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Item 158. Diagnostic Yield and Clinical Utility of Broad Range PCR Testing at a Tertiary Children’s Hospital(Oxford University Press, 2023-11-27) Schneider, Jack; Prabhudas-Strycker, Kirsten; Samaro, Matthew; Goings, Michael; Mellencamp, Kagan A.; Khan, Haseeba; Boyd, LaKeisha; Pediatrics, School of MedicineBackground: Broad range PCR testing (BR-PCR) targets highly conserved DNA sequences of bacteria, fungi, or mycobacteria to detect a broad range of organisms in various clinical samples. Given its potential impact in providing timely diagnoses that cannot always be made through conventional testing (CT), we evaluated the diagnostic yield and clinical impact of BR-PCR at our institution. Methods: We retrospectively evaluated all clinical specimen types obtained for BR-PCR at Riley Hospital for Children from October 2019 to May 2022. Percent positivity (PP) was determined by specific PCR test type (Bacterial/Fungal/NTM/TB), along with median turn-around times (in days) from sample collection. Medical charts were reviewed, and clinical impact of results was determined. Results: We identified 956 BR-PCR tests sent from 271 specimens collected from 178 patients. Only 14.5% yielded a positive result with a median days-to-result being the longest for fungal PCR at 8.1 days (7.0, 10.1) and TB PCR being the fastest at 7.8 days (6.8, 9.9). Bacterial BR-PCR yielded an overall PP of 42.6% while Fungal BR-PCR was 10.7%. Positivity rates for NTM and TB were 0% and 0.5%, respectively. Bronchial lavage was the most common specimen type (35.5%) with an overall PP of 19.9%. Of the 271 specimens, 245 returned conclusive results from both BR-PCR and clinical testing (CT) for comparison. A clinically significant organism based on CT was identified in 68 specimens (27.8%), 45 of which were confirmed by BR-PCR. 23 (33.8%) were detected by CT but not BR-PCR. 21 clinically significant organisms not detected by CT were identified by BR-PCR, which led to a change in clinical management in 12 instances: new diagnosis (91.7%); or appropriate initiation (91.7%), escalation (25.0%), or de-escalation (25.0%) of antimicrobial therapy. Conclusion: BR-PCR overall had low diagnostic yield at our institution but was influenced by specimen type. The clinical utility was predominantly seen in immunocompromised patients in which conventional testing was negative. Further data is needed to determine which specimen types and diagnoses will increase the yield and clinical value of BR-PCR and thus, aid in enhancing diagnostic stewardship.Item 582. Comparing Broad-range PCR Testing and The Biofire® FilmArray® Pneumonia (PN) Panel in the Diagnosis of Bacterial Pneumonia(Oxford University Press, 2023-11-27) Khan, Haseeba; Prabhudas-Strycker, Kirsten; Samaro, Matthew; Mellencamp, Kagan A.; Goings, Michael; Boyd, LaKeisha; Schneider, Jack; Emery, Christopher L.; Pediatrics, School of MedicineBackground: Given the low sensitivity of conventional microbial isolation methods for identifying respiratory pathogens in bacterial pneumonia, target-specific syndromic multiplex real-time PCR panels have been used in conjunction with culture methods to improve diagnostic yield. Additionally, broad-range polymerase chain reaction (BR-PCR) targeting bacterial 16s rRNA conserved region has shown higher sensitivity with certain specimen types, so we sought to evaluate the clinical performance of BR-PCR performed on bronchoalveolar lavage (BAL) specimens in comparison to The Biofire® FilmArray® Pneumonia (PN) Panel (BioFire Diagnostics, Salt Lake City, UT, USA). Methods: A retrospective chart review was performed on all BAL specimens that had both a PN panel test and BR-PCR performed from January 2020 to May 2022 at all Indiana University affiliated hospitals. The PN panel test was performed in-house as per laboratory protocol, while BR-PCR was performed in a reference laboratory. Outcomes assessed included turn-around times (TAT), sensitivity and specificity of BR-PCR and clinical impact, if any. Results: A total of 68 BAL specimens from 53 patients were identified (83% of patients were immunocompromised). Percent positivity for the PN panel was 19% and that of BR-PCR was 18%. With the PN panel used as the gold standard, the sensitivity and specificity of BR-PCR was 85% and 98%, respectively. Only one respiratory organism was detected by BR-PCR but not by the PN panel, and it was not considered pathogenic or to have a significant clinical impact. The median TAT for the PN panel was 2.1 hours (1.8, 3.2) versus 7.8 days (6.9, 10.4) for BR-PCR. Conclusion: In our cohort of patients, BR-PCR testing was