Digital Commons Network^™

A Review Of Medical Ethics In Orthopaedic Surgery: Current Foci And Future Considerations, Ryan X Lam, Zhi Mei Sonia He, Ruhi Thapar, Maggie Wang, Dion G Birhiray, Matthew Milad, Lara Ouellette, Umar Ghilzai, Tucker J Cushing, M Brent Price, Brenden B Ronna, Omar H Atassi, Christopher H Perkins, John R Dawson, William M Granberry, Melvyn A Harrington, Douglas R Dirschl, Lorenzo R Deveza

Library Staff Publications

Medical ethics education is a required component of orthopaedic surgery resident training per the Accreditation Council for Graduate Medical Education (ACGME) guidelines, although no standardized curriculum currently exists.

Beyond the 4 principles of bioethics (autonomy, beneficence, nonmaleficence, justice), additional ethical concepts relevant to orthopaedic care include utilitarianism, deontology, virtue ethics, moral intuitionism, microethics, and narrative ethics.

Ethical themes identified in the literature relevant to orthopaedic surgery include the ethics involved in medical decision-making, use of new technologies, caring for vulnerable patients, performing high-stakes procedures, the impacts of trainee status on patient care, and patient attitude regarding conflict of interest.

Ethical …

Subcortical Correlates Of Consciousness With Human Single Neuron Recordings, Michael Pereira, Nathan Faivre, Fosco Bernasconi, Nicholas Brandmeir, Jacob E Suffridge, Kaylee Tran, Shuo Wang, Victor Finomore, Peter Konrad, Ali Rezai, Olaf Blanke

2020-Current year OA Pubs

Subcortical brain structures such as the subthalamic nucleus or the thalamus are involved in regulating motor and cognitive behavior. However, their contribution to perceptual consciousness remains unclear, due to the inherent difficulties of recording subcortical neuronal activity in humans. Here, we asked neurological patients undergoing surgery for deep brain stimulation to detect weak vibrotactile stimuli applied on their hand while recording single neuron activity from the tip of a microelectrode. We isolated putative single neurons in the subthalamic nucleus and thalamus. A significant proportion of neurons modulated their activity while participants were expecting a stimulus. We found that the firing …

Conveying The Need For Mental Healthcare – A Qualitative Study Of How Patients Communicate Mental Health Challenges’, Marit Nymoen, Marit Lomeland, Eva Biringer, Mirjam Extedt, Øystein Hetlevik, Rod Sheaff, Olav Thorsen, Miriam Hartveit

Peninsula Medical School

Background: Access to timely mental healthcare relies on patients’ descriptions of their mental health problems. We therefore sought to better understand, from the patients’ perspective, how they communicate their need for specialised mental healthcare to their GPs or mental health specialists and what factors affect communication when patients are referred from their GPs to specialised mental healthcare. Methods: This was an exploratory interview study. Ten adults who started treatment in specialised mental healthcare facilities were interviewed individually. The interviews were audiotaped and transcribed verbatim. A method based on thematic analysis was used to develop patterns and themes within the dataset …

Patient-Reported Social Determinants Of Health In Patients With Heart Failure, Kenneth E Freedland, Brian C Steinmeyer, Judith A Skala, Robert M Carney, Michael W Rich

2020-Current year OA Pubs

BACKGROUND: Social determinants of health (SDOH) complicate medical care and affect clinical outcomes, but the lack of a reliable structured interview for medical patients has impeded clinical assessment and research on SDOH. We assessed the reliability and validity of a newly developed SDOH Patient Interview Form and investigated SDOH in patients with heart failure.

METHODS: The SDOH Patient Interview Form was administered to recently hospitalized patients with heart failure between January 2021 and April 2024. The interviews were recorded, and 50 were randomly selected for the interrater reliability analysis.

