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There is some evidence that rats benefit from social housing and from some forms of environmental enrichment, such as platforms and shelters. It is less clear whether they benefit from more spacious cages. There is a lack of information about the relative benefits of social contact, enrichment and increased space, because existing studies tend to concentrate on only one of these variables at a time. The current experiment used economic demand procedures as a method to compare, on a single scale, qualitatively different environments with a standard home cage. The data indicate that rats show a high demand for social contact, and a low demand for a larger cage or one containing pillars or novel objects. This finding suggests that social housing of laboratory rats should be strongly advocated.
Stereotypic behaviours (SBs) are linked with behavioural inflexibility and resemble symptoms of autism, suggesting that stereotypic animals could have autistic-like social impairments. SBs are also common in caged mice. We therefore hypothesised relationships between stereotypic and social behaviours, predicting that highly stereotypic mice would give/receive more agonism and be less effective in social learning tasks. Experiment One used C57BL/6 and DBA/2 mice in non-enriched or enriched housing (15 cages each); Experiment Two, more cages (six non-enriched, 44 enriched) plus a third strain (BALB/c). Across both experiments, enrichment reduced SB and agonism (aggression, plus ‘displacements’ where one mouse supplants another at a resource). These effects appeared related: housing effects on agonism became negligible when SB was statistically controlled for, and, at least in enriched cages, SB covaried with receiving aggression. In Experiment Three, 20 DBAs varying in SB from Experiment Two acted as demonstrators in a ‘social transmission of food preferences’ task. They were fed a novel flavour (shatavari powder), then each mingled with a familiar but flavour-naïve C57 observer. Observers were subsequently offered two novel flavours: shatavari or marjoram. Those spontaneously choosing more shatavari (n = 10) tended to have had less stereotypic demonstrators than the other ten observer mice. Overall, highly stereotypic mice thus received more agonism — an effect with obvious welfare implications that can be reduced with enrichment — and seemed potentially less effective at inducing flavour preferences in conspecifics. Such effects are consistent with social impairment, suggesting that reducing SB may perhaps enhance interactions between conspecifics.
Network modeling has been applied in a range of trauma-exposed samples, yet results are limited by an over reliance on cross-sectional data. The current analyses used posttraumatic stress disorder (PTSD) symptom data collected over a 5-year period to estimate a more robust between-subject network and an associated symptom change network.
A PTSD symptom network is measured in a sample of military veterans across four time points (Ns = 1254, 1231, 1106, 925). The repeated measures permit isolating between-subject associations by limiting the effects of within-subject variability. The result is a highly reliable PTSD symptom network. A symptom slope network depicting covariation of symptom change over time is also estimated.
Negative trauma-related emotions had particularly strong associations with the network. Trauma-related amnesia, sleep disturbance, and self-destructive behavior had weaker overall associations with other PTSD symptoms.
PTSD's network structure appears stable over time. There is no single ‘most important’ node or node cluster. The relevance of self-destructive behavior, sleep disturbance, and trauma-related amnesia to the PTSD construct may deserve additional consideration.
Alcohol, cannabis, and nicotine use are highly comorbid and alarmingly prevalent in young adults. The hippocampus may be particularly sensitive to substance exposure. This remains largely untested in humans and familial risk may confound exposure effects. We extend prior work on alcohol and hippocampal volume in women by testing common and unique substance use effects and the potential moderating role of sex on hippocampal volume during emerging adulthood. A quasi-experimental cotwin control (CTC) design was used to separate familial risk from exposure consequences.
In a population-based sample of 435 24-year-old same-sex twins (58% women), dimensional measures (e.g. frequency, amount) of alcohol, cannabis, and nicotine use across emerging adulthood were assessed. Hippocampal volume was assessed using MRI.
Greater substance use was significantly associated with lower hippocampal volume for women but not men. The same pattern was observed for alcohol, cannabis, and nicotine. CTC analyses provided evidence that hippocampal effects likely reflected familial risk and the consequence of substance use in general and alcohol and nicotine in particular; cannabis effects were in the expected direction but not significant. Within-pair mediation analyses suggested that the effect of alcohol use on the hippocampus may reflect, in part, comorbid nicotine use.
