Lauren E O'Brien

All Publications

• Successful Implementation of Nirsevimab and Factors Influencing Uptake in Neonatal Care. Hospital pediatrics Puckett, L., Kushner, L. E., Bio, L., Cornell, S., Wood, M., Schwenk, H. T. 2024

  Abstract

  Objective: To describe the implementation of nirsevimab for the prevention of respiratory syncytial virus (RSV)-associated lower respiratory tract disease in a pediatric hospital, focusing on strategies to ensure equitable access and address logistical challenges. Additionally, we aimed to identify predictors of nirsevimab deferral among eligible infants. Patients and Methods: Our hospital implemented a universal immunization campaign to all eligible infants, including those discharged from the newborn nursery, intermediate care nursery (ICN), and neonatal intensive care unit (NICU). We identified key drivers and barriers, formed a multidisciplinary team, and applied a systematic approach for integration of nirsevimab orders into existing workflows. We developed and disseminated educational resources for staff and caregivers. After the implementation, we conducted univariate and multivariate analyses to identify predictors of nirsevimab deferral to evaluate implementation success and possible gaps. Results: Despite challenges, we offered nirsevimab to 99% of eligible infants prior to discharge from the newborn nursery, ICN, and NICU with 71% receiving the immunization. On multivariate analysis, independent predictors of nirsevimab deferral included preferred language of English, deferral of hepatitis B vaccine, discharge from the newborn nursery, and public insurance. Conclusions: Our implementation strategy ensured equitable access to nirsevimab for newborns, with both our high uptake and acceptance rate underscoring the effectiveness of our approach. Key strategies for success included early stakeholder engagement, multidisciplinary collaboration, and proactive logistical planning. Our approach serves as a model for other institutions to offer nirsevimab prior to hospital discharge and highlights the importance of addressing both clinical and socioeconomic barriers.

  View details for DOI 10.1542/hpeds.2024-008070

  View details for PubMedID 39568114

• Utilization of Hepatitis C Virus-Infected Donor Hearts in Two Children and Two Young Adults: Initial Experience at a Pediatric Transplant Center. Pediatric transplantation Kushner, L. E., Puckett, L., Lee, J., Gans, H. A., Nadimpalli, S., Chen, S., Ma, M., Chen, S. F., Profita, E. L. 2024; 28 (7): e14879

  Abstract

  Although adult transplant centers are successfully transplanting organs from hepatitis C virus (HCV)-infected donors with detectable viral load by nucleic acid testing (NAT+) into HCV-negative recipients, this practice has not yet been adopted widely by the pediatric heart transplant community.We present a case series of four patients who received heart transplants from HCV NAT+ donors at a pediatric transplant center, including two pediatric patients < 18 years of age.All recipients tolerated a 12-week course of glecaprevir/pibrentasvir and achieved a sustained virologic response with no HCV or liver complications with over 1 year of follow-up (range 1.4-2.5 years). All four have had good post-heart transplant outcomes with normal graft function and good functional status without rejection or cardiac allograft vasculopathy at time of last follow-up.This case series details the successful multidisciplinary implementation of a protocol to accept cardiac allografts from HCV NAT+ donors for transplantation into HCV negative recipients at our pediatric transplant center. With the limited donor pool in pediatrics and the morbidity associated with prolonged durations on the transplant waitlist, pediatric centers should consider utilizing organs from HCV NAT+ donors to broaden the donor pool. Future work should evaluate other organs beyond heart and optimal timing and duration of direct acting antiviral therapy.

  View details for DOI 10.1111/petr.14879

  View details for PubMedID 39462680

• Application of cell-free DNA fungal polymerase chain reaction for invasive fungal disease evaluation in pediatric oncology and stem cell transplant patients. Pediatric blood & cancer Kushner, L. E., Schwenk, H. T., Qin, F., Boothroyd, D., Aftandilian, C. 2024: e31133

