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Journal of the Neurological Sciences Jan 2021In order to better educate patients, predictive models have been implemented to stratify surgical risk, thereby instituting greater uniformity across surgical practices...
In order to better educate patients, predictive models have been implemented to stratify surgical risk, thereby instituting greater uniformity across surgical practices and prioritizing the safety and outcomes of patients. The purpose of this study is to conduct a systematic review summarizing the major predictive models used to evaluate patients as candidates for spinal surgery. A search was conducted for articles related to predictive modeling in spinal surgeries using PubMed, MEDLINE, and Scopus databases. Papers with area under the receiver operating curve (AUROC) scores reported were included in the analysis. Models not relevant to spinal procedures were excluded. Comparison between models was only attainable for those that reported AUROCs for individual procedures. Based on a combination of AUROC scores and demonstrated applicability to spinal procedures, the models by Scheer et al. (0.89), Ratliff et al. (0.70), the Seattle Spine Score (0.712), Risk Assessment Tool (0.67-0.7), and the Spine Sage calculator (0.81-0.85) were determined to be ideal for predictive modeling in spinal surgeries and were subsequently broken down into their individual inputs and outputs to determine what elements a theoretical model should assimilate. Alongside the model by Scheer et al., the Spine Sage calculator, Seattle Spine Score, Risk Assessment Tool, and a model by Ratliff et al. showed the most promise for patients undergoing spinal procedures. Using the first model as a springboard, new spinal predictive models can be optimized through use of larger prospective databases, with longer follow-up times, and greater inclusion of reliable high impact variables.
Topics: Algorithms; Area Under Curve; Humans; Neurosurgical Procedures; Risk Assessment; Spine
PubMed: 33203588
DOI: 10.1016/j.jns.2020.117184 -
Chinese Journal of Natural Medicines Jul 2021The tubers and roots of Aconitum (Ranunculaceae) are widely used as heart medicine or analgesic agents for the treatment of coronary heart disease, chronic heart... (Review)
Review
The tubers and roots of Aconitum (Ranunculaceae) are widely used as heart medicine or analgesic agents for the treatment of coronary heart disease, chronic heart failure, rheumatoid arthritis and neuropathic pain since ancient times. As a type of natural products mainly extracted from Aconitum plants, Aconitum alkaloids have complex chemical structures and exert remarkable biological activity, which are mainly responsible for significant effects of Aconitum plants. The present review is to summarize the progress of the pharmacological, toxicological, and pharmacokinetic studies of Aconitum alkaloids, so as to provide evidence for better clinical application. Research data concerning pharmacological, toxicological and pharmacokinetic studies of Aconitum alkaloids were collected from different scientific databases (PubMed, CNKI, Google Scholar, Baidu Scholar, and Web of Science) using the phrase Aconitum alkaloids, as well as generic synonyms. Aconitum alkaloids are both bioactive compounds and toxic ingredients in Aconitum plants. They produce a wide range of pharmacological activities, including protecting the cardiovascular system, nervous system, and immune system and anti-cancer effects. Notably, Aconitum alkaloids also exert strong cardiac toxicity, neurotoxicity and liver toxicity, which are supported by clinical studies. Finally, pharmacokinetic studies indicated that cytochrome P450 proteins (CYPs) and efflux transporters (ETs) are closely related to the low bioavailability of Aconitum alkaloids and play an important role in their metabolism and detoxification in vivo.
Topics: Aconitum; Alkaloids; Biological Availability; Phytochemicals; Plant Roots
PubMed: 34247774
DOI: 10.1016/S1875-5364(21)60050-X -
American Journal of Nephrology 2016Concerns exist over the extrapolation of bioavailability studies of generic immunosuppressive drugs in healthy volunteers, regarding their efficacy and safety in kidney... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Concerns exist over the extrapolation of bioavailability studies of generic immunosuppressive drugs in healthy volunteers, regarding their efficacy and safety in kidney transplant recipients. We conducted a meta-analysis of trials examining the bioavailability of generic (test) immunosuppressive drugs relative to their brand (reference) counterparts in healthy volunteers, based on the US Food and Drug Administration requirements for approval of generics, and their efficacy and safety in kidney transplant recipients.
