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Redox Biology May 2024This systematic review provides an overview of the available evidence on the inter-individual variability (IIV) in the absorption, distribution, metabolism, and... (Review)
Review
This systematic review provides an overview of the available evidence on the inter-individual variability (IIV) in the absorption, distribution, metabolism, and excretion (ADME) of phenolic metabolites and its determinants. Human studies were included investigating the metabolism and bioavailability of (poly)phenols and reporting IIV. One hundred fifty-three studies met the inclusion criteria. Inter-individual differences were mainly related to gut microbiota composition and activity but also to genetic polymorphisms, age, sex, ethnicity, BMI, (patho)physiological status, and physical activity, depending on the (poly)phenol sub-class considered. Most of the IIV has been poorly characterised. Two major types of IIV were observed. One resulted in metabolite gradients that can be further classified into high and low excretors, as seen for all flavonoids, phenolic acids, prenylflavonoids, alkylresorcinols, and hydroxytyrosol. The other type of IIV is based on clusters of individuals defined by qualitative differences (producers vs. non-producers), as for ellagitannins (urolithins), isoflavones (equol and O-DMA), resveratrol (lunularin), and preliminarily for avenanthramides (dihydro-avenanthramides), or by quali-quantitative metabotypes characterized by different proportions of specific metabolites, as for flavan-3-ols, flavanones, and even isoflavones. Future works are needed to shed light on current open issues limiting our understanding of this phenomenon that likely conditions the health effects of dietary (poly)phenols.
Topics: Humans; Biological Availability; Phenols; Flavonoids; Isoflavones; Diet
PubMed: 38428187
DOI: 10.1016/j.redox.2024.103095 -
JAC-antimicrobial Resistance Feb 2024Population pharmacokinetic studies of β-lactam antimicrobials in critically ill patients derive models that inform their dosing. In non-linear mixed-effects modelling,... (Review)
Review
INTRODUCTION
Population pharmacokinetic studies of β-lactam antimicrobials in critically ill patients derive models that inform their dosing. In non-linear mixed-effects modelling, covariates are often used to improve model fit and explain variability. We aimed to investigate which covariates are most commonly assessed and which are found to be significant, along with global patterns of publication.
METHODS
We conducted a systematic review, searching MEDLINE, Embase, CENTRAL and Web of Science on 01 March 2023, including studies of critically ill adults receiving β-lactam antimicrobials who underwent blood sampling for population pharmacokinetic studies. We extracted and categorized all reported covariates and assessed reporting quality using the ClinPK checklist.
RESULTS
Our search identified 151 studies with 6018 participants. Most studies reported observational cohorts (120 studies, 80%), with the majority conducted in high-income settings (136 studies, 90%). Of the 1083 identified covariate instances, 237 were unique; the most common categories were patient characteristics ( = 404), biomarkers ( = 206) and physiological parameters ( = 163). Only seven distinct commonly reported covariates (CL, weight, glomerular filtration rate, diuresis, need for renal replacement, serum albumin and C-reactive protein) were significant more than 20% of the time.
CONCLUSIONS
Covariates are most commonly chosen based on biological plausibility, with patient characteristics and biomarkers the most frequently investigated. We developed an openly accessible database of reported covariates to aid investigators with covariate selection when designing population pharmacokinetic studies. Novel covariates, such as sepsis subphenotypes, have not been explored yet, leaving a research gap for future work.
PubMed: 38410250
DOI: 10.1093/jacamr/dlae030 -
Scientific Data Feb 2024The cutaneous absorption parameters of xenobiotics are crucial for the development of drugs and cosmetics, as well as for assessing environmental and occupational...
The cutaneous absorption parameters of xenobiotics are crucial for the development of drugs and cosmetics, as well as for assessing environmental and occupational chemical risks. Despite the great variability in the design of experimental conditions due to uncertain international guidelines, datasets like HuskinDB have been created to report skin absorption endpoints. This review updates available skin permeability data by rigorously compiling research published between 2012 and 2021. Inclusion and exclusion criteria have been selected to build the most harmonized and reusable dataset possible. The Generative Topographic Mapping method was applied to the present dataset and compared to HuskinDB to monitor the progress in skin permeability research and locate chemotypes of particular concern. The open-source dataset (SkinPiX) includes steady-state flux, maximum flux, lag time and permeability coefficient results for the substances tested, as well as relevant information on experimental parameters that can impact the data. It can be used to extract subsets of data for comparisons and to build predictive models.
