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Alirocumab In High-Risk Patients: Observations From The Open-Label Expanded Use Program, Charles J Glueck, Alan Brown, Anne C Goldberg, James M Mckenney, Louis Kantaros, John Stewart, Joseph Elassal, Andrew Koren May 2018

Alirocumab In High-Risk Patients: Observations From The Open-Label Expanded Use Program, Charles J Glueck, Alan Brown, Anne C Goldberg, James M Mckenney, Louis Kantaros, John Stewart, Joseph Elassal, Andrew Koren

Open Access Publications

BACKGROUND: The alirocumab expanded use program provided open-label access to alirocumab before its commercial availability to patients with severe hypercholesterolemia not controlled with maximally tolerated doses of standard-of-care lipid-lowering therapy.

OBJECTIVE: To describe the safety and lipid-lowering efficacy of alirocumab in high-risk patients who were likely to be early users of proprotein convertase subtilisin/kexin type 9 inhibitors after approval.

METHODS: Patients with heterozygous familial hypercholesterolemia (HeFH) and/or coronary heart disease (CHD) and baseline low-density lipoprotein cholesterol (LDL-C) of ≥160 mg/dL on maximally tolerated lipid-lowering therapy were enrolled and received alirocumab 150 mg every 2 weeks for 24 weeks. Patients were …


Validation Of A Novel Scoring System For Changes In Skeletal Manifestations Of Hypophosphatasia In Newborns, Infants, And Children: The Radiographic Global Impression Of Change Scale, Michael P Whyte, Kenji P Fujita, Scott Moseley, David D Thompson, William H Mcalister May 2018

Validation Of A Novel Scoring System For Changes In Skeletal Manifestations Of Hypophosphatasia In Newborns, Infants, And Children: The Radiographic Global Impression Of Change Scale, Michael P Whyte, Kenji P Fujita, Scott Moseley, David D Thompson, William H Mcalister

Open Access Publications

Hypophosphatasia (HPP) is the heritable metabolic disease characterized by impaired skeletal mineralization due to low activity of the tissue-nonspecific isoenzyme of alkaline phosphatase. Although HPP during growth often manifests with distinctive radiographic skeletal features, no validated method was available to quantify them, including changes over time. We created the Radiographic Global Impression of Change (RGI-C) scale to assess changes in the skeletal burden of pediatric HPP. Site-specific pairs of radiographs of newborns, infants, and children with HPP from three clinical studies of asfotase alfa, an enzyme replacement therapy for HPP, were obtained at baseline and during treatment. Each pair was …


Outcome Trends And Safety Measures After 30 Years Of Laparoscopic Cholecystectomy: A Systematic Review And Pooled Data Analysis, Philip H Pucher, L. Michael Brunt, Neil Davies, Ali Linsk, Amani Munshi, H Alejandro Rodriguez, Abe Fingerhut, Robert D Fanelli, Horacio Asbun, Rajesh Aggarwal, Sages Safe Cholecystectomy Task Force May 2018

Outcome Trends And Safety Measures After 30 Years Of Laparoscopic Cholecystectomy: A Systematic Review And Pooled Data Analysis, Philip H Pucher, L. Michael Brunt, Neil Davies, Ali Linsk, Amani Munshi, H Alejandro Rodriguez, Abe Fingerhut, Robert D Fanelli, Horacio Asbun, Rajesh Aggarwal, Sages Safe Cholecystectomy Task Force

Open Access Publications

BACKGROUND: Laparoscopic cholecystectomy (LC), one of the most commonly performed surgical procedures, remains associated with significant major morbidity including bile leak and bile duct injury (BDI). The effect of changes in practice over time, and of interventions to improve patient safety, on morbidity rates is not well understood. The aim of this review was to describe current incidence rates and trends for BDI and other complications during and after LC, and to identify risk factors and preventative measures associated with morbidity and BDI.

METHODS: PubMed, MEDLINE, and Web of Science database searches and data extraction were conducted for studies which …


Psychiatric And Cognitive Adverse Events: A Pooled Analysis Of Three Phase Iii Trials Of Adjunctive Eslicarbazepine Acetate For Partial-Onset Seizures., Eva Andermann, Victor Biton, Selim R Benbadis, Bassel Shneker, Aashit K Shah, Mar Carreño, Eugen Trinka, Elinor Ben-Menachem, Arnaud Biraben, Francisco Rocha, Helena Gama, Hailong Cheng, David Blum, Study 301, 302 And 304 Investigators May 2018

Psychiatric And Cognitive Adverse Events: A Pooled Analysis Of Three Phase Iii Trials Of Adjunctive Eslicarbazepine Acetate For Partial-Onset Seizures., Eva Andermann, Victor Biton, Selim R Benbadis, Bassel Shneker, Aashit K Shah, Mar Carreño, Eugen Trinka, Elinor Ben-Menachem, Arnaud Biraben, Francisco Rocha, Helena Gama, Hailong Cheng, David Blum, Study 301, 302 And 304 Investigators

Pharmacy Articles

OBJECTIVE: To evaluate the nature and incidence of psychiatric and cognitive adverse events (AEs) reported with eslicarbazepine acetate (ESL) used as adjunctive treatment for refractory partial-onset seizures (POS) in adults.

