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Journal of the Royal Society of Medicine Sep 2023The cardiorenal protective effects of sodium-glucose co-transporter 2 inhibitors (SGLT2-Is) and glucagon-like peptide 1 receptor agonists (GLP1-RAs) across racial and...
Racial, ethnic and regional differences in the effect of sodium-glucose co-transporter 2 inhibitors and glucagon-like peptide 1 receptor agonists on cardiovascular and renal outcomes: a systematic review and meta-analysis of cardiovascular outcome trials.
OBJECTIVES
The cardiorenal protective effects of sodium-glucose co-transporter 2 inhibitors (SGLT2-Is) and glucagon-like peptide 1 receptor agonists (GLP1-RAs) across racial and ethnic groups are not well defined. By conducting a systematic review and meta-analysis of all randomised, placebo-controlled, cardiovascular disease (CVD) outcomes trials (CVOTs), we aimed to compare racial/ethnic as well as regional patterns in the effects of SGLT2-Is and GLP1-RAs on cardiovascular and renal outcomes in patients with type 2 diabetes (T2D).
DESIGN
Trials were identified from MEDLINE, Embase, the Cochrane Library, and search of bibliographies to 7 July 2023. Setting North America, South/Central America, Europe (Eastern and Western), Asia, Australia-New Zealand (Pacific), Asia/Pacific, and Africa.
SETTING
North America, South/Central America, Europe (Eastern and Western), Asia, Australia-New Zealand (Pacific), Asia/Pacific, and Africa.
PARTICIPANTS
people with type 2 diabetes enrolled in cardiovascular outcome trials of SGLT2-Is and GLP1-RAs.
MAIN OUTCOME MEASURES
Outcomes were (i) major adverse cardiovascular events (MACE), (ii) composite CVD death/heart failure (HF) hospitalization; (iii) composite renal outcome; and (iv) their components. Study-specific hazard ratios (HRs) with 95% confidence intervals (CIs) were pooled.
RESULTS
In total, 14 unique CVOTs (7 comparing SGLT2-Is vs placebo and 7 comparing GLP1-RAs vs placebo) were eligible. The proportion of participants enrolled in the trials ranged from 66.6-93.2% for White populations, 1.2-21.6% for Asian populations, 2.4-8.3% for Black populations and 0.9-23.1% for Other populations. The HR (95% CI) for MACE comparing SGLT2-Is vs placebo was 0.92 (0.86-0.98), 0.69 (0.53-0.92) and 0.70 (0.54-0.91) for White, Asian and Hispanic/Latino populations, respectively. Comparing GLP1-RAs vs placebo, the corresponding HR (95% CI) was 0.88 (0.80-0.97), 0.76 (0.63-0.93) and 0.82 (0.70-0.95), respectively. SGLT2-Is reduced the risk of all other cardiorenal outcomes in White and Asian populations, except for HF hospitalizations in Asians. No effects were observed in Black populations except for a reduced risk of HF hospitalizations by SGLT2-I. SGLT1-Is reduced the risk of composite CVD death/HF hospitalization in North America and Europe, whereas GLP1-RAs reduced the risk of MACE in Europe. GRADE certainty of evidence ranged from moderate to high.
CONCLUSIONS
There appears to be substantial racial/ethnic differences in the cardiorenal effects of SGLT2-Is and GLP1-RAs in patients with T2D, with consistent benefits observed among White and Asian populations and consistent lack of benefits in Black populations. Whether the differences are due to issues with under-representation of Black populations and low statistical power or racial/ethnic variations in the pharmacokinetics, pharmacodynamics and safety of SGLT2-Is and GLP1-RAs need further investigation.PROSPERO Registration: CRD42023401734.
