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Journal of Hepatology Oct 2021Vibration-controlled transient elastography (VCTE), point shear wave elastography (pSWE), 2-dimensional shear wave elastography (2DSWE), magnetic resonance elastography... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
Vibration-controlled transient elastography (VCTE), point shear wave elastography (pSWE), 2-dimensional shear wave elastography (2DSWE), magnetic resonance elastography (MRE), and magnetic resonance imaging (MRI) have been proposed as non-invasive tests for patients with non-alcoholic fatty liver disease (NAFLD). This study evaluated their diagnostic accuracy for liver fibrosis and non-alcoholic steatohepatitis (NASH).
METHODS
PubMED/MEDLINE, EMBASE and the Cochrane Library were searched for studies examining the diagnostic accuracy of these index tests, against histology as the reference standard, in adult patients with NAFLD. Two authors independently screened and assessed methodological quality of studies and extracted data. Summary estimates of sensitivity, specificity and area under the curve (sAUC) were calculated for fibrosis stages and NASH, using a random effects bivariate logit-normal model.
RESULTS
We included 82 studies (14,609 patients). Meta-analysis for diagnosing fibrosis stages was possible in 53 VCTE, 11 MRE, 12 pSWE and 4 2DSWE studies, and for diagnosing NASH in 4 MRE studies. sAUC for diagnosis of significant fibrosis were: 0.83 for VCTE, 0.91 for MRE, 0.86 for pSWE and 0.75 for 2DSWE. sAUC for diagnosis of advanced fibrosis were: 0.85 for VCTE, 0.92 for MRE, 0.89 for pSWE and 0.72 for 2DSWE. sAUC for diagnosis of cirrhosis were: 0.89 for VCTE, 0.90 for MRE, 0.90 for pSWE and 0.88 for 2DSWE. MRE had sAUC of 0.83 for diagnosis of NASH. Three (4%) studies reported intention-to-diagnose analyses and 15 (18%) studies reported diagnostic accuracy against pre-specified cut-offs.
CONCLUSIONS
When elastography index tests are acquired successfully, they have acceptable diagnostic accuracy for advanced fibrosis and cirrhosis. The potential clinical impact of these index tests cannot be assessed fully as intention-to-diagnose analyses and validation of pre-specified thresholds are lacking.
LAY SUMMARY
Non-invasive tests that measure liver stiffness or use magnetic resonance imaging (MRI) have been suggested as alternatives to liver biopsy for assessing the severity of liver scarring (fibrosis) and fatty inflammation (steatohepatitis) in patients with non-alcoholic fatty liver disease (NAFLD). In this study, we summarise the results of previously published studies on how accurately these non-invasive tests can diagnose liver fibrosis and inflammation, using liver biopsy as the reference. We found that some techniques that measure liver stiffness had a good performance for the diagnosis of severe liver scarring.
Topics: Adult; Area Under Curve; Elasticity Imaging Techniques; Humans; Magnetic Resonance Imaging; Non-alcoholic Fatty Liver Disease; ROC Curve
PubMed: 33991635
DOI: 10.1016/j.jhep.2021.04.044 -
Nutrients Jan 2021Although creatine has been mostly studied as an ergogenic aid for exercise, training, and sport, several health and potential therapeutic benefits have been reported....
Although creatine has been mostly studied as an ergogenic aid for exercise, training, and sport, several health and potential therapeutic benefits have been reported. This is because creatine plays a critical role in cellular metabolism, particularly during metabolically stressed states, and limitations in the ability to transport and/or store creatine can impair metabolism. Moreover, increasing availability of creatine in tissue may enhance cellular metabolism and thereby lessen the severity of injury and/or disease conditions, particularly when oxygen availability is compromised. This systematic review assesses the peer-reviewed scientific and medical evidence related to creatine's role in promoting general health as we age and how creatine supplementation has been used as a nutritional strategy to help individuals recover from injury and/or manage chronic disease. Additionally, it provides reasonable conclusions about the role of creatine on health and disease based on current scientific evidence. Based on this analysis, it can be concluded that creatine supplementation has several health and therapeutic benefits throughout the lifespan.
