Digital Commons Network^™

Growth Parameters In Children With Achondroplasia: A 7-Year, Prospective, Multinational, Observational Study, Ravi Savarirayan, Melita Irving, Paul Harmatz, Borja Delgado, William R Wilcox, John Philips, Natalie Owen, Carlos A Bacino, Louise Tofts, Joel Charrow, Lynda E Polgreen, Julie Hoover-Fong, Paul Arundel, Ignacio Ginebreda, Howard M Saal, Donald Basel, Rosendo Ullot Font, Keiichi Ozono, Michael B Bober, Valerie Cormier-Daire, Kim-Hanh Le Quan Sang, Genevieve Baujat, Yasemin Alanay, Frank Rutsch, Daniel Hoernschemeyer, Klaus Mohnike, Hiroshi Mochizuki, Asako Tajima, Yumiko Kotani, David D Weaver, Klane K White, Clare Army, Kevin Larrimore, Keith Gregg, George Jeha, Claire Milligan, Elena Fisheleva, Alice Huntsman-Labed, Jonathan Day

Faculty, Staff and Students Publications

Purpose: This study was undertaken to collect baseline growth parameters in children with achondroplasia who might enroll in interventional trials of vosoritide, and to establish a historical control.

Methods: In this prospective, observational study, participants (≤17 years) underwent a detailed medical history and physical examination and were followed every 3 months until they finished participating in the study by enrolling in an interventional trial or withdrawing.

Results: A total of 363 children were enrolled (28 centers, 8 countries). Mean (SD) follow up was 20.4 (15.0) months. In participants < 1 year, mean annualized growth velocity (AGV) was 11.6 cm/year for girls and 14.6 cm/year for boys. By age 1 year, mean AGV decreased to 7.4 cm/year in girls and 7.1 cm/year in boys. By age 10 years, mean AGV decreased to 3.6 cm/year for both sexes. Mean height z-score in participants < 1 year was -2.5 for girls and -3.2 for boys and decreased up to the age 5 years (-5.3 for girls; -4.6 for boys). Girls and boys had a disproportionate upper-to-lower body segment ratio. Mean ratio was highest in participants aged < 1 year (2.9 for girls; 2.8 for boys) and decreased gradually to approximately 2 in both sexes from 4 years of age onward.

Conclusion: This study represents one of the largest datasets of prospectively collected …

Lipid-Lowering Therapy Use And Intensification Among United States Veterans Following Myocardial Infarction Or Coronary Revascularization Between 2015 And 2019, Alexander R Zheutlin, Catherine G Derington, Jennifer S Herrick, Robert S Rosenson, Bharat Poudel, Monika M Safford, Todd M Brown, Elizabeth A Jackson, Mark Woodward, Stephanie Reading, Kate Orroth, Jason Exter, Salim S Virani, Paul Muntner, Adam P Bress

Faculty, Staff and Students Publications

Background: Understanding how statins, ezetimibe, and PCSK9i (proprotein convertase subtilisin/kexin type 9 serine protease inhibitors) are prescribed after a myocardial infarction (MI) or elective coronary revascularization may improve lipid-lowering therapy (LLT) intensification and reduce recurrent atherosclerotic cardiovascular disease events. We described the use and intensification of LLT among US veterans who had a MI or elective coronary revascularization between July 24, 2015, and December 9, 2019, within 12 months of hospital discharge.

Methods: LLT intensification was defined as increasing statin dose, or initiating a statin, ezetimibe, or a PCSK9i, overall and among those with an LDL-C (low-density lipoprotein cholesterol) ≥ …

Wide Range Of Phenotypic Severity In Individuals With Late Truncations Unique To The Predominant Cdkl5 Transcript In The Brain, Laura Keehan, Isabel Haviland, Yoel Gofin, Lindsay C Swanson, Christelle Moufawad El Achkar, John Schreiber, Grace E Vannoy, Emily O'Heir, Anne O'Donnell-Luria, Richard Alan Lewis, Pilar Magoulas, Alyssa Tran, Mahshid S Azamian, Hsiao-Tuan Chao, Lisa Pham, Rodney C Samaco, Sarah Elsea, Erin Thorpe, Akanchha Kesari, Denise Perry, Brendan Lee, Seema R Lalani, Jill A Rosenfeld, Heather E Olson, Lindsay C Burrage

