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BACKGROUND: 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 pre-implementation planning. METHODS: 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. RESULTS: 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 don’t 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. CONCLUSION: CFIR domains and ERIC tools are applicable to an ED intervention for older adults. This pre-implementation process could be replicated in other EDs considering implementing geriatric screening.

Objectives National data reveal that 60% of the 4.5 million annual emergency department (ED) visits by patients with cancer result in admission. Many of these visits are due to a febrile illness. Current literature provides limited guidance on how to treat non‐neutropenic febrile ED patients. This study characterizes clinical outcomes of non‐neutropenic febrile patients with cancer presenting to an academic, Comprehensive Cancer Center affiliated ED. Methods Retrospective chart review of 101 randomly selected adult patients with active cancer presenting with a chief complaint of fever or a documented fever in the ED and an absolute neutrophil count above 1000 between October 2015 and September 2016. Descriptive statistics were calculated. Results The primary malignancies represented were hematologic (24%), gastrointestinal (13%), head and neck (13%), and genitourinary (8%). Sixty‐two percent were on chemotherapy, 15% on radiation therapy, and 12% were on targeted therapy. Severe illness outcomes occurred in 39% and 83% were admitted with a median length of stay of 4 days. Among admitted patients, 24% experienced a length of stay ≤2 days. A return visit to the ED or an in‐system hospitalization within 7 days of the index visit occurred in 10% and death occurred within 7 days of the index visit in 4%. Conclusion A majority of patients presenting to the ED with non‐neutropenic fever are admitted (83%), of whom nearly a quarter experience a length of stay of ≤2 days with infrequent serious illness outcomes. Future efforts should focus on the development of risk stratification tools in this population to avoid potentially unnecessary hospitalizations.

Evaluating population‐based data of hematologic malignancies (HMs) in older adults provides prognostic information for this growing demographic. Incidence rates and one‐ and five‐year relative survival rates were examined for specific HMs among adults ages ≥75 years using data from the Surveillance, Epidemiology and End Results (SEER) Program. Hematologic malignancy cases (Hodgkin lymphoma (HL), non‐Hodgkin lymphoma (NHL), multiple myeloma (MM), acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), acute myeloid leukemia (AML), and chronic myeloid leukemia (CML)) were reported to one of 18 SEER registries. Recent average annual (2010–2014) incidence rates and incidence trends from 1973 to 2014 were examined for cases ages ≥75 years. One‐ and five‐year relative cancer survival rates were examined for adults ages ≥75 years diagnosed 2007–2013, with follow‐up into 2014. From 1973 to 2014, incidence rates increased for NHL, MM, and AML, decreased for HL, and remained relatively stable for ALL, CLL, and CML among adults ages ≥75 years. The highest one‐ and five‐year relative survival rates were observed among adults with CLL ages 75–84 years (1 year: 91.8% (95% CI = 91.8–90.8)) and 5 years: 76.5% (95% CI = 74.2–78.6)). The lowest one‐ and five‐year survival rates were observed among adults with AML ages 75–84 (1 year: 18.2% (95% CI = 74.2–78.6) and 5 years: 2.7% (95% CI = 2.0–3.6)). Survival for older adults ages ≥75 years with HMs is poor, particularly for acute leukemia. Understanding the heterogeneity in HM outcomes among older patients may help clinicians better address the hematological cancer burden and mortality in the aging population.

OBJECTIVES: To determine whether fall-related injuries affect return to the ED after the initial visit. DESIGN: Retrospective chart review. SETTING: Academic Level 1 trauma center ED. PARTICIPANTS: Individuals aged 65 and older evaluated for a fall from standing height or less and discharged (N = 263, average age 77, 70% female). MEASUREMENTS: After institutional review board approval, electronic medical record data were queried. Univariate and multivariable logistic regression models were used to determine factors associated with risk of returning to the ED within 90 days. RESULTS: Injuries included fractures (45%, n = 117); head trauma (22%, n = 58); abrasions, lacerations, or contusions (34%, n = 88); and none (22%, n = 57). Emergency care was frequently required, with 13 (5%, 95% confidence interval (CI) = 2.3-7.6%) returning within 72 hours, 35 (13%, 95% CI = 9.2-17%] within 30 days, and 57 (22%, 95% CI = 17-27%) within 90 days. Univariately, the odds of returning to the ED within 90 days was more than two times as high for those with head trauma as for those without (odds ratio = 2.66). This remained significant in the multivariable model, which controlled for Charlson Comorbidity Index, fractures, soft tissue injuries, and ED observation unit use. CONCLUSION: More than one-third of older adults with minor head trauma from a fall will need to return to the ED in the following 90 days. These individuals should receive close attention from primary care providers. The link between minor head trauma and ED recidivism is a new finding.© 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society. Language: en

