Metagenomic next-generation sequencing (mNGS) of plasma cell-free DNA (cfDNA) is commercially available, but its role in the workup of infectious diseases is unclear. To understand the clinical utility of plasma mNGS, we retrospectively reviewed patients tested at a pediatric institution over 2 years to evaluate the clinical relevance of the organism(s) identified and the impact on antimicrobial management. We also investigated the effect of pretest antimicrobials and interpretation of molecules of microbial cfDNA per microliter (MPM) of plasma. Twenty-nine of 59 (49%) mNGS tests detected organism(s), and 28/51 (55%) organisms detected were clinically relevant. The median MPM of clinically relevant organisms was 1,533, versus 221 for irrelevant organisms (P = 0.01). mNGS test positive and negative percent agreements were 53% and 79%, respectively, and 50% of negative mNGS tests were true negatives. Fourteen percent of tests impacted clinical management by changing antimicrobial therapy. Immunocompromised status was the only patient characteristic that trended toward a significant clinical impact (P = 0.056). No patients with culture-negative endocarditis had organisms identified by mNGS. There were no significant differences in antimicrobial duration retest between tests with clinically relevant organism(s) and those that returned negative, nor were the MPMs different between pretreated and untreated organisms, suggesting that 10 days of antimicrobial therapy as observed in this cohort did not sterilize testing; however, no pretreated organisms identified resulted in a new diagnosis impacting clinical management. Plasma mNGS demonstrated higher utility for immunocompromised patients, but given the detection of many clinically irrelevant organisms (45%), cautious interpretation and infectious diseases consultation are prudent.

Background Little is known about depressive symptoms among adolescents in the United Arab Emirates (UAE). This study aimed to identify the prevalence of depression and its association with selfesteem, individual, parental and family factors among adolescents aged 12 to 18 in UAE. Methods Six hundred adolescents, aged 12 to 18 years were recruited from 4 of 111 schools in a cross-sectional study. We administered Beck Depression Inventory Scale and Rosenberg Self-esteem Scale to measure self-report symptoms of depression and self-esteem. We used multiple linear regression to identify significant predictors of depression. Results Over 86% of the identified sample participated to the survey. The mean age of the sample was 14.3 (±1.3) with an excess of girls (61%). Depressive symptoms were detected in 17.2% (95% CI 14.2-20.7). There was an inverse relationship between self-esteem scores and depressive symptoms. Positive predictors of depressive symptoms, having controlled for age, gender, and ethnicity included experiencing neglect, being verbally abused in school, having no monthly allowance to spend in school, a history of physical morbidities requiring treatment, being a current or past smoker and a low family income. Conclusion The high prevalence of depressive symptoms measured in this survey suggests a significant public health problem among adolescents in the UAE. Public health interventions aimed at

AbstractBackgroundMetagenomic next-generation sequencing (mNGS) of plasma cell-free DNA (cfDNA) is commercially available, but its role in the workup of infectious diseases is unclear.MethodsTo understand the clinical utility of plasma mNGS, we retrospectively reviewed patients tested at a pediatric institution over 2 years to evaluate the clinical relevance of the organism(s) identified and impact on antimicrobial management. We also investigated the effect of pre-test antimicrobials and interpretation of molecules of microbial cfDNA per microliter (MPM) plasma.Results29/59 (49%) mNGS tests detected organism(s), and 28/51 (55%) organisms detected were clinically relevant. Median MPM of clinically relevant organisms was 1533 versus 221 for irrelevant organisms (p=0.01). mNGS test sensitivity and specificity were 53% and 79%, respectively, with a positive predictive value (PPV) of 72% and negative predictive value (NPV) of 50%. 14% of tests impacted clinical management by changing antimicrobial therapy. Immunocompromised status was the only patient characteristic that trended towards a significant clinical impact (p=0.056). No patients with culture-negative endocarditis had organisms identified by mNGS. There were no significant differences in antimicrobial pre-test duration between tests with clinically relevant organism(s) versus those that returned negative, nor was the MPM different between pre-treated and un-treated organisms, suggesting that 10 days of antimicrobial therapy as observed in this cohort did not sterilize testing; however, no pre-treated organisms identified resulted in a new diagnosis impacting clinical managementConclusionsPlasma mNGS demonstrated higher utility for immunocompromised patients, but given the low PPV and NPV, cautious interpretation and Infectious Diseases consultation are prudent.SummaryWe evaluate the test performance characteristics and clinical utility of plasma metagenomic next-generation sequencing in a pediatric hospital cohort and demonstrate sensitivity and specificity of 53% and 79%, with 14% of tests impacting antimicrobial management.

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