bluuebunny/crossref_metadata_2025_split huggingface dataset:
61 Adherence to Daily Medication Regimens in Pediatric Asthma: Do Socioeconomic Status and Daily Dose Frequency have an Impact?
Authors: Armellin-Ducharme Frédérique , Drouin Olivier 
Published: October 2021

Abstract

Primary Subject area
Respirology

Background
Children with asthma from lower socioeconomic status (SES), and those with poor adherence to controller medications have worse health outcomes, including higher rates of exacerbations and hospitalizations. Simpler medication regimens could potentially improve medication adherence and asthma control.

Objectives
We aimed to determine if: (1) medication adherence (proportion of prescribed days covered [PPDC]) and primary non-adherence (PPDC = 0%) varied by SES; and if (2) there was an interaction between SES and daily dose frequency on adherence.

Design/Methods
This retrospective cohort study included children 2-17 years old followed at the asthma clinic of a large Canadian pediatric hospital between 2011 and 2020. Patients were prescribed one of five medication regimens that included one or more of the following medication classes: inhaled corticosteroids (ICS), long-acting beta-agonists (LABA) and leukotriene receptor antagonists (LTRA). Primary outcome was medication adherence, using the PPDC: the number of days for which a medication was dispensed divided by the number of days for which it was prescribed. For regimens with two different medications, total PPDC was the average of the PPDCs for each medication. The main predictor was SES, measured by the Pampalon’s material deprivation index, a compounded index of income, employment, and education, based on postal codes. It is divided in quintiles, with quintile 1 being the least materially deprived. Comparison of PPDC between quintiles of SES was achieved by a Kruskal-Wallis test. Chi-square testing was used to assess the relationship between the proportion of patients with primary non-adherence (PPDC=0) and quintiles of SES. In the subset of patients who did not have primary non-adherence (n = 462), interaction between SES and daily dose frequency on log transformed PPDC was examined using linear regression models.

Results
Among 551 patients, mean age was 7.1 years (SD 3.8) (Table1), and there was a similar number of patients in each quintile of SES based on a chi-square goodness of fit test (p=0.61). For the overall sample, mean PPDC was 38.1% (SD 27.6). PPDC was not statistically different between quintiles of SES (p=0.57) (Figure 1). Distribution of primary non-adherence (PPDC = 0) in the cohort was independent of the quintiles of SES (p=0.57). Keeping SES constant, twice-daily dose frequency was associated with a 1.1% decrease in PPDC (p=0.85). The interaction between daily dose frequency and SES was not statistically significant (p=0.66).

Conclusion
Medication adherence (PPDC) and primary non-adherence (PPDC = 0) did not vary significantly by SES, but twice-daily dose frequency was associated with a small decrease in mean PPDC. Quebec’s mandatory medication insurance could potentially explain the absence of difference in medication adherence across SES quintiles.
67 Are NICUs too busy?
Authors: Beltempo Marc , Platt Robert , Julien Anne-Sophie , Blais Regis , Valerie Bertelle , Lapointe Anie , Lacroix Guy , Gravel Sophie , Cabot Michèle , Piedboeuf Bruno 
Published: October 2021

Abstract

Primary Subject area
Neonatal-Perinatal Medicine

Background
In a health care system with limited resources, hospital organizational factors such as unit occupancy and nurse-to-patient ratios may contribute to patient outcomes.

Objectives
We aimed to assess the association of NICU occupancy and nurse staffing with outcomes of very preterm infants born &lt; 33 weeks gestational age (GA).

