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Articles 19261 - 19290 of 22213

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Long-Term Outcomes After Autologous Hematopoietic Stem Cell Transplantation For Multiple Sclerosis., Paolo A Muraro, Marcelo Pasquini, Harold L Atkins, James D Bowen, Dominique Farge, Athanasios Fassas, Mark S Freedman, George E Georges, Francesca Gualandi, Nelson Hamerschlak, Eva Havrdova, Vassilios K Kimiskidis, Tomas Kozak, Giovanni L Mancardi, Luca Massacesi, Daniela A Moraes, Richard A Nash, Steven Pavletic, Jian Ouyang, Montserrat Rovira, Albert Saiz, Belinda Simoes, Marek Trnený, Lin Zhu, Manuela Badoglio, Xiaobo Zhong, Maria Pia Sormani, Riccardo Saccardi Apr 2017

Long-Term Outcomes After Autologous Hematopoietic Stem Cell Transplantation For Multiple Sclerosis., Paolo A Muraro, Marcelo Pasquini, Harold L Atkins, James D Bowen, Dominique Farge, Athanasios Fassas, Mark S Freedman, George E Georges, Francesca Gualandi, Nelson Hamerschlak, Eva Havrdova, Vassilios K Kimiskidis, Tomas Kozak, Giovanni L Mancardi, Luca Massacesi, Daniela A Moraes, Richard A Nash, Steven Pavletic, Jian Ouyang, Montserrat Rovira, Albert Saiz, Belinda Simoes, Marek Trnený, Lin Zhu, Manuela Badoglio, Xiaobo Zhong, Maria Pia Sormani, Riccardo Saccardi

Articles, Abstracts, and Reports

Importance: Autologous hematopoietic stem cell transplantation (AHSCT) may be effective in aggressive forms of multiple sclerosis (MS) that fail to respond to standard therapies.

Objective: To evaluate the long-term outcomes in patients who underwent AHSCT for the treatment of MS in a large multicenter cohort.

Design, Setting, and Participants: Data were obtained in a multicenter, observational, retrospective cohort study. Eligibility criteria were receipt of AHSCT for the treatment of MS between January 1995 and December 2006 and the availability of a prespecified minimum data set comprising the disease subtype at baseline; the Expanded Disability Status Scale (EDSS) score at baseline; …


Csf Protein Changes Associated With Hippocampal Sclerosis Risk Gene Variants Highlight Impact Of Grn/Pgrn, David W. Fardo, Yuriko Katsumata, John S. K. Kauwe, Yuetiva Deming, Oscar Harari, Carlos Cruchaga, Alzheimer’S Disease Neuroimaging Initiative, Peter T. Nelson Apr 2017

Csf Protein Changes Associated With Hippocampal Sclerosis Risk Gene Variants Highlight Impact Of Grn/Pgrn, David W. Fardo, Yuriko Katsumata, John S. K. Kauwe, Yuetiva Deming, Oscar Harari, Carlos Cruchaga, Alzheimer’S Disease Neuroimaging Initiative, Peter T. Nelson

Sanders-Brown Center on Aging Faculty Publications

Objective—Hippocampal sclerosis of aging (HS-Aging) is a common cause of dementia in older adults. We tested the variability in cerebrospinal fluid (CSF) proteins associated with previously identified HS-Aging risk single nucleotide polymorphisms (SNPs).

Methods—Alzheimer’s Disease Neuroimaging Initiative cohort (ADNI; n=237) data, combining both multiplexed proteomics CSF and genotype data, were used to assess the association between CSF analytes and risk SNPs in four genes (SNPs): GRN (rs5848), TMEM106B (rs1990622), ABCC9 (rs704180), and KCNMB2 (rs9637454). For controls, non-HS-Aging SNPs in APOE (rs429358/rs7412) and MAPT (rs8070723) were also analyzed against Aβ1-42 and total tau CSF analytes.

Results—The GRN risk …


Evolutionary History Of Tibetans Inferred From Whole-Genome Sequencing., Hao Hu, Nayia Petousi, Gustavo Glusman, Yao Yu, Ryan Bohlender, Tsewang Tashi, Jonathan M Downie, Jared C Roach, Amy M Cole, Felipe R Lorenzo, Alan R Rogers, Mary E Brunkow, Gianpiero Cavalleri, Leroy Hood, Sama M Alpatty, Josef T Prchal, Lynn B Jorde, Peter A Robbins, Tatum S Simonson, Chad D Huff Apr 2017

Evolutionary History Of Tibetans Inferred From Whole-Genome Sequencing., Hao Hu, Nayia Petousi, Gustavo Glusman, Yao Yu, Ryan Bohlender, Tsewang Tashi, Jonathan M Downie, Jared C Roach, Amy M Cole, Felipe R Lorenzo, Alan R Rogers, Mary E Brunkow, Gianpiero Cavalleri, Leroy Hood, Sama M Alpatty, Josef T Prchal, Lynn B Jorde, Peter A Robbins, Tatum S Simonson, Chad D Huff

Articles, Abstracts, and Reports

The indigenous people of the Tibetan Plateau have been the subject of much recent interest because of their unique genetic adaptations to high altitude. Recent studies have demonstrated that the Tibetan EPAS1 haplotype is involved in high altitude-adaptation and originated in an archaic Denisovan-related population. We sequenced the whole-genomes of 27 Tibetans and conducted analyses to infer a detailed history of demography and natural selection of this population. We detected evidence of population structure between the ancestral Han and Tibetan subpopulations as early as 44 to 58 thousand years ago, but with high rates of gene flow until approximately 9 …


