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A systematic review of the efficacy and safety of anticoagulants in advanced chronic kidney disease.Journal of Nephrology Nov 2022Patients with chronic kidney disease (CKD) have an increased risk of venous thromboembolism (VTE) and atrial fibrillation (AF). Anticoagulants have not been studied in... (Review)
Review
BACKGROUND
Patients with chronic kidney disease (CKD) have an increased risk of venous thromboembolism (VTE) and atrial fibrillation (AF). Anticoagulants have not been studied in randomised controlled trials with CrCl < 30 ml/min. The objective of this review was to identify the impact of different anticoagulant strategies in patients with advanced CKD including dialysis.
METHODS
We conducted a systematic review of randomized controlled trials and cohort studies, searching electronic databases from 1946 to 2022. Studies that evaluated both thrombotic and bleeding outcomes with anticoagulant use in CrCl < 50 ml/min were included.
RESULTS
Our initial search yielded 14,503 papers with 53 suitable for inclusion. RCTs comparing direct oral anticoagulants (DOACs) versus warfarin for patients with VTE and CrCl 30-50 ml/min found no difference in recurrent VTE events (RR 0.68(95% CI 0.42-1.11)) with reduced bleeding (RR 0.65 (95% CI 0.45-0.94)). Observational data in haemodialysis suggest lower risk of recurrent VTE and major bleeding with apixaban versus warfarin. Very few studies examining outcomes were available for therapeutic and prophylactic dose low molecular weight heparin for CrCl < 30 ml/min. Findings for patients with AF on dialysis were that warfarin or DOACs had a similar or higher risk of stroke compared to no anticoagulation. For patients with AF and CrCl < 30 ml/min not on dialysis, anticoagulation should be considered on an individual basis, with limited studies suggesting DOACs may have a preferable safety profile.
CONCLUSION
Further studies are still required, some ongoing, in patients with advanced CKD (CrCl < 30 ml/min) to identify the safest and most effective treatment options for VTE and AF.
Topics: Humans; Anticoagulants; Warfarin; Venous Thromboembolism; Administration, Oral; Atrial Fibrillation; Hemorrhage; Renal Insufficiency, Chronic; Heparin, Low-Molecular-Weight
PubMed: 36006608
DOI: 10.1007/s40620-022-01413-x -
British Journal of Clinical Pharmacology Feb 2021To present an updated overview on the safety of concurrent use of food, herbal or dietary supplement and warfarin. (Review)
Review
AIMS
To present an updated overview on the safety of concurrent use of food, herbal or dietary supplement and warfarin.
METHODS
A systematic literature review was performed on 5 databases from inception up to 31 December 2019. These interactions were classified depending on the likelihood of interaction and supporting evidences.
RESULTS
A total of 149 articles describing 78 herbs, food or dietary supplements were reported to interact with warfarin. These reports described potentiation with 45 (57.7%) herbs, food or dietary supplements while 23 (29.5%) reported inhibition and 10 (12.8%) reported limited impact on warfarin pharmacokinetics and pharmacodynamics. Twenty unique herb and dietary supplements also reported to result in minor bleeding events, such as purpura and gum bleeding as well as major events such as intracranial bleeding that led to death.
CONCLUSION
While most food, herbs and supplements can be safely taken in moderation, healthcare professionals should be aware of the increased risk of bleeding when taking several food and herbs. These include Chinese wolfberry, chamomile tea, cannabis, cranberry, chitosan, green tea, Ginkgo biloba, ginger, spinach, St. John's Wort, sushi and smoking tobacco. Patients should be counselled to continue to seek advice from their healthcare professionals when starting any new herbs, food or supplement.