METHODS
Eligible studies were identified in PubMed, Cochrane Central Register of Controlled Trials, Scopus, ClinicalTrials.gov, and conference abstracts.
RESULTS
Twenty crossover trials of healthy volunteers (n = 641) and 6 parallel-arm randomized controlled trials of kidney transplant recipients (n = 594) were identified. The 90% CI of the pooled test-to-reference drug ratio for maximum or peak plasma concentration (Cmax) and area under the plasma concentration time-curve from time 0 to time of last determinable concentration (AUC(0-t)) fell within the required range (0.80-1.25) for cyclosporine (Cmax 0.91; 90% CI 0.86-0.95; and AUC(0-t) 0.97; 90% CI 0.94-1.00), tacrolimus (Cmax 1.17; 90% CI 1.09-1.24; and AUC(0-t) 1.00; 90% CI 0.97-1.03) and mycophenolate mofetil (Cmax 0.98; 90% CI 0.96-1.01; and AUC(0-t) 1.00; 90% CI 0.99-1.01). In subgroup analyses, some generic cyclosporine formulations did not meet criteria for bioequivalence. No significant differences were observed in the time to maximum plasma concentration and terminal plasma half-life between generic and brand drugs. In parallel-arm trials, generic cyclosporine was non-inferior to brand counterpart in terms of acute allograft rejection, infections, and death.
CONCLUSIONS
Not all generic immunosuppressive drugs have similar relative bioavailability to their brand name counterparts. Evidence on their efficacy and safety is inconclusive. Tighter regulatory requirement for approval of generic drugs with narrow therapeutic index is needed.
Topics: Biological Availability; Cyclosporine; Drugs, Generic; Humans; Immunosuppressive Agents; Kidney Transplantation; Mycophenolic Acid; Tacrolimus; Therapeutic Equivalency
PubMed: 27576318
DOI: 10.1159/000449020 -
Gastrointestinal Endoscopy Aug 2022This systematic review and meta-analysis aims to compare the pooled diagnostic accuracy of the currently available esophageal squamous cell carcinoma (ESCC) screening... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND AIMS
This systematic review and meta-analysis aims to compare the pooled diagnostic accuracy of the currently available esophageal squamous cell carcinoma (ESCC) screening tests.
METHODS
A comprehensive literature search of Embase and Medline (up to October 31, 2020) was performed to identify eligible studies. We pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio for ESCC screening tools using a bivariate random-effects model. The summary receiver operating characteristic curves with area under the curve (AUC) were plotted for each screening test.
RESULTS
We included 161 studies conducted in 81 research articles involving 32,209 subjects. The pooled sensitivity, specificity, and AUC of the major screening tools were respectively as follows: endoscopy (peroral endoscopy): .94 (95% confidence interval [CI], .87-.97), .92 (95% CI, .87-.95), and .97 (95% CI, .96-.99); endoscopy (transnasal endoscopy): .85 (95% CI, .70-.93), .96 (95% CI, .91-.98), and .97 (95% CI, .95-.98); microRNA: .77 (95% CI, .75-.80), .78 (95% CI, .75-.80), and .85 (95% CI, .81-.87); autoantibody: .45 (95% CI, .36-.53), .91 (95% CI, .89-.93), and .84 (95% CI, .81-.87); and cytology: .82 (95% CI, .60-.93), .97 (95% CI, .88-.99), and .97 (95% CI, .95-.98). There was high heterogeneity.
CONCLUSIONS
The diagnostic accuracy seemed to be comparable between cytology and endoscopy, whereas autoantibody and microRNAs bear potential as future noninvasive screening tools for ESCC. To reduce ESCC-related death in high-risk populations, it is important to develop a more accurate and less-invasive screening test.