Topics: Aging; Biological Availability; Chronic Disease; Creatine; Dietary Supplements; Humans; Wounds and Injuries
PubMed: 33572884
DOI: 10.3390/nu13020447 -
Journal of Cosmetic Dermatology Dec 2016Hyaluronic acid is a widely available, biocompatible, polysaccharide with distinguishing physiochemical properties which inspire its application throughout several... (Review)
Review
BACKGROUND
Hyaluronic acid is a widely available, biocompatible, polysaccharide with distinguishing physiochemical properties which inspire its application throughout several fields of medicine.
OBJECTIVE
We aim to investigate the application of hyaluronic acid and its effectiveness throughout several fields of medicine, including several therapies administered and prescribed by general health practitioners.
METHODS
We conducted a systematic review on randomized controlled trials about the physiochemical properties of hyaluronic acid and its application through primary care. Studies included in this review were peer reviewed and met our inclusion criteria.
FINDINGS
Factors were clustered into the following: uses throughout several fields of medicine, physiochemical properties, bioavailability, tolerance, effectiveness, and adverse effects. Therapies with hyaluronic acid provided long-lasting, pain relieving, moisturizing, lubricating, and dermal filling effect. Tissue hydration, elasticity, and durability improved.
CONCLUSIONS
Adjunct therapy with hyaluronic acid provides longer-lasting therapeutic effect when compared to the use of glucocorticosteroids and NSAIDs in osteoarthritic chronic diseases, is well-established in ophthalmology due to its lubricating properties for the corneal endothelium, and improves tissue hydration and cellular resistance to mechanical damage in aesthetic dermatology, and has marginal adverse effects. Several trials indicated its role in tumor markers, liver diseases, and in pharmaceuticals, but further research would be necessary to draw conclusive results in those fields.
Topics: Biological Availability; Cosmetic Techniques; Dermal Fillers; Dry Eye Syndromes; Humans; Hyaluronic Acid; Neoplasms; Osteoarthritis; Randomized Controlled Trials as Topic; Viscosupplements
PubMed: 27324942
DOI: 10.1111/jocd.12237 -
Nutrition (Burbank, Los Angeles County,... Sep 2021The market for food supplements is booming thanks to their increased consumption. European regulations include different ways in which vitamins and minerals are... (Review)
Review
OBJECTIVES
The market for food supplements is booming thanks to their increased consumption. European regulations include different ways in which vitamins and minerals are administered, without making it clear to the consumer whether one formulation has advantages over the other. The aim of this review was to compare the bioavailability of different forms of magnesium and analyze the differences between them.
METHODS
Based on a PICO (population, intervention, comparison, outcome) research question, a search strategy was established for magnesium bioavailability studies comparing different forms in the PubMed, Cochrane, Web of Science, and Scopus databases. We found 433 studies, out of which 14 were finally selected.
RESULTS
Inorganic formulations appear to be less bioavailable than organic ones, and the percentage of absorption is dose dependent.
CONCLUSIONS
All magnesium dietary supplements can maintain physiological levels in healthy people without prior deficit, although this cannot be assured in older people or those with illnesses or previous subphysiological levels.
Topics: Aged; Biological Availability; Dietary Supplements; Humans; Magnesium; Minerals; Vitamins
PubMed: 34111673
DOI: 10.1016/j.nut.2021.111294 -
Current Hypertension Reports Nov 2022To provide an overview of the literature regarding the use of machine learning algorithms to predict hypertension. A systematic review was performed to select recent... (Review)
Review
PURPOSE OF REVIEW
To provide an overview of the literature regarding the use of machine learning algorithms to predict hypertension. A systematic review was performed to select recent articles on the subject.