Faculty, Staff and Students Publications

Cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) is caused by heterozygous or hemizygous variants in CDKL5 and is characterized by refractory epilepsy, cognitive and motor impairments, and cerebral visual impairment. CDKL5 has multiple transcripts, of which the longest transcripts, NM_003159 and NM_001037343, have been used historically in clinical laboratory testing. However, the transcript NM_001323289 is the most highly expressed in brain and contains 170 nucleotides at the 3' end of its last exon that are noncoding in other transcripts. Two truncating variants in this region have been reported in association with a CDD phenotype. To clarify the significance and range …

Long-Term Relugolix Combination Therapy For Symptomatic Uterine Leiomyomas, Ayman Al-Hendy, Andrea S Lukes, Alfred N Poindexter, Roberta Venturella, Claudio Villarroel, Laura Mckain, Yulan Li, Rachel B Wagman, Elizabeth A Stewart

Faculty, Staff and Students Publications

OBJECTIVE: In the LIBERTY 1 and LIBERTY 2 placebo-controlled trials, once-daily relugolix combination therapy reduced menstrual blood loss volume and pain in women with heavy menstrual bleeding associated with uterine leiomyomas and was well tolerated, with preservation of bone mineral density (BMD) through 24 weeks. Here we report the long-term efficacy and safety of relugolix combination therapy treatment for up to 52 weeks.

METHODS: Women with uterine leiomyoma-associated heavy menstrual bleeding who completed any treatment arm in either the LIBERTY 1 or LIBERTY 2 trial were eligible to enroll in a 28-week long-term extension study. All participants received once-daily relugolix …

Wellness And Coping Of Physicians Who Worked In Icus During The Pandemic: A Multicenter Cross-Sectional North American Survey, Karen E. A. Burns, Rachel K. Mcdonald, Et Al.

2020-Current year OA Pubs

OBJECTIVES: Few surveys have focused on physician moral distress, burnout, and professional fulfilment. We assessed physician wellness and coping during the COVID-19 pandemic.

DESIGN: Cross-sectional survey using four validated instruments.

SETTING: Sixty-two sites in Canada and the United States.

SUBJECTS: Attending physicians (adult, pediatric; intensivist, nonintensivist) who worked in North American ICUs.

INTERVENTION: None.

MEASUREMENTS AND MAIN RESULTS: We analysed 431 questionnaires (43.3% response rate) from 25 states and eight provinces. Respondents were predominantly male (229 [55.6%]) and in practice for 11.8 ± 9.8 years. Compared with prepandemic, respondents reported significant intrapandemic increases in days worked/mo, ICU bed occupancy, and …

Loss Of Wnt4 In The Gubernaculum Causes Unilateral Cryptorchidism And Fertility Defects, Abhishek Seth, Juan C Bournat, Olga Medina-Martinez, Armando Rivera, Joshua Moore, Hunter Flores, Jill A Rosenfeld, Liya Hu, Carolina J Jorgez

Faculty, Staff and Students Publications

Undescended testis (UDT) affects 6% of male births. Despite surgical correction, some men with unilateral UDT may experience infertility with the contralateral descended testis (CDT) showing no A-dark spermatogonia. To improve our understanding of the etiology of infertility in UDT, we generated a novel murine model of left unilateral UDT. Gubernaculum-specific Wnt4 knockout (KO) mice (Wnt4-cKO) were generated using retinoic acid receptor β2-cre mice and were found to have a smaller left-unilateral UDT. Wnt4-cKO mice with abdominal UDT had an increase in serum follicle-stimulating hormone and luteinizing hormone and an absence of germ cells in the undescended testicle. Wnt4-cKO mice …

Human Loss-Of-Function Variants In The Serotonin 2c Receptor Associated With Obesity And Maladaptive Behavior, Yang He, Bas Brouwers, Hesong Liu, Hailan Liu, Katherine Lawler, Edson Mendes De Oliveira, Dong-Kee Lee, Yongjie Yang, Aaron R Cox, Julia M Keogh, Elana Henning, Rebecca Bounds, Aliki Perdikari, Vikram Ayinampudi, Chunmei Wang, Meng Yu, Longlong Tu, Nan Zhang, Na Yin, Junying Han, Nikolas A Scarcelli, Zili Yan, Kristine M Conde, Camille Potts, Jonathan C Bean, Mengjie Wang, Sean M Hartig, Lan Liao, Jianming Xu, Inês Barroso, Jacek Mokrosinski, Yong Xu, I Sadaf Farooqi

