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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 -
Lipids in Health and Disease Jan 2024Obstructive sleep apnea (OSA) has a bidirectional association with metabolic syndrome, and insulin resistance (IR). The triglyceride-glucose (TyG) index could be a... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Obstructive sleep apnea (OSA) has a bidirectional association with metabolic syndrome, and insulin resistance (IR). The triglyceride-glucose (TyG) index could be a simply calculated marker of IR in OSA. However, its clinical application appears still limited. Hence, this systematic review and meta-analysis aimed to respond to this question by analyzing all the existing studies showing an association between OSA and the TyG index.
METHODS
Four online databases, including PubMed, Scopus, the Web of Science, and Embase were searched for studies evaluating the TyG index in OSA. After screening and data extraction, a random-effect meta-analysis was performed to compare the TyG index in OSA patients vs. healthy controls by calculating standardized mean difference (SMD) and 95% confidence interval (CI) and pooling the area under the curves (AUCs) for diagnosis of OSA based on this index.
RESULTS
Ten studies involving 16,726 individuals were included in the current systematic review. Meta-analysis indicated that there was a significantly higher TyG index in patients with OSA, compared with the healthy controls (SMD 0.856, 95% CI 0.579 to 1.132, P < 0.001). Also, TyG had a diagnostic ability for OSA representing a pooled AUC of 0.681 (95% CI 0.627 to 0.735). However, based on the two studies' findings, no difference between different severities of OSA was observed. Finally, our data showed that the TyG index is a good potential predictor of adverse outcomes in these patients.
CONCLUSION
Our study revealed that the TyG index is an easy-to-measure marker of IR for assessing OSA, both in diagnosis and prognosis. Our study supports its implementation in routine practice to help clinicians in decision-making and patient stratification.
Topics: Humans; Area Under Curve; Databases, Factual; Glucose; Insulin Resistance; Sleep Apnea, Obstructive; Triglycerides
PubMed: 38185682
DOI: 10.1186/s12944-024-02005-3 -
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 -
The Journal of Infection Mar 2024Interest in phages as adjunctive therapy to treat difficult infections has grown in the last decade. However, phage dosing and delivery for orthopedic infections have... (Review)
Review
OBJECTIVES
Interest in phages as adjunctive therapy to treat difficult infections has grown in the last decade. However, phage dosing and delivery for orthopedic infections have not been systematically summarized.
METHODS
Following PRISMA-ScR guidelines, we conducted a SCOPING review through September 1st, 2023, of MEDLINE, Embase, Web of Science Core Collection, and Cochrane Central.
RESULTS
In total, 77 studies were included, of which 19 (24.7%) were in vitro studies, 17 (22.1%) were animal studies, and 41 (53.2%) were studies in humans. A total of 137 contemporary patients receiving phage therapy are described.
CONCLUSIONS
Direct phage delivery remains the most studied form of phage therapy, notably in prosthetic joint infections, osteomyelitis, and diabetic foot ulcers. Available evidence describing phage therapy in humans suggests favorable outcomes for orthopedic infections, though this evidence is composed largely of low-level descriptive studies. Several phage delivery devices have been described, though a lack of comparative and in-human evidence limits their therapeutic application. Limitations to the use of phage therapy for orthopedic infections that need to be overcome include a lack of understanding related to optimal dosing and phage pharmacokinetics, bacterial heterogeneity in an infection episode, and phage therapy toxicity.
Topics: Animals; Humans; Phage Therapy; Bacteria; Osteomyelitis; Arthritis, Infectious; Bacterial Infections
PubMed: 38373574
DOI: 10.1016/j.jinf.2024.106125 -
Progress in Neuro-psychopharmacology &... Jul 2024Increasing evidence suggests that the physiological changes of pregnancy may impact pharmacokinetics of antiseizure medications (ASM), and this may affect treatment... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Increasing evidence suggests that the physiological changes of pregnancy may impact pharmacokinetics of antiseizure medications (ASM), and this may affect treatment outcomes. The aim of this study was to quantify the pregnancy impact on the ASM pharmacokinetics.