RESULTS: The sample included 367 participants (mean age, 61.2±12.1 years; 42.5% …

Approach To The Patient: From Endocrinopathy To The Diagnosis Of A Histiocytic Disorder, Polyzois Makras, Dana Erickson, Caroline J Davidge-Pitts, Eli L Diamond, Carl E Allen, Kenneth L Mcclain, Jithma P Abeykoon, Ronald S Go, Krishmita Siwakoti, Houman Sotoudeh, Aishwarya Ravindran, Lucinda M Gruber, Gaurav Goyal

Faculty, Staff and Students Publications

Endocrinopathies are frequently the initial presentation of histiocytic neoplasms, which are rare hematologic disorders affecting multiple organ systems. Langerhans cell histiocytosis and Erdheim-Chester disease are 2 such disorders known to infiltrate the hypothalamus and/or pituitary gland, leading to arginine vasopressin deficiency (AVP-D) and anterior pituitary dysfunction (APD) in 20% to 30% of cases, often as the first manifestation. Conversely, histiocytic disorders account for a notable proportion (10-15%) of all pituitary stalk lesions. The diagnosis of histiocytoses is often delayed in such cases due to the nonspecific presentation of endocrinopathies and pituitary involvement. Consequently, endocrinologists are at the frontline and uniquely …

Enhancing Theory-Driven Design And Evaluation Of Patient-Facing Technologies, Yang Gong, Yuheng Shi, Eric Yang, Katie Gahn, Heidi Mason, Yun Jiang

Faculty, Staff and Student Publications

Patient-facing technologies (PFTs) are essential tools for patient-centered outcome research. The current designs of PFTs need solid theoretical support and face challenges with maintenance and sustainability. This paper identifies PFT features and theoretical frameworks that support patient engagement in cancer care. Six prevailing PFT features - feedback & alert, a summary of entries, education materials, aggregated review, dedicated staff, and reminders - were identified in the primary literature, and five theoretical frameworks were adopted to guide the design and evaluation of 20 PFTs. Further research into user-centered design, personalization, and social context in PFT development is recommended to connect system …

Identifying Distinct Subgroups With Severe Pain In Sickle Cell Disease: A Cluster Analysis Of The Grndad Multi-Center Registry, Martha O. Kenney, Samuel Wilson, Morgan Rosser, Sophie Lanzkron, Julie Kanter, Susan Padrino, Payal Desai, Deepa Manwani, Alice Cohen, Stephanie Guarino, Ward Hagar, Joshua Field, Jane Little

Department of Medicine Faculty Papers

Sickle cell disease (SCD) affects millions of individuals worldwide, and is characterized by both acute, episodic pain and chronic, persistent pain. Despite the significant burden of the disease, clinicians continue to face significant challenges in treating SCD pain due to variability in pain experiences. The objectives of this study were (1) to identify distinct pain subgroups based on demographic and biopsychosocial characteristics and (2) to evaluate the relationship between the subgroups and pain impact - a SCD-disease specific measure of pain interference. To achieve these objectives, we performed a hierarchical cluster analysis on a cross-sectional sample of adults with SCD …

Functional Brain Connectivity Of The Salience Network In Alcohol Use And Anxiety Disorders, Dhruv M Patel, Guillermo F Poblete, Alexandra Castellanos, Ramiro Salas

Staff and Researcher Publications

The interplay between alcohol use disorder (AUD) and anxiety disorders (ANX) is well-documented, yet the underlying neurobiological mechanisms remain elusive. This study aims to elucidate these mechanisms by examining the resting-state functional connectivity (RSFC) within the salience network and to the amygdala, both implicated in alcohol and anxiety disorders. We analyzed data from 264 inpatient participants culled from a wider group of 518 inpatients at The Menninger Clinic in Houston, TX, categorized into four groups (n = 66 each) based on DSM-IV diagnoses: AUD without ANX (AUD), ANX without AUD (ANX), concurrent AUD and ANX (BOTH), and neither (NEITHER). Our …

Genetic, Transcriptomic, And Epigenomic Insights Into Sjögren's Disease: An Integrative Network Investigation And Immune Diseases Comparison, Nitesh Enduru, Astrid M Manuel, Zhongming Zhao

Faculty, Staff and Student Publications

Sjögren's disease (SjD) is a systemic autoimmune disorder primarily causing dry eyes and mouth. It frequently overlaps with other autoimmune diseases (AIDs), including rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). However, the genetic basis of SjD remains underexplored, limiting our understanding of its connections to other immune-mediated conditions. In this study, we aimed to identify gene networks associated with SjD through the integration of genetic, transcriptomic, and epigenomic data. We further compared the genetic factors of SjD with other immune-mediated diseases. We analyzed genome-wide association studies (GWAS) summary statistics, DNA methylation, and transcriptomic data using our in-house network-based methods, …

White Matter Connections Within The Central Sulcus Subserving The Somato-Cognitive Action Network, Georgios P Skandalakis, Evan M Gordon, Nico U F Dosenbach, Et Al.