The observed hippocampal volume deviations in women likely reflected substance-related premorbid familial risk and the consequences of smoking and, to a lesser degree, drinking. Findings contribute to a growing body of work suggesting heightened risk among women toward experiencing deleterious effects of substance exposure on the still-developing young adult hippocampus.
Agitation is a common complication of Alzheimer’s dementia (Agit-AD) associated with substantial morbidity, high healthcare service utilization, and adverse emotional and physical impact on care partners. There are currently no FDA-approved pharmacological treatments for Agit-AD. We present the study design and baseline data for an ongoing multisite, three-week, double-blind, placebo-controlled, randomized clinical trial of dronabinol (synthetic tetrahydrocannabinol [THC]), titrated to a dose of 10 mg daily, in 80 participants to examine the safety and efficacy of dronabinol as an adjunctive treatment for Agit-AD. Preliminary findings for 44 participants enrolled thus far show a predominately female, white sample with advanced cognitive impairment (Mini Mental Status Examination mean 7.8) and agitation (Neuropsychiatric Inventory-Clinician Agitation subscale mean 14.1). Adjustments to study design in light of the COVID-19 pandemic are described. Findings from this study will provide guidance for the clinical utility of dronabinol for Agit-AD. ClinicalTrials.gov Identifier: NCT02792257.
Later Cambrian and earliest Ordovician trilobites and brachiopods spanning eight horizons from five localities within the Sông Mã, Hàm Rồng and Đông Sơn formations of the Thanh Hóa province of Việt Nam, constrain the age and faunal affinities of rocks within the Sông Đà terrane, one of several suture/fault-bounded units situated between South China to the north and Indochina to the south. ‘Ghost-like’ preservation in dolomite coupled with tectonic deformation leaves many of the fossils poorly preserved, and poor exposure precludes collecting within continuously exposed stratigraphic successions. Cambrian carbonate facies pass conformably into Lower Ordovician carbonate-rich strata that also include minor siliciclastic facies, and the recovered fauna spans several uppermost Cambrian and Lower Ordovician biozones. The fauna is of equatorial Gondwanan affinity, and comparable to that from South China, North China, Sibumasu and Australia. A new species of Miaolingian ‘ptychopariid’ trilobite, Kaotaia xuanensis, is described. Detrital zircon samples from Cambrian–Ordovician rocks of the North Việt Nam and Sông Đà terranes, and from Palaeozoic samples from the Trường Sơn sector of Indochina immediately to the south, contain a predominance of ages spanning the Neoproterozoic period and have a typical equatorial Gondwanan signature. We associate the Cambrian and Tremadocian of the Sông Đà terrane with areas immediately to the north of it, including the North Việt Nam terrane and the southern parts of Yunnan and Guangxi provinces of China.
Through drinking water, humans are commonly exposed to atrazine, a herbicide that acts as an endocrine and metabolic disruptor. It interferes with steroidogenesis, including promoting oestrogen production and altering cell metabolism. However, its precise impact on uterine development remains unknown. This study aimed to determine the effect of prolonged atrazine exposure on the uterus. Pregnant mice (n = 5/group) received 5 mg/kg body weight/day atrazine or DMSO in drinking water from gestational day 9.5 until weaning. Offspring continued to be exposed until 3 or 6 months of age (n = 5–9/group), when uteri were collected for morphological and molecular analyses and steroid quantification. Endometrial hyperplasia and leiomyoma were evident in the uteri of atrazine-exposed mice. Uterine oestrogen concentration, oestrogen receptor expression, and localisation were similar between groups, at both ages (P > 0.1). The expression and localisation of key epithelial-to-mesenchymal transition (EMT) genes and proteins, critical for tumourigenesis, remained unchanged between treatments, at both ages (P > 0.1). Hence, oestrogen-mediated changes to established EMT markers do not appear to underlie abnormal uterine morphology evident in atrazine exposure mice. This is the first report of abnormal uterine morphology following prolonged atrazine exposure starting in utero, it is likely that the abnormalities identified would negatively affect female fertility, although mechanisms remain unknown and require further study.