not superior to the Biofire® FilmArray® Pneumonia (PN) Panel when used to detect certain bacterial etiologies of pneumonia. Additionally, faster TAT for the panel test has the potential to enhance antimicrobial stewardship practices by enabling better antibiotic utilization. Adjunctive BR-PCR testing may be useful for clinical care when conventional testing is negative and patients are at risk for a variety of potential pathogens, including fungi.Item Acute kidney injury, persistent kidney disease, and post-discharge morbidity and mortality in severe malaria in children: A prospective cohort study(Elsevier, 2022-02-12) Namazzi, Ruth; Batte, Anthony; Opoka, Robert O.; Bangirana, Paul; Schwaderer, Andrew L.; Berrens, Zachary; Datta, Dibyadyuti; Goings, Michael; Ssenkusu, John M.; Goldstein, Stuart L.; John, Chandy C.; Conroy, Andrea L.; Pediatrics, School of MedicineBackground: Globally, 85% of acute kidney injury (AKI) cases occur in low-and-middle-income countries. There is limited information on persistent kidney disease (acute kidney disease [AKD]) following severe malaria-associated AKI. Methods: Between March 28, 2014, and April 18, 2017, 598 children with severe malaria and 118 community children were enrolled in a two-site prospective cohort study in Uganda and followed up for 12 months. The Kidney Disease: Improving Global Outcomes (KDIGO) criteria were used to define AKI (primary exposure) and AKD at 1-month follow-up (primary outcome). Plasma neutrophil gelatinase-associated lipocalin (NGAL) was assessed as a structural biomarker of AKI. Findings: The prevalence of AKI was 45·3% with 21·5% of children having unresolved AKI at 24 h. AKI was more common in Eastern Uganda. In-hospital mortality increased across AKI stages from 1·8% in children without AKI to 26·5% with Stage 3 AKI (p < 0·0001). Children with a high-risk plasma NGAL test were more likely to have unresolved AKI (OR, 7·00 95% CI 4·16 to 11·76) and die in hospital (OR, 6·02 95% CI 2·83 to 12·81). AKD prevalence was 15·6% at 1-month follow-up with most AKD occurring in Eastern Uganda. Risk factors for AKD included severe/unresolved AKI, blackwater fever, and a high-risk NGAL test (adjusted p < 0·05). Paracetamol use during hospitalization was associated with reduced AKD (p < 0·0001). Survivors with AKD post-AKI had higher post-discharge mortality (17·5%) compared with children without AKD (3·7%). Interpretation: Children with severe malaria-associated AKI are at risk of AKD and post-discharge mortality.Item Family-Centered Care Coordination in an Interdisciplinary Neurodevelopmental Evaluation Clinic: Outcomes From Care Coordinator and Caregiver Reports(Frontiers, 2020-10) McNally Keehn, Rebecca; Enneking, Brett; Ramaker, Margo; Goings, Michael; Yang, Ziyi; Carroll, Aaron; Ciccarelli, Mary; Pediatrics, School of MedicineChildren with neurodevelopmental disabilities experience many unmet healthcare needs. Care coordination is one critical solution to addressing the substantial strain on families, local communities, and the larger healthcare system. The purpose of this study was to implement a care coordination program in an interdisciplinary pediatric neurodevelopmental evaluation clinic and examine care coordinator and caregiver outcomes. Following neurodevelopmental diagnosis, children were provided with either care coordination (CC) or care as usual (CAU). For those receiving CC, the care coordinator documented family goals and care coordination activities, outcomes, and time spent. Caregivers in both groups completed a survey measuring access to needed services and caregiver stress and empowerment following their child's evaluation (T1) and 4-6 months post-evaluation (T2). Care coordinator findings demonstrated that over 85% of family goals focused on understanding the child's diagnosis, getting needed interventions and educational support, and accessing healthcare financing programs. More than half of care coordination activities were spent on engaging and educating the family; similarly, the most time-consuming care coordination efforts were in helping families understand their child's diagnosis and meeting family's basic needs. For those children referred to needed services, 54% were enrolled in one or more service at T2. Caregivers in both the CC and CAU groups reported an increase in stress related to interactions with their child as well as increased empowerment from T1 to T2. Contrary to our hypotheses, there were no significant group-by-time interactions across caregiver-report measures. While these findings further our understanding of care coordination delivery, they diverge from previous evidence demonstrating