Citations

Introduction Acute sore throat is a common complaint traditionally completed with an in-person visit. However, non-face-to-face telemedicine visits offer greater access at reduced cost. We evaluated patient/caregiver asynchronous text-based electronic visits (eVisits) for acute sore throat and whether there was concordance for individual components and total McIsaac score compared to a clinician’s assessment. eVisits were completed by patients and/or their caregivers via a secure patient portal. Methods In this retrospective study, we manually reviewed charts between February 2017 and July 2019 of patients who had an eVisit, in-person visit and group A streptococcal (GAS) test performed on the same day for an acute sore throat. We calculated a McIsaac score for eVisits and in-person visits, and compared each component and total score using Cohen’s kappa agreement statistic. Results There were 320 instances of patients who had an eVisit, in-person visit and GAS testing done on the same day. Approximately a third of eVisits were missing at least one McIsaac component, with the physical examination elements missing most commonly. Individual score congruence was moderate for cough (0.41), fair for fever (0.34) and slight for tonsillar swelling/exudate and lymphadenopathy (0.17 and 0.08, respectively), with total congruence being slight to fair (0.09–0.37). A McIsaac score of ≤1 showed moderate agreement (0.44). Visits with complete individual score components demonstrated improved congruence: substantial for cough (0.64), moderate for fever (0.57), fair for tonsillar swelling (0.3) and slight for lymphadenopathy (0.13). Discussion Overall agreement for individual score components was better for symptoms than it was for examination components, and was improved when data were complete. A McIsaac score of 1 or 0 had moderate agreement and thus could reasonably be safely used to exclude patients from GAS testing.

Objective: This study aims to determine if outpatient opioid prescriptions are associated with future SUD diagnoses and overdose in injured adolescents 5 years following hospital discharge. Summary of Background Data: Approximately, 1 in 8 adolescents are diagnosed with an SUD and 1 in 10 experience an overdose in the 5 years following injury. State laws have become more restrictive on opioid prescribing by acute care providers for treating pain, however, prescriptions from other outpatient providers are still often obtained. Methods: This was a retrospective cohort study of patients ages 12–18 admitted to 2 level I trauma centers. Demographic and clinical data contained in trauma registries were linked to a regional database containing 5 years of electronic health records and prescription data. Regression models assessed whether number of outpatient opioid prescription fills after discharge at different time points in recovery were associated with a new SUD diagnosis or overdose, while controlling for demographic and injury characteristics, and depression and posttraumatic stress disorder diagnoses. Results: We linked 669 patients (90.9%) from trauma registries to a regional health information exchange database. Each prescription opioid refill in the first 3 months after discharge increased the likelihood of new SUD diagnoses by 55% (odds ratio: 1.55, confidence interval: 1.04–2.32). Odds of overdose increased with ongoing opioid use over 2–4 years post-discharge (P = 0.016–0.025). Conclusions: Short-term outpatient opioid prescribing over the first few months of recovery had the largest effect on developing an SUD, while long-term prescription use over multiple years was associated with a future overdose.