METHODS: This was a post-hoc analysis of data pooled from three randomized double-blind, placebo-controlled trials (BIA-2093-301, -302, -304). After an 8-week baseline period, patients received placebo or adjunctive ESL 400mg (studies 301 and 302 only), 800mg, or 1200mg once daily (QD) for 14weeks (2-week titration period, 12-week maintenance period). Psychiatric and cognitive AEs were identified from individual patient data. Suicidality was also evaluated using the Columbia-Classification Algorithm of Suicide Assessment …


Analysis Of Clinical Data To Determine The Minimum Number Of Sensors Required For Adequate Skin Temperature Monitoring Of Superficial Hyperthermia Treatments., Akke Bakker, Rebecca Holman, Dario B. Rodrigues, Hana Dobšíček Trefná, Paul R. Stauffer, Geertjan Van Tienhoven, Coen R.N. Rasch, Hans Crezee Apr 2018

Analysis Of Clinical Data To Determine The Minimum Number Of Sensors Required For Adequate Skin Temperature Monitoring Of Superficial Hyperthermia Treatments., Akke Bakker, Rebecca Holman, Dario B. Rodrigues, Hana Dobšíček Trefná, Paul R. Stauffer, Geertjan Van Tienhoven, Coen R.N. Rasch, Hans Crezee

Department of Radiation Oncology Faculty Papers

PURPOSE: Tumor response and treatment toxicity are related to minimum and maximum tissue temperatures during hyperthermia, respectively. Using a large set of clinical data, we analyzed the number of sensors required to adequately monitor skin temperature during superficial hyperthermia treatment of breast cancer patients.

METHODS: Hyperthermia treatments monitored with >60 stationary temperature sensors were selected from a database of patients with recurrent breast cancer treated with re-irradiation (23 × 2 Gy) and hyperthermia using single 434 MHz applicators (effective field size 351-396 cm2). Reduced temperature monitoring schemes involved randomly selected subsets of stationary skin sensors, and another subset …


Bilateral Facial Spasm Following Guillain-Barré Syndrome, Zain Guduru, John Morgan, Kapil Sethi Apr 2018

Bilateral Facial Spasm Following Guillain-Barré Syndrome, Zain Guduru, John Morgan, Kapil Sethi

Neurology Faculty Publications

Background: We report a patient who developed lower facial muscle spasm at rest and bilateral facial synkinesis several months after treatment of Guillain–Barré syndrome (GBS); this finding, to our knowledge, is hitherto unreported.

Phenomenology Shown: Bilateral synkinesis, facial muscles spasm at rest, bilateral postparalytic facial syndrome.

Educational Value: Aberrant regeneration of nerve fibers post GBS, resulting in facial muscles spasm at rest, bilateral synkinesis.


Human Cancer And Platelet Interaction, A Potential Therapeutic Target, Shike Wang, Zhenyu Li, Ren Xu Apr 2018

Human Cancer And Platelet Interaction, A Potential Therapeutic Target, Shike Wang, Zhenyu Li, Ren Xu

Markey Cancer Center Faculty Publications

Cancer patients experience a four-fold increase in thrombosis risk, indicating that cancer development and progression are associated with platelet activation. Xenograft experiments and transgenic mouse models further demonstrate that platelet activation and platelet-cancer cell interaction are crucial for cancer metastasis. Direct or indirect interaction of platelets induces cancer cell plasticity and enhances survival and extravasation of circulating cancer cells during dissemination. In vivo and in vitro experiments also demonstrate that cancer cells induce platelet aggregation, suggesting that platelet-cancer interaction is bidirectional. Therefore, understanding how platelets crosstalk with cancer cells may identify potential strategies to inhibit cancer metastasis and to reduce …


An International Delphi Survey For The Definition Of The Variables For The Development Of New Classification Criteria For Periodic Fever Aphtous Stomatitis Pharingitis Cervical Adenitis (Pfapa)., Federica Vanoni, Silvia Federici, Jordi Antón, Karyl S Barron, Paul Brogan, Fabrizio De Benedetti, Fatma Dedeoglu, Erkan Demirkaya, Veronique Hentgen, Tilmann Kallinich, Ronald Laxer, Ricardo Russo, Natasa Toplak, Yosef Uziel, Alberto Martini, Nicolino Ruperto, Marco Gattorno, Michael Hofer Apr 2018

An International Delphi Survey For The Definition Of The Variables For The Development Of New Classification Criteria For Periodic Fever Aphtous Stomatitis Pharingitis Cervical Adenitis (Pfapa)., Federica Vanoni, Silvia Federici, Jordi Antón, Karyl S Barron, Paul Brogan, Fabrizio De Benedetti, Fatma Dedeoglu, Erkan Demirkaya, Veronique Hentgen, Tilmann Kallinich, Ronald Laxer, Ricardo Russo, Natasa Toplak, Yosef Uziel, Alberto Martini, Nicolino Ruperto, Marco Gattorno, Michael Hofer

Paediatrics Publications

Background

Diagnosis of Periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) is currently based on a set of criteria proposed in 1999 modified from Marshall's criteria. Nevertheless no validated evidence based set of classification criteria for PFAPA has been established so far. The aim of this study was to identify candidate classification criteria PFAPA syndrome using international consensus formation through a Delphi questionnaire survey.

