• Oligochaeta/chemistry
• Oligochaeta/enzymology
• Animals
• Chromatography, Ion Exchange/methods
• Ammonium Sulfate/chemistry
• Chromatography, Affinity/methods
• Chemical Precipitation
• Hydrophobic and Hydrophilic Interactions
• Chemical Fractionation/methods
• Endopeptidases

• Antithrombotic medication
• Biological aortic valve replacement
• bioAVR

• Humans
• Fibrinolytic Agents/therapeutic use
• Heart Valve Prosthesis
• Aortic Valve/surgery
• Heart Valve Prosthesis Implantation/methods
• Heart Valve Prosthesis Implantation/adverse effects
• Thromboembolism/prevention & control
• Thromboembolism/etiology
• Bioprosthesis
• Postoperative Complications/prevention & control
• Anticoagulants/therapeutic use
• Anticoagulants/administration & dosage
• Platelet Aggregation Inhibitors/therapeutic use

• Tampere University (including Tampere University Hospital)

• anticoagulants
• bleeding risk
• drug interaction
• gastrointestinal bleeding
• salicylates
• warfarin

• Humans
• Administration, Oral
• Anticoagulants/adverse effects
• Anticoagulants/administration & dosage
• Aspirin/adverse effects
• Aspirin/administration & dosage
• Drug Therapy, Combination/adverse effects
• Drug Therapy, Combination/methods
• Hemorrhage/chemically induced
• Hemorrhage/epidemiology
• Observational Studies as Topic
• Platelet Aggregation Inhibitors/adverse effects
• Platelet Aggregation Inhibitors/administration & dosage
• Randomized Controlled Trials as Topic

• Gastrointestinal hemorrhage
• Meta-analysis
• Predict
• Risk factor

• Humans
• Anemia
• Anticoagulants/adverse effects
• Diltiazem
• Gastrointestinal Hemorrhage/chemically induced
• Gemfibrozil
• Heart Failure
• Helicobacter Infections
• Helicobacter pylori
• Myocardial Infarction
• Risk Factors
• Verapamil

• Bleeding risk
• Direct oral anticoagulants
• Drug-drug interactions
• Nonsteroidal anti-inflammatory drugs
• Vitamin K antagonists

• Coumarin resistance
• Genetic testing
• Vitamin K
• Warfarin

• Drug-drug interaction
• antiaggregant
• anticoagulant
• anticoagulant and antiplatelet drugs

• Humans
• Adult
• Middle Aged
• Aged
• Anticoagulants/adverse effects
• Drug Interactions
• Polypharmacy

• cultivation
• edible mushrooms
• enzymes
• fibrin
• fibrin(ogen)olytic activity
• fibrinogen

• Humans
• Fibrin
• Fibrinolytic Agents/pharmacology
• Fibrinolytic Agents/therapeutic use
• Thrombosis/drug therapy
• Peptide Hydrolases

Warnings about drug-drug interactions (DDIs) between warfarin and nonsteroidal anti-inflammatory drugs (NSAIDs) within electronic health records indicate potential harm but fail to account for contextual factors and preferences. We developed a tool called DDInteract to enhance and support shared decision-making (SDM) between patients and physicians when both warfarin and NSAIDs are used concurrently. DDInteract was designed to be integrated into electronic health records using interoperability standards.

The purpose of this study was to conduct a formative evaluation of a DDInteract that incorporates patient and product contextual factors to estimate the risk of bleeding.

A randomized formative evaluation was conducted to compare DDInteract to usual care (UC) using physician-patient dyads. Using case vignettes, physicians and patients on warfarin participated in simulated virtual clinical encounters where they discussed the use of taking ibuprofen and warfarin concurrently and determined an appropriate therapeutic plan based on the patient’s individualized risk. Dyads were randomized to either DDInteract or UC. Participants completed a postsession interview and survey of the SDM process. This included the 9-item Shared Decision-Making Questionnaire (SDM-Q-9), tool usability and workload National Aeronautics and Space Administration (NASA) Task Load Index, Unified Theory of Acceptance and Use of Technology (UTAUT), Perceived Behavioral Control (PBC) scale, System Usability Scale (SUS), and Decision Conflict Scale (DCS). They also were interviewed after the session to obtain perceptions on DDInteract and UC resources for DDIs.