PubMed: 37734450
DOI: 10.1177/01410768231198442 -
Neurosurgical Review Sep 2023Chronic subdural hematoma (cSDH) is a common neurosurgical condition that can cause severe morbidity and mortality. cSDH recurs after surgical evacuation in 5-30% of... (Meta-Analysis)
Meta-Analysis Review
Chronic subdural hematoma (cSDH) is a common neurosurgical condition that can cause severe morbidity and mortality. cSDH recurs after surgical evacuation in 5-30% of patients, but drains may help reduce this risk. We aimed to investigate the effect of drainage versus no drainage on the rates of recurrence and mortality, as well as the clinical outcomes of cSDH. Following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, we searched four electronic databases (PubMed, Cochrane Library, Scopus, and Web of Science) to identify eligible studies reported up to June 2022. Using Review Manager software, we reported four primary outcomes as odds ratios (ORs) and confidence intervals (CIs). The meta-analysis included a total of 10 studies with 1961 patients. The use of drainage was found to be significantly more effective than non-drainage in reducing the "mortality rate" (OR = 0.65, 95% CI 0.43 to 0.97; P = 0.04), the "recurrence rate" (OR = 0.39, 95% CI 0.28 to 0.55; P < 0.00001), and occurrence of "gross focal neurological deficit" (OR = 0.58, 95% CI 0.37 to 0.89; P = 0.01). No significant difference was found in the occurrence of a Glasgow Coma Scale score of 15 (OR = 1.21, 95% CI 0.84 to 1.76; P = 0.30). The use of drains after burr-hole irrigation reduces the recurrence, mortality, and gross focal neurological deficit rates of chronic subdural hematomas.
Topics: Humans; Hematoma, Subdural, Chronic; Drainage; Databases, Factual; Glasgow Coma Scale; Odds Ratio
PubMed: 37726502
DOI: 10.1007/s10143-023-02153-7 -
Frontiers in Endocrinology 2023The performance in evaluating thyroid nodules on ultrasound varies across different risk stratification systems, leading to inconsistency and uncertainty regarding... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The performance in evaluating thyroid nodules on ultrasound varies across different risk stratification systems, leading to inconsistency and uncertainty regarding diagnostic sensitivity, specificity, and accuracy.
OBJECTIVE
Comparing diagnostic performance of detecting thyroid cancer among distinct ultrasound risk stratification systems proposed in the last five years.
EVIDENCE ACQUISITION
Systematic search was conducted on PubMed, EMBASE, and Web of Science databases to find relevant research up to December 8, 2022, whose study contents contained elucidation of diagnostic performance of any one of the above ultrasound risk stratification systems (European Thyroid Imaging Reporting and Data System[Eu-TIRADS]; American College of Radiology TIRADS [ACR TIRADS]; Chinese version of TIRADS [C-TIRADS]; Computer-aided diagnosis system based on deep learning [S-Detect]). Based on golden diagnostic standard in histopathology and cytology, single meta-analysis was performed to obtain the optimal cut-off value for each system, and then network meta-analysis was conducted on the best risk stratification category in each system.
EVIDENCE SYNTHESIS
This network meta-analysis included 88 studies with a total of 59,304 nodules. The most accurate risk category thresholds were TR5 for Eu-TIRADS, TR5 for ACR TIRADS, TR4b and above for C-TIRADS, and possible malignancy for S-Detect. At the best thresholds, sensitivity of these systems ranged from 68% to 82% and specificity ranged from 71% to 81%. It identified the highest sensitivity for C-TIRADS TR4b and the highest specificity for ACR TIRADS TR5. However, sensitivity for ACR TIRADS TR5 was the lowest. The diagnostic odds ratio (DOR) and area under curve (AUC) were ranked first in C-TIRADS.
CONCLUSION
Among four ultrasound risk stratification options, this systemic review preliminarily proved that C-TIRADS possessed favorable diagnostic performance for thyroid nodules.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero, CRD42022382818.
Topics: Humans; Thyroid Nodule; Network Meta-Analysis; Thyroid Neoplasms; Area Under Curve
PubMed: 37720531
DOI: 10.3389/fendo.2023.1227339 -
European Journal of Clinical... Nov 2023Investigate inhaled nitric oxide's influence on mortality rates, mechanical ventilation and cardiopulmonary bypass duration, and length of stay in the intensive care... (Meta-Analysis)
Meta-Analysis Review
The beneficial use of nitric oxide during cardiopulmonary bypass on postoperative outcomes in children and adult patients: a systematic review and meta-analysis of 2897 patients.
PURPOSE
Investigate inhaled nitric oxide's influence on mortality rates, mechanical ventilation and cardiopulmonary bypass duration, and length of stay in the intensive care unit and hospital when administered during cardiopulmonary bypass.
METHODS
Following the PRISMA guidelines, we searched four electronic databases (PubMed, EMBASE, Cochrane Library, and Web of Science) up to 4th March 2023. The protocol was registered in the PROSPERO database with ID: CRD42023423007. Using Review Manager software, we reported outcomes as risk ratios (RRs) or mean difference (MD) and confidence intervals (CIs).
