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Genome-wide meta-analysis identifies five new susceptibility loci for pancreatic cancer

Klein, Alison P; Wolpin, Brian M; Risch, Harvey A; Stolzenberg-Solomon, Rachael Z; Mocci, Evelina; Zhang, Mingfeng; Canzian, Federico; Childs, Erica J; Hoskins, Jason W; Jermusyk, Ashley; Zhong, Jun; Chen, Fei; Albanes, Demetrius; Andreotti, Gabriella; Arslan, Alan A; Babic, Ana; Bamlet, William R; Beane-Freeman, Laura; Berndt, Sonja I; Blackford, Amanda; Borges, Michael; Borgida, Ayelet; Bracci, Paige M; Brais, Lauren; Brennan, Paul; Brenner, Hermann; Bueno-de-Mesquita, Bas; Buring, Julie; Campa, Daniele; Capurso, Gabriele; Cavestro, Giulia Martina; Chaffee, Kari G; Chung, Charles C; Cleary, Sean; Cotterchio, Michelle; Dijk, Frederike; Duell, Eric J; Foretova, Lenka; Fuchs, Charles; Funel, Niccola; Gallinger, Steven; M Gaziano, J Michael; Gazouli, Maria; Giles, Graham G; Giovannucci, Edward; Goggins, Michael; Goodman, Gary E; Goodman, Phyllis J; Hackert, Thilo; Haiman, Christopher; Hartge, Patricia; Hasan, Manal; Hegyi, Peter; Helzlsouer, Kathy J; Herman, Joseph; Holcatova, Ivana; Holly, Elizabeth A; Hoover, Robert; Hung, Rayjean J; Jacobs, Eric J; Jamroziak, Krzysztof; Janout, Vladimir; Kaaks, Rudolf; Khaw, Kay-Tee; Klein, Eric A; Kogevinas, Manolis; Kooperberg, Charles; Kulke, Matthew H; Kupcinskas, Juozas; Kurtz, Robert J; Laheru, Daniel; Landi, Stefano; Lawlor, Rita T; Lee, I-Min; LeMarchand, Loic; Lu, Lingeng; Malats, Núria; Mambrini, Andrea; Mannisto, Satu; Milne, Roger L; Mohelníková-Duchoňová, Beatrice; Neale, Rachel E; Neoptolemos, John P; Oberg, Ann L; Olson, Sara H; Orlow, Irene; Pasquali, Claudio; Patel, Alpa V; Peters, Ulrike; Pezzilli, Raffaele; Porta, Miquel; Real, Francisco X; Rothman, Nathaniel; Scelo, Ghislaine; Sesso, Howard D; Severi, Gianluca; Shu, Xiao-Ou; Silverman, Debra; Smith, Jill P; Soucek, Pavel; Sund, Malin; Talar-Wojnarowska, Renata; Tavano, Francesca; Thornquist, Mark D; Tobias, Geoffrey S; Van Den Eeden, Stephen K; Vashist, Yogesh; Visvanathan, Kala; Vodicka, Pavel; Wactawski-Wende, Jean; Wang, Zhaoming; Wentzensen, Nicolas; White, Emily; Yu, Herbert; Yu, Kai; Zeleniuch-Jacquotte, Anne; Zheng, Wei; Kraft, Peter; Li, Donghui; Chanock, Stephen; Obazee, Ofure; Petersen, Gloria M; Amundadottir, Laufey T
In 2020, 146,063 deaths due to pancreatic cancer are estimated to occur in Europe and the United States combined. To identify common susceptibility alleles, we performed the largest pancreatic cancer GWAS to date, including 9040 patients and 12,496 controls of European ancestry from the Pancreatic Cancer Cohort Consortium (PanScan) and the Pancreatic Cancer Case-Control Consortium (PanC4). Here, we find significant evidence of a novel association at rs78417682 (7p12/TNS3, P = 4.35 × 10-8). Replication of 10 promising signals in up to 2737 patients and 4752 controls from the PANcreatic Disease ReseArch (PANDoRA) consortium yields new genome-wide significant loci: rs13303010 at 1p36.33 (NOC2L, P = 8.36 × 10-14), rs2941471 at 8q21.11 (HNF4G, P = 6.60 × 10-10), rs4795218 at 17q12 (HNF1B, P = 1.32 × 10-8), and rs1517037 at 18q21.32 (GRP, P = 3.28 × 10-8). rs78417682 is not statistically significantly associated with pancreatic cancer in PANDoRA. Expression quantitative trait locus analysis in three independent pancreatic data sets provides molecular support of NOC2L as a pancreatic cancer susceptibility gene.
PMCID:5805680
PMID: 29422604
ISSN: 2041-1723
CID: 2947002

