Digital Commons Network^™

Longitudinal Dynamics Of Skin Bacterial Communities In The Context Of Staphylococcus Aureus Decolonization, Stephanie A Fritz, Todd N Wylie, Haley Gula, Patrick G Hogan, Mary G Boyle, Carol E Muenks, Melanie L Sullivan, Carey-Ann D Burnham, Kristine M Wylie

Open Access Publications

Decolonization with topical antimicrobials is frequently prescribed in health care and community settings to prevent Staphylococcus aureus infection. However, effects on commensal skin microbial communities remains largely unexplored. Within a household affected by recurrent methicillin-resistant S. aureus skin and soft tissue infections (SSTI), skin swabs were collected from the anterior nares, axillae, and inguinal folds of 14 participants at 1- to 3-month intervals over 24 months. Four household members experienced SSTI during the first 12-months (observational period) and were prescribed a 5-day decolonization regimen with intranasal mupirocin and bleach water baths at the 12-month study visit. We sequenced the 16S …

A Cryptic Pocket In Ebola Vp35 Allosterically Controls Rna Binding, Matthew A Cruz, Thomas E Frederick, Upasana L Mallimadugula, Sukrit Singh, Neha Vithani, Maxwell I Zimmerman, Justin R Porter, Katelyn E Moeder, Gaya K Amarasinghe, Gregory R Bowman

Open Access Publications

Protein-protein and protein-nucleic acid interactions are often considered difficult drug targets because the surfaces involved lack obvious druggable pockets. Cryptic pockets could present opportunities for targeting these interactions, but identifying and exploiting these pockets remains challenging. Here, we apply a general pipeline for identifying cryptic pockets to the interferon inhibitory domain (IID) of Ebola virus viral protein 35 (VP35). VP35 plays multiple essential roles in Ebola's replication cycle but lacks pockets that present obvious utility for drug design. Using adaptive sampling simulations and machine learning algorithms, we predict VP35 harbors a cryptic pocket that is allosterically coupled to a key …

Circadian Pacemaker Neurons Display Cophasic Rhythms In Basal Calcium Level And In Fast Calcium Fluctuations, Xitong Liang, Timothy E Holy, Paul H Taghert

Open Access Publications

SignificanceDaily rhythms in the molecular clock, in calcium, and in electrical activity all interact to support the functions of circadian pacemaker neurons. However, the regulatory mechanisms that unify these properties are not defined. Here, we utilize the cellular resolution of the

Oncogenic Kras-Mediated Cytokine Ccl15 Regulates Pancreatic Cancer Cell Migration And Invasion Through Ros, Justin K Messex, Kiyah L A Adams, William G Hawkins, David Denardo, Nabeel Bardeesy, Daniel D Billadeau, Geou-Yarh Liou

Open Access Publications

Pancreatic ductal adenocarcinoma (PDAC) is well known for its high death rate due to prompt cancer metastasis caused by cancer cell migration and invasion within the early stages of its development. Here, we reveal a new function of cytokine CCL15, namely the upregulation of PDAC cell migration and invasion. We showed increased levels of CCL15 transcripts and protein expressions in human PDAC tissue samples, as well as in cultured cell lines. Furthermore, PDAC cells also expressed CCL15 receptors, including CCR1 and CCR3. Murine PDAC cell lines and tissues strengthened this finding. The manipulation of CCL15 in metastatic Panc-1 cells through …

Shared And Unique Brain Network Features Predict Cognitive, Personality, And Mental Health Scores In The Abcd Study, Jianzhong Chen, Angela Tam, Valeria Kebets, Csaba Orban, Leon Qi Rong Ooi, Christopher L Asplund, Scott Marek, Nico U F Dosenbach, Simon B Eickhoff, Danilo Bzdok, Avram J Holmes, B T Thomas Yeo

Open Access Publications

How individual differences in brain network organization track behavioral variability is a fundamental question in systems neuroscience. Recent work suggests that resting-state and task-state functional connectivity can predict specific traits at the individual level. However, most studies focus on single behavioral traits, thus not capturing broader relationships across behaviors. In a large sample of 1858 typically developing children from the Adolescent Brain Cognitive Development (ABCD) study, we show that predictive network features are distinct across the domains of cognitive performance, personality scores and mental health assessments. On the other hand, traits within each behavioral domain are predicted by similar network …