To better characterize brain-based mechanisms of polygenic liability for psychopathology and psychological traits, we extended our previous report (Liu et al. Psychophysiological endophenotypes to characterize mechanisms of known schizophrenia genetic loci. Psychological Medicine, 2017), focused solely on schizophrenia, to test the association between multivariate psychophysiological candidate endophenotypes (including novel measures of θ/δ oscillatory activity) and a range of polygenic scores (PGSs), namely alcohol/cannabis/nicotine use, an updated schizophrenia PGS (containing 52 more genome-wide significant loci than the PGS used in our previous report) and educational attainment.
A large community-based twin/family sample (N = 4893) was genome-wide genotyped and imputed. PGSs were constructed for alcohol use, regular smoking initiation, lifetime cannabis use, schizophrenia, and educational attainment. Eleven endophenotypes were assessed: visual oddball task event-related electroencephalogram (EEG) measures (target-related parietal P3 amplitude, frontal θ, and parietal δ energy/inter-trial phase clustering), band-limited resting-state EEG power, antisaccade error rate. Principal component analysis exploited covariation among endophenotypes to extract a smaller number of meaningful dimensions/components for statistical analysis.
Endophenotypes were heritable. PGSs showed expected intercorrelations (e.g. schizophrenia PGS correlated positively with alcohol/nicotine/cannabis PGSs). Schizophrenia PGS was negatively associated with an event-related P3/δ component [β = −0.032, nonparametric bootstrap 95% confidence interval (CI) −0.059 to −0.003]. A prefrontal control component (event-related θ/antisaccade errors) was negatively associated with alcohol (β = −0.034, 95% CI −0.063 to −0.006) and regular smoking PGSs (β = −0.032, 95% CI −0.061 to −0.005) and positively associated with educational attainment PGS (β = 0.031, 95% CI 0.003–0.058).
Evidence suggests that multivariate endophenotypes of decision-making (P3/δ) and cognitive/attentional control (θ/antisaccade error) relate to alcohol/nicotine, schizophrenia, and educational attainment PGSs and represent promising targets for future research.
Domestic dogs (Canis familiaris) provide important benefits to human beings but can also transmit pathogens. Information on the breadth of canine zoonoses and vectorborne research in North America is scarce. A scoping review was conducted to examine (1) the number and type of canine zoonoses and vectorborne studies in domestic dogs conducted in North America since the start of the 21st century; (2) the main research methods reported; (3) the Inequality-adjusted Human Development Index (IHDI) countries in which research was conducted; and (4) whether collaborative integrated terminology was reported in objectives or methods sections. Title/abstract screening, full-text screening, and data-charting were completed by two reviewers. We identified 507 publications evaluating 43 zoonotic or vectorborne pathogens in domestic dogs. Most studies (n = 391 of 512 (76.37%)) were conducted in the USA. The five most frequently researched pathogens were Ehrlichia spp. (n = 81 of 507 (15.98%)), Borrelia burgdorferi (n = 64 of 507 (12.62%)), Leptospira spp. (n = 54 of 507 (10.65%)), Rabies virus (n = 42 of 507 (8.28%)), and Influenza viruses (n = 41 of 507 (8.09%)). These pathogens can cause moderate to severe health outcomes in human beings and in dogs irrespective of IHDI ranking; our review highlights important counts of research conduct among North American countries.
This research investigates the impact of deprivation on demographic inequalities in England and Wales among adults. Using demographic measures including the modal age at death, life expectancy, lifespan variation and mortality, it shows a negative correlation with deprivation as measured by the 2015 Index of Multiple Deprivation. Although it finds that life expectancy is increasing overall and the gap between men and women is lessening, improvements are slower paced in more deprived areas such that the gap between rich and poor is slowly worsening over time. Men are more adversely impacted by deprivation than women with the gap in period life expectancy at age 30 in 2015 between the top and bottom 1% of deprived neighbourhoods at 10.9 years for men and 8.4 years for women. Between 2001 and 2015 inequalities in male mortality rates at age 44 were 4.4 times greater in the most deprived 10% of neighbourhoods than those in the 10% least deprived and were much higher than in intervening deciles. The worst deprivation is concentrated in specific areas. For example, in 22 out of 326 English districts, 25% or more of neighbourhoods are in the most deprived 10% and in 5 districts it is 40% or above.
