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Introduction: Patients on nonvitamin K antagonist (NVKA) are usually taking other drugs. Potential interaction may increase the gastrointestinal (GI) bleeding risk associated with NVKA. Methods: Observational cohort study using Medicare data from 2017 to 2020. Participants receiving a NVKA were included. A concomitant overlapping period while on NVKA was assessed for nonsteroidal anti‐inflammatory drugs (NSAIDS), selective serotonin reuptake inhibitors (SSRI), antiplatelets, glucocorticoids, aspirin and proton pump inhibitors (PPI). A logistic regression predicting either any bleeding or GI bleeding was conducted estimating the odds ratio (OR) and 95% confidence interval (CI). Results: A total of 102 531 people on NVKA with mean age 77 years (SD = 9.8) and 55% females (N = 56 671) were included. Previous history of GI bleeding occurred in 2 908 (2.8%) participants, concomitant exposure to PPI occurred in 38 713 (38%), SSRI in 16 487 (16%), clopidogrel in 15 795 (15.4%), NSAIDs in 13 715 (13.4%) and glucocorticoids in 13 715 (13.4%). Risk for any bleeding was shown for clopidogrel (OR: 1.37, 95% CI: 1.30, 1.44), prasugrel/ticagrelor (OR: 1.36, 95% CI: 1.18, 1.58), glucocorticoids (OR: 1.26, 95% CI: 1.19, 1.34), and SSRIs (OR: 1.13, 95% CI: 1.07, 1.19). GI bleeding risk was shown for clopidogrel (OR: 1.44, 95% CI: 1.34, 1.55), prasugrel/ticagrelor (OR: 1.47, 95% CI: 1.20, 1.79), SSRIs (OR: 1.09, 95% CI: 1.01, 1.17) and glucocorticoids (OR: 1.33, 95% CI: 1.23, 1.44). PPI use was correlated with both NSAID (r = 0.07, p ≤ 0.0001) and SSRI use (r = 0.09, p ≤ 0.0001). Conclusion: NVKA concomitantly taken with antiplatelets, glucocorticoids, and SSRIs showed an increased risk for any bleeding and GI bleeding. [ABSTRACT FROM AUTHOR]

Aim: To develop a cognitive dysfunction (CD) focused questionnaire to evaluate caregiver burden in glioblastoma. Materials & methods: The survey was developed from stakeholder consultations and a pilot study, and disseminated at eight US academic cancer centers. Caregivers self-reported caring for an adult with glioblastoma and CD. Results: The 89-item survey covered demographics, CD symptoms and caregiver burden domains. Among 185 caregivers, most were white, educated females and reported memory problems as the most common CD symptom. An exposure-effect was observed, with increase in number of CD symptoms significantly associated with greater caregiver burden. Conclusion: This questionnaire could guide caregiver interventions and be adapted for use longitudinally, in community cancer settings, and in patients with brain metastases. Glioblastoma (GBM) is a very aggressive brain cancer. People who have GBM have trouble remembering things and are unable to do things they used to do. These changes can be very hard. Researchers are trying to better understand what it is like for people who take care of people with GBM (or caregivers). In this study, researchers created a new survey for caregivers. The survey included questions about what caregivers see happening in their loved one with GBM. Caregivers said that memory problems were common. Also, when the patient had more problems the caregiver had a harder time, too. Researchers hope to improve the survey and use it in the future for more studies. [ABSTRACT FROM AUTHOR]

Background: 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. Objective: 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. Methods: 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. Results: 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. Conclusions: 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. [ABSTRACT FROM AUTHOR]