Topics: Area Under Curve; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Humans; ROC Curve; Sensitivity and Specificity
PubMed: 35413332
DOI: 10.1016/j.gie.2022.04.005 -
Food Research International (Ottawa,... Jun 2020Anthocyanins, a kind of phenolic compounds are present in plant kingdom. They exhibit biological activities such as anti-inflammatory and anti-cancer properties as well... (Meta-Analysis)
Meta-Analysis
Anthocyanins, a kind of phenolic compounds are present in plant kingdom. They exhibit biological activities such as anti-inflammatory and anti-cancer properties as well as imparting colors to various plants. The objective of this review is to provide a systematic evaluation of the evidence and a meta-analysis of published researches on the nano/microencapsulation of anthocyanins. A comprehensive literature search was conducted for articles published in 2016 to 2019 on PubMed, Web of Sciences and Scopus databases. Overall 45 eligible articles (51 cases; some authors studied 2 or more encapsulation methods) with appropriate data were included in the statistical analysis. In the current work, based on the technique and equipment applied for the formulation of micro/nanoencapsulation systems, the anthocyanin-loaded nano/microcarriers were classified into five main classes: (a) spray dried particles (spray-drying); (b) freeze-dried particles (freeze-drying); (c) lipid-based particles (emulsification and liposomal encapsulation); (d) electrospun fibers and electrosprayed particles (electrohydrodynamic encapsulation); and (e) nano/micro-gels (gelation). Based on the results from the meta-analysis, the studied technique for encapsulation of anthocyanins can be ordered as: spray-drying (33.33%), freeze-drying (27.08%), gelation (20.83%), lipid-based particles (14.58%) and electrohydrodynamic processes (4.17%). In addition, carbohydrates such as maltodextrin (19.56%) and gums (15.22%) have been the most frequently used biopolymers for encapsulation of anthocyanins in the selected studies.
Topics: Anthocyanins; Biological Availability; Color; Databases, Factual; Drug Compounding; Freeze Drying; Nanotechnology; Particle Size; Phenols; Polysaccharides
PubMed: 32331692
DOI: 10.1016/j.foodres.2020.109077 -
Nutrients Mar 2023In the last decade, most of the evidence on the clinical benefits of including cruciferous foods in the diet has been focused on the content of glucosinolates (GSL) and...
In the last decade, most of the evidence on the clinical benefits of including cruciferous foods in the diet has been focused on the content of glucosinolates (GSL) and their corresponding isothiocyanates (ITC), and mercapturic acid pathway metabolites, based on their capacity to modulate clinical, biochemical, and molecular parameters. The present systematic review summarizes findings of human studies regarding the metabolism and bioavailability of GSL and ITC, providing a comprehensive analysis that will help guide future research studies and facilitate the consultation of the latest advances in this booming and less profusely researched area of GSL for food and health. The literature search was carried out in Scopus, PubMed and the Web of Science, under the criteria of including publications centered on human subjects and the use of Brassicaceae foods in different formulations (including extracts, beverages, and tablets), as significant sources of bioactive compounds, in different types of subjects, and against certain diseases. Twenty-eight human intervention studies met inclusion criteria, which were classified into three groups depending on the dietary source. This review summarizes recent studies that provided interesting contributions, but also uncovered the many potential venues for future research on the benefits of consuming cruciferous foods in our health and well-being. The research will continue to support the inclusion of GSL-rich foods and products for multiple preventive and active programs in nutrition and well-being.
