Blood culture collection practices in NICU; A national survey.

Background: Sepsis is the leading cause of mortality and morbidity in neonates. Blood cultures are the gold standard in diagnosing neonatal sepsis; however, there are currently no consensus guidelines for blood culture collection in neonates and significant practice variation exists in Neonatal Intensive Care Units (NICUs) globally. Objective: To examine current practices in obtaining blood cultures in the evaluation of neonatal sepsis in NICUs across Canada. Methods: A nine-item electronic survey was sent to each of the 29 level-3 NICUs in Canada, which are equipped to provide highly specialized care for newborns. Results: Responses were received from 90% (26/29) of sites. Sixty-five percent (17/26) of sites have blood culture collection guidelines for the investigation of neonatal sepsis. Forty-eight percent (12/25) of sites routinely target 1.0 mL per culture bottle. In late-onset sepsis (LOS), 58% (15/26) of sites process one aerobic culture bottle, whereas four sites routinely add anaerobic culture bottles. In early-onset sepsis (EOS) in very low birth weight infants (BW <1.5 kg), 73% (19/26) of sites use umbilical cord blood, and 72% (18/25) use peripheral venipuncture. Two sites routinely collect cord blood for culture in EOS. Only one site applies the concept of differential time-to-positivity to diagnose central-line-associated bloodstream infection. Conclusions: There is significant practice variation in methods used to obtain blood cultures in level-3 NICUs across Canada. Standardization of blood culture collection practices can provide reliable estimates of the true incidence of neonatal sepsis and help to develop appropriate antimicrobial stewardship strategies.

A call for a streamlined ethics review process for multijurisdictional, child health research studies.

To be time and resource efficient in neonatal research and to answer clinically relevant questions with validity and generalizability, large numbers of infants from multiple hospitals need to be included. Multijurisdictional research in Canada is currently fraught with research ethics review process hurdles that lead to delays, administrative costs, and possibly termination of projects. We describe our experience applying for ethics review to 13 sites in 7 provinces for a project comparing two standard of care therapies for preterm born infants with respiratory distress syndrome. We welcome the current opportunity created by the Institute of Human Development Child and Youth Health and the Institute for Genetics, to collaboratively identify practical solutions that would benefit Canadian researchers, Research Ethics Boards, and children and families.

Untargeted metabolomics analysis of the upper respiratory tract of ferrets following influenza A virus infection and oseltamivir treatment.

INTRODUCTION: Influenza is a highly contagious respiratory disease that causes high global morbidity and mortality each year. The dynamics of an influenza infection on the host metabolism, and how metabolism is altered in response to neuraminidase inhibitor drug therapy, is still in its infancy but of great importance. OBJECTIVES: We aim to investigate the suitability of ferret nasal wash samples for metabolomics-based analysis and characterization of influenza infections and oseltamivir treatment. METHODS: Virological and metabolic analyses were performed on nasal wash samples collected from ferrets treated with oseltamivir or a placebo. Untargeted metabolomics was performed using a gas chromatography coupled with mass spectrometery (GC-MS) based protocol that comprised a retention time (RT) locked method and the use of a commercial metabolomics library. RESULTS: Ferret activity was reduced at 2-3 days post infection, which coincided with the highest influenza viral titre. The metabolomics data indicated a shift in metabolism during various stages of infection. The neuraminidase inhibitor oseltamivir created considerable downregulation of energy center metabolites (glucose, sucrose, glycine and glutamine), which generated high levels of branched amino acids. This further increased branched amino acid degradation and deregulation via glycerate-type intermediates and biosynthesis of fatty acids in oseltamivir-treated animals where abrogated weight loss was observed. CONCLUSION: Metabolomics was used to profile influenza infection and antiviral drug treatment in ferrets. This has the potential to provide indicators for the early diagnosis of influenza infection and assess the effectiveness of drug therapies.

No. 347-Obstetric Management at Borderline Viability.