2020-Current year OA Pubs

The somato-cognitive action network (SCAN) consists of three nodes interspersed within Penfield's motor effector regions. The configuration of the somato-cognitive action network nodes resembles the one of the 'plis de passage' of the central sulcus: small gyri bridging the precentral and postcentral gyri. Thus, we hypothesize that these may provide a structural substrate of the somato-cognitive action network. Using microdissections of 16 human hemispheres, we consistently identified a chain of three distinct plis de passage with increased underlying white matter in locations analogous to the somato-cognitive action network nodes. We mapped localizations of plis de passage into standard stereotactic space …

Narratives Or Not? Examining The Roles Of Message Format And Individuals' Stages Of Change In The Context Of Hpv Vaccination Promotion, Mengfei Guan, Shawn C. Chiang, Regan M. Murray, Wen-Juo Lo, Larry T. Hill, Ann C. Klassen, Jennifer A. Manganello, Amy E. Leader, Philip M. Massey

Department of Medical Oncology Faculty Papers

Narrative persuasion has been widely used in health communication campaigns and persuasive message design. However, several meta-analyses showed that the relative effectiveness of narratives in promoting behavior change was not consistently observed in the existing literature. With the goal of exploring boundary conditions of narrative effects, this study investigates the interaction effects of narrative persuasion and stages of change on promoting behavior change in the context of encouraging parents to vaccinate their children against human papillomavirus (HPV). Findings from an online experiment (N = 593) showed that non-narrative messages were more effective in bolstering behavioral intention than narrative messages among …

A Comparison Of Resurgence Following Dra And Dro, Alysa Georgopoulos

Theses & Dissertations

Resurgence, a form of behavioral relapse, occurs when a previously reduced target behavior reemerges after an alternative source of reinforcement is discontinued. Differential reinforcement of alternative behavior (DRA) and differential reinforcement of other behavior (DRO) are commonly used strategies to reduce undesired behaviors. Although both are effective, unanticipated periods of extinction (e.g., service lapses or staff turnover) may lead to resurgence of the original target behavior. Romano and St. Peter (2017) found that behavior reduced via DRO was more prone to resurgence than behavior reduced via DRA. However, their study used a different number of response options between conditions (one …

Exploring The International Terminology Associated With Nurses Caring For Neonates, Infants, Children, Young People And Their Families., Matt Carey, Jane Coad, Imelda Coyne, Suja Somanadhan, Sarah Neill

School of Nursing and Midwifery

The terminology used for Registered Nurses specializing in caring for neonates, infants, children, young people (CYP), and their families varies globally. While many countries’ nursing students qualify as “Registered Nurses” upon completion of undergraduate education, specialist titles like “Children’s Nurses” in the United Kingdom or “Pediatric Nurses” in Italy denote expertise in CYP care. In countries like the United States and Canada, neonatal and pediatric nursing specialization typically requires postgraduate study. However, there is limited evidence on the range of international terms for nurses in this field. This expert opinion paper presents the results from a scoping survey designed to …

Overconfidence And Financial Risk Tolerance In Older Age, Colleen C Frank, Gary R Mottola, Meiru Chen, Lei Yu, Patricia A Boyle, Gregory R Samanez-Larkin, Kendra L Seaman

Faculty, Staff and Student Publications

Objectives: Excessive financial risk-taking in older age can have harmful consequences as opportunities to recover lost wealth are limited. Understanding financial risk-taking in older age is important for identifying vulnerabilities and developing interventions to empower aging investors to make wise financial choices. In this paper, we explore how overconfidence in financial knowledge affects financial risk-taking among older adults.

