loss; Disease Models, Animal; Rats
PubMed: 38782075
DOI: 10.1016/j.bcp.2024.116300 -
Scientific Reports May 2024Despite the availability of various drugs for benign prostatic hyperplasia (BPH), alpha(α)-blockers are the preferred first-line treatment. However, there remains a... (Meta-Analysis)
Meta-Analysis Comparative Study
Despite the availability of various drugs for benign prostatic hyperplasia (BPH), alpha(α)-blockers are the preferred first-line treatment. However, there remains a scarcity of direct comparisons among various α-blockers. Therefore, this network meta-analysis (NMA) of randomized controlled trials (RCTs) aimed to evaluate the efficacy and safety of α-blockers in the management of BPH. A comprehensive electronic search covered PubMed, Embase, Ovid MEDLINE, and Cochrane Library until August 2023. The primary endpoints comprised international prostate symptom score (IPSS), maximum flow rate (Qmax), quality of life (QoL), and post-void residual volume (PVR), while treatment-emergent adverse events (TEAEs) were considered as secondary endpoints. This NMA synthesized evidence from 22 studies covering 3371 patients with six kinds of α-blockers with 12 dose categories. IPSS has been considerably improved by tamsulosin 0.4 mg, naftopidil 50 mg and silodosin 8 mg as compared to the placebo. Based on the p-score, tamsulosin 0.4 mg had the highest probability of ranking for IPSS, PVR, and Qmax, whereas doxazosin 8 mg had the highest probability of improving QoL. A total of 297 adverse events were reported among all the α-blockers, silodosin has reported a notable number of TEAEs. Current evidence supports α-blockers are effective in IPSS reduction and are considered safer. Larger sample size with long-term studies are needed to refine estimates of IPSS, QoL, PVR, and Qmax outcomes in α-blocker users.
Topics: Humans; Prostatic Hyperplasia; Male; Network Meta-Analysis; Adrenergic alpha-Antagonists; Treatment Outcome; Quality of Life; Randomized Controlled Trials as Topic; Tamsulosin
PubMed: 38750153
DOI: 10.1038/s41598-024-61977-5 -
Arthritis Research & Therapy May 2024Targeted small-molecule drugs in the treatment of systemic lupus erythematosus (SLE) have attracted increasing attention from clinical investigators. However, there is... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Targeted small-molecule drugs in the treatment of systemic lupus erythematosus (SLE) have attracted increasing attention from clinical investigators. However, there is still a lack of evidence on the difference in the efficacy and safety of different targeted small-molecule drugs. Therefore, this study was conducted to assess the efficacy and safety of different targeted small-molecule drugs for SLE.
METHODS
Randomized controlled trials (RCTs) on targeted small-molecule drugs in the treatment of SLE in PubMed, Web of Science, Embase, and Cochrane Library were systematically searched as of April 25, 2023. Risk of bias assessment was performed for included studies using the Cochrane's tool for evaluating the risk of bias. The primary outcome indicators were SRI-4 response, BICLA response, and adverse reaction. Because different doses and courses of treatment were used in the included studies, Bayesian network meta-regression was used to investigate the effect of different doses and courses of treatment on efficacy and safety.
RESULTS
A total of 13 studies were included, involving 3,622 patients and 9 targeted small-molecule drugs. The results of network meta-analysis showed that, in terms of improving SRI-4, Deucravacitinib was significantly superior to that of Baricitinib (RR = 1.32, 95% CI (1.04, 1.68), P < 0.05). Deucravacitinib significantly outperformed the placebo in improving BICLA response (RR = 1.55, 95% CI (1.20, 2.02), P < 0.05). In terms of adverse reactions, targeted small-molecule drugs did not significantly increase the risk of adverse events as compared to placebo (P > 0.05).
CONCLUSION
Based on the evidence obtained in this study, the differences in the efficacy of targeted small-molecule drugs were statistically significant as compared to placebo, but the difference in the safety was not statistically significant. The dose and the course of treatment had little impact on the effect of targeted small-molecule drugs. Deucravacitinib could significantly improve BICLA response and SRI-4 response without significantly increasing the risk of AEs. Therefore, Deucravacitinib is very likely to be the best intervention measure. Due to the small number of included studies, more high-quality clinical evidence is needed to further verify the efficacy and safety of targeted small-molecule drugs for SLE.
Topics: Humans; Lupus Erythematosus, Systemic; Randomized Controlled Trials as Topic; Treatment Outcome; Azetidines; Purines; Molecular Targeted Therapy; Sulfonamides; Pyrazoles
PubMed: 38730460
DOI: 10.1186/s13075-024-03331-8 -
Journal of Clinical Medicine Apr 2024: to evaluate the effectiveness of different topical agents in biofilm disaggregation during non-surgical periodontal therapy. : the search strategy was conducted... (Review)
Review
: to evaluate the effectiveness of different topical agents in biofilm disaggregation during non-surgical periodontal therapy. : the search strategy was conducted according to the PRISMA 2020 on Pubmed, Cochrane Library, Scopus, and Web of Science, and it was registered in PROSPERO, ID: CRD42023474232. It included studies comparing non-surgical periodontal therapy (NSPT) with and without the application of topical agents for biofilm disruption. A risk of bias analysis, a qualitative analysis, and a quantitative analysis were performed. : out of 1583 records, 11 articles were included: 10 randomized clinical trials and one retrospective analysis. The total number of participants considered in the 11 articles included in the study was 386. The primary outcomes were probing pocket depth (PPD), clinical attachment level (CAL), and bleeding indices. The secondary outcomes were plaque indices, gingival recessions, and microbiological parameters. The meta-analysis revealed the following: [Weighted mean difference (WMD): -0.37; 95% confidence interval (CI) (-0.62, -0.12), heterogeneity I: 79%, statistical significance = 0.004]. : the meta-analysis of probing pocket depth reduction (PPD) between baseline and follow-up at 3-6 months showed a statistically significant result in favor of sulfonated phenolics gel. The scientific evidence is still limited and heterogeneous; further randomized clinical trials are required.
