Identifying developmental endophenotypes on the pathway between genetics and behavior is critical to uncovering the mechanisms underlying neurodevelopmental conditions. In this proof-of-principle study, we explored whether early disruptions in visual attention are a unique or shared candidate endophenotype of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD). We calculated the duration of the longest look (i.e., peak look) to faces in an array-based eye-tracking task for 335 14-month-old infants with and without first-degree relatives with ASD and/or ADHD. We leveraged parent-report and genotype data available for a proportion of these infants to evaluate the relation of looking behavior to familial (n = 285) and genetic liability (using polygenic scores, n = 185) as well as ASD and ADHD-relevant temperament traits at 2 years of age (shyness and inhibitory control, respectively, n = 272) and ASD and ADHD clinical traits at 6 years of age (n = 94).

Results showed that longer peak looks at the face were associated with elevated polygenic scores for ADHD (β = 0.078, p = .023), but not ASD (β = 0.002, p = .944), and with elevated ADHD traits in mid-childhood (F(1,88) = 6.401, p = .013, $\eta _p^2$ =0.068; ASD: F (1,88) = 3.218, p = .076), but not in toddlerhood (ps > 0.2). This pattern of results did not emerge when considering mean peak look duration across face and nonface stimuli. Thus, alterations in attention to faces during spontaneous visual exploration may be more consistent with a developmental endophenotype of ADHD than ASD. Our work shows that dissecting paths to neurodevelopmental conditions requires longitudinal data incorporating polygenic contribution, early neurocognitive function, and clinical phenotypic variation.

Background: A prolonged outbreak of carbapenemase-producing Serratia marcescens (CPSM) was identified in our quaternary healthcare center over a 2-year period from 2015 through 2017. A reservoir of IMP-4–producing S. marcescens in sink drains of clinical hand basins (CHB) was implicated in propagating transmission, supported by evidence from whole-genome sequencing (WGS). We assessed the impact of manual bioburden reduction intervention on further transmission of CPSM. Methods: Environmental sampling of frequently touched wet and dry areas around CPSM clinical cases was undertaken to identify potential reservoirs and transmission pathways. After identifying CHB as a source of CPSM, a widespread annual CHB cleaning intervention involving manual scrubbing of sink drains and the proximal pipes was implemented. Pre- and postintervention point prevalence surveys (PPS) of CHB drains performed to assess for CPSM colonization. Surveillance for subsequent transmission was conducted through weekly screening of patients and annual screening of CHB in transmission areas, and 6-monthly whole-hospital PPS of patients. All CPSM isolates were assessed by WGS. Results: In total, 6 patients were newly identified with CPSM from 2015 to 2017 (4.3 transmission events per 100,000 surveillance bed days [SBD]; 95% CI, 1.6–9.4). All clinical CPSM isolates were linked to CHB isolates by WGS. The CHB cleaning intervention resulted in a reduction in CHB colonization with CPSM in transmission areas from 72% colonization to 28% (ARR, 0.44; 95% CI, 0.25–0.63). A single further clinical case of CPSM linked to the CHB isolates was detected over 2 years of surveillance from 2017 to 2019 following the implementation of the annual CHB cleaning program (0.7 transmissions per 100,000 SBD; 95% CI, 0.0–3.9). No transmissions were linked to undertaking the cleaning intervention. Conclusions: A simple intervention targeted at reducing the biological burden of CPSM in CHB drains at regular intervals was effective in preventing transmission of carbapenemase-producing Enterobacterales from the hospital environment to patients over a prolonged period of intensive surveillance. These findings highlight the importance of detailed cleaning for controlling the spread of multidrug-resistant organisms from healthcare environments.

Funding: None

Disclosures: Jason Kwong, Austin Health

Infants struggle to understand familiar words spoken in unfamiliar accents. Here, we examine whether accent exposure facilitates accent-specific adaptation. Two types of pre-exposure were examined: video-based (i.e., listening to pre-recorded stories; Experiment 1) and live interaction (reading books with an experimenter; Experiments 2 and 3). After video-based exposure, Canadian English-learning 15- to 18-month-olds failed to recognize familiar words spoken in an unfamiliar accent. However, after face-to-face interaction with a Mandarin-accented talker, infants showed enhanced recognition for words produced in Mandarin English compared to Australian English. Infants with live exposure to an Australian talker were not similarly facilitated, perhaps due to the lower vocabulary scores of the infants assigned to the Australian exposure condition. Thus, live exposure can facilitate accent adaptation, but this ability is fragile in young infants and is likely influenced by vocabulary size and the specific mapping between the speaker and the listener's phonological system.

