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Primary melanoma histologic subtype (HS) impacts melanoma specific survival (MSS) and response to systemic therapy [Meeting Abstract]

Lattanzi, M; Lee, Y; Robinson, E M; Weiss, S A; Moran, U; Simpson, D; Shapiro, R L; Berman, R S; Pavlick, A C; Wilson, M; Kirchhoff, T; Zhong, J; Osman, I
Background: Unlike other solid tumors, the impact of primary HS on melanoma survival and response to systemic therapy is not well studied. Nodular melanoma (NM) has a worse prognosis than superficial spreading melanoma (SSM), which is usually attributed to thicker primary tumors. Herein, we examine the hypothesis that HS might have an impact on MSS independent of thickness and that NM and SSM exhibit different mutational landscapes that associate with response to checkpoint inhibitor immunotherapy (IT) and BRAF targeted therapy (TT) in the metastatic setting. Methods: Primary NM and SSM patients prospectively enrolled at NYU (2002 - 2016) were compared to the most recent SEER cohort (1973 - 2012) and analyzed with respect to MSS. Next-Generation Sequencing (NGS) was performed on a subset of matched tumor-germline pairs, allowing a comparison of the mutational landscape between NM and SSM. In the metastatic setting, survival analyses were used to compare outcomes and responses to treatment across HS. Results: The NYU cohort of 1,621 patients with either NM (n = 510) or SSM (n = 1,111) was representative of the analogous SEER cohort (21,339 NM, 97,169 SSM), with NM presenting as thicker, more ulcerated, and later stage (all p < 0.001). Among the NYU cohort, NM was found to have lower rates of TIL (p = 0.047), higher mitotic index (p < 0.001), and higher rates of NRAS mutation (p < 0.001). In multivariate Cox models, NM was a significant predictor of worse MSS, independent of thickness and stage (p = 0.01). NM had a significantly lower mutational burden across the exome (p < 0.001). Some of the most under-mutated genes noted in NM were NOTCH4, BCL2L12 and RPS6KA6 (all p < 0.01). Among patients treated with TT (n = 56), NM remained a significant predictor of worse MSS (p = 0.004). However, there was no difference in response to IT. Conclusions: NM and SSM show divergent mutational patterns which may contribute to their different clinical behaviors and responses to BRAF targeted therapy. More studies are needed to better understand the key molecular and cellular processes driving such differences. Integration of HS data into prospective clinical trial reporting is needed to better assess its impact on response to treatment
EMBASE:617435330
ISSN: 0732-183x
CID: 2651132

DSM-5 substance use disorders among adult primary care patients: Results from a multisite study

Wu, Li-Tzy; McNeely, Jennifer; Subramaniam, Geetha A; Brady, Kathleen T; Sharma, Gaurav; VanVeldhuisen, Paul; Zhu, He; Schwartz, Robert P
BACKGROUND: There are limited data about the extent of DSM-5 substance use disorders (SUDs) among primary care patients. METHODS: This study analyzed data from a multisite validation study of a substance use screening instrument conducted in a diverse sample of 2000 adults aged >/=18 years recruited from five primary care practices in four states. Prevalence and correlates of 12-month DSM-5 SUDs were examined. RESULTS: Overall, 75.5% of the sample used any substance, including alcohol (62.0%), tobacco (44.1%), or illicit drugs/nonmedical medications (27.9%) in the past 12 months (marijuana 20.8%, cocaine 7.3%, opioids 4.8%, sedatives 4.1%, heroin 3.9%). The prevalence of any 12-month SUD was 36.0% (mild disorder 14.2%, moderate/severe disorder 21.8%): tobacco 25.3% (mild 11.5%, moderate/severe 13.8%); alcohol 13.9% (mild 6.9%, moderate/severe 7.0%); and any illicit/nonmedical drug 14.0% (mild 4.0%, moderate/severe 10.0%). Among past 12-month users, a high proportion of tobacco or drug users met criteria for a disorder: tobacco use disorder 57.4% (26.1% mild, 31.3% moderate/severe) and any drug use disorder 50.2% (14.3% mild, 35.8% moderate/severe); a lower proportion of alcohol users (22.4%) met criteria for alcohol use disorder (11.1% mild, 11.3% moderate/severe). Over 80% of adults with opioid/heroin use disorder met criteria for a moderate/severe disorder. Younger ages, male sex, and low education were associated with increased odds of having SUD. CONCLUSION: These findings reveal the high prevalence of SUDs in primary care and underscore the need to identify and address them.
PMCID:5599360
PMID: 28753480
ISSN: 1879-0046
CID: 2652072