RECENT FINDINGS
The screening of the articles was conducted using a machine learning algorithm (ASReview). A total of 21 articles published between January 2018 and May 2021 were identified and compared according to variable selection, train-test split, data balancing, outcome definition, final algorithm, and performance metrics. Overall, the articles achieved an area under the ROC curve (AUROC) between 0.766 and 1.00. The algorithms most frequently identified as having the best performance were support vector machines (SVM), extreme gradient boosting (XGBoost), and random forest. Machine learning algorithms are a promising tool to improve preventive clinical decisions and targeted public health policies for hypertension. However, technical factors such as outcome definition, availability of the final code, predictive performance, explainability, and data leakage need to be consistently and critically evaluated.
Topics: Algorithms; Area Under Curve; Humans; Hypertension; Machine Learning; Support Vector Machine
PubMed: 35731335
DOI: 10.1007/s11906-022-01212-6 -
Drug Metabolism and Disposition: the... Nov 2015Modeling and simulation of drug disposition has emerged as an important tool in drug development, clinical study design and regulatory review, and the number of... (Review)
Review
Modeling and simulation of drug disposition has emerged as an important tool in drug development, clinical study design and regulatory review, and the number of physiologically based pharmacokinetic (PBPK) modeling related publications and regulatory submissions have risen dramatically in recent years. However, the extent of use of PBPK modeling by researchers, and the public availability of models has not been systematically evaluated. This review evaluates PBPK-related publications to 1) identify the common applications of PBPK modeling; 2) determine ways in which models are developed; 3) establish how model quality is assessed; and 4) provide a list of publically available PBPK models for sensitive P450 and transporter substrates as well as selective inhibitors and inducers. PubMed searches were conducted using the terms "PBPK" and "physiologically based pharmacokinetic model" to collect published models. Only papers on PBPK modeling of pharmaceutical agents in humans published in English between 2008 and May 2015 were reviewed. A total of 366 PBPK-related articles met the search criteria, with the number of articles published per year rising steadily. Published models were most commonly used for drug-drug interaction predictions (28%), followed by interindividual variability and general clinical pharmacokinetic predictions (23%), formulation or absorption modeling (12%), and predicting age-related changes in pharmacokinetics and disposition (10%). In total, 106 models of sensitive substrates, inhibitors, and inducers were identified. An in-depth analysis of the model development and verification revealed a lack of consistency in model development and quality assessment practices, demonstrating a need for development of best-practice guidelines.
Topics: Animals; Computer Simulation; Drug Interactions; Humans; Models, Biological; Pharmaceutical Preparations; Pharmacokinetics
PubMed: 26296709
DOI: 10.1124/dmd.115.065920 -
Pharmacotherapy Sep 2022Vancomycin is commonly used to treat methicillin-resistant Staphylococcus aureus infections and is known to cause nephrotoxicity. Previous Vancomycin Consensus... (Meta-Analysis)
Meta-Analysis Review
Vancomycin is commonly used to treat methicillin-resistant Staphylococcus aureus infections and is known to cause nephrotoxicity. Previous Vancomycin Consensus Guidelines recommended targeting trough concentrations but the 2020 Guidelines suggest monitoring vancomycin area under the curve (AUC) given the reduced risk of acute kidney injury (AKI) at similar levels of efficacy. This meta-analysis compares vancomycin-induced AKI incidence using AUC-guided dosing strategies versus trough-based monitoring. Literature was queried from Medline (Ovid), Web of Science, and Google Scholar from database inception through November 5, 2021. Interventional or observational studies reporting the incidence of vancomycin-induced AKI between AUC- and trough-guided dosing strategies were included. In the primary analysis, the Vancomycin Consensus Guidelines definition for AKI was used if reported; otherwise, the Risk, Injury, and Failure; and Loss, and End-stage kidney disease (RIFLE) or Kidney Disease Improving Global Outcomes (KDIGO) definitions were used. The incidence of nephrotoxicity was evaluated between the two strategies using a Mantel-Haenszel random-effects model, and odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Subgroup analyses for adjusted ORs and AKI definitions were performed. Heterogeneity was identified using Cochrane's Q test and I statistics. A total of 10 studies with 4231 patients were included. AUC-guided dosing strategies were associated with significantly less vancomycin-induced AKI than trough-guided strategies [OR 0.625, 95% CI (0.469-0.834), p = 0.001; I = 25.476]. A subgroup analysis of three studies reporting adjusted ORs yielded similar results [OR 0.475, 95% CI (0.261-0.863), p = 0.015]. Stratification by AKI definition showed a significant reduction in AKI with the Vancomycin Consensus Guidelines definition [OR 0.552, 95% CI (0.341-0.894), p = 0.016] but failed to find significance in the alternative definitions. Area under the curve-guided dosing strategies are associated with a lower incidence of vancomycin-induced AKI versus trough-guided dosing strategies (GRADE, low). Limitations included the variety of AKI definitions and the potential for confounding bias.
