Medicine and Health Sciences Commons^™

Surgical And Percutaneous Revascularization Outcomes Based On Syntax I, Ii, And Residual Scores: A Long-Term Follow-Up Study, Eduardo Bello Martins, Whady Hueb, David L Brown, Thiago Luis Scudeler, Eduardo Gomes Lima, Paulo Cury Rezende, Paulo Rogério Soares, Cibele Larrosa Garzillo, Jaime Paula Pessoa Linhares Filho, Daniel Valente Batista, Jose Antonio Franchini Ramires, Roberto Kalil Filho

2020-Current year OA Pubs

BACKGROUND: The objective of this study was to evaluate the association of SYNTAX scores I, II, and residual with cardiovascular outcomes of patients undergoing coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) and compare both procedures in a long-term follow-up.

METHODS: This is a retrospective single-center study from the MASS registry at the Heart Institute of the University of São Paulo, Brazil in which 969 patients with stable coronary artery disease undergoing CABG (559) or PCI (410) were included. We assessed the SYNTAX scores I, II and residual in both interventions. Clinical endpoints were the first occurrence of …

Msisensor-Ct: Microsatellite Instability Detection Using Cfdna Sequencing Data, Xinyin Han, Shuying Zhang, Daniel Cui Zhou, Dongliang Wang, Xiaoyu He, Danyang Yuan, Ruilin Li, Jiayin He, Xiaohong Duan, Michael C Wendl, Li Ding, Beifang Niu

2020-Current year OA Pubs

MOTIVATION: Microsatellite instability (MSI) is a promising biomarker for cancer prognosis and chemosensitivity. Techniques are rapidly evolving for the detection of MSI from tumor-normal paired or tumor-only sequencing data. However, tumor tissues are often insufficient, unavailable, or otherwise difficult to procure. Increasing clinical evidence indicates the enormous potential of plasma circulating cell-free DNA (cfNDA) technology as a noninvasive MSI detection approach.

RESULTS: We developed MSIsensor-ct, a bioinformatics tool based on a machine learning protocol, dedicated to detecting MSI status using cfDNA sequencing data with a potential stable MSIscore threshold of 20%. Evaluation of MSIsensor-ct on independent testing datasets with various …

Genome Assemblies Across The Diverse Evolutionary Spectrum Of Leishmania Protozoan Parasites, Wesley C. Warren, Natalia S. Akopyants, Deborah E. Dobson, Christiane Hertz-Fowler, Lon-Fye Lye, Peter J. Myler, Gowthaman Ramasamy, Achchuthan Shanmugasundram, Fatima Silva-Franco, Sascha Steinbiss, Chad Tomlinson, Richard K. Wilson, Stephen M. Beverley

2020-Current year OA Pubs

We report the high-quality draft assemblies and gene annotations for 13 species and/or strains of the protozoan parasite genera

Cognitive Correlates Of Instrumental Activities Of Daily Living Performance In Parkinson Disease Without Dementia, Erin R Foster, Tasha Doty

2020-Current year OA Pubs

OBJECTIVE: To investigate cognitive correlates of instrumental activities of daily living (IADL) performance among people with Parkinson disease (PD) without dementia.

DESIGN: Cross-sectional.

SETTING: Academic medical center.

PARTICIPANTS: Volunteer sample (N=161) comprising participants with PD without dementia (n=102) and healthy comparison (HC) participants (n=59).

INTERVENTIONS: Not applicable.

MAIN OUTCOME MEASURES: Performance-based assessment of cognitively-demanding IADL (meal preparation, bill paying, shopping, medication management, small home repair), neuropsychological tests (attentional control/flexibility, planning, working memory, memory, crystallized intelligence), and measures of motor function and other characteristics (eg, depressive symptoms).

RESULTS: There were no group differences in neuropsychological test performance (

CONCLUSIONS: The PD …

A Phase 1 Study Evaluating Rovalpituzumab Tesirine In Frontline Treatment Of Patients With Extensive-Stage Sclc, Christine L. Hann, Timothy F. Burns, Afshin Dowlati, Daniel Morgensztern, Patrick J. Ward, Martina M. Koch, Chris Chen, Carrianne Ludwig, Maulik Patel, Halla Nimeiri, Philip Komarnitsky, D. Ross Camidge

2020-Current year OA Pubs

INTRODUCTION: Rovalpituzumab tesirine (Rova-T) is an antibody-drug conjugate targeting DLL3, a Notch pathway ligand highly expressed on SCLC cells. Rova-T was evaluated alone or in combination with platinum-based chemotherapy (cisplatin or carboplatin combined with etoposide [CE]) in frontline treatment of extensive-stage SCLC.