Children’s Nutrition Research Center Staff Publications

Serotonin reuptake inhibitors and receptor agonists are used to treat obesity, anxiety and depression. Here we studied the role of the serotonin 2C receptor (5-HT2CR) in weight regulation and behavior. Using exome sequencing of 2,548 people with severe obesity and 1,117 control individuals without obesity, we identified 13 rare variants in the gene encoding 5-HT2CR (HTR2C) in 19 unrelated people (3 males and 16 females). Eleven variants caused a loss of function in HEK293 cells. All people who carried variants had hyperphagia and some degree of maladaptive behavior. Knock-in male mice harboring a human loss-of-function HTR2C variant developed …

Clinical And Demographic Factors Contributing To Asparaginase-Associated Toxicities In Children With Acute Lymphoblastic Leukemia, Priyadarshani Dharia, Michael D Swartz, M Brooke Bernhardt, Han Chen, M Monica Gramatges, Philip J Lupo, Austin L Brown, Michael E Scheurer

Center for Medical Ethics and Health Policy Staff Publications

A total of 548 patients (age range: 1-22 years, 60.4% Hispanic, 55.8% male) diagnosed with acute lymphoblastic leukemia were reviewed for pegaspargase-associated hypersensitivity (14.8%), hyperbilirubinemia (9.7%), venous thromboembolism (VTE, 9.7%), and pancreatitis (5.3%). Odds ratios (OR) and 95% confidence intervals (CI) evaluated associations between clinical factors and each toxicity, cumulative number of toxicities, and toxicity clusters identified using k-mode analysis. Most (68.9%) did not experience any toxicity, 24.6% experienced one toxicity, and 6.3% two or more. Age >10 years was associated with hyperbilirubinemia (OR = 3.83; 95% CI: 1.64-8.95), pancreatitis (OR = 3.72; 95% CI: 1.29-10.68), VTE (OR = 4.65; …

Prenatal Phenotyping Of Fetal Tubulinopathies: A Multicenter Retrospective Case Series, Bobby K Brar, Marisa Gilstrop Thompson, Neeta L Vora, Kelly Gilmore, Karin Blakemore, Kristen A Miller, Jessica Giordano, Andreas Dufke, Beatrix Wong, Samantha Stover, Billie Lianoglou, Ignatia Van Den Veyver, Esther Dempsey, Mara Rosner, Karen Chong, David Chitayat, Teresa N Sparks, Mary E Norton, Ronald Wapner, Kristin Baranano, Angie C Jelin, Fetal Sequencing Consortium

Center for Medical Ethics and Health Policy Staff Publications

Objective: Tubulinopathies refer to conditions caused by genetic variants in isotypes of tubulin resulting in defective neuronal migration. Historically, diagnosis was primarily via postnatal imaging. Our objective was to establish the prenatal phenotype/genotype correlations of tubulinopathies identified by fetal imaging.

Methods: A large, multicenter retrospective case series was performed across nine institutions in the Fetal Sequencing Consortium. Demographics, fetal imaging reports, genetic screening and diagnostic testing results, delivery reports, and neonatal imaging reports were extracted for pregnancies with a confirmed molecular diagnosis of a tubulinopathy.

Results: Nineteen pregnancies with a fetal tubulinopathy were identified. The most common prenatal imaging findings …

Cic Missense Variants Contribute To Susceptibility For Spina Bifida, Xiao Han, Xuanye Cao, Vanessa Aguiar-Pulido, Wei Yang, Menuka Karki, Paula Andrea Pimienta Ramirez, Robert M Cabrera, Ying Linda Lin, Bogdan J Wlodarczyk, Gary M Shaw, M Elizabeth Ross, Cuilian Zhang, Richard H Finnell, Yunping Lei

Faculty, Staff and Students Publications

Neural tube defects (NTDs) are congenital malformations resulting from abnormal embryonic development of the brain, spine, or spinal column. The genetic etiology of human NTDs remains poorly understood despite intensive investigation. CIC, homolog of the Capicua transcription repressor, has been reported to interact with ataxin-1 (ATXN1) and participate in the pathogenesis of spinocerebellar ataxia type 1. Our previous study demonstrated that CIC loss of function (LoF) variants contributed to the cerebral folate deficiency syndrome by downregulating folate receptor 1 (FOLR1) expression. Given the importance of folate transport in neural tube formation, we hypothesized that CIC variants could contribute to increased …