Methods

A first open-ended questionnaire was sent to adult and pediatric clinicians/researchers, asking to identify the variables thought most likely to be helpful and relevant for the diagnosis of PFAPA. In a second survey, respondents …


Differential Effects Of Linkers On The Activity Of Amphiphilic Tobramycin Antifungals, Marina Y. Fosso, Sanjib K. Shrestha, Nishad Thamban Chandrika, Emily K. Dennis, Keith D. Green, Sylvie Garneau-Tsodikova Apr 2018

Differential Effects Of Linkers On The Activity Of Amphiphilic Tobramycin Antifungals, Marina Y. Fosso, Sanjib K. Shrestha, Nishad Thamban Chandrika, Emily K. Dennis, Keith D. Green, Sylvie Garneau-Tsodikova

Pharmaceutical Sciences Faculty Publications

As the threat associated with fungal infections continues to rise and the availability of antifungal drugs remains a concern, it becomes obvious that the need to bolster the antifungal armamentarium is urgent. Building from our previous findings of tobramycin (TOB) derivatives with antifungal activity, we further investigate the effects of various linkers on the biological activity of these aminoglycosides. Herein, we analyze how thioether, sulfone, triazole, amide, and ether functionalities affect the antifungal activity of alkylated TOB derivatives against 22 Candida, Cryptococcus, and Aspergillus species. We also evaluate their impact on the hemolysis of murine erythrocytes and the …


An Inpatient Patient Safety Curriculum For Pediatric Residents., John Szymusiak, Michael D Fox, Catherine Polak, Kwonho Jeong, Doris Rubio, Stephanie Dewar, Andrew Urbach, Alda Maria Gonzaga Apr 2018

An Inpatient Patient Safety Curriculum For Pediatric Residents., John Szymusiak, Michael D Fox, Catherine Polak, Kwonho Jeong, Doris Rubio, Stephanie Dewar, Andrew Urbach, Alda Maria Gonzaga

Department of Pediatrics Faculty Papers

Introduction: Patient safety is recognized as an important part of pediatric resident education. There is a lack of published safety curricula targeting pediatric residents. A local needs assessment showed that while residents felt safety was an important part of their current and future jobs, they did not feel prepared to apply safety principles to their future careers or participate in a root cause analysis (RCA).

Methods: This curriculum was delivered to senior-level pediatric and multiple-board residents during five monthly, hour-long, multidisciplinary sessions. Sessions covered systems-based thinking, terminology, the second victim phenomenon, RCA, and medication errors, while providing feedback on recent …


Predictive Value For Cardiovascular Events Of Common Carotid Intima Media Thickness And Its Rate Of Change In Individuals At High Cardiovascular Risk - Results From The Prog-Imt Collaboration, Matthias W Lorenz, Lu Gao, Kathrin Ziegelbauer, Giuseppe Danilo Norata, Jean Philippe Empana, Irene Schmidtmann, Hung-Ju Lin, Stela Mclachlan, Lena Bokemark, Kimmo Ronkainen, Mauro Amato, Ulf Schminke, Sathanur R Srinivasan, Lars Lind, Shuhei Okazaki, Coen D A Stehouwer, Peter Willeit, Joseph F Polak, Helmuth Steinmetz, Dirk Sander, Holger Poppert, Moise Desvarieux, M Arfan Ikram, Stein Harald Johnsen, Daniel Staub, Cesare R Sirtori, Bernhard Iglseder, Oscar Beloqui, Gunnar Engström, Alfonso Friera, Francesco Rozza, Wuxiang Xie, Grace Parraga, Liliana Grigore, Matthieu Plichart, Stefan Blankenberg, Ta-Chen Su, Caroline Schmidt, Tomi-Pekka Tuomainen, Fabrizio Veglia, Henry Völzke, Giel Nijpels, Johann Willeit, Ralph L Sacco, Oscar H Franco, Heiko Uthoff, Bo Hedblad, Carmen Suarez, Raffaele Izzo, Dong Zhao, Thapat Wannarong, Alberico Catapano, Pierre Ducimetiere, Christine Espinola-Klein, Kuo-Liong Chien, Jackie F Price, Göran Bergström, Jussi Kauhanen, Elena Tremoli, Marcus Dörr, Gerald Berenson, Kazuo Kitagawa, Jacqueline M Dekker, Stefan Kiechl, Matthias Sitzer, Horst Bickel, Tatjana Rundek, Albert Hofman, Ellisiv B Mathiesen, Samuela Castelnuovo, Manuel F Landecho, Maria Rosvall, Rafael Gabriel, Nicola De Luca, Jing Liu, Damiano Baldassarre, Maryam Kavousi, Eric De Groot, Michiel L Bots, David N Yanez, Simon G Thompson Apr 2018

