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Garakani A.,New Hill | Jaffe R.J.,New York | Welch A.K.,New York | Protin C.A.,Pennsylvania | Bryson E.O.,New York
American Journal on Addictions | Year: 2016

Background/Objectives: Nitrous oxide (N2O) is known to have abuse potential, although debate regarding the toxic effects of such abuse continues. Our objective was to review the case literature and present the neurologic, psychiatric and medical consequences of N2O abuse. Methods: A systematic literature review was completed for case reports using keywords "nitrous oxide" with "abuse/abusing" or "misuse/misusing" or "overuse/overusing" or "addiction." Non-English-language cases and cases not involving direct toxic effects of N2O were excluded as were commentaries or personal essays. Clinical presentation, frequency of N2O abuse, laboratory studies, imaging, ancillary tests, treatments and outcomes were collected from case reports. Results: Our review returned 335 Pubmed, 204 Web of Science, 73 PsycINFO, 6 CINAHL, 55 EMBASE and 0 Grey Literature results, and after exclusion and removal of duplicates, 91 individual cases across 77 publications were included. There were also 11 publications reporting 29 cases of death related to N2O abuse. The majority of cases (N=72) reported neurologic sequelae including myeloneuropathy and subacute combined degeneration, commonly (N=39) with neuroimaging changes. Psychiatric (N=11) effects included psychosis while other medical effects (N=8) included pneumomediastinum and frostbite. Across all cases N2O abuse was correlated with low or low-normal Vitamin B12 (cyanocobalamin) levels (N=52) and occasionally elevated homocysteine and methylmalonic acid. Conclusions/Scientific Significance: N2O abuse represents a significant problem because of the difficulty involved with identification and the toxicity related to chronic abuse including possible death. Health professionals should be aware of the toxic effects of N2O and be able to identify potential N2O abuse. © 2016 American Academy of Addiction Psychiatry.

Reed G.W.,Ohio | Cannon C.P.,Cardiovascular DivisionBrigham and Womens HospitalBoston | Waalen J.,Scripps Research Institute | Teirstein P.S.,Ohio | And 3 more authors.
Catheterization and Cardiovascular Interventions | Year: 2016

Objective: To examine the influence of smoking on the antiplatelet effect of clopidogrel following percutaneous coronary intervention (PCI). Background: Certain studies suggest smokers may have enhanced clopidogrel-induced platelet inhibition compared to non-smokers after PCI. Whether this is affected by clopidogrel dose is unknown. Methods: In this study, we conducted an analysis of 5,429 patients in the Gauging Responsiveness With A VerifyNow P2Y12 Assay: Impact on Thrombosis and Safety (GRAVITAS) trial. Platelet reactivity was assessed 12-24 hr after PCI (baseline). Patients with high on-treatment platelet reactivity (OTR) (P2Y12 reaction units [PRU]≥230) were randomized to clopidogrel 75 mg or 150 mg daily. Reactivity was subsequently assessed at 30-days, and 6-months. Patients were stratified by smoking status. Results: Smoking was independently associated with lower PRU (P=0.001), and smokers were less likely to have high OTR (odds ratio 0.80, 95% confidence interval 0.68-0.94; P=0.006) at baseline. Among patients assigned to clopidogrel 75 mg, smokers had lower PRU and were less likely to still have high OTR at 30-days (P<0.001) and 6-months (P<0.001). However, in patients assigned clopidogrel 150 mg, PRU and high OTR did not differ by smoking status at any time. Tests demonstrated an interaction between smoking and dose at 30 days (P=0.007), and a trend at 6-months (P=0.098). Conclusions: Smokers treated with clopidogrel exhibit reduced platelet reactivity and are less likely to have persistent high OTR than non-smokers. This difference is mitigated by clopidogrel 150 mg, indicating non-smokers may require double-dose therapy to achieve a similar antiplatelet effect after PCI. © 2016 Wiley Periodicals, Inc.

Bassi D.E.,Cancer Biology ProgramFox Chase Cancer CenterPhiladelphia | Zhang J.,Cancer Biology ProgramFox Chase Cancer CenterPhiladelphia | Renner C.,Pennsylvania | Klein-Szanto A.J.,Cancer Biology ProgramFox Chase Cancer CenterPhiladelphia
Molecular Carcinogenesis | Year: 2016

Proprotein convertases (PCs) are serine proteases with an active role in the post-translational processing of numerous inactive proteins to active proteins including many substrates of paramount importance in cancer development and progression. Furin (PCSKC3), a well-studied member of this family, is overexpressed in numerous human and experimental malignancies. In the present communication, we treated two furin-overexpressing non-small cell carcinoma (NSCLC) cell lines (Calu-6 and HOP-62) with the PC inhibitor CMK (Decanoyl-Arg-Val-Lys-Arg-chloromethylketone). This resulted in a diminished IGF-1R processing and a simultaneous decrease in cell proliferation of two NSCLC lines. Similarly, growth of subcutaneous xenografts of both cell lines, were partially inhibited by an in vivo treatment with the same drug. These observations point to a potential role of PC inhibitors in cancer therapy. © 2016 Wiley Periodicals, Inc.