Modernizing the World Health Organization List of Essential Medicines for Preventing and Controlling Cardiovascular Diseases

Kishore, Sandeep P; Blank, Evan; Heller, David J; Patel, Amisha; Peters, Alexander; Price, Matthew; Vidula, Mahesh; Fuster, Valentin; Onuma, Oyere; Huffman, Mark D; Vedanthan, Rajesh
The World Health Organization (WHO) Model List of Essential Medicines (EML) is a key tool for improving global access to medicines for all conditions, including cardiovascular diseases (CVDs). The WHO EML is used by member states to determine their national essential medicine lists and policies and to guide procurement of medicines in the public sector. Here, we describe our efforts to modernize the EML for global CVD prevention and control. We review the recent history of applications to add, delete, and change indications for CVD medicines, with the aim of aligning the list with contemporary clinical practice guidelines. We have identified 4 issues that affect decisions for the EML and may strengthen future applications: 1) cost and cost-effectiveness; 2) presence in clinical practice guidelines; 3) feedback loops; and 4) community engagement. We share our lessons to stimulate others in the global CVD community to embark on similar efforts.
PMID: 29406862
ISSN: 1558-3597
CID: 3240252

Overweight or obese BMI is associated with earlier, but not later survival after common acute illnesses

Prescott, Hallie C; Chang, Virginia W
BACKGROUND:Obesity has been associated with improved short-term mortality following common acute illness, but its relationship with longer-term mortality is unknown. METHODS:Observational study of U.S. Health and Retirement Study (HRS) participants with federal health insurance (fee-for-service Medicare) coverage, hospitalized with congestive heart failure (N = 4287), pneumonia (N = 4182), or acute myocardial infarction (N = 2001), 1996-2012. Using cox proportional hazards models, we examined the association between overweight or obese BMI (BMI ≥ 25.0 kg/m2) and mortality to 5 years after hospital admission, adjusted for potential confounders measured at the same time as BMI, including age, race, sex, education, partnership status, income, wealth, and smoking status. Body mass index (BMI) was calculated from self-reported height and weight collected at the HRS survey prior to hospitalization (a median 1.1 year prior to hospitalization). The referent group was patients with a normal BMI (18.5 to < 25.0 kg/m2). RESULTS:Patients were a median of 79 years old (IQR 71-85 years). The majority of patients were overweight or obese: 60.3% hospitalized for heart failure, 51.5% for pneumonia, and 61.6% for acute myocardial infarction. Overweight or obese BMI was associated with lower mortality at 1 year after hospitalization for congestive heart failure, pneumonia, and acute myocardial infarction-with adjusted hazard ratios of 0.68 (95% CI 0.59-0.79), 0.74 (95% CI: 0.64-0.84), and 0.65 (95%CI: 0.53-0.80), respectively. Among participants who lived to one year, however, subsequent survival was similar between patients with normal versus overweight/obese BMI. CONCLUSIONS:In older Americans, overweight or obese BMI was associated with improved survival following hospitalization for congestive heart failure, pneumonia, and acute myocardial infarction. This association, however, is limited to the shorter-term. Conditional on surviving to one year, we did not observe a survival advantage associated with excess weight.
PMCID:5801673
PMID: 29409463
ISSN: 1471-2318
CID: 2947612

What is the Skill of Teaching? A New Framework of Teachers’ Social Emotional Cognition

Chapter by: Rodriguez, Vanessa; Mascio, Bryan
in: Transformative Pedagogies for Teacher Education: Moving Towards Critical Praxis in an Era of Change by Lopez, Ann E; Olan, Elsie L
Information Age Publishing
pp. -
ISBN: 9781641131070
CID: 5688632

No Evidence of Disease Activity in Natalizumab-Treated Patients with Early Relapsing-Remitting Multiple Sclerosis: A 2-Year Analysis of STRIVE [Meeting Abstract]

Perumal, Jai S.; Fox, Robert J.; Balabanov, Roumen; Makh, Shavy S.; Dong, Qunming; Balcer, Laura J.; Galetta, Steven; Hotermans, Christophe; Lee, Lily
ISI:000429034600060
ISSN: 1352-4585
CID: 3039252