Predictive Value For Cardiovascular Events Of Common Carotid Intima Media Thickness And Its Rate Of Change In Individuals At High Cardiovascular Risk - Results From The Prog-Imt Collaboration, Matthias W Lorenz, Lu Gao, Kathrin Ziegelbauer, Giuseppe Danilo Norata, Jean Philippe Empana, Irene Schmidtmann, Hung-Ju Lin, Stela Mclachlan, Lena Bokemark, Kimmo Ronkainen, Mauro Amato, Ulf Schminke, Sathanur R Srinivasan, Lars Lind, Shuhei Okazaki, Coen D A Stehouwer, Peter Willeit, Joseph F Polak, Helmuth Steinmetz, Dirk Sander, Holger Poppert, Moise Desvarieux, M Arfan Ikram, Stein Harald Johnsen, Daniel Staub, Cesare R Sirtori, Bernhard Iglseder, Oscar Beloqui, Gunnar Engström, Alfonso Friera, Francesco Rozza, Wuxiang Xie, Grace Parraga, Liliana Grigore, Matthieu Plichart, Stefan Blankenberg, Ta-Chen Su, Caroline Schmidt, Tomi-Pekka Tuomainen, Fabrizio Veglia, Henry Völzke, Giel Nijpels, Johann Willeit, Ralph L Sacco, Oscar H Franco, Heiko Uthoff, Bo Hedblad, Carmen Suarez, Raffaele Izzo, Dong Zhao, Thapat Wannarong, Alberico Catapano, Pierre Ducimetiere, Christine Espinola-Klein, Kuo-Liong Chien, Jackie F Price, Göran Bergström, Jussi Kauhanen, Elena Tremoli, Marcus Dörr, Gerald Berenson, Kazuo Kitagawa, Jacqueline M Dekker, Stefan Kiechl, Matthias Sitzer, Horst Bickel, Tatjana Rundek, Albert Hofman, Ellisiv B Mathiesen, Samuela Castelnuovo, Manuel F Landecho, Maria Rosvall, Rafael Gabriel, Nicola De Luca, Jing Liu, Damiano Baldassarre, Maryam Kavousi, Eric De Groot, Michiel L Bots, David N Yanez, Simon G Thompson

Medical Biophysics Publications

AIMS: Carotid intima media thickness (CIMT) predicts cardiovascular (CVD) events, but the predictive value of CIMT change is debated. We assessed the relation between CIMT change and events in individuals at high cardiovascular risk.

METHODS AND RESULTS: From 31 cohorts with two CIMT scans (total n = 89070) on average 3.6 years apart and clinical follow-up, subcohorts were drawn: (A) individuals with at least 3 cardiovascular risk factors without previous CVD events, (B) individuals with carotid plaques without previous CVD events, and (C) individuals with previous CVD events. Cox regression models were fit to estimate the hazard ratio (HR) of …


Macrophage-Derived Il-1Β/Nf-Κb Signaling Mediates Parenteral Nutrition-Associated Cholestasis., Karim C El Kasmi, Padade M Vue, Aimee L Anderson, Michael W Devereaux, Swati Ghosh, Natarajan Balasubramaniyan, Sophie A Fillon, Carola Dahrenmoeller, Ayed Allawzi, Crystal Woods, Sarah Mckenna, Clyde J Wright, Linda Johnson, Angelo D'Alessandro, Julie A Reisz, Eva Nozik-Grayck, Frederick J Suchy, Ronald J Sokol Apr 2018

Macrophage-Derived Il-1Β/Nf-Κb Signaling Mediates Parenteral Nutrition-Associated Cholestasis., Karim C El Kasmi, Padade M Vue, Aimee L Anderson, Michael W Devereaux, Swati Ghosh, Natarajan Balasubramaniyan, Sophie A Fillon, Carola Dahrenmoeller, Ayed Allawzi, Crystal Woods, Sarah Mckenna, Clyde J Wright, Linda Johnson, Angelo D'Alessandro, Julie A Reisz, Eva Nozik-Grayck, Frederick J Suchy, Ronald J Sokol

Articles, Abstracts, and Reports

In infants intolerant of enteral feeding because of intestinal disease, parenteral nutrition may be associated with cholestasis, which can progress to end-stage liver disease. Here we show the function of hepatic macrophages and phytosterols in parenteral nutrition-associated cholestasis (PNAC) pathogenesis using a mouse model that recapitulates the human pathophysiology and combines intestinal injury with parenteral nutrition. We combine genetic, molecular, and pharmacological approaches to identify an essential function of hepatic macrophages and IL-1β in PNAC. Pharmacological antagonism of IL-1 signaling or genetic deficiency in CCR2, caspase-1 and caspase-11, or IL-1 receptor (which binds both IL-1α and IL-1β) prevents PNAC in …


A Behavioral Lifestyle Intervention Enhanced With Multiple-Behavior Self-Monitoring Using Mobile And Connected Tools For Underserved Individuals With Type 2 Diabetes And Comorbid Overweight Or Obesity: Pilot Comparative Effectiveness Trial, Jing Wang, Chunyan Cai, Nikhil Padhye, Philip Orlander, Mohammad Zare Apr 2018

A Behavioral Lifestyle Intervention Enhanced With Multiple-Behavior Self-Monitoring Using Mobile And Connected Tools For Underserved Individuals With Type 2 Diabetes And Comorbid Overweight Or Obesity: Pilot Comparative Effectiveness Trial, Jing Wang, Chunyan Cai, Nikhil Padhye, Philip Orlander, Mohammad Zare

Faculty, Staff and Student Publications

BACKGROUND: Self-monitoring is a cornerstone of behavioral lifestyle interventions for obesity and type 2 diabetes mellitus. Mobile technology has the potential to improve adherence to self-monitoring and patient outcomes. However, no study has tested the use of a smartphone to facilitate self-monitoring in overweight or obese adults with type 2 diabetes mellitus living in the underserved community.