Design/Methods
This was a multicenter retrospective cohort study of infants born 23-32 weeks GA without major congenital anomaly, admitted within 2 days after birth to one of four Level 3 NICUs in Quebec, Canada (2015-2018). For each 8 h shift, data on unit occupancy were obtained from a central provincial database (SiteNeo) and linked to the hospital nursing hours database (Logibec). Unit occupancy rates and nursing provision ratios (nursing hours/recommended nursing hours based on patient dependency categories) were pooled for the first shift, 24 h, and 7 days of admission for each infant. Patient data were obtained from the Canadian Neonatal Network database. Primary outcome was mortality and/or morbidity (severe neurological injury, bronchopulmonary dysplasia, necrotizing enterocolitis, and late-onset sepsis, severe retinopathy of prematurity). Adjusted odds ratios (AOR) for association of exposure with outcomes were estimated using generalized linear mixed models with a random effect for center, while adjusting for confounders (gestational age, small for gestational age, sex, outborn, Score for Neonatal Acute Physiology version 2, mode of delivery, and the other organizational variables).

Results
Among 1870 infants included in analyses, 796 (43%) had mortality/morbidity. Median occupancy was 89% (IQR 82-94) and median nursing provision was 1.13 (IQR 0.97-1.37). Overall higher NICU occupancy on shift of admission, first 24 h, and 7 days were associated with higher odds of mortality/morbidity (Figure 1) but nursing provision was not (Figure 2). Subgroup analysis by GA (&lt; 29 and 29-32 weeks) yielded similar results (not shown). Generalized linear mixed model analyses showed that a 5% reduction in occupancy in the first 24 h of admission was associated with a 6% reduction in mortality/morbidity.

Conclusion
NICU occupancy is associated with mortality/morbidity among very preterm infants and may reflect lack of adequate resources in periods of high activity. Interventions aimed at reducing occupancy and maintaining adequate resources need to be considered as strategies to improve patient outcomes.
84 Looking back to move forward; can fetal placental inflammatory response play a role in risk of sepsis and clinical decision making in preterm infant
Authors: Hudson Jo-Anna , Viel-Thériault Isabelle , El Demellawy Dina , Ruschkowski Brittany , Tan Yvonne , Bijelic Vid , Rouvinez Bouali Nicole 
Published: October 2021

Abstract

Primary Subject area
Neonatal-Perinatal Medicine

Background
Sepsis adversely impacts the survival of very low birth weight infants (VLBW), with a mortality risk up to 50%. Its diagnosis in premature infants is challenging. Conversely, prolonged antibiotic use is associated with perilous potential consequences, propelling the need to better identify those at risk of sepsis. The presence of a histological intra-amniotic inflammation (IAI) response may be associated with an increased risk of early onset sepsis (EOS). Currently, it is unknown how the diagnosis of histological IAI impacts the risk of sepsis.

Objectives
Our research goal is to explore histological fetal and maternal inflammation in the placenta in VLBW infants and to evaluate if specific recommendations about antibiotic management of VLBW infants with histological fetal response can be proposed.

Design/Methods
Retrospective cohort study of all infants &lt; 1500 g born to a mother with histologically confirmed IAI. Demographic information about the pregnancy, delivery and postnatal course up to 28 days of life was extracted. Descriptive statistical analysis was conducted to compare the characteristics of infants with histological fetal response using χ2 test or Fisher’s exact test and Wilcoxon rank sum test or ANOVA.

Results
Seventy-three mother-baby pairs were reviewed. EOS prevalence (19%) in our IAI group of VLBW infants is much higher than EOS observed in all VLBW infants from the Canadian Neonatal Network database (below 3%). In our cohort, the majority had fetal inflammatory stage 1 (31.6%) and fetal inflammatory grade 0 (50%). There was no statistically significant distribution amongst the fetal stages or grades. Time to sepsis event analysis showed that the earlier fetal inflammatory grade was associated with positive cultures occurring earlier, while in the later grades there demonstrated longer latency to positive cultures. This trend was also true when looking at the maternal inflammatory stages. Nine infants who had antibiotics discontinued from day of life (DOL) 2-5 developed a positive blood culture ≤ DOL8.