Topics: Permeability; Skin; Skin Absorption; Xenobiotics; Datasets as Topic; Humans
PubMed: 38383523
DOI: 10.1038/s41597-024-03026-4 -
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 -
Annals of Intensive Care Feb 2024The two latest studies on prolonged versus intermittent use of β-lactam antibiotics in patients with sepsis did not reach consistent conclusions, further contributing... (Review)
Review
BACKGROUND
The two latest studies on prolonged versus intermittent use of β-lactam antibiotics in patients with sepsis did not reach consistent conclusions, further contributing to the controversy surrounding the effectiveness of the prolonged β-lactam antibiotics infusion strategy. We conducted a systemic review and meta-analysis to evaluate the efficacy and safety of prolonged and intermittent β-lactam infusion in adult patients with sepsis.
METHODS
We systematically searched PubMed, EMBASE, and Cochrane Library databases for original randomized controlled trials comparing prolonged and intermittent β-lactam infusion in sepsis patients. A random-effects model was used to evaluate mortality, clinical success, microbiological success, and adverse events. We also conducted subgroup analyses to explore the impact of various factors on the mortality rates. Relative risk (RR) and corresponding 95% confidence intervals (CIs) were used to calculate the overall effect sizes for dichotomous outcomes. This meta-analysis was registered in PROSPERO (CRD42023463905).
RESULTS
We assessed 15 studies involving 2130 patients. In our comprehensive assessment, we found a significant reduction in all-cause mortality (RR, 0.83; 95% CI 0.72-0.97; P = 0.02) and a notable improvement in clinical success (RR, 1.16; 95% CI 1.03-1.31; P = 0.02) in the prolonged infusion group compared to the intermittent infusion group, whereas microbiological success did not yield statistically significant results (RR, 1.10; 95% CI 0.98-1.23; P = 0.11). No significant differences in adverse events were observed between the two groups (RR, 0.91; 95% CI 0.64-1.29; P = 0.60). Additionally, remarkable conclusions were drawn from subgroup analyses including studies with sample sizes exceeding 20 individuals per group (RR, 0.84; 95%CI 0.72-0.98; P = 0.03), research conducted post-2010 (RR, 0.84; 95%CI 0.72-0.98; P = 0.03), cases involving infections predominantly caused by Gram-negative bacteria (RR, 0.81; 95%CI 0.68-0.96; P = 0.02), as well as the administration of a loading dose (RR, 0.84; 95% CI 0.72-0.97; P = 0.02) and the use of penicillin (RR, 0.61; 95% CI 0.38-0.98; P = 0.04).
CONCLUSIONS
Compared to intermittent infusion, prolonged infusion of β-lactam antibiotics significantly decreases all-cause mortality among patients with sepsis and enhances clinical success without increasing adverse events.
PubMed: 38368588
DOI: 10.1186/s13613-024-01263-9 -
Cureus Feb 2024The conventional method of heparin and protamine management during cardiopulmonary bypass (CPB) is based on total body weight which fails to account for the... (Review)
Review
BACKGROUND
The conventional method of heparin and protamine management during cardiopulmonary bypass (CPB) is based on total body weight which fails to account for the heterogeneous response to heparin in each patient. On the other hand, the literature is inconclusive on whether individualized anticoagulation management based on real-time blood heparin concentration improves post-CBP outcomes.
METHODS
We searched databases of Medline, Excerpta Medica dataBASE (EMBASE), PubMed, Cumulative Index to Nursing and Allied Health Literature (CINHL), and Google Scholar, recruiting randomized controlled trials (RCTs) and prospective studies comparing the outcomes of dosing heparin and/or protamine based on measured heparin concentration versus patient's total body weight for CPB. Random effects meta-analyses and meta-regression were conducted to compare the outcome profiles. Primary endpoints include postoperative blood loss and the correlation with heparin and protamine doses, the reversal protamine and loading heparin dose ratio; secondary endpoints included postoperative platelet counts, antithrombin III, fibrinogen levels, activated prothrombin time (aPTT), incidences of heparin rebound, and re-exploration of chest wound for bleeding.
RESULTS
Twenty-six studies, including 22 RCTs and four prospective cohort studies involving 3,810 patients, were included. Compared to body weight-based dosing, patients of individualized, heparin concentration-based group had significantly lower postoperative blood loss (mean difference (MD)=49.51 mL, 95% confidence interval (CI): 5.33-93.71), lower protamine-to-heparin dosing ratio (MD=-0.20, 95% CI: -0.32 ~ -0.12), and higher early postoperative platelet counts (MD=8.83, 95% CI: 2.07-15.59). The total heparin doses and protamine reversal were identified as predictors of postoperative blood loss by meta-regression.
