Citations

AbstractDecision aids are evidenced‐based tools designed to increase patient understanding of medical options and possible outcomes, facilitate conversation between patients and clinicians, and improve patient engagement. Decision aids have been used for shared decision making (SDM) interventions outside of the ED setting for more than a decade. Their use in the ED has only recently begun to be studied. This article provides background on this topic and the conclusions of the 2016 Academic Emergency Medicine consensus conference SDM in practice work group regarding “Shared Decision Making in the Emergency Department: Development of a Policy‐Relevant, Patient‐Centered Research Agenda.” The goal was to determine a prioritized research agenda for the development and testing of SDM interventions for use in emergency care that was most important to patients, clinicians, caregivers, and other key stakeholders. Using the nominal group technique, the consensus working group proposed prioritized research questions in six key domains: 1) content (i.e., clinical scenario or decision area), 2) level of evidence available, 3) tool design strategies, 4) risk communication, 5) stakeholders, and 6) outcomes.

Objectives: Approximately half of ICU admissions are comprised of patients older than 65 years old. Mild cognitive impairment is a common disorder affecting 10–20% of patients in the same age group. A need exists for exploring mild cognitive impairment and risk of critical illness. As mild cognitive impairment may be a contributor to poorer overall health or be a result of it, we sought to determine whether the presence of mild cognitive impairment independently increases the risk of critical illness admissions. Design: Data from the Mayo Clinic Study of Aging were analyzed. All study participants underwent prospective comprehensive cognitive testing and expert panel consensus diagnosis of both cognitive function and clinical state at baseline and subsequent visits. Comparisons were made between those with normal cognitive function and mild cognitive impairment regarding baseline health and frequency of critical illness. Setting: Single-center population-based cohort out of Olmsted County, MN. Participants: All individuals 70–89 years old were screened for prospective enrollment in the Mayo Clinic Study of Aging. Patients with preexisting dementia and ICU admission within 3 years of entry to the study were excluded from this analysis. Interventions: None. Measurements and Main Results: Of 2,425 patients analyzed from the Mayo Clinic Study of Aging, 1,734 patients (71%) were included in the current study. Clinical factors associated with baseline mild cognitive impairment included age, male gender, stroke, and poorer health self-rating. Using a Cox regression model adjusting for these and a priori variables of baseline health, the presence of mild cognitive impairment remained a significant predictor of ICU admission (hazard ratio, 1.50 [1.15–1.96]; p = 0.003). Conclusions and Relevance: The presence of mild cognitive impairment is independently associated with increased critical illness admission. Further prospective studies are needed to analyze the impact of critical illness on cognitive function.

Abstract Proinflammatory consequences have been described for lysophosphatidylcholine, a lipid product of cellular injury, signaling via the G protein–coupled receptor G2A on myeloid and lymphoid inflammatory cells. This prompted the hypothesis that genetic deletion of G2A would limit intestinal inflammation in a mouse model of colitis induced by dextran sodium sulfate. Surprisingly, G2A−/− mice exhibited significantly worsened colitis compared with wild-type mice, as demonstrated by disease activity, colon shortening, histology, and elevated IL-6 and IL-5 in colon tissues. Investigation of inflammatory cells recruited to inflamed G2A−/− colons showed significantly more TNF-α+ and Ly6ChiMHCII− proinflammatory monocytes and eosinophils than in wild-type colons. Both monocytes and eosinophils were pathogenic as their depletion abolished the excess inflammation in G2A−/− mice. G2A−/− mice also had less IFN-γ in inflamed colon tissues than wild-type mice. Fewer CD4+ lymphocytes were recruited to inflamed G2A−/− colons, and fewer colonic lymphocytes produced IFN-γ upon ex vivo stimulation. Administration of IFN-γ to G2A−/− mice during dextran sodium sulfate exposure abolished the excess colitic inflammation and reduced colonic IL-5 and eosinophil numbers to levels seen in wild-type mice. Furthermore, IFN-γ reduced the numbers of TNF-α+ monocyte and enhanced their maturation from Ly6ChiMHCII− to Ly6CintMHCII+. Taken together, the data suggest that G2A signaling serves to dampen intestinal inflammation via the production of IFN-γ, which, in turn, enhances monocyte maturation to a less inflammatory program and ultimately reduces eosinophil-induced injury of colonic tissues.