OBJECTIVE: The aim of this study was to examine the feasibility of and compare preliminary efficacy of a behavioral lifestyle intervention using smartphone- or paper-based self-monitoring of multiple behaviors on weight loss and glycemic control in a sample of overweight or obese adults …


Sall1 Functions As A Tumor Suppressor In Breast Cancer By Regulating Cancer Cell Senescence And Metastasis Through The Nurd Complex, Chunling Ma, Fang Wang, Bing Han, Xiaoli Zhong, Fusheng Si, Jian Ye, Eddy C Hsueh, Lynn Robbins, Susan M Kiefer, Yanping Zhang, Pamela Hunborg, Mark A Varvares, Michael Rauchman, Guangyong Peng Apr 2018

Sall1 Functions As A Tumor Suppressor In Breast Cancer By Regulating Cancer Cell Senescence And Metastasis Through The Nurd Complex, Chunling Ma, Fang Wang, Bing Han, Xiaoli Zhong, Fusheng Si, Jian Ye, Eddy C Hsueh, Lynn Robbins, Susan M Kiefer, Yanping Zhang, Pamela Hunborg, Mark A Varvares, Michael Rauchman, Guangyong Peng

Open Access Publications

BACKGROUND: SALL1 is a multi-zinc finger transcription factor that regulates organogenesis and stem cell development, but the role of SALL1 in tumor biology and tumorigenesis remains largely unknown.

METHODS: We analyzed SALL1 expression levels in human and murine breast cancer cells as well as cancer tissues from different types of breast cancer patients. Using both in vitro co-culture system and in vivo breast tumor models, we investigated how SALL1 expression in breast cancer cells affects tumor cell growth and proliferation, metastasis, and cell fate. Using the gain-of function and loss-of-function strategies, we dissected the molecular mechanism responsible for SALL1 tumor …


Does Specialist Physician Supply Affect Pediatric Asthma Health Outcomes?, Guido Filler, Tom Kovesi, Erik Bourdon, Sarah Ann Jones, Laurentiu Givelichian, Cheryl Rockman-Greenberg, Jason Gilliland, Marion Williams, Elaine Orrbine, Bruno Piedboeuf Apr 2018

Does Specialist Physician Supply Affect Pediatric Asthma Health Outcomes?, Guido Filler, Tom Kovesi, Erik Bourdon, Sarah Ann Jones, Laurentiu Givelichian, Cheryl Rockman-Greenberg, Jason Gilliland, Marion Williams, Elaine Orrbine, Bruno Piedboeuf

Paediatrics Publications

Background

Pediatrician and pediatric subspecialist density varies substantially among the various Canadian provinces, as well as among various states in the US. It is unknown whether this variability impacts health outcomes. To study this knowledge gap, we evaluated pediatric asthma admission rates within the 2 Canadian provinces of Manitoba and Saskatchewan, which have similarly sized pediatric populations and substantially different physician densities.

Methods

This was a retrospective cross-sectional cohort study. Health regions defined by the provincial governments, have, in turn, been classified into "peer groups" by Statistics Canada, on the basis of common socio-economic characteristics and socio-demographic determinants of health. …


Evaluation Of The Impact Of Telementoring Using Echo© Technology On Healthcare Professionals' Knowledge And Self-Efficacy In Assessing And Managing Pain For People With Advanced Dementia Nearing The End Of Life, Bannin De Witt Jansen, Kevin Brazil, Peter Passmore, Hilary Buchanan, Doreen Maxwell, Sonja J Mcilfatrick, Sharon M Morgan, Max Watson, Carole Parsons Apr 2018

Evaluation Of The Impact Of Telementoring Using Echo© Technology On Healthcare Professionals' Knowledge And Self-Efficacy In Assessing And Managing Pain For People With Advanced Dementia Nearing The End Of Life, Bannin De Witt Jansen, Kevin Brazil, Peter Passmore, Hilary Buchanan, Doreen Maxwell, Sonja J Mcilfatrick, Sharon M Morgan, Max Watson, Carole Parsons

Project ECHO Bibliography

BACKGROUND: Pain assessment and management in advanced and end-stage dementia are challenging; patients are at risk of under-diagnosis, under-assessment and under-treatment. Previous research has highlighted the importance of needs-driven training and development in this area for physicians, nurses and healthcare assistants (HCAs) across specialties, disciplines and care settings. This study used teleconferencing technology to connect healthcare professionals across multiple settings and disciplines in real-time clinics, based on the Project ECHO© model. This paper reports the evaluation of the clinics by physicians, nurses and HCAs, including their knowledge and self-efficacy in pain assessment and management for patients with advanced and end-stage …


Left Frontal Hub Connectivity Delays Cognitive Impairment In Autosomal-Dominant And Sporadic Alzheimer's Disease, Nicolai Franzmeier, Anne M Fagan, Katrina Paumier, Tammie Benzinger, John C Morris, Randall J Bateman, Et Al. Apr 2018

Left Frontal Hub Connectivity Delays Cognitive Impairment In Autosomal-Dominant And Sporadic Alzheimer's Disease, Nicolai Franzmeier, Anne M Fagan, Katrina Paumier, Tammie Benzinger, John C Morris, Randall J Bateman, Et Al.