OBJECTIVE: The primary objective of this guideline was to develop consensus statements to guide clinical practice and recommendations for obstetric management of a pregnancy at borderline viability, currently defined as prior to 25+6 weeks. INTENDED USERS: Clinicians involved in the obstetric management of women whose fetus is at the borderline of viability. TARGET POPULATION: Women presenting for possible birth at borderline viability. EVIDENCE: This document presents a summary of the literature and a general consensus on the management of pregnancies at borderline viability, including maternal transfer and consultation, administration of antenatal corticosteroids and magnesium sulfate, fetal heart rate monitoring, and considerations in mode of delivery. Medline, EMBASE, and Cochrane databases were searched using the following keywords: extreme prematurity, borderline viability, preterm, pregnancy, antenatal corticosteroids, mode of delivery. The results were then studied, and relevant articles were reviewed. The references of the reviewed studies were also searched, as were documents citing pertinent studies. The evidence was then presented at a consensus meeting, and statements were developed. VALIDATION METHODS: The content and recommendations were developed by the consensus group from the fields of Maternal-Fetal Medicine, Neonatology, Perinatal Nursing, Patient Advocacy, and Ethics. The quality of evidence was rated using criteria described in the Grading of Recommendations Assessment, Development and Evaluation methodology framework (reference 1). The Board of the Society of Obstetricians and Gynaecologists of Canada approved the final draft for publication. METHODS: The quality of evidence was rated using the criteria described in the Grading of Recommendations, Assessment, Development, and Evaluation methodology framework. The interpretation of strong and weak recommendations is described later. The Summary of Findings is available upon request. BENEFITS, HARMS, AND COSTS: A multidisciplinary approach should be used in counselling women and families at borderline viability. The impact of obstetric interventions in the improvement of neonatal outcomes is suggested in the literature, and if active resuscitation is intended, then active obstetric interventions should be considered. GUIDELINE UPDATE: Evidence will be reviewed 5 years after publication to decide whether all or part of the guideline should be updated. However, if important new evidence is published prior to the 5-year cycle, the review process may be accelerated for a more rapid update of some recommendations. SPONSORS: This guideline was developed with resources funded by the Society of Obstetricians and Gynaecologists of Canada and the Women and Babies Program at Sunnybrook Health Sciences Centre.

Chemometric Analysis of Lavender Essential Oils Using Targeted and Untargeted GC-MS Acquired Data for the Rapid Identification and Characterization of Oil Quality.

Standard raw material test methods such as the ISO Standard 11024 are focused on the identification of lavender oil and not the actual class/quality of the oil. However, the quality of the oil has a significant effect on its price at market. As such, there is a need for raw material tests to identify not only the type of oil but its quality. This paper describes two approaches to rapidly identifying and classifying lavender oil. First, the ISO Standard 11024 test method was evaluated in order to determine its suitability to assess lavender oil quality but due to its targeted and simplistic approach, it has the potential to miss classify oil quality. Second, utilizing the data generated by the ISO Standard 11024 test methodology, an untargeted chemometric predicative model was developed in order to rapidly assess and characterize lavender oils (Lavandulaangustifolia L.) for geographical/environmental adulteration that impact quality. Of the 170 compounds identified as per the ISO Standard 11024 test method utilizing GC-MS analyses, 15 unique compounds that greatly differentiate between the two classes of lavender were identified. Using these 15 compounds, a predicative multivariate chemometric model was developed that enabled lavender oil samples to be reliably differentiated based on quality. A misclassification analysis was performed and it was found that the predictions were sound (100% matching rate). Such an approach will enable producers, distributers, suppliers and manufactures to rapidly screen lavender essential oil. The authors concede that the validation and implementation of such an approach is more difficult than a conventional chromatographic assay. However, the rapid, reliable and less problematic screening is vastly superior and easily justifies any early implementation validation difficulties and costs.

Determination of vancomycin pharmacokinetics in neonates to develop practical initial dosing recommendations.

