-
1.
Gene-environment interactions and colorectal cancer risk: An umbrella review of systematic reviews and meta-analyses of observational studies.
Yang, T, Li, X, Montazeri, Z, Little, J, Farrington, SM, Ioannidis, JPA, Dunlop, MG, Campbell, H, Timofeeva, M, Theodoratou, E
International journal of cancer. 2019;(9):2315-2329
-
-
Free full text
-
Abstract
The cause of colorectal cancer (CRC) is multifactorial, involving both genetic variants and environmental risk factors. We systematically searched the MEDLINE, EMBASE, China National Knowledge Infrastructure (CNKI) and Wanfang databases from inception to December 2016, to identify systematic reviews and meta-analyses of observational studies that investigated gene-environment (G×E) interactions in CRC risk. Then, we critically evaluated the cumulative evidence for the G×E interactions using an extension of the Human Genome Epidemiology Network's Venice criteria. Overall, 15 articles reporting systematic reviews of observational studies on 89 G×E interactions, 20 articles reporting meta-analyses of candidate gene- or single-nucleotide polymorphism-based studies on 521 G×E interactions, and 8 articles reporting 33 genome-wide G×E interaction analyses were identified. On the basis of prior and observed scores, only the interaction between rs6983267 (8q24) and aspirin use was found to have a moderate overall credibility score as well as main genetic and environmental effects. Though 5 other interactions were also found to have moderate evidence, these interaction effects were tenuous due to the lack of main genetic effects and/or environmental effects. We did not find highly convincing evidence for any interactions, but several associations were found to have moderate strength of evidence. Our conclusions are based on application of the Venice criteria which were designed to provide a conservative assessment of G×E interactions and thus do not include an evaluation of biological plausibility of an observed joint effect.
-
2.
Clinical updates in aspirin-exacerbated respiratory disease.
Laidlaw, TM
Allergy and asthma proceedings. 2019;(1):4-6
-
-
Free full text
-
Abstract
Background: Aspirin-exacerbated respiratory disease (AERD), a syndrome that includes asthma, recurrent nasal polyps, and pathognomonic reactions to aspirin and other nonselective cyclooxygenase inhibitors, is still not fully understood and lacks specific disease-modifying therapeutic options. Objective: To review the most recent clinical updates in the evaluation and treatment of patients with AERD. Methods: Recent clinical research studies relevant to patients with AERD were reviewed. Results: Multiple new biologics are available for the treatment of severe asthma, several of which have been specifically studied and determined to be efficacious in the subset of patients with asthma who are also aspirin sensitive. Zileuton continues to be underprescribed for AERD and is considered to be very effective by many patients with AERD. Dietary modifications toward a diet that is high in omega-3 fatty acids and low in omega-6 fatty acids can reduce the production of the inflammatory leukotriene and prostaglandin D₂ lipids and help improve symptoms for patients with AERD. Conclusion: A lack of definitive understanding of the causative mechanisms of AERD and the absence of an AERD-specific patient-reported outcome measure are obstacles that remain in this field, but much progress has been made over the past decade.
-
3.
Prescription of Aspirin and Statins in Primary Prevention.
Hennekens, CH, Schuttenberg, N, Pfeffer, MA
Primary care. 2019;(1):13-25
Abstract
The increasing burden of cardiovascular disease worldwide, including the United States, underscores the need for the more widespread use of adjunctive drug therapies of proven net benefit in the primary prevention of cardiovascular disease. These include aspirin to reduce mortality from cardiovascular disease, statins to lower LDL-cholesterol levels, appropriate use of multiple antihypertensive drug therapies to lower blood pressure, and aggressive multifactorial management of diabetes. This article reviews randomized evidence to provide guidance to primary care providers regarding the use of adjunctive drug therapies.
-
4.
Long-Term Management of Venous Thromboembolism: Lessons from EINSTEIN CHOICE and Other Extension Trials.
Weitz, JI, Chan, NC
Thrombosis and haemostasis. 2019;(5):689-694
Abstract
Many patients with venous thromboembolism (VTE) are at risk of recurrence if anticoagulant therapy is stopped. Whereas 3 months of anticoagulation treatment is sufficient for patients with VTE provoked by major surgery or trauma, in many cases a longer course is needed. Extended therapy with vitamin K antagonists (VKAs) requires frequent coagulation monitoring and dose adjustments to ensure that the international normalized ratio (INR) remains within the therapeutic range; furthermore, there is a risk of major bleeding even if a therapeutic INR is maintained. Therefore, more convenient and safer anticoagulants are needed.The non-VKA oral anticoagulants (NOACs)-apixaban, dabigatran, edoxaban and rivaroxaban-simplify extended therapy because they can be given in fixed doses without routine coagulation monitoring. Randomized clinical trials have demonstrated the efficacy and safety of NOACs for extended VTE treatment, but bleeding remains a concern. Patients and physicians may, therefore, be reluctant to continue anticoagulation beyond 3 to 6 months except in patients at high risk of recurrence. Acetylsalicylic acid (ASA) is often prescribed instead of an anticoagulant because of its perceived lower risk of bleeding; however, the recent EINSTEIN CHOICE trial demonstrated that once-daily rivaroxaban at a dose of either 20 or 10 mg reduced the risk of recurrent VTE by 70% compared with ASA without significantly increasing the risk of bleeding. In this review, we discuss the EINSTEIN CHOICE trial in the context of previous trials for extended VTE treatment and examine some of the lessons that can be applied to clinical practice.