2010-2019 OA Pubs

Patients with Alzheimer's disease vary in their ability to sustain cognitive abilities in the presence of brain pathology. A major open question is which brain mechanisms may support higher reserve capacity, i.e. relatively high cognitive performance at a given level of Alzheimer's pathology. Higher functional MRI-assessed functional connectivity of a hub in the left frontal cortex is a core candidate brain mechanism underlying reserve as it is associated with education (i.e. a protective factor often associated with higher reserve) and attenuated cognitive impairment in prodromal Alzheimer's disease. However, no study has yet assessed whether such hub connectivity of the left …


Seeing The Forest And The Trees: Default Local Processing In Individuals With High Autistic Traits Does Not Come At The Expense Of Global Attention., Ryan A Stevenson, Sol Z Sun, Naomi Hazlett, Jonathan S Cant, Morgan D Barense, Susanne Ferber Apr 2018

Seeing The Forest And The Trees: Default Local Processing In Individuals With High Autistic Traits Does Not Come At The Expense Of Global Attention., Ryan A Stevenson, Sol Z Sun, Naomi Hazlett, Jonathan S Cant, Morgan D Barense, Susanne Ferber

Brain and Mind Institute Researchers' Publications

Atypical sensory perception is one of the most ubiquitous symptoms of autism, including a tendency towards a local-processing bias. We investigated whether local-processing biases were associated with global-processing impairments on a global/local attentional-scope paradigm in conjunction with a composite-face task. Behavioural results were related to individuals' levels of autistic traits, specifically the Attention to Detail subscale of the Autism Quotient, and the Sensory Profile Questionnaire. Individuals showing high rates of Attention to Detail were more susceptible to global attentional-scope manipulations, suggesting that local-processing biases associated with Attention to Detail do not come at the cost of a global-processing deficit, but …


Nephrocalcinosis: A Diagnostic Conundrum, Lalathaksha Kumbar, Jerry Yee Apr 2018

Nephrocalcinosis: A Diagnostic Conundrum, Lalathaksha Kumbar, Jerry Yee

Nephrology Articles

No abstract provided.


Hospital-Based Physicians' Intubation Decisions And Associated Mental Models When Managing A Critically And Terminally Ill Older Patient., Shannon Haliko, Julie Downs, Deepika Mohan, Robert Arnold, Amber E Barnato Apr 2018

Hospital-Based Physicians' Intubation Decisions And Associated Mental Models When Managing A Critically And Terminally Ill Older Patient., Shannon Haliko, Julie Downs, Deepika Mohan, Robert Arnold, Amber E Barnato

Articles, Abstracts, and Reports

BACKGROUND: Variation in the intensity of acute care treatment at the end of life is influenced more strongly by hospital and provider characteristics than patient preferences.

OBJECTIVE: We sought to describe physicians' mental models (i.e., thought processes) when encountering a simulated critically and terminally ill older patient, and to compare those models based on whether their treatment plan was patient preference-concordant or preference-discordant.

METHODS: Seventy-three hospital-based physicians from 3 academic medical centers engaged in a simulated patient encounter and completed a mental model interview while watching the video recording of their encounter. We used an "expert" model to code the …


Genetic Variants In Hsd17b3, Smad3, And Ipo11 Impact Circulating Lipids In Response To Fenofibrate In Individuals With Type 2 Diabetes, Daniel M. Rotroff, Sonja S. Pijut, Skylar W. Marvel, John R. Jack, Tammy M. Havener, Aurora Pujol, Agatha Schluter, Gregory A. Graf, Henry N. Ginsberg, Hetal S. Shah, He Gao, Mario-Luca Morieri, Alessandro Doria, Josyf C. Mychaleckyi, Howard L. Mcleod, John B. Buse, Michael J. Wagner, Alison A. Motsinger-Reif, Accord/Accordion Investigators Apr 2018

Genetic Variants In Hsd17b3, Smad3, And Ipo11 Impact Circulating Lipids In Response To Fenofibrate In Individuals With Type 2 Diabetes, Daniel M. Rotroff, Sonja S. Pijut, Skylar W. Marvel, John R. Jack, Tammy M. Havener, Aurora Pujol, Agatha Schluter, Gregory A. Graf, Henry N. Ginsberg, Hetal S. Shah, He Gao, Mario-Luca Morieri, Alessandro Doria, Josyf C. Mychaleckyi, Howard L. Mcleod, John B. Buse, Michael J. Wagner, Alison A. Motsinger-Reif, Accord/Accordion Investigators

Pharmaceutical Sciences Faculty Publications

Individuals with type 2 diabetes (T2D) and dyslipidemia are at an increased risk of cardiovascular disease. Fibrates are a class of drugs prescribed to treat dyslipidemia, but variation in response has been observed. To evaluate common and rare genetic variants that impact lipid responses to fenofibrate in statin‐treated patients with T2D, we examined lipid changes in response to fenofibrate therapy using a genomewide association study (GWAS). Associations were followed‐up using gene expression studies in mice. Common variants in SMAD3 and IPO11 were marginally associated with lipid changes in black subjects (P < 5 × 10‐6). Rare variant and gene expression changes …


Menopausal-Related Symptoms In Women One Year After Breast Cancer Surgery., Melissa Mazor, Kathryn Lee, Anand Dhruva, Janine K Cataldo, Steven M Paul, Michelle Melisko, Betty J Smoot, Jon D Levine, Charles Elboim, Yvette P Conley, Christine Miaskowksi Apr 2018

Menopausal-Related Symptoms In Women One Year After Breast Cancer Surgery., Melissa Mazor, Kathryn Lee, Anand Dhruva, Janine K Cataldo, Steven M Paul, Michelle Melisko, Betty J Smoot, Jon D Levine, Charles Elboim, Yvette P Conley, Christine Miaskowksi

Articles, Abstracts, and Reports

CONTEXT: Approximately 60% to 100% of women with breast cancer experience at least one menopausal-related symptom. Little is known about associations between menopausal status and symptoms in women 12 months after breast cancer surgery.

OBJECTIVES: The purpose of this study was to evaluate for differences in occurrence, severity, and distress of symptoms between pre- and postmenopausal women 12 months after breast cancer surgery.