Methods: We examine this research question in older adults aged 58-101 (N = 1,242) using data from the Rush Memory and Aging Project (MAP).

Results: After controlling for demographics, overconfidence was associated with self-reported financial risk tolerance such that those who were …

Empathy And Psychological Outcomes In Informal Caregivers Of Community-Dwelling Older Adults: A Systematic Review And Meta-Analysis, Meng Huo, Thi Vu, Tomiko Yoneda, Jingkai Wei, Bruce Abbott, Joan K Monin

Faculty, Staff and Student Publications

Objectives: Scholars have increasingly recognized the crucial role that empathy plays as informal caregivers provide unpaid care to their older family and friends (i.e., care recipients). Yet, the existing literature exhibits substantial variability in study approaches and results, which limits the extent to which this literature can inform interventions intended to benefit informal caregivers. We sought to address this critical gap by synthesizing research that examined how caregivers' and care recipients' empathy were associated with caregivers' psychological health.

Methods: We conducted a literature search using PubMed, PsycInfo, CINAHL (Cumulative Index to Nursing and Allied Health Literature), EMBASE, and Scopus databases …

Residential Proximity, Duration, And Health-Related Quality Of Life: Insights From The Fernald Cohort, Sara Burcham, Wei-Wen Hsu, Sharon L. Larson, Phd, Jack Rubinstein, Susan M. Pinney

College of Population Health Faculty Papers

The impact of living near environmental contamination on the health-related quality of life (HRQoL) is not well understood. This study examined the impacts of the residential proximity (RP) and time spent near a former Department of Energy uranium processing facility (located in Fernald, Ohio) on the surrounding community’s HRQoL outcomes. A cross-sectional analysis was conducted using the data collected from participants using the Short Form-36 survey at the time of the enrollment in the Fernald Medical Monitoring Program (n = 7957). Mental and physical component summary scores (MCS and PCS, respectively) were computed for each participant. The scores were compared …

Multilevel Factors Influencing Perceived Barriers To Adjuvant Endocrine Therapy Among Breast Cancer Patients At Medication Onset, Timothy Cocozza, Rita Smith, Ana Maria Lopez, Shari Rudoler, Rachel Slamon, Tingting Zhan, Jazmarie L. Vega, Minal Dhamankar, Aruna Padmanabhan, Suzanne M. Miller, Kuang-Yi Wen

Department of Medical Oncology Faculty Papers

Purpose: Adjuvant endocrine therapy (AET) significantly diminishes recurrence and mortality risks in hormone receptor-positive breast cancer (BCa) patients. Nonetheless, suboptimal adherence and premature discontinuation during the initial year of treatment undermine these positive outcomes. This study aims to understand the potential diverse factors associated with perceived barriers to AET compliance at the onset of medication. Methods: We assessed perceived barriers to AET using the ASK-20 instrument for BCa patients initiating AET within 3 months. Our survey also included demographic variables (e.g., musculoskeletal symptoms) and clinical traits (e.g., medication type). Stepwise regression analyses were employed to elucidate the links between multilevel …

Lifespan Reference Curves For Harmonizing Multi-Site Regional Brain White Matter Metrics From Diffusion Mri, Alyssa H Zhu, Talia M Nir, Shayan Javid, Julio E Villalón-Reina, Amanda L Rodrigue, Lachlan T Strike, Greig I De Zubicaray, Katie L Mcmahon, Margaret J Wright, Sarah E Medland, John Blangero, David C Glahn, Peter Kochunov, Douglas E Williamson, Asta K Håberg, Paul M Thompson, Neda Jahanshad

Faculty, Staff and Student Publications

Age-related white matter (WM) microstructure maturation and decline occur throughout the human lifespan, complementing the process of gray matter development and degeneration. Here, we create normative lifespan reference curves for global and regional WM microstructure by harmonizing diffusion MRI (dMRI)-derived data from ten public datasets (N = 40,898 subjects; age: 3-95 years; 47.6% male). We tested three harmonization methods on regional diffusion tensor imaging (DTI) based fractional anisotropy (FA), a metric of WM microstructure, extracted using the ENIGMA-DTI pipeline. ComBat-GAM harmonization provided multi-study trajectories most consistent with known WM maturation peaks. Lifespan FA reference curves were validated with test-retest data …