Conclusion
Our results suggest that the presence of mild fetal inflammatory changes is associated with earlier positive cultures. We hypothesize that later grades may be associated with longer infection exposure leading to prolonged maternal antibiotics, resulting in less EOS. Majority of positive cultures were within the 3-8 day window, suggesting a role of knowing the fetal inflammatory response when deciding duration of antibiotic treatment.
119 Communicating Sensitive Information - An Exploration of Parental Perspectives on Prognostication of High Risk Infants
Authors: Fong Emily , Mesterman Ronit 
Published: October 2021

Abstract

Primary Subject area
Neonatal-Perinatal Medicine

Background
Preterm infants are at high risk of experiencing a range of impairments that may contribute to long-term challenges such as neurocognitive deficits. Physicians are often expected to give an outlook on future developmental outcomes of high-risk infants, often before sufficient time has elapsed to observe whether that particular child will demonstrate neurologic recovery from the initial injury. Clinicians often struggle with communicating this information, especially a poor prognosis, because of the worry about how these conversations affect families and their future expectations of the child.

Objectives
Our aim was to capture parents' retrospective perceptions of how their infant’s prognosis was communicated to them during their NICU stay.

Design/Methods
Semi-structured interviews were conducted over the phone with parents of former preterm infants with a birthweight below 1500 grams or parents of term infants who have sustained HIE requiring cooling. Parents were invited to participate when their child was between 12-36 months old at the time of the interview, so that parents would be able to have a sense of their child’s development and possible impairments. The data was analyzed thematically, with particular focus around the discourse of communication and prognostication.

Results
Twenty-three interviews were conducted: 20 with the biological mother, two with both biological parents, and one with the biological father. The average length of the interviews was 30 minutes. The main themes that recurred in the interviews included parental loss of control, needing to prepare for the unexpected, the value of shared decision making between the health care practitioners and parents, recognition and conveyance of uncertainty by the physician, and the importance of celebrating the present. Above all, a recurring theme mentioned by the majority of interviewees was the power of hope. While wanting to receive transparent and honest updates, parents felt strongly that giving them realistic hope was of utmost importance.

Conclusion
Although clinicians often feel pressured to deliver answers, parents found it helpful when clinicians acknowledged and explained the uncertainty that surrounds prognostication. While healthcare providers may feel the need to prepare parents for the worst, the importance of balancing this information with hope and positivity is what families remember and value years after the prognosis was given.
122 Comparing the External Validity of Clinical Prediction Tools Incorporating Serum Procalcitonin to Identify Febrile Infants (0-90 days) at Low Risk for Serious Bacterial Infection: A Retrospective Analysis
Authors: Harper Chris , Trottier-Boucher Marie-Noelle , Chen Michael 
Published: October 2021

Abstract

Primary Subject area
Hospital Paediatrics

Background
Procalcitonin (PCT), a serum inflammatory biomarker, has recently been incorporated into several clinical decision tools to identify febrile infants at low risk for serious bacterial infection (SBI). These include the Pediatric Emergency Care Applied Research Network (PECARN) tool, the “Step-by-Step” approach, and the “Laboratory-Score.” Our institution is one of a few in Canada to incorporate serum PCT routinely, allowing us to complete these clinical decision tools. Thus, the objectives of this study were to externally validate and compare these tools in a Canadian pediatric population, indirectly assessing the utility of serum PCT in clinical practice.

Objectives
The primary outcomes were to derive the sensitivity, specificity, and negative predictive value (NPV) of each stratification tool in predicting SBI.

Design/Methods
We retrospectively reviewed the medical records of all infants less than 90 days of age presenting to our emergency departments between April 2016 and October 2019 with fever without a source, who had sufficient investigations to apply one (or more) of the above clinical decision tools.

Results
We applied the PECARN tool to 51 cases, and had sufficient data to apply the Step-by-Step and Lab Score criteria to 43 of these patients. Seventeen of the 51 patients (33%) were identified to have a SBI. The PECARN and Step-by-Step tools both had NPV of 100%; both were sensitive enough to detect all patients with SBI. They had poor specificity (0.47 and 0.55 respectively). These two tools were in agreement in 38 of 43 (88%) cases. Though the Laboratory-Score had the highest positive predictive value (0.88) and specificity (0.85), it failed to identify 3 of 16 true cases of SBI and had a suboptimal sensitivity of 0.81.