Effect Of Problem-Solving Treatment On Self-Reported Disability Among Veterans With Gulf War Illness: A Randomized Clinical Trial, Lisa M Mcandrew, Karen S Quigley, Shou-En Lu, David Litke, Joseph F Rath, Gudrun Lange, Susan L Santos, Nicole Anastasides, Beth Ann Petrakis, Lauren Greenberg, Drew A Helmer, Wilfred R Pigeon

Center for Medical Ethics and Health Policy Staff Publications

Importance: Few evidence-based treatments are available for Gulf War illness (GWI). Behavioral treatments that target factors known to maintain the disability from GWI, such as problem-solving impairment, may be beneficial. Problem-solving treatment (PST) targets problem-solving impairment and is an evidence-based treatment for other conditions.

Objective: To examine the efficacy of PST to reduce disability, problem-solving impairment, and physical symptoms in GWI.

Design, setting, and participants: This multicenter randomized clinical trial conducted in the US Department of Veterans Affairs compared PST with health education in a volunteer sample of 511 Gulf War veterans with GWI and disability (January 1, 2015, to …

Avpcancerfree: Impact Of A Digital Behavior Change Intervention On Parental Hpv Vaccine –Related Perceptions And Behaviors, Ross Shegog, Lara S Savas, C Mary Healy, Erica L Frost, Sharon P Coan, Efrat K Gabay, Sharice M Preston, Stanley W Spinner, Mathew Wilbur, Elisabeth Becker, Travis Teague, Sally W Vernon

Faculty, Staff and Student Publications

Parent hesitancy contributes to reduced HPV vaccination rates. The HPVcancerfree app (HPVCF) was designed to assist parents in making evidence-based decisions regarding HPV vaccination. This study examined if parents of vaccine-eligible youth (11-12 yrs.) who use HPVCF in addition to usual care demonstrate significantly more positive intentions and attitudes toward HPV vaccination and greater HPV vaccination rates compared to those not using HPVCF. Clinics (n = 51) within a large urban pediatric network were randomly assigned to treatment (HPVCF + usual care) or comparison (usual care only) conditions in a RCT conducted between September 2017 and February 2019. Parents completed …

Synaptic Development In Diverse Olfactory Neuron Classes Uses Distinct Temporal And Activity-Related Programs, Michael A. Aimino, Alison T. Depew, Lucas Restrepo, Timothy J. Mosca

Farber Institute for Neuroscience Faculty Papers

Developing neurons must meet core molecular, cellular, and temporal requirements to ensure the correct formation of synapses, resulting in functional circuits. However, because of the vast diversity in neuronal class and function, it is unclear whether or not all neurons use the same organizational mechanisms to form synaptic connections and achieve functional and morphologic maturation. Moreover, it remains unknown whether neurons united in a common goal and comprising the same sensory circuit develop on similar timescales and use identical molecular approaches to ensure the formation of the correct number of synapses. To begin to answer these questions, we took advantage …

Criterion Validity Of A Short Food Frequency Questionnaire For Mexican American Adults, Natalia I Heredia, Deanna M Hoelscher, Vanessa Vega, Belinda M Reininger

Faculty, Staff and Student Publications

Background: The purpose of this study was to validate the School Physical Activity and Nutrition (SPAN) Food Frequency Questionnaire (FFQ) for Mexican American adults (SPAN MAA). Methods: A sample of 100 Mexican American adult participants was drawn from the Cameron County Hispanic Cohort (on the Texas–Mexico border). We used Spearman rank order correlation coefficients, kappa statistics, and percent agreement to compare the SPAN MAA questionnaire to a 24 h recall collected on the same day. Results: Of 100 participants, 93 were included in the analyses. One item showed substantial (>0.6), five items moderate (>0.4), five items fair ( …

Using Genomic Variation To Distinguish Ovarian High-Grade Serous Carcinoma From Benign Fallopian Tubes, Jesus Gonzalez-Bosquet, Nicholas D Cardillo, Henry D Reyes, Brian J Smith, Kimberly K Leslie, David P Bender, Michael J Goodheart, Eric J Devor

Department of Obstetrics and Gynecology Faculty Papers

The preoperative diagnosis of pelvic masses has been elusive to date. Methods for characterization such as CA-125 have had limited specificity. We hypothesize that genomic variation can be used to create prediction models which accurately distinguish high grade serous ovarian cancer (HGSC) from benign tissue.