RESULTS
The meta-analysis included a total of 17 studies with 2897 patients. Overall, there were no significant differences in using nitric oxide over control concerning mortality (RR = 1.03, 95% CI 0.73 to 1.45; P = 0.88) or cardiopulmonary bypass duration (MD = -0.14, 95% CI - 0.96 to 0.69; P = 0.74). The intensive care unit days were significantly lower in the nitric oxide group than control (MD = -0.80, 95% CI - 1.31 to -0.29; P = 0.002). Difference results were obtained in terms of the length of stay in the hospital according to sensitivity analysis (without sensitivity [MD = -0.41, 95% CI - 0.79 to -0.02; P = 0.04] vs. with sensitivity [MD = -0.31, 95% CI - 0.69 to 0.07; P = 0.11]. Subgroup analysis shows that, in children, nitric oxide was favored over control in significantly reducing the duration of mechanical ventilation (MD = -4.58, 95% CI - 5.63 to -3.53; P < 0.001).
CONCLUSION
Using inhaled nitric oxide during cardiopulmonary bypass reduces the length of stay in the intensive care unit, and for children, it reduces the duration of mechanical ventilation.
Topics: Humans; Child; Adult; Nitric Oxide; Cardiopulmonary Bypass; Intensive Care Units; Respiration, Artificial
PubMed: 37650923
DOI: 10.1007/s00228-023-03554-9 -
Molecules (Basel, Switzerland) Aug 2023Fruits and vegetables are used not only for nutritional purposes but also as therapeutics to treat various diseases and ailments. These food items are prominent sources... (Review)
Review
Fruits and vegetables are used not only for nutritional purposes but also as therapeutics to treat various diseases and ailments. These food items are prominent sources of phytochemicals that exhibit chemopreventive and therapeutic effects against several diseases. Hirsutine (HSN) is a naturally occurring indole alkaloid found in various Uncaria species and has a multitude of therapeutic benefits. It is found in foodstuffs such as fish, seafood, meat, poultry, dairy, and some grain products among other things. In addition, it is present in fruits and vegetables including corn, cauliflower, mushrooms, potatoes, bamboo shoots, bananas, cantaloupe, and citrus fruits. The primary emphasis of this study is to summarize the pharmacological activities and the underlying mechanisms of HSN against different diseases, as well as the biopharmaceutical features. For this, data were collected (up to date as of 1 July 2023) from various reliable and authentic literature by searching different academic search engines, including PubMed, Springer Link, Scopus, Wiley Online, Web of Science, ScienceDirect, and Google Scholar. Findings indicated that HSN exerts several effects in various preclinical and pharmacological experimental systems. It exhibits anti-inflammatory, antiviral, anti-diabetic, and antioxidant activities with beneficial effects in neurological and cardiovascular diseases. Our findings also indicate that HSN exerts promising anticancer potentials via several molecular mechanisms, including apoptotic cell death, induction of oxidative stress, cytotoxic effect, anti-proliferative effect, genotoxic effect, and inhibition of cancer cell migration and invasion against various cancers such as lung, breast, and antitumor effects in human T-cell leukemia. Taken all together, findings from this study show that HSN can be a promising therapeutic agent to treat various diseases including cancer.
Topics: Animals; Humans; Biological Products; Alkaloids; Vegetables; Agaricales
PubMed: 37630393
DOI: 10.3390/molecules28166141 -
Cureus Jul 2023Drugs that act on the calcitonin gene-related peptide (CGRP) pathway herald the dawn of a new era in the management of migraine headaches. The blockade of CGRP... (Review)
Review
Drugs that act on the calcitonin gene-related peptide (CGRP) pathway herald the dawn of a new era in the management of migraine headaches. The blockade of CGRP alleviates neural inflammation and has been associated with reduced pain sensitization. Zavegepant is a third-generation drug and is the first intranasal CGRP antagonist to be developed. This systematic review aims to assess the safety, efficacy, pharmacokinetics, and tolerability of Zavegepant as an abortive treatment for migraine. Studies that assessed the safety, tolerability, and efficacy of Zavegepant for migraine were identified through a systematic literature review of PubMed, Clinicaltrials.gov, and Cochrane databases in April 2023. Our systematic review yielded a total of six studies that fit our inclusion criteria. Of these, data from only two randomized control trials (RCTs) was homogenous; hence, forest plots of results pooled from the included studies were not reported. The included studies showed that Zavegepant is an efficacious and well-tolerated abortive treatment modality for episodic migraine in adult patients. Zavegepant showed safety and efficacy in migraine treatment according to various parameters throughout the six included studies. These parameters include adverse events, pharmacokinetic properties, CGRP inhibition, effect on blood pressure/electrocardiogram, pain freedom, and freedom from most bothersome symptoms.