METHODS: One cycle of CE pre-enrollment was permitted (later mandated). The following four cohorts were enrolled: Rova-T monotherapy (0.3 mg/kg, every 6 [q6] wk × 2; cohort 1; n = 4); Rova-T induction (0.3 mg/kg, q6 wk × 2) followed by CE every 21 days (q21) × 4 (cohort 2; n = 5); Rova-T (0.1 or 0.2 mg/kg, …

A Phase 1-2 Study Of Rovalpituzumab Tesirine In Combination With Nivolumab Plus Or Minus Ipilimumab In Patients With Previously Treated Extensive-Stage Sclc, Jyoti Malhotra, Daniel Morgensztern, Et Al.

2020-Current year OA Pubs

INTRODUCTION: This open-label, phase 1-2 study evaluated the safety and efficacy of rovalpituzumab tesirine (Rova-T), an antibody-drug conjugate targeting DLL3, plus immune checkpoint inhibitors nivolumab plus or minus ipilimumab in previously treated extensive-stage SCLC (ES SCLC).

METHODS: Patients with histologically or cytologically confirmed, previously treated (two or more lines of therapy) ES SCLC were enrolled into two cohorts. Cohort 1 received 0.3 mg/kg Rova-T (once every 6 wk for two cycles) plus 360 mg nivolumab (two 3-wk cycles beginning on week 4). Cohort 2 received the same dosage of Rova-T as cohort 1 plus 1 mg/kg nivolumab (four 3-wk cycles) …

Differential Effects Of The Novel Neurosteroid Hypnotic (3Β,5Β,17Β)-3-Hydroxyandrostane-17-Carbonitrile On Electroencephalogram Activity In Male And Female Rats, Srdjan M Joksimovic, Dayalan Sampath, Kathiresan Krishnan, Douglas F Covey, Vesna Jevtovic-Todorovic, Yogendra H Raol, Slobodan M Todorovic

2020-Current year OA Pubs

BACKGROUND: We recently showed that a neurosteroid analogue, (3β,5β,17β)-3-hydroxyandrostane-17-carbonitrile (3β-OH), induced hypnosis in rats. The aim of the present study was to evaluate the hypnotic and anaesthetic potential of 3β-OH further using electroencephalography.

METHODS: We used behavioural assessment and cortical electroencephalogram (EEG) spectral power analysis to examine hypnotic and anaesthetic effects of 3β-OH (30 and 60 mg kg

RESULTS: We found dose-dependent sex differences in 3β-OH-induced hypnosis and EEG changes. Both male and female rats responded similarly to i.p. 3β-OH 30 mg kg

CONCLUSIONS: Based on its behavioural effects and EEG signature, 3β-OH is a potent hypnotic in rats, with …

American Society Of Transplantation And Cellular Therapy, Center Of International Blood And Marrow Transplant Research, And European Society For Blood And Marrow Transplantation Clinical Practice Recommendations For Transplantation And Cellular Therapies In Mantle Cell Lymphoma, Pashna N Munshi, Brad Kahl, Amanda F Cashen, Et Al.

2020-Current year OA Pubs

Autologous (auto-) and allogeneic (allo-) hematopoietic cell transplantation (HCT) are accepted treatment modalities in contemporary treatment algorithms for mantle cell lymphoma (MCL). Chimeric antigen receptor (CAR) T cell therapy recently received approval for MCL; however, its exact place and sequence in relation to HCT remain unclear. The American Society of Transplantation and Cellular Therapy, Center of International Blood and Marrow Transplant Research, and the European Society for Blood and Marrow Transplantation jointly convened an expert panel to formulate consensus recommendations for role, timing, and sequencing of auto-HCT, allo-HCT, and CAR T cell therapy for patients with newly diagnosed and relapsed/refractory …