Pictograms, Units and Dosing Tools, and Parent Medication Errors: A Randomized Study

Yin, H Shonna; Parker, Ruth M; Sanders, Lee M; Mendelsohn, Alan; Dreyer, Benard P; Bailey, Stacy Cooper; Patel, Deesha A; Jimenez, Jessica J; Kim, Kwang-Youn A; Jacobson, Kara; Smith, Michelle C J; Hedlund, Laurie; Meyers, Nicole; McFadden, Terri; Wolf, Michael S
BACKGROUND AND OBJECTIVES: Poorly designed labels and dosing tools contribute to dosing errors. We examined the degree to which errors could be reduced with pictographic diagrams, milliliter-only units, and provision of tools more closely matched to prescribed volumes. METHODS: This study involved a randomized controlled experiment in 3 pediatric clinics. English- and Spanish-speaking parents (n = 491) of children 20% deviation), and large error (>2x dose). RESULTS: We found that 83.5% of parents made >/=1 dosing error (overdosing was present in 12.1% of errors) and 29.3% of parents made >/=1 large error (>2x dose). The greatest impact on errors resulted from the provision of tools more closely matched to prescribed dose volumes. For the 2-mL dose, the fewest errors were seen with the 5-mL syringe (5- vs 10-mL syringe: adjusted odds ratio [aOR] = 0.3 [95% confidence interval: 0.2-0.4]; cup versus 10-mL syringe: aOR = 7.5 [5.7-10.0]). For the 7.5-mL dose, the fewest errors were with the 10-mL syringe, which did not necessitate measurement of multiple instrument-fulls (5- vs 10-mL syringe: aOR = 4.0 [3.0-5.4]; cup versus 10-mL syringe: aOR = 2.1 [1.5-2.9]). Milliliter/teaspoon was associated with more errors than milliliter-only (aOR = 1.3 [1.05-1.6]). Parents who received text only (versus text and pictogram) instructions or milliliter/teaspoon (versus milliliter-only) labels and tools made more large errors (aOR = 1.9 [1.1-3.3], aOR = 2.5 [1.4-4.6], respectively). CONCLUSIONS: Provision of dosing tools more closely matched to prescribed dose volumes is an especially promising strategy for reducing pediatric dosing errors.
PMCID:5495522
PMID: 28759396
ISSN: 1098-4275
CID: 2652182

Electronic cigarette marketing tactics in mainland China

Jiang, Nan; Ho, Sai Yin; Lam, Tai Hing
PMID: 27071732
ISSN: 1468-3318
CID: 2645422

The relationship of waterpipe use with cigarette smoking susceptibility and nicotine dependence: A cross-sectional study among Hong Kong adolescents

Jiang, Nan; Ho, Sai Yin; Wang, Man Ping; Leung, Lok Tung; Lam, Tai Hing
INTRODUCTION: Waterpipe smoking has become increasingly popular in adolescents. We examined the association of waterpipe smoking with cigarette smoking susceptibility and nicotine dependence among adolescents in Hong Kong. METHODS: We analyzed the data of School-based Survey on Smoking among Students 2012/13 from a representative sample of 45,857 secondary school students (US grades 7-12) in Hong Kong. Among never cigarette smokers (n=37,740), we conducted chi-square test to compare cigarette smoking susceptibility by current (past 30-day) waterpipe smoking status, and used multivariate logistic regression to examine the association between current waterpipe smoking and cigarette smoking susceptibility controlling for age, sex, peer cigarette smoking, and living with a cigarette smoker. Then we conducted chi-square test and multivariate logistic regression among current cigarette smokers (n=1694) to examine the relationship of current waterpipe smoking with two nicotine dependence outcomes, including heavier smoking (>/=5 cigarettes/day) and first cigarette within 30min of waking, controlling for demographics and the number of smoking days in the past 30days. RESULTS: Among never cigarette smokers, current waterpipe use was associated with cigarette smoking susceptibility (adjusted odds ratio [AOR]=3.58, 95% confidence interval [CI]: 1.61-7.97). Of current cigarette smokers, waterpipe use was associated with heavier smoking (AOR=1.56, 95% CI: 1.00-2.43) and first cigarette within 30min of waking (AOR=2.08, 95% CI: 1.35-3.19). CONCLUSIONS: Surveillance, prevention, and intervention programs should address waterpipe use in addition to cigarette smoking. Educational programs need to inform youth about the harmful and addictive effects of waterpipe smoking. Public health campaigns deglamourizing waterpipe use may help reduce waterpipe smoking among youth.
PMID: 27608324
ISSN: 1873-6327
CID: 2645392

