Citations

Abstract Background: Data regarding patients (pts) and physicians' preferences for modern adjuvant chemotherapy (CT) are limited. Prior studies suggested that most pts with early stage breast cancer were willing to receive 6 months of adjuvant cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) for modest survival benefits (e.g. most women would have accepted 3-6 months extension of life). Methods: E5103 was a phase III trial which randomized node positive or high risk node negative breast cancer pts to receive adjuvant CT (doxorubicin, cyclophosphamide and paclitaxel) with either placebo or bevacizumab. Telephone based surveys were administered to all pts enrolled on E5103 between 01/Jan/10 and 08/Jun/10, as part of a Decision-Making/Quality of Life component. Results presented here are part of the 18 months post-enrollment follow-up. Pts were asked to rate the survival benefit needed to justify 6 months of CT. A complementary survey was sent to all physicians who registered at least one pt on E5103. Results: 465 out of 519 eligible pts (90%) responded to this survey at 18 months. Main reasons for non response were: inability to reach the patient (6%) or patient refusal (2%). Median pts age was 51 (25-76); 42% of pts had at least a college degree. The majority had at least Stage II cancer. 179 (16%) physicians participated, among whom median age was 50 (35-70). The median years in practice was 17 (3-38); 78% of physicians worked on large size practices, 72% saw at least 5 new breast cancer pts/month, and 77% enroll between 1-4 pts on trials/month. We found considerable variation in pts preferences particularly for modest survival benefits: a substantial minority of pts (24%) would consider 6 months of CT definitely worthwhile for 1 month survival benefit, 18% would possibly consider it and 56% would not. The percentage considering CT definitely worthwhile increased with greater benefit, but did not reach 100%, even with 24 months survival benefit. About half of pts considered 6 months of CT definitely worthwhile for 9 months benefit, 70% for 12 months and 84% for 24 months. Physicians were less likely to accept CT for a small chance of benefit (34% of pts vs. 5% of physicians would definitely consider CT worthwhile for 2 months of benefit). For longer benefit, pts and physicians choices were similar (84% of pts vs. 92% of physicians would definitely consider CT worthwhile for 24 months benefit). Table Yes, definitely worthwhileYes, maybeNo, not worthwhileNo answerConsider 6 months of CT to live:PtsPhysiciansPtsPhysiciansPtsPhysiciansPts/Physicians*1 month longer24%3%18%15%56%80%2%2 months longer34%5%23%32%41%60%2%6 months longer44%32%35%54%19%12%2%9 months longer53%51%34%42%11%5%2%12 months longer70%75%23%22%5%1%2%24 months longer84%92%12%5%2%1%2%n Pts= 465; n Physicians= 179; * equal results in both groups Conclusions: This subgroup of pts who had undergone modern adjuvant CT in a large multicenter randomized controlled trial and these physicians who registered pts on the same trial had different cutoffs for acceptable levels of benefits and risks when considering adjuvant chemotherapy. It is important to engage pts in determining whether CT is or is not a "reasonable" option for treatment. Citation Format: Vaz Luis I, O'Neill A, Sepucha K, Miller KD, Baker E, Dang CT, Northfelt DW, Winer EP, Sledge GW, Schneider BP, Partridge A. Survival benefit needed to undergo chemotherapy: Patients and physicians preferences. [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 P5-11-02.

AbstractBackgroundEarly life events have been found to be associated with irritable bowel syndrome (IBS) suggesting a role in development of functional disorders. The study aim was to identify potential perinatal risk factors for adult IBS.MethodsUtilizing a population‐based nested case–control design, cases who met modified Rome III criteria for IBS and age‐ and‐gender matched controls were identified using responses from prior mailed surveys to a random sample of Olmsted County residents. Medical records of eligible respondents were reviewed for perinatal events of interest. The association of early life events with subsequent case status was assessed using conditional logistic regression.Key ResultsOf 3 417 respondents, 513 were born in Olmsted County and 108 met criteria for IBS. Due to missing records, 89 pairs were included in the final analyses. Logistic regression revealed only birth weight as a predictor of IBS. Lower birth weight increased the odds for IBS (OR = 1.54 [95% CI = (1.12, 2.08), p = 0.008]). Median birth weight was 3.35 kg (range: 1.96–5.24) and 3.57 kg (range: 2.18–4.59) for cases and controls, respectively. Maternal age, delivery method, and antibiotic exposure were not associated with IBS status but this study was only powered to detect large odds ratios.Conclusions and InferencesLower birth weight was observed as a risk factor for IBS. It is not clear if in utero developmental delays directly lead to IBS or if low birth weight is a prospective marker for subsequent early life problems leading to IBS.

SummaryInfluenza causes significant morbidity and mortality annually. Although vaccination offers a considerable amount of protection, it is far from perfect, especially in aging populations. This is due to age‐related defects in immune function, a process called immunosenescence. To date, there are no assays or methods to predict or explain variations in an individual's level of response to influenza vaccination. In this study, we measured levels of several immune cell subsets at baseline (Day 0) and at Days 3 and 28 post‐vaccination using flow cytometry. Statistical modelling was performed to assess correlations between levels of cell subsets and Day 28 immune responses – haemagglutination inhibition (HAI) assay, virus neutralizing antibody (VNA) assay, and memory B cell ELISPOT. Changes in several groups of cell types from Day 0 to Day 28 and Day 3 to Day 28 were found to be significantly associated with immune response. Baseline levels of several immune cell subsets, including B cells and regulatory T cells, were able to partially explain variation in memory B‐cell ELISPOT results. Increased expression of HLA‐DR on plasmacytoid dendritic cells after vaccination was correlated with increased HAI and VNA responses. Our data suggest that the expression of activation markers (HLA‐DR and CD86) on various immune cell subsets, as well as the relative distribution of cell subsets, both have value in predicting immune responses to influenza vaccination in older individuals.