Ascaris Suum Informs Extrasynaptic Volume Transmission In Nematodes, Louise E Atkinson, Yang Liu, Fiona Mckay, Elke Vandewyer, Charles Viau, Allister Irvine, Bruce A Rosa, Zihui Li, Qingxiao Liang, Nikki J Marks, Aaron G Maule, Makedonka Mitreva, Isabel Beets, Lingjun Li, Angela Mousley

2020-Current year OA Pubs

Neural circuit synaptic connectivities (the connectome) provide the anatomical foundation for our understanding of nematode nervous system function. However, other nonsynaptic routes of communication are known in invertebrates including extrasynaptic volume transmission (EVT), which enables short- and/or long-range communication in the absence of synaptic connections. Although EVT has been highlighted as a facet of

Implementation Of A Non-Emergent Medical Transportation Programme At An Integrated Health System, Patrick G Lyons, Brett A Ramsey, Michael Welker, Megan Guinn, Janice K Ernest, Ali Kosydor, Thomas M Maddox

2020-Current year OA Pubs

OBJECTIVES: To implement a unified non-emergency medical transportation (NEMT) service across a large integrated healthcare delivery network.

METHODS: We assessed needs among key organisational stakeholders, then reviewed proposals. We selected a single NEMT vendor best aligned with organisational priorities and implemented this solution system-wide.

RESULTS: Our vendor's hybrid approach combined rideshares with contracted vehicles able to serve patients with equipment and other needs. After 6195 rides in the first year, we observed shorter wait times and lower costs compared with our prior state.

DISCUSSION: Essential lessons included (1) understanding user and patient needs, (2) obtaining complete, accurate and comprehensive baseline …

Alzheimer's Disease Alters Oligodendrocytic Glycolytic And Ketolytic Gene Expression, Erin R Saito, Justin B Miller, Oscar Harari, Carlos Cruchaga, Kathie A Mihindukulasuriya, John S K Kauwe, Benjamin T Bikman

2020-Current year OA Pubs

INTRODUCTION: Sporadic Alzheimer's disease (AD) is strongly correlated with impaired brain glucose metabolism, which may affect AD onset and progression. Ketolysis has been suggested as an alternative pathway to fuel the brain.

METHODS: RNA-seq profiles of post mortem AD brains were used to determine whether dysfunctional AD brain metabolism can be determined by impairments in glycolytic and ketolytic gene expression. Data were obtained from the Knight Alzheimer's Disease Research Center (62 cases; 13 controls), Mount Sinai Brain Bank (110 cases; 44 controls), and the Mayo Clinic Brain Bank (80 cases; 76 controls), and were normalized to cell type: astrocytes, microglia, …

Bioactive In Situ Crosslinkable Polymer-Peptide Hydrogel For Cell Delivery To The Intervertebral Disc In A Rat Model, Marcos N Barcellona, Julie E Speer, Liufang Jing, Deepanjali S Patil, Munish C Gupta, Jacob M Buchowski, Lori A Setton

2020-Current year OA Pubs

Degeneration of the intervertebral disc (IVD) is associated with significant biochemical and morphological changes that include a loss of disc height, decreased water content and decreased cellularity. Cell delivery has been widely explored as a strategy to supplement the nucleus pulposus (NP) region of the degenerated IVD in both pre-clinical and clinical trials, using progenitor or primary cell sources. We previously demonstrated an ability for a polymer-peptide hydrogel, serving as a culture substrate, to promote adult NP cells to undergo a shift from a degenerative fibroblast-like state to a juvenile-like NP phenotype. In the current study, we evaluate the ability …

Consensus Recommendations On The Treatment Of Opioid Use Disorder In The Emergency Department, Kathryn Hawk, Jason Hoppe, Eric Ketcham, Alexis Lapietra, Aimee Moulin, Lewis Nelson, Evan Schwarz, Sam Shahid, Donald Stader, Michael P Wilson, Gail D'Onofrio

2020-Current year OA Pubs

The treatment of opioid use disorder with buprenorphine and methadone reduces morbidity and mortality in patients with opioid use disorder. The initiation of buprenorphine in the emergency department (ED) has been associated with increased rates of outpatient treatment linkage and decreased drug use when compared to patients randomized to receive standard ED referral. As such, the ED has been increasingly recognized as a venue for the identification and initiation of treatment for opioid use disorder, but no formal American College of Emergency Physicians (ACEP) recommendations on the topic have previously been published. The ACEP convened a group of emergency physicians …

