Citations

Abstract Background: Microsatellite instability (MSI) and BRAF mutation status are associated with colorectal cancer survival, whereas the role of body mass index (BMI) is less clear. We evaluated the association between BMI and colorectal cancer survival, overall and by strata of MSI, BRAF mutation, sex, and other factors. Methods: This study included 5,615 men and women diagnosed with invasive colorectal cancer who were followed for mortality (maximum: 14.7 years; mean: 5.9 years). Prediagnosis BMI was derived from self-reported weight approximately one year before diagnosis and height. Tumor MSI and BRAF mutation status were available for 4,131 and 4,414 persons, respectively. Multivariable hazard ratios (HR) and 95% confidence intervals (CI) were estimated from delayed-entry Cox proportional hazards models. Results: In multivariable models, high prediagnosis BMI was associated with higher risk of all-cause mortality in both sexes (per 5-kg/m2; HR, 1.10; 95% CI, 1.06–1.15), with similar associations stratified by sex (Pinteraction: 0.41), colon versus rectum (Pinteraction: 0.86), MSI status (Pinteraction: 0.84), and BRAF mutation status (Pinteraction: 0.28). In joint models, with MS-stable/MSI-low and normal BMI as the reference group, risk of death was higher for MS-stable/MSI-low and obese BMI (HR, 1.32; P value: 0.0002), not statistically significantly lower for MSI-high and normal BMI (HR, 0.86; P value: 0.29), and approximately the same for MSI-high and obese BMI (HR, 1.00; P value: 0.98). Conclusions: High prediagnosis BMI was associated with increased mortality; this association was consistent across participant subgroups, including strata of tumor molecular phenotype. Impact: High BMI may attenuate the survival benefit otherwise observed with MSI-high tumors. Cancer Epidemiol Biomarkers Prev; 24(8); 1229–38. ©2015 AACR.

Almost 50% of trauma‐related fatalities within the first 24 hours of injury are related to hemorrhage. Improved survival in severely injured patients has been demonstrated when massive transfusion protocols are rapidly invoked as part of a therapeutic approach known as damage control resuscitation (DCR). DCR incorporates the early use of plasma to prevent or correct trauma‐induced coagulopathy. DCR often requires the transfusion of plasma before determination of the recipient's ABO group. Historically, group AB plasma has been considered the “universal donor” plasma product. At our facility, the number of AB plasma products produced on an annual basis was found to be inadequate to support the trauma service's DCR program. A joint decision was made by the transfusion medicine and trauma services to provide group A thawed plasma (TP) for in‐hospital and prehospital DCR protocols. A description of the implementation of group A TP into the DCR program is provided as well as outcome data pertaining to the use of TP in trauma patients.

BACKGROUNDThere is little research regarding characteristics of effective continuing medical education (CME) presentations in hospital medicine (HM). Therefore, we sought to identify associations between validated CME teaching effectiveness scores and characteristics of CME presentations in the field of HM.DESIGN/SETTINGThis was a cross‐sectional study of participants and didactic presentations from a national HM CME course in 2014.MEASUREMENTSParticipants provided CME teaching effectiveness (CMETE) ratings using an instrument with known validity evidence. Overall CMETE scores (5‐point scale: 1 = strongly disagree; 5 = strongly agree) were averaged for each presentation, and associations between scores and presentation characteristics were determined using the Kruskal‐Wallis test. The threshold for statistical significance was set at P < 0.05.RESULTSA total of 277 out of 368 participants (75.3%) completed evaluations for the 32 presentations. CMETE scores (mean [standard deviation]) were significantly associated with the use of audience response (4.64 [0.16]) versus no audience response (4.49 [0.16]; P = 0.01), longer presentations (≥30 minutes: 4.67 [0.13] vs <30 minutes: 4.51 [0.18]; P = 0.02), and larger number of slides (≥50: 4.66 [0.17] vs <50: 4.55 [0.17]; P = 0.04). There were no significant associations between CMETE scores and use of clinical cases, defined goals, or summary slides.CONCLUSIONSTo our knowledge, this is the first study regarding associations between validated teaching effectiveness scores and characteristics of effective CME presentations in HM. Our findings, which support previous research in other fields, indicate that CME presentations may be improved by increasing interactivity through the use of audience response systems and allowing longer presentations. Journal of Hospital Medicine 2015;10:569–573. © 2015 Society of Hospital Medicine