Immunotherapy Of Head And Neck Cancer: Emerging Clinical Trials From A National Cancer Institute Head And Neck Cancer Steering Committee Planning Meeting., Julie E Bauman, Ezra Cohen, Robert L Ferris, David J Adelstein, David M Brizel, John A Ridge, Brian O'Sullivan, Barbara A Burtness, Lisa H Butterfield, William E Carson, Mary L Disis, Bernard A Fox, Thomas F Gajewski, Maura L Gillison, James W Hodge, Quynh-Thu Le, David Raben, Scott E Strome, Jean Lynn, Shakun Malik Apr 2017

Immunotherapy Of Head And Neck Cancer: Emerging Clinical Trials From A National Cancer Institute Head And Neck Cancer Steering Committee Planning Meeting., Julie E Bauman, Ezra Cohen, Robert L Ferris, David J Adelstein, David M Brizel, John A Ridge, Brian O'Sullivan, Barbara A Burtness, Lisa H Butterfield, William E Carson, Mary L Disis, Bernard A Fox, Thomas F Gajewski, Maura L Gillison, James W Hodge, Quynh-Thu Le, David Raben, Scott E Strome, Jean Lynn, Shakun Malik

Articles, Abstracts, and Reports

Recent advances have permitted successful therapeutic targeting of the immune system in head and neck squamous cell carcinoma (HNSCC). These new immunotherapeutic targets and agents are being rapidly adopted by the oncologic community and hold considerable promise. The National Cancer Institute sponsored a Clinical Trials Planning Meeting to address the issue of how to further investigate the use of immunotherapy in patients with HNSCC. The goals of the meeting were to consider phase 2 or 3 trial designs primarily in 3 different patient populations: those with previously untreated, human papillomavirus-initiated oropharyngeal cancers; those with previously untreated, human papillomavirus-negative HNSCC; and …


Outcomes After Diagnosis Of Mild Cognitive Impairment In A Large Autopsy Series, Erin L. Abner, Richard J. Kryscio, Frederick A. Schmitt, David W. Fardo, Daniela C. Moga, Eseosa T. Ighodaro, Gregory A. Jicha, Lei Yu, Hiroko H. Dodge, Chengjie Xiong, Randall L. Woltjer, Julie A. Schneider, Nigel J. Cairns, David A. Bennett, Peter T. Nelson Apr 2017

Outcomes After Diagnosis Of Mild Cognitive Impairment In A Large Autopsy Series, Erin L. Abner, Richard J. Kryscio, Frederick A. Schmitt, David W. Fardo, Daniela C. Moga, Eseosa T. Ighodaro, Gregory A. Jicha, Lei Yu, Hiroko H. Dodge, Chengjie Xiong, Randall L. Woltjer, Julie A. Schneider, Nigel J. Cairns, David A. Bennett, Peter T. Nelson

Epidemiology and Environmental Health Faculty Publications

OBJECTIVE: To determine clinical and neuropathological outcomes following a clinical diagnosis of mild cognitive impairment (MCI).

METHODS: Data were drawn from a large autopsy series (N = 1,337) of individuals followed longitudinally from normal or MCI status to death, derived from 4 Alzheimer Disease (AD) Centers in the United States.

RESULTS: Mean follow‐up was 7.9 years. Of the 874 individuals ever diagnosed with MCI, final clinical diagnoses were varied: 39.2% died with an MCI diagnosis, 46.8% with a dementia diagnosis, and 13.9% with a diagnosis of intact cognition. The latter group had pathological features resembling those with a final clinical …


Crispr: Redefining Gmos—One Edit At A Time, Eric E. Williams Apr 2017

Crispr: Redefining Gmos—One Edit At A Time, Eric E. Williams

University of Arkansas at Little Rock Law Review

No abstract provided.


Natural History Of Gutter-Related Type Ia Endoleaks After Snorkel/Chimney Endovascular Aneurysm Repair., Brant W Ullery, Kenneth Tran, Nathan K Itoga, Ronald L Dalman, Jason T Lee Apr 2017

Natural History Of Gutter-Related Type Ia Endoleaks After Snorkel/Chimney Endovascular Aneurysm Repair., Brant W Ullery, Kenneth Tran, Nathan K Itoga, Ronald L Dalman, Jason T Lee

Articles, Abstracts, and Reports

OBJECTIVE: Alternative endovascular strategies using parallel or snorkel/chimney (chimney endovascular aneurysm repair [ch-EVAR]) techniques have been developed to address the lack of widespread availability and manufacturing limitations with branched/fenestrated aortic devices for the treatment of complex abdominal aortic aneurysms. Despite high technical success and midterm patency of snorkel stent configurations, concerns remain regarding the perceived increased incidence of early gutter-related type Ia endoleaks. We aimed to evaluate the incidence and natural history of gutter-related type Ia endoleaks following ch-EVAR.