The Incidence Of Adding-On Or Distal Junctional Kyphosis In Adolescent Idiopathic Scoliosis Treated By Anterior Spinal Fusion To L3 Was Significantly Higher Than By Posterior Spinal Fusion To L3, Seung-Jae Hyun, Lawrence G Lenke, Yongjung Kim, Keith H Bridwell, Meghan Cerpa, Kathy M Blanke

2020-Current year OA Pubs

OBJECTIVE: To compare and identify risk factors for distal adding-on (AO) or distal junctional kyphosis (DJK) in adolescent idiopathic scoliosis (AIS) treated by anterior- (ASF) and posterior spinal fusion (PSF) to L3.

METHODS: AIS patients undergoing ASF versus PSF to L3 from 2000-2010 were analyzed. Distal AO and DJK were deemed poor radiographic results. New stable (SV) and neutral vertebra (NV) scores were defined for this study. The total stability (TS) score was the sum of the SV and NV scores.

RESULTS: Twenty of 42 (ASF group: 47.6%) and 8 of 72 patients (PSF group: 11.1%) showed poor radiographic outcome. …

Initial Antimicrobial Management Of Sepsis, Michael S Niederman, Rebecca M Baron, Lila Bouadma, Thierry Calandra, Nick Daneman, Jan Dewaele, Marin H Kollef, Jeffrey Lipman, Girish B Nair

2020-Current year OA Pubs

Sepsis is a common consequence of infection, associated with a mortality rate > 25%. Although community-acquired sepsis is more common, hospital-acquired infection is more lethal. The most common site of infection is the lung, followed by abdominal infection, catheter-associated blood steam infection and urinary tract infection. Gram-negative sepsis is more common than gram-positive infection, but sepsis can also be due to fungal and viral pathogens. To reduce mortality, it is necessary to give immediate, empiric, broad-spectrum therapy to those with severe sepsis and/or shock, but this approach can drive antimicrobial overuse and resistance and should be accompanied by a commitment to …

Improved Integration Of Single-Cell Transcriptome And Surface Protein Expression By Linq-View, Lei Li, Christopher Nelson, Daved H Fremont, Et Al.

2020-Current year OA Pubs

Multimodal advances in single-cell sequencing have enabled the simultaneous quantification of cell surface protein expression alongside unbiased transcriptional profiling. Here, we present LinQ-View, a toolkit designed for multimodal single-cell data visualization and analysis. LinQ-View integrates transcriptional and cell surface protein expression profiling data to reveal more accurate cell heterogeneity and proposes a quantitative metric for cluster purity assessment. Through comparison with existing multimodal methods on multiple public CITE-seq datasets, we demonstrate that LinQ-View efficiently generates accurate cell clusters, especially in CITE-seq data with routine numbers of surface protein features, by preventing variations in a single surface protein feature from affecting …

The Impact Of A Community Based Rehabilitation Program In Afghanistan: A Longitudinal Analysis Using Propensity Score Matching And Difference In Difference Analysis, Jean-Francois Trani, Juanita Vasquez-Escallon, Parul Bakhshi

2020-Current year OA Pubs

BACKGROUND: The 2006 United Nations Convention on the Rights of Persons with Disabilities states that the achievement of equal rights, empowerment and social inclusion of people with disabilities requires comprehensive rehabilitation services encompassing all components of the World Health Organization Community based rehabilitation (CBR) matrix: health, education, livelihood, social and empowerment. CBR programs specifically aim to deliver such comprehensive interventions. In the present study, we investigate the impact of a CBR program in Afghanistan on all these components.

METHODS: We enrolled 1861 newly recruited CBR participants with disabilities in the study, from 169 villages between July 2012 and December 2013 …

Favorable Outcomes With Reduced Steroid Use In Juvenile Dermatomyositis, Amir B Orandi, Lampros Fotis, Jamie Lai, Hallie Morris, Andrew J White, Anthony R French, Kevin W Baszis

2020-Current year OA Pubs

BACKGROUND: High-intensity glucocorticoid regimens are commonly used to induce and maintain remission in Juvenile Dermatomyositis but are associated with several adverse side-effects. Evidence-based treatment guidelines from North American and European pediatric rheumatology research societies both advocate induction with intravenous pulse steroids followed by high dose oral steroids (2 mg/kg/day), which are then tapered. This study reports the time to disease control with reduced glucocorticoid dosing.