The Association Of Discrimination, Inflammation, And Coping Style On Self-Rated Health Among South Asian Individuals In The Masala Study, Raji Pillai, Sahiti Myneni, Constance M Johnson, Nilay S Shah, Alka M Kanaya, Jennifer E S Beauchamp

Faculty, Staff and Student Publications

Objectives: South Asian individuals (SAs) may have heightened levels of inflammatory markers, such as C reactive protein (CRP), Tumor Necrosis Factor-α (TNF-α), leptin, and resistin, and decreased levels of anti-inflammatory adiponectin, contributing to higher cardiovascular disease (CVD) incidence. Social determinants of health, like discrimination, are also associated with risks for CVD in SAs. This study examined the associations between discrimination and inflammation and whether coping styles moderated the association between discrimination and self-rated health (SRH) among SAs in the United States.

Design: Secondary analysis of data obtained from 1164 SAs (mean age = 57 years, SD = 9.4, 48% women) …

Trajectories Of Attention Problems In Preschoolers Born Very Preterm., Marie Camerota, Francisco Xavier Castellanos, Brian S. Carter, Jennifer Check, Jennifer Helderman, Julie A. Hofheimer, Elisabeth C. Mcgowan, Charles R. Neal, Steven L. Pastyrnak, Lynne M. Smith, Thomas Michael O'Shea, Carmen J. Marsit, Barry M. Lester

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Children born preterm are at heightened risk for neurodevelopmental impairment, including specific deficits in attention. Few studies have investigated change over time in attention problems prior to school entry. The current study aims to describe trajectories of attention problems from age 2 through 5 years in a cohort of children born(GA), identify sociodemographic, medical, and neurobehavioral characteristics associated with attention trajectories, and test whether attention problem trajectories predict the risk of a reported attention-deficit/hyperactivity disorder (ADHD) diagnosis.

METHODS: We studied 608 infants from the Neonatal Neurobehavior and Outcomes in Very Preterm Infants (NOVI) Study, a prospective, multisite study of …

Neuroimaging-Based Variability In Subtyping Biomarkers For Psychiatric Heterogeneity, Zhenfu Wen, Mira Z Hammoud, Carole E Siegel, Eugene M Laska, Duna Abu-Amara, Amit Etkin, Mohammed R Milad, Charles R Marmar

Faculty, Staff and Student Publications

Neuroimaging-based subtyping is increasingly used to explain heterogeneity in psychiatric disorders. However, the clinical utility of these subtyping efforts remains unclear, and replication has been challenging. Here we examined how the choice of neuroimaging measures influences the derivation of neuro-subtypes and the consequences for clinical delineation. On a clinically heterogeneous dataset (total n = 566) that included controls (n = 268) and cases (n = 298) of psychiatric conditions, including individuals diagnosed with post-traumatic stress disorder (PTSD), traumatic brain injury (TBI), and comorbidity of both (PTSD&TBI), we identified neuro-subtypes among the cases using either structural, resting-state, or task-based measures. The …

Randomized Controlled Trial Of "Bounce Back Now," A Mobile App To Reduce Post-Disaster Symptoms Of Posttraumatic Stress, Depressed Mood, And Sleep Disturbance, Kenneth J Ruggiero, Arthur Andrews, Tatiana M Davidson, Yulia Gavrilova, Brian E Bunnell, Jennifer Dahne, Matthew Price, Zoe M F Brier, Gregory Cohen, Dean Kilpatrick, Ron Acierno, Sandro Galea

Faculty, Staff and Student Publications

Objective: There is tremendous public health interest in cost-efficient, scalable interventions to improve post-disaster mental health. The authors examined the efficacy of Bounce Back Now (BBN), a mobile application, versus an enhanced usual care app (EUC).

