Aims
The aim of this study was to describe the 1‐year direct and indirect transition probabilities to premature discontinuation of statin therapy after concurrently initiating statins and ...CYP3A4‐inhibitor drugs.
Methods
A retrospective new‐user cohort study design was used to identify (N = 160 828) patients who concurrently initiated CYP3A4 inhibitors (diltiazem, ketoconazole, clarithromycin, others) and CYP3A4‐metabolized statins (statin DDI exposed, n = 104 774) vs. other statins (unexposed to statin DDI, n = 56 054) from the MarketScan commercial claims database (2012–2017). The statin DDI exposed and unexposed groups were matched (2:1) through propensity score matching techniques. We applied a multistate transition model to compare the 1‐year transition probabilities involving four distinct states (start, adverse drug events ADEs, discontinuation of CYP3A4‐inhibitor drugs, and discontinuation of statin therapy) between those exposed to statin DDIs vs. those unexposed. Statistically significant differences were assessed by comparing the 95% confidence intervals (CIs) of probabilities.
Results
After concurrently starting stains and CYP3A, patients exposed to statin DDIs, vs. unexposed, were significantly less likely to discontinue statin therapy (71.4% 95% CI: 71.1, 71.6 vs. 73.3% 95% CI: 72.9, 73.6) but more likely to experience an ADE (3.4% 95% CI: 3.3, 3.5 vs. 3.2% 95% CI: 3.1, 3.3) and discontinue with CYP3A4‐inhibitor therapy (21.0% 95% CI: 20.8, 21.3 vs. 19.5% 95% CI: 19.2, 19.8). ADEs did not change these associations because those exposed to statin DDIs, vs. unexposed, were still less likely to discontinue statin therapy but more likely to discontinue CYP3A4‐inhibitor therapy after experiencing an ADE.
Conclusion
We did not observe any meaningful clinical differences in the probability of premature statin discontinuation between statin users exposed to statin DDIs and those unexposed.
Dyspnea is the second most common symptom experienced by the approximately 4.5 million patients with cancer presenting to emergency departments (ED) each year. Distinguishing pneumonia, the most ...common reason for presentation, from other causes of dyspnea is challenging. This report characterizes the diagnostic uncertainty in patients with dyspnea and pneumonia presenting to an ED by establishing the rates of co-diagnosis, co-treatment, and misdiagnosis.
Visits by individuals ≥18 years old with cancer who presented with a complaint of dyspnea were identified using the National Hospital Ambulatory Medical Care Survey between 2012-2014 and analyzed for rates of co-diagnosis, co-treatment (treatment or diagnosis for >1 of pneumonia, chronic obstructive pulmonary disease COPD, and heart failure), and misdiagnosis of pneumonia. Additionally, we assessed rates of diagnostic uncertainty (co-diagnosis, co-treatment, or a lone diagnosis of dyspnea not otherwise specified NOS).
Among dyspneic cancer visits (1,593,930), 15.2% (95% confidence interval CI, 11.1-20.5%) were diagnosed with pneumonia, 22.5% (95% CI, 16.7-29.7%) with COPD, and 7.4% (95% CI 4.7-11.4%) with heart failure. Dyspnea NOS was diagnosed in 32.3% (95% CI, 25.7-39.7%) of visits and as the only diagnosis in 23.1% (95% CI, 16.3-31.6%) of all visits. Co-diagnosis occurred in 4.0% (95% CI, 2.0-7.6%) of dyspneic adults with cancer and co-treatment in 12.1% (95% CI, 7.5-18.9%). Agreement between emergency physician and inpatient documentation for presence of pneumonia was 57.7% (95% CI, 37.0-76.1%).
Diagnostic uncertainty remains a significant concern in patients with cancer presenting to the ED with dyspnea. Clinical uncertainty among dyspneic patients results in both misdiagnosis and under-treatment of patients with pneumonia and cancer.
Polypharmacy is common and is associated with higher risk of adverse drug event (ADE) among older adults. Knowledge on the ADE risk level of exposure to different drug combinations is critical for ...safe polypharmacy practice, while approaches for this type of knowledge discovery are limited. The objective of this study was to apply an innovative data mining approach to discover high-risk and alternative low-risk high-order drug combinations (e.g., three- and four-drug combinations).
A cohort of older adults (≥ 65 years) who visited an emergency department (ED) were identified from Medicare fee-for-service and MarketScan Medicare supplemental data. We used International Classification of Diseases (ICD) codes to identify ADE cases potentially induced by anticoagulants, antidiabetic drugs, and opioids from ED visit records. We assessed drug exposure data during a 30-day window prior to the ED visit dates. We investigated relationships between exposure of drug combinations and ADEs under the case-control setting. We applied the mixture drug-count response model to identify high-order drug combinations associated with an increased risk of ADE. We conducted therapeutic class-based mining to reveal low-risk alternative drug combinations for high-order drug combinations associated with an increased risk of ADE.