Twelve dyad encounters were performed using virtual software. Most (n=11, 91.7%) patients were over 50 years of age, and 9 (75%) had been taking warfarin for more than 2 years (75%). Regarding scores on the SDM-Q-9, participants rated DDInteract higher than UC for questions pertaining to helping patients clarify the decision (P=.03), involving patients in the decision (P=.01), displaying treatment options (P<.001), identifying advantages and disadvantages (P=.01), and facilitating patient understanding (P=.01) and discussion of preferences (P=.01). Five of the 8 UTAUT constructs showed differences between the 2 groups, favoring DDInteract (P<.05). Usability ratings from the SUS were significantly higher (P<.05) for physicians using DDInteract compared to those in the UC group but showed no differences from the patient’s perspective. No differences in patient responses were observed between groups using the DCS. During the session debrief, physicians indicated little concern for the additional time or workload entailed by DDInteract use. Both clinicians and patients indicated that the tool was beneficial in simulated encounters to understand and mitigate the risk of harm from this DDI.

Overall, DDInteract may improve encounters where there is a risk of bleeding due to a potential drug-drug interaction involving anticoagulants. Participants rated DDInteract as logical and useful for enhancing SDM. They reported that they would be willing to use the tool for an interaction involving warfarin and NSAIDs.

• NSAID
• UTAUT
• anti-inflammatory
• decision making
• decision making, shared
• decision support
• decision support systems, clinical
• drug interaction
• non-steroidal
• patient-centered care
• pharmaceutical
• pharmacotherapy
• pharmacy
• risk management
• unified theory of acceptance and use of technology
• user-centered design
• warfarin

• Pharmacovigilance
• adverse drug reactions
• antithrombotic
• drug interactions
• drug safety
• nonsteroidal anti-inflammatory drugs (NSAIDs)

Exposure to life-threatening drug-drug interactions (DDIs) occurs despite the widespread use of clinical decision support. The DDI between warfarin and nonsteroidal anti-inflammatory drugs is common and potentially life-threatening. Patients can play a substantial role in preventing harm from DDIs; however, the current model for DDI decision-making is clinician centric.

This study aims to design and study the usability of DDInteract, a tool to support shared decision-making (SDM) between a patient and provider for the DDI between warfarin and nonsteroidal anti-inflammatory drugs.

We used an SDM framework and user-centered design methods to guide the design and usability of DDInteract—an SDM electronic health record app to prevent harm from clinically significant DDIs. The design involved iterative prototypes, qualitative feedback from stakeholders, and a heuristic evaluation. The usability evaluation included patients and clinicians. Patients participated in a simulated SDM discussion using clinical vignettes. Clinicians were asked to complete eight tasks using DDInteract and to assess the tool using a survey adapted from the System Usability Scale.

The designed DDInteract prototype includes the following features: a patient-specific risk profile, dynamic risk icon array, patient education section, and treatment decision tree. A total of 4 patients and 11 clinicians participated in the usability study. After an SDM session where patients and clinicians review the tool concurrently, patients generally favored pain treatments with less risk of gastrointestinal bleeding. Clinicians successfully completed the tasks with a mean of 144 (SD 74) seconds and rated the usability of DDInteract as 4.32 (SD 0.52) of 5.

This study expands the use of SDM to DDIs. The next steps are to determine if DDInteract can improve shared decision-making quality and to implement it across health systems using interoperable technology.

• clinical decision support
• drug interaction
• shared decision-making
• user-centered design

The incidence of cardiovascular diseases has increased due to the aging of the population. Therefore, antithrombotic therapy is increasingly prescribed for cardiovascular prevention. However, long-term use of antithrombotic drugs can cause damage to the digestive tract. Gastrointestinal complications, including ulcer and bleeding, are relatively common during antithrombotic therapy. In order to minimize the digestive tract damage induced by antithrombotic drugs, there are several strategies available, including reducing modifiable risk factors, using the most optimal antithrombotic regimen to ensure gastrointestinal risk-cardiovascular benefit balance, and using gastroprotective agents. In recent years, researchers are attempting to find new solutions from traditional Chinese medicine. Studies have shown that traditional Chinese medicine has its own characteristics and clinical advantages in preventing and treating diseases. In this review, we provide a summary of recent updates regarding gastrointestinal damage induced by antithrombotic therapy as well as its prevention and treatment with both traditional Chinese and Western medicine.