METHODS: Women with breast cancer (n = 327) completed the Menopausal Symptoms Scale, which evaluated the occurrence, severity, and distress of 46 common menopausal-related symptoms. Regression analyses were used to evaluate between-group differences in the seven symptoms …


A Test Of Multisession Automatic Action Tendency Retraining To Reduce Alcohol Consumption Among Young Adults In The Context Of A Human Laboratory Paradigm., Robert F Leeman, Christine Nogueira, Reinout W Wiers, Janna Cousijn, Kelly Serafini, Kelly S Demartini, John A Bargh, Stephanie S O'Malley Apr 2018

A Test Of Multisession Automatic Action Tendency Retraining To Reduce Alcohol Consumption Among Young Adults In The Context Of A Human Laboratory Paradigm., Robert F Leeman, Christine Nogueira, Reinout W Wiers, Janna Cousijn, Kelly Serafini, Kelly S Demartini, John A Bargh, Stephanie S O'Malley

Articles, Abstracts, and Reports

BACKGROUND: Young adult heavy drinking is an important public health concern. Current interventions have efficacy but with only modest effects, and thus, novel interventions are needed. In prior studies, heavy drinkers, including young adults, have demonstrated stronger automatically triggered approach tendencies to alcohol-related stimuli than lighter drinkers. Automatic action tendency retraining has been developed to correct this tendency and consequently reduce alcohol consumption. This study is the first to test multiple iterations of automatic action tendency retraining, followed by laboratory alcohol self-administration.

METHODS: A total of 72 nontreatment-seeking, heavy drinking young adults ages 21 to 25 were randomized to automatic …


Opportunities And Obstacles For Deep Learning In Biology And Medicine, Travers Ching, S Joshua Swamidass, Et Al Apr 2018

Opportunities And Obstacles For Deep Learning In Biology And Medicine, Travers Ching, S Joshua Swamidass, Et Al

2010-2019 OA Pubs

Deep learning describes a class of machine learning algorithms that are capable of combining raw inputs into layers of intermediate features. These algorithms have recently shown impressive results across a variety of domains. Biology and medicine are data-rich disciplines, but the data are complex and often ill-understood. Hence, deep learning techniques may be particularly well suited to solve problems of these fields. We examine applications of deep learning to a variety of biomedical problems-patient classification, fundamental biological processes and treatment of patients-and discuss whether deep learning will be able to transform these tasks or if the biomedical sphere poses unique …


Validation Of An Icd Code For Accurately Identifying Emergency Department Patients Who Suffer An Out-Of-Hospital Cardiac Arrest., Shelby K. Shelton, Steve B. Chukwulebe, David F. Gaieski, Benjamin S. Abella, Brendan G. Carr, Sarah M. Perman Apr 2018

Validation Of An Icd Code For Accurately Identifying Emergency Department Patients Who Suffer An Out-Of-Hospital Cardiac Arrest., Shelby K. Shelton, Steve B. Chukwulebe, David F. Gaieski, Benjamin S. Abella, Brendan G. Carr, Sarah M. Perman

Department of Emergency Medicine Faculty Papers

AIM: International classification of disease (ICD-9) code 427.5 (cardiac arrest) is utilized to identify cohorts of patients who suffer out-of-hospital cardiac arrest (OHCA), though the use of ICD codes for this purpose has never been formally validated. We sought to validate the utility of ICD-9 code 427.5 by identifying patients admitted from the emergency department (ED) after OHCA.

METHODS: Adult visits to a single ED between January 2007 and July 2012 were retrospectively examined and a keyword search of the electronic medical record (EMR) was used to identify patients. Cardiac arrest was confirmed; and ICD-9 information and location of return …


High Sodium Continuous Veno-Venous Hemodialysis With Regional Citrate Anticoagulation And Online Dialysate Generation In Patients With Acute Liver Failure And Cerebral Edema, Tamim Hamdi, Lenar Yessayan, Jerry Yee, Balazs Szamosfalvi Apr 2018

High Sodium Continuous Veno-Venous Hemodialysis With Regional Citrate Anticoagulation And Online Dialysate Generation In Patients With Acute Liver Failure And Cerebral Edema, Tamim Hamdi, Lenar Yessayan, Jerry Yee, Balazs Szamosfalvi

Nephrology Articles

INTRODUCTION: Acute liver failure is associated with a high mortality rate. Induction of plasma hypertonicity with mannitol or hypertonic saline remains the cornerstone in the management of resultant cerebral edema. Significant disadvantages of this approach include poor or unpredictable control of serum sodium concentration and volume expansion, among others.

METHODS: We used high sodium continuous veno-venous hemodialysis with regional citrate anticoagulation and online dialysate generation to accurately control the serum sodium in eleven patients with acute liver failure, renal failure, and cerebral edema. We used a Fresenius 2008 K/K2 machine in hemodialysis mode to deliver a blood flow of 60 …


Early Relapse After Autologous Hematopoietic Cell Transplantation Remains A Poor Prognostic Factor In Multiple Myeloma But Outcomes Have Improved Over Time, Shaji K. Kumar, Angela Dispenzieri, Raphael Fraser, Fei Mingwei, Gorgun Akpek, Robert Cornell, Mohamed Kharfan-Dabaja, Cesar Freytes, Shahrukh Hashmi, Gerhard C. Hildebrandt, Leona Holmberg, Robert Kyle, Hillard Lazarus, Cindy Lee, Jospeh Mikhael, Taiga Nishihori, Jason Tay, Saad Usmani, David Vesole, Ravi Vij, Baldeep Wirk, Amrita Krishnan, Cristina Gasparetto, Tomer Mark, Yago Nieto, Parameswaran Hari, Anita D'Souza Apr 2018

