Citations

AbstractImmune checkpoint inhibitors (ICPis) are a novel class of immunotherapeutic agents that have revolutionized the treatment of cancer; however, these drugs can also cause a unique spectrum of autoimmune toxicity. Autoimmune hemolytic anemia (AIHA) is a rare, but often severe, complication of ICPis. We identified 14 patients from nine institutions across the United States who developed ICPi‐AIHA. The median interval from ICPi initiation to development of AIHA was 55 days (interquartile range [IQR], 22‐110 days). Results from the direct antiglobulin test (DAT) were available for 13 of 14 patients: 8 patients (62%) had a positive DAT and 5 (38%) had a negative DAT. The median pretreatment and nadir hemoglobin concentrations were 11.8 g/dL (IQR, 10.2‐12.9 g/dL) and 6.3 g/dL (IQR, 6.1‐8.0 g/dL), respectively. Four patients (29%) had a preexisting lymphoproliferative disorder, and two (14%) had a positive DAT prior to initiation of ICPi therapy. All patients were treated with glucocorticoids, with three requiring additional immunosuppressive therapy. Complete and partial recoveries of hemoglobin were achieved in 12 (86%) and 2 (14%) patients, respectively. Seven patients (50%) were rechallenged with ICPis, and one (14%) developed recurrent AIHA. Clinical and laboratory features of ICPi‐AIHA were similar in DAT positive and negative patients. ICPi‐AIHA shares many clinical features with primary AIHA; however, a unique aspect of ICPi‐AIHA is a high incidence of DAT negativity. Glucocorticoids are an effective first‐line treatment in the majority of patients with ICPi‐AIHA, and most patients who are rechallenged with an ICPi do not appear to develop recurrence of AIHA.

Abstract Purpose: To increase women's adherence with one tribe's mammographic screening guidelines. This tribe recommends annual mammograms beginning at age 40. Currently, adherence stands at 36%. Our previous work identified a demographic feature and variables within four theoretical models of health behavior that significantly differentiated nonadherent women from adherent women. In “No Squeeze Can Defeat Me: Mammograms for Life!” (No Squeeze) we are developing a messaging menu (e.g., posters, pamphlets, videos, digital stories, articles, and letters) that is guided by the differentiating variables and features. The program also is developing a supplement to an existing intake form for women to complete before they see their providers for annual Well Woman exams. The supplement intake form will help providers tailor face-to-face messages to encourage screening of known nonscreeners, known nonadherent screeners, and women approaching screening age. Procedures: This program works through a Community Advisory Project Board (CAPB) consisting of tribal health, Indian Health Service, and community members of varied ages, screening status, and cancer history status. The CAPB members take the lead on all aspects of messaging and intake form design. In their role, they have designed a logo, determined wording and design of posters; identified locations for messaging; recruited community women for video interviews and use of their images on materials; determined incentive amounts; and delegated tasks to a project implementation team (PIT) made of tribal and IHS staff. PIT members' responsibilities include posting new messages every six to eight weeks, obtaining feedback on messaging and intake forms, implementing the intake form, and organizing video interviews and photographic sessions. At this time, effort is being devoted to poster development, placement, and a refreshment schedule and to final design of intake forms. Evaluation of progress on this project involves collection and analysis of community women's surveys related to messaging and intake forms, CAPB feedback on messaging, documentation of poster placements and refresh dates, and tracking changes in screening participation. First-year analysis covers a seven-month period ending on June 30, 2017. Data Summary: Early analysis shows that: 1) community women find poster messaging generally interesting, appealing, important, and mostly persuasive. They prefer images of community women and favor fewer words in most messages. 2) The intake form supplement is easy to answer (little time to complete), appropriate as an addition to the existing Well Woman intake questions, and noninvasive. The questions were considered reasonable and women held mixed opinions regarding whether the form should be self-administered or filled in during an interview by a nurse. The CAPB assessments of messaging showed 19 of 78 posters were recommended for some revision and 10 posters were not liked at all. In general, wording was not offensive and more than half of the posters conveyed the central message in the fewest words possible. Half of the posters were rated visually attractive. As of the first poster placement period, 5 posters have been placed in two of three targeted communities and in 38 individual locations, including clinic/hospitals, post office and grocery store bulletin boards, an exercise facility, and in one casino. Between January 2017 and April 2017, radiology reported a 19% increase in screening. Conclusions: While these data are from the early period of implementation, results show that developing messages and intake forms focused on influential variables derived from demographic and theoretical models of health behavior are generally well received by the community and with continued refinement could result in sustained increases in screening. At this point we cannot discern whether documented increases are from the existing population of nonadherent screeners. Citation Format: Wesley O. Petersen, Ann M. Nicometo, Robert A. Vierkant. Launch of an intervention to improve mammographic screening adherence in women of one Bemidji Area tribe: The “No squeeze can defeat me: Mammograms for life!” project [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr C86.