Topics: Humans; Biological Availability; Brassicaceae; Diet; Glucosinolates; Isothiocyanates; Vegetables
PubMed: 36986155
DOI: 10.3390/nu15061424 -
Journal of Applied Toxicology : JAT Jun 2022Water and/or soap and water solutions have historically been used as first-line decontamination strategies for a wide variety of dermal contaminants from workplace... (Review)
Review
Water and/or soap and water solutions have historically been used as first-line decontamination strategies for a wide variety of dermal contaminants from workplace exposure, environmental pesticides, and civilian chemical warfare. Although water and/or soap and water solutions are often considered a gold standard of decontamination, many studies have found other decontamination methods to be superior. This systematic review summarizes the available data on in vitro animal models contaminated with a various chemicals and their decontamination with water and/or soap and water solutions using in vitro animal models. A comprehensive literature search was performed using Concordance, Embase, PubMed, Medline, Web of Science, and Google Scholar to find in vitro animal studies that provided data on dermal decontamination using water and/or soap and water solutions. Five studies were included that analyzed 11 contaminants across two in vitro animal models (rats and pigs). Water alone was used as a decontamination method for 63.6% of the contaminants (n = 7/11) and water and soap solutions for decontamination in 54.6% of contaminants (n = 6/11). Water alone provided incomplete contaminant removal of five of seven contaminants studied; soap and water did not show significant difference in decontamination when compared with other solutions for all four contaminants and was superior to water for both contaminants studied. Water and/or soap and water are used as decontamination strategies for a variety of dermal contamination events, but for many contaminants, they do not provide complete contamination when compared with newer decontamination solutions studied with in vitro animal models.
Topics: Animals; Decontamination; Rats; Skin; Skin Absorption; Soaps; Swine; Water
PubMed: 34942017
DOI: 10.1002/jat.4274 -
Expert Review of Clinical Pharmacology May 2023Isoniazid (INH) plays an important role in prevention and treatment of tuberculosis (TB). However, large pharmacokinetic (PK) variations are observed in patients...
INTRODUCTION
Isoniazid (INH) plays an important role in prevention and treatment of tuberculosis (TB). However, large pharmacokinetic (PK) variations are observed in patients receiving standard INH dosages. Considering the influence of PK variations on INH efficacy or adverse reactions, we reviewed the population PK studies of INH and explored significant covariates that influence INH PK.
METHODS
The PubMed and Embase databases were systematically searched from their inception to 30 January 2023. PPK studies on INH using a parametric nonlinear mixed-effect approach were included in this review. The characteristics and identified significant covariates of the included studies were summarized.
RESULTS
Twenty-one studies conducted in adults, and seven in pediatrics were included. A two-compartment model with first-order absorption and elimination was the frequently used structural model for INH. NAT2 genotype, body size, and age were identified as significant covariates affecting INH PK variation. The median clearance (CL) value in the fast metabolizers was 2.55-fold higher than that in the slow metabolizers. Infants and children had higher CL per weight values than adults with the same metabolic phenotype. In pediatric patients, CL value increased with postnatal age.
CONCLUSIONS
Compared with slow metabolizers, the daily dose of INH should be increased by 200-600 mg in fast metabolizers. To achieve effective treatment, pediatric patients need a higher dose per kilogram than adults. Further PPK studies of anti-tuberculosis drugs are needed to comprehensively understand the covariates that affect their PK characteristics and to achieve accurate dose adjustments.