Topics: Humans; Acute Kidney Injury; Anti-Bacterial Agents; Area Under Curve; Electrolytes; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Retrospective Studies; Vancomycin
PubMed: 35869689
DOI: 10.1002/phar.2722 -
Clinical Pharmacokinetics Feb 2020Pharmacokinetics (PK) are severely altered in critically ill patients due to changes in volume of distribution (Vd) and/or drug clearance (Cl). This affects the target...
BACKGROUND
Pharmacokinetics (PK) are severely altered in critically ill patients due to changes in volume of distribution (Vd) and/or drug clearance (Cl). This affects the target attainment of antibiotics in critically ill children. We aimed to identify gaps in current knowledge and to compare published PK parameters and target attainment of antibiotics in critically ill children to healthy children and critically ill adults.
METHODS
Systematic literature search in PubMed, EMBASE and Web of Science. Articles were labelled as relevant when they included information on PK of antibiotics in critically ill, non-neonatal, pediatric patients. Extracted PK-parameters included Vd, Cl, (trough) concentrations, AUC, probability of target attainment, and elimination half-life.
RESULTS
50 relevant articles were identified. Studies focusing on vancomycin were most prevalent (17/50). Other studies included data on penicillins, cephalosporins, carbapenems and aminoglycosides, but data on ceftriaxone, ceftazidime, penicillin and metronidazole could not be found. Critically ill children generally show a higher Cl and larger Vd than healthy children and critically ill adults. Reduced target-attainment was described in critically ill children for multiple antibiotics, including amoxicillin, piperacillin, cefotaxime, vancomycin, gentamicin, teicoplanin, amikacin and daptomycin. 38/50 articles included information on both Vd and Cl, but a dosing advice was given in only 22 articles.
CONCLUSION
The majority of studies focus on agents where TDM is applied, while other antibiotics lack data altogether. The larger Vd and higher Cl in critically ill children might warrant a higher dose or extended infusions of antibiotics in this patient population to increase target-attainment. Studies frequently fail to provide a dosing advice for this patient population, even if the necessary information is available. Our study shows gaps in current knowledge and encourages future researchers to provide dosing advice for special populations whenever possible.
Topics: Acute Kidney Injury; Adolescent; Aminoglycosides; Anti-Bacterial Agents; Area Under Curve; Carbapenems; Cephalosporins; Child; Child, Preschool; Critical Illness; Drug Monitoring; Female; Half-Life; Humans; Infant; Infusions, Intravenous; Male; Penicillins; Vancomycin; Young Adult
PubMed: 31432468
DOI: 10.1007/s40262-019-00813-w -
British Journal of Clinical Pharmacology Sep 2015It is common to advise that analgesics, and especially non-steroidal anti-inflammatory drugs (NSAIDs), be taken with food to reduce unwanted gastrointestinal adverse... (Review)
Review
AIMS
It is common to advise that analgesics, and especially non-steroidal anti-inflammatory drugs (NSAIDs), be taken with food to reduce unwanted gastrointestinal adverse effects. The efficacy of single dose analgesics depends on producing high, early, plasma concentrations; food may interfere with this. This review sought evidence from single dose pharmacokinetic studies on the extent and timing of peak plasma concentrations of analgesic drugs in the fed and fasting states.