Topics: Dietary Supplements; Ginkgo biloba; Herb-Drug Interactions; Humans; Phytotherapy; Warfarin
PubMed: 32478963
DOI: 10.1111/bcp.14404 -
Pharmacotherapy Apr 2022Rifamycins (rifampin, rifabutin, and rifapentine) play an essential role in the treatment of mycobacterial and some nonmycobacterial infections. They also induce the... (Review)
Review
Rifamycins (rifampin, rifabutin, and rifapentine) play an essential role in the treatment of mycobacterial and some nonmycobacterial infections. They also induce the activity of various drug transporting and metabolizing enzymes, which can impact the concentrations and efficacy of substrates. Many anticoagulant and antiplatelet (AC/AP) agents are substrates of these enzymes and have narrow therapeutic indices, leading to risks of thrombosis or bleeding when coadministered with rifamycins. The objective of this systematic review was to evaluate the effects on AC/AP pharmacokinetics, laboratory markers, and clinical safety and efficacy of combined use with rifamycins. A systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidance was performed. The PubMed, Embase, and Web of Science databases were queried for English-language reports on combination use of rifamycins and AC/AP agents from database inception through August 2021. The 29 studies identified examined warfarin (n = 17), direct oral anticoagulants (DOACs) (n = 8), and antiplatelet agents (n = 4) combined with rifampin (n = 28) or rifabutin (n = 1). Eleven studies were case reports or small case series; 14 reported on pharmacokinetic or laboratory markers in healthy volunteers. Rifampin-warfarin combinations led to reductions in warfarin area under the curve (AUC) of 15%-74%, with variability by warfarin isomer and study. Warfarin dose increases of up to 3-5 times prerifampin doses were required to maintain coagulation parameters in the therapeutic range. DOAC AUCs were decreased by 20%-67%, with variability by individual agent and with rifampin versus rifabutin. The active metabolite of clopidogrel increased substantially with rifampin coadministration, whereas prasugrel was largely unaffected and ticagrelor saw decreases. Our review suggests most combinations of AC/AP agents and rifampin are problematic. Further studies are required to determine whether rifabutin or rifapentine could be safe alternatives for coadministration with AC/AP drugs.
Topics: Anticoagulants; Drug Interactions; Humans; Platelet Aggregation Inhibitors; Rifabutin; Rifampin; Rifamycins; Warfarin
PubMed: 35152432
DOI: 10.1002/phar.2672 -
British Journal of Clinical Pharmacology Nov 2021The objective of this paper is to systematically review the literature on drug-drug interactions with warfarin, with a focus on patient-important clinical outcomes. (Meta-Analysis)
Meta-Analysis Review
AIMS
The objective of this paper is to systematically review the literature on drug-drug interactions with warfarin, with a focus on patient-important clinical outcomes.
METHODS
MEDLINE, EMBASE and the International Pharmaceutical Abstract (IPA) databases were searched from January 2004 to August 2019. We included studies describing drug-drug interactions between warfarin and other drugs. Screening and data extraction were conducted independently and in duplicate. We synthesized pooled odds ratios (OR) with 95% confidence intervals (CIs), comparing warfarin plus another medication to warfarin alone. We assessed the risk of bias at the study level and evaluated the overall certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.
RESULTS
Of 42 013 citations identified, a total of 72 studies reporting on 3 735 775 patients were considered eligible, including 11 randomized clinical trials and 61 observational studies. Increased risk of clinically relevant bleeding when added to warfarin therapy was observed for antiplatelet (AP) regimens (OR = 1.74; 95% CI 1.56-1.94), many antimicrobials (OR = 1.63; 95% CI 1.45-1.83), NSAIDs including COX-2 NSAIDs (OR = 1.83; 95% CI 1.29-2.59), SSRIs (OR = 1.62; 95% CI 1.42-1.85), mirtazapine (OR = 1.75; 95% CI 1.30-2.36), loop diuretics (OR = 1.92; 95% CI 1.29-2.86) among others. We found a protective effect of proton pump inhibitors (PPIs) against warfarin-related gastrointestinal (GI) bleeding (OR = 0.69; 95% CI 0.64-0.73). No significant effect on thromboembolic events or mortality of any drug group used with warfarin was found, including single or dual AP regimens.
CONCLUSIONS
This review found low to moderate certainty evidence supporting the interaction between warfarin and a small group of medications, which result in increased bleeding risk. PPIs are associated with reduced hospitalization for upper GI bleeding for patients taking warfarin. Further studies are required to better understand drug-drug interactions leading to thromboembolic outcomes or death.