-
5.
Effects of six types of aspirin combination medications for treatment of acute cerebral infarction in China: A network meta-analysis.
Jin, L, Zhou, J, Shi, W, Xu, L, Sheng, J, Fan, J, Yuan, Y, Yuan, H
Journal of clinical pharmacy and therapeutics. 2019;(1):91-101
Abstract
WHAT IS KNOWN AND OBJECTIVE Previous studies have shown that various aspirin combinations might be beneficial for the treatment of acute cerebral infarction (ACI). The aim of this study was to evaluate the efficacy of six aspirin combinations in the treatment of ACI using network meta-analysis (NMA). The performance of these combinations is then ranked according to results of this analysis. METHODS Multiple databases were consulted to find randomized controlled trials (RCT) of six different aspirin combinations for the treatment of ACI. NMA was conducted on the data using stata (13.0) software. The odds ratio (OR) was calculated. The studies included in this paper were divided into a control group (aspirin alone) and an observation group (one of six aspirin combinations). RESULTS A total of 103 eligible RCTs were identified. A total of 13 317 cases were included in the study, and the results showed that the six types of aspirin combinations (aspirin with atorvastatin, ozagrel sodium, low molecular weight heparin [LMWH], clopidogrel, cilostazol and ginkgo damo) were all significantly superior (P < 0.05) to aspirin alone. The combination of aspirin with LMWH had the highest probability of being the most clinically efficacious intervention, with a surface under the cumulative ranking (SUCRA) curve of 79.1. The combination of aspirin with ozagrel sodium was the worst, with a SUCRA value of 29.7. WHAT IS NEW AND CONCLUSION A combination of aspirin with LMWH is the best option among the six aspirin combinations considered for the treatment of ACI. The combination of aspirin with ozagrel sodium was ranked the last.
-
6.
Integrative Medicine on Optimizing Clopidogrel and Aspirin Therapy.
Chen, H
Chinese journal of integrative medicine. 2019;(5):395-400
Abstract
This article reviews the available published data on optimizing clopidogrel and aspirin therapy using translational and integrative medicine. Translational and evidence-based medical studies show that the CYP2C19 gene mutation (CYP2C19*2 and CYP2C19*3) could affect > 50% of the Chinese population, and that this mutation is closely associated with clopidogrel resistance and an increased risk of major adverse cardiovascular events, particularly stent thrombosis in patients following percutaneous coronary intervention (PCI). Adjusted-dose warfarin and aspirin reduce stroke in patients with atrial fibrillation (AF), and warfarin is substantially more efficacious than aspirin. However, a poor compliance is a big problem in warfarin use especially in China. The genetic variants of vitamin K expoxide reductase might account for the universally lower warfarin dosage used in Chinese population. The available evidence indicates that the integrating mainstream treatments (e.g., clopidogrel, CYP2C19 genotyping) and non-mainstream medicines [e.g., Chinese medicines, Naoxintong Capsule (, NXT)] to treat CYP2C19 gene mutation patients following PCI can be effective. Aspirin combined NXT and the adjusted-dose warfarin was equally effective in elderly patients with non-valvular AF in prevention of ischemic stroke.
-
7.
Could Aspirin and Diets High in Fiber Act Synergistically to Reduce the Risk of Colon Cancer in Humans?
Pan, P, Huang, YW, Oshima, K, Yearsley, M, Zhang, J, Yu, J, Arnold, M, Wang, LS
International journal of molecular sciences. 2018;(1)
Abstract
Early inhibition of inflammation suppresses the carcinogenic process. Aspirin is the most commonly used non-steroid anti-inflammatory drugs (NSAIDs), and it irreversibly inhibits cyclooxygenase-1 and -2 (COX1, COX2). Multiple randomized clinical trials have demonstrated that aspirin offers substantial protection from colon cancer mortality. The lower aspirin doses causing only minimal gastrointestinal disturbance, ideal for long-term use, can achieve only partial and transitory inhibition of COX2. Aspirin's principal metabolite, salicylic acid, is also found in fruits and vegetables that inhibit COX2. Other phytochemicals such as curcumin, resveratrol, and anthocyanins also inhibit COX2. Such dietary components are good candidates for combination with aspirin because they have little or no toxicity. However, obstacles to using phytochemicals for chemoprevention, including bioavailability and translational potential, must be resolved. The bell/U-shaped dose-response curves seen with vitamin D and resveratrol might apply to other phytochemicals, shedding doubt on 'more is better'. Solutions include: (1) using special delivery systems (e.g., nanoparticles) to retain phytochemicals; (2) developing robust pharmacodynamic biomarkers to determine efficacy in humans; and (3) selecting pharmacokinetic doses relevant to humans when performing preclinical experiments. The combination of aspirin and phytochemicals is an attractive low-cost and low-toxicity approach to colon cancer prevention that warrants testing, particularly in high-risk individuals.