266 Background: CCA is a rare cancer for which there are limited effective therapies. IDH1 mutations occur in ~20% of intrahepatic CCAs, resulting in production of the oncometabolite D-2-hydroxyglutarate, which promotes oncogenesis. IVO (AG-120) is a first-in-class, oral, small-molecule inhibitor of mutant IDH1 (m IDH1). ClarIDHy aimed to demonstrate the efficacy of IVO vs PBO in pts with unresectable or metastatic m IDH1 CCA. The primary endpoint was met with significant improvement in progression-free survival (PFS) by independent radiology center (IRC) with IVO vs PBO (hazard ratio [HR] = 0.37, p < 0.0001). Objective response rate (ORR) and stable disease for IVO were 2.4% (3 partial responses) and 50.8% (n = 63) vs 0% and 27.9% (n = 17) for PBO. IVO pts experienced significantly less decline in physical and emotional functioning domains of quality of life at cycle 2 day 1 vs PBO pts (nominal p < 0.05). Methods: Pts with m IDH1 CCA were randomized 2:1 to IVO (500 mg PO QD) or matched PBO and stratified by prior systemic therapies (1 or 2). Key eligibility: unresectable or metastatic m IDH1 CCA based on central testing; ECOG PS 0–1; measurable disease (RECIST v1.1). Crossover from PBO to IVO was permitted at radiographic progression. Primary endpoint: PFS by IRC. Secondary endpoints included overall survival (OS; by intent-to-treat), ORR, PFS (by investigator), safety, and quality of life. The planned crossover-adjusted OS was derived using the rank-preserving structural failure time (RPSFT) model. Results: As of 31 May 2020, ~780 pts were prescreened for an IDH1 mutation and 187 were randomized to IVO (n = 126) or PBO (n = 61); 13 remain on IVO. Median age 62 y; M/F 68/119; 91% intrahepatic CCA; 93% metastatic disease; 47% had 2 prior therapies. 70% of PBO pts crossed over to IVO. OS data were mature, with 79% OS events in IVO arm and 82% in PBO. Median OS (mOS) was 10.3 months for IVO and 7.5 months for PBO (HR = 0.79; 95% CI 0.56–1.12; one-sided p = 0.093). The RPSFT-adjusted mOS was 5.1 months for PBO (HR = 0.49; 95% CI 0.34–0.70; p < 0.0001). Common all-grade treatment emergent adverse events (TEAEs, ≥ 15%) in the IVO arm: nausea 41%, diarrhea 35%, fatigue 31%, cough 25%, abdominal pain 24%, decreased appetite 24%, ascites 23%, vomiting 23%, anemia 18%, and constipation 15%. Grade ≥ 3 TEAEs were reported in 50% of IVO pts vs 37% of PBO pts, with grade ≥ 3 treatment-related AEs in 7% of IVO pts vs 0% in PBO. 7% of IVO pts experienced an AE leading to treatment discontinuation vs 9% of PBO pts. There were no treatment-related deaths. Conclusions: IVO was well tolerated and resulted in a favorable OS trend vs PBO despite a high rate of crossover. These data – coupled with statistical improvement in PFS, supportive quality of life data, and favorable safety profile – demonstrate the clinical benefit of IVO in advanced m IDH1 CCA. Clinical trial information: NCT02989857.

Abstract Prostate cancer is the second most common new cancer diagnosis in the United States. The prostate gland sits beneath the urinary bladder and surrounds the first part of the urethra. Usually, prostate cancer is slow-growing; stays confined to the prostate gland; and can be treated conservatively (active surveillance) or with surgery. However, if the cancer has spread beyond the prostate, such as to the lymph nodes, then that suggests the cancer is more aggressive and surgery is not adequate. In those cases, radiation and/or systemic therapies (e.g., chemotherapy, immunotherapy) are required. The challenge is that it is often difficult for radiologists to differentiate malignant lymph nodes from non-malignant ones with current medical imaging technology. In this study, we design a scalable hybrid approach utilizing a deep learning model to extract features into a machine learning classifier to automatically identify malignant lymph nodes in patients with prostate cancer.