Topics: Anticoagulants; Drug Interactions; Gastrointestinal Hemorrhage; Humans; Pharmaceutical Preparations; Randomized Controlled Trials as Topic; Warfarin
PubMed: 33769581
DOI: 10.1111/bcp.14833 -
Medicina Clinica Jul 2023The objective of the systematic review is to analyze the efficacy of direct-acting oral anticoagulants (DOAC) in the prophylaxis of thrombosis in antiphospholipid... (Review)
Review
The objective of the systematic review is to analyze the efficacy of direct-acting oral anticoagulants (DOAC) in the prophylaxis of thrombosis in antiphospholipid syndrome (APS). We searched for clinical trials, cohort studies and meta-analyses published from January 1, 2012 to September 30, 2022. Articles that analyzed the efficacy of DOAC in the prevention of thrombosis recurrence, with or without comparison with antivitamin K (VKA) drugs, were selected. DOACs, specifically rivaroxaban and apixaban, were significantly less effective than VKAs in preventing recurrence of thrombosis in patients with APS and prior arterial thrombosis or the concomitant presence of two or three different antiphospholipid antibodies. The proportion of patients with severe bleeding as side effect are similar in those treated with DOAC and with VKA. The results argue against the use of DOAC in the treatment of patients with thrombotic APS.
Topics: Humans; Antiphospholipid Syndrome; Anticoagulants; Factor Xa Inhibitors; Warfarin; Thrombosis; Administration, Oral
PubMed: 37105842
DOI: 10.1016/j.medcli.2023.03.011 -
International Journal of Molecular... Apr 2022Glyphosate, a non-selective systemic biocide with broad-spectrum activity, is the most widely used herbicide in the world. It can persist in the environment for days or... (Review)
Review
Glyphosate, a non-selective systemic biocide with broad-spectrum activity, is the most widely used herbicide in the world. It can persist in the environment for days or months, and its intensive and large-scale use can constitute a major environmental and health problem. In this systematic review, we investigate the current state of our knowledge related to the effects of this pesticide on the nervous system of various animal species and humans. The information provided indicates that exposure to glyphosate or its commercial formulations induces several neurotoxic effects. It has been shown that exposure to this pesticide during the early stages of life can seriously affect normal cell development by deregulating some of the signaling pathways involved in this process, leading to alterations in differentiation, neuronal growth, and myelination. Glyphosate also seems to exert a significant toxic effect on neurotransmission and to induce oxidative stress, neuroinflammation and mitochondrial dysfunction, processes that lead to neuronal death due to autophagy, necrosis, or apoptosis, as well as the appearance of behavioral and motor disorders. The doses of glyphosate that produce these neurotoxic effects vary widely but are lower than the limits set by regulatory agencies. Although there are important discrepancies between the analyzed findings, it is unequivocal that exposure to glyphosate produces important alterations in the structure and function of the nervous system of humans, rodents, fish, and invertebrates.
Topics: Animals; Central Nervous System Depressants; Glycine; Herbicides; Neurotoxicity Syndromes; Glyphosate
PubMed: 35562999
DOI: 10.3390/ijms23094605 -
The Ocular Surface Oct 2019We conducted a systematic review and meta-analysis to evaluate the efficacy of different treatment for Demodex blepharitis. Parameters studied were mites count,... (Meta-Analysis)
Meta-Analysis
PURPOSE
We conducted a systematic review and meta-analysis to evaluate the efficacy of different treatment for Demodex blepharitis. Parameters studied were mites count, improvement of symptoms and mites' eradication, stratified on type of treatments and mode of delivery of treatments (local or systemic).
METHOD
The PubMed, Cochrane Library, Embase, ClinicalTrials.gov, Google scholar and Science Direct databases were searched for studies reporting an efficacy of treatments for Demodex blepharitis.
RESULTS
We included 19 studies (14 observational and 5 randomized clinical trials), for a total of 934 patients, 1741 eyes, and 13 different treatments. For mites count, eradication rate, and symptoms improvement, meta-analysis included fifteen, fourteen and thirteen studies, respectively. The overall effect sizes for efficiency of all treatments, globally, were 1.68 (95CI 1.25 to 2.12), 0.45 (0.26-0.64), and 0.76 (0.59-0.90), respectively. Except usual lid hygiene for mites count, Children's Hospital of Eastern Ontario ointment (CHEO) for both eradication rate and symptoms, and CHEO, 2% metronidazole ointment, and systemic metronidazole for eradication rate, all treatments were efficient. Stratified meta-analysis did not show significant differences between local and systemic treatments (1.22, 0.83 to 1.60 vs 2.24, 1.30 to 3.18 for mites count; 0.37, 0.21 to 0.54 vs 0.56, 0.06 to 0.99 for eradication rate; and 0.77, 0.58 to 0.92 vs 0.67, 0.25 to 0.98 for symptoms improvement).