Background: The importance of physical activity in preventing major vascular events has received increased attention in the past decade. Due to the inclusion of the INTERVENT lifestyle modification program, the CREST2 trial provides a unique opportunity to study physical activity profiles in patients with severe asymptomatic extracranial carotid stenosis. Hypothesis: Based on data from a trial of intracranial stenosis patients, we aimed to evaluate the hypothesis that <40% of carotid stenosis subjects will have optimal physical activity levels. We also assessed key subgroups to determine patterns of physical activity. Methods: We analyzed 1087 CREST2 participants with baseline data on physical activity. The Physician-based Assessment and Counseling for Exercise (PACE) score is recorded for each patient and dichotomized as “in target” (4-8 points) or “out of target” (<4 points). A PACE score of <4 indicates a subject who does not engage in regular exercise. Results are analyzed for the entire trial. Chi square testing and t-tests were performed for evaluation of subgroup differences. Results: The mean age of the study population is 69.5±7.8 years (60% male). The median PACE score at baseline is 4.0 (mean 3.8±2.1; IQR 2 to 6). The Table shows baseline characteristics of patients by mean PACE score. Being male, not having diabetes mellitus, having a body mass index <30kg/m2, being a non-smoker, and not having a history of peripheral arterial disease were associated with significantly higher mean PACE scores (P<0.01). Conclusions: We have defined several patient groups with asymptomatic carotid stenosis that have suboptimal physical activity. These results provide opportunities for targeted efforts to improve primary stroke prevention. These baseline data will also allow investigators to determine if trial involvement and the INTERVENT program leads to improvement in the level of physical activity.

Objectives: Assessment of carotid disease is most commonly performed with duplex ultrasonography (DUS). Measures of plaque area and tissue composition from DUS images may identify patients at risk for future neurologic events, and may assess the effects of vascular risk-factor modification (by measuring change in plaque area and/or tissue constituents). We quantified plaque area and tissue constituents from DUS images of CREST-2 participants at baseline and correlated them with their baseline vascular risk factors. Methods: CREST-2 consists of two multicenter, randomized trials in patients with asymptomatic ≥70% carotid stenosis comparing intensive medical management (IMM) plus endarterectomy or stenting vs IMM alone. Baseline B-mode DUS images from 500 patients underwent manual plaque outlining and automatic pixel brightness assessment. Plaque area, grayscale median (GSM), Gray-Weale score for heterogeneity, and areas for intraplaque hemorrhage and lipid were the output parameters. We computed the parameter estimates (95% confidence intervals) for baseline patient characteristics (age, sex, race, diabetes, smoking, BMI, blood pressure and LDL levels) versus plaque characteristics. Results: High-risk plaque features (larger plaque area, lower GSM , lower Gray-Weale scores, or larger areas of hemorrhage and lipid) were present in older patients, males, and those with elevated diastolic blood pressure and LDL levels (Table). Conclusions: In a randomized trial of asymptomatic patients with high-grade carotid stenosis, DUS-based computation of plaque geometry and tissue composition is feasible. Elevated diastolic blood pressure and LDL levels at baseline are associated with high-risk plaque characteristics. These novel findings identify potentially modifiable targets for aggressive treatment to reduce stroke-risk in patients with carotid stenosis.