Smoke-Free Laws and Hazardous Drinking: A Cross-Sectional Study among U.S. Adults

Jiang, Nan; Gonzalez, Mariaelena; Ling, Pamela M; Young-Wolff, Kelly C; Glantz, Stanton A
Tobacco and alcohol use are strongly associated. This cross-sectional study examined the relationship of smoke-free law coverage and smoke-free bar law coverage with hazardous drinking behaviors among a representative sample of U.S. adult drinkers (n = 17,057). We merged 2009 National Health Interview Survey data, American Nonsmokers' Rights Foundation U.S. Tobacco Control Laws Database, and Census Population Estimates. Hazardous drinking outcomes included heavy drinking (>14 drinks/week for men; >7 drinks/week for women) and binge drinking (>/=5 drinks on one or more days during past year). Chi-square tests compared hazardous drinking by sociodemographic factors. Multivariable logistic regression models were used to examine if smoke-free law and bar law coverages were associated with hazardous drinking, controlling for sociodemographics and smoking status. Subset analyses were conducted among drinkers who also smoked (n = 4074) to assess the association between law coverages and hazardous drinking. Among all drinkers, smoke-free law coverage was not associated with heavy drinking (adjusted odds ratio (AOR) = 1.22, 95% confidence interval (CI) = 0.99-1.50) or binge drinking (AOR = 1.09, 95% CI = 0.93-1.26). Smoke-free bar law coverage was also found to be unrelated to hazardous drinking. Similar results were found among those drinkers who smoked. Findings suggest that smoke-free laws and bar laws are not associated with elevated risk for alcohol-related health issues.
PMCID:5409613
PMID: 28406443
ISSN: 1660-4601
CID: 2645312

Examining an Executive Function Battery for Use with Preschool Children with Disabilities

Kuhn, Laura J; Willoughby, Michael T; Blair, Clancy B; McKinnon, Rachel
Performance-based assessments of EF for use with young children who have or are at risk for disabilities are lacking. The current study investigates the use of a computerized battery for children with subclinical behaviors (N = 846) across a variety of developmental disabilities and evaluates practical information about feasibility of task administration. Results reveal that children with disabilities performed similarly to their typically developing peers across a variety of metrics for evaluating the battery, ranging from percent correct scores to administrator quality ratings. Thus, the battery may be considered an easy-to-administer, performance-based assessment tool in which children with disabilities do not perform systemically worse than typically developing peers.
PMID: 28577276
ISSN: 1573-3432
CID: 2638862

Rapid sideline performance meets outpatient clinic: Results from a multidisciplinary concussion center registry

Kyle Harrold, G; Hasanaj, Lisena; Moehringer, Nicholas; Zhang, Isis; Nolan, Rachel; Serrano, Liliana; Raynowska, Jenelle; Rucker, Janet C; Flanagan, Steven R; Cardone, Dennis; Galetta, Steven L; Balcer, Laura J
OBJECTIVE: This study investigated the utility of sideline concussion tests, including components of the Sports Concussion Assessment Tool, 3rd Edition (SCAT3) and the King-Devick (K-D), a vision-based test of rapid number naming, in an outpatient, multidisciplinary concussion center treating patients with both sports-related and non-sports related concussions. The ability of these tests to predict clinical outcomes based on the scores at the initial visit was evaluated. METHODS: Scores for components of the SCAT3 and the K-D were fit into regression models accounting for age, gender, and sport/non-sport etiology in order to predict clinical outcome measures including total number of visits to the concussion center, whether the patient reached a SCAT3 symptom severity score
PMID: 28716270
ISSN: 1878-5883
CID: 2639932

Global Burden of Hypertension and Systolic Blood Pressure of at Least 110 to 115 mm Hg, 1990-2015