Variability in neonatal vancomycin pharmacokinetics and the lack of consensus for optimal trough concentrations in neonatal intensive care units pose challenges to dosing vancomycin in neonates. Our objective was to determine vancomycin pharmacokinetics in neonates and evaluate dosing regimens to identify whether practical initial recommendations that targeted trough concentrations most commonly used in neonatal intensive care units could be determined. Fifty neonates who received vancomycin with at least one set of steady-state levels were evaluated retrospectively. Mean pharmacokinetic values were determined using first-order pharmacokinetic equations, and Monte Carlo simulation was used to evaluate initial dosing recommendations for target trough concentrations of 15 to 20 mg/liter, 5 to 20 mg/liter, and ≤20 mg/liter. Monte Carlo simulation revealed that dosing by mg/kg of body weight was optimal where intermittent dosing of 9 to 12 mg/kg intravenously (i.v.) every 8 h (q8h) had the highest probability of attaining a target trough concentration of 15 to 20 mg/liter. However, continuous infusion with a loading dose of 10 mg/kg followed by 25 to 30 mg/kg per day infused over 24 h had the best overall probability of target attainment. Initial intermittent dosing of 9 to 15 mg/kg i.v. q12h was optimal for target trough concentrations of 5 to 20 mg/liter and ≤20 mg/liter. In conclusion, we determined that the practical initial vancomycin dose of 10 mg/kg vancomycin i.v. q12h was optimal for vancomycin trough concentrations of either 5 to 20 mg/liter or ≤20 mg/liter and that the same initial dose q8h was optimal for target trough concentrations of 15 to 20 mg/liter. However, due to large interpatient vancomycin pharmacokinetic variability in neonates, monitoring of serum concentrations is recommended when trough concentrations between 15 and 20 mg/liter or 5 and 20 mg/liter are desired.

Association between physical activity and substance use behaviors among high school students participating in the 2009 Youth Risk Behavior Survey.

This study examined the relationship between physical activity, physical education class, and sports participation on the substance use practices of adolescents. Data was derived from the 2009 Youth Risk Behavior Survey study of adolescent behaviors. The results of this study indicated that recreational physical activity, attending PE class, and participating in sports were independent protective factors for many cigarette use behaviors but not for smokeless tobacco use. Additionally, recreational physical activity and sports participation appears to be a protective factor for marijuana use among females but not males. On the other hand, recreational physical activity and sports participation appears to be a risk factor for alcohol use behaviors among males.

Extraintestinal Manifestations and Family History of Inflammatory Bowel Disease Increase the Risk of Pouchitis in a State-Level Epidemiology Study.

INTRODUCTION: Our understanding of the epidemiology of inflammatory conditions of the pouch and effectiveness of treatment is largely based on selected populations. We created a state-level registry to evaluate the incidence of pouchitis and the effectiveness of treatments used in an initial episode of pouchitis. METHODS: In a state-level retrospective cohort of all patients undergoing proctocolectomy with ileal pouch-anal anastomosis (IPAA) for ulcerative colitis between January 1, 2018, and December 31, 2020, we evaluated the incidence of pouchitis and compared the proportion of patients developing recurrent pouchitis and chronic antibiotic-dependent pouchitis according to initial antibiotic therapy. RESULTS: A total of 177 patients underwent surgery with 49 (28%) developing pouchitis within the 12 months after the final stage of IPAA. Patients with extraintestinal manifestations of inflammatory bowel disease (IBD) were significantly more likely to develop pouchitis within the first 12 months after IPAA (adjusted odds ratio 2.45, 95% confidence interval 1.03-5.81) after adjusting for family history of IBD (adjusted odds ratio 3.50, 95% 1.50-8.18). When comparing the proportion of patients who developed recurrent pouchitis or chronic antibiotic-dependent pouchitis with those who experienced an isolated episode of pouchitis, there were no significant differences among the initial antibiotic regimens used. DISCUSSION: In a state-level examination of outcomes after IPAA for ulcerative colitis, patients with extraintestinal manifestations of IBD were more likely to develop pouchitis; however, the initial antibiotic regimen chosen did not seem to affect long-term outcomes.