Conclusion
The ability to identify febrile infants at low risk for SBI in a reliable way would have significant clinical potential to change practice. Given the strong NPV of both the PECARN and Step-by-Step tools, we conclude that their use, incorporating the measurement of serum PCT, may be of use in reducing pediatric hospitalization, use of empiric broad-spectrum antibiotics, and investigations such as lumbar punctures, in these low-risk patients. This study had a small sample size. We look forward to analyzing a larger population of febrile infants, particularly in infants of a chronologic age (28-90 days) more amenable to clinical practice change.
127 Impact of CYP2D6, CYP3A4, and CYP2C9 pharmacogenomic profile on pain relief and adverse events in Canadian children treated with oxycodone and ibuprofen
Authors: Yukseloglu Aran , Ali Samina , Drendel Amy , Carleton Bruce , Ross Colin , Le May Sylvie , Manaloor Robin , Rosychuk Rhonda , Johnson David 
Published: October 2021

Abstract

Primary Subject area
Clinical Pharmacology and Toxicology

Background
Genomic variation impacts drug pharmacokinetics for commonly used children’s pain medications such as oxycodone and ibuprofen. In order to personalize and best treat children’s pain, how cytochrome enzyme polymorphisms for CYP2D6, CYP3A4, and CYP2C9 impact clinical effectiveness and safety for oxycodone and ibuprofen were studied.

Objectives
Primary objectives were to evaluate if allelic variations of CYP2D6, CYP2C9, and CYP3A4 would a) alter clinical effectiveness of ibuprofen and oxycodone for pain relief, and b) impact the occurrence of adverse events. Secondary objectives were to determine the degree to which these genetic and other clinical factors influence analgesic effectiveness and safety.

Design/Methods
This prospective, observational cohort included children aged 4-16 years who were seen in a pediatric emergency department (between June 2010 - July 2014) with an acute fracture and used ibuprofen OR oxycodone for at-home pain management. Saliva samples were obtained prior to discharge, and daily telephone follow-up collected self-reported pain scores, medication use, adverse events, and functional limitations for 3 days. Genotyping identified allelic variants of CYP2D6, CYP3A4, and CYP2C9. Pain was measured using the Faces Pain Scale-Revised. CYP2D6 metabolic phenotypes were determined based on identified variants. Regression analyses were employed to determine relationships between clinical and genomic patient characteristics, pain relief, and adverse events.

Results
We included 210 children (n=140 ibuprofen, n=70 oxycodone); mean age was 11.1 (±3.5) years, 66.2% were male, and 79.5% self-identified as Caucasian. The median pain reduction in the ibuprofen group was 4 (±2.0) and 4 (±3.5) in the oxycodone group on Day 1 (p = 0.69). Adverse events were experienced by 53.2% of the ibuprofen group and 78.3% of the oxycodone group (p &lt; 0.001). CYP2D6 Intermediate Metabolizers had significantly less pain relief using oxycodone than Extensive Metabolizers (p = 0.04). CYP3A4 variants did not significantly impact pain relief or adverse events. Those with the decreased functioning CYP2C9*2 allele experienced less adverse events compared to the normal functioning allele CYP2C9*1 (p = 0.003) when using ibuprofen. Males (p = 0.035) and all children using non-pharmacological pain strategies (p = 0.02) experienced less pain relief with oxycodone.

Conclusion
A better understanding of pharmacogenomic variation could help personalize medication choice. Sex and non-pharmacologic pain management impact pain relief with oxycodone, warranting further study to better understand their relationship with opioid pain relief in children.
151 For The Parent, By The Parent: Defining the Characteristics of a Novel Program to Empower Parents of Refugee Background Using the Participatory Approaches
Authors: Kaur Pardeep , Minhas Ripudaman , Ho Bernice 
Published: October 2021

Abstract

Primary Subject area
Developmental Paediatrics

Background
With more than 28 million individuals of refugee or asylum-seeking background globally, the current situation has been described as one of the largest humanitarian crises of all time. Families of refugee background have complex, multigenerational mental health and developmental needs that are not accounted for in current programming frameworks. Difficulties in resettlement have been further compounded by COVID-19-related lockdowns, straining parental mental health and placing children at an increased risk for developmental or behavioural problems. Providing appropriate support services and educational resources that address the multigenerational concerns of families of refugee background will address these challenges, allowing for improved parental mental health, family cohesion, and developmental outcomes for children.

