Citations

Objectives: Delirium severity is independently associated with longer hospital stays, nursing home placement, and death in patients outside the ICU. Delirium severity in the ICU is not routinely measured because the available instruments are difficult to complete in critically ill patients. We designed our study to assess the reliability and validity of a new ICU delirium severity tool, the Confusion Assessment Method for the ICU-7 delirium severity scale. Design: Observational cohort study. Setting: Medical, surgical, and progressive ICUs of three academic hospitals. Patients: Five hundred eighteen adult (≥ 18 yr) patients. Interventions: None. Measurements and Main Results: Patients received the Confusion Assessment Method for the ICU, Richmond Agitation-Sedation Scale, and Delirium Rating Scale-Revised-98 assessments. A 7-point scale (0–7) was derived from responses to the Confusion Assessment Method for the ICU and Richmond Agitation-Sedation Scale items. Confusion Assessment Method for the ICU-7 showed high internal consistency (Cronbach’s α = 0.85) and good correlation with Delirium Rating Scale-Revised-98 scores (correlation coefficient = 0.64). Known-groups validity was supported by the separation of mechanically ventilated and nonventilated assessments. Median Confusion Assessment Method for the ICU-7 scores demonstrated good predictive validity with higher odds (odds ratio = 1.47; 95% CI = 1.30–1.66) of in-hospital mortality and lower odds (odds ratio = 0.8; 95% CI = 0.72–0.9) of being discharged home after adjusting for age, race, gender, severity of illness, and chronic comorbidities. Higher Confusion Assessment Method for the ICU-7 scores were also associated with increased length of ICU stay (p = 0.001). Conclusions: Our results suggest that Confusion Assessment Method for the ICU-7 is a valid and reliable delirium severity measure among ICU patients. Further research comparing it to other delirium severity measures, its use in delirium efficacy trials, and real-life implementation is needed to determine its role in research and clinical practice.

49 Background: Predicting nodal positivity can guide surgical planning in breast cancer. Memorial Sloan-Kettering Cancer Center (MSKCC) and MD Anderson Cancer Center (MDACC) have established nomograms to predict sentinel node positivity. We propose that addition of distance of tumor from the nipple (DFN) can improve their performance. Methods: With IRB approval clinical T1/T2 tumors with pre-biopsy ultrasound were reviewed. MSKCC and MDACC nomogram predictions and the AUC-ROC were calculated. The addition of DFN was examined using multiple logistic regression and comparison of AUC-ROC values. Results: 401 breast cancers with clinical T1 (85%) or T2 (15%) tumors in 395 patients were included; of which 79/401 (19.7%) were node positive. Tumors were significantly closer to the nipple in those with positive nodes. 17/33 (51.5%) tumors within 2 cm of the nipple were node-positive versus 62/368 (16.8%) tumors > 2 cm from the nipple (p<0.0001). The MSKCC and MDACC nomograms each demonstrated good discrimination between node positive and negative patients with AUC-ROC values of 0.71 (95% CI: 0.64-0.77) and 0.74 (95% CI: 0.68-0.81), respectively. When added to the MSKCC nomogram, DFN ≤2 cm contributed significantly (OR 4.78, p=0.0001) to prediction of node positivity and improved the AUC-ROC to 0.73 (95% CI: 0.67-0.80). Similarly, DFN ≤2 cm was significant (OR 4.73, p=0.0002) when added to the MDACC nomogram and improved the AUC to 0.76 (95% CI: 0.70-0.82). Within nomogram probability categories, the proportion with positive nodes was consistently higher with DFN ≤2 cm. Conclusions: Tumor distance from nipple is associated with nodal positivity. When added to nomograms it improves prediction of node positivity. DFN should be considered when considering likelihood of nodal positivity for treatment planning. [Table: see text]