Effect of clinical and histological chorioamnionitis on the outcome of preterm infants.

Chorioamnionitis contributes to neonatal and maternal morbidity and mortality. We aimed to evaluate of the impact of clinical and histological chorioamnionitis on mortality and morbidity of preterm infants. Maternal and neonatal data were collected in a retrospective cohort of preterm infants less than 30 weeks' gestation. Infants were divided into three groups: those born to mothers with clinical chorioamnionitis, histological chorioamnionitis, or no chorioamnionitis. Of 274 identified preterm infants, 33 infants were born to mothers with clinical chorioamnionitis, 95 to mothers with histological chorioamnionitis, and 146 to mothers with no chorioamnionitis. Data were available for 180 (78%) of the 230 survivors at 18 months corrected age. Infants in the study groups were similar in gestational age, birth weight, and sex distribution. Clinical and histological chorioamnionitis were not predictive of infant mortality, cerebral palsy, bronchopulmonary dysplasia, periventricular leukomalacia, or retinopathy of prematurity. Infants in the clinical chorioamnionitis group had significantly lower cognitive (88 ± 10), language (82 ± 12), and motor (89 ± 11) scores compared with infants in the histological chorioamnionitis group (101 ± 13, p < 0.01; 91 ± 13, p < 0.05; and 99 ± 13, p < 0.05, respectively) and to infants in the no chorioamnionitis group (99 ± 13, p < 0.01; 92 ± 15, p < 0.05; and 97 ± 13, p < 0.05, respectively). Clinical chorioamnionitis is associated with developmental delay in preterm infants despite adequate treatment.

Comparison of Contraception Method and Associated Risk Among US High School Students.

Adolescent unintentional pregnancy and sexual transmitted infections (STIs) are at an alarming rating in the United States. The factors that contribute to high rates of unintentional pregnancy and STIs among adolescents are lack of contraception use and other risk behaviors. As such, this study sought to assess the relationship between type of contraception used during last sexual intercourse and risk behaviors among high school adolescents. Data for this study were derived from the 2019 Youth Risk Behavior Study (YRBS). A total of 13,677 participants completed the YRBS in 2019. Multiple logistic regression was used to estimate the association between contraceptive type (i.e., condom, oral birth control, withdrawal, no method) and risk behavior. Results found that those students who reported condom use were less likely to engage in certain substance use behaviors and sexual risk taking compared to those who used no contraceptive method, oral birth control, or withdrawal. The results seem to suggest that condom use and risk-taking behaviors are somewhat interconnected in that condom users were found to be more protective in their behaviors.

Extensive Colitis and Smoking Are Associated With Postoperative Complications Within 30 Days of Ileal Pouch-Anal Anastomosis.

BACKGROUND: Our understanding of outcomes after proctocolectomy with ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC) is largely based on analyses of selected populations. We created a state-level registry to evaluate the epidemiology of IPAA surgery and pouch-related outcomes across the major healthcare systems performing these surgeries in our state. METHODS: We created a retrospective cohort of all patients undergoing restorative proctocolectomy with IPAA for UC at 1 of 4 centers between January 1, 2018, and December 31, 2020. The primary outcomes of this study were the rate of complications and all-cause readmissions within the first 30 days of the final stage of IPAA surgery. RESULTS: During the study period, 177 patients underwent IPAA surgery with 66 (37%) experiencing a complication within 30 days. After adjusting for the number of stages in IPAA surgery, patients with extensive UC (odds ratio, 3.61; 95% confidence interval, 1.39-9.33) and current or former smokers (odds ratio, 2.98; 95% confidence interval, 1.38-6.45) were more likely to experience a complication. Among all patients, 57 (32%) required readmission within 30 days. The most common reasons for readmission were ileus/small bowel obstruction (22%), peripouch abscess (19%), and dehydration (16%). CONCLUSION: In this first state-level examination of the epidemiology of IPAA for UC, we demonstrated that the complication rate after IPAA for UC was 37%, with one-third of patients being readmitted within 30 days. Extensive disease at the time of colectomy appears to be an indicator of more severe disease and may portend a worse prognosis after IPAA.