Methods: A population-based trial was conducted with a diverse sample of 1,357 adults affected by Hurricane Harvey, Irma, Maria, Florence, or Michael in 2017 and 2018. Participants were eligible if they were ≥18 years of age, had access to an Internet-accessible device, were English speaking, and lived in a hurricane-affected area. BBN is designed to address symptoms of posttraumatic stress, depression, and sleep disturbance …

Widespread Pain Phenotypes Impact Treatment Efficacy Results In Randomized Clinical Trials For Interstitial Cystitis/Bladder Pain Syndrome: A Multidisciplinary Approach To The Study Of Chronic Pelvic Pain Network Study, John T. Farrar, Siobhan Sutcliffe, Et Al.

2020-Current year OA Pubs

Pain clinical trials are notoriously complex and often inefficient in demonstrating efficacy, even for known efficacious treatments. A major issue is the difficulty in the a priori identification of specific phenotypes to include in the study population. Recent work has identified the extent of widespread pain as an important determinant of the likelihood of response to therapy, but it has not been tested in clinical trials for the treatment of interstitial cystitis/bladder pain syndrome (IC/BPS). We explored this hypothesis using data from 3 previously published trials testing treatments for IC/BPS, which suggested modest benefits but did not meet a priori …

Azetukalner, A Novel Kv7 Potassium Channel Opener, In Adults With Major Depressive Disorder: A Randomized Clinical Trial, Noam N Butterfield, Constanza Luzon Rosenblut, Maurizio Fava, Christoph U Correll, Anthony J Rothschild, James W Murrough, Sanjay J Mathew, Gregory N Beatch, Celene Grayson, Cynthia Harden, Jenny Qian, Joe Mcintosh, Rostam Namdari, Christopher Kenney

Staff and Researcher Publications

Importance: Available antidepressants provide inadequate therapeutic responses in many patients with major depressive disorder (MDD), highlighting a substantial unmet need.

Objective: To evaluate the efficacy and safety of azetukalner, a novel, potent KV7 potassium channel opener, in participants with MDD.

Design, setting, and participants: X-NOVA was a multicenter, proof-of-concept, phase 2, randomized, double-blind, parallel-group, placebo-controlled clinical trial that evaluated azetukalner in participants (adults aged ≥18 to ≤65 years) with moderate to severe MDD in a current depressive episode. Participants were enrolled between April 2022 and October 2023, and data analysis occurred from January 2023 to January 2024.

Intervention: Participants were …

Cdc’S Core Elements To Promote Diagnostic Excellence, Daniel J Morgan, Hardeep Singh, Arjun Srinivasan, Andrea Bradford, L Clifford Mcdonald, Preeta K Kutty

Faculty, Staff and Students Publications

Nearly a decade after the National Academy of Medicine released the "Improving Diagnosis in Health Care" report, diagnostic errors remain common, often leading to physical, psychological, emotional, and financial harm. Despite a robust body of research on potential solutions and next steps, the translation of these efforts to patient care has been limited. Improvement initiatives are still narrowly focused on selective themes such as diagnostic stewardship, preventing overdiagnosis, and enhancing clinical reasoning without comprehensively addressing vulnerable systems and processes surrounding diagnosis. To close this implementation gap, the US Centers for Disease Control and Prevention (CDC) released the Core Elements of …

Clerkship Students' Use Of Clinical Reasoning Concepts After A Pre-Clinical Reasoning Course, Shradha A Kulkarni, Gurpreet Dhaliwal, Arianne Teherani, Denise M Connor

Faculty, Staff and Students Publications

Background: Many medical schools have incorporated clinical reasoning (CR) courses into their pre-clinical curricula to address the quality and safety issue of diagnostic error. It is unknown how students use concepts and practices from pre-clinical CR courses once in clerkships.

Objective: We sought to understand how students utilize CR concepts from a pre-clinical course during clerkships and to identify facilitators and barriers to the use of reasoning concepts.

Design: We used structured interviews to gain insight into medical students' experiences with CR concepts in clerkships.

