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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 -
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 -
Infection and Drug Resistance 2023Isavuconazole (ISA) is a second generation broad-spectrum triazole antifungal drug derived from voriconazole structure, and its oral capsules is currently the only oral... (Review)
Review
Isavuconazole (ISA) is a second generation broad-spectrum triazole antifungal drug derived from voriconazole structure, and its oral capsules is currently the only oral preparation approved for invasive mucormycosis. In recent years, population pharmacokinetic studies of ISA have been reported continuously. This paper aims to summarize the characteristics of population pharmacokinetic models of ISA in adults, and provide theoretical basis for individualized administration of ISA. We systematically searched PubMed, Embase, CNKI, Wanfang, VIP and other databases to collect population pharmacokinetic models published from the establishment of the database to March 2023. A total of 6 studies were included in this review, including healthy men and women, invasive fungal infections with malignant tumors or neutropenia, solid organ transplantation. The dose of ISA was 40-400mg for single-dose. The multiple-dose of ISA was 200mg every 8 hours for the first 48 hours and then 200mg once daily. All studies used a two-compartment model, first-order elimination. For oral formulations, except for one study that used first-order absorption, the others used Weibull absorption. Body mass index (BMI) was the most common covariable, followed by total body weight, lean body mass, race, sex, population type (healthy volunteers/patients), and creatinine clearance. These studies included several covariates, and the clearance rate (CL) was similar among populations. In the future, external validation and population pharmacokinetic studies in special populations such as patients with severe liver disease and ECMO support are needed.
PubMed: 38089964
DOI: 10.2147/IDR.S434622 -
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 -
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 -
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 -
BMC Pregnancy and Childbirth Nov 2023In this meta-analysis, we aimed to update the clinical evidence regarding the efficacy and safety of TXA in the prevention of PPH. (Meta-Analysis)
Meta-Analysis
BACKGROUND
In this meta-analysis, we aimed to update the clinical evidence regarding the efficacy and safety of TXA in the prevention of PPH.
METHODS
A literature search of PubMed, Scopus, Web of Science, Google Scholar, and Cochrane Library from inception until December 2022 was conducted. We included randomized controlled trials (RCTs) comparing TXA with a placebo among pregnant women. All relevant outcomes, such as total blood loss, the occurrence of nausea and/or vomiting, and changes in hemoglobin, were combined as odds ratios (OR) or mean differences (MD) in the meta-analysis models using STATA 17 MP.
RESULTS
We included 59 RCTs (18,649 patients) in this meta-analysis. For cesarean birth, TXA was favored over the placebo in reducing total blood loss (MD= -2.11 mL, 95%CI [-3.09 to -1.14], P < 0.001), and occurrence of nausea or/and vomiting (OR = 1.36, 95%CI [1.07 to 1.74], P = 0.01). For vaginal birth, the prophylactic use of TXA was associated with lower total blood loss, and higher occurrence of nausea and/or vomiting (MD= -0.89 mL, 95%CI [-1.47 to -0.31], OR = 2.36, 95%CI [1.32 to 4.21], P = 0.02), respectively. However, there were no differences between the groups in changes in hemoglobin during vaginal birth (MD = 0.20 g/dl, 95%CI [-0.07 to 0.48], P = 0.15). The overall risk of bias among the included studies varies from low to high risk of bias using ROB-II tool for RCTs.
CONCLUSIONS
This meta-analysis suggested that TXA administration is effective among women undergoing cesarean birth or vaginal birth in lowering total blood loss and limiting the occurrence of PPH. Further clinical trials are recommended to test its efficacy on high-risk populations.
Topics: Pregnancy; Female; Humans; Tranexamic Acid; Antifibrinolytic Agents; Postpartum Hemorrhage; Vomiting; Nausea; Hemoglobins; Blood Loss, Surgical
PubMed: 38001439
DOI: 10.1186/s12884-023-06100-8 -
International Journal of Antimicrobial... Sep 2023Pyrazinamide (PZA) is a first-line antituberculosis drug with potent sterilising activity. Variability in drug exposure may translate into suboptimal treatment... (Review)
Review
Pyrazinamide (PZA) is a first-line antituberculosis drug with potent sterilising activity. Variability in drug exposure may translate into suboptimal treatment responses. This systematic review, conducted according to PRISMA guidelines, aimed to evaluate the concentration-effect relationship. In vitro/in vivo studies had to contain information on the infection model, PZA dose and concentration, and microbiological outcome. Human studies had to present information on PZA dose, measures of drug exposure and maximum concentration, and microbiological response parameter or overall treatment outcome. A total of 34 studies were assessed, including in vitro (n = 2), in vivo (n = 3) and clinical studies (n = 29). Intracellular and extracellular models demonstrated a direct correlation between PZA dose of 15-50 mg/kg/day and reduction in bacterial count between 0.50-27.7 log CFU/mL. Consistent with this, higher PZA doses (>150 mg/kg) were associated with a greater reduction in bacterial burden in BALB/c mice models. Human pharmacokinetic studies displayed a linear positive correlation between PZA dose (i.e. 21.4-35.7 mg/kg/day) and drug exposure (AUC range 220.6-514.5 mg·h/L). Additionally, human studies confirmed a dose-effect relationship, with an increased 2-month sputum culture conversion rate at AUC/MIC targets of 8.4-11.3 with higher exposure/susceptibility ratios leading to greater efficacy. A 5-fold variability in AUC was observed at PZA dose of 25 mg/kg. A direct concentration-effect relationship and increased treatment efficacy with higher PZA exposure to susceptibility ratios was observed. Taking into account variability in drug exposure and treatment response, further studies on dose optimisation are justified.