  Abstract

  Molecular diagnostics may enable early, noninvasive detection of invasive fungal disease (IFD) in immunocompromised patients. Cell-free deoxyribonucleic acid (cfDNA) fungal polymerase chain reaction (PCR) assays were recently incorporated into institutional prolonged febrile neutropenia pathways. We aimed to evaluate the performance of plasma cfDNA PCR panels (mold and Candida panels) in pediatric oncology and hematopoietic stem cell transplant (HSCT) patients with clinical concern for IFD.This single-center, observational study assessed plasma cfDNA fungal PCR performance for noninvasive IFD detection in hospitalized pediatric oncology and HSCT patients. The primary outcome was IFD diagnosis per published consensus definitions within 1 month. Positive and negative agreement between plasma cfDNA fungal PCR and consensus definitions were calculated. We also described test turnaround time and patient survival.From October 2021 to 2022, 54 patients underwent 60 evaluations with 11 proven/probable IFD cases. Comparing plasma cfDNA fungal PCRs to consensus definitions for proven/probable IFD, there was 73% positive agreement and 96% negative agreement. Two proven/probable cases with negative PCRs were caused by organisms not included on either panel. Median time to cfDNA fungal PCR result was 35 hours (interquartile range: 19-69) in eight proven/probable cases detected by cfDNA fungal PCR. There were 17 deaths among 54 patients, and IFD contributed to 45% of deaths in patients with proven/probable IFD.Plasma cfDNA fungal PCRs detected relevant molds or yeast in most cases classified as proven/probable IFD. However, this targeted approach missed some cases. More studies are required to determine optimal utilization of molecular diagnostics in pediatric patients.

  View details for DOI 10.1002/pbc.31133

  View details for PubMedID 38943234

• Vaccine Associated Measles Complicated by Suspected Measles Inclusion Body Encephalitis in a Pediatric Leukemia Patient and Stem Cell Transplant Recipient: A Focus on Clinical Evolution and Management. The Pediatric infectious disease journal Kushner, L. E., Kamens, J., Bertaina, A., Shyr, D., Gans, H. A. 2024

  Abstract

  Immunocompromised individuals are at increased risk for severe disease and complications from viral infections, highlighting the importance of vaccination. However, in extremely rare situations, vaccine associated viral infections can be associated with disseminated disease and complications in immunocompromised hosts.Herein, we present a case of a 1-year-old child diagnosed with acute myeloid leukemia less than 2 weeks after receiving live viral vaccines who developed acute vaccine-strain measles virus disease, later complicated by central nervous system involvement following hematopoietic stem cell transplantation. A brain biopsy specimen was positive for vaccine-strain measles virus detected by reverse transcriptase polymerase chain reaction.She was treated with intravenous ribavirin, inosine pranobex, intrathecal interferon-alpha and donor lymphocyte infusion following measles-mumps-rubella vaccine boost. Despite these measures, the patient suffered neurologic decline and dysautonomia, expiring after compassionate extubation. Management and ideal risk mitigation strategies are discussed within the context of existing literature for this rare complication.

  View details for DOI 10.1097/INF.0000000000004299

  View details for PubMedID 38380931

• Laying the Groundwork for a Fulfilling Career in Pediatric Infectious Diseases: The Transition from Fellowship to Faculty. Journal of the Pediatric Infectious Diseases Society Kushner, L. E., Ristagno, E. H., Dong, S. W., Konold, V. J., Fatemi, Y., Stillwell, T. L., Wohrley, J. D., Sattler, M. M., Kalu, I. C., Boguniewicz, J. 2023

  Abstract

  There are limited resources for guidance on the transition from fellowship into a new faculty role in pediatric infectious diseases. This review aims to address this gap and provides a framework for a successful transition that is composed of four essential pillars-1) stepping into your role, 2) finding your niche, 3) building your network, and 4) self-care-all of which are supported by strong mentorship/sponsorship and continual re-alignment with one's personal mission statement. In addition to providing general principles and guidance, this review also outlines specific steps that a junior faculty member can take to expand their influence and build a successful, fulfilling career in pediatric infectious diseases.

