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Biomarker Insights 2023The use of biomarkers varies from disease etiognosis and diagnosis to signal detection, risk prediction, and management. Biomarker use has expanded in recent years,... (Review)
Review
BACKGROUND
The use of biomarkers varies from disease etiognosis and diagnosis to signal detection, risk prediction, and management. Biomarker use has expanded in recent years, however, there are limited reviews on the use of biomarkers in pharmacovigilance and specifically in the monitoring and management of adverse drug reactions (ADRs).
OBJECTIVE
The objective of this manuscript is to identify the multiple uses of biomarkers in pharmacovigilance irrespective of the therapeutic area.
DESIGN
This is a systematic review of the literature.
DATA SOURCES AND METHODS
Embase and MEDLINE database searches were conducted for literature published between 2010-March 19, 2021. Scientific articles that described the potential use of biomarkers in pharmacovigilance in sufficient detail were reviewed. Papers that did not fulfill the United States Food and Drug Administration (US FDA) definition of a biomarker were excluded, which is based on the International Conference on Harmonisation (ICH)-E16 guidance.
RESULTS
Twenty-seven articles were identified for evaluation. Most articles involved predictive biomarkers (41%), followed by safety biomarkers (38%), pharmacodynamic/response biomarkers (14%), and diagnostic biomarkers (7%). Some articles described biomarkers that applied to multiple categories.
CONCLUSION
Various categories of biomarkers including safety, predictive, pharmacodynamic/response, and diagnostic biomarkers are being investigated for potential use in pharmacovigilance. The most frequent potential uses of biomarkers in pharmacovigilance in the literature were the prediction of the severity of an ADR, mortality, response, safety, and toxicity. The safety biomarkers identified were used to evaluate patient safety during dose escalation, identify patients who may benefit from further biomarker testing during treatment, and monitor ADRs.
PubMed: 37077840
DOI: 10.1177/11772719231164528 -
British Journal of Clinical Pharmacology Nov 2012The rate of medication errors is high, and these errors can cause adverse drug reactions. Elderly individuals are most vulnerable to adverse drug reactions. One cause of... (Review)
Review
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT
The rate of medication errors is high, and these errors can cause adverse drug reactions. Elderly individuals are most vulnerable to adverse drug reactions. One cause of medication errors is the lack of drug knowledge on the part of different health professionals. Medical curricula have changed in recent years, resulting in less education in the basic sciences, such as pharmacology.
WHAT THIS STUDY ADDS
Our study shows that little curricular time is devoted to geriatric pharmacology and that educational programmes in geriatric pharmacology have not been thoroughly evaluated. While interest in pharmacology education has increased recently, this is not the case for geriatric pharmacology education. Education on geriatric pharmacology should have more attention in the curricula of health professionals, given the often complex pharmacotherapy in elderly patients. Educational topics should be related to the known risk factors of medication errors, such as polypharmacy, dose adjustments in organ dysfunction and psychopharmacotherapeutics.
AIMS
Given the reported high rates of medication errors, especially in elderly patients, we hypothesized that current curricula do not devote enough time to the teaching of geriatric pharmacology. This review explores the quantity and nature of geriatric pharmacology education in undergraduate and postgraduate curricula for health professionals.
METHODS
Pubmed, Embase and PsycINFO databases were searched (from 1 January 2000 to 11 January 2011), using the terms 'pharmacology' and 'education' in combination. Articles describing content or evaluation of pharmacology education for health professionals were included. Education in general and geriatric pharmacology was compared.
RESULTS
Articles on general pharmacology education (252) and geriatric pharmacology education (39) were included. The number of publications on education in general pharmacology, but not geriatric pharmacology, has increased over the last 10 years. Articles on undergraduate and postgraduate education for 12 different health disciplines were identified. A median of 24 h (from 15 min to 4956 h) devoted to pharmacology education and 2 h (1-935 h) devoted to geriatric pharmacology were reported. Of the articles on education in geriatric pharmacology, 61.5% evaluated the teaching provided, mostly student satisfaction with the course. The strength of findings was low. Similar educational interventions were not identified, and evaluation studies were not replicated.
CONCLUSIONS
Recently, interest in pharmacology education has increased, possibly because of the high rate of medication errors and the recognized importance of evidence-based medical education. Nevertheless, courses on geriatric pharmacology have not been evaluated thoroughly and none can be recommended for use in training programmes. Suggestions for improvements in education in general and geriatric pharmacology are given.
