BACKGROUND: Respiratory syncytial virus (RSV) is a major cause of hospitalized acute respiratory illness (ARI) among young children. With RSV vaccines and immunoprophylaxis agents in clinical development, we sought to update estimates of US pediatric RSV hospitalization burden.METHODS: Children ,5 years old hospitalized for ARI were enrolled through active, prospective, population-based surveillance from November 1, 2015, to June 30, 2016, at 7 US pediatric hospital sites. Clinical information was obtained from parent interviews and medical records. Midturbinate nasal and throat flocked swabs were collected and tested for RSV by using molecular diagnostic assays at each site. We conducted descriptive analyses and calculated population-based rates of RSV-associated hospitalizations.RESULTS: Among 2969 hospitalized children included in analyses, 1043 (35%) tested RSVpositive; 903 (87%) children who were RSV-positive were ,2 years old, and 526 (50%) were ,6 months old. RSV-associated hospitalization rates were 2.9 per 1000 children ,5 years old and 14.7 per 1000 children ,6 months old; the highest age-specific rate was observed in 1-month-old infants (25.1 per 1000). Most children who were infected with RSV (67%) had no underlying comorbid conditions and no history of preterm birth.CONCLUSIONS: During the 2015-2016 season, RSV infection was associated with one-third of ARI hospitalizations in our study population of young children. Hospitalization rates were highest in infants ,6 months. Most children who were RSV-positive had no history of prematurity or underlying medical conditions, suggesting that all young children could benefit from targeted interventions against RSV.WHAT'S KNOWN ON THIS SUBJECT: Respiratory syncytial virus (RSV) infection is a major cause of hospitalization among young children. The US pediatric burden of hospitalized RSV is substantial, with the most recent prospective populationbased estimates of burden coming from 3 counties in 2000-2005.WHAT THIS STUDY ADDS: During 2015-2016, prospective population-based surveillance over a broader geographic area detected RSV in one-third of acute respiratory illness hospitalizations in our study population of young US children and yielded updated burden estimates that should help inform RSV-specific intervention strategies.

IMPORTANCE Prior evidence suggests that racial differences exist in tau biomarkers in mild cognitive impairment (MCI) and Alzheimer disease (AD). Whether this reported disparity is associated with a differential level of neurodegeneration and disease stage or with underlying mechanisms separate from amyloid or tau is unclear. OBJECTIVES To compare cerebrospinal fluid (CSF) biomarkers in African American and white individuals with normal cognition and MCI, to estimate race-based cutoffs for these biomarkers that maximize diagnostic discrimination between normal cognition and MCI, and to study the association of demographic characteristics, cognitive performance, and common vascular risk factors with these differences.

Background Human papillomavirus (HPV) vaccine was recommended in 2006 for routine vaccination of US females aged 11–12 years. Most vaccine used through 2014 was quadrivalent vaccine (4vHPV), which prevents HPV-6, -11, -16, and -18 infection. To evaluate vaccine impact, we measured HPV prevalence in the National Health and Nutrition Examination Survey (NHANES). Methods We analyzed HPV DNA types detected in self-collected cervicovaginal specimens and demographic, sexual behavior, and self-reported vaccination data from females 14–34 years old. We estimated HPV prevalence in the prevaccine (2003–2006) and vaccine eras (2007–2010 and 2011–2014). Results Among 14- to 19-year-olds, 4vHPV-type prevalence decreased from 11.5% (95% confidence interval [CI], 9.1%–14.4%) in 2003–2006 to 3.3% (95% CI, 1.9%–5.8%) in 2011–2014, when ≥1-dose coverage was 55%. Among 20- to 24-year-olds, prevalence decreased from 18.5% (95% CI, 14.9%–22.8%) in 2003–2006 to 7.2% (95% CI, 4.7%–11.1%) in 2011–2014, when ≥1-dose coverage was 43%. Compared to 2003–2006, 4vHPV prevalence in sexually active 14- to 24-year-olds in 2011–2014 decreased 89% among those vaccinated and 34% among those unvaccinated. Vaccine effectiveness was 83%. Conclusions Within 8 years of vaccine introduction, 4vHPV-type prevalence decreased 71% among 14- to 19-year-olds and 61% among 20- to 24-year-olds. Estimated vaccine effectiveness was high. The decrease in 4vHPV-type prevalence among unvaccinated females suggests herd protection.