Topics: Animals; Mice; Humans; Pyrazinamide; Mycobacterium tuberculosis; Tuberculosis; Antitubercular Agents; Mice, Inbred BALB C; Microbial Sensitivity Tests
PubMed: 37419292
DOI: 10.1016/j.ijantimicag.2023.106914 -
Journal of Psychopharmacology (Oxford,... Jan 2024Classic psychedelics, including lysergic acid diethylamide (LSD), psilocybin, mescaline, N,N-dimethyltryptamine (DMT) and 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT),... (Review)
Review
Classic psychedelics, including lysergic acid diethylamide (LSD), psilocybin, mescaline, N,N-dimethyltryptamine (DMT) and 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), are potent psychoactive substances that have been studied for their physiological and psychological effects. However, our understanding of the potential interactions and outcomes when using these substances in combination with other drugs is limited. This systematic review aims to provide a comprehensive overview of the current research on drug-drug interactions between classic psychedelics and other drugs in humans. We conducted a thorough literature search using multiple databases, including PubMed, PsycINFO, Web of Science and other sources to supplement our search for relevant studies. A total of 7102 records were screened, and studies involving human data describing potential interactions (as well as the lack thereof) between classic psychedelics and other drugs were included. In total, we identified 52 studies from 36 reports published before September 2, 2023, encompassing 32 studies on LSD, 10 on psilocybin, 4 on mescaline, 3 on DMT, 2 on 5-MeO-DMT and 1 on ayahuasca. These studies provide insights into the interactions between classic psychedelics and a range of drugs, including antidepressants, antipsychotics, anxiolytics, mood stabilisers, recreational drugs and others. The findings revealed various effects when psychedelics were combined with other drugs, including both attenuated and potentiated effects, as well as instances where no changes were observed. Except for a few case reports, no serious adverse drug events were described in the included studies. An in-depth discussion of the results is presented, along with an exploration of the potential molecular pathways that underlie the observed effects.
Topics: Humans; Hallucinogens; Psilocybin; Mescaline; N,N-Dimethyltryptamine; Drug Interactions; Lysergic Acid Diethylamide
PubMed: 37982394
DOI: 10.1177/02698811231211219 -
Environmental Research Feb 2024Per- and polyfluoroalkyl substances (PFAS) constitute a heterogeneous group of synthetic compounds widely used in industrial applications. The estimation of PFAS... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Per- and polyfluoroalkyl substances (PFAS) constitute a heterogeneous group of synthetic compounds widely used in industrial applications. The estimation of PFAS half-life (t) is essential to quantify their persistence, their toxicity and mechanism of action in humans.
OBJECTIVES
The purpose of this review is to summarize the evidence on PFAS half-lives in humans from the available literature, and to investigate the limitations and uncertainties characterizing half-life estimation.
METHODS
The search was conducted on PubMed, Scopus, and Embase databases up to July 03, 2023 and was aimed at identifying all papers that estimated PFAS half-life in human populations. We excluded studies on temporal trends or providing estimates of half-life based solely on renal clearance. As persistent and ongoing exposures can influence half-life estimation, we decided to include only studies that were conducted after the main source of exposure to PFAS had ceased. A random-effects meta-analysis was conducted on studies that reported perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS) or perfluorohexanesulfonic acid (PFHxS) half-life estimation. Risk of bias was evaluated using the OHAT tool.
RESULTS
A total of 13 articles were included in the review, with 5 studies conducted in exposed general populations and 8 studies conducted in exposed workers; the estimated mean half-life ranged from 1.48 to 5.1 years for PFOA, from 3.4 to 5.7 years for total PFOS, and from 2.84 to 8.5 years for PFHxS. High heterogeneity among studies was observed; potential reasons include the variability among the investigated populations, discrepancies in considering ongoing exposures, variability in PFAS isomeric compositions, accounting for background exposure, time since exposure stopped and methods used for half-life estimation.
DISCUSSION
Despite the efforts made to better understand PFAS toxicokinetics, further studies are needed to identify important characteristics of these persistent chemicals. Biomonitoring studies should focus on persistent and unaccounted sources of exposure to PFAS and on individual characteristics potentially determining half-life, to ensure accurate estimates.
Topics: Humans; Alkanesulfonic Acids; Caprylates; Environmental Pollutants; Fluorocarbons; Half-Life; Sulfonic Acids
PubMed: 38008199
DOI: 10.1016/j.envres.2023.117743