METHODS
A systematic literature search was conducted in PubMed/EMBASE in November 2022 and updated in August 2023 for studies comparing levels of ASM in the same individuals during pregnancy and in the preconception/postpartum period. Alteration ratios between the 3rd trimester and baseline were estimated. We also performed a random-effects meta-analysis calculating between-timepoint differences in mean differences (MDs) and 95% confidence intervals (95%CIs) for dose-adjusted plasma concentrations (C/D ratios). Study quality was assessed using the ClinPK guidelines.
RESULTS
A total of 65 studies investigating 15 ASMs in 674 pregnancies were included. The largest differences were reported for lamotrigine, oxcarbazepine and levetiracetam (alteration ratio 0.42, range 0.07-2.45, 0.42, range 0.08-0.82 and 0.52, range 0.04-2.77 respectively): accordingly, C/D levels were lower in the 3rd trimester for lamotrigine, levetiracetam and the main oxcarbazepine metabolite monohydroxycarbazepine (MD = -12.33 × 10, 95%CI = -16.08 to -8.58 × 10 (μg/mL)/(mg/day), p < 0.001, MD = -7.16 (μg/mL)/(mg/day), 95%CI = -9.96 to -4.36, p < 0.001, and MD = -4.87 (μg/mL)/(mg/day), 95%CI = -9.39 to -0.35, p = 0.035, respectively), but not for oxcarbazepine (MD = 1.16 × 10 (μg/mL)/(mg/day), 95%CI = -2.55 to 0.24 × 10, p = 0.10). The quality of studies was acceptable with an average rating score of 11.5.
CONCLUSIONS
Data for lamotrigine, oxcarbazepine (and monohydroxycarbazepine) and levetiracetam demonstrate major changes in pharmacokinetics during pregnancy, suggesting the importance of therapeutic drug monitoring to assist clinicians in optimizing treatment outcomes.
Topics: Humans; Pregnancy; Anticonvulsants; Female; Pregnancy Complications; Levetiracetam; Lamotrigine; Epilepsy; Oxcarbazepine
PubMed: 38762161
DOI: 10.1016/j.pnpbp.2024.111030 -
Antibiotics (Basel, Switzerland) Sep 2023Oritavancin (ORI) is a semisynthetic lipoglycopeptide approved as a single 1200 mg dose intravenous infusion for the treatment of acute bacterial skin and skin structure... (Review)
Review
Oritavancin (ORI) is a semisynthetic lipoglycopeptide approved as a single 1200 mg dose intravenous infusion for the treatment of acute bacterial skin and skin structure infections (ABSSSIs) caused by Gram-positive organisms in adults. The pharmacokinetic/pharmacodynamic (PK/PD) linear kinetic profile and long terminal half-life (~393 h) of ORI make it therapeutically attractive for the treatment of other Gram-positive infections for which prolonged therapy is needed. Multidose regimens are adopted in real-world clinical practice with promising results, but aggregated efficacy data are still lacking. A comprehensive search on PubMed/Medline, Scopus, Cochrane and Google Scholar databases was performed to include papers published up to the end of January 2023. All articles on ORI multiple doses usage, including case reports, with quantitative data and relevant clinical information were included. Two reviewers independently assessed papers against the inclusion/exclusion criteria and for methodological quality. Differences in opinion were adjudicated by a third party. From 1751 potentially relevant papers identified by this search, a total of 16 studies met the inclusion criteria and were processed further in the final data analysis. We extracted data concerning clinical response, bacteriologic response, mortality and adverse events (AEs). From the 16 included papers, 301 cases of treatment with multidose ORIs were identified. Multidose regimens comprised an initial ORI dose of 1200 mg followed by 1200 mg or 800 mg subsequent doses with a varying total number and frequency of reinfusions. The most often treated infections and isolates were osteomyelitis (148; 54.4%), ABSSSI (35; 12.9%) and cellulitis (14; 5.1%); and MRSA (121), MSSA (66), CoNS (17), (13) and (12), respectively. Clinical cure and improvement by multidose ORI regimens were observed in 85% (231/272) and 8% (22/272) patients, respectively. Multidose ORI was safe and well tolerated; the most frequent AEs were infusion-related reactions and hypoglycemia. A multidose ORI regimen may be beneficial in treating other Gram-positive infections besides ABSSSIs, with a good safety profile. Further studies are warranted to ascertain the superiority of one multidose ORI scheme or posology over the other.