AbstractObjectiveThe risk of hypertension in adults who regularly take a nap is controversial. The objective of this meta‐analysis was to assess the associations between napping and hypertension.MethodsA literature search was performed using MEDLINE, EMbase and The Cochrane Database of Systematic Reviews from inception through October, 2015. Studies that reported relative risks, odd ratios or hazard ratios comparing the risk of hypertension in individuals who regularly take nap were included. Pooled risk ratios (RR) and 95% confidence interval (CI) were calculated using a random‐effect, generic inverse variance method.ResultsNine observational studies with 112,267 individuals were included in the analysis to assess the risk of hypertension in nappers. The pooled RR of hypertension in nappers was 1.13 with 95% CI (0.98 to 1.30). When meta‐analysis was limited only to studies assessing the risk of hypertension in daytime nappers, the pooled RR of hypertension was 1.19 with 95% CI (1.06 to 1.35). The data on association between nighttime napping in individuals who work night shift and hypertension were limited, only one observational study reported reduced risk of hypertension in nighttime nappers with odds ratio of 0.79 with 95% CI (0.63 to 1.00).ConclusionsOur meta‐analysis demonstrates a significant association between daytime napping and hypertension. Future study is needed to assess the potential benefits of HTN screening for daytime nappers.

The concept of optimizing health care by understanding and generating knowledge from previous evidence, ie, the Learning Health-care System (LHS), has gained momentum and now has national prominence. Meanwhile, the rapid adoption of electronic health records (EHRs) enables the data collection required to form the basis for facilitating LHS. A prerequisite for using EHR data within the LHS is an infrastructure that enables access to EHR data longitudinally for health-care analytics and real time for knowledge delivery. Additionally, significant clinical information is embedded in the free text, making natural language processing (NLP) an essential component in implementing an LHS. Herein, we share our institutional implementation of a big data-empowered clinical NLP infrastructure, which not only enables health-care analytics but also has real-time NLP processing capability. The infrastructure has been utilized for multiple institutional projects including the MayoExpertAdvisor, an individualized care recommendation solution for clinical care. We compared the advantages of big data over two other environments. Big data infrastructure significantly outperformed other infrastructure in terms of computing speed, demonstrating its value in making the LHS a possibility in the near future.

SAGE-Journals-Accessible-Video-Player 10.1089/vid.2016.0030.M1 sj-vid-1-vid-10.1089_vid.2016.0030

Abstract Importance: 20-25% of patients with early stage HER2-positive breast cancer develop tumor relapse after adjuvant trastuzumab. Identification of such patients is a key goal for clinical management decisions. Objective: To assess molecular heterogeneity among early stage HER2-positive patients using the Prosigna™ algorithm, to define intrinsic subtypes, and to determine the clinical significance of such heterogeneity. Design: The NanoString® platform was used to measure the abundance of the PAM50 subtype signature transcripts. Samples from the NCCTG (Alliance) N9831 trial were analyzed using the Prosigna™ algorithm to define intrinsic subtype and risk scores. Subtypes were evaluated for recurrence-free survival following chemotherapy with or without trastuzumab. Setting: Samples were obtained from a multi-center randomized phase III trial of chemotherapy versus chemotherapy plus trastuzumab. Participants: All tumors were centrally evaluated for HER2 positivity, defined as IHC 3+ and/or FISH >2.0; 1392 patients were evaluated for molecular subtype. Intervention(s): Patients received adjuvant chemotherapy (doxorubicin plus cyclophosphamide followed by paclitaxel) (n=484) or chemotherapy plus trastuzumab (n=908). Main Outcome Measure(s): The primary outcome was recurrence-free survival as a function of subtype and treatment. Results: Patients with HER2-positive tumors with HER2-enriched features comprised about 70% of the sample cohort, and these individuals received significant benefit from adjuvant trastuzumab (HR=0.68, 95%CI: 0.52, 0.89, p=0.005), as did the relatively fewer patients (291/1392) with Luminal-type tumors (HR=0.52, 95%CI: 0.32, 0.85, p=0.01). The sample cohort contained a small number of patients with tumors having Basal-like features (97/1392), and the data suggest that these individuals may have received less benefit from trastuzumab, beyond that received from chemotherapy alone (HR=1.06, 95%CI:0.53,2.13, p=0.87). Conclusions: The majority of HER2-positive tumors are classified as HER2-enriched or Luminal using the Prosigna algorithm, and patients with such tumors benefit from adjuvant trastuzumab. About 10% of HER2-positive tumors exhibit Basal-like genomic features, and such tumors appear to recur at fairly similar frequency irrespective of treatment with chemotherapy or chemotherapy plus trastuzumab. Patients with HER2-positive/Basal-like tumors may represent a cohort that should be considered for enrollment in trials to evaluate emerging novel HER2-targeted agents, other targeted therapies, or combinations of both approaches. Support provided in part by CA129949 and CA15083. Citation Format: Perez EA, Ballman KV, Mashadi-Hossein A, Tenner KS, Kachergus JM, Norton N, Necela BM, Carr JM, Ferree S, Perou CM, Cheang MCU, Thompson EA. Intrinsic subtype and therapeutic response among early stage HER2-positive breast tumors from the North Central cancer treatment group (Alliance) N9831 trial. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-07-04.