PubMed: 37593294
DOI: 10.7759/cureus.41991 -
Frontiers in Pharmacology 2023Tacrolimus (Tac) is a widely used immunosuppressive agent in kidney transplantation. Cytochrome P450 (CYP), especially enzymes are responsible for the metabolism of...
Tacrolimus (Tac) is a widely used immunosuppressive agent in kidney transplantation. Cytochrome P450 (CYP), especially enzymes are responsible for the metabolism of drugs. However, the correlation between plasma Tac concentration and gene variants is controversial. This meta-analysis aims to evaluate the association between polymorphism and the dose-adjusted trough concentration (C/D) of Tac in adult kidney transplant patients. We conducted a literature review for qualifying studies using the PubMed, Web of Science, and Embase databases until July 2023. For the continuous variables (C/D and daily dose), mean difference (MD) and corresponding 95% confidence intervals (CIs) were calculated to evaluate the association between the and Tac pharmacokinetics. We performed an additional analysis on the relationship of with Tac PKs and analyzed the effects of in CYP3A5 non-expressers. Overall, eight eligible studies with 2,683 renal transplant recipients were included in this meta-analysis. The allele was significantly associated with a higher C/D (MD 0.57 ng/mL/mg (95% CI: 0.28 to 0.86; = 0.0001) and lower mean daily dose requirement (MD -2.02 mg/day, 95% CI: -2.55 to -1.50; < 0.00001). An additional meta-analysis demonstrated that carrying the polymorphism greatly impacted Tac blood concentration. From the result with CYP3A5 non-expressers, showed significant effects on the Tac C/D and dose requirement even after adjusting the effect of . Patients with allele showed significantly higher plasma C/D of Tac and required lower daily dose to achieve the therapeutic trough level after kidney transplantation. These findings of our meta-analysis may provide further evidence for the effects of genetic polymorphism in on the PKs of Tac, which will improve individualized treatment in a clinical setting.
PubMed: 37564175
DOI: 10.3389/fphar.2023.1201083 -
Frontiers in Public Health 2023Variants in organic cation transporter (OCT) genes play a crucial role in metformin pharmacokinetics and are critical for diabetes treatment. However, studies... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Variants in organic cation transporter (OCT) genes play a crucial role in metformin pharmacokinetics and are critical for diabetes treatment. However, studies investigating the effect of OCT genetic polymorphisms on metformin response have reported inconsistent results. This review and meta-analysis aimed to evaluate the associations between OCT genetic polymorphisms and metformin response and intolerance in individuals with type 2 diabetes mellitus (T2DM).
METHOD
A systematic search was conducted on PubMed, EMBASE, CNKI, WANFANG DATA, and VIP database for identifying potential studies up to 10 November 2022. The Q-Genie tool was used to evaluate the quality of included studies. Pooled odds ratios (OR) or standardized mean differences (SMD) and 95% confidence intervals (95% CI) were calculated to determine the associations between OCT genetic polymorphisms and metformin response and intolerance that were reflected by glycemic response indexes, such as glycated hemoglobin level (HbA1c%) or change in glycated hemoglobin level (ΔHbA1c%), fasting plasma level (FPG) or change in fasting plasma glucose level (ΔFPG), the effectiveness rate of metformin treatment, and the rate of metformin intolerance. A qualitative review was performed for the variants identified just in one study and those that could not undergo pooling analysis.
RESULTS
A total of 30 related eligible studies about OCT genes (, and ) and metformin pharmacogenetics were identified, and 14, 3, and 6 single nucleotide polymorphisms (SNPs) in , and , respectively, were investigated. Meta-analysis showed that the rs622342 polymorphism was associated with a reduction in HbA1c level (AA vs. AC: SMD [95% CI] = -0.45 [-0.73--0.18]; = 0.001). The GG genotype of the rs628031 polymorphism was associated with a reduction in FPG level (GG vs. AA: SMD [95 %CI] = -0.60 [-1.04-0.16], = 0.007; GG vs. AG: -0.45 [-0.67-0.20], < 0.001). No statistical association was found between the remaining variants and metformin response and intolerance.
CONCLUSION
rs622342 and rs628031 polymorphisms were potentially associated with glycemic response to metformin. This evidence may provide novel insight into gene-oriented personalized medicine for diabetes.