Participants: We interviewed 16 students who had completed a pre-clinical CR course and subsequently completed …

Translational Genomics Of Osteoarthritis In 1,962,069 Individuals, Konstantinos Hatzikotoulas, Lorraine Southam, Lilja Stefansdottir, Cindy G Boer, Merry-Lynn Mcdonald, J Patrick Pett, Young-Chan Park, Margo Tuerlings, Rick Mulders, Andrei Barysenka, Ana Luiza Arruda, Vinicius Tragante, Alison Rocco, Norbert Bittner, Shibo Chen, Susanne Horn, Vinodh Srinivasasainagendra, Ken To, Georgia Katsoula, Peter Kreitmaier, Amabel M M Tenghe, Arthur Gilly, Liubov Arbeeva, Lane G Chen, Agathe M De Pins, Daniel Dochtermann, Cecilie Henkel, Jonas Höijer, Shuji Ito, Penelope A Lind, Bitota Lukusa-Sawalena, Aye Ko Ko Minn, Marina Mola-Caminal, Akira Narita, Chelsea Nguyen, Ene Reimann, Micah D Silberstein, Anne-Heidi Skogholt, Hemant K Tiwari, Michelle S Yau, Ming Yue, Wei Zhao, Jin J Zhou, George Alexiadis, Karina Banasik, Søren Brunak, Archie Campbell, Jackson T S Cheung, Joseph Dowsett, Tariq Faquih, Jessica D Faul, Lijiang Fei, Anne Marie Fenstad, Takamitsu Funayama, Maiken E Gabrielsen, Chinatsu Gocho, Kirill Gromov, Thomas Hansen, Georgi Hudjashov, Thorvaldur Ingvarsson, Jessica S Johnson, Helgi Jonsson, Saori Kakehi, Juha Karjalainen, Elisa Kasbohm, Susanna Lemmelä, Kuang Lin, Xiaoxi Liu, Marieke Loef, Massimo Mangino, Daniel Mccartney, Iona Y Millwood, Joshua Richman, Mary B Roberts, Kathleen A Ryan, Dino Samartzis, Manu Shivakumar, Søren T Skou, Sachiyo Sugimoto, Ken Suzuki, Hiroshi Takuwa, Maris Teder-Laving, Laurent Thomas, Kohei Tomizuka, Constance Turman, Stefan Weiss, Tian T Wu, Eleni Zengini, Yanfei Zhang, Arcogen Consortium, Argo Consortium, Dbds Genomic Consortium, Estonian Biobank Research Team, Finngen, Genes & Health Research Team, Hunt All-In Pain, Million Veteran Program, Regeneron Genetics Center, Manuel Allen Revez Ferreira, George Babis, Aris Baras, Tyler Barker, David J Carey, Kathryn S E Cheah, Zhengming Chen, Jason Pui-Yin Cheung, Mark Daly, Renée De Mutsert, Charles B Eaton, Christian Erikstrup, Ove Nord Furnes, Yvonne M Golightly, Daniel F Gudbjartsson, Nils P Hailer, Caroline Hayward, Marc C Hochberg, Georg Homuth, Laura M Huckins, Kristian Hveem, Shiro Ikegawa, Muneaki Ishijima, Minoru Isomura, Marcus Jones, Jae H Kang, Sharon L R Kardia, Margreet Kloppenburg, Peter Kraft, Nobuyuki Kumahashi, Suguru Kuwata, Ming Ta Michael Lee, Phil H Lee, Robin Lerner, Liming Li, Steve A Lietman, Luca Lotta, Michelle K Lupton, Reedik Mägi, Nicholas G Martin, Timothy E Mcalindon, Sarah E Medland, Karl Michaëlsson, Braxton D Mitchell, Dennis O Mook-Kanamori, Andrew P Morris, Toru Nabika, Fuji Nagami, Amanda E Nelson, Sisse Rye Ostrowski, Aarno Palotie, Ole Birger Pedersen, Frits R Rosendaal, Mika Sakurai-Yageta, Carsten Oliver Schmidt, Pak Chung Sham, Jasvinder A Singh, Diane T Smelser, Jennifer A Smith, You-Qiang Song, Erik Sørensen, Gen Tamiya, Yoshifumi Tamura, Chikashi Terao, Gudmar Thorleifsson, Anders Troelsen, Aspasia Tsezou, Yuji Uchio, A G Uitterlinden, Henrik Ullum, Ana M Valdes, David A Van Heel, Robin G Walters, David R Weir, J Mark Wilkinson, Bendik S Winsvold, Masayuki Yamamoto, John-Anker Zwart, Kari Stefansson, Ingrid Meulenbelt, Sarah A Teichmann, Joyce B J Van Meurs, Unnur Styrkarsdottir, Eleftheria Zeggini