Blackham A.U.,Florida | Greenleaf E.,Pennsylvania | Yamamoto M.,Florida | Hollenbeak C.,Pennsylvania | And 4 more authors.
Journal of Surgical Oncology | Year: 2016

Background: The clinical value and prognostic implications of histologic response to neoadjuvant chemotherapy in gastric cancer is unknown. Methods: Tumor regression grade (TRG) was recorded in 58 gastric cancer patients identified from two institutional surgical databases. TRG 1a/b represented histologic responders (<10% viable tumor), while TRG 2/3 represented non-responders (>10% viable tumor). Results: TRG 1a/b was recorded in 10 patients (17%), while 48 patients (83%) had a TRG 2/3 response. Larger tumor size (OR 0.24; 95%CI 0.09, 0.64; P=0.004) and clinical downstaging (OR 30.0; 95%CI 3.26, 276; P=0.003) were the only factors predictive of histologic response. TRG 1a/b responders had 3-year survival of 70.0% and an estimated overall survival of >69.8 months compared to 38.2% and 22.8 months in non-responders; however, this trend was not statistically significant (P=0.535). While TRG could not predict survival (OR 2.40; 95%CI 0.46, 12.57; P=0.300), patient age (OR 1.06; 95%CI 1.00, 1.11; P=0.035), and the number of positive lymph nodes (≥7; OR 0.05; 95%CI 0.07, 0.27; P<0.001) were independent predictors of survival. Conclusions: Few gastric cancers demonstrate histologic response to neoadjuvant chemotherapy. While TRG may be a valid marker for treatment response, its predictive value and clinical application in gastric cancer remains unclear. J. Surg. Oncol. © 2016 Wiley Periodicals, Inc.

Westneat D.F.,University of Kentucky | Hatch M.I.,Pennsylvania | Wetzel D.P.,University of Kentucky | Ensminger A.L.,University of Kentucky
American Naturalist | Year: 2011

Personality (consistent differences between individuals in behavior) and plasticity (changes within individuals in behavior) are often viewed as separate and opposing phenomena. We tested this idea by analyzing parental care reaction norms in a bird that exhibits biparental care. Personality in provisioning behavior existed (r IC = 0.11) and persisted despite being reduced after accounting for IC individual differences in environment. Plasticity was also evident and differed between the sexes. Male visit rate was associated with changes in brood size and time of day, but female visit rate was associated with changes in nestling age and date. In both sexes changes in visit rate were positively correlated with changes in their partner's visit rate. Both sexes also exhibited multidimensional reaction norms; interaction terms revealed that within-individual visit rates increased more steeply with brood size when nestlings were older, and the effect of the partner's visit rate was sensitive to variation in date, precipitation, and the focal bird's age. Individuals also varied in how they responded (reaction norm slope) to changes in nestling age and partner visits. Moreover, parental personality was interdependent with individual plasticity in several ways. Individuals of both sexes with a high visit rate also responded more positively to changes in nestling age, and males also showed this pattern with changes in partner visit rate. Explicit use of the behavioral reaction norm integrated personality and plasticity, revealed that these are not opposing concepts, and stimulated new hypotheses about sexual conflict over care and provisioning as a life-history trait. © 2011 by The University of Chicago.

Dunn G.P.,Pennsylvania | Miller N.,The American College
Journal of Surgical Oncology | Year: 2014

Surgeons can more effectively meet the public's increased expectation of patient-centered care by directing attention to pain, non-pain symptoms, including depression and anxiety, in addition to the patient's personal preferences, resources, and support needs. Patient navigation and palliative care, both pioneered by surgeons, provide complementary frameworks for the screening, assessment and intervention needed to achieve enhanced patient outcomes including adherence to care, improved quality of life and patient satisfaction. © 2014 Wiley Periodicals, Inc.

Kaldy J.,Pennsylvania
Consultant Pharmacist | Year: 2015

As health care payment reform continues to evolve, reimbursement increasingly is being linked to outcomes as well as to expenditures. Toward this end, the Centers for Medicare & Medicaid Services has established models for "bundled" payments to long-term care providers, using predetermined payments based on historical spending rates, in a new pay-for-performance landscape. The goal is to reward providers for quality and cost-effective care as well as penalize them for adverse patient outcomes and hospital readmissions based on the target spending rates. Pharmacists have a role in these new models of care, but need to broaden their partnerships and relationships with providers and be prepared to prove they are contributing both to quality care and to reducing costs. © 2015 American Society of Consultant Pharmacists, Inc. All rights reserved.

Poremba S.M.,Pennsylvania
EContent | Year: 2010

This need for organizational agility is leading the way for new technologies in content management systems (CMS). A CMS allows business users to manage the content and functionality on a website and lets them contribute, collaborate, and audit textual, visual, or rich media content for the organization. The CMS includes the following areas: enterprise content management, enterprise capture, customer communications management, and information governance. The companies EMC works with use CMS in many different ways. Social media is certainly one of the most transformative forces in business today. Ektron has found that social software is becoming increasingly common on enterprise websites. This will enable companies to properly communicate and service their customers. The service will be highly individual, no matter what medium the customer chooses to engage with.

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