Purpose Due to the low specificity of drug-drug interaction (DDI) warnings, hospitals and healthcare systems would benefit from the ability to customize alerts, thereby reducing the burden of alerts while simultaneously preventing harm. We developed a tool, called the Drug Interaction Customization Editor (DICE), as a prototype to identify features and functionality that could assist healthcare organizations in customizing DDI alerts. Methods A team of pharmacists, physicians, and DDI experts identified attributes expected to be useful for filtering DDI warnings. A survey was sent to pharmacists with informatics responsibilities and other medication safety committee members to obtain their opinions about the tool. The survey asked participants to evaluate the 4 sections of the DICE tool (General, Medication, Patient, and Visit) on a scale ranging from 0 (not useful) to 100 (very useful). The survey provided an opportunity for participants to express their opinions on the overall usefulness of the DICE tool and to provide other comments. Results The 50 survey respondents were mainly pharmacists (n = 47, 94%) with almost half (n = 23, 47%) having health information technology/informatics training. Most respondents (n = 33, 80%) were employed by organizations with over 350 beds. Respondents indicated the most useful features of the DICE tool were the ability to filter DDI warnings based on routes of administrations (mean [SD] rating scale score, 86.5 [21.6]), primary drug properties (85.7 [20.5]), patient attributes (85.6 [16.7]) and laboratory attributes (88.8 [18.0]). The overall impression of the DICE tool was rated at 82.8 (19.0), and when asked about the potential to reduce DDI alerts, respondents rated the tool at 83.7 (21.8). Conclusion The ability to customize DDI alerts using data elements currently within the electronic health records (EHRs) has the potential to decrease alert fatigue and override rates. This prototype DICE tool could be used by end users and vendors as a template for developing a more advanced DDI filtering tool within EHR systems. [ABSTRACT FROM AUTHOR]

Purpose To provide evidence of serum potassium changes in individuals taking angiotensin-converting enzyme inhibitors (ACEIs) and/or angiotensin receptor blockers (ARBs) concomitantly with spironolactone compared to ACEI/ARB therapy alone. Methods PubMed, Embase, Scopus, and Web of Science were searched for studies including exposure to both spironolactone and ACEI/ARB therapy compared to ACEI/ARB therapy alone. The primary outcome was serum potassium change over time. Main effects were calculated to estimate average treatment effect using random effects models. Heterogeneity was assessed using Cochran's Q and I 2. Risk of bias was assessed using the revised Cochrane risk of bias tool. Results From the total of 1,225 articles identified, 20 randomized controlled studies were included in the meta-analysis. The spironolactone plus ACEI/ARB group included 570 patients, while the ACEI/ARB group included 547 patients. Treatment with spironolactone and ACEI/ARB combination therapy compared to ACEI/ARB therapy alone increased the mean serum potassium concentration by 0.19 mEq/L (95% CI, 0.12-0.26 mEq/L), with intermediate heterogeneity across studies (Q statistic = 46.5, P = 0.004; I 2 = 59). Sensitivity analyses showed that the direction and magnitude of this outcome did not change with the exclusion of individual studies, indicating a high level of reliability. Reporting risk of bias was low for 16 studies (80%), unclear for 3 studies (15%) and high for 1 study (5%). Conclusion Treatment with spironolactone in combination with ACEI/ARB therapy increases the mean serum potassium concentration by less than 0.20 mEq/L compared to ACEI/ARB therapy alone. However, serum potassium and renal function must be monitored in patients starting combination therapy to avoid changes in serum potassium that could lead to hyperkalemia. [ABSTRACT FROM AUTHOR]

Single phase monoclinic Li4MgOsO6 is prepared by solid state reaction of a stoichiometric mixture of Li5OsO6, Os, OsO2, and MgO (pressed pellet, Al2O3 crucible in evacuated silica tubes, 800 °C, 24 h; heating and cooling rates of 100 °C/h). [ABSTRACT FROM AUTHOR]

Objective: Despite the benefits of the tailored drug-drug interaction (DDI) alerts and the broad dissemination strategy, the uptake of our tailored DDI alert algorithms that are enhanced with patient-specific and context-specific factors has been limited. The goal of the study was to examine barriers and health care system dynamics related to implementing tailored DDI alerts and identify the factors that would drive optimization and improvement of DDI alerts., Methods: We employed a qualitative research approach, conducting interviews with a participant interview guide framed based on Proctor's taxonomy of implementation outcomes and informed by the Theoretical Domains Framework. Participants included pharmacists with informatics roles within hospitals, chief medical informatics officers, and associate medical informatics directors/officers. Our data analysis was informed by the technique used in grounded theory analysis, and the reporting of open coding results was based on a modified version of the Safety-Related Electronic Health Record Research Reporting Framework., Results: Our analysis generated 15 barriers, and we mapped the interconnections of these barriers, which clustered around three entities (i.e., users, organizations, and technical stakeholders). Our findings revealed that misaligned interests regarding DDI alert performance and misaligned expectations regarding DDI alert optimizations among these entities within health care organizations could result in system inertia in implementing tailored DDI alerts., Conclusion: Health care organizations primarily determine the implementation and optimization of DDI alerts, and it is essential to identify and demonstrate value metrics that health care organizations prioritize to enable tailored DDI alert implementation. This could be achieved via a multifaceted approach, such as partnering with health care organizations that have the capacity to adopt tailored DDI alerts and identifying specialists who know users' needs, liaise with organizations and vendors, and facilitate technical stakeholders' work. In the future, researchers can adopt the systematic approach to study tailored DDI implementation problems from other system perspectives (e.g., the vendors' system)., Competing Interests: None declared., (Thieme. All rights reserved.)