We present a detailed overview of the cosmological surveys that we aim to carry out with Phase 1 of the Square Kilometre Array (SKA1) and the science that they will enable. We highlight three main surveys: a medium-deep continuum weak lensing and low-redshift spectroscopic HI galaxy survey over 5 000 deg2; a wide and deep continuum galaxy and HI intensity mapping (IM) survey over 20 000 deg2 from
$z = 0.35$
to 3; and a deep, high-redshift HI IM survey over 100 deg2 from
$z = 3$
to 6. Taken together, these surveys will achieve an array of important scientific goals: measuring the equation of state of dark energy out to
$z \sim 3$
with percent-level precision measurements of the cosmic expansion rate; constraining possible deviations from General Relativity on cosmological scales by measuring the growth rate of structure through multiple independent methods; mapping the structure of the Universe on the largest accessible scales, thus constraining fundamental properties such as isotropy, homogeneity, and non-Gaussianity; and measuring the HI density and bias out to
$z = 6$
. These surveys will also provide highly complementary clustering and weak lensing measurements that have independent systematic uncertainties to those of optical and near-infrared (NIR) surveys like Euclid, LSST, and WFIRST leading to a multitude of synergies that can improve constraints significantly beyond what optical or radio surveys can achieve on their own. This document, the 2018 Red Book, provides reference technical specifications, cosmological parameter forecasts, and an overview of relevant systematic effects for the three key surveys and will be regularly updated by the Cosmology Science Working Group in the run up to start of operations and the Key Science Programme of SKA1.
To date, there are no published data on the association of patient-centered outcomes and accurate public-safety answering point (PSAP) dispatch in an American population. The goal of this study is to determine if PSAP dispatcher recognition of out-of-hospital cardiac arrest (OHCA) is associated with neurologically intact survival to hospital discharge.
This retrospective cohort study is an analysis of prospectively collected Quality Assurance/Quality Improvement (QA/QI) data from the San Antonio Fire Department (SAFD; San Antonio, Texas USA) OHCA registry from January 2013 through December 2015. Exclusion criteria were: Emergency Medical Services (EMS)-witnessed arrest, traumatic arrest, age <18 years old, no dispatch type recorded, and missing outcome data. The primary exposure was dispatcher recognition of cardiac arrest. The primary outcome was neurologically intact survival (defined as Cerebral Performance Category [CPC] 1 or 2) to hospital discharge. The secondary outcomes were: bystander cardiopulmonary resuscitation (CPR), automated external defibrillator (AED) use, and prehospital return of spontaneous return of circulation (ROSC).
Of 3,469 consecutive OHCA cases, 2,569 cases were included in this analysis. The PSAP dispatched 1,964/2,569 (76.4%) of confirmed OHCA cases correctly. The PSAP dispatched 605/2,569 (23.6%) of confirmed OHCA cases as another chief complaint. Neurologically intact survival to hospital discharge occurred in 99/1,964 (5.0%) of the recognized cardiac arrest group and 28/605 (4.6%) of the unrecognized cardiac arrest group (OR = 1.09; 95% CI, 0.71–1.70). Bystander CPR occurred in 975/1,964 (49.6%) of the recognized cardiac arrest group versus 138/605 (22.8%) of the unrecognized cardiac arrest group (OR = 3.34; 95% CI, 2.70–4.11).
This study found no association between PSAP dispatcher identification of OHCA and neurologically intact survival to hospital discharge. Dispatcher identification of OHCA remains an important, but not singularly decisive link in the OHCA chain of survival.
Subclinical adolescent alcohol use is highly prevalent and may have deleterious effects on important psychosocial and brain outcomes. Prior research has focused on identifying endophenotypes of pathological drinking, and the predictors of normative drinking remain understudied. This study investigated the incremental predictive value of two potential psychophysiological endophenotypes, P3 amplitude (an index of decision making) and midfrontal theta power (a correlate of attentional control), for prospectively predicting the expression and initiation of alcohol use emerging in adolescence.
A large (N = 594) epidemiological sample was prospectively assessed at ages 11/14/17. Alcohol/substance use was assessed at all ages via a computerized self-report inventory. EEG was recorded at age-14 during a visual oddball task to elicit P3 and theta.
Reduced target-related P3 and theta at age-14 prospectively predicted drinking at age-17 independent of one another. Among alcohol-naive individuals at age-14, attenuated P3 and theta increased the odds of new-onset alcohol behaviors 3 years later. Importantly, the endophenotypes provided significant incremental predictive power of future non-clinical alcohol use beyond relevant risk factors (prior alcohol use; tobacco/illicit drug initiation; parental alcohol use disorder).