METHODS
A systematic review of comparisons of oral analgesics in fed and fasting states published to October 2014 reporting kinetic parameters of bioavailability, time to maximum plasma concentration (tmax ), and its extent (Cmax ) was conducted. Delayed-release formulations were not included.
RESULTS
Bioavailability was not different between fasted and fed states. Food typically delayed absorption for all drugs where the fasting tmax was less than 4 h. For the common analgesics (aspirin, diclofenac, ibuprofen, paracetamol) fed tmax was 1.30 to 2.80 times longer than fasted tmax . Cmax was typically reduced, with greater reduction seen with more rapid absorption (fed Cmax only 44-85% of the fasted Cmax for aspirin, diclofenac, ibuprofen and paracetamol).
CONCLUSION
There is evidence that high, early plasma concentrations produces better early pain relief, better overall pain relief, longer lasting pain relief and lower rates of remedication. Taking analgesics with food may make them less effective, resulting in greater population exposure. It may be time to rethink research priorities and advice to professionals, patients and the public.
Topics: Acetaminophen; Administration, Oral; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Biological Availability; Dipyrone; Drug Liberation; Food-Drug Interactions; Humans
PubMed: 25784216
DOI: 10.1111/bcp.12628 -
PLoS Medicine Nov 2016Women are commonly prescribed a variety of medications during pregnancy. As most organ systems are affected by the substantial anatomical and physiological changes that... (Review)
Review
BACKGROUND
Women are commonly prescribed a variety of medications during pregnancy. As most organ systems are affected by the substantial anatomical and physiological changes that occur during pregnancy, it is expected that pharmacokinetics (PK) (absorption, distribution, metabolism, and excretion of drugs) would also be affected in ways that may necessitate changes in dosing schedules. The objective of this study was to systematically identify existing clinically relevant evidence on PK changes during pregnancy.
METHODS AND FINDINGS
Systematic searches were conducted in MEDLINE (Ovid), Embase (Ovid), Cochrane Central Register of Controlled Trials (Ovid), and Web of Science (Thomson Reuters), from database inception to August 31, 2015. An update of the search from September 1, 2015, to May 20, 2016, was performed, and relevant data were added to the present review. No language or date restrictions were applied. All publications of clinical PK studies involving a group of pregnant women with a comparison to nonpregnant participants or nonpregnant population data were eligible to be included in this review. A total of 198 studies involving 121 different medications fulfilled the inclusion criteria. In these studies, commonly investigated drug classes included antiretrovirals (54 studies), antiepileptic drugs (27 studies), antibiotics (23 studies), antimalarial drugs (22 studies), and cardiovascular drugs (17 studies). Overall, pregnancy-associated changes in PK parameters were often observed as consistent findings among many studies, particularly enhanced drug elimination and decreased exposure to total drugs (bound and unbound to plasma proteins) at a given dose. However, associated alterations in clinical responses and outcomes, or lack thereof, remain largely unknown.
CONCLUSION
This systematic review of pregnancy-associated PK changes identifies a significant gap between the accumulating knowledge of PK changes in pregnant women and our understanding of their clinical impact for both mother and fetus. It is essential for clinicians to be aware of these unique pregnancy-related changes in PK, and to critically examine their clinical implications.
Topics: Female; Humans; Pharmaceutical Preparations; Pharmacokinetics; Pregnancy
PubMed: 27802281
DOI: 10.1371/journal.pmed.1002160