Methods: In this retrospective, pilot study, we extracted DNA and RNA from HGSC specimens and from benign fallopian tubes. Then, we performed whole exome sequencing and RNA sequencing, and identified single nucleotide variants (SNV), copy number variants (CNV) and structural variants (SV). We used these variants to create prediction models to distinguish cancer from benign …

Variation In Human Water Turnover Associated With Environmental And Lifestyle Factors, Yosuke Yamada, Xueying Zhang, Mary E T Henderson, Hiroyuki Sagayama, Herman Pontzer, Daiki Watanabe, Tsukasa Yoshida, Misaka Kimura, Philip N Ainslie, Lene F Andersen, Liam J Anderson, Lenore Arab, Issad Baddou, Kweku Bedu-Addo, Ellen E Blaak, Stephane Blanc, Alberto G Bonomi, Carlijn V C Bouten, Pascal Bovet, Maciej S Buchowski, Nancy F Butte, Stefan G Camps, Graeme L Close, Jamie A Cooper, Richard Cooper, Sai Krupa Das, Lara R Dugas, Simon Eaton, Ulf Ekelund, Sonja Entringer, Terrence Forrester, Barry W Fudge, Annelies H Goris, Michael Gurven, Lewis G Halsey, Catherine Hambly, Asmaa El Hamdouchi, Marije B Hoos, Sumei Hu, Noorjehan Joonas, Annemiek M Joosen, Peter Katzmarzyk, Kitty P Kempen, William E Kraus, Wantanee Kriengsinyos, Robert F Kushner, Estelle V Lambert, William R Leonard, Nader Lessan, Corby K Martin, Anine C Medin, Erwin P Meijer, James C Morehen, James P Morton, Marian L Neuhouser, Theresa A Nicklas, Robert M Ojiambo, Kirsi H Pietiläinen, Yannis P Pitsiladis, Jacob Plange-Rhule, Guy Plasqui, Ross L Prentice, Roberto A Rabinovich, Susan B Racette, David A Raichlen, Eric Ravussin, Leanne M Redman, John J Reilly, Rebecca M Reynolds, Susan B Roberts, Albertine J Schuit, Luis B Sardinha, Analiza M Silva, Anders M Sjödin, Eric Stice, Samuel S Urlacher, Giulio Valenti, Ludo M Van Etten, Edgar A Van Mil, Jonathan C K Wells, George Wilson, Brian M Wood, Jack A Yanovski, Alexia J Murphy-Alford, Cornelia U Loechl, Amy H Luke, Jennifer Rood, Klaas R Westerterp, William W Wong, Motohiko Miyachi, Dale A Schoeller, John R Speakman

Children’s Nutrition Research Center Staff Publications

Water is essential for survival, but one in three individuals worldwide (2.2 billion people) lack access to safe drinking water. Water intake requirements largely reflect water turnover (WT), the water used by the body each day. We investigated the determinants of human WT in 5,604 people from the ages of 8 days to 96 years from 26 countries using isotope tracking (2H) methods. Age, body size, and composition were significantly associated with WT as were physical activity, athletic status, pregnancy, socioeconomic status, and environmental characteristics (latitude, altitude, air temperature, and humidity). People in countries with low human development index (HDI) …

Factors Associated With Meeting Physical Activity Guidelines During The Covid-19 Pandemic, Natalia I Heredia, Michael Machiorlatti, Belinda M Reininger, Candace Robledo

Faculty, Staff and Student Publications

INTRODUCTION: The COVID-19 pandemic impacted individual physical activity levels. Less is known regarding how factors such as sociodemographic and built environment were associated with physical activity engagement during the pandemic. Understanding these factors is critical to informing future infectious disease mitigation policies that promote, rather than hinder physical activity. The purpose of this study was to assess predictors of physical activity levels during the beginning of the pandemic (April-June 2020), including Stay-at-Home length and orders, neighborhood safety, and sociodemographic characteristics.

METHODS: Data included 517 participants who responded to an anonymous online survey. Physical activity was assessed with a modified Godin …

Oleuropein Suppresses Endometriosis Progression And Improves The Fertility Of Mice With Endometriosis, Yuri Park, Yeon Jean Cho, Nuri Sung, Mi Jin Park, Xiaoming Guan, William E Gibbons, Bert W O'Malley, Sang Jun Han

Faculty, Staff and Students Publications

BACKGROUND: Endometriosis is an estrogen-dependent inflammatory reproductive disease. Therefore, systematic estrogen depletion and anti-inflammatory drugs are the current treatment for endometriosis. However, current endometriosis treatments have low efficacy and cause adverse effects in endometriosis patients. Consequently, alternative endometriosis treatments targeting endometriosis-specific factors are in demand. In this context, ERβ was selected as a druggable target for endometriosis due to its critical role in progression. Therefore, selective targeting of ERβ without inhibiting ERα activity would be a new paradigm for endometriosis treatment to overcome the low efficacy and adverse effects of hormonal endometriosis therapy.