The current report is the first of our knowledge to demonstrate that deviations in parietal P3 and midfrontal theta prospectively predict the emergence of normative/non-pathological drinking. P3 and theta provide modest yet significant explanatory variance beyond prominent self-report and familial risk measures. Findings offer strong evidence supporting the predictive utility of P3 and theta as candidate endophenotypes for adolescent drinking.
Use of the herbicide atrazine (ATR) is banned in the European Union; yet, it is still widely used in the USA and Australia. ATR is known to alter testosterone and oestrogen production and thus reproductive characteristics in numerous species. In this proof of concept study, we examined the effect of ATR exposure, at a supra-environmental dose (5 mg/kg bw/day), beginning on E9.5 in utero, prior to sexual differentiation of the reproductive tissues, until 26 weeks of age, on the development of the mouse penis. Notably, this is the first study to specifically investigate whether ATR can affect penis characteristics. We show that ATR exposure, beginning in utero, causes a shortening (demasculinisation) of penis structures and increases the incidence of hypospadias in mice. These data indicate the need for further studies of ATR on human reproductive development and fertility, especially considering its continued and widespread use.
Background: Spinal muscular atrophy (SMA) is a children’s neuromuscular disorder. Although motor neuron loss is a major feature of the disease, we have identified fatty acid abnormalities in SMA patients and in preclinical animal models, suggesting metabolic perturbation is also an important component of SMA. Methods: Biochemical, histological, proteomic, and high resolution respirometry were used. Results: SMA patients are more susceptible to dyslipidemia than the average population as determined by a standard lipid profile in a cohort of 72 pediatric patients. As well, we observed a non-alcoholic liver disease phenotype in apreclinical mouse model. Denervation alone was not sufficient to induce liver steatosis, as a mouse model of ALS, did not develop fatty liver. Hyperglucagonemia in Smn2B/-mice could explain the hepatic steatosis by increasing plasma substrate availability via glycogen depletion and peripheral lipolysis. Proteomic analysis identified mitochondrion and lipid metabolism as major clusters. Alterations in mitochondrial function were revealed by high-resolution respirometry. Finally, low-fat diets led to increased survival in Smn2B/-mice. Conclusions: These results provide strong evidence for lipid metabolism defects in SMA. Further investigation will be required to establish the primary mechanism of these alterations and understand how they lead to additional co-morbidities in SMA patients.
A new protocol has been devised for determining elastic properties of natural biocomposites in the form of bivalve shells under wet and dry conditions. Four-point bending on shell slices of Mytilus edulis, Ensis siliqua, and Pecten maximus give generally lower and more reliable values of Young’s modulus, E, than those in the literature from three-point bending, due to the more even distribution of strain. Finite element analysis of the prismatic microstructure of Pinna nobilis, obtained by X-ray tomography, shows that values of E ≈ 20 GPa can be understood in terms of the real microstructure containing a small proportion of organic matrix phase with E ≈ 1 GPa and a dominant proportion of calcite with E ≈ 90 GPa. Higher values of E obtained by nanoindentation give results which are biased toward the properties of the carbonate phase rather than of the biocomposite as a whole.
Lowering dietary protein concentration is known to decrease urinary nitrogen (N) losses and increase milk N efficiency in dairy cows, but it may negatively affect animal productivity. Plant-derived essential oils (EO) may alleviate these negative effects by improving the efficiency of rumen fermentation in cows fed reduced feed protein diets. The experiment was conducted to investigate the effects of lowering crude protein (CP) supply alone or in a combination with an EO product on feed intake, milk production and composition, rumen fermentation, total tract digestibility and N utilization in dairy cows. Twenty-one Holstein cows were used in a replicated 3 × 3 Latin square design experiment. Each period consisted of 14 days for adaptation and 14 days for data collection and sampling. Cows were randomly assigned to one of three experimental diets: a 165 g/kg CP diet (control), a 155 g/kg CP diet (LCP) and LCP supplemented with 35 g/day per cow EO (LCPEO). The dry matter (DM) intake was decreased by LCP and LCPEO compared with the control; there was no effect of EO on DM intake. Milk yield and composition and feed efficiency were similar among treatments. Ruminal pH, lactate, ammonia and volatile fatty acids concentrations were not affected by treatment, except increased valerate concentration by LCPEO compared with LCP. The supplementation of EO tended to decrease protozoal counts. The LCP and LCPEO increased total tract digestibility of DM and organic matter and decreased CP digestibility compared with the control. Supplementation with EO did not affect total tract digestibility of dietary nutrients compared with the control or LCP. The LCP and LCPEO decreased urinary and fecal N excretions and increased milk N efficiency; nitrogen losses were not affected by EO. In this study, lowering dietary CP by 10 g/kg decreased urinary and fecal N excretion without affecting productivity. The supplementation of EO to LCP had only minor effects on rumen fermentation and did not affect productivity, digestibility and N excretion in lactating dairy cows.