Early Relapse After Autologous Hematopoietic Cell Transplantation Remains A Poor Prognostic Factor In Multiple Myeloma But Outcomes Have Improved Over Time, Shaji K. Kumar, Angela Dispenzieri, Raphael Fraser, Fei Mingwei, Gorgun Akpek, Robert Cornell, Mohamed Kharfan-Dabaja, Cesar Freytes, Shahrukh Hashmi, Gerhard C. Hildebrandt, Leona Holmberg, Robert Kyle, Hillard Lazarus, Cindy Lee, Jospeh Mikhael, Taiga Nishihori, Jason Tay, Saad Usmani, David Vesole, Ravi Vij, Baldeep Wirk, Amrita Krishnan, Cristina Gasparetto, Tomer Mark, Yago Nieto, Parameswaran Hari, Anita D'Souza

Internal Medicine Faculty Publications

Duration of initial disease response remains a strong prognostic factor in multiple myeloma (MM) particularly for upfront autologous hematopoietic cell transplant (AHCT) recipients. We hypothesized that new drug classes and combinations employed prior to AHCT as well as after post-AHCT relapse may have changed the natural history of MM in this population. We analyzed the Center for International Blood and Marrow Transplant Research database to track overall survival (OS) of MM patients receiving single AHCT within 12 months after diagnosis (N=3256) and relapsing early post-AHCT (< 24 months), and to identify factors predicting for early vs late relapses (24−48 months post-AHCT). Over three periods (2001–2004, 2005–2008, 2009–2013), patient characteristics were balanced except for lower proportion of Stage III, higher likelihood of one induction therapy with novel triplets and higher rates of planned post-AHCT maintenance over time. The proportion of patients relapsing early was stable over time at 35–38%. Factors reducing risk of early relapse included lower stage, chemosensitivity, transplant after 2008 and post-AHCT maintenance. Shorter post-relapse OS was associated with early relapse, IgA MM, Karnofsky < 90, stage III, > 1 line of induction and lack of maintenance. Post-AHCT early relapse remains …


Short Term Development And Fate Of Mge-Like Neural Progenitor Cells In Jaundiced And Non-Jaundiced Rat Brain., Fu-Chen Yang, Julia Draper, Peter G Smith, Jay L. Vivian, Steven Shapiro, John A. Stanford Apr 2018

Short Term Development And Fate Of Mge-Like Neural Progenitor Cells In Jaundiced And Non-Jaundiced Rat Brain., Fu-Chen Yang, Julia Draper, Peter G Smith, Jay L. Vivian, Steven Shapiro, John A. Stanford

Manuscripts, Articles, Book Chapters and Other Papers

Neonatal hyperbilirubinemia targets specific brain regions and can lead to kernicterus. One of the most debilitating symptoms of kernicterus is dystonia, which results from bilirubin toxicity to the globus pallidus (GP). Stem cell transplantation into the GP to replace lost neurons and restore basal ganglia circuits function is a potential therapeutic strategy to treat dystonia in kernicterus. In this study we transplanted human medial ganglionic eminence (MGE)-like neural progenitor cells (NPCs) that we differentiated into a primarily gamma-aminobutyric acid (GABA)ergic phenotype, into the GP of non-immunosuppressed jaundiced (jj) and non-jaundiced (Nj) rats. We assessed the survival and development of graft …


Opioid-Related Critical Care Resource Use In Us Children's Hospitals., Jason M. Kane, Jeffrey D. Colvin, Allison H. Bartlett, Matt Hall Apr 2018

Opioid-Related Critical Care Resource Use In Us Children's Hospitals., Jason M. Kane, Jeffrey D. Colvin, Allison H. Bartlett, Matt Hall

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND AND OBJECTIVES: There has been a rapid increase in the rate of pediatric opioid-related hospitalizations. It is unknown how this increase has impacted the use of pediatric critical care. Our objective in this study was to assess the trends in pediatric hospitalization for opioid ingestions in a cohort of US children's hospitals and, specifically, to evaluate the impact on pediatric critical care resource use.

METHODS: A retrospective cohort study of the Pediatric Health Information System was performed to identify hospitalizations for opioid ingestions from 2004 to 2015. Admission to the PICU and the use of naloxone, vasopressors, and ventilation …


Identifying Health Conditions, Priorities, And Relevant Multilevel Health Promotion Intervention Strategies In African American Churches: A Faith Community Health Needs Assessment., Jannette Berkley-Patton, Carole Bowe Thompson, Andrea Bradley-Ewing, Marcie Berman, Alexandria Bauer, Delwyn Catley, Kathy Goggin, Eric Williams, Cassandra Wainright, Therese Petty, Natasha Aduloju-Ajijola Apr 2018

Identifying Health Conditions, Priorities, And Relevant Multilevel Health Promotion Intervention Strategies In African American Churches: A Faith Community Health Needs Assessment., Jannette Berkley-Patton, Carole Bowe Thompson, Andrea Bradley-Ewing, Marcie Berman, Alexandria Bauer, Delwyn Catley, Kathy Goggin, Eric Williams, Cassandra Wainright, Therese Petty, Natasha Aduloju-Ajijola

Manuscripts, Articles, Book Chapters and Other Papers

No abstract provided.