METHODS: Review of medical records and available imaging studies, including completion angiography and serial computed tomographic angiography, was performed for all …


Susceptibility Loci Of Cnot6 In The General Mrna Degradation Pathway And Lung Cancer Risk-A Re-Analysis Of Eight Gwass., Fei Zhou, Yanru Wang, Hongliang Liu, Neal Ready, Younghun Han, Rayjean J Hung, Yonathan Brhane, John Mclaughlin, Paul Brennan, Heike Bickeböller, Albert Rosenberger, Richard S Houlston, Neil Caporaso, Maria Teresa Landi, Irene Brüske, Angela Risch, Yuanqing Ye, Xifeng Wu, David C Christiani, Gary Goodman, Chu Chen, Christopher I Amos, Qingyi Wei Apr 2017

Susceptibility Loci Of Cnot6 In The General Mrna Degradation Pathway And Lung Cancer Risk-A Re-Analysis Of Eight Gwass., Fei Zhou, Yanru Wang, Hongliang Liu, Neal Ready, Younghun Han, Rayjean J Hung, Yonathan Brhane, John Mclaughlin, Paul Brennan, Heike Bickeböller, Albert Rosenberger, Richard S Houlston, Neil Caporaso, Maria Teresa Landi, Irene Brüske, Angela Risch, Yuanqing Ye, Xifeng Wu, David C Christiani, Gary Goodman, Chu Chen, Christopher I Amos, Qingyi Wei

Articles, Abstracts, and Reports

PURPOSE: mRNA degradation is an important regulatory step for controlling gene expression and cell functions. Genetic abnormalities involved in mRNA degradation genes were found to be associated with cancer risks. Therefore, we systematically investigated the roles of genetic variants in the general mRNA degradation pathway in lung cancer risk.

EXPERIMENTAL DESIGN: Meta-analyses were conducted using summary data from six lung cancer genome-wide association studies (GWASs) from the Transdisciplinary Research in Cancer of the Lung and additional two GWASs from Harvard University and deCODE in the International Lung Cancer Consortium. Expression quantitative trait loci analysis (eQTL) was used for in silico …


Diet And Polycystic Kidney Disease: A Pilot Intervention Study., Jacob M. Taylor, Jill M. Hamilton-Reeves, Debra K. Sullivan, Cheryl A. Gibson, Catherine Creed, Susan E. Carlson, Donald E. Wesson, Jared J. Grantham Apr 2017

Diet And Polycystic Kidney Disease: A Pilot Intervention Study., Jacob M. Taylor, Jill M. Hamilton-Reeves, Debra K. Sullivan, Cheryl A. Gibson, Catherine Creed, Susan E. Carlson, Donald E. Wesson, Jared J. Grantham

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND & AIMS: Dietary sodium, protein, acid precursors, and water have been linked to cyst growth in polycystic kidney disease; yet, no studies in patients have examined the feasibility of using a dietary intervention that controls all of these factors. The aim of this study was to determine if a diet, appropriate for persons of most ages, reduces the excretion of sodium, urea, acid, and decreases mean urine osmolality while gaining acceptance by patients with autosomal dominant polycystic kidney disease (ADPKD).

METHODS: Twelve adults with ADPKD enrolled in a pre-post pilot feasibility study and served as their own controls. Individuals …


Physician Satisfaction With Integrated Behavioral Health In Pediatric Primary Care., Jeffrey F. Hine, Allison Q. Grennan, Kathryn M. Menousek, Gail Robertson, Rachel J. Valleley, Joseph H. Evans Apr 2017

Physician Satisfaction With Integrated Behavioral Health In Pediatric Primary Care., Jeffrey F. Hine, Allison Q. Grennan, Kathryn M. Menousek, Gail Robertson, Rachel J. Valleley, Joseph H. Evans

Manuscripts, Articles, Book Chapters and Other Papers

As the benefits of integrated behavioral health care services are becoming more widely recognized, this study investigated physician satisfaction with ongoing integrated psychology services in pediatric primary care clinics. Data were collected across 5 urban and 6 rural clinics and demonstrated the specific factors that physicians view as assets to having efficient access to a pediatric behavioral health practitioner. Results indicated significant satisfaction related to quality and continuity of care and improved access to services. Such models of care may increase access to care and reduce other service barriers encountered by individuals and their families with behavioral health concerns (ie, …


Evaluating Parents' Self-Efficacy For Diabetes Management In Pediatric Type 1 Diabetes., Amy E. Noser, Susana R. Patton, Jason Van Allen, Michael B. Nelson, Mark A. Clements Apr 2017

Evaluating Parents' Self-Efficacy For Diabetes Management In Pediatric Type 1 Diabetes., Amy E. Noser, Susana R. Patton, Jason Van Allen, Michael B. Nelson, Mark A. Clements

Manuscripts, Articles, Book Chapters and Other Papers

Objective: To examine the factor structure and construct validity of the Maternal Self-Efficacy for Diabetes Management Scale (MSED) in 135 youth ( Mage  = 13.50  ±  1.83 years), with type 1 diabetes mellitus.

Method: The study used exploratory factor analysis (EFA) to examine the factor structure and correlations to examine relationships among MSED factors and select parent and child diabetes-related health behaviors and outcomes.

Results: EFA identified an 11-item three-factor solution (χ 2 (25, n  = 133)  = 40.22, p  < .03, RMSEA = 0.07, CFI = 0.98, TLI = 0.97), with factors corresponding to parents' perceived ability to manage their child's diabetes (MSED-M), problem-solve issues surrounding glycemic control (MSED-P), and teach their child about diabetes care (MSED-T). Correlational analyses revealed significant associations between the MSED-M and MSED-T and parent-reported optimism and youth's diabetes-specific self-efficacy. The MSED-T was also associated with glycated hemoglobin and self-monitoring blood glucose.