Combining Plasma Extracellular Vesicle Let-7b-5p, Mir-184 And Circulating Mir-22-3p Levels For Nsclc Diagnosis And Drug Resistance Prediction, G P Vadla, B Daghat, N Patterson, V Ahmad, G Perez, A Garcia, Y Manjunath, J T Kaifi, G Li, C Y Chabu

Open Access Publications

Low-dose computed tomography (LDCT) Non-Small Cell Lung (NSCLC) screening is associated with high false-positive rates, leading to unnecessary expensive and invasive follow ups. There is a need for minimally invasive approaches to improve the accuracy of NSCLC diagnosis. In addition, NSCLC patients harboring sensitizing mutations in epidermal growth factor receptor EGFR (T790M, L578R) are treated with Osimertinib, a potent tyrosine kinase inhibitor (TKI). However, nearly all patients develop TKI resistance. The underlying mechanisms are not fully understood. Plasma extracellular vesicle (EV) and circulating microRNA (miRNA) have been proposed as biomarkers for cancer screening and to inform treatment decisions. However, the …

A Somatic Mutation In Moesin Drives Progression Into Acute Myeloid Leukemia, Ouyang Yuan, Jeffrey A Magee, Et Al.

Open Access Publications

Acute myeloid leukemia (AML) arises when leukemia-initiating cells, defined by a primary genetic lesion, acquire subsequent molecular changes whose cumulative effects bypass tumor suppression. The changes that underlie AML pathogenesis not only provide insights into the biology of transformation but also reveal novel therapeutic opportunities. However, backtracking these events in transformed human AML samples is challenging, if at all possible. Here, we approached this question using a murine in vivo model with an MLL-ENL fusion protein as a primary molecular event. Upon clonal transformation, we identified and extensively verified a recurrent codon-changing mutation (Arg

Dissemination And Implementation Science Resources, Training, And Scientific Activities Provided Through Ctsa Programs Nationally: Opportunities To Advance D&I Research And Training Capacity, Rachel C Shelton, Rowena J Dolor, Jonathan Tobin, Ana Baumann, Catherine Rohweder, Sapana Patel, Laura-Mae Baldwin

Open Access Publications

Introduction: Clinical and Translational Science Award (CTSA) Program hubs are well-positioned to advance dissemination and implementation (D&I) research and training capacity nationally, though little is known about what D&I research support and services CTSAs provide. To address this gap, the CTSA Dissemination, Implementation, and Knowledge Transfer Working Group conducted an environmental scan of CTSAs (2017-2018).

Methods: Of 67 CTSA institutions, we contacted 43 that previously reported delivering D&I research services. D&I experts from these institutions were emailed a survey assessing D&I resources, services, training, and scientific projects. Responses were categorized and double-coded by study authors using a content analysis approach. …

Odach: A One-Shot Distributed Algorithm For Cox Model With Heterogeneous Multi-Center Data, Chongliang Luo, Rui Duan, Adam C Naj, Henry R Kranzler, Jiang Bian, Yong Chen

Open Access Publications

We developed a One-shot Distributed Algorithm for Cox proportional-hazards model to analyze Heterogeneous multi-center time-to-event data (ODACH) circumventing the need for sharing patient-level information across sites. This algorithm implements a surrogate likelihood function to approximate the Cox log-partial likelihood function that is stratified by site using patient-level data from a lead site and aggregated information from other sites, allowing the baseline hazard functions and the distribution of covariates to vary across sites. Simulation studies and application to a real-world opioid use disorder study showed that ODACH provides estimates close to the pooled estimator, which analyzes patient-level data directly from all …

Cisplatin Resistance Can Be Curtailed By Blunting Bnip3-Mediated Mitochondrial Autophagy, Caterina Vianello, Gerald W Dorn 2nd, Et Al

Open Access Publications

Cisplatin (CDDP) is commonly used to treat a multitude of tumors including sarcomas, ovarian and cervical cancers. Despite recent investigations allowed to improve chemotherapy effectiveness, the molecular mechanisms underlying the development of CDDP resistance remain a major goal in cancer research. Here, we show that mitochondrial morphology and autophagy are altered in different CDDP resistant cancer cell lines. In CDDP resistant osteosarcoma and ovarian carcinoma, mitochondria are fragmented and closely juxtaposed to the endoplasmic reticulum; rates of mitophagy are also increased. Specifically, levels of the mitophagy receptor BNIP3 are higher both in resistant cells and in ovarian cancer patient samples …