care coordination efficacy. This study paves the way for future opportunities to evaluate what kinds of care coordination supports family need at varying times in their child's healthcare journey and how the outcomes important to all stakeholders are measured to reflect true evaluation of efficacy.Item Identifying Risk Factors That Distinguish Symptomatic Severe Acute Respiratory Syndrome Coronavirus 2 Infection From Common Upper Respiratory Infections in Children(2021) Schneider, Jack G.; Relich, Ryan F.; Datta, Dibyadyuti; Bond, Caitlin; Goings, Michael; Hall, Dylan; Lei, Guang-Sheng; Kedra, Jennifer; John, Chandy C.; Medicine, School of MedicineBackground Demographic and clinical risk factors for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children presenting with respiratory viral symptoms are not well defined. An understanding of risk factors for SARS-CoV-2 infection can help prioritize testing. Methodology We evaluated potential demographic and clinical factors in children who had respiratory viral symptoms and were tested by polymerase chain reaction (PCR) for SARS-CoV-2 and other respiratory viral infections. Results Among the 263 symptomatic children tested for routine seasonal respiratory viruses by PCR, 18 (6.8%) tested positive for SARS-CoV-2. Overall, 22.2% of SARS-CoV-2-infected children and 37.1% of SARS-CoV-2-uninfected children had infection with one or more non-SARS-CoV-2 pathogens (p = 0.31). Higher proportions of children with compared to without SARS-CoV-2 infection were male (77.8 vs. 51.8%, p = 0.05), Hispanic (44.4% vs. 9.8%, p < 0.001), or had the symptoms of fatigue (22.2% vs. 2.5%, p = 0.003) or anosmia/ageusia (11.1% vs. 0%, p = 0.004). History of hypoxic-ischemic encephalopathy (HIE) and obesity were more common in children with versus without SARS-CoV-2 infection (11.1% vs. 1.2%, p = 0.04, and 11.1% vs. 0%, p = 0.004, respectively). In a multivariate analysis, Hispanic ethnicity, symptoms of fatigue or anosmia/ageusia, and presence of obesity (as noted on physical examination) or HIE were independently associated with SARS-CoV-2 infection. Numbers in each category were small, and these preliminary associations require confirmation in future studies. Conclusions In this area of the United States, infection with other viruses did not rule out infection with SARS-CoV-2. Additionally, children with respiratory viral symptoms who were of Hispanic ethnicity, had symptoms of weakness/fatigue, or had obesity or HIE were at an increased risk for SARS-CoV-2 infection. Future studies should assess if these factors are associated with risk in populations in other areas of the United States.Item Level and Duration of IgG and Neutralizing Antibodies to SARS-CoV-2 in Children with Symptomatic or Asymptomatic SARS-CoV-2 Infection(AAI, 2022-06-01) Khaitan, Alka; Datta, Dibyadyuti; Bond, Caitlin; Goings, Michael; Co, Katrina; Odhiambo, Eliud O.; Miller, Lucy; Zhang, Lin; Beasley, Stephanie; Poorbaugh, Josh; John, Chandy C.; Pediatrics, School of MedicineThere are conflicting data about level and duration of Abs to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in children after symptomatic or asymptomatic infection. In this human population, we enrolled adults and children in a prospective 6-mo study in the following categories: 1) symptomatic, SARS-CoV-2 PCR+ (SP+; children, n = 8; adults, n = 16), 2) symptomatic, PCR−, or untested (children, n = 27), 3) asymptomatic exposed (children, n = 13), and 4) asymptomatic, no known exposure (children, n = 19). Neutralizing Abs (nAbs) and IgG Abs to SARS-CoV-2 Ags and spike protein variants were measured by multiplex serological assay. All SP+ children developed nAb, whereas 81% of SP+ adults developed nAb. Decline in the presence of nAb over 6 mo was not significant in symptomatic children (100 to 87.5%; p = 0.32) in contrast to adults (81.3 to 50.0%; p = 0.03). Among children with nAb (n = 22), nAb titers and change in titers over 6 mo were similar in symptomatic and asymptomatic children. In children and adults, nAb levels postinfection were 10-fold lower than those reported after SARS-CoV-2 mRNA vaccination. Levels of IgG Abs in children to SARS-CoV-2 Ags and spike protein variants were similar to those in adults. IgG levels to primary Ags decreased over time in children and adults, but levels to three spike variants decreased only in children. Children with asymptomatic or symptomatic SARS-CoV-2 infection develop nAbs that remain present longer than in adults but wane in titer over time and broad IgG Abs that also wane in level over time. However, nAb levels were lower postinfection than those reported after immunization.