CONCLUSION
We reported the efficiency of the different treatments of Demodex blepharitis. Because of less systemic side effects, local treatments seem promising molecules in the treatment of Demodex blepharitis.
Topics: Animals; Anti-Infective Agents, Local; Antiparasitic Agents; Blepharitis; Eye Infections, Parasitic; Humans; Ivermectin; Metronidazole; Miotics; Mite Infestations; Mites; Pilocarpine; Tea Tree Oil
PubMed: 31229586
DOI: 10.1016/j.jtos.2019.06.004 -
Critical Reviews in Food Science and... 2022Endocrine-disrupting compounds (EDCs) are ubiquitous substances that are found in our everyday lives, including pesticides, plasticizers, pharmaceutical agents, personal...
BACKGROUND
Endocrine-disrupting compounds (EDCs) are ubiquitous substances that are found in our everyday lives, including pesticides, plasticizers, pharmaceutical agents, personal care products, and also in food products and food packaging. Increasing epidemiological evidence suggest that EDCs may affect the development or progression of breast cancer and consequently lead to lifelong harmful health consequences, especially when exposure occurs during early life in humans. Yet so far no appraisal of the available evidence has been conducted on this topic.
OBJECTIVE
To systematically review all the available epidemiological studies about the association of the levels of environmental exposures of EDCs with breast cancer risk.
METHODS
The search was performed in accordance with the PRISMA guidelines. We retrieved articles from PubMed (MEDLINE) until 10 March 2021. The key words used in this research were: "Endocrine disruptor(s)" OR "Endocrine disrupting chemical(s)" OR any of the EDCs mentioned below AND "Breast cancer" to locate all relevant articles published. We included only cohort studies and case-control studies. All relevant articles were accessed in full text and were evaluated and summarized in tables.
RESULTS
We identified 131 studies that met the search criteria and were included in this systematic review. EDCs reviewed herein included pesticides (e.g. p,p'-dichlorodiphenyltrichloroethane (DDT), p,p'-dichlorodiphenyldichloroethylene (DDE), atrazine, 2,3,7,8-tetrachloridibenzo-p-dioxin (TCDD or dioxin)), synthetic chemicals (e.g. bisphenol A (BPA), phthalates, per- and polyfluoroalkyl substances (PFAS), parabens, polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), contraceptive pills), phytoestrogens (e.g. genistein, resveratrol), and certain mycotoxins (e.g. zearalenone). Most studies assessed environmental EDCs exposure via biomarker measurements.
CONCLUSION
We identified certain EDC exposures could potentially elevate the risk of breast cancer. As majority of EDCs are highly persistent in the environment and bio-accumulative, it is essential to assess the long-term impacts of EDC exposures, especially multi-generational and transgenerational. Also, since food is often a major route of exposure to EDCs, well-designed exposure assessments of potential EDCs in food and food packing are necessary and their potential link to breast cancer development need to be carefully evaluated for subsequent EDC policy making and regulations.
Topics: Case-Control Studies; Endocrine Disruptors; Environmental Exposure; Environmental Pollutants; Epidemiologic Studies; Humans; Neoplasms; Pesticides
PubMed: 33819127
DOI: 10.1080/10408398.2021.1903382 -
Neurotoxicology Sep 2022Investigation of the toxicity triggered by chemicals on the human brain has traditionally relied on approaches using rodent in vivo models and in vitro cell models... (Review)
Review
Investigation of the toxicity triggered by chemicals on the human brain has traditionally relied on approaches using rodent in vivo models and in vitro cell models including primary neuronal cultures and cell lines from rodents. The issues of species differences between humans and rodents, the animal ethical concerns and the time and cost required for neurotoxicity studies on in vivo animal models, do limit the use of animal-based models in neurotoxicology. In this context, human cell models appear relevant in elucidating cellular and molecular impacts of neurotoxicants and facilitating prioritization of in vivo testing. The SH-SY5Y human neuroblastoma cell line (ATCC® CRL-2266™) is one of the most used cell lines in neurosciences, either undifferentiated or differentiated into neuron-like cells. This review presents the characteristics of the SH-SY5Y cell line and proposes the results of a systematic review of literature on the use of this in vitro cell model for neurotoxicity research by focusing on organic environmental pollutants including pesticides, 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD), flame retardants, PFASs, parabens, bisphenols, phthalates, and PAHs. Organic environmental pollutants are widely present in the environment and increasingly known to cause clinical neurotoxic effects during fetal & child development and adulthood. Their effects on cultured SH-SY5Y cells include autophagy, cell death (apoptosis, pyroptosis, necroptosis, or necrosis), increased oxidative stress, mitochondrial dysfunction, disruption of neurotransmitter homeostasis, and alteration of neuritic length. Finally, the inherent advantages and limitations of the SH-SY5Y cell model are discussed in the context of chemical testing.