Forouzanfar, Mohammad H; Liu, Patrick; Roth, Gregory A; Ng, Marie; Biryukov, Stan; Marczak, Laurie; Alexander, Lily; Estep, Kara; Hassen Abate, Kalkidan; Akinyemiju, Tomi F; Ali, Raghib; Alvis-Guzman, Nelson; Azzopardi, Peter; Banerjee, Amitava; Barnighausen, Till; Basu, Arindam; Bekele, Tolesa; Bennett, Derrick A; Biadgilign, Sibhatu; Catala-Lopez, Ferran; Feigin, Valery L; Fernandes, Joao C; Fischer, Florian; Gebru, Alemseged Aregay; Gona, Philimon; Gupta, Rajeev; Hankey, Graeme J; Jonas, Jost B; Judd, Suzanne E; Khang, Young-Ho; Khosravi, Ardeshir; Kim, Yun Jin; Kimokoti, Ruth W; Kokubo, Yoshihiro; Kolte, Dhaval; Lopez, Alan; Lotufo, Paulo A; Malekzadeh, Reza; Melaku, Yohannes Adama; Mensah, George A; Misganaw, Awoke; Mokdad, Ali H; Moran, Andrew E; Nawaz, Haseeb; Neal, Bruce; Ngalesoni, Frida Namnyak; Ohkubo, Takayoshi; Pourmalek, Farshad; Rafay, Anwar; Rai, Rajesh Kumar; Rojas-Rueda, David; Sampson, Uchechukwu K; Santos, Itamar S; Sawhney, Monika; Schutte, Aletta E; Sepanlou, Sadaf G; Shifa, Girma Temam; Shiue, Ivy; Tedla, Bemnet Amare; Thrift, Amanda G; Tonelli, Marcello; Truelsen, Thomas; Tsilimparis, Nikolaos; Ukwaja, Kingsley Nnanna; Uthman, Olalekan A; Vasankari, Tommi; Venketasubramanian, Narayanaswamy; Vlassov, Vasiliy Victorovich; Vos, Theo; Westerman, Ronny; Yan, Lijing L; Yano, Yuichiro; Yonemoto, Naohiro; Zaki, Maysaa El Sayed; Murray, Christopher J L
Importance: Elevated systolic blood (SBP) pressure is a leading global health risk. Quantifying the levels of SBP is important to guide prevention policies and interventions. Objective: To estimate the association between SBP of at least 110 to 115 mm Hg and SBP of 140 mm Hg or higher and the burden of different causes of death and disability by age and sex for 195 countries and territories, 1990-2015. Design: A comparative risk assessment of health loss related to SBP. Estimated distribution of SBP was based on 844 studies from 154 countries (published 1980-2015) of 8.69 million participants. Spatiotemporal Gaussian process regression was used to generate estimates of mean SBP and adjusted variance for each age, sex, country, and year. Diseases with sufficient evidence for a causal relationship with high SBP (eg, ischemic heart disease, ischemic stroke, and hemorrhagic stroke) were included in the primary analysis. Main Outcomes and Measures: Mean SBP level, cause-specific deaths, and health burden related to SBP (>/=110-115 mm Hg and also >/=140 mm Hg) by age, sex, country, and year. Results: Between 1990-2015, the rate of SBP of at least 110 to 115 mm Hg increased from 73119 (95% uncertainty interval [UI], 67949-78241) to 81373 (95% UI, 76814-85770) per 100000, and SBP of 140 mm Hg or higher increased from 17307 (95% UI, 17117-17492) to 20526 (95% UI, 20283-20746) per 100000. The estimated annual death rate per 100000 associated with SBP of at least 110 to 115 mm Hg increased from 135.6 (95% UI, 122.4-148.1) to 145.2 (95% UI 130.3-159.9) and the rate for SBP of 140 mm Hg or higher increased from 97.9 (95% UI, 87.5-108.1) to 106.3 (95% UI, 94.6-118.1). For loss of DALYs associated with systolic blood pressure of 140 mm Hg or higher, the loss increased from 95.9 million (95% uncertainty interval [UI], 87.0-104.9 million) to 143.0 million (95% UI, 130.2-157.0 million) [corrected], and for SBP of 140 mm Hg or higher, the loss increased from 5.2 million (95% UI, 4.6-5.7 million) to 7.8 million (95% UI, 7.0-8.7 million). The largest numbers of SBP-related deaths were caused by ischemic heart disease (4.9 million [95% UI, 4.0-5.7 million]; 54.5%), hemorrhagic stroke (2.0 million [95% UI, 1.6-2.3 million]; 58.3%), and ischemic stroke (1.5 million [95% UI, 1.2-1.8 million]; 50.0%). In 2015, China, India, Russia, Indonesia, and the United States accounted for more than half of the global DALYs related to SBP of at least 110 to 115 mm Hg. Conclusions and Relevance: In international surveys, although there is uncertainty in some estimates, the rate of elevated SBP (>/=110-115 and >/=140 mm Hg) increased substantially between 1990 and 2015, and DALYs and deaths associated with elevated SBP also increased. Projections based on this sample suggest that in 2015, an estimated 3.5 billion adults had SBP of at least 110 to 115 mm Hg and 874 million adults had SBP of 140 mm Hg or higher.
PMID: 28097354
ISSN: 1538-3598
CID: 2642012