We investigated frequent high-order drug combinations from 8.4 million ED visit records (5.1 million from Medicare data and 3.3 million from MarketScan data). We identified 5213 high-order drug combinations associated with an increased risk of ADE by controlling the false discovery rate at 0.01. We identified 1904 high-order, high-risk drug combinations had potential low-risk alternative drug combinations, where each high-order, high-risk drug combination and its corresponding low-risk alternative drug combination(s) have similar therapeutic classes.
We demonstrated the application of a data mining technique to discover high-order drug combinations associated with an increased risk of ADE. We identified high-risk, high-order drug combinations often have low-risk alternative drug combinations in similar therapeutic classes.
The Geriatric Emergency Department (ED) Guidelines recommend screening older adults during their ED visit for delirium, fall risk/safe mobility, and home safety needs. We used the Consolidated ...Framework for Implementation Research (CFIR) and the Expert Recommendations for Implementation Change (ERIC) tool for preimplementation planning.
The cross-sectional survey was conducted among ED nurses at an academic medical center. The survey was adapted from the CFIR Interview Guide Tool and consisted of 21 Likert scale questions based on four CFIR domains. Potential barriers identified by the survey were mapped to identify recommended implementation strategies using ERIC.
Forty-six of 160 potential participants (29%) responded. Intervention Characteristics: Nurses felt geriatric screening should be standard practice for all EDs (76.1% agreed some/very much) and that there was good evidence (67.4% agreed some/very much). Outer setting: The national and regional practices such as the existence of guidelines or similar practices in other hospitals were unknown to many (20.0%). Nurses did agree some/very much (64.4%) that the intervention was good for the hospital/health system. Inner Setting: 67.4% felt more staff or infrastructure and 63.0% felt more equipment were needed for the intervention. When asked to pick from a list of potential barriers, the most commonly chosen were motivational (I often do not remember (n = 27, 58.7%) and It is not a priority (n = 14, 30.4%)). The identified barriers were mapped using the ERIC tool to rate potential implementation strategies. Strategies to target culture change were identifying champions, improve adaptability, facilitate the nurses performing the intervention, and increase demand for the intervention.
CFIR domains and ERIC tools are applicable to an ED intervention for older adults. This preimplementation process could be replicated in other EDs considering implementing geriatric screening.
Antimicrobial peptides (AMPs) are key effectors of urinary tract innate immunity. Identifying differences in urinary AMP levels between younger and older adults is important in understanding older ...adults' susceptibility and response to urinary tract infections (UTI) and AMP use as diagnostic biomarkers. We hypothesized that uninfected older adults have higher urinary human neutrophil peptides 1-3 (HNP 1-3), human alpha-defensin-5 (HD-5), and human beta-defensin-2 (hBD-2), but lower urinary cathelicidin (LL-37) than younger adults.
We conducted a cross-sectional study of patients aged ≥18 years completing a family medicine clinic nonacute visit. Enzyme-linked immunosorbent assays were performed for AMPs. We identified associations between age and AMPs using unadjusted and multivariable linear regression models.
Of the 308 subjects, 144 (46.8%) were ≥65 years of age. Comparing age ≥65 versus < 65 years, there were no significant differences in HNP 1-3 (p = .371), HD5 (p = .834), or LL-37 (p = .348) levels. Values for hBD-2 were lower in older adults versus younger (p < .001). In multivariable analyses, older males and females had significantly lower hBD-2 levels (p < .001 and p = .004). Models also showed urine leukocyte esterase was associated with increased levels of HNP 1-3 and HD5; hematuria with increased hBD-2; and urine cultures with contamination with increased HNP 1-3 and hBD-2.
Baseline urinary HNP 1-3, HD-5, and LL-37 did not vary with age. Older adults had lower baseline hBD-2. This finding has implications for the potential use of urinary AMPs as diagnostic markers and will facilitate further investigation into the role of innate immunity in UTI susceptibility in older adults.
Sepsis is a life-threatening condition with a high in-hospital mortality rate. The timing of antibiotic administration poses a critical problem for sepsis management. Existing work studying ...antibiotic timing either ignores the temporality of the observational data or the heterogeneity of the treatment effects. Here we propose a novel method (called T4) to estimate treatment effects for time-to-treatment antibiotic stewardship in sepsis. T4 estimates individual treatment effects by recurrently encoding temporal and static variables as potential confounders, and then decoding the outcomes under different treatment sequences. We propose mini-batch balancing matching that mimics the randomized controlled trial process to adjust the confounding. The model achieves interpretability through a global-level attention mechanism and a variable-level importance examination. Meanwhile, we equip T4 with an uncertainty quantification to help prevent overconfident recommendations. We demonstrate that T4 can identify effective treatment timing with estimated individual treatment effects for antibiotic stewardship on two real-world datasets. Moreover, comprehensive experiments on a synthetic dataset exhibit the outstanding performance of T4 compared with the state-of-the-art models on estimation of individual treatment effect.Sepsis treatment needs to be well timed to be effective and to avoid antibiotic resistance. Machine learning can help to predict optimal treatment timing, but confounders in the data hamper reliability. Liu and colleagues present a method to predict patient-specific treatment effects with increased accuracy, accompanied by an uncertainty estimate.