Conclusions: Results provide preliminary evidence for the reliability and validity of a three-factor solution of the MSED.


The Randomized, Controlled Trial Of Late Surfactant: Effects On Respiratory Outcomes At 1-Year Corrected Age., Roberta L. Keller, Eric C. Eichenwald, Anna Maria Hibbs, Elizabeth E. Rogers, Katherine C. Wai, Dennis M. Black, Philip L. Ballard, Jeanette M. Asselin, William E Truog, Jeffrey D. Merrill, Mark C. Mammel, Robin H. Steinhorn, Rita M. Ryan, David J. Durand, Catherine M. Bendel, Ellen M. Bendel-Stenzel, Sherry E. Courtney, Ramasubbareddy Dhanireddy, Mark L. Hudak, Frances R. Koch, Dennis E. Mayock, Victor J. Mckay, Jennifer Helderman, Nicolas F. Porta, Rajan Wadhawan, Lisa Palermo, Roberta A. Ballard, Tolsurf Study Group Apr 2017

The Randomized, Controlled Trial Of Late Surfactant: Effects On Respiratory Outcomes At 1-Year Corrected Age., Roberta L. Keller, Eric C. Eichenwald, Anna Maria Hibbs, Elizabeth E. Rogers, Katherine C. Wai, Dennis M. Black, Philip L. Ballard, Jeanette M. Asselin, William E Truog, Jeffrey D. Merrill, Mark C. Mammel, Robin H. Steinhorn, Rita M. Ryan, David J. Durand, Catherine M. Bendel, Ellen M. Bendel-Stenzel, Sherry E. Courtney, Ramasubbareddy Dhanireddy, Mark L. Hudak, Frances R. Koch, Dennis E. Mayock, Victor J. Mckay, Jennifer Helderman, Nicolas F. Porta, Rajan Wadhawan, Lisa Palermo, Roberta A. Ballard, Tolsurf Study Group

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: To determine the effects of late surfactant on respiratory outcomes determined at 1-year corrected age in the Trial of Late Surfactant (TOLSURF), which randomized newborns of extremely low gestational age (≤28 weeks' gestational age) ventilated at 7-14 days to late surfactant and inhaled nitric oxide vs inhaled nitric oxide-alone (control).

STUDY DESIGN: Caregivers were surveyed in a double-blinded manner at 3, 6, 9, and 12 months' corrected age to collect information on respiratory resource use (infant medication use, home support, and hospitalization). Infants were classified for composite outcomes of pulmonary morbidity (no PM, determined in infants with no reported …


Glucocorticoid Receptor Polymorphisms And Outcomes In Pediatric Septic Shock., Natalie Z. Cvijanovich, Nick Anas, Geoffrey L. Allen, Neal J. Thomas, Michael T. Bigham, Scott L. Weiss, Julie Fitzgerald, Paul A. Checchia, Keith Meyer, Michael Quasney, Rainer Gedeit, Robert J. Freishtat, Jeffrey Nowak, Shekhar S. Raj, Shira Gertz, Jocelyn R. Grunwell, Amy Opoka, Hector R. Wong Apr 2017

Glucocorticoid Receptor Polymorphisms And Outcomes In Pediatric Septic Shock., Natalie Z. Cvijanovich, Nick Anas, Geoffrey L. Allen, Neal J. Thomas, Michael T. Bigham, Scott L. Weiss, Julie Fitzgerald, Paul A. Checchia, Keith Meyer, Michael Quasney, Rainer Gedeit, Robert J. Freishtat, Jeffrey Nowak, Shekhar S. Raj, Shira Gertz, Jocelyn R. Grunwell, Amy Opoka, Hector R. Wong

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: Polymorphisms of the glucocorticoid receptor gene are associated with outcome and corticosteroid responsiveness among patients with inflammatory disorders. We conducted a candidate gene association study to test the hypothesis that these polymorphisms are associated with outcome and corticosteroid responsiveness among children with septic shock.

DESIGN: We genotyped 482 children with septic shock for the presence of two glucocorticoid receptor polymorphisms (rs56149945 and rs41423247) associated with increased sensitivity and one glucocorticoid receptor polymorphism (rs6198) associated with decreased sensitivity to corticosteroids. The primary outcome variable was complicated course, defined as 28-day mortality or the persistence of two or more organ failures …


Rod-Shaped Microglia Morphology Is Associated With Aging In 2 Human Autopsy Series, Adam D. Bachstetter, Eseosa T. Ighodaro, Yasmin Hassoun, Danah Aldeiri, Janna H. Neltner, Ela Patel, Erin L. Abner, Peter T. Nelson Apr 2017

Rod-Shaped Microglia Morphology Is Associated With Aging In 2 Human Autopsy Series, Adam D. Bachstetter, Eseosa T. Ighodaro, Yasmin Hassoun, Danah Aldeiri, Janna H. Neltner, Ela Patel, Erin L. Abner, Peter T. Nelson

Spinal Cord and Brain Injury Research Center Faculty Publications

A subtype of microglia is defined by the morphological appearance of the cells as rod-shaped. Little is known about this intriguing cell type, as there are only a few case reports describing rod-shaped microglia in the neuropathological literature. Rod-shaped microglia were shown recently to account for a substantial proportion of the microglia cells in the hippocampus of both demented and cognitively intact aged individuals. We hypothesized that aging could be a defining feature in the occurrence of rod-shaped microglia. To test this hypothesis, two independent series of autopsy cases (total n=168 cases), which covered the adult lifespan from 20 – …