Antibiotic use in Canadian neonatal intensive care units: a national survey for developing antimicrobial stewardship targets.

A survey was conducted among Canadian tertiary neonatal intensive care units. Of the 27 sites who responded, 9 did not have any form of antimicrobial stewardship, and 11 used vancomycin for empirical coverage in late-onset-sepsis evaluations. We detected significant variations in the diagnostic criteria for urinary tract infection and ventilator-associated pneumonia.

Practice Summary of Antimicrobial Therapy for Commonly Encountered Conditions in the Neonatal Intensive Care Unit: A Canadian Perspective.

Neonates are highly susceptible to infections owing to their immature cellular and humoral immune functions, as well the need for invasive devices. There is a wide practice variation in the choice and duration of antimicrobial treatment, even for relatively common conditions in the NICU, attributed to the lack of evidence-based guidelines. Early decisive treatment with broad-spectrum antimicrobials is the preferred clinical choice for treating sick infants with possible bacterial infection. Prolonged antimicrobial exposure among infants without clear indications has been associated with adverse neonatal outcomes and increased drug resistance. Herein, we review and summarize the best practices from the existing literature regarding antimicrobial use in commonly encountered conditions in neonates.

Characterization of neural breathing pattern in spontaneously breathing preterm infants.

The aim was to characterize the neural breathing pattern in nonintubated preterm infants. The diaphragm electrical activity (EAdi) and heart rate were simultaneously measured repeatedly for 1 h over several days using a modified feeding tube equipped with miniaturized sensors. The EAdi waveform was quantified for phasic and tonic activity, neural timings, and prevalence of recurring patterns, including central apnea. Ten infants with mean age 7 d (range, 3-13 d) were studied. Their birth weight was 1512 g (1158-1800 g) and GA at birth 31 wk (28-36 wk). Neural inspiratory and expiratory times were 278 ms (195-450 ms) and 867 ms (668-1436 ms) and correlated with GA (p < 0.001). Tonic EAdi represented 29.5% of phasic EAdi (16-40%) and was related to GA (r = 0.61, p < 0.001). For the group, 68% of the time was regular phasic breathing (without tonic activity) and 29% of the time with elevated tonic activity. Central apneas >5 s occurred on average 10 times per hour (2-29). Heart rate reductions were correlated to central apnea duration. In conclusion, esophageal recordings of the EAdi waveform demonstrate that neural breathing pattern is variable, with regards to timing, amplitude, and pattern with a distinct amount of tonic diaphragm activity.

Towards an architecture of flexibility.

OBJECTIVE: Our objective was to explore the case for adoption of flexibility as a core value in the design process for Neonatal Intensive Care Units (NICUs). METHODS: Guidelines for NICU design and care of NICU patients and families were examined to identify opportunities for building flexibility into NICU design to optimize function and experience. RESULTS: Benefits of building flexibility into NICU design included the ability for units to adapt quickly and economically to unpredictable events and demographic changes. Further, by centering family presence as a design necessity, NICUs may better protect families from experiencing additional harm due to separation and interruption of restorative activities. We were able to highlight several examples of current NICUs, which have successfully adopted flexible design and operational models to provide optimal levels of clinical and family-centered care. CONCLUSION: By intentionally incorporating flexibility into the design of an NICU, infants, families, and healthcare providers can be provided with an environment that can adapt to shifting needs to optimally support unit function and clinical outcomes.

Development of a national neonatal intensive care unit-specific antimicrobial stewardship programme in Canada: protocol for a cohort study.