Lebanon has a need for innovative approaches to increase access to mental health care to meet the country's current high demand. E-mental health has been included in its national mental health strategy while in parallel the World Health Organization has produced an online intervention called ‘Step-by-Step’ to treat symptoms of depression that is being tested in Lebanon over the coming years.
The primary aim of this study is to conduct bottom-up, community-driven qualitative cognitive interviewing from a multi-stakeholder perspective to inform the cultural adaptation of an Internet-delivered mental health intervention based on behavioural activation in Lebanon.
National Mental Health Programme staff conducted a total of 11 key informant interviews with three mental health professionals, six front-line workers in primary health care centres (PHCCs) and two community members. Also, eight focus group discussions, one with seven front-line workers and seven others with a total of 66 community members (Lebanese, Syrians and Palestinians) were conducted in several PHCCs to inform the adaptation of Step-by-Step. Results were transcribed and analysed thematically by the project coordinator and two research assistants.
Feedback generated from the cognitive interviewing mainly revolved around amending the story, illustrations and the delivery methods to ensure relevance and sensitivity to the local context. The results obtained have informed major edits to the content of Step-by-Step and also to the model of provision. Notably, the intervention was made approximately 30% shorter; it includes additional videos of content alongside the originally proposed comic book-style delivery; there is less emphasis on total inactivity as a symptom of low mood and more focus on enjoyable activities to lift mood; the story and ways to contact participants to provide support were updated in line with local gender norms; and many of the suggested or featured activities have been revised in line with suggestions from community members.
These findings promote and advocate the use of community-driven adaptation of evidence-based psychological interventions. Some of the phenomena recorded mirror findings from other research about barriers to care seeking in the region and so changes made to the intervention should be useful in improving utility and uptake of ‘Step-by-Step’.
To assess variability in antimicrobial use and associations with infection testing in pediatric ventilator-associated events (VAEs).
Descriptive retrospective cohort with nested case-control study.
Pediatric intensive care units (PICUs), cardiac intensive care units (CICUs), and neonatal intensive care units (NICUs) in 6 US hospitals.
Children≤18 years ventilated for≥1 calendar day.
We identified patients with pediatric ventilator-associated conditions (VACs), pediatric VACs with antimicrobial use for≥4 days (AVACs), and possible ventilator-associated pneumonia (PVAP, defined as pediatric AVAC with a positive respiratory diagnostic test) according to previously proposed criteria.
Among 9,025 ventilated children, we identified 192 VAC cases, 43 in CICUs, 70 in PICUs, and 79 in NICUs. AVAC criteria were met in 79 VAC cases (41%) (58% CICU; 51% PICU; and 23% NICU), and varied by hospital (CICU, 20–67%; PICU, 0–70%; and NICU, 0–43%). Type and duration of AVAC antimicrobials varied by ICU type. AVAC cases in CICUs and PICUs received broad-spectrum antimicrobials more often than those in NICUs. Among AVAC cases, 39% had respiratory infection diagnostic testing performed; PVAP was identified in 15 VAC cases. Also, among AVAC cases, 73% had no associated positive respiratory or nonrespiratory diagnostic test.
Antimicrobial use is common in pediatric VAC, with variability in spectrum and duration of antimicrobials within hospitals and across ICU types, while PVAP is uncommon. Prolonged antimicrobial use despite low rates of PVAP or positive laboratory testing for infection suggests that AVAC may provide a lever for antimicrobial stewardship programs to improve utilization.