Thiamine Deficiency Induces Endoplasmic Reticulum Stress And Oxidative Stress In Human Neurons Derived From Induced Pluripotent Stem Cells, Xin Wang, Mei Xu, Jacqueline A. Frank, Zun-Ji Ke, Jia Luo Apr 2017

Thiamine Deficiency Induces Endoplasmic Reticulum Stress And Oxidative Stress In Human Neurons Derived From Induced Pluripotent Stem Cells, Xin Wang, Mei Xu, Jacqueline A. Frank, Zun-Ji Ke, Jia Luo

Pharmacology and Nutritional Sciences Faculty Publications

Thiamine (vitamin B1) deficiency (TD) plays a major role in the etiology of Wernicke's encephalopathy (WE) which is a severe neurological disorder. TD induces selective neuronal cell death, neuroinflammation, endoplasmic reticulum (ER) stress and oxidative stress in the brain which are commonly observed in many aging-related neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and progressive supranuclear palsy (PSP). However, the underlying cellular and molecular mechanisms remain unclear. The progress in this line of research is hindered due to the lack of appropriate in vitro models. The neurons derived for the human induced pluripotent stem …


Carisbamate Blockade Of T-Type Voltage-Gated Calcium Channels, Do Young Kim, Fang-Xiong Zhang, Stan T. Nakanishi, Timothy Mettler, Ik-Hyun Cho, Younghee Ahn, Florian Hiess, Lina Chen, Patrick G. Sullivan, S. R. Wayne Chen, Gerald W. Zamponi, Jong M. Rho Apr 2017

Carisbamate Blockade Of T-Type Voltage-Gated Calcium Channels, Do Young Kim, Fang-Xiong Zhang, Stan T. Nakanishi, Timothy Mettler, Ik-Hyun Cho, Younghee Ahn, Florian Hiess, Lina Chen, Patrick G. Sullivan, S. R. Wayne Chen, Gerald W. Zamponi, Jong M. Rho

Spinal Cord and Brain Injury Research Center Faculty Publications

Objectives

Carisbamate (CRS) is a novel monocarbamate compound that possesses antiseizure and neuroprotective properties. However, the mechanisms underlying these actions remain unclear. Here, we tested both direct and indirect effects of CRS on several cellular systems that regulate intracellular calcium concentration [Ca2+]i.

Methods

We used a combination of cellular electrophysiologic techniques, as well as cell viability, Store Overload‐Induced Calcium Release (SOICR), and mitochondrial functional assays to determine whether CRS might affect [Ca2+]i levels through actions on the endoplasmic reticulum (ER), mitochondria, and/or T‐type voltage‐gated Ca2+ channels.

Results

In CA3 pyramidal neurons, kainic …


Pharmacokinetics Of Clindamycin In Obese And Nonobese Children., Michael J. Smith, Daniel Gonzalez, Jennifer L Goldman, Ram Yogev, Janice E. Sullivan, Michael D. Reed, Ravinder Anand, Karen Martz, Katherine Berezny, Daniel K. Benjamin, P Brian Smith, Michael Cohen-Wolkowiez, Kevin Watt Apr 2017

Pharmacokinetics Of Clindamycin In Obese And Nonobese Children., Michael J. Smith, Daniel Gonzalez, Jennifer L Goldman, Ram Yogev, Janice E. Sullivan, Michael D. Reed, Ravinder Anand, Karen Martz, Katherine Berezny, Daniel K. Benjamin, P Brian Smith, Michael Cohen-Wolkowiez, Kevin Watt

Manuscripts, Articles, Book Chapters and Other Papers

Although obesity is prevalent among children in the United States, pharmacokinetic (PK) data for obese children are limited. Clindamycin is a commonly used antibiotic that may require dose adjustment in obese children due to its lipophilic properties. We performed a clindamycin population PK analysis using data from three separate trials. A total of 420 samples from 220 children, 76 of whom had a body mass index greater than or equal to the 95th percentile for age, were included in the analysis. Compared to other metrics, total body weight (TBW) was the most robust measure of body size. The final model …


Acute Effects Of Implantable Cardioverter-Defibrillator Shocks On Biomarkers Of Myocardial Injury, Apoptosis, Heart Failure, And Systemic Inflammation, Jordan Brewster, Travis Sexton, Gary Dhaliwal, Richard Charnigo, Gustavo Morales, Kevin Parrott, Yousef Darrat, John C. Gurley, Susan S. Smyth, Claude S. Elayi Apr 2017

Acute Effects Of Implantable Cardioverter-Defibrillator Shocks On Biomarkers Of Myocardial Injury, Apoptosis, Heart Failure, And Systemic Inflammation, Jordan Brewster, Travis Sexton, Gary Dhaliwal, Richard Charnigo, Gustavo Morales, Kevin Parrott, Yousef Darrat, John C. Gurley, Susan S. Smyth, Claude S. Elayi

Internal Medicine Faculty Publications

Background: Implantable cardioverter‐defibrillator (ICD) shocks are potentially associated with myocardial injury, altered hemodynamics, apoptosis, and inflammatory signaling. Their precise cellular impact can be explored after defibrillation testing (DFT) via biomarkers. We evaluated changes in biomarkers after ICD shocks during DFT.

Methods: We prospectively enrolled outpatients presenting for first implantation of a cardiac device. Biomarkers indicative of myocardial injury, inflammation, and apoptosis were measured before and after implantation, and compared between patients receiving DFT (DFT+) to those not (DFT−).