• Antithrombotic therapy
• Digestive tract damage
• Traditional Chinese and Western medicine
• Prevention and treatment

• CYP4F11
• GSTP-1
• Single nucleotide polymorphism
• Small bowel bleeding

• Angiotensin converting enzyme inhibitor
• Bleeding
• Clopidogrel
• Drug–drug interaction
• Dual antiplatelet

• COVID-19
• antithrombotics
• drug-drug interactions

• Age-related diseases
• Aging
• Aspirin
• Geroprotector
• Geroscience
• NSAID

• Anti-Inflammatory Agents
• Anti-Inflammatory Agents, Non-Steroidal
• Aspirin
• Cyclooxygenase 2
• Platelet Aggregation

• COVID-19
• drug-drug interaction
• risk factor

• Adherence
• Antithrombotic
• Health education
• Patients’ knowledge

• adverse drug reaction
• emergency departments
• network analysis
• older adults
• symptoms

• Adverse Drug Reaction Reporting Systems
• Aged
• Drug-Related Side Effects and Adverse Reactions/diagnosis
• Drug-Related Side Effects and Adverse Reactions/epidemiology
• Emergency Service, Hospital
• Humans
• Pharmaceutical Preparations
• Phenotype
• Physicians

Imrecoxib is a registered treatment for osteoarthritis pain symptoms in China. This study aims to assess the effect of imrecoxib on the pharmacodynamics and pharmacokinetics of warfarin. 12 healthy male volunteers with CYP2C9*3 AA and VKORC1 AA genotypes took a 5 mg dose of warfarin both alone and concomitantly with steady-state imrecoxib. Both warfarin alone and concomitantly with imrecoxib have safey and good tolerance across the trial. Following warfarin and imrecoxib co-administration, neither C_max, AUC_0-t and t_1/2 of warfarin enantiomers nor AUC of international normalized ratio (INR) were markedly different from those of warfarin alone. The geometric mean ratios (GMRs) (warfarin + imrecoxib: warfarin alone) of INR_(AUC) was 1 (0.99, 1.01). The GMRs of warfarin AUC_0-∞ (90% confidence interval, CIs) for warfarin + imrecoxib: warfarin alone were 1.12 (1.08, 1.16) for R-warfarin and 1.13 (1.07, 1.18) for S- warfarin. The 90% CIs of the GMRs of AUC_0-∞, C_max and INR _(AUC) were all within a 0.8–1.25 interval. The combination of warfarin and imrecoxib did not impact the pharmacodynamics and pharmacokinetics of single-dose warfarin; therefore, when treating a patient with imrecoxib and warfarin, it is not required to adjust the dosage of warfarin.

Nonsteroidal anti-inflammatory drugs (NSAIDs), one of the most commonly used medications worldwide, are frequently associated with gastrointestinal adverse events. Primary care physicians often face the challenge of achieving adequate pain relief with NSAIDs, while keeping their adverse events to a minimum. This is especially true when long-term use of NSAIDs is required such as in patients with osteoarthritis and rheumatoid arthritis. To help primary care physicians deal with such challenges more effectively, a panel of expert gastroenterologists came together with the aim of developing practice recommendations.

A modified ‘Delphi’ process was used to reach consensus and develop practice recommendations. Twelve gastroenterologists from nine countries provided their expert inputs to formulate the recommendations. These recommendations were carefully developed taking into account existing literature, current practices, and expert opinion of the panelists.

The expert panel developed a total of fifteen practice recommendations. Following are the key recommendations: NSAIDs should be prescribed only when necessary; before prescribing NSAIDs, associated modifiable and non-modifiable risk factors should be considered; H. pylori infection should be considered and treated before initiating NSAIDs; patients should be properly educated regarding NSAIDs use; patients who need to be on long-term NSAIDs should be prescribed a gastroprotective agent, preferably a proton pump inhibitor and these patients should be closely monitored for any untoward adverse events.

These practice recommendations will serve as an important tool for primary care physicians and will guide them in making appropriate therapeutic choices for their patients.

How to cite this article: Hunt R, Lazebnik LB, Marakhouski YC, Manuc M, Ramesh GN, Aye KS, Bordin DS, Bakulina NV, Iskakov BS, Khamraev AA, Stepanov YM, Ally R, Garg A. International Consensus on Guiding Recommendations for Management of Patients with Nonsteroidal Anti-inflammatory Drugs Induced Gastropathy-ICON-G. Euroasian J Hepatogastroenterol, 2018;8(2):148-160.

• Gastropathy
• Gastroprotective agents
• Non-prescription drugs
• Nonsteroidal Anti-inflammatory Agents
• Proton pump inhibitor.

Although all implemented and ongoing initiatives, drug-drug interactions (DDIs) are still a global problem. Most published studies about DDIs in Saudi Arabia are carried out in hospital settings. In addition, assessing the knowledge of drug interactions in Saudi Arabia is limited. The aim of our study is to evaluate the knowledge of potential common drug-drug interactions among community pharmacists particularly in Saudi Arabia.