The Geriatric Emergency Care Applied Research (Gear) Network Approach: A Protocol To Advance Stakeholder Consensus And Research Priorities In Geriatrics And Dementia Care In The Emergency Department, Ula Hwang, Christopher Carpenter, Scott Dresden, Jeffrey Dussetschleger, Angela Gifford, Ly Hoang, Jesseca Leggett, Armin Nowroozpoor, Zachary Taylor, Manish Shah, The Gear And Gear 2.0 Networks

Open Access Publications

INTRODUCTION: Increasingly, older adults are turning to emergency departments (EDs) to address healthcare needs. To achieve these research demands, infrastructure is needed to both generate evidence of intervention impact and advance the development of implementation science, pragmatic trials evaluation and dissemination of findings from studies addressing the emergency care needs of older adults. The Geriatric Emergency Care Applied Research Network (https://gearnetwork.org) has been created in response to these scientific needs-to build a transdisciplinary infrastructure to support the research that will optimise emergency care for older adults and persons living with dementia.

METHODS AND ANALYSIS: In this paper, we describe our …

Longitudinal Gut Virome Analysis Identifies Specific Viral Signatures That Precede Necrotizing Enterocolitis Onset In Preterm Infants, Emily A Kaelin, Cynthia Rodriguez, Carla Hall-Moore, Julie A Hoffmann, Laura A Linneman, I Malick Ndao, Barbara B Warner, Phillip I Tarr, Lori R Holtz, Efrem S Lim

Open Access Publications

Necrotizing enterocolitis (NEC) is a serious consequence of preterm birth and is often associated with gut bacterial microbiome alterations. However, little is known about the development of the gut virome in preterm infants, or its role in NEC. Here, using metagenomic sequencing, we characterized the DNA gut virome of 9 preterm infants who developed NEC and 14 gestational age-matched preterm infants who did not. Infants were sampled longitudinally before NEC onset over the first 11 weeks of life. We observed substantial interindividual variation in the gut virome between unrelated preterm infants, while intraindividual variation over time was significantly less. We …

Murine Respiratory Tract Infection With Classical Klebsiella Pneumoniae Induces Bronchus-Associated Lymphoid Tissue, Rachel K Wasbotten, Aubree A Dahler, Joseph J Mackel, Catherine Morffy Smith, David A Rosen

Open Access Publications

Klebsiella pneumoniae is a Gram-negative, opportunistic pathogen that commonly causes nosocomial pneumonia, urinary tract infection, and septicemia. Our recent work utilizing a murine model of respiratory tract infection with classical K. pneumoniae demonstrated leukocyte aggregates in the lungs of mice at 28 days postinfection. Here, we sought to characterize the composition and development of these structures. Histopathological analyses of murine lungs revealed immune cell clusters surrounding the pulmonary vasculature and airways by 14 days postinfection, resembling inducible bronchus-associated lymphoid tissue (iBALT). Further investigation of these structures demonstrated central B cell aggregates with concomitant dispersed T cells. At day 28 postinfection, …

Persistent Methicillin-Susceptible Bacteremia Rapidly Cleared With Cefazolin And Ertapenem Combination Therapy In A Patient With Covid-19, Dan Ilges, Gayathri Krishnan, Elvin Geng

Open Access Publications

Methicillin-susceptible

Development And Validation Of The Rcos Prognostic Index: A Bedside Multivariable Logistic Regression Model To Predict Hypoxaemia Or Death In Patients With Sars-Cov-2 Infection, Gerardo Alvarez-Uria, Sumanth Gandra, Venkata R Gurram, Raghu P Reddy, Manoranjan Midde, Praveen Kumar, Ketty E Arce

Open Access Publications

Introduction: Previous COVID-19 prognostic models have been developed in hospital settings and are not applicable to COVID-19 cases in the general population. There is an urgent need for prognostic scores aimed to identify patients at high risk of complications at the time of COVID-19 diagnosis.

Methods: The RDT COVID-19 Observational Study (RCOS) collected clinical data from patients with COVID-19 admitted regardless of the severity of their symptoms in a general hospital in India. We aimed to develop and validate a simple bedside prognostic score to predict the risk of hypoxaemia or death.