PubMed: 37887199
DOI: 10.3390/antibiotics12101498 -
ACS Pharmacology & Translational Science Jul 2023Methamphetamine exists as two stereoisomers: -(+)-methamphetamine ((+)-MAMP) and -(-)-methamphetamine ((-)-MAMP). The (+)-MAMP stereoisomer is a well-known central... (Review)
Review
Methamphetamine exists as two stereoisomers: -(+)-methamphetamine ((+)-MAMP) and -(-)-methamphetamine ((-)-MAMP). The (+)-MAMP stereoisomer is a well-known central nervous system stimulant, available as a pharmaceutical and clandestine drug of abuse. However, the (-)-MAMP stereoisomer is less well understood despite commercial availability for over 30 years as an over-the-counter (OTC) nasal decongestant in the Vicks Vapor Inhaler (a product of Procter & Gamble). Recently, several generic versions have become available, decreasing the cost and increasing the availability of (-)-MAMP-containing nasal sprays to consumers. Despite widespread commercial availability and use in the United States, a paucity of literature exists on the pharmacology of (-)-MAMP in humans. This knowledge gap is problematic, given the difficulty in separating (-)-MAMP and (+)-MAMP isomers in laboratory assays for workplace drug testing, suspected impaired drivers, post-mortem investigations, and assessment of drug involvement in crimes. In response, this systematic review of the literature coalesces and summarizes available knowledge of (-)-MAMP pharmacology in humans. It was found that available knowledge relies heavily on urine drug and metabolite concentrations, systematic pharmacokinetics studies are lacking, and existing knowledge has been derived from a total of 99 unique participants. The impacts of highlighted gaps in the literature are discussed, focusing on forensic toxicology and law enforcement, and future research directions are suggested.
PubMed: 37470013
DOI: 10.1021/acsptsci.3c00019 -
Journal of Medical Internet Research Oct 2023Frailty syndrome (FS) is one of the most common noncommunicable diseases, which is associated with lower physical and mental capacities in older adults. FS diagnosis is... (Review)
Review
BACKGROUND
Frailty syndrome (FS) is one of the most common noncommunicable diseases, which is associated with lower physical and mental capacities in older adults. FS diagnosis is mostly focused on biological variables; however, it is likely that this diagnosis could fail owing to the high biological variability in this syndrome. Therefore, artificial intelligence (AI) could be a potential strategy to identify and diagnose this complex and multifactorial geriatric syndrome.
OBJECTIVE
The objective of this scoping review was to analyze the existing scientific evidence on the use of AI for the identification and diagnosis of FS in older adults, as well as to identify which model provides enhanced accuracy, sensitivity, specificity, and area under the curve (AUC).
METHODS
A search was conducted using PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) guidelines on various databases: PubMed, Web of Science, Scopus, and Google Scholar. The search strategy followed Population/Problem, Intervention, Comparison, and Outcome (PICO) criteria with the population being older adults; intervention being AI; comparison being compared or not to other diagnostic methods; and outcome being FS with reported sensitivity, specificity, accuracy, or AUC values. The results were synthesized through information extraction and are presented in tables.
RESULTS
We identified 26 studies that met the inclusion criteria, 6 of which had a data set over 2000 and 3 with data sets below 100. Machine learning was the most widely used type of AI, employed in 18 studies. Moreover, of the 26 included studies, 9 used clinical data, with clinical histories being the most frequently used data type in this category. The remaining 17 studies used nonclinical data, most frequently involving activity monitoring using an inertial sensor in clinical and nonclinical contexts. Regarding the performance of each AI model, 10 studies achieved a value of precision, sensitivity, specificity, or AUC ≥90.
CONCLUSIONS
The findings of this scoping review clarify the overall status of recent studies using AI to identify and diagnose FS. Moreover, the findings show that the combined use of AI using clinical data along with nonclinical information such as the kinematics of inertial sensors that monitor activities in a nonclinical context could be an appropriate tool for the identification and diagnosis of FS. Nevertheless, some possible limitations of the evidence included in the review could be small sample sizes, heterogeneity of study designs, and lack of standardization in the AI models and diagnostic criteria used across studies. Future research is needed to validate AI systems with diverse data sources for diagnosing FS. AI should be used as a decision support tool for identifying FS, with data quality and privacy addressed, and the tool should be regularly monitored for performance after being integrated in clinical practice.