METHODS: Cell-based ERβ and ERα activity assay …

Let's Talk About Antibiotics: A Randomised Trial Of Two Interventions To Reduce Antibiotic Misuse., Kathy Goggin, Emily A. Hurley, Brian R. Lee, Andrea Bradley-Ewing, Carey Bickford, Kimberly Pina, Evelyn Donis De Miranda, David Yu, Kirsten Weltmer, Sebastian Linnemayr, Christopher C. Butler, Jason G. Newland, Angela Myers

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Children with acute respiratory tract infections (ARTIs) receive ≈11.4 million unnecessary antibiotic prescriptions annually. A noted contributor is inadequate parent-clinician communication, however, efforts to reduce overprescribing have only indirectly targeted communication or been impractical.

OBJECTIVES: Compare two feasible (higher vs lower intensity) interventions for enhancing parent-clinician communication on the rate of inappropriate antibiotic prescribing.

DESIGN: Multisite, parallel group, cluster randomised comparative effectiveness trial. Data collected between March 2017 and March 2019.

SETTING: Academic and private practice outpatient clinics.

PARTICIPANTS: Clinicians (n=41, 85% of eligible approached) and 1599 parent-child dyads (ages 1-5 years with ARTI symptoms, 71% of eligible approached). …

Let's Talk About Antibiotics: A Randomised Trial Of Two Interventions To Reduce Antibiotic Misuse, Kathy Goggin, Emily A. Hurley, Brian R. Lee, Andrea Bradley-Ewing, Carey Bickford, Kimberly Pina, Evelyn Donis De Miranda, David Yu, Kirsten Weltmer, Sebastian Linnemayr, Christopher C. Butler, Jason G. Newland, Angela L Myers

2020-Current year OA Pubs

BACKGROUND: Children with acute respiratory tract infections (ARTIs) receive ≈11.4 million unnecessary antibiotic prescriptions annually. A noted contributor is inadequate parent-clinician communication, however, efforts to reduce overprescribing have only indirectly targeted communication or been impractical.

OBJECTIVES: Compare two feasible (higher vs lower intensity) interventions for enhancing parent-clinician communication on the rate of inappropriate antibiotic prescribing.

DESIGN: Multisite, parallel group, cluster randomised comparative effectiveness trial. Data collected between March 2017 and March 2019.

SETTING: Academic and private practice outpatient clinics.

PARTICIPANTS: Clinicians (n=41, 85% of eligible approached) and 1599 parent-child dyads (ages 1-5 years with ARTI symptoms, 71% of eligible approached). …

Increased Circulating Cortisol After Vaginal Birth Is Associated With Increased Fgf19 Secretion In Neonatal Pigs, Caitlin Vonderohe, Gregory Guthrie, Barbara Stoll, Valeria Melendez Hebib, Harry Dawson, Douglas Burrin

Children’s Nutrition Research Center Staff Publications

The influence of birth modality (scheduled cesarean or spontaneous vaginal) on the development of the newborn has been a source of controversy in neonatology. The impact of cesarean vs vaginal birth on the development of bile acid and fibroblast growth factor 19 (FGF19) signaling is unknown. Our aim was to determine the effect of birth modality and gestational age (preterm vs term) on plasma hormone levels, bile acid pool distribution, expression of genes in the bile acid-FXR-FGF19 pathway, and plasma levels of FGF19 at birth and on day 3 of life in neonatal pigs. Four sows underwent cesarean delivery on …

Antibody-Drug Conjugates For The Treatment Of Her2-Positive Breast Cancer, Mariana K Najjar, Sara G Manore, Angelina T Regua, Hui-Wen Lo