Topics: Curriculum; Drug-Related Side Effects and Adverse Reactions; Education, Graduate; Education, Professional; Geriatrics; Health Personnel; Humans; Medication Errors; Pharmaceutical Preparations; Pharmacology; Risk Factors
PubMed: 22416832
DOI: 10.1111/j.1365-2125.2012.04268.x -
Alimentary Pharmacology & Therapeutics Apr 2012The nonselective 5-HT(4) receptor agonists, cisapride and tegaserod have been associated with cardiovascular adverse events (AEs). (Review)
Review
BACKGROUND
The nonselective 5-HT(4) receptor agonists, cisapride and tegaserod have been associated with cardiovascular adverse events (AEs).
AIM
To perform a systematic review of the safety profile, particularly cardiovascular, of 5-HT(4) agonists developed for gastrointestinal disorders, and a nonsystematic summary of their pharmacology and clinical efficacy.
METHODS
Articles reporting data on cisapride, clebopride, prucalopride, mosapride, renzapride, tegaserod, TD-5108 (velusetrag) and ATI-7505 (naronapride) were identified through a systematic search of the Cochrane Library, Medline, Embase and Toxfile. Abstracts from UEGW 2006-2008 and DDW 2008-2010 were searched for these drug names, and pharmaceutical companies approached to provide unpublished data.
RESULTS
Retrieved articles on pharmacokinetics, human pharmacodynamics and clinical data with these 5-HT(4) agonists, are reviewed and summarised nonsystematically. Articles relating to cardiac safety and tolerability of these agents, including any relevant case reports, are reported systematically. Two nonselective 5-HT(4) agonists had reports of cardiovascular AEs: cisapride (QT prolongation) and tegaserod (ischaemia). Interactions with, respectively, the hERG cardiac potassium channel and 5-HT(1) receptor subtypes have been suggested to account for these effects. No cardiovascular safety concerns were reported for the newer, selective 5-HT(4) agonists prucalopride, velusetrag, naronapride, or for nonselective 5-HT(4) agonists with no hERG or 5-HT(1) affinity (renzapride, clebopride, mosapride).
CONCLUSIONS
5-HT(4) agonists for GI disorders differ in chemical structure and selectivity for 5-HT(4) receptors. Selectivity for 5-HT(4) over non-5-HT(4) receptors may influence the agent's safety and overall risk-benefit profile. Based on available evidence, highly selective 5-HT(4) agonists may offer improved safety to treat patients with impaired GI motility.
Topics: Cardiovascular Diseases; Cisapride; Gastrointestinal Agents; Gastrointestinal Diseases; Humans; Indoles; Randomized Controlled Trials as Topic; Serotonin 5-HT4 Receptor Agonists
PubMed: 22356640
DOI: 10.1111/j.1365-2036.2012.05011.x -
PloS One 2013Soy and red clover isoflavones are controversial due to purported estrogenic activity and possible effects on breast cancer. We conducted a systematic review of soy and... (Review)
Review
BACKGROUND
Soy and red clover isoflavones are controversial due to purported estrogenic activity and possible effects on breast cancer. We conducted a systematic review of soy and red clover for efficacy in improving menopausal symptoms in women with breast cancer, and for potential impact on risk of breast cancer incidence or recurrence.
METHODS
We searched MEDLINE, Embase, the Cochrane Library, and AMED from inception to March 2013 for human interventional or observational data pertaining to the safety and efficacy of soy and red clover isoflavones in patients with or at risk of breast cancer.
RESULTS
Of 4179 records, we included a total of 131 articles: 40 RCTs, 11 uncontrolled trials, and 80 observational studies. Five RCTs reported on the efficacy of soy for hot flashes, showing no significant reductions in hot flashes compared to placebo. There is lack of evidence showing harm from use of soy with respect to risk of breast cancer or recurrence, based on long term observational data. Soy intake consistent with that of a traditional Japanese diet (2-3 servings daily, containing 25-50mg isoflavones) may be protective against breast cancer and recurrence. Human trials show that soy does not increase circulating estradiol or affect estrogen-responsive target tissues. Prospective data of soy use in women taking tamoxifen does not indicate increased risk of recurrence. Evidence on red clover is limited, however existing studies suggest that it may not possess breast cancer-promoting effects.
CONCLUSION
Soy consumption may be associated with reduced risk of breast cancer incidence, recurrence, and mortality. Soy does not have estrogenic effects in humans. Soy intake consistent with a traditional Japanese diet appears safe for breast cancer survivors. While there is no clear evidence of harm, better evidence confirming safety is required before use of high dose (≥ 100 mg) isoflavones can be recommended for breast cancer patients.