Germline mutations in the DNA base excision repair gene MUTYH are known to increase a carrier's risk of colorectal cancer. However, the risks of other (extracolonic) cancers for MUTYH mutation carriers are not well defined. We identified 266 probands (91% Caucasians) with a MUTYH mutation (41 biallelic and 225 monoallelic) from the Colon Cancer Family Registry. Mutation status, sex, age and histories of cancer from their 1,903 first‐ and 3,255 second‐degree relatives were analyzed using modified segregation analysis conditioned on the ascertainment criteria. Compared with incidences for the general population, hazard ratios (HRs) (95% confidence intervals [CIs]) for biallelic MUTYH mutation carriers were: urinary bladder cancer 19 (3.7–97) and ovarian cancer 17 (2.4–115). The HRs (95% CI) for monoallelic MUTYH mutation carriers were: gastric cancer 9.3 (6.7–13); hepatobiliary cancer 4.5 (2.7–7.5); endometrial cancer 2.1 (1.1–3.9) and breast cancer 1.4 (1.0–2.0). There was no evidence for an increased risk of cancers at the other sites examined (brain, pancreas, kidney or prostate). Based on the USA population incidences, the estimated cumulative risks (95% CI) to age 70 years for biallelic mutation carriers were: bladder cancer 25% (5–77%) for males and 8% (2–33%) for females and ovarian cancer 14% (2–65%). The cumulative risks (95% CI) for monoallelic mutation carriers were: gastric cancer 5% (4–7%) for males and 2.3% (1.7–3.3%) for females; hepatobiliary cancer 3% (2–5%) for males and 1.4% (0.8–2.3%) for females; endometrial cancer 3% (2%–6%) and breast cancer 11% (8–16%). These unbiased estimates of both relative and absolute risks of extracolonic cancers for people, mostly Caucasians, with MUTYH mutations will be important for their clinical management.

Immune checkpoint therapy with PD-1 blockade has emerged as an effective therapy for many advanced cancers; however, only a small fraction of patients achieve durable responses. To date, there is no validated blood-based means of predicting the response to PD-1 blockade. We report that Bim is a downstream signaling molecule of the PD-1 pathway, and its detection in T cells is significantly associated with expression of PD-1 and effector T cell markers. High levels of Bim in circulating tumor-reactive (PD-1 + CD11a hi CD8 + ) T cells were prognostic of poor survival in patients with metastatic melanoma who did not receive anti–PD-1 therapy and were also predictive of clinical benefit in patients with metastatic melanoma who were treated with anti–PD-1 therapy. Moreover, this circulating tumor-reactive T cell population significantly decreased after successful anti–PD-1 therapy. Our study supports a crucial role of Bim in both T cell activation and apoptosis as regulated by PD-1 and PD-L1 interactions in effector CD8 + T cells. Measurement of Bim levels in circulating T cells of patients with cancer may provide a less invasive strategy to predict and monitor responses to anti–PD-1 therapy, although future prospective analyses are needed to validate its utility.