LBA7005 Background: The phase III HELIOS study evaluated the first-in-class, oral covalent BTK inhibitor ibrutinib in combination with BR (BR+ibr) vs BR plus placebo (BR+plb) in patients (pts) with previously treated CLL/SLL. The preplanned interim analysis reported here showed that the primary end point was met, upon which the IDMC recommended unblinding the study. Methods: Pts received BR ( ≤ 6 cycles) and were randomized 1:1 to ibr (420 mg daily) or plb. Purine analog refractoriness was a stratification factor. Pts with del17p ( > 20% of cells) were excluded. Primary end point was independent review committee (IRC)-assessed progression-free survival (PFS). Secondary end points included overall survival (OS) and overall response rate (ORR) per IRC. Results: 578 pts were randomized (289 per arm); median age 64 yrs; 38% Rai Stage III/IV; median 2 prior therapies. 6 cycles of BR were completed in 83% and 78% of pts in the ibr and plb arms, respectively. At a median follow-up of 17.2 months, IRC-assessed PFS was significantly longer with BR+ibr vs BR+plb (median not reached vs 13.3 months; HR: 0.203, 95% CI: 0.150-0.276, P< 0.0001); PFS results were consistent across high-risk subgroups. ORR and CR/CRi rates were 82.7% vs 67.8% (P< 0.0001) and 10.4% vs 2.8%. Median OS was not reached. 90 pts (31%) in the BR+plb arm with confirmed PD crossed over to receive ibr, as permitted per the protocol. Incidence of most AEs was similar between arms. The most common all-grade AEs with BR+ibr and BR+plb were neutropenia (58.2% vs 54.7%) and nausea (36.9% vs 35.2%); most common grade 3/4 AEs were neutropenia (53.7% vs 50.5%) and thrombocytopenia (15.0% each arm). Rates of grade 3/4 atrial fibrillation were 2.8% and 0.7%, and major hemorrhage were 2.1% and 1.7%. Fatigue (FACIT-Fatigue) was improved with BR+ibr vs BR+plb. Conclusions: The addition of ibr to BR reduced the risk of progression or death by 80% compared with BR+plb. ORR was also significantly improved. Safety of BR+ibr was consistent with the known profiles for BR and ibr. The data further support ibr as an important treatment option for pts with previously treated CLL/SLL. Clinical trial information: EudraCT No. 2012-000600-15; UTN No. U1111-1135-3745.

Abstract Background Thyroid carcinoma, which is rare in pediatric patients (age 0–18 years) but more common in adolescent and young adult (AYA) patients (age 15–39 years), carries the potential for morbidity and mortality. Methods Hybrid-capture-based comprehensive genomic profiling (CGP) was performed prospectively on 512 consecutively submitted thyroid carcinomas, including 58 from pediatric and AYA (PAYA) patients, to identify genomic alterations (GAs), including base substitutions, insertions/deletions, copy number alterations, and rearrangements. This PAYA data series includes 41 patients with papillary thyroid carcinoma (PTC), 3 with anaplastic thyroid carcinoma (ATC), and 14 with medullary thyroid carcinoma (MTC). Results GAs were detected in 93% (54/58) of PAYA cases, with a mean of 1.4 GAs per case. In addition to BRAF V600E mutations, detected in 46% (19/41) of PAYA PTC cases and in 1 of 3 AYA ATC cases, oncogenic fusions involving RET, NTRK1, NTRK3, and ALK were detected in 37% (15/41) of PAYA PTC and 33% (1/3) of AYA ATC cases. Ninety-three percent (13/14) of MTC patients harbored RET alterations, including 3 novel insertions/deletions in exons 6 and 11. Two of these MTC patients with novel alterations in RET experienced clinical benefit from vandetanib treatment. Conclusion CGP identified diverse clinically relevant GAs in PAYA patients with thyroid carcinoma, including 83% (34/41) of PTC cases harboring activating kinase mutations or activating kinase rearrangements. These genomic observations and index cases exhibiting clinical benefit from targeted therapy suggest that young patients with advanced thyroid carcinoma can benefit from CGP and rationally matched targeted therapy.

Purpose: We sought to assess for impact on management trends in new patients presenting to our institution with stress urinary incontinence (SUI) following the release of the FDA Health Notification in July 2011 for vaginal mesh. Materials and methods: Chart analysis was performed on patients assigned a primary International Classification of Diseases (ICD-9) diagnosis code of 625.6 for SUI at initial consultation by two providers at our institution between June 1, 2010 and November 30, 2014. Rates of treatment and types of procedures performed were analyzed: urethral bulking, mesh sling, or pubovaginal sling. Results: A total of 333 new patients were identified with an increasing trend over time. One hundred and twenty-three patients underwent 153 procedures for stress incontinence. The mean proportion that had a procedure per six-month period was 37%, with decreasing proportions over time. Initially all procedures were midurethral mesh slings, with a decline at the time of and after the notification, and a temporary increase in bulking procedures. Subsequently, there was a rise again in sling placement, namely with an increase in pubovaginal slings. Of the 20 pubovaginal slings placed, 13 were placed in patients who had a prior anti-incontinence surgery (eight for sling failure, vaginal mesh, or fixed urethra, and two in patients with mesh extrusion/erosion). Seven were performed in patients who had never had prior surgery (two for very high-grade incontinence, two with urethral diverticulectomy, and three in patients who expressed concern about mesh). Conclusions: Although there were an increasing number of patients seen for management of SUI over time, there was a progressive decrease in the proportion of patients having anti-incontinence procedures after release of the FDA notification. There was an overall decrease in the use of mesh slings and an increase in bulking, and more notably, placement of pubovaginal slings.