Faculty, Staff and Student Publications

Human epidermal growth factor receptor 2 (HER2) receptor tyrosine kinase is overexpressed in 20–30% of breast cancers and is associated with poor prognosis and worse overall patient survival. Most women with HER2-positive breast cancer receive neoadjuvant chemotherapy plus HER2-targeted therapies. The development of HER2-directed therapeutics is an important advancement in targeting invasive breast cancer. Despite the efficacy of anti-HER2 monoclonal antibodies, they are still being combined with adjuvant chemotherapy to improve overall patient outcomes. Recently, significant progress has been made towards the development of a class of therapeutics known as antibody-drug conjugates (ADCs), which leverage the high specificity of HER2-targeted …

Prevalence Of Sleep-Related Problems And Risks In A Community-Dwelling Older Adult Population: A Cross-Sectional Survey-Based Study, Nancy P Gordon, Jimmy H Yao, Leslea A Brickner, Joan C Lo

Faculty, Staff and Student Publications

BACKGROUND: Despite evidence of adverse health consequences of inadequate restorative sleep for older adults, assessment of sleep quantity, quality, and use of sleep aids is not routinely done. We aimed to characterize sleep problems, sleep risks, and advice received about sleep in a community-dwelling older adult population, overall and in subgroups with health conditions and functional difficulties.

METHODS: This cross-sectional study used weighted self-report data for 5074 Kaiser Permanente Northern California members aged 65-79y who responded to a 2017 or 2020 Member Health Survey. We estimated usual amount of sleep (< 6, 6 to < 7, ≥7 hours) and prevalence of sleep problems (frequent insomnia, frequent daytime fatigue, poor quality sleep, and potential sleep apnea (OSA) symptoms (frequent very loud snoring, apnea episodes)) for older adults overall, by self-rated health, and in subgroups reporting hypertension, diabetes, heart disease, frequent problems with balance/walking, and frequent memory problems. We also estimated percentages who regularly used sleep aids and had discussed sleep adequacy with a healthcare professional in the past year.

RESULTS: Approximately 30% of older adults usually got less …

Association Between Preoperative Hemodialysis Timing And Postoperative Mortality In Patients With End-Stage Kidney Disease, Vikram Fielding-Singh, Matthew W Vanneman, Tristan Grogan, Jacques P Neelankavil, Wolfgang C Winkelmayer, Tara I Chang, Vincent X Liu, Eugene Lin

Faculty, Staff and Students Publications

Importance: For patients with end-stage kidney disease treated with hemodialysis, the optimal timing of hemodialysis prior to elective surgical procedures is unknown.

Objective: To assess whether a longer interval between hemodialysis and subsequent surgery is associated with higher postoperative mortality in patients with end-stage kidney disease treated with hemodialysis.

Design, setting, and participants: Retrospective cohort study of 1 147 846 procedures among 346 828 Medicare beneficiaries with end-stage kidney disease treated with hemodialysis who underwent surgical procedures between January 1, 2011, and September 30, 2018. Follow-up ended on December 31, 2018.

Exposures: One-, two-, or three-day intervals between the most …

Elective Surgery System Strengthening: Development, Measurement, And Validation Of The Surgical Preparedness Index Across 1632 Hospitals In 119 Countries, Nihr Global Health Unit On Global Surgery, Covidsurg Collaborative

Faculty, Staff and Student Publications

BACKGROUND: The 2015 Lancet Commission on global surgery identified surgery and anaesthesia as indispensable parts of holistic health-care systems. However, COVID-19 exposed the fragility of planned surgical services around the world, which have also been neglected in pandemic recovery planning. This study aimed to develop and validate a novel index to support local elective surgical system strengthening and address growing backlogs.

METHODS: First, we performed an international consultation through a four-stage consensus process to develop a multidomain index for hospital-level assessment (surgical preparedness index; SPI). Second, we measured surgical preparedness across a global network of hospitals in high-income countries (HICs), …

Microrna Analysis In Maternal Blood Of Pregnancies With Preterm Premature Rupture Of Membranes Reveals A Distinct Expression Profile, Michail Spiliopoulos, Andrew Haddad, Huda B Al-Kouatly, Saeed Haleema, Michael J Paidas, Sara N Iqbal, Robert I Glazer

Department of Obstetrics and Gynecology Faculty Papers

OBJECTIVE: To determine the expression profile of microRNAs in the peripheral blood of pregnant women with preterm premature rupture of membranes (PPROM) compared to that of healthy pregnant women.