  View details for DOI 10.1093/jpids/piad079

  View details for PubMedID 37815429

• Impact of cell-free DNA fungal polymerase chain reaction panels on healthcare-associated infection mould investigations. Journal of infection prevention Rosenthal, A., Prati, A., Kushner, L. E., Valencia, A., Mathew, R. 2023; 24 (5): 223-227

  Abstract

  Launch of in-house sensitive cell-free deoxyribonucleic acid (cfDNA) mould polymerase chain reaction (PCR) assays increased detection of moulds meeting suspected healthcare-associated infection (HAI) criteria. Definition was based on time from admission and mould detection in culture or via molecular methods. We created a modified mould HAI algorithm incorporating clinical context into the case definition, which allowed for better capture of possible mould HAIs, decreased number of investigations, and improved utilization of Infection Prevention and Control (IPC) resources.

  View details for DOI 10.1177/17571774231197603

  View details for PubMedID 37736124

• Successful nasoenteric administration of glecaprevir/pibrentasvir for donor-derived hepatitis C in two young adult heart transplant recipients at a pediatric transplant center. Pediatric transplantation Kushner, L. E., Puckett, L., Lee, J., Joerger, T., Chen, S. F., Profita, E. 2022: e14360

  View details for DOI 10.1111/petr.14360

  View details for PubMedID 35854405

• Vaccine-Associated Measles Encephalitis in Immunocompromised Child, California, USA. Emerging infectious diseases Costales, C., Sahoo, M. K., Huang, C., Guimaraes, C. V., Born, D., Kushner, L., Gans, H. A., Doan, T. A., Pinsky, B. A. 2022; 28 (4): 906-908

  Abstract

  We report a fatal case of vaccine-associated measles encephalitis in an immunocompromised child in California, USA. The infection was confirmed by whole-genome RNA sequencing of measles virus from brain tissue. We observed biased matrix-gene hypermutation consistent with persistent measles virus central nervous system infection.

  View details for DOI 10.3201/eid2804.212357

  View details for PubMedID 35318930

• "For COVID" or "With COVID": Classification of SARS-CoV-2 Hospitalizations in Children. Hospital pediatrics Kushner, L. E., Schroeder, A. R., Kim, J., Mathew, R. 2021

  View details for DOI 10.1542/hpeds.2021-006001

  View details for PubMedID 34011566

• Assessment of Sensitivity and Specificity of Patient-Collected Lower Nasal Specimens for Sudden Acute Respiratory Syndrome Coronavirus 2 Testing. JAMA network open Altamirano, J. n., Govindarajan, P. n., Blomkalns, A. L., Kushner, L. E., Stevens, B. A., Pinsky, B. A., Maldonado, Y. n. 2020; 3 (6): e2012005

  View details for DOI 10.1001/jamanetworkopen.2020.12005

  View details for PubMedID 32530469

• Oral Antibiotics for Treating Children With Community-Acquired Pneumonia Complicated by Empyema. Clinical pediatrics Kushner, L. E., Nieves, D. J., Osborne, S., Vora, H., Arrieta, A., Singh, J. 2019: 9922819850494

  Abstract

  No consensus exists on management of children with community-acquired pneumonia complicated by empyema (CAP-Em). We evaluated outpatient oral (O-Abx) compared with parenteral antibiotics (OPAT) in children with CAP-Em. We also evaluated inflammatory markers to guide length of treatment. We conducted a retrospective cohort study of patients discharged (2006-2016) with CAP-Em. Primary outcome measured was treatment success (no change in antibiotics or readmission to hospital for treatment of CAP-Em). White blood cell (WBC) count, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) serial measurements were identified. Success was achieved in 133/144 (92.4%) O-Abx and 7/12 (58%) OPAT patients ( P = .0031). WBC and CRP decreased early; and ESR increased initially (admit and switch to O-Abx) and decreased by end of treatment. O-Abx is the modality of choice for treatment of CAP-Em after hospital discharge. WBC and CRP are useful to monitor success of O-Abx switch; and ESR provides guidance for length of treatment.