A crosses-sectional study utilizing a self- administered questionnaire was conducted among community pharmacy in Riyadh city Saudi Arabia. DDIs' knowledge was assessed by 26 drug pairs. Community pharmacists were asked to select the DDIs as “contraindication”, “may be used together with monitoring”, “no interaction” and “not sure”.

A total of 283 of community pharmacists completed the survey with response rate of 80.9%. Among the 26 drug pairs only 5 of them were identified correctly by most of the participants. To add more 3 out of the 5 pairs had a cutoff of less than 10% between the correct and wrong answer, meaning there still a majority that couldn't identify the correct answer. All the 26 pairs had a statistically significant difference between the correct and incorrect answer.

The results of this study showed that knowledge of community pharmacists about DDIs was inadequate. Community pharmacist should have specific courses in drug interactions to cover the most possible interactions that can be seen in this setting.

• Community pharmacist
• Drug-drug interaction

• Chemoprophylaxis
• Clot
• Prophylaxis
• Thromboembolism
• Venous

• Anticoagulant
• Antiplatelet
• Aspirin
• Peptic ulcer
• Upper gastrointestinal bleeding

To determine the clinical characteristics of elderly patients of hemorrhagic gastroduodenal ulcer on low-dose aspirin (LDA) therapy.

A total of 1105 patients with hemorrhagic gastroduodenal ulcer treated in our hospital between January 2000 and March 2016 were grouped by age and drugs used, and these groups were compared in several factors. These groups were compared in terms of length of hospital stay, presence/absence of hemoglobin (Hb) decrease, presence/absence of blood transfusion, Forrest I, percentage of Helicobacter pylori infection, presence/absence of underlying disease, and percentage of severe cases.

The percentage of blood transfusion (62.6% vs 47.7 %, P < 0.001), Hb decrease (53.8% vs 40.8%, P < 0.001), and the length of hospital stay (23.5 d vs 16.7 d, P < 0.001) were significantly greater in those on drug therapy. The percentage of blood transfusion (65.3% vs 47.8%, P < 0.001), Hb decrease (54.2% vs 42.1%, P < 0.001), and length of hospital stay (23.3 d vs 17.5 d, P < 0.001) were significantly greater in the elderly. In comparison with the LDA monotherapy group, the percentage of severe cases was significantly higher in the LDA combination therapy group when elderly patients were concerned (16.1% vs 34.0%, P = 0.030). Meanwhile, among those on LDA monotherapy, there was no significant difference between elderly and non-elderly (16.1% vs 16.0%, P = 0.985).

A combination of LDA with antithrombotic drugs or non-steroidal anti-inflammatory drugs (NSAIDs) contributes to aggravation. And advanced age is not an aggravating factor when LDA monotherapy is used.

• Hemorrhagic gastroduodenal ulcer
• Low-dose aspirin
• Antithrombotic drugs
• Elderly patients
• Proton pump inhibitor

• Age Factors
• Aged
• Aged, 80 and over
• Anti-Inflammatory Agents, Non-Steroidal/adverse effects
• Aspirin/adverse effects
• Cerebrovascular Disorders/prevention & control
• Drug Therapy, Combination/adverse effects
• Drug Therapy, Combination/methods
• Female
• Fibrinolytic Agents/adverse effects
• Helicobacter Infections/complications
• Helicobacter Infections/epidemiology
• Helicobacter Infections/microbiology
• Helicobacter pylori/isolation & purification
• Humans
• Japan/epidemiology
• Male
• Middle Aged
• Myocardial Ischemia/prevention & control
• Peptic Ulcer Hemorrhage/epidemiology
• Peptic Ulcer Hemorrhage/etiology
• Retrospective Studies
• Risk Factors
• Stomach Ulcer/chemically induced
• Stomach Ulcer/complications