METHODS: We retrospectively reviewed the records at a single tertiary-care children's hospital of patients diagnosed with Juvenile Dermatomyositis between 2000 and 2014 who had a minimum of 2 years of follow-up. The primary outcome measure …

A Systematic Review And Network Meta-Analyses To Assess The Effectiveness Of Human Immunodeficiency Virus (Hiv) Self-Testing Distribution Strategies, Ingrid Eshun-Wilson, Muhammad S Jamil, T Charles Witzel, David V Glidded, Cheryl Johnson, Noelle Le Trouneau, Nathan Ford, Kathleen Mcgee, Chris Kemp, Stefan Baral, Sheree Schwartz, Elvin H Geng

2020-Current year OA Pubs

BACKGROUND: We conducted a systematic review and network meta-analysis to identify which human immunodeficiency virus (HIV) self-testing (HIVST) distribution strategies are most effective.

METHODS: We abstracted data from randomized controlled trials and observational studies published between 4 June 2006 and 4 June 2019.

RESULTS: We included 33 studies, yielding 6 HIVST distribution strategies. All distribution strategies increased testing uptake compared to standard testing: in sub-Saharan Africa, partner HIVST distribution ranked highest (78% probability); in North America, Asia, and the Pacific regions, web-based distribution ranked highest (93% probability), and facility based distribution ranked second in all settings. Across HIVST distribution strategies …

Differential Classification Of States Of Consciousness Using Envelope- And Phase-Based Functional Connectivity, Catherine Duclos, Michael S Avidan, Et Al.

2020-Current year OA Pubs

The development of sophisticated computational tools to quantify changes in the brain's oscillatory dynamics across states of consciousness have included both envelope- and phase-based measures of functional connectivity (FC), but there are very few direct comparisons of these techniques using the same dataset. The goal of this study was to compare an envelope-based (i.e. Amplitude Envelope Correlation, AEC) and a phase-based (i.e. weighted Phase Lag Index, wPLI) measure of FC in their classification of states of consciousness. Nine healthy participants underwent a three-hour experimental anesthetic protocol with propofol induction and isoflurane maintenance, in which five minutes of 128-channel electroencephalography were …

Developing Methods To Detect And Diagnose Chronic Traumatic Encephalopathy During Life: Rationale, Design, And Methodology For The Diagnose Cte Research Project, Michael L Alosco, Daniel S Marcus, Et Al.

2020-Current year OA Pubs

BACKGROUND: Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease that has been neuropathologically diagnosed in brain donors exposed to repetitive head impacts, including boxers and American football, soccer, ice hockey, and rugby players. CTE cannot yet be diagnosed during life. In December 2015, the National Institute of Neurological Disorders and Stroke awarded a seven-year grant (U01NS093334) to fund the "Diagnostics, Imaging, and Genetics Network for the Objective Study and Evaluation of Chronic Traumatic Encephalopathy (DIAGNOSE CTE) Research Project." The objectives of this multicenter project are to: develop in vivo fluid and neuroimaging biomarkers for CTE; characterize its clinical presentation; refine …

Ceftolozane/Tazobactam Versus Meropenem In Patients With Ventilated Hospital-Acquired Bacterial Pneumonia: Subset Analysis Of The Aspect-Np Randomized, Controlled Phase 3 Trial, Jean-François Timsit, Jennifer A Huntington, Richard G Wunderink, Nobuaki Shime, Marin H Kollef, Ülo Kivistik, Martin Nováček, Álvaro Réa-Neto, Ignacio Martin-Loeches, Brian Yu, Erin H Jensen, Joan R Butterton, Dominik J Wolf, Elizabeth G Rhee, Christopher J Bruno

2020-Current year OA Pubs

BACKGROUND: Ceftolozane/tazobactam is approved for treatment of hospital-acquired/ventilator-associated bacterial pneumonia (HABP/VABP) at double the dose approved for other infection sites. Among nosocomial pneumonia subtypes, ventilated HABP (vHABP) is associated with the lowest survival. In the ASPECT-NP randomized, controlled trial, participants with vHABP treated with ceftolozane/tazobactam had lower 28-day all-cause mortality (ACM) than those receiving meropenem. We conducted a series of post hoc analyses to explore the clinical significance of this finding.