INTRODUCTION: Early empiric treatment with broad-spectrum antimicrobials is common in neonatal intensive care units (NICU) due to the non-specific clinical presentation of infection. However, excessive and inappropriate antimicrobial use can lead to the emergence of drug-resistant organisms and adverse neonatal outcomes. This study aims to develop and implement a nationwide NICU-specific antimicrobial stewardship programme (ASP) to promote judicious antimicrobial use and control the emergence of multidrug-resistant organisms (MDROs) in Canada. METHODS AND ANALYSIS: Our study population will include all very low-birth-weight neonates admitted to participating tertiary NICU in Canada. Based on the existing limited literature, we will develop consensus on NICU antimicrobial stewardship interventions to enhance best practices. Using an expanded Canadian Neonatal Network (CNN) platform, we will collect data on antimicrobial use and the susceptibility of organisms identified in clinical samples from blood and cerebrospinal fluid over a period of 2 years. These data will be used to provide all NICU stakeholders with benchmarked centre-adjusted antimicrobial use and MDRO prevalence reports. An ASP plan will be developed at both individual unit and national levels in the subsequent years. Knowledge translation strategies will be implemented through the well-established Evidence-based Practice for Improving Quality methodology. ETHICS AND DISSEMINATION: Ethics for the study has been granted by the University of British Columbia Children's & Women's Research Ethics Board (H19-02490) and supported by CNN Executive Committee. The study results will be disseminated through national organisations and open access peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT04388293.

Patient-ventilator interaction during neurally adjusted ventilatory assist in low birth weight infants.

Neurally adjusted ventilatory assist (NAVA), a mode of mechanical ventilation controlled by diaphragmatic electrical activity (EAdi), may improve patient-ventilator interaction. We examined patient-ventilator interaction by comparing EAdi to ventilator pressure during conventional ventilation (CV) and NAVA delivered invasively and non-invasively. Seven intubated infants [birth weight 936 g (range, 676-1266 g); gestational age 26 wk (range, 25-29)] were studied before and after extubation, initially during CV and then NAVA. NAVA-intubated and NAVA-extubated demonstrated similar delays between onset of EAdi and onset of ventilator pressure of 74 +/- 17 and 72 +/- 23 ms (p = 0.698), respectively. During CV, the mean trigger delays were not different from NAVA, however 13 +/- 8.5% of ventilator breaths were triggered on average 59 +/- 27 ms before onset of EAdi. There was no difference in off-cycling delays between NAVA-intubated and extubated (32 +/- 34 versus 28 +/- 11 ms). CV cycled-off before NAVA (120 +/- 66 ms prior, p < 0.001). During NAVA, EAdi and ventilator pressure were correlated [mean determination coefficient (NAVA-intubated 0.8 +/- 0.06 and NAVA-extubated 0.73 +/- 0.22)]. Pressure delivery during conventional ventilation was not correlated to EAdi. Neural expiratory time was longer (p = 0.044), and respiratory rate was lower (p = 0.004) during NAVA. We conclude that in low birth weight infants, NAVA can improve patient-ventilator interaction, even in the presence of large leaks.

Volume of foremilk, hindmilk, and total milk produced by mothers of very preterm infants born at less than 28 weeks of gestation.

The purpose of this study is to describe foremilk volume (milk produced in the first 3 minutes of pumping), hindmilk volume (remainder of milk produced), and total milk volume produced by mothers of very preterm infants at 3 weeks postpartum and associated factors. Mothers (n = 24) mechanically pump their breasts a median (minimum, maximum) of 7 times (5, 9 times) per 24 hours for a total of 15 minutes (9.4, 23.9 minutes) each time. Foremilk, hindmilk, and total milk volumes are 183 mL per 24 hours (80, 810), 318 mL per 24 hours (98, 1007), and 545 mL per 24 hours (224, 1817), respectively. Milk volumes are not associated with mother's age, race or ethnic background, education, parity, reported prepregnancy body mass index, previous breastfeeding experience, frequency of milk pumping, longest time between pumps, infant birth weight, or multiple births. The degree of pre-maturity (<26 weeks vs 26(0/7)-27(6/7) weeks) is significantly related to the relative proportion of foremilk/hindmilk volumes (45:55 vs 36:65, respectively).