Lumbrokinase is used as an oral supplement to support and maintain healthy cardiovascular function, and to treat cardiovascular diseases in clinical for more than 10 years. Up until now, the mechanism of the cardioprotective effects of post-ischemic treatment with lumbrokinase has remained unclear. We therefore investigated the signaling pathways involved in the amelioration of myocardial ischemia-reperfusion (I-R) injury in rats treated with lumbrokinase 20 min after myocardial ischemia. Compared to vehicle-treated rats, post-ischemic treatment with lumbrokinase was associated with significant reductions in myocardial I-R-induced arrhythmias and myocardial damage, and an improvement in cardiac function. Moreover, lumbrokinase significantly upregulated levels of silent information regulator 1 (Sirt1). In addition, lumbrokinase significantly increased manganese-dependent superoxide dismutase expression, decreased Cleaved-Caspase-3 expression, and induced deacetylation of FoxO1. On the other hand, lumbrokinase also significantly downregulated levels of succinate dehydrogenase, cytochrome c oxidase, nuclear factor kappa B (NF-κB) and elevated levels of microtubule-associated protein light chain 3. Notably, the cardioprotective effects of lumbrokinase were abolished by administration of the specific Sirt1 inhibitor EX527. These findings demonstrate that post-ischemic treatment with lumbrokinase attenuates myocardial I-R injury through the activation of Sirt1 signaling, and thus enhances autophagic flux and reduces I-R-induced oxidative damage, inflammation and apoptosis.

• Sirt1
• cardioprotection
• ischemia
• lumbrokinase
• reperfusion

To analyze the clinical importance of VKORC1 polymorphism and its correlation with stability of oral anticoagulation.

In a hospital-based study, the patients on oral anticoagulant (OAC) were included during 2013–2016. The patients received OAC for cardioembolic stroke, cerebral venous sinus thrombosis (CVST), and prevention of deep vein thrombosis (DVT). Demographic, clinical, and neurological findings were recorded. Stability of anticoagulation was determined by percentage of time international normalized ratio (INR) values were in therapeutic range. Time in therapeutic range (TTR) >65% was defined as stable and <65% was defined unstable. VKORC 1 polymorphism was studied by polymerase chain reaction and correlated with daily dose of OAC and stability of INR.

A total of 157 patients with a median age of 40 years were included in the study. Ninety-two patients received OAC for secondary stroke prevention, 62 for CVST, and 3 for DVT. Out of 2976 INR reports, 1458 (49%) were in the therapeutic range, 997 (33.1%) were below the therapeutic range, and 521 (17.5%) were above the therapeutic level. Stable INR was obtained in 75 (47.77%) patients which was improved by drug modification in 3 and dietary adjustment in 12 patients. VKORC1 polymorphism revealed GG genotype in 127 (80.9%), GA genotype in 22 (14%), and AA genotype in 8 (5.1%) patients. Therapeutic range of INR was seen in 49%, below therapeutic range was seen in 31.5%, and above in 17.5%.

VKORC1 polymorphism was related to mean daily dose of OAC but not to the stability of INR.

• Cardioembolic stroke
• VKORC1 gene polymorphism
• Vitamin K antagonist
• international normalized ratio stability
• oral anticoagulation

• Thailand
• non-steroidal anti-inflammatory drugs
• orthopaedic physicians
• risk communication

• cardiovascular diseases
• diabetes
• dyslipidemia
• gut microbiota
• hypertension
• metabolic syndrome
• obesity
• pharmabiotics

• Cardiovascular Diseases/complications
• Cardiovascular Diseases/therapy
• Diabetes Mellitus/therapy
• Gastrointestinal Microbiome
• Humans
• Hypertension/complications
• Hypertension/therapy
• Metabolic Syndrome/complications
• Metabolic Syndrome/prevention & control
• Metabolic Syndrome/therapy
• Obesity/complications
• Obesity/therapy
• Probiotics
• Risk Factors

• anticoagulants/antithrombins
• antiplatelet therapy
• aortic valve disease
• bleeding
• percutaneous intervention
• percutaneous valve therapy
• transcatheter valve implantation

• MedDRA
• OntoADR
• Pharmacovigilance
• SNOMED CT
• UGIB
• ontology
• signal detection

• Acute Disease
• Adult
• Aged
• Aged, 80 and over
• Anti-Inflammatory Agents, Non-Steroidal/adverse effects
• Aspirin/adverse effects
• Case-Control Studies
• Colonoscopy
• Female
• Gastrointestinal Hemorrhage/epidemiology
• Gastrointestinal Hemorrhage/etiology
• Hospitals, University
• Humans
• Iceland/epidemiology
• Male
• Middle Aged
• Multivariate Analysis
• Prospective Studies
• Risk Factors
• Severity of Illness Index
• Warfarin/adverse effects

• Aspirin
• Cytokines
• Gastritis
• Inflammation
• Microcirculation
• Rat

• Cyclooxygenase
• fluoxetine
• gastric ulcer
• histamine
• serotonin

• NSAID enteropathy
• acetylsalicylic acid (aspirin)
• antiplatelet therapy
• clopidogrel
• drug interaction
• gastrointestinal bleeding
• rebamipide