Effect of Ocrelizumab on Visual Outcomes in Patients with Baseline Visual Impairment in the OPERA Studies in Relapsing Multiple Sclerosis [Meeting Abstract]

Balcer, Laura J.; Hauser, Stephen L.; Kappos, Ludwig; Leocani, Letizia; Saidha, Shiv; Julian, Laura; Pei, Jinglan; Comi, Giancarlo
ISI:000429034600037
ISSN: 1352-4585
CID: 3039282

Mobile Universal Lexicon Evaluation System (MULES) in MS: Evaluation of a New Visual Test of Rapid Picture Naming [Meeting Abstract]

Seay, Meagan; Akhand, Omar; Cobbs, Lucy; Hasanaj, Lisena; Amorapanth, Prin; Rizzo, John-Ross; Nolan, Rachel; Serrano, Liliana; Jordan, Barry; Rucker, Janet; Galetta, Steven; Balcer, Laura J.
ISI:000429034600043
ISSN: 1352-4585
CID: 3039272

The use of Twitter to facilitate sharing of clinical expertise in urology [Case Report]

Sternberg, Kevan M; Loeb, Stacy L; Canes, David; Donnelly, Laura; Tsai, Mitchell H
The use of social media in the urologic community is common and increasing. Although the potential benefits of platforms like Twitter have been described in the literature, the use of social media in the clinical context of Urology has not been explored.In this case report, we describe how we used Twitter to share ideas about the clinical management of a complex urologic patient. By posting a clinical scenario, a timely discussion was generated with global participation and expert suggestions. This knowledge was applied to the surgical management of a patient with positive clinical outcomes.The ability of Twitter to facilitate rapid communication with a wide network of contributors makes it a potentially useful tool for clinical decision making. Care must be taken to ensure patient confidentiality and caution used appropriately when evaluating the sources and content of the clinical information shared.
PMID: 28591771
ISSN: 1527-974x
CID: 4115652

Contralateral Prophylactic Mastectomy in Young Breast Cancer Patients: Is there a Difference Between Public and Private Hospitals? [Meeting Abstract]

Warnack, E.; Ma, S.; Schnabel, F.; Joseph, K.; Axelrod, D.; Dhage, S.
ISI:000431188600201
ISSN: 1068-9265
CID: 3113852

Characteristics of drug use among pregnant women in the United States: Opioid and non-opioid illegal drug use

Metz, Verena E; Brown, Qiana L; Martins, Silvia S; Palamar, Joseph J
BACKGROUND:The opioid epidemic in the US is affecting pregnant women and their offspring, with rising numbers of maternal and neonatal treatment episodes. The aim of this study was to characterize pregnant drug users in order to inform intervention strategies based on sociodemographic, mental health, and substance use characteristics. METHODS:Data on pregnant women aged 18-44 reporting past-year, nonmedical opioid use or use of non-opioid illegal drugs (other than marijuana) were analyzed from the National Survey on Drug Use and Health (2005-2014). Women (N = 818) were categorized into 3 groups: 1) use of opioids only (n = 281), 2) opioid-polydrug users (n = 241), and 3) other (non-opioid) illegal drug users (n = 296). Characteristics between the 3 groups of women were compared using bivariable analyses. RESULTS:Most women were non-Hispanic White (67.6%), had a high school diploma or less education (61.0%), a household income <$20,000/year (72.2%), and health insurance coverage (84.3%). No significant differences between the three groups were found regarding sociodemographic characteristics. Past-30-day marijuana use was less prevalent among opioid-only users (10.9%) compared to opioid-polydrug users (43.6%) and other pregnant illegal drug users (27.6%) (P < 0.001) and past-year drug/alcohol treatment was less prevalent among opioid-only users (6.3%) compared to opioid-polydrug users (20.3%) and other illegal drug users (8.3%) (P = 0.002). Opioid-only users also reported lower prevalence of past-year depression (P < 0.001) and anxiety (P = 0.039). CONCLUSIONS:Pregnant drug-using women were often of low socioeconomic status, with mental health and substance use patterns suggesting the need for targeted mental health/substance use screening and interventions before and during pregnancy, particularly for opioid-polydrug users.
PMCID:5803362
PMID: 29310077
ISSN: 1879-0046
CID: 2906562