The objective of this analysis of 4500 inpatients was to identify the experience and expectations of 18–35 year olds regarding chaplain visitation and to compare results with data from older adults. 71% of young adults reported wanting to be visited by a chaplain; 45.5% were visited; 68% indicated that this was important. Young adults value chaplains' role as a sign of God's care and presence (77.4%), in providing support for family (73.6%), being present during times of anxiety (66.0%), and praying/reading scripture with them (62.3%). Results were similar to older respondents, but young adults were more likely to value ethical counsel from chaplains (58.5% vs. 38.2%). This study provides clinically relevant information and suggestions for further research.

Abstract Background: Racial disparities in breast cancer (BC) outcomes are well-documented. As guidelines for BC screening change, it is particularly important that women have accurate knowledge of risk factors in order to meaningfully participate in screening decisions. We examined knowledge of risk factors for BC among a nationally representative sample of women for whom mammography screening is routinely recommended. Method: Non-Hispanic black (B), non-Hispanic white (W), Hispanic (H), and women of other/multiple races (O) were surveyed using a probability-based web panel weighted to match the known U.S. population of females aged 40-74 years. A total of 17 items were presented in English or Spanish; response options included: “does not put you at increased risk,” “puts you at a small increased risk,” and “puts you at a large increased risk.” For scoring, the latter two categories were combined to reflect “increased risk.” Items included 9 established risk factors: having mammographically dense breasts, first-degree relative diagnosed with BC, second-degree relative diagnosed with BC, drinking alcohol in excess, history of a breast biopsy, having a first child after age 30, use of hormone therapy for postmenopausal symptoms, BRCA gene mutation, late onset of menopause; 5 protective factors: menarche after age 15, having children, breastfeeding, having a diet rich in fruits and vegetables, exercising or being active; one factor with no clear association: being a smoker (correct response was no increased risk); and 2 distractors (beliefs for which there is no evidence, correct response was no increased risk): using antiperspirant/talc under your arms, experiencing injury/trauma to the breast. The survey cooperation rate was 65% (1,506 responders out of 2,311). Items were scored correct if the respondent's answer matched the actual risk profile (either does/does not put you at increased risk). Percent correct was calculated for each item overall and by race/ethnicity. All reported percentages and analyses are weighted to be nationally representative and compared for differences based on race/ethnicity using logistic regression models. P-values represent differences in percent correct between the racial/ethnic groups. Results: Knowledge of risk factors varied across items (range &gt;90% to 20% correct). Percent correct was high overall for classifying a first-degree relative with BC as a risk factor and differed by race/ethnicity, with 86% B, 98% W, 92% H and 92% O recognizing this risk factor (p&lt;0.001); similar percentages were observed for second-degree relatives (p=0.003). Lower knowledge overall was observed for risk factors including BRCA mutation (25% B, 44% W, 24% H, 38% O, p=0.002), later onset of menopause (41% B, 38% W, 42% H, 37% O, p=0.92), and having the first child after age 30 (39% B, 41% W, 38% H, 33% O, p=0.53). Having mammographically dense breasts is one of the strongest risk factors for BC, however knowledge of this was only moderate and did not differ by race/ethnicity (61% B, 54% W, 56% H, 52% O, p=0.64). Relative to risk factors, knowledge of protective factors was generally higher; only correct classification of fruits/vegetables as a protective factor differed by race/ethnicity (84% B, 93% W, 88% H, 89% O, p=0.03). Most women correctly responded that use of antiperspirant/talc does not increase risk of BC, however 60% of H women incorrectly classified injury/trauma to the breast as a risk factor, relative to 50% B, 41% W, and 40% O (p=0.02). Conclusions: Among U.S. women, there is wide variation in knowledge across several established BC risk factors and only moderate knowledge of breast density as an important risk factor. Differences in knowledge by race/ethnicity for several risk factors highlight the need for targeted education. Citation Format: Carmen Radecki Breitkopf, Deborah J. Rhodes, Sarah M. Jenkins, Jeanette Y. Ziegenfuss, Celine M. Vachon. Racial and ethnic differences in knowledge of risk factors for breast cancer: Findings from a recent national survey. [abstract]. In: Proceedings of the Sixth AACR Conference: The Science of Cancer Health Disparities; Dec 6–9, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2014;23(11 Suppl):Abstract nr B42. doi:10.1158/1538-7755.DISP13-B42

