Citations

Background: Graves’ disease (GD) can both aggravate pre-existing cardiac disease and cause de novo heart failure (HF). Due to the rarity of thyrotoxic HF, population-based studies are lacking, and data from smaller studies are widely variable. Methods: We reviewed the medical records of 1371 consecutive patients with GD evaluated at our clinic between 2009 and 2019. HF was defined according to Framingham criteria. GD-related HFrEF was defined by left ventricular ejection fraction of <50%, while HFpEF was defined according to the Heart Failure Association of the European Society of Cardiology. Outcomes of major cardiovascular events, all-cause mortality, and cardiac hospitalizations were analyzed with adjustments for age, gender, and history of coronary artery disease (CAD). 1:1 matching with controls (age, gender, and CAD) was additionally done. Results: HF occurred in 74 patients (31 HFrEF; 43 HFpEF). Incidence of GD-related HF, HFrEF, and HFpEF was 5.4%, 2.3%, and 3.1%, respectively. In HFrEF, atrial fibrillation (AF) (RR 10.05, p <0.001) and thyrotropin receptor antibodies (TRAb) level (RR 1.05 per unit, p=0.005) were independent predisposing factors. In HFpEF, independent risk factors were COPD (RR 5.78, p < 0.001), older age (RR 1.48 per 10 years, p = 0.003), overt hyperthyroidism (RR 5.37, p = 0.021), higher BMI (1.06 per unit, p = 0.003), and HTN (RR 3.03, p = 0.011). Rates of cardiac hospitalizations were higher in HFrEF (41.9% vs 3.2%, p <0.001) and HFpEF (44.2% vs 4.7%, p < 0.001) compared to controls. Furthermore, while both increased risk of strokes (HFrEF: RR 4.12, p = 0.027; HFpEF: RR 4.64, p = 0.009), only HFrEF increased risk of all-cause mortality (RR 3.78, p = 0.045). Conclusion: De novo HF occurs in 5.4% of patients with GD and increases the rate of cardiovascular events. HF occurs more frequently in GD patients with AF, higher TRAb, higher BMI, and overt hyperthyroidism, suggesting that these may be targets for treatment to prevent cardiovascular complications, especially in older multimorbid patients.

Background: Hyperthyroidism is associated with atrial fibrillation (AF) with a reported prevalence of 16-60%. However, risk factors for onset of AF with hyperthyroidism are not well defined. We sought to identify patients with hyperthyroidism most likely to develop AF. Methods: We reviewed the medical records of 1371 consecutive patients with GD evaluated at our clinic between 2009 and 2019. GD-related AF was defined as AF diagnosed up to 30 days before or at any time after Grave’s disease (GD). Spontaneous recovery was defined as sinus rhythm after attainment of euthyroidism without the need for pharmacologic or electrical cardioversion. Outcomes of major cardiovascular events, all-cause mortality, and cardiac hospitalizations were compared between cases and controls (GD without AF) matched 1:1 for age, gender, and history of coronary artery disease. Results: AF occurred in 140 patients with an incidence of 10.2%. Older age (RR 1.63 per 10 years, p <0.001), male gender (RR 2.06, p < 0.001), overt hyperthyroidism (RR 2.48, p = 0.002), COPD (RR 2.14, p =0.006), and higher BMI (RR 1.03 per unit, p=0.023) were independent risk factors for AF. Spontaneous AF recovery occurred in 44 of 128 (34.6%) patients with adequate follow up. The multivariate risk factor for failed recovery was the presence of heart failure (HF) (OR =3.52, p= 0.004). GD patients with AF had higher rates of cardiac hospitalizations (Figure) that persisted even after adjusting to HF presence (27.9% vs 2.9%, p < 0.001). Conclusion: Risk factors for AF in GD are similar to those in the general population, although overt hyperthyroidism conferred the highest risk. These data argue for careful monitoring of GD patients with multimorbidity who may be at high risk of developing AF.

Abstract Background Although electronic health records (EHRs) are designed to improve patient safety, they have been associated with serious patient harm. An agreed-upon and standard taxonomy for classifying health information technology (HIT) related patient safety events does not exist. Objectives We aimed to develop and evaluate a taxonomy for medication-related patient safety events associated with HIT and validate it using a set of events involving pediatric patients. Methods We performed a literature search to identify existing classifications for HIT-related safety events, which were assessed using real-world pediatric medication-related patient safety events extracted from two sources: patient safety event reporting system (ERS) reports and information technology help desk (HD) tickets. A team of clinical and patient safety experts used iterative tests of change and consensus building to converge on a single taxonomy. The final devised taxonomy was applied to pediatric medication-related events assess its characteristics, including interrater reliability and agreement. Results Literature review identified four existing classifications for HIT-related patient safety events, and one was iteratively adapted to converge on a singular taxonomy. Safety events relating to usability accounted for a greater proportion of ERS reports, compared with HD tickets (37 vs. 20%, p = 0.022). Conversely, events pertaining to incorrect configuration accounted for a greater proportion of HD tickets, compared with ERS reports (63 vs. 8%, p < 0.01). Interrater agreement (%) and reliability (kappa) were 87.8% and 0.688 for ERS reports and 73.6% and 0.556 for HD tickets, respectively. Discussion A standardized taxonomy for medication-related patient safety events related to HIT is presented. The taxonomy was validated using pediatric events. Further evaluation can assess whether the taxonomy is suitable for nonmedication-related events and those occurring in other patient populations. Conclusion Wider application of standardized taxonomies will allow for peer benchmarking and facilitate collaborative interinstitutional patient safety improvement efforts.