Results: 4035 patients were included in the development …

Naturalistic Driving Measures Of Route Selection Associate With Resting State Networks In Older Adults, Julie K Wisch, Catherine M Roe, Ganesh M Babulal, Nicholas Metcalf, Ann M Johnson, Samantha Murphy, Jamie Hicks, Jason M Doherty, John C Morris, Beau M Ances

Open Access Publications

Our objective was to identify functional brain changes that associate with driving behaviors in older adults. Within a cohort of 64 cognitively normal adults (age 60+), we compared naturalistic driving behavior with resting state functional connectivity using machine learning. Functional networks associated with the ability to interpret and respond to external sensory stimuli and the ability to multi-task were associated with measures of route selection. Maintenance of these networks may be important for continued preservation of driving abilities.

The Impact Of Implementing The Virtuo Blood Culture System On The Characteristics And Management Of Patients With Staphylococcus Aureus Bacteremia, Miguel A Chavez, Satish Munigala, Carey-Ann D Burnham, Melanie L Yarbrough, David K Warren

Open Access Publications

Persistent Staphylococcus aureus bacteremia (SAB) has been associated with increased mortality. Enhanced microbial detection with new blood culture technology may improve detection of S. aureus in patients with SAB. We performed a 24-month retrospective study of hospitalized adults with SAB and an infectious diseases consult comparing two time periods pre- (January to December 2018) and postimplementation (January to December 2019) in which the VersaTREK and BacT/Alert Virtuo blood culture systems were used, respectively. Measurements included SAB duration, time to positivity, source of bacteremia, antimicrobial therapy, and mortality. A total of 416 episodes of SAB occurred during the study period: 176 …

Development And Validation Of A Novel Anaerobic Carbapenem Inactivation Method (Ana-Cim) For The Detection Of Carbapenemase Production In Bacteroides Fragilis, Allison R Eberly, Meghan A Wallace, Samantha Shannon, Angela K Heitman, Audrey N Schuetz, Carey-Ann D Burnham, Sophonie Jean

Open Access Publications

Antibiotic resistance, particularly to carbapenems, is of increasing concern in Bacteroides fragilis. Carbapenem resistance in B. fragilis is most often mediated by the activation of chromosomally encoded metallo-β-lactamase

Applying Systems Thinking To Identify Enablers And Challenges To Scale-Up Interventions For Hypertension And Diabetes In Low-Income And Middle-Income Countries: Protocol For A Longitudinal Mixed-Methods Study, Anusha Ramani-Chander, Mark D Huffman, Et Al

Open Access Publications

INTRODUCTION: There is an urgent need to reduce the burden of non-communicable diseases (NCDs), particularly in low-and middle-income countries, where the greatest burden lies. Yet, there is little research concerning the specific issues involved in scaling up NCD interventions targeting low-resource settings. We propose to examine this gap in up to 27 collaborative projects, which were funded by the Global Alliance for Chronic Diseases (GACD) 2019 Scale Up Call, reflecting a total funding investment of approximately US$50 million. These projects represent diverse countries, contexts and adopt varied approaches and study designs to scale-up complex, evidence-based interventions to improve hypertension and …

Integrin-Mediated Adhesion Promotes Centrosome Separation In Early Mitosis, Siamak A Kamranvar, Deepesh Kumar Gupta, Anishia Wasberg, Liangwen Liu, Joan Roig, Staffan Johansson

Open Access Publications

Integrin-mediated adhesion to the extracellular matrix is a key regulator of the cell cycle, as demonstrated for the passage of the G1/S checkpoint and the completion of cytokinetic abscission. Here, integrin-dependent regulation of the cell cycle in G2 and early M phases was investigated. The progression through the G2 and M phases was monitored by live-cell imaging and immunofluorescence staining in adherent and non-adherent fibroblast cells. Non-adherent cells, as well as adherent cells lacking FAK activity due to suppressed expression or pharmacological inhibition, exhibited a prolonged G2 phase and severely defect centrosome separation, resulting in delayed progress through the early …

Clinical Classification Of Symptomatic Heterotopic Pancreas Of The Stomach And Duodenum: A Case Series And Systematic Literature Review, Michael T. Lecompte, Brandon Mason, Keenan J. Robbins, Matoya Yano, Deyali Chatterjee, Ryan C. Fields, Steven M. Strasberg, William G. Hawkins

Open Access Publications

No abstract provided.