CONCLUSIONS
There was a significant correlation between the doses of heparin and protamine with postoperative blood loss; therefore, précised dosing of both could be critical for reducing bleeding and transfusion requirements. Data from the enrolled studies indicated that compared to conventional weight-based dosing, individualized, blood concentration-based heparin and protamine dosing may have outcome benefits reducing postoperative blood loss. The dosing calculation of heparin based on the assumption of a one-compartment pharmacokinetic/pharmacodynamic (PK/PD) model and linear relationship between the calculated dose and blood heparin concentration may be inaccurate. With the recent advancement of the technologies of machine learning, individualized, precision management of anticoagulation for CPB may be possible in the near future.
PubMed: 38357407
DOI: 10.7759/cureus.54144 -
Epilepsia Open Apr 2024Antiseizure medications (ASMs) constitute the principal of treatment for patients with epilepsy, where long-term treatment is usually necessary. The purpose of this... (Review)
Review
Antiseizure medications (ASMs) constitute the principal of treatment for patients with epilepsy, where long-term treatment is usually necessary. The purpose of this systematic review is to provide practical and useful information regarding various aspects of the interactions between ASMs and foods and drinks. MEDLINE and ScienceDirect, from the inception to July 15, 2023, were searched for related publications. In both electronic databases, the following search strategy was applied, and the following keywords were used (in title/abstract): "food OR drink" AND "antiepileptic OR antiseizure." The primary search yielded 738 studies. After implementing our inclusion and exclusion criteria, we could identify 19 studies on the issue of interest for our endeavor. Four studies were identified in the recheck process and not by the primary search. All studies provided low level of evidence. Interactions between foods and ASMs are a common phenomenon. Many factors may play a role for such an interaction to come to play; these include drug properties, administration route, and administration schedule, among others. Drugs-foods (-drinks) interactions may change the drug exposure or plasma levels of drugs (e.g., grapefruit juice increases carbamazepine concentrations and the bioavailability of cannabidiol is increased 4-5 folds with concomitant intake of fat-rich food); this may require dosage adjustments. Interactions between ASMs and foods and drinks may be important. This should be taken seriously into consideration when consulting patients and their caregivers about ASMs. Future well-designed investigations should explore the specific interactions between foods (and drinks) and ASMs to clarify whether they are clinically important. PLAIN LANGUAGE SUMMARY: Interactions between antiseizure medications and foods and drinks may be important. This should be taken into consideration in patients with epilepsy.
Topics: Humans; Anticonvulsants; Biological Availability; Benzodiazepines; Food; Epilepsy
PubMed: 38345419
DOI: 10.1002/epi4.12918 -
BMC Nephrology Feb 2024This study aimed to investigate the association between cytochrome P450 (CYP) 3A4*22 and cytochrome P450 oxidoreductase (POR)*28 variations and the pharmacokinetics of... (Meta-Analysis)
Meta-Analysis
PURPOSE
This study aimed to investigate the association between cytochrome P450 (CYP) 3A4*22 and cytochrome P450 oxidoreductase (POR)*28 variations and the pharmacokinetics of tacrolimus.
METHODS
Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science (SCI), MEDLINE, and Embase were systematically searched from inception to August 2022. The outcomes were weight-adjusted daily dose and dose-adjusted trough concentration (C/Dose).
RESULTS
The study included 2931 renal transplant recipients from 18 publications. Weight-adjusted daily dose of CYP3A4*1/*1 carriers was 0.04 (WMD = 0.04, 95% CI: 0.02 to 0.06), 0.03 (WMD = 0.03, 95% CI: 0.02 to 0.05), 0.02 (WMD = 0.02, 95% CI: 0.01 to 0.03), or 0.02 mg/kg/day (WMD = 0.02, 95% CI: 0.00 to 0.04) higher than CYP3A4*22 carriers in Caucasians at 1 month, 3 months, 6 months, or 12 months post-transplantation. Conversely, C0/Dose was lower for CYP3A4*1/*1 carriers at 3 days (SMD = -0.35, 95% CI: -0.65 to -0.06), 1 month (SMD = -0.67, 95% CI: -1.16 to -0.18), 3 months (SMD = -0.60, 95% CI: -0.89 to -0.31), 6 months (SMD = -0.76, 95% CI: -1.49 to -0.04), or 12 months post-transplantation (SMD = -0.69, 95% CI: -1.37 to 0.00). Furthermore, C/Dose of POR*1/*1 carriers was 22.64 (WMD = 22.64, 95% CI: 2.54 to 42.74) or 19.41 (ng/ml)/(mg/kg/day) (WMD = 19.41, 95% CI: 9.58 to 29.24) higher than POR*28 carriers in CYP3A5 expressers at 3 days or 7 days post-transplantation, and higher in Asians at 6 months post-transplantation (SMD = 0.96, 95% CI: 0.50 to 1.43).