Topics: Adult; Animals; Cell Line, Tumor; Cell Survival; Child; Environmental Pollutants; Flame Retardants; Fluorocarbons; Humans; Neuroblastoma; Neurotoxicity Syndromes; Parabens; Pesticides; Polychlorinated Dibenzodioxins
PubMed: 35914637
DOI: 10.1016/j.neuro.2022.07.008 -
JAMA Nov 2020Incidence rates for lower extremity deep vein thrombosis (DVT) range from 88 to 112 per 100 000 person-years and increase with age. Rates of recurrent VTE range from...
IMPORTANCE
Incidence rates for lower extremity deep vein thrombosis (DVT) range from 88 to 112 per 100 000 person-years and increase with age. Rates of recurrent VTE range from 20% to 36% during the 10 years after an initial event.
OBSERVATIONS
PubMed and Cochrane databases were searched for English-language studies published from January 2015 through June 2020 for randomized clinical trials, meta-analyses, systematic reviews, and observational studies. Risk factors for venous thromboembolism (VTE), such as older age, malignancy (cumulative incidence of 7.4% after a median of 19 months), inflammatory disorders (VTE risk is 4.7% in patients with rheumatoid arthritis and 2.5% in those without), and inherited thrombophilia (factor V Leiden carriers with a 10-year cumulative incidence of 10.9%), are associated with higher risk of VTE. Patients with signs or symptoms of lower extremity DVT, such as swelling (71%) or a cramping or pulling discomfort in the thigh or calf (53%), should undergo assessment of pretest probability followed by D-dimer testing and imaging with venous ultrasonography. A normal D-dimer level (ie, D-dimer <500 ng/mL) excludes acute VTE when combined with a low pretest probability (ie, Wells DVT score ≤1). In patients with a high pretest probability, the negative predictive value of a D-dimer less than 500 ng/mL is 92%. Consequently, D-dimer cannot be used to exclude DVT without an assessment of pretest probability. Postthrombotic syndrome, defined as persistent symptoms, signs of chronic venous insufficiency, or both, occurs in 25% to 50% of patients 3 to 6 months after DVT diagnosis. Catheter-directed fibrinolysis with or without mechanical thrombectomy is appropriate in those with iliofemoral obstruction, severe symptoms, and a low risk of bleeding. The efficacy of direct oral anticoagulants-rivaroxaban, apixaban, dabigatran, and edoxaban-is noninferior to warfarin (absolute rate of recurrent VTE or VTE-related death, 2.0% vs 2.2%). Major bleeding occurs in 1.1% of patients treated with direct oral anticoagulants vs 1.8% treated with warfarin.
CONCLUSIONS AND RELEVANCE
Greater recognition of VTE risk factors and advances in anticoagulation have facilitated the clinical evaluation and treatment of patients with DVT. Direct oral anticoagulants are noninferior to warfarin with regard to efficacy and are associated with lower rates of bleeding, but costs limit use for some patients.
Topics: Age Factors; Biomarkers; Factor Xa Inhibitors; Fibrin Fibrinogen Degradation Products; Humans; Life Style; Lower Extremity; Medical Illustration; Postthrombotic Syndrome; Predictive Value of Tests; Risk Factors; Sex Factors; Symptom Assessment; Thrombectomy; Thrombophilia; Ultrasonography; Vena Cava Filters; Venous Thromboembolism; Warfarin
PubMed: 33141212
DOI: 10.1001/jama.2020.17272