Diagnosis and management of dementia with Lewy bodies: Fourth consensus report of the DLB Consortium

McKeith, Ian G; Boeve, Bradley F; Dickson, Dennis W; Halliday, Glenda; Taylor, John-Paul; Weintraub, Daniel; Aarsland, Dag; Galvin, James; Attems, Johannes; Ballard, Clive G; Bayston, Ashley; Beach, Thomas G; Blanc, Frederic; Bohnen, Nicolaas; Bonanni, Laura; Bras, Jose; Brundin, Patrik; Burn, David; Chen-Plotkin, Alice; Duda, John E; El-Agnaf, Omar; Feldman, Howard; Ferman, Tanis J; Ffytche, Dominic; Fujishiro, Hiroshige; Galasko, Douglas; Goldman, Jennifer G; Gomperts, Stephen N; Graff-Radford, Neill R; Honig, Lawrence S; Iranzo, Alex; Kantarci, Kejal; Kaufer, Daniel; Kukull, Walter; Lee, Virginia M Y; Leverenz, James B; Lewis, Simon; Lippa, Carol; Lunde, Angela; Masellis, Mario; Masliah, Eliezer; McLean, Pamela; Mollenhauer, Brit; Montine, Thomas J; Moreno, Emilio; Mori, Etsuro; Murray, Melissa; O'Brien, John T; Orimo, Sotoshi; Postuma, Ronald B; Ramaswamy, Shankar; Ross, Owen A; Salmon, David P; Singleton, Andrew; Taylor, Angela; Thomas, Alan; Tiraboschi, Pietro; Toledo, Jon B; Trojanowski, John Q; Tsuang, Debby; Walker, Zuzana; Yamada, Masahito; Kosaka, Kenji
The Dementia with Lewy Bodies (DLB) Consortium has refined its recommendations about the clinical and pathologic diagnosis of DLB, updating the previous report, which has been in widespread use for the last decade. The revised DLB consensus criteria now distinguish clearly between clinical features and diagnostic biomarkers, and give guidance about optimal methods to establish and interpret these. Substantial new information has been incorporated about previously reported aspects of DLB, with increased diagnostic weighting given to REM sleep behavior disorder and 123iodine-metaiodobenzylguanidine (MIBG) myocardial scintigraphy. The diagnostic role of other neuroimaging, electrophysiologic, and laboratory investigations is also described. Minor modifications to pathologic methods and criteria are recommended to take account of Alzheimer disease neuropathologic change, to add previously omitted Lewy-related pathology categories, and to include assessments for substantia nigra neuronal loss. Recommendations about clinical management are largely based upon expert opinion since randomized controlled trials in DLB are few. Substantial progress has been made since the previous report in the detection and recognition of DLB as a common and important clinical disorder. During that period it has been incorporated into DSM-5, as major neurocognitive disorder with Lewy bodies. There remains a pressing need to understand the underlying neurobiology and pathophysiology of DLB, to develop and deliver clinical trials with both symptomatic and disease-modifying agents, and to help patients and carers worldwide to inform themselves about the disease, its prognosis, best available treatments, ongoing research, and how to get adequate support.
PMCID:5496518
PMID: 28592453
ISSN: 1526-632x
CID: 2630922