OBJECTIVES: With increasing complexity of critical care medicine comes an increasing need for multidisciplinary involvement in care. In many institutions, pharmacists are an integral part of this team, but long-term data on the interventions performed by pharmacists and their effects on patient care and outcomes are limited. We aimed to describe the role of pediatric clinical pharmacists in pediatric intensive care unit (PICU) practice. METHODS: We retrospectively reviewed the records of pharmacy interventions in the PICU at the Mayo Clinic in Rochester, Minnesota, from 2003-2013, with a distinct period of increased pharmacist presence in the PICU from 2008 onward. We compared demographic and outcome data on patients who did and who did not have pharmacy interventions during 2 periods (2003–2007 and 2008–2013). RESULTS: We identified 27,773 total interventions by pharmacists during the 11-year period, of which 79.8% were accepted by the clinical team. These interventions were made on 10,963 unique PICU admissions and prevented 5867 order entry errors. Pharmacists' interventions increased year over year, including a significant change in 2008. Patients who required pharmacy involvement were younger, sicker, and had longer intensive care unit, hospital, and ventilator duration. Average central line infections and central line entry rates decreased significantly over the study period. CONCLUSIONS: Increased pharmacist presence in the PICU is associated with increased interventions and prevention of adverse drug events. Pharmacist participation during rounds and order entry substantially improved the care of critically sick children and should be encouraged.

AbstractBackgroundThe electronic health record (EHR) is a contributor to serious patient harm occurring within a sociotechnical system. Chemotherapy ordering is a high‐risk task due to the complex nature of ordering workflows and potential detrimental effects if wrong chemotherapeutic doses are administered. Many chemotherapy ordering errors cannot be mitigated through systems‐based changes due to the limited extent to which individual institutions are able to customize proprietary EHR software. We hypothesized that simulation‐based training could improve providers’ ability to identify and mitigate common chemotherapy ordering errors.MethodsPediatric hematology/oncology providers voluntarily participated in simulations using an EHR testing (“Playground”) environment. The number of safety risks identified and mitigated by each provider at baseline was recorded. Risks were reviewed one‐on‐one after initial simulations and at a group “lunch‐and‐learn” session. At three‐month follow‐up, repeat simulations assessed for improvements in error identification and mitigation, and providers were surveyed about prevention of real‐life safety events.ResultsThe 8 participating providers identified and mitigated an average of 5.5 out of 10 safety risks during the initial simulation, compared 7.4 safety risks at the follow up simulation (p=0.030). Two of the providers (25%) reported preventing at least one real‐world patient safety event in the clinical setting as a result of the initial training session.ConclusionsSimulation‐based training may reduce providers’ susceptibility to chemotherapy ordering safety vulnerabilities within the EHR. This approach may be used when systems‐based EHR improvements are not feasible due to limited ability to customize local instances of proprietary EHR software.

Calf muscle pump (CMP) promotes venous return from the lower extremity and contributes to preload and cardiac output. Impaired CMP function may reflect a measure of frailty or cumulative disease burden or may impede cardiac function. The study objective was to test the hypothesis that impaired CMP negatively impacts survival. Consecutive adult patients who underwent venous strain gauge plethysmography at the Mayo Clinic Gonda Vascular Laboratory (January 1, 1998 – December 31, 2011) were assessed for overall survival. Patients with venous incompetence, venous obstruction or unilateral calf pump dysfunction were excluded. Risk of mortality was assessed with Cox proportional hazard ratios and after adjusting for Charlson Comorbidity Index variables. Over the study period, 2728 patients were included in the analysis. Compared to patients with normal CMP, those with impaired CMP were older ( p < 0.001), predominantly female ( p = 0.01) and had higher mean Charlson scores ( p < 0.001). Patients with impaired CMP had a higher mortality rate at 5 (8.9% vs 2.4%), 10 (17.5% vs 5.9%), and 15 years (22.8% vs 8.3%) compared to those with normal CMP ( p < 0.001 for each comparison). Of patients with heart failure, those with impaired CMP had worse survival at each 5-year increment compared to those with normal CMP ( p < 0.05 at each increment). In conclusion, impaired CMP appears to be an independent predictor of poor outcomes after adjusting for variables within the Charlson Comorbidity Index. The association between impaired CMP, heart failure, and mortality may represent a negative impact on circulatory function or a surrogate measure of frailty.