Topics: Female; Humans; Isoflavones; Phytoestrogens; Glycine max; Trifolium
PubMed: 24312387
DOI: 10.1371/journal.pone.0081968 -
American Journal of Kidney Diseases :... Nov 2016The pharmacokinetics and pharmacodynamics of antidiabetic therapies for patients with type 2 diabetes are often altered in the context of chronic kidney disease (CKD). (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The pharmacokinetics and pharmacodynamics of antidiabetic therapies for patients with type 2 diabetes are often altered in the context of chronic kidney disease (CKD).
STUDY DESIGN
Systematic review and meta-analysis.
SETTING & POPULATION
Patients with type 2 diabetes and CKD.
SELECTION CRITERIA FOR STUDIES
2 reviewers independently screened studies identified through bibliographic databases (Cochrane Library, PubMed, Embase, International Pharmaceutical Abstracts), clinical trial registries, and references from pertinent articles and clinical practice guidelines. Eligible studies included randomized controlled trials evaluating incretin-based therapy in adults with type 2 diabetes and estimated glomerular filtration rates < 60mL/min/1.73m.
INTERVENTIONS
Incretin-based therapies (dipeptidyl peptidase 4 inhibitors and glucagon-like peptide 1 receptor agonists) compared to placebo or active antidiabetic therapies.
OUTCOMES
Changes in glycated hemoglobin (HbA), hypoglycemia, mortality, change in fasting plasma glucose, cardiovascular events, and end-stage renal disease.
RESULTS
Of 1,619 nonduplicate records screened, 13 studies were included. Compared to placebo, incretin-based therapies significantly reduced HbA levels (n = 9; weighted mean difference, -0.64; 95% CI, -0.79 to -0.48; I = 43%); however, compared with active comparators, they did not (n = 4; weighted mean difference, -0.07; 95% CI, -0.25 to 0.12; I = 38%). Incretin-based therapies significantly increased the risk for hypoglycemia compared to placebo (n = 7; relative risk [RR], 1.38; 95% CI, 1.01-1.89; I = 0%) but no effect was observed versus active comparators (n = 4; RR, 0.24; 95% CI, 0.03-1.94; I = 52%). Limited evidence exists for all-cause mortality (placebo: n = 7 [RR, 1.21; 95% CI, 0.64-2.29; I = 0%]; active comparators: n = 3 [RR, 0.70; 95% CI, 0.32-1.54; I = 0%]).
LIMITATIONS
Variation among interventions, small number of studies, heterogeneity between studies, and high risk for attrition bias in 7 of the selected studies.
CONCLUSIONS
In patients with moderate or severe CKD, incretin-based therapies are effective in reducing HbA levels. Hypoglycemic events are rare, and wide CIs for the association preclude any definitive conclusions. Likewise, wide CIs were observed for mortality, cardiovascular events, and end-stage renal disease.
Topics: Diabetes Mellitus, Type 2; Diabetic Nephropathies; Humans; Incretins; Randomized Controlled Trials as Topic; Renal Insufficiency, Chronic; Treatment Outcome
PubMed: 27528374
DOI: 10.1053/j.ajkd.2016.06.014 -
Neurosurgical Review Apr 2021Given the median survival of 15 months after diagnosis, novel treatment strategies are needed for glioblastoma. Beta-blockers have been demonstrated to inhibit...
Given the median survival of 15 months after diagnosis, novel treatment strategies are needed for glioblastoma. Beta-blockers have been demonstrated to inhibit angiogenesis and tumor cell proliferation in various cancer types. The aim of this study was to systematically review the evidence on the effect of beta-blockers on glioma growth. A systematic literature search was performed in the PubMed, Embase, Google Scholar, Web of Science, and Cochrane Central to identify all relevant studies. Preclinical studies concerning the pharmacodynamic effects of beta-blockers on glioma growth and proliferation were included, as well as clinical studies that studied the effect of beta-blockers on patient outcomes according to PRISMA guidelines. Among the 980 citations, 10 preclinical studies and 1 clinical study were included after title/abstract and full-text screening. The following potential mechanisms were identified: reduction of glioma cell proliferation (n = 9), decrease of glioma cell migration (n = 2), increase of drug sensitivity (n = 1), induction of glioma cell death (n = 1). Beta-blockers affect glioma proliferation by inducing a brief reduction of cAMP and a temporary cell cycle arrest in vitro. Contrasting results were observed concerning glioma cell migration. The identified clinical study did not find an association between beta-blockers and survival in glioma patients. Although preclinical studies provide scarce evidence for the use of beta-blockers in glioma, they identified potential pathways for targeting glioma. Future studies are needed to clarify the effect of beta-blockers on clinical endpoints including survival outcomes in glioma patients to scrutinize the value of beta-blockers in glioma care.