Results: Sixty‐three patients were enrolled, 40 in the DFT+ group and 23 in the DFT− group. Average levels of troponin I, hsCRP, …


A Prospective Study Of Maternal, Fetal And Neonatal Outcomes In The Setting Of Cesarean Section In Low- And Middle-Income Countries., Margo S. Harrison, Omrana Pasha, Sarah Saleem, Sumera Ali, Elwyn Chomba, Waldemar A. Carlo, Ana L. Garces, Nancy F. Krebs, K. Michael Hambidge, Shivaprasad S. Goudar, Bhala Kodkany, Sangappa Dhaded, Richard J. Derman, Archana Patel, Patricia L. Hibberd, Fabian Esamai, Edward A. Liechty, Janet L. Moore, Dennis Wallace, Elizabeth M. Mcclure, Menachem Miodovnik, Marion Koso-Thomas, Jose Belizan, Antoinette K. Tshefu, Melissa Bauserman, Robert L. Goldenberg Apr 2017

A Prospective Study Of Maternal, Fetal And Neonatal Outcomes In The Setting Of Cesarean Section In Low- And Middle-Income Countries., Margo S. Harrison, Omrana Pasha, Sarah Saleem, Sumera Ali, Elwyn Chomba, Waldemar A. Carlo, Ana L. Garces, Nancy F. Krebs, K. Michael Hambidge, Shivaprasad S. Goudar, Bhala Kodkany, Sangappa Dhaded, Richard J. Derman, Archana Patel, Patricia L. Hibberd, Fabian Esamai, Edward A. Liechty, Janet L. Moore, Dennis Wallace, Elizabeth M. Mcclure, Menachem Miodovnik, Marion Koso-Thomas, Jose Belizan, Antoinette K. Tshefu, Melissa Bauserman, Robert L. Goldenberg

Global Health Articles

INTRODUCTION: Cesarean section (CS) rates are increasing globally with an unclear effect on pregnancy outcomes. The study objective was to quantify maternal and perinatal morbidity and mortality associated with CS compared with vaginal delivery (VD) both within and across sites in low- and middle-income countries.

MATERIAL AND METHODS: A prospective population-based study including home and facility births in 337 153 women with a VD and 47 308 women with a CS from 2010 to 2015 was performed in Guatemala, India, Kenya, Pakistan, Zambia and Democratic Republic of Congo. Women were enrolled during pregnancy; delivery and 6-week follow-up data were collected. …


Buprenorphine Physician Supply: Relationship With State-Level Prescription Opioid Mortality, Hannah K. Knudsen, Jennifer R. Havens, Michelle R. Lofwall, Jamie L. Studts, Sharon L. Walsh Apr 2017

Buprenorphine Physician Supply: Relationship With State-Level Prescription Opioid Mortality, Hannah K. Knudsen, Jennifer R. Havens, Michelle R. Lofwall, Jamie L. Studts, Sharon L. Walsh

Behavioral Science Faculty Publications

Background: Buprenorphine is an effective treatment for opioid use disorder but the supply of buprenorphine physicians is currently inadequate to address the nation’s prescription opioid crisis. Perception of need due to rising opioid overdose rates is one possible reason for physicians to adopt buprenorphine. This study examined associations between rates of growth in buprenorphine physicians and prescription opioid overdose mortality rates in US states.

Methods: The total buprenorphine physician supply and number of physicians approved to treat 100 patients (per 100,000 population) were measured from June 2013 to January 2016. States were divided into two groups: those with rates of …


A Randomized Controlled Trial Of Ethyl Glucuronide-Based Contingency Management For Outpatients With Co-Occurring Alcohol Use Disorders And Serious Mental Illness., Michael G Mcdonell, Emily Leickly, Sterling Mcpherson, Jordan Skalisky, Debra Srebnik, Frank Angelo, Roger Vilardaga, Jenny R Nepom, John M Roll, Richard K Ries Apr 2017

A Randomized Controlled Trial Of Ethyl Glucuronide-Based Contingency Management For Outpatients With Co-Occurring Alcohol Use Disorders And Serious Mental Illness., Michael G Mcdonell, Emily Leickly, Sterling Mcpherson, Jordan Skalisky, Debra Srebnik, Frank Angelo, Roger Vilardaga, Jenny R Nepom, John M Roll, Richard K Ries

Articles, Abstracts, and Reports

OBJECTIVE: The authors examined whether a contingency management intervention using the ethyl glucuronide (EtG) alcohol biomarker resulted in increased alcohol abstinence in outpatients with co-occurring serious mental illnesses. Secondary objectives were to determine whether contingency management was associated with changes in heavy drinking, treatment attendance, drug use, cigarette smoking, psychiatric symptoms, and HIV-risk behavior.