Background Oral anticoagulants ( OACs ) in patients with atrial fibrillation ( AF ), in addition to reducing stroke risk, could also prevent adverse cognitive outcomes. The purpose of this study was to compare the risk of dementia incidence across patients with AF initiating different OAC s. Methods and Results We identified patients with nonvalvular AF initiating OAC s in 2 US healthcare claim databases, MarketScan (2007–2015) and Optum Clinformatics (2009–2015). Dementia, comorbidities, and use of medications were defined on the basis of inpatient and outpatient claims. We performed head‐to‐head comparisons of warfarin, dabigatran, rivaroxaban, and apixaban in propensity score–matched cohorts. We calculated hazard ratios ( HR s) and 95% confidence intervals ( CI s) of incident dementia for each propensity score–matched cohort and meta‐analyzed database‐specific results. We analyzed 307 099 patients with AF from the MarketScan database and 161 346 from the Optum database, of which 6572 and 4391, respectively, had a diagnosis of incident dementia. The mean follow‐up of each cohort ranged between 0.7 and 2.2 years. Patients initiating direct OACs experienced lower rates of dementia than those initiating warfarin (dabigatran: HR , 0.85; 95% CI , 0.71–1.01; rivaroxaban: HR , 0.85; 95% CI , 0.76–0.94; apixaban: HR , 0.80; 95% CI , 0.65–0.97). There were no differences in rates of dementia comparing direct OAC user groups (dabigatran versus rivaroxaban: HR , 1.02; 95% CI , 0.79–1.32; dabigatran versus apixaban: HR , 0.92; 95% CI , 0.63–1.36; apixaban versus rivaroxaban: HR , 1.01; 95% CI , 0.86–1.19). Conclusions Patients with AF initiating direct OACs experienced lower rates of incident dementia than warfarin users. No obvious benefit was observed for any particular direct OAC in relation to dementia rates.

Whereas VHL inactivation is a primary event in clear cell renal cell carcinoma (ccRCC), the precise mechanism(s) of how this interacts with the secondary mutations in tumor suppressor genes, including PBRM1 , KDM5C / JARID1C , SETD2 , and/or BAP1 , remains unclear. Gene expression analyses reveal that VHL, PBRM1, or KDM5C share a common regulation of interferon response expression signature. Loss of HIF2α, PBRM1, or KDM5C in VHL-/- cells reduces the expression of interferon stimulated gene factor 3 (ISGF3), a transcription factor that regulates the interferon signature. Moreover, loss of SETD2 or BAP1 also reduces the ISGF3 level. Finally, ISGF3 is strongly tumor-suppressive in a xenograft model as its loss significantly enhances tumor growth. Conversely, reactivation of ISGF3 retards tumor growth by PBRM1-deficient ccRCC cells. Thus after VHL inactivation, HIF induces ISGF3, which is reversed by the loss of secondary tumor suppressors, suggesting that this is a key negative feedback loop in ccRCC.

Background: In CREST2, intensive medical management of subjects’ vascular risk factors is overseen by the site Principal Investigator (PI) and implemented by a designated Medical Management Physician (MMP) and coordinator. These physicians have different specialties and experience with risk factor management. We sought to determine the relationship between risk factor control and PI and MMP specialty. Methods: Data on 613 patients with at least 1 follow-up visit from 105 CREST2 sites were used for these analyses. CREST2 sites were categorized based on both PI specialty and MMP specialty. Specialty of the site-designated primary MMP was used for sites with more than one MMP. We compared the percentage of patients in target at last follow-up visit for the primary risk factors, LDL < 70 mg/dL and SBP <140 mm Hg, among PI specialties and MMP specialties, using the chi-square test. Results: The table shows the number of patients by PI and MMP specialty, as well as their control of SBP and LDL. There were no significant differences in control of SBP or LDL by PI specialty. There was a trend toward an association between LDL control and MMP specialty, with higher rates of LDL control at sites with Internal Medicine MMP specialists and lower rates of control with Vascular Surgery MMPs. SBP control rates were not significantly different across MMP specialties. Conclusions: In this early analysis of risk factor control in the CREST2 study, site PI and MMP specialty did not have a significant effect on LDL and SBP during follow-up. This suggests that protocol care pathways are generalizable to diverse physicians.

The aim of this study was twofold—(1) to compare the current ED staffing workload alert system to clinicians’ perceptions of workload in the ED, and (2) to examine the potential impact of a multi-faceted, systems-level intervention on clinicians’ perceptions of workload. Constant flow of patients into the Emergency Departments (ED) regularly increases the workload of clinicians and can compromise the quality of care delivery and patient safety. An automatic staffing workload alert system was created and implemented in response to an observed shift in patient volume to the overnight hours at one academic quaternary care center. Surveys addressing workload and interruptions were administered to ED clinicians, pre-and post-intervention implementation. Output from the staffing workload alert system was recorded for each clinician shift. Clinicians’ perceptions of workload were able to predict swing shift activations, χ 2 (6) = 14.14, p = 0.028. Only the performance subscale significantly correlated with swing shift activations, p=0.006. A Kruskal-Wallis H test found perceived interruptions changed following systems-level changes, χ 2 (1) = 7.195, p = 0.007. Utilizing subjective measure of clinicians’ workload validated an objective, automated staffing workload alert system that determined if swing shift activations are necessary.