Abstract Background: Physical activity is associated with a lower incidence of colorectal cancer; however, the relationship of physical activity with colorectal cancer survival is not yet clear. We evaluated the association between prediagnostic physical activity and colorectal cancer survival, overall and accounting for tumor markers associated with colorectal cancer survival: BRAF and KRAS mutation status and microsatellite instability (MSI) status. Methods: Participants were 20- to 74-year-old colorectal cancer patients diagnosed between 1998 and 2007 from the population-based Seattle Colon Cancer Family Registry (S-CCFR). Self-reported physical activity in the years preceding colorectal cancer diagnosis was summarized as average metabolic equivalent task hours per week (MET-h/wk; n = 1,309). Somatic BRAF and KRAS mutations and MSI status were evaluated on a subset of patients (n = 1043). Cox regression was used to estimate HRs and 95% confidence intervals (CI) for overall and disease-specific survival after adjusting for relevant confounders. Stratified analyses were conducted across categories of BRAF, KRAS, and MSI, as well as tumor stage and site. Results: Higher prediagnostic recreational physical activity was associated with significantly more favorable overall survival (HR for highest vs. lowest category, 0.70; 95% CI, 0.52–0.96); associations were similar for colorectal cancer–specific survival. Results consistently indicated a favorable association with physical activity across strata defined by tumor characteristics. Conclusion: Individuals who were physically active before colorectal cancer diagnosis experienced better survival than those who were inactive or minimally active. Impact: Our results support existing physical activity recommendations for colorectal cancer patients and suggest that the beneficial effect of activity is not specific to a particular molecular phenotype of colorectal cancer. Cancer Epidemiol Biomarkers Prev; 24(7); 1130–7. ©2015 AACR.

Abstract Background: High body mass index (BMI) is consistently linked to increased risk of colorectal cancer for men, whereas the association is less clear for women. As risk estimates from observational studies may be biased and/or confounded, we conducted a Mendelian randomization study to estimate the causal association between BMI and colorectal cancer. Methods: We used data from 10,226 colorectal cancer cases and 10,286 controls of European ancestry. The Mendelian randomization analysis used a weighted genetic risk score, derived from 77 genome-wide association study–identified variants associated with higher BMI, as an instrumental variable (IV). We compared the IV odds ratio (IV-OR) with the OR obtained using a conventional covariate-adjusted analysis. Results: Individuals carrying greater numbers of BMI-increasing alleles had higher colorectal cancer risk [per weighted allele OR, 1.31; 95% confidence interval (CI), 1.10–1.57]. Our IV estimation results support the hypothesis that genetically influenced BMI is directly associated with risk for colorectal cancer (IV-OR per 5 kg/m2, 1.50; 95% CI, 1.13–2.01). In the sex-specific IV analyses higher BMI was associated with higher risk of colorectal cancer among women (IV-OR per 5 kg/m2, 1.82; 95% CI, 1.26–2.61). For men, genetically influenced BMI was not associated with colorectal cancer (IV-OR per 5 kg/m2, 1.18; 95% CI, 0.73–1.92). Conclusions: High BMI was associated with increased colorectal cancer risk for women. Whether abdominal obesity, rather than overall obesity, is a more important risk factor for men requires further investigation. Impact: Overall, conventional epidemiologic and Mendelian randomization studies suggest a strong association between obesity and the risk of colorectal cancer. Cancer Epidemiol Biomarkers Prev; 24(7); 1024–31. ©2015 AACR.