IMPORTANCE Observational studies have suggested that angiotensin receptor blockers are associated with a unique cognitive protection. It is unclear if this is due to reduced blood pressure (BP) or angiotensin receptors type 1 blockade. OBJECTIVE To determine neurocognitive effects of candesartan vs lisinopril in older adults with mild cognitive impairment (MCI). DESIGN, SETTING, AND PARTICIPANTS This randomized clinical trial included participants aged 55 years or older with MCI and hypertension. Individuals were withdrawn from prior antihypertensive therapy and randomized in a 1 to 1 ratio to candesartan or lisinopril from June 2014 to December 2018. Participants underwent cognitive assessments at baseline and at 6 and 12 months. Brain magnetic resonance images were obtained at baseline and 12 months. This intent-to-treat study was double-blind and powered for a sample size accounting for 20% dropout. Data were analyzed from May to October 2019. INTERVENTIONS Escalating doses of oral candesartan (up to 32 mg) or lisinopril (up to 40 mg) once daily. Open-label antihypertensive drug treatments were added as needed to achieve BP less than 140/90 mm Hg. MAIN OUTCOMES AND MEASURES The primary outcome was executive function (measured using the Trail Making Test, Executive Abilities: Measures and Instruments for Neurobehavioral Evaluation and Research tool) and secondary outcomes were episodic memory (measured using the Hopkins Verbal Learning Test-Revised) and microvascular brain injury reflected by magnetic resonance images of white matter lesions. RESULTS Among 176 randomized participants (mean [SD] age, 66.0 [7.8] years; 101 [57.4%] women; 113 [64.2%] African American), 87 were assigned to candesartan and 89 were assigned to lisinopril. Among these, 141 participants completed the trial, including 77 in the candesartan group and 64 in the lisinopril group. Although the lisinopril vs candesartan groups achieved similar BP (12-month mean [SD] systolic BP: 130 [17] mm Hg vs 134 [20] mm Hg; P = .20; 12-month mean [SD] diastolic BP: 77 [10] mm Hg vs 78 [11] mm Hg; P = .52), candesartan was superior to lisinopril on the primary outcome of executive function measured by Trail Making Test Part B (effect size [ES] = −12.8 [95% CI, −22.5 to −3.1]) but not Executive Abilities: Measures and Instruments for Neurobehavioral Evaluation and Research score (ES = −0.03 [95% CI, −0.08 to 0.03]). Candesartan was also superior to lisinopril on the secondary outcome of Hopkins Verbal Learning Test-Revised delayed recall (ES = 0.4 [95% CI, 0.02 to 0.8]) and retention (ES = 5.1 [95% CI, 0.7 to 9.5]).

Background: African Americans (AA) have a higher Alzheimer’s disease (AD) prevalence and report more perceived stress than White Americans. The biological basis of the stress-AD link is unclear. This study investigates the connection between stress and AD biomarkers in a biracial cohort. Objective: Establish biomarker evidence for the observed association between stress and AD, especially in AA. Methods: A cross-sectional study (n = 364, 41.8% AA) administering cognitive tests and the perceived stress scale (PSS) questionnaire. A subset (n = 309) provided cerebrospinal fluid for measurement of Aβ42, Tau, Ptau, Tau/Aβ42 (TAR), and Ptau/Aβ42 (PTAR). Multivariate linear regression, including factors that confound racial differences in AD, was performed. Results: Higher PSS scores were associated with higher Ptau (β= 0.43, p = 0.01) and PTAR (β= 0.005, p = 0.03) in AA with impaired cognition (mild cognitive impairment). Conclusion: Higher PSS scores were associated with Tau-related AD biomarker indices in AA/MCI, suggesting a potential biological connection for stress with AD and its racial disparity.