METHOD: Seventy-nine (37% female, 44% nonwhite) outpatients with serious mental illness and alcohol dependence receiving treatment as usual completed a 4-week observation period and were randomly assigned to 12 weeks of contingency management for EtG-negative urine samples and addiction treatment attendance, or reinforcement only for study …


Thin Melanoma With Nodal Involvement: Analysis Of Demographic, Pathologic, And Treatment Factors With Regard To Prognosis., Giorgos Karakousis, Phyllis A Gimotty, Edmund K Bartlett, Myung-Shin Sim, Madalyn G Neuwirth, Douglas Fraker, Brian J Czerniecki, Mark B Faries Apr 2017

Thin Melanoma With Nodal Involvement: Analysis Of Demographic, Pathologic, And Treatment Factors With Regard To Prognosis., Giorgos Karakousis, Phyllis A Gimotty, Edmund K Bartlett, Myung-Shin Sim, Madalyn G Neuwirth, Douglas Fraker, Brian J Czerniecki, Mark B Faries

Articles, Abstracts, and Reports

BACKGROUND: Although only a small proportion of thin melanomas result in lymph node metastasis, the abundance of these lesions results in a relatively large absolute number of patients with a diagnosis of nodal metastases, determined by either sentinel lymph node (SLN) biopsy or clinical nodal recurrence (CNR).

METHODS: Independent cohorts with thin melanoma and either SLN metastasis or CNR were identified at two melanoma referral centers. At both centers, SLN metastasis patients were included. At center 1, the CNR cohort included patients with initial negative clinical nodal evaluation followed by CNR. At center 2, the CNR cohort was restricted to …


Lethal Neonatal Case And Review Of Primary Short-Chain Enoyl-Coa Hydratase (Sceh) Deficiency Associated With Secondary Lymphocyte Pyruvate Dehydrogenase Complex (Pdc) Deficiency., Jirair K Bedoyan, Samuel P Yang, Sacha Ferdinandusse, Rhona M Jack, Alexander Miron, George Grahame, Suzanne D Debrosse, Charles L Hoppel, Douglas S Kerr, Ronald J A Wanders Apr 2017

Lethal Neonatal Case And Review Of Primary Short-Chain Enoyl-Coa Hydratase (Sceh) Deficiency Associated With Secondary Lymphocyte Pyruvate Dehydrogenase Complex (Pdc) Deficiency., Jirair K Bedoyan, Samuel P Yang, Sacha Ferdinandusse, Rhona M Jack, Alexander Miron, George Grahame, Suzanne D Debrosse, Charles L Hoppel, Douglas S Kerr, Ronald J A Wanders

Articles, Abstracts, and Reports

Mutations in ECHS1 result in short-chain enoyl-CoA hydratase (SCEH) deficiency which mainly affects the catabolism of various amino acids, particularly valine. We describe a case compound heterozygous for ECHS1 mutations c.836T>C (novel) and c.8C>A identified by whole exome sequencing of proband and parents. SCEH deficiency was confirmed with very low SCEH activity in fibroblasts and nearly absent immunoreactivity of SCEH. The patient had a severe neonatal course with elevated blood and cerebrospinal fluid lactate and pyruvate concentrations, high plasma alanine and slightly low plasma cystine. 2-Methyl-2,3-dihydroxybutyric acid was markedly elevated as were metabolites of the three branched-chain α-ketoacids …


Social Franchising And A Nationwide Mass Media Campaign Increased The Prevalence Of Adequate Complementary Feeding In Vietnam: A Cluster-Randomized Program Evaluation, Rahul Rawat, Phuong Hong Nguyen, Lan Mai Tran, Nemat Hajeebhoy, Huan Van Nguyen, Jean Baker, Edward A. Frongillo Jr., Marie T. Ruel, Purnima Menon Apr 2017

Social Franchising And A Nationwide Mass Media Campaign Increased The Prevalence Of Adequate Complementary Feeding In Vietnam: A Cluster-Randomized Program Evaluation, Rahul Rawat, Phuong Hong Nguyen, Lan Mai Tran, Nemat Hajeebhoy, Huan Van Nguyen, Jean Baker, Edward A. Frongillo Jr., Marie T. Ruel, Purnima Menon

Faculty Publications

Rigorous evaluations of health system-based interventions in large-scale programs to improve complementary feeding (CF) practices are limited. Alive & Thrive applied principles of social franchising within the government health system in Vietnam to improve the quality of interpersonal counseling (IPC) for infant and young child feeding combined with a national mass media (MM) campaign and community mobilization (CM). We evaluated the impact of enhanced IPC + MM + CM (intensive) compared with standard IPC + less-intensive MM and CM (nonintensive) on CF practices and anthropometric indicators. A cluster-randomized, nonblinded evaluation design with cross-sectional surveys ( = ∼500 children aged 6-23.9 …


Ventilator-Associated Pneumonia: New Definitions., M Chance Spalding, Michael W Cripps, Christian T Minshall Apr 2017

Ventilator-Associated Pneumonia: New Definitions., M Chance Spalding, Michael W Cripps, Christian T Minshall

Trauma and Acute Care Articles

The National Healthcare Safety Network's new classification characterizes all adverse ventilator-associated events (VAE) into a tiered system designed to shift the focus away from ventilator-associated pneumonia as the only important cause or morbidity in ventilated patients. This new surveillance definition of VAE eliminates subjectivity by using clearly defined criteria and facilitates the automated collection of data. This allows for easier comparison and analysis of factors affecting rates of VAE. Numerous studies have been published that demonstrate its clinical application. This article presents the VAE criteria, contrasts the difference from the previous ventilator-associated pneumonia definition, and discusses its implementation over the …


State Emergency Department Opioid Guidelines: Current Status., Robert I Broida, Tanner Gronowski, Andrew F Kalnow, Andrew G Little, Christopher M Lloyd Apr 2017

State Emergency Department Opioid Guidelines: Current Status., Robert I Broida, Tanner Gronowski, Andrew F Kalnow, Andrew G Little, Christopher M Lloyd

Trauma and Acute Care Articles

INTRODUCTION: The purpose of this study was to evaluate and categorize current state-sponsored opioid guidelines for the practice of emergency medicine (EM).