Topics: Humans; Metformin; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Hypoglycemic Agents; Polymorphism, Single Nucleotide; Cations
PubMed: 37546319
DOI: 10.3389/fpubh.2023.1183879 -
Pharmaceuticals (Basel, Switzerland) Jun 2023Curcumin is a polyphenolic compound, derived from Curcuma longa, and it has several pharmacological effects such as antioxidant, anti-inflammatory, and antitumor.... (Review)
Review
Curcumin is a polyphenolic compound, derived from Curcuma longa, and it has several pharmacological effects such as antioxidant, anti-inflammatory, and antitumor. Although it is a pleiotropic molecule, curcumin's free form, which is lipophilic, has low bioavailability and is rapidly metabolized, limiting its clinical use. With the advances in techniques for loading curcumin into nanostructures, it is possible to improve its bioavailability and extend its applications. In this review, we gather evidence about the comparison of the pharmacokinetics (biodistribution and bioavailability) between free curcumin (Cur) and nanostructured curcumin (Cur-NPs) and their respective relationships with antitumor efficacy. The search was performed in the following databases: Cochrane, LILACS, Embase, MEDLINE/Pubmed, Clinical Trials, BSV regional portal, ScienceDirect, Scopus, and Web of Science. The selected studies were based on studies that used High-Performance Liquid Chromatography (HPLC) as the pharmacokinetics evaluation method. Of the 345 studies initially pooled, 11 met the inclusion criteria and all included studies classified as high quality. In this search, a variety of nanoparticles used to deliver curcumin (polymeric, copolymeric, nanocrystals, nanovesicles, and nanosuspension) were found. Most Cur-NPs presented negative Zeta potential ranging from -25 mV to 12.7 mV, polydispersion index (PDI) ranging from 0.06 to 0.283, and hydrodynamic diameter ranging from 30.47 to 550.1 nm. Selected studies adopted mainly oral and intravenous administrations. In the pharmacokinetics analysis, samples of plasma, liver, tumor, lung, brain, kidney, and spleen were evaluated. The administration of curcumin, in nanoparticle systems, resulted in a higher level of curcumin in tumors compared to free curcumin, leading to an improved antitumor effect. Thus, the use of nanoparticles can be a promising alternative for curcumin delivery since this improves its bioavailability.
PubMed: 37513855
DOI: 10.3390/ph16070943 -
Biomedicine & Pharmacotherapy =... Sep 2023Neurodegenerative diseases (NDDs) encompass a range of conditions that involve progressive deterioration and dysfunction of the nervous system. Some of the common NDDs... (Review)
Review
Neurodegenerative diseases (NDDs) encompass a range of conditions that involve progressive deterioration and dysfunction of the nervous system. Some of the common NDDs include Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS). Although significant progress has been made in understanding the pathological mechanisms of NDDs in recent years, the development of targeted and effective drugs for their treatment remains challenging. Kaempferol is a flavonoid whose derivatives include kaempferol-O-rhamnoside, 3-O-β-rutinoside/6-hydroxykaempferol 3,6-di-O-β-d-glucoside, and kaempferide. Emerging studies have suggested that kaempferol and its derivatives possess neuroprotective properties and may have potential therapeutic benefits in NDDs. Here, we aimed to provide a theoretical basis for the use of kaempferol and its derivatives in the clinical treatment of NDDs. We systematically reviewed the literature in the PubMed, Web of Science, and Science Direct databases until June 2022 using the search terms "kaempferol," "kaempferol derivatives," "NDDs," "pharmacokinetics," and "biosynthesis" according to the reporting items for systematic review (PRISMA) standard. Based on combined results of in vivo and in vitro studies, we summarize the basic mechanisms and targets of kaempferol and its derivatives in the management of AD, PD, HD, and ALS. Kaempferol and its derivatives exert a neuroprotective role mainly by preventing the deposition of amyloid fibrils (such as Aβ, tau, and α-synuclein), inhibiting microglia activation, reducing the release of inflammatory factors, restoring the mitochondrial membrane to prevent oxidative stress, protecting the blood-brain barrier, and inhibiting specific enzyme activities (such as cholinesterase). Kaempferol and its derivatives are promising natural neuroprotective agents. By determining their pharmacological mechanism, kaempferol and its derivatives may be new candidate drugs for the treatment of NDDs.
Topics: Humans; Neurodegenerative Diseases; Neuroprotective Agents; Amyotrophic Lateral Sclerosis; Kaempferols; Alzheimer Disease; Parkinson Disease; Huntington Disease
PubMed: 37494786
DOI: 10.1016/j.biopha.2023.115215