-
8.
Aspirin exacerbated respiratory disease: Current topics and trends.
Rodríguez-Jiménez, JC, Moreno-Paz, FJ, Terán, LM, Guaní-Guerra, E
Respiratory medicine. 2018;:62-75
Abstract
Aspirin-exacerbated respiratory disease is a chronic and treatment-resistant disease, characterized by the presence of eosinophilic rhinosinusitis, nasal polyposis, bronchial asthma, and nonsteroidal anti-inflammatory drugs hypersensitivity. Alterations in arachidonic acid metabolism may induce an imbalance between pro-inflammatory and anti-inflammatory substances, expressed as an overproduction of cysteinyl leukotrienes and an underproduction of prostaglandin E2. Although eosinophils play a key role, recent studies have shown the importance of other cells and molecules in the development of the disease like mast cells, basophils, lymphocytes, platelets, neutrophils, macrophages, epithelial respiratory cells, IL-33 and thymic stromal lymphopoietin, making each of them promissory diagnostic and treatment targets. In this review, we summarize the most important clinical aspects of the disease, including the current topics about diagnosis and treatment, like provocation challenges and aspirin desensitization. We also discuss recent findings in the pathogenesis of the disease, as well as future trends in diagnosis and treatment, including monoclonal antibodies and a low salicylate diet as a treatment option.
-
9.
[Aspirin and colorectal cancer].
Grancher, A, Michel, P, Di Fiore, F, Sefrioui, D
Bulletin du cancer. 2018;(2):171-180
Abstract
Colorectal cancer is a worldwide public health problem. Aspirin has been identified as a protective factor against the apparition of colorectal cancer. There are several mechanisms about the actions by aspirin on colorectal tumorogenesis. These are not perfectly known nowadays. On one hand, there are direct mechanisms on colorectal mucosa, on the other hand there are indirect mechanisms through platelet functions. Aspirin also plays a role by its anti-inflammatory action and the stimulation of antitumor immunity. Several studies show that long-term treatment with low-doses of aspirin decreases the incidence of adenomas and colorectal cancers. In the United States, aspirin is currently recommended for primary prevention of the risk of colorectal cancer in all patients aged 50 to 59, with a 10-year risk of cardiovascular event greater than 10 %. However, primary prevention with aspirin should not be a substitute for screening in colorectal cancer. Furthermore, aspirin seems to be beneficial when used in post-diagnosis of colorectal cancer. It could actually decrease the risk of metastasis in case of a localized colorectal cancer, and increase the survival in particular, concerning PIK3CA mutated tumors. The association of aspirin with neoadjuvant treatment of colorectal cancer by radiochimiotherapy seems to have beneficial effects. French prospective randomized study is currently being conducted to investigate postoperative aspirin in colorectal cancers with a PIK3CA mutation.
-
10.
Pre-eclampsia and the foetus: a cardiovascular perspective.
Bhorat, I
Cardiovascular journal of Africa. 2018;(6):387-393
-
-
Free full text
-
Abstract
Pre-eclampsia is the leading cause of perinatal morbidity and mortality. A full understanding of the pathogenesis of this enigmatic condition is essential if we are to develop new prophylactic and therapeutic interventions. Central to our understanding of the pathogenesis of early-onset preeclampsia is absolute utero-placental ischaemia, which is lack of placental vascular transformation in early pregnancy. By contrast, relative utero-placental ischaemia, due to a mismatch between utero-placental blood flow and increased demand for nutrients occurring later in pregnancy, may be central to the development of late-onset pre-eclampsia. These pathogenic mechanisms have advanced our understanding of this condition, leading to better prediction, screening and intervention modalities. Screening for pre-eclampsia in the first and second trimesters by investigating the maternoplacental circulation and placental hormones could identify a high-risk subgroup. The advantage of screening in the first trimester is that a prophylactic intervention is available in the form of low-dose aspirin, if started before 16 weeks' gestation in the high-risk group, resulting in a substantial reduction in severe early-onset pre-eclampsia, while identification of a high-risk group in the second trimester will lead to focused management in this group. Using a combination of cardiac Doppler, multi-vessel Doppler assessment of the foetal circulation and biomarkers in established pre-eclampsia in the third trimester could predict adverse outcomes and guide clinicians to timeous delivery. Hopefully, advances in our understanding of this enigmatic disease will lead to further prophylactic and new therapeutic interventions.