Acute illness causes physical function decline and mortality in older adults (age ≥ 65 years).1, 2 Older adults admitted or discharged from the emergency department (ED)1, 2 are particularly at risk ...for functional decline and some never return to their pre-illness baseline.2 Functional status determines whether a person can manage their new illness or injury at home and therefore impacts disposition decisions.The Geriatric ED Guidelines,3 Geriatric ED Accreditation, and growth of geriatric EDs has placed a new focus on identifying older adults at risk for functional decline during ED visits. Although a recent umbrella review demonstrated low evidence of benefit of ED interventions to prevent or reduce functional decline in older adults, these previous efforts focus on the long-term trajectory of functional status after acute illness, trauma, or heterogenous patient groups prior to Geriatric ED Accreditation. There is limited understanding of acute functional impairment due to medical illness in older adults at the point of ED presentation since the advent of Geriatric ED Guidelines. The purpose of this study was to describe the prevalence of acute decline in ability to perform activities of daily living (ADL) in older adults presenting to the ED with suspected pneumonia.
Implementation of evidence-based care processes (EBP) into the Emergency Department (ED) is challenging and there are only a few studies of real-world use of theory-based implementation frameworks. ...We report final implementation results and sustainability of an EBP geriatric screening program in the ED using the Consolidated Framework for Implementation Research (CFIR).
The EBP involved nurses screening older patients for delirium (Delirium Triage Screen), fall risk (4 Stage Balance Test), and vulnerability (Identifying Seniors at Risk Score) with subsequent appropriate referrals to physicians, therapy specialists or social workers. The proportions of screened adults ≥65 years old were tracked monthly. Outcomes are reported January 2021 - December 2022. Barriers encountered were classified according to CFIR. Implementation strategies were classified according to the CFIR-Expert Recommendations for Implementing Change (ERIC).
Implementation strategies increased geriatric screening from 5% to 68%. This did not meet our pre-specified goal of 80%. Change was sustained through several COVID-19 waves. Inner Setting barriers included culture and implementation climate. Initially, the ED was treated as a single Inner Setting, but we found different cultures and uptake between ED units, including night vs day shifts. Characteristics of Individuals barriers included high levels of staff turnover in both clinical and administrative roles and very low self-efficacy from stress and staff turnover. Initial attempts with individualized audit and feedback were not successful in improving self-efficacy and may have caused moral injury. Adjusting feedback to a team/unit level approach with unit-wide stretch goals worked better. Identifying early adopters and conducting on-shift education increased uptake. Lessons learned regarding ED culture, implementation in interconnected health systems, and rapid cycle process improvement are reported.
The pandemic exacerbated barriers to implementation in the ED. Cognizance of a large ED as a sum of smaller units and using the CFIR model resulted in improvements.
Medical research across all fields has historically excluded older adults (aged 65 years and older). Because older adults have a higher burden of chronic illness, respond differently to treatment, ...and are more prone to medication side effects, the results of current research may not be applicable to this important population. To address this major research deficiency, the National Institutes of Health established the Inclusion Across the Lifespan policy, effective January 2019. We present important considerations and proven strategies for successful inclusion of older adults in emergency care research relating to study design, participant recruitment and retention, and sources of support for investigators.
Objectives
The American College of Emergency Physicians' geriatric emergency department (GED) guidelines recommend additional staff and geriatric equipment, which may not be financially feasible for ...every ED. Data from an accredited Level 1 GED was used to report equipment costs and to develop a business model for financial sustainability of a GED.
Methods
Staff salaries including the cost of fringe benefits were obtained from a Midwestern hospital with an academic ED of 80,000 annual visits. Reimbursement assumptions included 100% Medicare/Medicaid insurance payor and 8‐hour workdays with 4.5 weeks of leave annually. Equipment costs from hospital invoices were collated. Operational and patient safety metrics were compared before and after the GED.
Results
A geriatric nurse practitioner in the ED is financially self‐sustaining at 7.1 consultations, a pharmacist is self‐sustaining at 7.7 medication reconciliation consultations, and physical and occupational therapist evaluations are self‐sustaining at 5.7 and 4.6 consults per workday, respectively. Total annual equipment costs for mobility aids, delirium aids, sensory aids, and personal care items for the GED was $4,513. Comparing the 2 years before and after, in regard to operational metrics the proportions of patients with lengths of stay > 8 hours and patients placed in observation did not change. In regard to patient safety, the rate of falls decreased from 0.60/1,000 patient visits to 0.42/1,000 in the ED observation unit and 0.42/1,000 to 0.36/1,000 in the ED. ED recidivism at 7 and 30 days did not change. Estimated cost savings from the reduction in falls was $80,328.
Conclusion
The additional equipment and personnel costs for comprehensive geriatric assessment in the ED are potentially financially justified by revenue generation and improvements in patient safety measures. A geriatric ED was associated with a decrease in patient falls in the ED but did not decrease admissions or ED recidivism.
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