Abstract Background GIP offers detection via PCR for a wide array of common microbes associated with diarrheal illness. Its rapid turnaround time and high sensitivity has made GIP testing commonplace for the evaluation of diarrhea. The purpose of this study is to determine if GIP influences antibiotic management in patients hospitalized with diarrhea. Methods Fifty patients hospitalized at Mayo Clinic Arizona between July and December 2019 who underwent BioFire® FilmArray™ GI PCR Panel testing were randomly selected. Medical records were reviewed to capture gender, age, immunocompromised state, antibiotic use within 30 days, prior hospitalization within 3 months, history of Clostridioides difficile infection, time from admission to testing and GIP results, and to determine if GIP results directly contributed towards antibiotic management. This study was exempt from Institutional Review Board approval. Results Twenty-six patients were male and twenty-four were female. The average age was 61.7 years. Thirty-four patients (68%) were immunocompromised. Forty-one GIPs were ordered within 24 hours of admission. Twenty-two patients (44%) had a positive GIP result; five were positive for 2 concurrent organisms. C. difficile was the most commonly detected organism, found in 16/24 (66.7%) positive tests. Eleven patients (68.8%) with C. difficile had a recent hospitalization, antibiotics within 30 days, or a history of C. difficile infection. There were 3 cases of Enteropathogenic Escherichia coli, 2 of Enterotoxigenic Escherichia coli, 2 of adenovirus, 2 of norovirus, 1 of rotavirus, and 1 of Vibrio cholerae. Excluding C. difficile positive patients, GIP testing contributed in changing antibiotic management in 3/50 (6%) patients tested. One patient had antibiotics stopped, one received correct antibiotics, and one received inappropriate antimicrobial therapy. Conclusion These results suggest that except in the setting of C. difficile infection, GIP has little utility in guiding antimicrobial management, even in the immunocompromised patient. GIP testing is expensive and it may be more resourceful to screen patients hospitalized with diarrhea for C. difficile alone, especially in those with risk factors for C. difficile infection. Furthermore, GIP testing can lead to antibiotic overuse. Disclosures All Authors: No reported disclosures

AbstractBackgroundPractice effects can obscure interpretation of longitudinal cognitive performance. Reliable change indices (RCIs) provide data for determining a significant change, typically for a single repeat assessment, but multiple follow‐up visits are common clinically and in research cohorts. Further, regression‐based or linear mixed effects models improve prediction of future cognitive decline and have higher correlations with neuroimaging biomarkers than RCI approaches. We present norms for change for the Auditory Verbal Learning Tests (AVLT) with conditional normative z‐scores for up to 7 repeat assessments, and demonstrate application of this method to individuals with preclinical Alzheimer’s disease (AD).MethodNormative Sample: Robust conditional norms were derived from 1001 adults ages 50‐90 from the Mayo Clinic Study of Aging (MCSA) who completed the AVLT across 4‐8 visits approximately 15 months apart and remained cognitively unimpaired (CU) across all available visits. Linear mixed effects models were used to compute a conditional normative z‐score for AVLT 30‐minute recall and sum of trials. Models included adjustment for baseline performance, number of prior test exposures, demographic factors (age, sex, education), and interactions (baseline*time; sex*time). Test Sample: We used a preclinical AD sample with positive amyloid and tau imaging (n= 27 CU A+T+; Jack et al. 2017) expected to have a higher rate of intra‐individual cognitive decline relative to CU A‐T‐ individuals (n = 268) to compare mean performances of conditional normative z‐scores to typical age‐corrected Mayo’s Older Americans Normative Studies (MOANS) norms. Participants had at least 1 and up to 4 follow‐up visits, with their most recent AT data used for classification.ResultAVLT performance based on typical norms did not differ across A+T+ and A‐T‐ groups. Specifically, across 2‐4 follow‐up visits, the typical norms mean z‐score was similar across groups (p=0.945; see Table 1). However, the conditional norms mean z‐score that accounts for practice effects and typical trajectories of AVLT performance was lower in the A+T+ relative to the A‐T‐ group for 30‐minute recall (p=0.055) and sum of trials (p=0.060).ConclusionConditional normative methods that account for practice effects are more sensitive to preclinical AD than typical norms, and show promise for identifying transitional cognitive decline.