CONCLUSIONS
CYP3A4*22 variant in Caucasians restrains the metabolism of tacrolimus, while POR*28 variant in CYP3A5 expressers enhances the metabolism of tacrolimus for renal transplant recipients. However, further well-designed prospective studies are necessary to substantiate these conclusions given some limitations.
Topics: Humans; Tacrolimus; Cytochrome P-450 CYP3A; Immunosuppressive Agents; Kidney Transplantation; Prospective Studies; Polymorphism, Single Nucleotide; Transplant Recipients; Genotype
PubMed: 38321419
DOI: 10.1186/s12882-024-03467-4 -
European Geriatric Medicine Feb 2024Dysphagia is associated with long-term conditions including strokes, dementia, Parkinson's disease and frailty. Dysphagia affects 30-40% of the population aged over...
INTRODUCTION
Dysphagia is associated with long-term conditions including strokes, dementia, Parkinson's disease and frailty. Dysphagia affects 30-40% of the population aged over 65 years-old. Adults with dysphagia often experience long-term conditions requiring multiple medications (often > 5) to manage these. The thickening of liquids is a common compensatory strategy in dysphagia management. Studies suggest that immersion in thickened liquids affects medicines' solubility in vitro. Clinicians and pharmacists are unaware of the pharmacokinetic/therapeutic effects of thickened liquids on oral medicines. We conducted a systematic review of existing literature on thickeners' effects on drug bioavailability.
METHODOLOGY
We performed a literature search of MEDLINE & EMBASE. Search terms included: dysphagia/thickened diet (EMBASE only)/ bioavailability or absorption of medicines or pharmacokinetics; excluded: NG feeds/animal studies.
STUDIES INCLUDED
all genders, countries, > 18 years, community and hospital settings. PRISMA guidance was followed.
RESULTS
Five hundred seventy results were found, and 23 articles identified following the reference list review. Following an abstract and full-text review, 18 were included. Most articles evaluated thickeners on dissolution profiles in-vitro, with a few investigating in-vivo. Most studies were single-centre prospective studies identifying that thickeners generally affect dissolution rates of medications. Few studies assessed bioavailability or used clinical outcomes.
CONCLUSION
Dysphagia and polypharmacy are common in older adults, but little is known about the effects of altering liquid viscosity on the therapeutic effect of most medications. Further larger-scale studies are required to evaluate the therapeutic impact of thickener, on a bigger range of medications, factoring in other variables such as type of thickener, viscosity of thickener and duration of immersion.
Topics: Animals; Female; Male; Deglutition Disorders; Beverages; Biological Availability; Prospective Studies; Food Additives
PubMed: 38280090
DOI: 10.1007/s41999-023-00896-6 -
BMC Public Health Jan 2024Self-medication during pregnancy is of great interest. The use of drugs during pregnancy requires a careful reflection on the benefits to the mother and the risks to the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Self-medication during pregnancy is of great interest. The use of drugs during pregnancy requires a careful reflection on the benefits to the mother and the risks to the fetus. Selecting a drug or drugs for treating pregnant women can be difficult for clinicians owing to the various pharmacokinetic and physiological changes encountered during pregnancy. This systematic review and meta-analysis aimed to estimate the pooled prevalence of self-medication and associated factors among women during pregnancy.
METHODS
Searches were carried out at PubMed, Science Direct, Web of Science, and Google Scholar. The quality of the studies and the risk of bias were analyzed using the Joanna Briggs Critical Appraisal Checklist for Analytical Cross-Sectional Studies instrument. The extracted data were tabulated and analyzed qualitatively and quantitatively through meta-analysis.
RESULTS
The overall prevalence of self-medication among pregnant women was 44.50% (95% CI: 38.92-50.23). Subgroup analyses showed differences in self-medication prevalence influenced by region, county income, and study design. The Heterogeneity, assessed by the statistical test I2 varied from 96 to 99% and was statistically significant. The result of this funnel plot showed that the funnel plot was symmetry with p-value = 0.36, and there is no publication bias.
CONCLUSION
The results obtained from this study showed that the prevalence of self-medication among pregnant women is relatively high. This requires effective measures and interventions to reduce self-medication.
TRIAL REGISTRATION
ID = CRD42022312333 .
Topics: Female; Humans; Pregnancy; Cross-Sectional Studies; Pregnant Women; Prevalence; Self Medication; Geography; Socioeconomic Factors
PubMed: 38279083
DOI: 10.1186/s12889-023-17195-1