METHODS: We conducted a comprehensive search of EM-specific opioid prescribing guidelines and/or policies in each state to determine current state involvement in EM opioid prescribing, as well as to evaluate some of the specifics of each guideline or policy. The search was conducted using an online query and a follow-up email request to each state chapter of ACEP.

RESULTS: We found that 17 states had emergency department-specific guidelines. We further organized the guidelines into four categories: limiting prescriptions …


Long-Term Excess Risk Of Stroke In People With Type 2 Diabetes In Sweden According To Blood Pressure Level: A Population-Based Case-Control Study., C Hedén Ståhl, M Lind, A-M Svensson, M Kosiborod, S Gudbjörnsdottir, A Pivodic, Mark A. Clements, A Rosengren Apr 2017

Long-Term Excess Risk Of Stroke In People With Type 2 Diabetes In Sweden According To Blood Pressure Level: A Population-Based Case-Control Study., C Hedén Ståhl, M Lind, A-M Svensson, M Kosiborod, S Gudbjörnsdottir, A Pivodic, Mark A. Clements, A Rosengren

Manuscripts, Articles, Book Chapters and Other Papers

AIMS: To estimate the risk of stroke in people with Type 2 diabetes with different blood pressure levels compared with the risk in the general population in Sweden.

METHODS: This prospective case-control study included 408 076 people with Type 2 diabetes, aged ≥ 18 years, and free of prior stroke, registered in the Swedish National Diabetes Register 1998-2011. Age- and sex-matched control subjects (n = 1 913 507) without stroke from the general population were included. Stroke diagnoses were retrieved using International Classification of Disease codes from the Swedish patient and death registers. Cox hazard ratios and 95% confidence intervals …


Genomic Contraindications For Heart Transplantation., Danton S. Char, Gabriel Lázaro-Muñoz, Aliessa Barnes, David Magnus, Michael J. Deem, John Lantos Apr 2017

Genomic Contraindications For Heart Transplantation., Danton S. Char, Gabriel Lázaro-Muñoz, Aliessa Barnes, David Magnus, Michael J. Deem, John Lantos

Manuscripts, Articles, Book Chapters and Other Papers

Genome sequencing raises new ethical challenges. Decoding the genome produces new forms of diagnostic and prognostic information; however, the information is often difficult to interpret. The connection between most genetic variants and their phenotypic manifestations is not understood. This scenario is particularly true for disorders that are not associated with an autosomal genetic variant. The analytic uncertainty is compounded by moral uncertainty about how, exactly, the results of genomic testing should influence clinical decisions. In this Ethics Rounds, we present a case in which genomic findings seemed to play a role in deciding whether a patient was to be listed …


Increasing Ed Use Of Jet Injection Of Lidocaine For Iv-Related Pain Management., Shobhit Jain, Mary A. Hegenbarth, Sharon Humiston, Erin Gunter, Lynn Anson, Joan Giovanni Apr 2017

Increasing Ed Use Of Jet Injection Of Lidocaine For Iv-Related Pain Management., Shobhit Jain, Mary A. Hegenbarth, Sharon Humiston, Erin Gunter, Lynn Anson, Joan Giovanni

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND AND OBJECTIVE: Venipuncture is a leading cause of procedural pain for children. Jet injection of lidocaine (JIL; J-Tip) has been demonstrated to be effective in controlling intravenous (IV) placement-related pain and, due to its rapid onset, is particularly suited to emergency department (ED) use. Our objective was to increase JIL use with IV placements in our ED from 11% at baseline to 50% within 12 months.

METHODS: We initiated the project at our urban, tertiary pediatric ED in July 2014. We surveyed medical and nursing teams to identify barriers to JIL use. We initiated changes at monthly intervals: (1) …


Impact Of Cyp2d6 Genotype On Amitriptyline Efficacy For The Treatment Of Diabetic Peripheral Neuropathy: A Pilot Study., Mamoonah Chaudhry, Marco Alessandrini, Jacobus Rademan, Tyren M. Dodgen, Francois E. Steffens, Danie G. Van Zyl, Andrea Gaedigk, Michael S. Pepper Apr 2017

Impact Of Cyp2d6 Genotype On Amitriptyline Efficacy For The Treatment Of Diabetic Peripheral Neuropathy: A Pilot Study., Mamoonah Chaudhry, Marco Alessandrini, Jacobus Rademan, Tyren M. Dodgen, Francois E. Steffens, Danie G. Van Zyl, Andrea Gaedigk, Michael S. Pepper

Manuscripts, Articles, Book Chapters and Other Papers

AIM: Therapy with low-dose amitriptyline is commonly used to treat painful diabetic peripheral neuropathy. There is a knowledge gap, however, regarding the role of variable CYP2D6-mediated drug metabolism and side effects (SEs). We aimed to generate pilot data to demonstrate that SEs are more frequent in patients with variant CYP2D6 alleles.

METHOD: To that end, 31 randomly recruited participants were treated with low-dose amitriptyline for painful diabetic peripheral neuropathy and their CYP2D6 gene sequenced.

RESULTS: Patients with predicted normal or ultra-rapid metabolizer phenotypes presented with less SEs compared with individuals with decreased CYP2D6 activity.

CONCLUSION: Hence, CYP2D6 genotype contributes to …