Topics: Adrenergic beta-Antagonists; Brain Neoplasms; Cell Death; Cell Proliferation; Clinical Trials as Topic; Drug Evaluation, Preclinical; Glioblastoma; Glioma; Humans; Neovascularization, Pathologic
PubMed: 32172480
DOI: 10.1007/s10143-020-01277-4 -
Molecules (Basel, Switzerland) Apr 2021Osteoporosis results from excessive bone resorption and reduced bone formation, triggered by sex hormone deficiency, oxidative stress and inflammation. Tanshinones are a...
BACKGROUND
Osteoporosis results from excessive bone resorption and reduced bone formation, triggered by sex hormone deficiency, oxidative stress and inflammation. Tanshinones are a class of lipophilic phenanthrene compounds found in the roots of with antioxidant and anti-inflammatory activities, which contribute to its anti-osteoporosis effects. This systematic review aims to provide an overview of the skeletal beneficial effects of tanshinones.
METHODS
A systematic literature search was conducted in January 2021 using Pubmed, Scopus and Web of Science from the inception of these databases. Original studies reporting the effects of tanshinones on bone through cell cultures, animal models and human clinical trials were considered.
RESULTS
The literature search found 158 unique articles on this topic, but only 20 articles met the inclusion criteria and were included in this review. The available evidence showed that tanshinones promoted osteoblastogenesis and bone formation while reducing osteoclastogenesis and bone resorption.
CONCLUSIONS
Tanshinones modulates bone remodelling by inhibiting osteoclastogenesis and osteoblast apoptosis and stimulating osteoblastogenesis. Therefore, it might complement existing strategies to prevent bone loss.
Topics: Abietanes; Animals; Antioxidants; Humans; Osteoblasts; Osteogenesis
PubMed: 33923673
DOI: 10.3390/molecules26082319 -
The Pharmacogenomics Journal Oct 2017Rheumatoid arthritis (RA) is a chronic inflammatory disease that affects ~1% of the Caucasian population. Over the last decades, the availability of biological drugs... (Meta-Analysis)
Meta-Analysis Review
Rheumatoid arthritis (RA) is a chronic inflammatory disease that affects ~1% of the Caucasian population. Over the last decades, the availability of biological drugs targeting the proinflammatory cytokine tumour necrosis factor α, anti-TNF drugs, has improved the treatment of patients with RA. However, one-third of the patients do not respond to the treatment. We wanted to evaluate the status of pharmacogenomics of anti-TNF treatment. We performed a PubMed literature search and all studies reporting original data on associations between genetic variants and anti-TNF treatment response in RA patients were included and results evaluated by meta-analysis. In total, 25 single nucleotide polymorphisms were found to be associated with anti-TNF treatment response in RA (19 from genome-wide association studies and 6 from the meta-analyses), and these map to genes involved in T cell function, NFκB and TNF signalling pathways (including CTCN5, TEC, PTPRC, FCGR2A, NFKBIB, FCGR2A, IRAK3). Explorative prediction analyses found that biomarkers for clinical treatment selection are not yet available.
Topics: Antirheumatic Agents; Arthritis, Rheumatoid; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Pharmacogenetics; Polymorphism, Single Nucleotide; Treatment Outcome; Tumor Necrosis Factor-alpha
PubMed: 28607508
DOI: 10.1038/tpj.2017.26 -
Journal of Ethnopharmacology Aug 2015Buruli ulcer (BU) is the third most common mycobacterial infection in the world, after tuberculosis and leprosy and has recently been recognized as an important emerging... (Review)
Review
ETHNOPHARMACOLOGICAL RELEVANCE
Buruli ulcer (BU) is the third most common mycobacterial infection in the world, after tuberculosis and leprosy and has recently been recognized as an important emerging disease. This disease is common in West Africa where more than 99% of the burden is felt and where most affected people live in remote areas with traditional medicine as primary or only option. Reports indicate that the ethnopharmacological control approach of the disease in such settings has shown promise. However, no or very few compilations of traditional knowledge in using medicinal plants to treat BU have been attempted so far. This review aimed to record medicinal plants used traditionally against BU in three countries in West Africa: Ivory Coast, Ghana and Benin and for which ethnopharmacological knowledge supported by pharmacological investigations has been reported. The information recorded in this review will support further pharmacological research to develop appropriate drugs for a better BU control.