STUDY DESIGN: This was a pilot study with case-control design in pregnant patients enrolled between January 2017 and June 2019. Patients with healthy pregnancies and those affected by PPROM between 20- and 33+6 weeks of gestation were matched by gestational age and selected for inclusion to the study. Patients were excluded for multiple gestation and presence of a major obstetrical complication such as preeclampsia, diabetes, fetal growth restriction and stillbirth. A …

Ovarian Steroid Cell Tumors, Not Otherwise Specified: Analysis Of Nine Cases With A Literature Review, Mengyan Lin, Kechun Bao, Lingjia Lu, Shuhang Xu, Yun Liang, Xiaodong Cheng, Fenfen Wang

Faculty, Staff and Student Publications

BACKGROUND: Ovarian steroid cell tumors (SCTs), not otherwise specified (NOS), are rare, with few large studies. The purpose of this study was to analyze the clinical features, prognosis, and treatment choices for these patients of different age groups.

METHODS: This was a retrospective study. We identified nine cases of ovarian steroid cell tumor, not otherwise specified, confirmed by post-operative histopathological examination, and analyzed clinical features, surgical procedures, and follow up outcomes. We also reviewed cases reports of ovarian steroid cell tumors, not otherwise specified.

RESULTS: A total of nine cases were included. The age range was 9-68 years (mean, 41.89 …

Active Vs Traditional Methods Of Recruiting Children For A Clinical Trial In Rural Primary Care Clinics: A Cluster-Randomized Clinical Trial, Paul M Darden, Ann M Davis, Jeannette Y Lee, Milan Bimali, Alan E Simon, Andrew M Atz, Crystal S Lim, Thao-Ly Phan, James R Roberts, Russell J Mcculloh, Lee Pyles, Michelle Shaffer, Jessica N Snowden

Department of Pediatrics Faculty Papers

Importance: To our knowledge, there are no published randomized clinical trials of recruitment strategies. Rigorously evaluated successful recruitment strategies for children are needed.

Objective: To evaluate the feasibility of 2 recruitment methods for enrolling rural children through primary care clinics to assess whether either or both methods are sufficiently effective for enrolling participants into a clinical trial of a behavioral telehealth intervention for children with overweight or obesity.

Design, setting, and participants: This cluster-randomized clinical trial of 2 recruitment methods was conducted at 4 primary care clinics in 4 separate states. Each clinic used both recruitment methods in random order. …

Tdap-Hpv Vaccination Bundling In The Usa: Trends, Predictors, And Implications For Vaccine Series Completion, Yenan Zhu, Chi-Fang Wu, Anna R Giuliano, Maria E Fernandez, Ana P Ortiz, Cecilia Ganduglia Cazaban, Ruosha Li, Ashish A Deshmukh, Kalyani Sonawane

Faculty, Staff and Student Publications

The Centers for Disease Control and Prevention (CDC) promotes taking a 'bundling approach' (i.e., administering Tetanus, diphtheria toxoids, and acellular pertussis [Tdap] and human papillomavirus [HPV] vaccines in the same way and on the same day) for adolescent vaccinations. Recent trends and patterns in Tdap-HPV vaccination bundling in the USA remain undocumented. In addition, the implications of bundling Tdap-HPV vaccination for HPV vaccine series completion remain unknown. to address these critical knowledge gaps, we performed a retrospective study using a nationwide sample of privately insured adolescents (Optum's de-identified Clinformatics® Data Mart Database). Tdap-HPV vaccination bundling (per 100 Tdap vaccination encounters) …

Assessing Urinary Phenol And Paraben Mixtures In Pregnant Women With And Without Gestational Diabetes Mellitus: A Case-Control Study, Wei-Jen Chen, Candace Robledo, Erin M Davis, Jean R Goodman, Chao Xu, Jooyeon Hwang, Amanda E Janitz, Tabitha Garwe, Antonia M Calafat, Jennifer D Peck

Faculty, Staff and Student Publications

Prior studies have identified the associations between environmental phenol and paraben exposures and increased risk of gestational diabetes mellitus (GDM), but no study addressed these exposures as mixtures. As methods have emerged to better assess exposures to multiple chemicals, our study aimed to apply Bayesian kernel machine regression (BKMR) to evaluate the association between phenol and paraben mixtures and GDM. This study included 64 GDM cases and 237 obstetric patient controls from the University of Oklahoma Medical Center. Mid-pregnancy spot urine samples were collected to quantify concentrations of bisphenol A (BPA), benzophenone-3, triclosan, 2,4-dichlorophenol, 2,5-dichlorophenol, butylparaben, methylparaben, and propylparaben. Multivariable …