Abstract To identify genetic variants that contribute to colorectal cancer (CRC) susceptibility, we performed a meta-analysis of two genome-wide association studies in 2,627 cases and 3,797 controls of Japanese ancestry and 1,894 cases and 4,703 controls of African ancestry, followed by a replication of genome-wide statistically significant associations (P &lt; 5E-8) in 16,823 cases and 18,211 controls of European ancestry. This study revealed a new pan-ethnic CRC risk locus at 10q25 (rs12241008, intronic to VTI1A; P=1.5E-9), providing additional insight into the etiology of CRC and highlighting the value of association mapping in diverse populations. Citation Format: Hansong Wang, Terrilea Burnett, Suminori Kono, Christopher Haiman, Motoki Iwasaki, Lynne Wilkens, Lenora Loo, David Van Den Berg, Laurence Kolonel, Brian Henderson, Temitope Keku, Robert Sandler, Lisa Signorello, William Blot, Polly Newcomb, Mala Pande, Christopher Amos, Dee West, Stéphane Bézieau, Sonja Berndt, Brent Zanke, Li Hsu, Noralane Lindor, Robert Haile, John Hopper, Mark Jenkins, Steven Gallinger, Graham Casey, Stephanie Stenzel, Fredrick Schumacher, Ulrike Peters, Stephen Gruber, Shoichiro Tsugane, Dan Stram, Loic Le Marchand. Transethnic genome-wide association study of colorectal cancer identifies a new susceptibility locus in VTI1A. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-282. doi:10.1158/1538-7445.AM2014-LB-282

Abstract Background: Specific germline alterations within the TERT, EGFR, CCDC26, CDKN2A/B, PHLDB1, TP53 and RTEL1 regions are associated with development of glioma. While some of these germline variants are associated with all gliomas (e.g. rs2736100 in TERT), others are associated with a specific morphologic and/or molecular subtype. For example, the RTEL1 region variants are associated with primary glioblastoma and rs55705857 in CCDC26 is associated with 1p/19q co-deleted oligodendrogliomas and with IDH mutant astrocytic gliomas. We hypothesized that germline variants in these regions will be associated with other molecular subtypes. The Cancer Genome Atlas (TCGA) and other groups have described molecular subtypes of glioma based on acquired somatic mutation patterns. Herein, we grouped glioma patients into mutation-based molecular subgroups based on three molecular alterations and determined if germline polymorphisms are associated with these mutation-based molecular subtypes. Methods: Five molecular subtypes were defined based on combinations of the following molecular alterations: TERT promoter mutation (TERTmut vs. TERTwt), IDH1/2 mutation (IDH mut vs. IDH wt) and 1p/19q co-deletion (1p19qcodel vs. 1p19q noncodel). Germline single nucleotide polymorphisms (SNPs) were evaluated by custom Illumina array analysis of blood-derived DNA and 1K genome imputation. Results: One hundred ninety-nine gliomas (24 oligodendrogliomas, 59 mixed oligoastrocytomas, 41 grade 2-3 astrocytomas and 75 glioblastomas) had both SNP data and mutation data available in order to assign them into the five molecular subgroups. The prevalence of each of the molecular subtypes was as follows: TERTmut/IDHmut/1p19qcodel (20%), TERTmut/IDHmut/1p19qnoncodel (5%), TERTmut/IDHwt/1p19qnoncodel (32%), TERTwt/IDHmut/1p19qnondel (35%) and TERTwt/IDHwt/1p19qnoncodel (8%). The TERT SNP (rs2736100) was protective for TERTmut/IDHmut/1p19qnoncodel and TERTwt/IDHmut/1p19qnoncodel gliomas. The CCDC26 SNP (rs55705857) was strongly associated with the risk of developing TERTmut/IDHmut/1p19qcodel and TERTwt/IDHmut/1p19qnoncodel gliomas. The TP53 SNP (rs7837822) was strongly associated with risk of developing TERTmut/IDHmut/1p19qnoncodel and TERTwt/IDHmut/1p19qnoncodel gliomas. Interestingly, while one RTEL1 region SNP (rs6062297) was strongly associated with glioma risk, RTEL1 SNPs rs6010620 and rs2297440 were protective for the development of TERTmut/IDHwt/1p19qnoncodel gliomas. We are currently in the process of validating these results using the TCGA glioblastoma and low grade glioma data. Conclusions: Glioma patients can be meaningfully classified according to their acquired mutation subtype. Importantly, our results suggest that there are significant associations between germline polymorphisms and mutation-based glioma molecular subtypes. Citation Format: Jeanette E. Eckel-Passow, Thomas M. Kollmeyer, Gobinda Sarkar, Anisha Chada, Paul A. Decker, Matthew L. Kosel, Alissa A. Caron, Hugues Sicotte, Kannabiran Nandakumar, Naresh Prodduturi, Brian P. O'Neill, Daniel H. Lachance, Robert B. Jenkins. The association of glioma germline risk SNPs with mutation-based molecular subgroups. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4714. doi:10.1158/1538-7445.AM2014-4714