Hereditary Alpha-Tryptasemia Modifies Clinical Phenotypes Among Individuals With Congenital Hypermobility Disorders, Maribel Vazquez, Jack Chovanec, Jiwon Kim, Thomas Dimaggio, Joshua D Milner, Clair A Francomano, Christina A Gurnett, Marco Ritelli, Marina Colombi, Jonathan J Lyons

Open Access Publications

Hereditary alpha-tryptasemia (HαT) is an autosomal dominant (AD) genetic trait characterized by elevated basal serum tryptase ≥8 ng/mL, caused by increased α-tryptase-encoding

Convection Enhanced Delivery Of The Oncolytic Adenovirus Delta24-Rgd In Patients With Recurrent Gbm: A Phase I Clinical Trial Including Correlative Studies, Erik H P Van Putten, David T Curiel, Et Al

Open Access Publications

PURPOSE: Testing safety of Delta24-RGD (DNX-2401), an oncolytic adenovirus, locally delivered by convection enhanced delivery (CED) in tumor and surrounding brain of patients with recurrent glioblastoma.

PATIENTS AND METHODS: Dose-escalation phase I study with 3+3 cohorts, dosing 107 to 1 × 1011 viral particles (vp) in 20 patients. Besides clinical parameters, adverse events, and radiologic findings, blood, cerebrospinal fluid (CSF), brain interstitial fluid, and excreta were sampled over time and analyzed for presence of immune response, viral replication, distribution, and shedding.

RESULTS: Of 20 enrolled patients, 19 received the oncolytic adenovirus Delta24-RGD, which was found to be safe and feasible. …

Linc00355 Regulates P27 Kip Expression By Binding To Menin To Induce Proliferation In Late-Stage Relapse Breast Cancer, Abdallah M Eteleeb, Prasanth K Thunuguntla, Kyla Z Gelev, Emily B Rozycki, Alexander Miller, Reyka G Jayasinghe, Ha X Dang, Nicole M White, Li Ding, Jessica M Silva-Fisher, Christopher A Maher, Et Al

Open Access Publications

Late-stage relapse (LSR) in patients with breast cancer (BC) occurs more than five years and up to 10 years after initial treatment and has less than 30% 5-year relative survival rate. Long non-coding RNAs (lncRNAs) play important roles in BC yet have not been studied in LSR BC. Here, we identify 1127 lncRNAs differentially expressed in LSR BC via transcriptome sequencing and analysis of 72 early-stage and 24 LSR BC patient tumors. Decreasing expression of the most up-regulated lncRNA, LINC00355, in BC and MCF7 long-term estrogen deprived cell lines decreases cellular invasion and proliferation. Subsequent mechanistic studies show that LINC00355 …

Heparanase Blockade As A Novel Dual-Targeting Therapy For Covid-19, Jingyu Xiang, Mijia Lu, Min Shi, Xiaogang Cheng, Kristin A Kwakwa, Jennifer L Davis, Xinming Su, Suzanne J Bakewell, Yuexiu Zhang, Francesca Fontana, Yalin Xu, Deborah J Veis, John F Dipersio, Lee Ratner, Ralph D Sanderson, Alessandro Noseda, Shamim Mollah, Jianrong Li, Katherine N Weilbaecher

Open Access Publications

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused over 5 million deaths worldwide. Pneumonia and systemic inflammation contribute to its high mortality. Many viruses use heparan sulfate proteoglycans as coreceptors for viral entry, and heparanase (HPSE) is a known regulator of both viral entry and inflammatory cytokines. We evaluated the heparanase inhibitor Roneparstat, a modified heparin with minimum anticoagulant activity, in pathophysiology and therapy for COVID-19. We found that Roneparstat significantly decreased the infectivity of SARS-CoV-2, SARS-CoV-1, and retroviruses (human T-lymphotropic virus 1 [HTLV-1] and HIV-1)

An International Analysis Evaluating Frontline Bendamustine With Rituximab In Extranodal Marginal Zone Lymphoma, Juan Pablo Alderuccio, Marcus P Watkins, Raya Saba, Brad S Kahl, Et Al