METHODS: ASPECT-NP was a multinational, phase 3, noninferiority trial comparing ceftolozane/tazobactam with meropenem for treating vHABP and VABP; study design, efficacy, and safety results have been reported previously. The …

Das181 Treatment Of Severe Lower Respiratory Tract Parainfluenza Virus Infection In Immunocompromised Patients: A Phase 2 Randomized, Placebo-Controlled Study, Roy F Chemaly, Francisco M Marty, Cameron R Wolfe, Steven J Lawrence, Sanjeet Dadwal, Rosemary Soave, Jason Farthing, Stephen Hawley, Paul Montanez, Jimmy Hwang, Jennifer Hui-Chun Ho, Stanley Lewis, George Wang, Michael Boeckh

2020-Current year OA Pubs

BACKGROUND: There are no antiviral therapies for parainfluenza virus (PIV) infections. DAS181, a sialidase fusion protein, has demonstrated activity in in vitro and in animal models of PIV.

METHODS: Adult immunocompromised patients diagnosed with PIV lower respiratory tract infection (LRTI) who required oxygen supplementation were randomized 2:1 to nebulized DAS181 (4.5 mg/day) or matching placebo for up to 10 days. Randomization was stratified by need for mechanical ventilation (MV) or supplemental oxygen (SO). The primary endpoint was the proportion of patients reaching clinical stability survival (CSS) defined as returning to room air (RTRA), normalization of vital signs for at least …

Long-Term Evaluation Of A Course On Evidence-Based Public Health In The U.S. And Europe, Rebekah R Jacob, Carol A Brownson, Anjali D Deshpande, Amy A Eyler, Kathleen N Gillespie, Jennie Hefelfinger, Paul C Erwin, Marti Macchi, Ross C Brownson

2020-Current year OA Pubs

The evidence-based public health course equips public health professionals with skills and tools for applying evidence-based frameworks and processes in public health practice. To date, training has included participants from all the 50 U.S. states, 2 U.S. territories, and multiple other countries besides the U.S. This study pooled follow-up efforts (5 surveys, with 723 course participants, 2005-2019) to explore the benefits, application, and barriers to applying the evidence-based public health course content. All analyses were completed in 2020. The most common benefits (reported by >80% of all participants) were identifying ways to apply knowledge in their work, acquiring new knowledge, …

Association Of Low Center Performance Evaluations And Pediatric Heart Transplant Center Behavior In The United States, Shahnawaz Amdani, Gerard Boyle, Joseph Rossano, Janet Scheel, Marc Richmond, Susana Arrigain, Jesse D Schold

2020-Current year OA Pubs

BACKGROUND: To date, no study has evaluated the effects of low center performance evaluations (CPE) on pediatric heart transplant center behavior. We sought to assess the impact of low CPE flags on pediatric heart transplant center listing and transplant volumes and center recipient and donor characteristics.

METHODS: We included centers performing at least 10 pediatric (age <18 years) transplants during the Scientific Registry of Transplant Recipients reporting period January 2009-June 2011 and evaluated consecutive biannual program specific reports until the last reporting period January 2016-June 2018. We evaluated changes in center behavior at following time points: a year before flagging, a year and two years after the flag; and at last reporting period.

RESULTS: During our study period, 24 pediatric centers were non-flagged and 6 were flagged. Compared to non-flagged centers, there was a decline in candidate listings in flagged centers at the last reporting period (mean increase of 5.5 ± 12.4 listings vs"?> mean decrease of …

Phase Ii Study Of Durvalumab Plus Tremelimumab As Therapy For Patients With Previously Treated Anti-Pd-1/Pd-L1 Resistant Stage Iv Squamous Cell Lung Cancer (Lung-Map Substudy S1400f, Nct03373760), Natasha B Leighl, Jeffrey D Bradley, Et Al

2020-Current year OA Pubs

INTRODUCTION: S1400F is a non-match substudy of Lung Cancer Master Protocol (Lung-MAP) evaluating the immunotherapy combination of durvalumab and tremelimumab to overcome resistance to anti-programmed death ligand 1 (PD-(L)1) therapy in patients with advanced squamous lung carcinoma (sq non-small-cell lung cancer (NSCLC)).