Objective: The goal of this work is to evaluate if there is an increase in the risk of thromboembolic events (TEEs) due to concomitant exposure to dexamethasone and apixaban or rivaroxaban. Direct oral anticoagulants (DOACs), as well as corticosteroid dexamethasone, are commonly used to treat individuals hospitalised with COVID-19. Dexamethasone induces cytochrome P450-3A4 enzyme that also metabolises DOACs apixaban and rivaroxaban. This raises a concern about possible interaction between dexamethasone and DOACs that may reduce the efficacy of the DOACs and result in an increased risk of TEE., Design: We used nested case-control study design., Setting: This study was conducted in the National COVID Cohort Collaborative (N3C), the largest electronic health records repository for COVID-19 in the USA., Participants: Study participants were adults over 18 years who were exposed to a DOAC for 10 or more consecutive days. Exposure to dexamethasone was at least 5 or more consecutive days., Primary and Secondary Outcome Measures: Our primary exposure variable was concomitant exposure to dexamethasone for 5 or more days after exposure to either rivaroxaban or apixaban for 5 or more consecutive days. We used McNemar's Χ 2 test and adjusted logistic regression to evaluate association between concomitant use of dexamethasone with either apixaban or rivaroxaban., Results: McNemar's Χ 2 test did not find a discernible association of TEE in patients concomitantly exposed to dexamethasone and a DOAC (χ 2 =0.5, df=1, p=0.48). In addition, a conditional logistic regression model did not find an increase in the risk of TEE (adjusted OR 1.15, 95% CI 0.32 to 4.18)., Conclusion: This nested case-control study did not find evidence of an association between concomitant exposure to dexamethasone and a DOAC with an increase in risk of TEE. Due to small sample size, an association cannot be completely ruled out., Competing Interests: Competing interests: After the completion of this work, KMA became a full-time employee of Pfizer. GCA is past Chair and a current member of Food and Drug Administration's(FDA) Peripheral and Central Nervous System Advisory Committee; is a co-founding Principal and equity holder in Monument Analytics, a healthcare consultancy whose clients include the life sciences industry as well as plaintiffs in opioid litigation; and is a past member of OptumRx’s National P&T Committee. This arrangement has been reviewed and approved by Johns Hopkins University in accordance with its conflict of interest policies. CEL is an Executive Committee Member of the University of Pennsylvania’s Center for Pharmacoepidemiology Research and Training. The centre receives funds from Pfizer and Sanofi to support pharmacoepidemiology education. CEL recently received honoraria from the American College of Clinical Pharmacy Foundation, the University of Florida, the University of Massachusetts, and the Scientific and Data Coordinating Center for the NIDDK-funded Chronic Renal Insufficiency Cohort Study. CEL is a Special Government Employee of the US FDA and consults for their Reagan-Udall Foundation. CEL receives travel support from John Wiley & Sons. CEL’s spouse is an employee of Merck. Neither CEL nor his spouse owns stock in the company. There are no other disclosures to report., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: 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., Objective: 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., Methods: 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., Results: 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., Conclusions: 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., (©Ainhoa Gomez Lumbreras, Thomas J Reese, Guilherme Del Fiol, Malinda S Tan, Jorie M Butler, Jason T Hurwitz, Mary Brown, Kensaku Kawamoto, Henrik Thiess, Maria Wright, Daniel C Malone. Originally published in JMIR Formative Research (https://formative.jmir.org), 19.10.2022.)