Open Access Publications

Extranodal marginal zone lymphoma (EMZL) is a heterogeneous non-Hodgkin lymphoma. No consensus exists regarding the standard-of-care in patients with advanced-stage disease. Current recommendations are largely adapted from follicular lymphoma, for which bendamustine with rituximab (BR) is an established approach. We analyzed the safety and efficacy of frontline BR in EMZL using a large international consortium. We included 237 patients with a median age of 63 years (range, 21-85). Most patients presented with Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1 (n = 228; 96.2%), stage III/IV (n = 179; 75.5%), and intermediate (49.8%) or high (33.3%) Mucosa Associated …

Machine Learning-Based Scoring Models To Predict Hematopoietic Stem Cell Mobilization In Allogeneic Donors, Jingyu Xiang, Min Shi, Mark A Fiala, Feng Gao, Michael P Rettig, Geoffrey L Uy, Mark A Schroeder, Katherine N Weilbaecher, Keith E Stockerl-Goldstein, Shamim Mollah, John F Dipersio

Open Access Publications

Mobilized peripheral blood has become the primary source of hematopoietic stem cells for both autologous and allogeneic stem cell transplantation. Granulocyte colony-stimulating factor (G-CSF) is currently the standard agent used in the allogeneic setting. Despite the high mobilization efficacy in most donors, G-CSF requires 4-5 days of daily administration, and a small percentage of the donors fail to mobilize an optimal number of stem cells necessary for a safe allogeneic stem cell transplant. In this study, we retrospectively reviewed 1361 related allogeneic donors who underwent stem cell mobilization at Washington University. We compared the standard mobilization agent G-CSF with five …

Identification Of Small Regions Of Overlap From Copy Number Variable Regions In Patients With Hypospadias, Carter H Scott, Ina E Amarillo

Open Access Publications

Hypospadias is a common form of congenital atypical sex development that is often associated with other congenital comorbidities. Many genes have been associated with the condition, most commonly single sequence variations. Further investigations of recurrent and overlapping copy number variations (CNVs) have resulted in the identification of genes and chromosome regions associated with various conditions, including differences of sex development (DSD). In this retrospective study, we investigated the DECIPHER database, as well as an internal institutional database, to identify small recurrent CNVs among individuals with isolated and syndromic hypospadias. We further investigated these overlapping recurrent CNVs to identify 75 smallest …

From Self-Efficacy To Imposter Syndrome: The Intrapersonal Traits Of Surgeons, Alexandra Medline, Helyn Grissom, Ndéye F Guissé, Victoria Kravets, Sandra Hobson, Julie Balch Samora, Mara Schenker

Open Access Publications

BACKGROUND: Demographic differences among surgical trainees regarding intrapersonal traits, such as imposter syndrome and assertiveness, have become widely acknowledged. However, many of these characteristics have not been examined in tandem, nor among both trainees and surgeons in practice. This study aimed to address these knowledge gaps.

METHODS: This was an anonymous, voluntary survey study comprised of validated measures of (1) self-efficacy, (2) imposter syndrome, (3) assertiveness, (4) perfectionism, and (5) self-rated likeability. A multimodal recruitment strategy was used and surgeons across all subspecialties were eligible for inclusion.

RESULTS: A total of 296 participants were included, with 54% identifying as female …

Serum Phosphorus And Pill Burden Among Hemodialysis Patients Prescribed Sucroferric Oxyhydroxide: One-Year Follow-Up On A Contemporary Cohort, Jessica B Kendrick, Meijiao Zhou, Linda H Ficociello, Vidhya Parameswaran, Claudy Mullon, Michael S Anger, Daniel W Coyne

Open Access Publications

Purpose: In prior analyses of real-world cohorts of hemodialysis patients switched from one phosphate binder (PB) to sucroferric oxyhydroxide (SO), SO therapy has been associated with improvements in serum phosphorus (sP) and reductions in daily PB pill burden. To characterize how SO initiation patterns have changed over time, we examined the long-term effectiveness of SO in a contemporary (2018-2019) cohort.

Patients and Methods: Adult Fresenius Kidney Care hemodialysis patients first prescribed SO monotherapy as part of routine care between May 2018 and May 2019 (N = 1792) were followed for 1 year. All patients received a non-SO PB during a …