Topics: Humans; Aged; Artificial Intelligence; Frail Elderly; Frailty; Machine Learning; Area Under Curve
PubMed: 37862082
DOI: 10.2196/47346 -
International Journal of Medical... Dec 2023Medication prescription is a complex process that could benefit from current research and development in machine learning through decision support systems. Particularly... (Review)
Review
BACKGROUND
Medication prescription is a complex process that could benefit from current research and development in machine learning through decision support systems. Particularly pediatricians are forced to prescribe medications "off-label" as children are still underrepresented in clinical studies, which leads to a high risk of an incorrect dose and adverse drug effects.
METHODS
PubMed, IEEE Xplore and PROSPERO were searched for relevant studies that developed and evaluated well-performing machine learning algorithms following the PRISMA statement. Quality assessment was conducted in accordance with the IJMEDI checklist. Identified studies were reviewed in detail, including the required variables for predicting the correct dose, especially of pediatric medication prescription.
RESULTS
The search identified 656 studies, of which 64 were reviewed in detail and 36 met the inclusion criteria. According to the IJMEDI checklist, five studies were considered to be of high quality. 19 of the 36 studies dealt with the active substance warfarin. Overall, machine learning algorithms based on decision trees or regression methods performed superior regarding their predictive power than algorithms based on neural networks, support vector machines or other methods. The use of ensemble methods like bagging or boosting generally enhanced the accuracy of the dose predictions. The required input and output variables of the algorithms were considerably heterogeneous and differ strongly among the respective substance.
CONCLUSIONS
By using machine learning algorithms, the prescription process could be simplified and dosing correctness could be enhanced. Despite the heterogenous results among the different substances and cases and the lack of pediatric use cases, the identified approaches and required variables can serve as an excellent starting point for further development of algorithms predicting drug doses, particularly for children. Especially the combination of physiologically-based pharmacokinetic models with machine learning algorithms represents a great opportunity to enhance the predictive power and accuracy of the developed algorithms.
Topics: Humans; Child; Algorithms; Neural Networks, Computer; Machine Learning; Prescriptions
PubMed: 37939541
DOI: 10.1016/j.ijmedinf.2023.105241 -
Cureus Oct 2023Atrial fibrillation (AF) is a common cardiac arrhythmia that increases the risk of stroke and thromboembolism. Anticoagulation therapy can reduce this risk, but the... (Review)
Review
Atrial fibrillation (AF) is a common cardiac arrhythmia that increases the risk of stroke and thromboembolism. Anticoagulation therapy can reduce this risk, but the optimal choice of anticoagulant in patients with AF and renal dysfunction is challenging. Renal dysfunction is a common comorbidity seen in patients with AF. Renal dysfunction would affect the pharmacokinetics and pharmacodynamics of anticoagulants and make the patient more prone to bleeding complications. This complicates the assessment of the risks, benefits, and ratio for starting anticoagulant drugs in patients with renal dysfunction. Therefore, there is always a therapeutic conundrum due to the increased risk of bleeding and thromboembolic events in AF patients with renal dysfunction. We conducted a systematic review to summarize the current literature and identify the challenges of anticoagulation strategies in AF with renal dysfunction. We examined 180 articles from reputable journals published from 2018 to June 2023 and selected eight papers for detailed analysis. The studies we chose included a variety of drug treatments, such as traditional therapies like vitamin K antagonists, factor Xa inhibitors, heparins, and direct thrombin inhibitors. This systematic review will provide comprehensive information on the latest data on the effectiveness of various pharmacological treatments (anticoagulation strategies) in AF patients with renal dysfunction. The aim is to help doctors and other healthcare decision-makers choose the best anticoagulation strategy in AF patients with renal dysfunction and to overcome their dilemma between bleeding risk and systemic thromboembolic events.
PubMed: 38046493
DOI: 10.7759/cureus.48072