Cancers have a mutator phenotype [1]. An elevated mutation rate is central to tumorigenesis in human malignancies and significantly contributes to the disruption of regulatory processes essential to genomic stability. Endometrial cancers (ECs) are frequently defective in DNA mismatch repair (MMR). Reduced post-replication surveillance and repair results in a 100-fold increase in somatic mutations in human tumor cell lines [2]. Recently, loss of DNA proofreading function in the DNA polymerase e (POLE) has similarly been shown to be important in tumorigenesis in EC. Approximately 7% of ECs harbor mutations in the exonuclease domain of POLE [3, 4]. POLE encodes the major catalytic and proofreading subunits of the Pole DNA polymerase enzyme complex [5]. The Pole enzyme complex synthesizes the leading strand [5-8]. The proofreading (exonuclease) function locates and replaces erroneous bases in the daughter strand through failed complementary pairing with the parental strand. High fidelity incorporation of bases by POLE, coupled with its exonuclease proofreading function ensures a low mutation rate. POLE exonuclease domain mutations (EDMs) have shown to increase spontaneous mutation rates contributing to tumorigenesis in yeast and mouse models [9-14]. The Cancer Genome Atlas (TCGA) reported a POLE mutant subtype of EC [3]. Tumors with POLE EDMs are referred to as “POLE ultra-mutated”. ECs in this molecularly defined group are of endometrioid histology, predominantly have normal DNA MMR (microsatellite stable (MSS)) and have thousands of somatic mutations. Clinically, patients in the POLE ultra-mutated group were reported to have improved progression-free survival (PFS) [3]. We undertook an analysis of POLE mutations in a large cohort of endometrioid ECs to better understand clinicopathologic significance of POLE EDMs.

Cyclin A2 regulates replication origin firing during S-phase. It binds to Cdk1 and Cdk2 to direct phosphorylation of proteins for DNA synthesis. The goals of this study were to determine the role of Cyclin A2 in the prevention of DNA double strand breaks (DSB). We deleted Cyclin A2 in mouse neural stem cells (NSC) using a cre/lox approach. Cyclin A2-null NSC showed increased BrdU incorporation, as well as increased staining for the mitotic marker pH3. However, the growth rate in these Cyclin A2-null cells was slowed. To explain this discordance, we examined the DSB marker γH2AX. Cyclin A2-null NSC show increased levels of γH2AX as compared to Cyclin A2-preserved cells. When a DSB forms, the cell cycle is arrested until the break is repaired. Rad51, a marker of homologous recombination repair, and 53BP1, a marker of non-homologous end joining, both localized to the site of DSB in Cyclin A2-null cells. This indicates that Cyclin A2-null NSC can repair these breaks. Our results suggest that Cyclin A2 does no...

We have investigated the effect of aluminum (Al) on the activity of glucose-6-phosphate dehydrogenase (G6PDH; EC 1.1.1.49) and 6-phosphogluconate dehydrogenase (6PGDH; EC 1.1.1.44) isolated from 5-mm root apices of 4-day-old wheat (Triticum aestivum) cultivars differing in resistance to Al. Rapid increases in G6PDH and 6PGDH activities were observed in Al-resistant cultivars (PT741 and Atlas 66) during the first 10 h of treatment with 100 μM Al, while no change in the activity of either enzyme was observed in Al-sensitive cultivars (Katepwa and Neepawa) during a 24-h exposure to Al. The Al-induced increases in enzyme activities observed in the Al-resistant PT741 appear to reflect an induction of protein synthesis since the increases were completely abolished by 1 mM cycloheximide. No differences in G6PDH and 6PGDH activities were observed between the Al-sensitive and the Al-resistant genotypes when Al was supplied in vitro. Under these conditions, an increase in Al concentration from 0 to 1.4 mM caused a gradual decrease in activity of both enzymes, irrespective of the Al-resistance of whole seedlings. Aluminum-sensitive and aluminum-resistant cultivars also differed in the rate and extent of accumulation of slowly-exchanging Al in 5-mm root apices. During the first 6 h of Al treatment, Al accumulation was only 10% more rapid in Katepwa than in PT741. After 24-h exposure, accumulation in the Al-sensitive Katepwa, was two-fold higher. A decline in Al accumulation in a slowly exchanging compartment as well as a decrease in activities of G6PDH and 6PGDH were found in the Al-resistant PT741, when seedlings were transferred to Al-free treatment solutions after 16-h exposure to 100 μM Al. These results suggest that rapid induction of G6PDH and 6PGDH in the Al-resistant line PT741 by Al may play a role in the mechanism of Al resistance, possibly by regulation of the pentose phosphate pathway.