Faculty, Staff and Students Publications

Osteoarthritis is the third most rapidly growing health condition associated with disability, after dementia and diabetes1. By 2050, the total number of patients with osteoarthritis is estimated to reach 1 billion worldwide2. As no disease-modifying treatments exist for osteoarthritis, a better understanding of disease aetiopathology is urgently needed. Here we perform a genome-wide association study meta-analyses across up to 489,975 cases and 1,472,094 controls, establishing 962 independent associations, 513 of which have not been previously reported. Using single-cell multiomics data, we identify signal enrichment in embryonic skeletal development pathways. We integrate orthogonal lines of evidence, including …

Navacaprant, A Novel And Highly Selective Kappa Opioid Receptor Antagonist, In Adults With Major Depressive Disorder: A Randomized, Double-Blind Phase 2 Clinical Trial, Sanjay J Mathew, Andrew J Cutler, Nicole C Visitacion, Michael Gold, Jason Yuan, Bill Aurora

Staff and Researcher Publications

PURPOSE/BACKGROUND: This phase 2a randomized, double-blind, placebo-controlled, 8-week trial assessed the efficacy and safety of navacaprant, a highly selective kappa opioid receptor antagonist, in adults with major depressive disorder (MDD).

METHODS/PROCEDURES: Participants with 17-Item Hamilton Depression Rating Scale (HAMD-17) scores of 14 to 30 were randomized 1:1 to once-daily navacaprant 80 mg or placebo (n = 102 each). The primary endpoint was HAMD-17 change from baseline (CFB) to week 8. Secondary endpoints included CFB in Snaith-Hamilton Pleasure Scale (SHAPS). No adjustment for multiple comparisons was made.

FINDINGS/RESULTS: At week 8, HAMD-17 CFB was not statistically significantly improved with navacaprant vs …

Prevalence And Patterns Of Opioid Use In Chronic Pancreatitis, Anna Evans Phillips, Darwin L Conwell, Shuang Li, Jami L Saloman, Phil A Hart, Evan L Fogel, Santhi Swaroop Vege, Dana K Andersen, William E Fisher, Christopher E Forsmark, Stephen Pandol, Walter G Park, Mark D Topazian, Stephen K Van Den Eeden, Jose Serrano, Liang Li, Dhiraj Yadav

Faculty, Staff and Student Publications

Introduction: Opioids are used to treat pain in chronic pancreatitis (CP), but little is known about current use patterns. The aim of this study was to characterize the utilization of opioids and associations with clinical characteristics in adult patients with CP.

Methods: This cross-sectional analysis used baseline data from participants with definite CP enrolled in a cohort study in the United States (PROspective Evaluation of CP for EpidEmiologic and Translational StuDies). Data on demographics, pain medication use, healthcare utilization, disability, and pain patterns were systematically collected in case report forms while quality of life was assessed with patient-reported outcome instruments. …

Cortical Structure In Nodes Of The Default Mode Network Estimates General Intelligence, Abhinav Yadav, Archana Purushotham

Faculty, Staff and Students Publications

Introduction: A growing number of studies implicate functional brain networks in intelligence, but it is unclear if network nodal structure relates to intelligence.

Methods: Using MRI, we studied the relationship of the general intelligence factor (g) with cortical thickness (CT), local gyrification index (LGI), and voxel-based morphometry in the nodes of the default mode network (DMN) and task-positive network (TPN) in a cohort of 44 young, healthy adults. Employing a novel strategy, we performed repeated analyses with multiple sets of g estimates to remove false positives.

Results: CT and LGI in medial and temporal nodes of the DMN were reliably …