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BackgroundViral infections are a significant cause of severe acute respiratory illnesses (ARI) in young children. Understanding the current epidemiology of these viruses is important for informing treatment and prevention measures. We describe the New Vaccine Surveillance Network (NVSN) and report preliminary results from 2015 to 2016.MethodsProspective active surveillance for hospitalized ARI was conducted from November 1, 2015 to June 30, 2016 among children <5 years of age at seven pediatric hospital sites (figure) using a broad case definition based on admission diagnoses. Parent interviews and medical chart reviews were performed, and mid-turbinate nasal and throat flocked swabs and/or tracheal aspirates were tested for adenovirus, human metapneumovirus (HMPV), influenza, parainfluenza viruses (PIV) 1–3, respiratory syncytial virus (RSV), and rhinovirus/enterovirus using molecular diagnostic assays at each site. Asymptomatic controls <5 years of age were also enrolled.ResultsAmong 2,974 hospitalized children with ARI whose specimens were tested for viruses, 2,228 (75%) were <2 years old, with 745 (25%) 0–2 months, and 309 (10%) 3–5 months old. The majority were male (58%; n = 1,732) and 63% (n = 1,093) had no documented comorbid conditions. The median length of stay was 2 days; 1,683 (57%) received supplemental oxygen, 435 (15%) were admitted to intensive care, 95 (3%) required mechanical ventilation, and 1 (<1%) died. Viruses were detected in 2,242 (75%) children with ARI, with >1 virus detected in 234 (8%). RSV was detected in 1,039 (35%) children with ARI, HMPV in 245 (8%), influenza in 104 (4%), and PIV-1, PIV-2, and PIV-3 in 49 (2%), 2 (<1%), and 78 (3%), respectively. Rhinovirus/enterovirus was detected in 849 (29%) and adenovirus in 118 (4%) children with ARI, but were also detected in 18% (n = 227) and 5% (n = 60), respectively, of the 1,243 controls tested; the other viruses were more rarely detected in controls.ConclusionDuring the 2015–2016 season, viral detections were common in young children hospitalized for ARI at seven US sites. NVSN combines clinical data with current molecular laboratory techniques to describe respiratory virus epidemiology in cases of hospitalized pediatric ARI in order to inform current and future prevention, treatment, and healthcare utilization measures. Disclosures N. Halasa, Sanofi Pasteur: Investigator, Research support. GSK: Consultant, Consulting fee. Moderna: Consultant, Consulting fee. J. Englund, Gilead: Consultant and Investigator, Consulting fee and Research support. Novavax: Investigator, Research support. GlaxoSmithKline: Investigator, Research support. Alios: Investigator, Research support. MedImmune: Investigator, Research support. J. V. Williams, Quidel: Board Member, Consulting fee. GlaxoSmithKline: Consultant, Consulting fee.

BackgroundRespiratory syncytial virus (RSV) is a major cause of severe acute respiratory illness (ARI) among young children. With several vaccines and immunoprophylaxis agents for RSV currently in development, updated estimates of severe RSV disease in young children in the United States (US) are needed.MethodsProspective active surveillance for hospitalized ARI was conducted from 11/1/2015 to 6/30/2016 among children <5 years of age at seven pediatric hospital sites participating in the New Vaccine Surveillance Network. Demographic and clinical information for enrolled subjects were gathered through parent interviews and medical chart reviews. Mid-turbinate nasal and throat flocked swabs (combined for testing when available) and/or tracheal aspirates (when pertinent) were collected for respiratory pathogen testing. Specimens were tested for RSV using molecular diagnostic assays at each site.ResultsIn preliminary data analyses, 2,948 hospitalized children with a median age of 11 months were enrolled during the study period, of whom 1,030 (35%) tested positive for RSV. Most RSV-detections occurred in children <2 years of age (87%; n = 893), with 340 (33%) RSV-positive children aged 0–2 months, 184 (18%) aged 3–5 months, 174 (17%) aged 6–11 months, and 195 (19%) aged 12–23 months. The majority of RSV-positive children (75%; n = 776) had no chart-documented comorbid conditions. Among 893 RSV-positive children <2 years of age, 161 (18%) reported a history of preterm birth, with 99 (11%) reporting birth at 34–36 weeks gestational age (WGA), 33 (4%) at 30–33 WGA, 20 (2%) at <30 WGA, and 9 (1%) with no further gestational age information available. Among all RSV-positive subjects, the median length of stay was 2 days; 706 (69%) received supplemental oxygen during hospitalization, 226 (22%) were admitted to an intensive care unit, and 28 (3%) required mechanical ventilation.ConclusionDuring the 2015–16 season, RSV was associated with one-third of ARI hospitalizations in young children, the majority of which occurred in children aged <2 years. Most RSV-positive children were previously healthy, and nearly one fifth of those <2 years of age reported a history of preterm birth. RSV continues to be a major cause of morbidity among young children in the US.Disclosures N. B. Halasa, sanofi pasteur: Research Contractor, Research support; Astra Zeneca: Research Contractor, Grant recipient; J. Englund, Gilead: Consultant and Investigator, Research support; Chimerix: Investigator, Research support; Alios: Investigator, Research support; Novavax: Investigator, Research support; MedImmune: Investigator, Research support; GlaxoSmithKline: Investigator, Research support; J. V. Williams, Quidel: Scientific Advisor, Consulting fee; GlaxoSmithKline: Scientific Advisor, Consulting fee; F. M. Munoz, Novavax: Investigator, Research support; Regeneron: Investigator, Research support; GSK: Investigator, Research support