PubMed: 38673451
DOI: 10.3390/jcm13082179 -
Complementary Therapies in Medicine Jun 2024Traditional Chinese medicine injection for Activating Blood Circulation (TCMi-ABC), which exhibits comparable anticoagulant and antiplatelet effects, is commonly used as... (Meta-Analysis)
Meta-Analysis
Traditional chinese medicine injections with activating blood circulation, equivalent effect of anticoagulation or antiplatelet, for acute myocardial infarction: A systematic review and meta-analysis of randomized clinical trials.
BACKGROUND
Traditional Chinese medicine injection for Activating Blood Circulation (TCMi-ABC), which exhibits comparable anticoagulant and antiplatelet effects, is commonly used as an adjuvant treatment for acute myocardial infarction (AMI) in China.
OBJECTIVE
The aim of this study was to conduct a meta-analysis to assess the efficacy and safety of TCMi-ABC in combination with conventional western medicine in reducing mortality associated with AMI.
METHODS
We conducted a comprehensive search of PubMed, Cochrane Library, EMBASE, Web of Science, CBM, WanFang Data, and CNKI databases. Randomized controlled trials (RCTs) investigating the use of TCMi-ABC (including Danhong injection, sodium tanshinone IIA sulfonate injection, salvia miltiorrhiza ligupyrazine injection, and puerarin injection) for the treatment of AMI were included. The search included studies published from the inception of the databases up to December 2022. Two authors independently screened RCTs, extracted data, and assessed the risk of bias. Meta-analysis was performed using RevMan 5.3 and Stata 17.0. The quality of evidence was evaluated using the GRADE approach.
RESULTS
A total of 52 RCTs involving 5363 patients were included in the analysis, none of which described independent testing of the purity or potency of the TCMi-ABC product used. 19/52 reported random sequence generation. All RCTs lack adequate description of allocation concealment. 51/52 failed to assess blinding. The meta-analysis results demonstrated that the combined application of TCMi-ABC, compared with conventional western medicine treatment alone, significantly reduced in-hospital mortality in AMI patients [RR= 0.41, 95% CI (0.29, 0.59), P < 0.05], decreased the incidence of malignant arrhythmia [RR= 0.40, 95% CI (0.26, 0.61), P < 0.05], and increased left ventricular ejection fraction (LVEF) [MD= 5.53, 95% CI (3.81, 7.26), P < 0.05]. There was no significant difference in the incidence of adverse events between the two groups (P > 0.05). The GRADE evidence quality classification indicated that the evidence for in-hospital mortality, malignant arrhythmia, and adverse events was of moderate quality, while the evidence for LVEF was of low quality.
CONCLUSION
TCMi-ABC demonstrates additional clinical value in reducing mortality and the risk of malignant arrhythmia in patients with AMI. However, further validation of these findings is warranted through high-quality clinical trials due to methodological weaknesses in randomization, blinding, allocation concealment, and insufficient assessing for the purity/potency of herbs and the gram amount of active constituents.
SYSTEMATIC REVIEW REGISTRATION
[INPLASY], identifier [INPLASY202170082].
Topics: Humans; Anticoagulants; Blood Circulation; Drugs, Chinese Herbal; Injections; Medicine, Chinese Traditional; Myocardial Infarction; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic
PubMed: 38616000
DOI: 10.1016/j.ctim.2024.103039 -
BMC Cardiovascular Disorders Apr 2024The latest evidence indicates that ATP-binding cassette superfamily G member 2 (ABCG2) is critical in regulating lipid metabolism and mediating statin or cholesterol... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The latest evidence indicates that ATP-binding cassette superfamily G member 2 (ABCG2) is critical in regulating lipid metabolism and mediating statin or cholesterol efflux. This study investigates whether the function variant loss within ABCG2 (rs2231142) impacts lipid levels and statin efficiency.
METHODS
PubMed, Cochrane Library, Central, CINAHL, and ClinicalTrials.gov were searched until November 18, 2023.
RESULTS
Fifteen studies (34,150 individuals) were included in the analysis. The A allele [Glu141Lys amino acid substitution was formed by a transversion from cytosine (C) to adenine (A)] of rs2231142 was linked to lower levels of high-density lipoprotein cholesterol (HDL-C), and higher levels of low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC). In addition, the A allele of rs2231142 substantially increased the lipid-lowering efficiency of rosuvastatin in Asian individuals with dyslipidemia. Subgroup analysis indicated that the impacts of rs2231142 on lipid levels and statin response were primarily in Asian individuals.
CONCLUSIONS
The ABCG2 rs2231142 loss of function variant significantly impacts lipid levels and statin efficiency. Preventive use of rosuvastatin may prevent the onset of coronary artery disease (CAD) in Asian individuals with dyslipidemia.
Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Rosuvastatin Calcium; Genetic Predisposition to Disease; Cholesterol, LDL; Dyslipidemias; ATP Binding Cassette Transporter, Subfamily G, Member 2; Neoplasm Proteins
PubMed: 38589776
DOI: 10.1186/s12872-024-03821-2