MATERIAL AND METHODS
A systematic review of the literature on ethnobotanical use and anti-BU activity of plants reported for BU treatment was performed. The approach consisted to search several resources, including Technical Reports, Books, Theses, Conference proceedings, web-based scientific databases such as publications on PubMed, Science direct, Springer, ACS, Scielo, PROTA, Google and Google scholar reporting ethnobotanical surveys and screening of natural products against Mycobacterium ulcerans. This study was limited to papers and documents published either in English or French reporting ethnopharmacological knowledge in BU treatment or pharmacological potency in vitro. This review covered the available literature up to December 2014.
RESULTS
The majority of reports originated from the three most affected West African countries (Cote d'Ivoire, Ghana and Benin). Though, 98 plant species belonging to 48 families have been identified as having anti-BU use, many have received no or little attention. Most of the pharmacological studies were performed only on 54 species. To a lesser extent, ethnopharmacological knowledge was validated in vitro for only 13 species. Of those, seven species including Ricinus comminus, Cyperus cyperoides (cited as Mariscus alternifolius), Nicotiana tabacum, Mangifera indica, Solanum rugosum, Carica papaya, and Moringa oleifera demonstrated efficacy in hospitalised BU patients. Four isolated and characterized compounds were reported to have moderate bioactivity in vitro against M. ulcerans.
CONCLUSIONS
This review compiles for the first time ethnopharmacologically useful plants against BU. The phamacological potential of 13 of them has been demonstrated in vitro and support BU evidence-based traditional medicines. In addition, 7 species showed activity in BU patients and have emerged as a promising source of the traditional medicine for treatment of BU. Yet, further safety and efficacy study should be initiated prior any approval as alternative therapy. Overall, a huge gap in knowledge appeared, suggesting further well-planned and detailed investigations of the in vitro, in vivo, and safety properties of the claimed anti-BU plants. Therefore, plants with medicinal potential should be scrutinized for biologically active compounds, using bioassay-guided fractionation approach to provide new insights to find novel therapeutics for BU control.
Topics: Africa, Western; Anti-Bacterial Agents; Buruli Ulcer; Ethnopharmacology; Humans; Mycobacterium ulcerans; Plant Preparations; Plants, Medicinal
PubMed: 26099634
DOI: 10.1016/j.jep.2015.06.024 -
Phytotherapy Research : PTR Aug 2017Searching for new natural drugs that are capable of targeting Th1 and Th17 may lead to development of more effective treatments for inflammatory and autoimmune diseases.... (Review)
Review
Searching for new natural drugs that are capable of targeting Th1 and Th17 may lead to development of more effective treatments for inflammatory and autoimmune diseases. Most of the natural drugs can be derived from plants that are used in traditional medicine and folk medicine. The aim of this systematic review is to identify and introduce plants or plant derivatives that are effective on inflammatory diseases by inhibiting Th1 and Th17 responses. To achieve this purpose, the search terms herb, herbal medicine, herbal drug, medicinal plant, phytochemical, traditional Chinese medicine, Ayurvedic medicine, natural compound, inflammation, inflammatory diseases, Th1, Th17, T helper 1 or T helper 17 were used separately in Title/Keywords/Abstract in Web of Science and PubMed databases. In articles investigating the effect of the medicinal plants and their derivatives in inhibiting Th1 and Th17 cells, the effects of eight extracts of the medicinal plants, 21 plant-based compounds and some of their derivatives, and eight drugs derived from the medicinal plants' compounds in inhibiting Th1 and Th17 cells were reviewed. The results showed that medicinal plants and their derivates are able to suppress Th17 and Th1 T cell functions as well as cytokine secretion and differentiation. The results can be used to produce herbal drugs that suppress Th, especially Th17, responses. Copyright © 2017 John Wiley & Sons, Ltd.
Topics: Animals; Cell Differentiation; Herbal Medicine; Humans; Inflammation; Medicine, Traditional; Phytotherapy; Plant Extracts; Plants, Medicinal; Th1 Cells; Th17 Cells
PubMed: 28568565
DOI: 10.1002/ptr.5837