AbstractBackgroundNeuropsychiatric symptoms (NPS) are associated with the risk of incident mild cognitive impairment (MCI) and dementia. However, the association between NPS and global and domain‐specific cognitive trajectories among older adults free of dementia remains unclear.MethodWe conducted a longitudinal study derived from the population‐based Mayo Clinic Study of Aging, including individuals aged ≥ 50 years who were free of dementia. Participants completed the Neuropsychiatric Inventory Questionnaire at baseline and underwent neuropsychological testing assessing four cognitive domains (i.e., memory, language, attention, visuospatial skills) every 15 months. We calculated linear mixed‐effect models with random subject‐specific intercepts and slopes to examine the association between presence of twelve different NPS (i.e., delusions, hallucinations, agitation, depression, anxiety, euphoria, apathy, disinhibition, irritability, motor behavior, nighttime behavior, appetite) at baseline and trajectories for individual yearly change in global and domain‐specific cognitive z‐scores. The models were adjusted for age, sex, education, and whether or not this was the first time the cognitive battery had been administered.ResultThe sample included 5081 persons (51% males; 4439 cognitively unimpaired, 642 with MCI). The median [IQR] age was 74 [67, 81] years, and the median [IQR] education was 14 [12, 16] years. Regardless of NPS status, participants declined in cognition over time, on average. However, presence of NPS was significantly associated with an increased decline in cognition, i.e., the annualized change in global cognition z‐scores for participants with compared to without the given NPS ranged from ‐0.018 (p = 0.011) for irritability to ‐0.16 (p = 0.001) for hallucinations. These associations between NPS and annual decline in global cognition were significant for all NPS except euphoria and disinhibition. Similar results were seen for the individual cognitive domains, e.g., participants with depression, apathy and nighttime behavior had a greater longitudinal decline in all domain specific z‐scores, whereas presence of delusions and anxiety was associated with a more pronounced decline in language, attention and visuospatial skills.ConclusionNeuropsychiatric symptoms are associated with greater longitudinal decline of both global and domain‐specific cognitive functions in community‐dwelling older adults free of dementia. More research is needed to confirm these preliminary findings.

AbstractBackgroundDecreased brain insulin levels exacerbate cognitive decline in AD. Insulin in the brain is derived from systemic circulation via the blood‐brain barrier (BBB). We hypothesize that type II diabetes (T2D) sequelae and Aβ peptide exposure disrupt insulin signaling at the BBB and inhibit insulin delivery to brain. Further, we propose insulin signaling defects at the BBB contribute to Aβ accumulation in AD brain.MethodsThe following studies were performed in wild‐type (WT) mice on regular chow (RC) diet, WT mice on high fat (HF) diet (manifest insulin resistance), APP/PS1 transgenic mice on RC diet (overexpress Aβ), and APP/PS1 mice on HF diet (overexpress Aβ + insulin resistance). After femoral injection of 125I‐insulin or 125I‐Aβ42, the brain accumulation was monitored between 0‐40 min by dynamic SPECT/CT imaging. The brain influx clearance was estimated by the slope obtained from Gjedde‐Patlak graphical analysis. Cerebral microvessels were harvested, and reverse phase protein array (RPPA) was performed to examine insulin signaling changes. Differentially expressed targets were subsequently confirmed by western blot. The brain influx of 125I‐insulin and 125I‐Aβ42 were further assessed in WT‐RC mice after internal carotid infusion with AG1024, a kinase inhibitor of the insulin receptor (IR) and insulin‐like growth factor receptor (IGF‐1R).ResultsCompared to WT‐RC, 125I‐insulin influx was decreased in WT‐HF and APP/PS1‐RC, and was further decreased in APP/PS1‐HF (4.1, 3.4, 3.5 and 2.6*10‐4 mL/min, respectively). Compared to WT‐RC, 125I‐Aβ42 influx was increased in WT‐HF and APP/PS1‐RC (8.6, 28 and 23*10‐4 mL/min, respectively). RPPA analysis revealed global disruptions in BBB insulin signaling pathways. Western blots confirmed reduced expression of IR‐β, p‐AKT and p‐GSK3β in WT‐HF and APP/PS1‐RC compared to WT‐RC. Moreover, the largest decreases were observed in APP/PS1‐HF. Infusion with AG1024 was shown to decrease 125I‐insulin influx, but increase 125I‐Aβ42 influx.ConclusionsBoth T2D and AD mice exhibited decreased brain influx of insulin and increased influx of Aβ42. This was associated with altered expression/activity of insulin signaling kinases at the BBB. Further, IR and/or IGF‐1R kinase activity were shown to differentially regulate BBB trafficking of insulin and Aβ42. Thus, BBB insulin signaling is important for delivering insulin to brain and restricting pathological uptake of Aβ.