Abstract Individuals from pancreatic cancer families are at increased risk, not only of pancreatic cancer, but also of melanoma, breast, ovarian, and colon cancers. While some of the increased risk may be due to mutations in high-penetrance genes (i.e., BRCA2, PALB2, ATM, p16/CDKN2A or DNA mismatch repair genes), common genetic variants may also be involved. In a high-risk population of cases with either a family history of pancreatic cancer or early-onset pancreatic cancer (diagnosis before the age of 50 years), we examined the role of genetic variants previously associated with risk of pancreatic, breast, ovarian, or prostate cancer. We genotyped 985 cases (79 early-onset cases, 906 cases with a family history of pancreatic cancer) and 877 controls for 215,389 SNPs using the iSelect Collaborative Oncological Gene-Environment Study (iCOGS) array with custom content. Logistic regression was performed using a log-linear additive model. We replicated several previously reported pancreatic cancer susceptibility loci, including recently identified variants on 2p13.3 and 7p13 (2p13.3, rs1486134: OR = 1.36; 95% CI, 1.13–1.63; P = 9.29 × 10−4; 7p13, rs17688601: OR = 0.76; 95% CI, 0.63–0.93; P = 6.59 × 10−3). For the replicated loci, the magnitude of association observed in these high-risk patients was similar to that observed in studies of unselected patients. In addition to the established pancreatic cancer loci, we also found suggestive evidence of association (P < 5 × 10−5) to pancreatic cancer for SNPs at HDAC9 (7p21.1) and COL6A2 (21q22.3). Even in high-risk populations, common variants influence pancreatic cancer susceptibility. Cancer Epidemiol Biomarkers Prev; 25(7); 1185–91. ©2016 AACR.

Guidelines for performing concomitant procedures (CPs) in patients undergoing continuous flow-left ventricular assist device (CF-LVAD) implantation are unclear. The impact of an increased surgical complexity outside the constraint of landmark clinical trials has not been reported. From May 2004 to December 2013, 614 patients (499 males, 81%) underwent CF-LVAD implant at our institutions. Median age was 57 ± 13 years and 364 (59%) were bridge to transplantation (BTT). Survival and device-related complications were analyzed and stratified based on the surgical intervention. A total of 398 patients (65%) underwent CF-LVAD implantation without CPs. The remaining patients (35%, n = 216) were grouped according to various CPs. Survival was comparable between groups and not influenced by the CP, device type, or indication for implant. Time-to-first device-related adverse event was shorter in patients with CPs. Regression analysis revealed only increased age (p = 0.03), increase in baseline creatinine (p = 0.002), cardiopulmonary bypass time (p = 0.03), and decreased body mass index (p = 0.03) were predictors of mortality, whereas only age (p = 0.006) and prior sternotomy (p = 0.02) were related to adverse device-related events. Performing CPs leads to comparable survival and device-related outcomes after implant. The decision to perform CPs should be balanced with age, preoperative renal dysfunction, and projected complexity of surgery.

Objective: In this systematic review, we aimed to evaluate methodological and reporting trends present in the current literature by investigating published usability studies of electronic health records (EHRs). Methods: A literature search was conducted for articles published through January 2015 using MEDLINE (Ovid), EMBASE, Scopus, and Web of Science, supplemented by citation and reference list reviews. Studies were included if they tested the usability of hospital and clinic EHR systems in the inpatient, outpatient, emergency department, or operating room setting. Results: A total of 4848 references were identified for title and abstract screening. Full text screening was performed for 197 articles, with 120 meeting the criteria for study inclusion. Conclusion: A review of the literature demonstrates a paucity of quality published studies describing scientifically valid and reproducible usability evaluations at various stages of EHR system development. A lack of formal and standardized reporting of EHR usability evaluation results is a major contributor to this knowledge gap, and efforts to improve this deficiency will be one step of moving the field of usability engineering forward.

This review of 29 patients with relapsing polychondritis seen at the Mayo Clinic between 1962 and 1976 emphasizes the head and neck manifestations of the disease and the role of the otolaryngologist in its diagnosis and treatment. The major clinical features included inflammation of the pinna, eye involvement, nasal cartilage involvement, laryngotracheal involvement, arthropathy, hearing loss, costal chondritis, and fever. The erythrocyte sedimentation rate was often elevated, and mild anemia was not uncommon.

Abstract Identifying genetic variants with pleiotropic associations can uncover common pathways influencing multiple cancers. We took a two-stage approach to conduct genome-wide association studies for lung, ovary, breast, prostate, and colorectal cancer from the GAME-ON/GECCO Network (61,851 cases, 61,820 controls) to identify pleiotropic loci. Findings were replicated in independent association studies (55,789 cases, 330,490 controls). We identified a novel pleiotropic association at 1q22 involving breast and lung squamous cell carcinoma, with eQTL analysis showing an association with ADAM15/THBS3 gene expression in lung. We also identified a known breast cancer locus CASP8/ALS2CR12 associated with prostate cancer, a known cancer locus at CDKN2B-AS1 with different variants associated with lung adenocarcinoma and prostate cancer, and confirmed the associations of a breast BRCA2 locus with lung and serous ovarian cancer. This is the largest study to date examining pleiotropy across multiple cancer-associated loci, identifying common mechanisms of cancer development and progression. Cancer Res; 76(17); 5103–14. ©2016 AACR.