METHODS: Patients with previously treated sqNSCLC with disease progression after anti-PD-(L)1 monotherapy, who did not qualify for any active molecularly targeted Lung-MAP substudies, were eligible. Patients received tremelimumab 75 mg plus durvalumab 1500 mg once every 28 days for four cycles then durvalumab alone every 28 days until disease progression. The primary endpoint was the objective response rate …

Use Of Convalescent Plasma In Covid-19 Patients With Immunosuppression, Jonathon W Senefeld, Jeffrey P Henderson, Et Al.

2020-Current year OA Pubs

In the absence of effective countermeasures, human convalescent plasma has been widely used to treat severe acute respiratory syndrome coronavirus 2, the causative agent of novel coronavirus disease 19 (COVID-19), including among patients with innate or acquired immunosuppression. However, the association between COVID-19-associated mortality in patients with immunosuppression and therapeutic use of convalescent plasma is unknown. We review 75 reports, including one large matched-control registry study of 143 COVID-19 patients with hematological malignancies, and 51 case reports and 23 case series representing 238 COVID-19 patients with immunosuppression. We review clinical features and treatment protocols of COVID-19 patients with immunosuppression after …

Variants In Prkar1b Cause A Neurodevelopmental Disorder With Autism Spectrum Disorder, Apraxia, And Insensitivity To Pain, Felix Marbach, Marisa V Andrews, Dorothy K Grange, Et Al.

2020-Current year OA Pubs

PURPOSE: We characterize the clinical and molecular phenotypes of six unrelated individuals with intellectual disability and autism spectrum disorder who carry heterozygous missense variants of the PRKAR1B gene, which encodes the R1β subunit of the cyclic AMP-dependent protein kinase A (PKA).

METHODS: Variants of PRKAR1B were identified by single- or trio-exome analysis. We contacted the families and physicians of the six individuals to collect phenotypic information, performed in vitro analyses of the identified PRKAR1B-variants, and investigated PRKAR1B expression during embryonic development.

RESULTS: Recent studies of large patient cohorts with neurodevelopmental disorders found significant enrichment of de novo missense variants in …

Effective Recruitment Strategies For A Sickle Cell Patient Registry Across Sites From The Sickle Cell Disease Implementation Consortium (Scdic), Rita V Masese, Taniya Varughese, Et Al.

2020-Current year OA Pubs

Sickle cell disease (SCD) is a genetic disorder predominantly affecting people of African descent and is associated with significant morbidity and mortality. To improve SCD outcomes, the National Heart Lung and Blood Institute funded eight centers to participate in the SCD Implementation Consortium. Sites were required to each recruit 300 individuals with SCD, over 20 months. We aim to describe recruitment strategies and challenges encountered. Participants aged 15-45 years with confirmed diagnosis of SCD were eligible. Descriptive statistics were used to analyze the effectiveness of each recruitment strategy. A total of 2432 participants were recruited. Majority (95.3%) were African American. …

Examining The Patient And Caregiver Experience With Diazepam Nasal Spray For Seizure Clusters: Results From An Exit Survey Of A Phase 3, Open-Label, Repeat-Dose Safety Study, Patricia Penovich, James W Wheless, R Edward Hogan, Cynthia Guerra, David F Cook, Enrique Carrazana, Adrian L Rabinowicz

2020-Current year OA Pubs

BACKGROUND: Ideal rescue treatments for acute treatment of seizure clusters should be easy to administer, so it is important to assess user perceptions of these treatments. Diazepam nasal spray is designed to have a rapid, noninvasive, and socially acceptable route of administration. Patient and caregiver (including care partner) responses to surveys from a phase 3 safety study of diazepam nasal spray are reported.

METHODS: The study enrolled patients aged 6-65 years with seizure clusters. Surveys distributed to patients and caregivers at study end, completion, or discontinuation collected data on comfort using diazepam nasal spray outside the home, timing of administration …