Abstract Background: Oncolytic viruses selectively infect tumors and activate antitumor immune responses via innate and adaptive pathways, which may potentiate the efficacy of immune checkpoint inhibitors. MEDI5395 is a recombinant Newcastle disease virus incorporating a granulocyte macrophage colony-stimulating factor (GM-CSF) transgene that exhibits tumor cell-specific viral replication, stimulates PD-L1 expression, and induces tumor regression in murine and patient-derived xenograft models. Increased T cell recruitment and expression of IFNγ-inducible genes observed in vitro suggest immune activation in the tumor microenvironment (TME). Antitumor activity is enhanced by concurrent PD-L1 blockade. This clinical study is evaluating IV MEDI5395 in combination with the anti-PD-L1 antibody durvalumab in patients with advanced solid tumors. Methods: This is a Phase 1, first-in-human, multicenter, open-label trial (NCT03889275) enrolling patients with breast cancer, colorectal cancer, hepatocellular carcinoma, head and neck squamous cell carcinoma, renal cell carcinoma, non-small-cell lung cancer or melanoma. Eligibility criteria include relapsed/refractory disease or intolerance to standard therapy after ≥1 prior line of treatment for recurrent/metastatic disease, and ≥1 tumor measurable by RECIST v1.1. Exclusion criteria include rapidly progressing disease precluding a break of ≥8 weeks from systemic therapy, life expectancy ≥12 weeks by GRIm Score, uncontrolled metastatic central nervous system disease, and concomitant immunosuppressive therapy. The initial dose escalation phase will enroll up to 84 patients across all eligible tumor types. Three sequentially ascending dose levels of MEDI5395 will be evaluated. Durvalumab is administered either sequentially or concurrently with MEDI5395, for up to 2 years or until radiologically confirmed disease progression, clinical deterioration, withdrawal of consent, or unacceptable toxicity. The subsequent dose expansion phase will include 2 cohorts of ~40 patients, each enrolling a single tumor type. The tumor types, MEDI5395 dose level and schedule will be selected based on dose escalation data. On-treatment biopsies of the primary tumor or a metastatic site are required in the dose escalation phase and optional in the dose expansion phase. Primary objectives are evaluating the safety, tolerability and incidence of dose-limiting toxicities of MEDI5395, and identifying the optimal dose/schedule in combination with durvalumab. Secondary objectives include assessing MEDI5395 pharmacokinetics (viremia and GM-CSF transgene expression), pharmacodynamics in the TME, immunogenicity, and initial efficacy in combination with durvalumab. The trial is actively accruing. Citation Format: Grace K. Dy, Diwakar Davar, Evanthia Galanis, Danielle Townsley, Djuro Karanovic, Maria Schwaederle, Beth Kelly, Dmitriy Zamarin, Mitesh Borad, Kevin Harrington. A phase 1 study of IV MEDI5395, an oncolytic virus, in combination with durvalumab in patients with advanced solid tumors [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT244.

AbstractBackgroundExtraskeletal myxoid chondrosarcoma (ESMC) is a rare type of soft‐tissue sarcoma with limited series reporting outcome of treatment. Currently there is limited data on the incidence and impact on patient outcome in those with metastatic disease to lymph nodes in ESMC.MethodsThirty (21 males, 9 females) patients, mean age 50 ± 16 years, with ESMC were reviewed. The tumors were most commonly located in the lower extremity (n = 23, 77%) and the mean tumor size and volume were 9 ± 5 cm and 490 ± 833 cm3. Mean follow up was 7 ± 4 years.ResultsSix (20%) patients either presented (n = 3, 10%) or developed (n = 3, 10%) lymph node metastatic disease. When comparing patients without, with lymph node metastasis and metastasis elsewhere, patients with lymph nodes metastasis had worse survival than those without metastasis, however better 10‐year disease specific survival than those with metastasis elsewhere (100% vs 62% vs 0%; P < .001).ConclusionThere is a high incidence of lymph node metastatic disease in patients with ESMC. Although survival in these patients is worse compared to those without metastasis, their survival is better than those with metastasis elsewhere. Due to the high incidence of lymph node metastatic disease, preoperative staging of the lymph node should be considered.

Abstract The management of human epidermal growth factor receptor (HER2)–positive breast cancer (BC) has rapidly evolved over the last 20 years. Major advances have led to US Food and Drug Administration approval of 7 HER2‐targeted therapies for the treatment of early‐stage and/or advanced‐stage disease. Although oncologic outcomes continue to improve, most patients with advanced HER2‐positive BC ultimately die of their disease because of primary or acquired resistance to therapy, and patients with HER2‐positive early BC who have residual invasive disease after preoperative systemic therapy are at a higher risk of distant recurrence and death. The concept of treatment de‐escalation and escalation is increasingly important to optimally tailor therapy for patients with HER2‐positive BC and is a major focus of the current review. Research efforts in this regard are discussed as well as updates regarding the evolving standard of care in the (neo)adjuvant and metastatic settings, including the use of novel combination therapies. The authors also briefly discuss ongoing challenges in the management of HER2‐positive BC (eg, intrinsic vs acquired drug resistance, the identification of predictive biomarkers, the integration of imaging techniques to guide clinical practice), and the treatment of HER2‐positive brain metastases. Research aimed at superseding these challenges will be imperative to ensure continued progress in the management of HER2‐positive BC going forward.