  View details for DOI 10.1177/0009922819850494

  View details for PubMedID 31122051

• Acute and chronic immune biomarker changes during interferon/ribavirin treatment in HIV/HCV co-infected patients JOURNAL OF VIRAL HEPATITIS Jain, M. K., Adams-Huet, B., Terekhova, D., Kushner, L. E., Bedimo, R., Li, X., Holodniy, M. 2015; 22 (1): 25-36

  Abstract

  Chronic viral infections lead to persistent immune activation, which is alleviated by eradicating or suppressing the infection. To understand the effects of interferon treatment on immune system activation by chronic infections, we evaluated kinetic patterns of a broad spectrum of serum biomarkers during HCV treatment in HIV/HCV co-infected patients. HCV viral load and 50 biomarkers were analysed at baseline and 27 time points during pegylated interferon-alpha and ribavirin (IFN/RBV) treatment of 12 HIV/HCV co-infected patients. We evaluated biomarker changes from baseline for each time point and biomarker correlations with clinical parameters, treatment response and liver histopathology. IL-1α, IL-12p40, IL-1RA, IP-10, MIG, MIP-1α/1β, HGF, sCD40L, TRAIL and leptin increased in the first day. IL-12p70, IL-17A, IL-10, GROα, IL-8, MCP-3, IL-4 and M-CSF peaked later during week 1. IL-1α, HGF, IP-10, MIP-1α, TRAIL, sCD40L, IL-10, IL-12p70, MCP-3, FGFb, ENA-78, TGF-β, IL-2, IFN-γ, IL-6, IL-15, IL-7 and PDGF-BB decreased below baseline over the course of treatment. Higher BMI, baseline HCV viral load and leptin levels were associated with lack of sustained virologic response. ENA-78 was associated with sustained viral response. Positive correlations were found between liver inflammation and baseline CD4 count, sVCAM and HGF; fibrosis stage and HGF; liver steatosis, BMI and leptin. Our findings suggest IFN/RBV treatment initially increases levels of several biomarkers, but eventually leads to a decline in many immune markers. These findings shed light on the relationship between IFN treatment and immune activation by chronic viral infections, such as HCV.

  View details for DOI 10.1111/jvh.12226

  View details for Web of Science ID 000346826600005

  View details for PubMedID 24506344

• A feasibility study to determine if minimally trained medical students can identify markers of chronic parasitic infection using bedside ultrasound in rural Tanzania WORLD JOURNAL OF EMERGENCY MEDICINE Barsky, M., Kushner, L., Ansbro, M., Bowman, K., Sassounian, M., Gustafson, K., Lahham, S., Joseph, L., Fox, J. C. 2015; 6 (4): 293-298

  Abstract

  Parasitic infections pose a significant health risk in developing nations and are a major cause of morbidity and mortality worldwide. In the Republic of Tanzania, the CDC estimates that 51.5% of the population is infected with one or more intestinal parasites. If diagnosed early, the consequences of chronic parasitic infection can potentially be avoided.Six first-year medical students were recruited to enroll patients in the study. They underwent ten hours of formal, hands-on, ultrasound which included basic cardiac, hepatobiliary, renal, pulmonary and FAST scan ultrasound. A World Health Organization protocol with published grading scales was adapted and used to assess for pathology in each patient's liver, bladder, kidneys, and spleen.A total of 59 patients were enrolled in the study. Students reported a sensitivity of 96% and specificity of 100% for the presence of a dome shaped bladder, a sensitivity and specificity of 100% for bladder thickening, a sensitivity and specificity of 100% for portal hypertension and ascites. The sensitivity was 81% with a specificity of 100% for presence of portal vein distention. The sensitivity was 100% with a specificity of 90% for dilated bowel.Ultrasound has shown a promise at helping to identify pathology in rural communities with limited resources such as Tanzania. Our data suggest that minimally trained first year medical students are able to perform basic ultrasound scans that can identify ultrasonographic markers of parasitic infections.

  View details for DOI 10.5847/wjem.j.1920-8642.2015.04.008

  View details for Web of Science ID 000382242900008

  View details for PubMedID 26693265

  View details for PubMedCentralID PMC4677073

• Immune biomarker differences and changes comparing HCV mono-infected, HIV/HCV co-infected, and HCV spontaneously cleared patients. PloS one Kushner, L. E., Wendelboe, A. M., Lazzeroni, L. C., Chary, A., Winters, M. A., Osinusi, A., Kottilil, S., Polis, M. A., Holodniy, M. 2013; 8 (4)

  View details for DOI 10.1371/journal.pone.0060387

  View details for PubMedID 23593207