We examined whether change in added sugar intake is associated with change in δ13C, a novel sugar biomarker, in thirty-nine children aged 5–10 years selected from a Colorado (USA) prospective cohort of children at increased risk for type 1 diabetes. Reported added sugar intake via FFQ and δ13C in erythrocytes were measured at two time points a median of 2 years apart. Change in added sugar intake was associated with change in the δ13C biomarker, where for every 1-g increase in added sugar intake between the two time points, there was an increase in δ13C of 0⋅0082 (P = 0⋅0053), independent of change in HbA1c and δ15N. The δ13C biomarker may be used as a measure of compliance in an intervention study of children under the age of 10 years who are at increased risk for type 1 diabetes, in which the goal was to reduce dietary sugar intake.

There is increasing evidence that both black and green tea are beneficial for prevention of cardiovascular disease (CVD). We conducted a systematic review and meta-analysis evaluating the effects of tea flavonoids on cardiovascular (CVD) and all-cause mortality outcomes.Searches across five databases including PubMed and Embase were conducted through November 2018 to identify randomized controlled trials (RCTs) and prospective cohort studies reporting cardiovascular and all-cause mortality outcomes. Two investigators independently conducted abstract and full-text screenings, data extractions, and risk of bias (ROB) assessments using the Nutrition Evidence Library Bias Assessment Tool (NEL BAT). Mixed-effects dose-response meta-regression and standard random-effects meta-analyses for outcomes with ≥ 4 studies were performed. 0 RCTs and 38 prospective cohort studies were included in the systematic review. NEL BAT scores ranged from 0–15 (0 being the lowest risk). Our linear meta-regression model showed that each cup increase in daily tea consumption (about 280 mg and 338 mg of total flavonoids for black and green tea, respectively) was associated with 3–4% lower risk of CVD mortality (predicted adjusted RR = 0.96; CI 0.93–0.99 for green tea and RR = 0.97; CI 0.94–0.99 for black tea). Furthermore, eachcup increase in daily tea consumption was associated a 2% lower risk of all-cause mortality (predicted adjusted relative risk (RR) = 0.98; 95% CI 0.97–0.99 for black tea and RR = 0.98; CI 0.96–0.99 for green tea, respectively). Two studies reported multivariable Cox regression analysis results for the relationship between black tea intake and risks of all-cause mortality outcomes. The results from these two studies were combined with our linear meta-regression result in a random-effects model meta-analysis and showed that each cup increase in daily black tea consumption was associated with an average of 3% lower risk of all-cause mortality (pooled adjusted RR = 0.97; 95% CI 0.87- 1.00) with large heterogeneity (I2 = 81.4%; p = 0.005). Current evidence indicates that increased tea consumption may reduce cardiovascular and all-cause mortality in a dose-response manner. This systematic review was registered on PROSPERO.

We analyzed antibiotic use data from 29 southeastern US hospitals over a 5-year period to determine changes in antibiotic use after the fluoroquinolone US Food and Drug Administration (FDA) advisory update in 2016. Fluoroquinolone use declined both before and after the FDA announcement, and the use of select, alternative antibiotics increased after the announcement.

Fluoroquinolones are among the 4 most commonly prescribed antibiotic classes.1,2 Postmarketing reports of serious adverse events linked to fluoroquinolones include tendonitis, neuropathy, hypoglycemia, psychiatric side effects, and possible aortic vessel rupture, leading to safety label changes in July 2008 and August 2013.3 In July 2016, the US Food and Drug Administration (FDA) strengthened the “black box” warning following an initial safety announcement in May 2016, recommending avoidance of fluoroquinolones for uncomplicated infections such as acute exacerbation of chronic bronchitis, uncomplicated urinary tract infections, and acute bacterial sinusitis.4 Concerns over safety and the association with Clostridiodes difficile infection have led inpatient antimicrobial stewardship programs (ASPs) to develop initiatives to promote avoidance of quinolones. The objective of this study was to quantify the effect of the 2016 FDA “black box” update on inpatient antibiotic use among a cohort of southeastern US hospitals.

In 2018, the Clostridium difficile LabID event methodology changed so that hospitals doing 2-step tests, nucleic acid amplification test (NAAT) plus enzyme immunofluorescence assay (EIA), had their adjustment modified to EIA-based tests, and only positive final tests (eg, EIA) were counted in the numerator. We report the immediate impact of this methodological change at 3 Milwaukee hospitals.