Topics: Humans; Child; Isoniazid; Antitubercular Agents; Genotype; Phenotype; Area Under Curve; Arylamine N-Acetyltransferase
PubMed: 36971782
DOI: 10.1080/17512433.2023.2196401 -
Molecular Aspects of Medicine Feb 2023This systematic review summarizes findings from human studies investigating the different routes of absorption, metabolism, distribution and excretion (ADME) of dietary... (Review)
Review
This systematic review summarizes findings from human studies investigating the different routes of absorption, metabolism, distribution and excretion (ADME) of dietary flavan-3-ols and their circulating metabolites in healthy subjects. Literature searches were performed in PubMed, Scopus and the Web of Science. Human intervention studies using single and/or multiple intake of flavan-3-ols from food, extracts, and pure compounds were included. Forty-nine human intervention studies met inclusion criteria. Up to 180 metabolites were quantified from blood and urine samples following intake of flavan-3-ols, mainly as phase 2 conjugates of microbial catabolites (n = 97), with phenyl-γ-valerolactones being the most representative ones (n = 34). Phase 2 conjugates of monomers and phenyl-γ-valerolactones, the main compounds in both plasma and urine, reached two peak plasma concentrations (C) of 260 and 88 nmol/L at 1.8 and 5.3 h (T) after flavan-3-ol intake. They contributed to the bioavailability of flavan-3-ols for over 20%. Mean bioavailability for flavan-3-ols was moderate (31 ± 23%, n bioavailability values = 20), and it seems to be scarcely affected by the amount of ingested compounds. While intra- and inter-source differences in flavan-3-ol bioavailability emerged, mean flavan-3-ol bioavailability was 82% (n = 1) and 63% (n = 2) after (-)-epicatechin and nut (hazelnuts, almonds) intake, respectively, followed by 25% after consumption of tea (n = 7), cocoa (n = 5), apples (n = 3) and grape (n = 2). This highlights the need to better clarify the metabolic yield with which monomer flavan-3-ols and proanthocyanidins are metabolized in humans. This work clarified in a comprehensive way for the first time the ADME of a (poly)phenol family, highlighting the pool of circulating compounds that might be determinants of the putative beneficial effects linked to flavan-3-ol intake. Lastly, methodological inputs for implementing well-designed human and experimental model studies were provided.
Topics: Humans; Biological Availability; Catechin; Proanthocyanidins; Diet
PubMed: 36207170
DOI: 10.1016/j.mam.2022.101146 -
Current Drug Metabolism Jun 2013The amount of drug remaining after previous doses, or drug accumulation, is closely related to drug efficacy and safety. An accurate calculation of the accumulation... (Review)
Review
The amount of drug remaining after previous doses, or drug accumulation, is closely related to drug efficacy and safety. An accurate calculation of the accumulation index or ratio (R(ac)) is crucial for dose finding. However, in drug accumulation studies little consensus exists with regard to experimental design or data analysis. We conducted a systematic review of the literature to produce a detailed profile of drug accumulation studies of the last 30 years (1980-2011). Ninety-six articles comprising 122 studies were analyzed. A typical drug accumulation study enrolled 10 to 20 subjects randomly assigned into treatment groups of 1 or 2 dose levels to observe pharmacokinetic behaviors. The median washout period between single and multiple dosing was 7 days, and the dose interval was 1-2 elimination half-lives in non- or one-compartmental models. Generally, the number of repeated times of administration for multiple dosing was 7-14, and the median number of sampling time points was 11. Eight different methods were used to calculate R(ac). The most frequently used method, in 72.9% of the studies, was to set R(ac) equal to the ratio of the area under a plasma concentration-time curve (AUC) during a dosage interval at steady state to the AUC of a dosage interval after the first dose, i.e., R(ac) = AUC(0-τ,ss) / AUC(0-τ,1). The values of R(ac) in the included studies ranged from 0.85 to 18.8, and 68.03% were <2. We suggest that sample size estimation for an accumulation study should be similar to that of a bioequivalence study, and in most studies, 18-24 subjects will be needed. Appropriate calculation methods for R(ac) should be selected based on the experimental design and data characteristics. The crucial values for non-, weak, moderate, and strong accumulation can be set at R(ac) < 1.2, 1.2 ≤ R(ac) < 2, 2 ≤ R(ac) < 5, and R(ac) ≥ 5, respectively. Accumulations studies should also give more regard to drug metabolism and increased accumulation in kidney or liver damaged patients.
Topics: Animals; Area Under Curve; Half-Life; Humans; Pharmaceutical Preparations; Pharmacokinetics; Sample Size; Time Factors
PubMed: 23701162
DOI: 10.2174/13892002113149990002