Objectives
To gather data about the experiences, resources, referral pathways and barriers that impact the experience of parents of refugee background in the Greater Toronto Area (GTA) and to develop a novel, multi-dimensional parenting program model using Community-Based Participatory Research (CBPR) principles.

Design/Methods
This was a qualitative community-based participatory study using a formative research framework, in accordance with COREQ guidelines. In-depth interviews (IDIs) were conducted with parents of refugee background and care providers that work closely with this population. Data were recorded, transcribed, and coded using deductive and inductive coding methods by two independent coders. A peer debriefing strategy was used to verify the coding approach and interpretation of findings in accordance with the RATS (relevancy, appropriateness, transparency and soundness) guidelines for qualitative research.

Results
A total of 20 IDIs were conducted (7 parents and 13 care providers). The main topics that were identified to be incorporated into the program include features of child development, how to address resettlement issues, child advocacy, and parenting in the Canadian context. Participants felt that tackling the language barriers, addressing the overlapping responsibilities of the mothers attending the sessions, providing incentives, increasing awareness of the program, and using an anti-racist and anti-oppressive approach is key to the program’s success. Participants emphasized the need for trauma-informed mental health support within the program model.

Conclusion
This study describes the key considerations for a novel parenting program for families of refugee background, by engaging them as key stakeholders in the program design process. Future iteration of this project would involve a pilot and evaluation of the program.
Increased endogenous reactive oxygen species normalizes proliferation defects of Bmi1 heterozygous knockout neural stem cells
Authors: Cao Qiuchen , Wang Tianqi , Xiao Ming , Bai Lei 
Published: October 2021

Objectives
The Bmi1gene, one of transcriptional suppressor genes in multi-comb family, maintains proliferation of neural stem cells (NSCs) and redox homeostasis. However, heterozygous deletion of the Bmi1 gene (Bmi1+/−) does not reduce the proliferative ability of NSCs. The aim of the present study was to reveal the underlying mechanism of this phenotype.

Methods
NSCs derived from the cortex of newborn Bmi1+/− and wild-type (WT) mice were treated with different concentrations of hydrogen peroxide (H2O2) and antioxidant N-acetyl-L-cysteine (NAC) for 24 h followed by analyses of NSC proliferation and oxidative stress-related indexes.

Results
The levels of reactive oxygen species (ROS) of Bmi1+/−-NSCs were slightly higher than that of WT-NSCs at baseline. H2O2 increased ROS and NAC reduced ROS in a concentration-dependent pattern, but the change was significantly greater in Bmi1+/−-NSCs than WT-NSCs. The proliferation and self-renewal ability of Bmi1+/−-NSCs and WT-NSCs were comparable in a basic state. After 1 μM H2O2 treatment, Brdu incorporation ratio, cell viability, total antioxidant capacity (T-AOC) and total superoxide dismutase activity were increased slightly in WT-NSCs, but decreased in Bmi1+/−-NSCs. H2O2 at 10 μM decreased proliferation and self-renewal ability of both genotype NSCs, with greater effect in Bmi1+/−. After treatment with 1 mM NAC, the number and diameter of neurospheres, Brdu incorporation rate, cell viability, T-AOC and total superoxide dismutase activity of Bmi1+/−-NSCs were lower than those of WT-NSCs.

Conclusion
These results suggest that Bmi1+/−-NSCs exhibit normal proliferation and self-renewal due to a slight increase in ROS, but are more vulnerable to changes in redox status.
Neuronally Produced Betaine Acts via a Novel Ligand Gated Ion Channel to Control Behavioural States
Authors: Hardege I , Morud J , Yu J , Wilson TS , Schroeder FC , Schafer WR 
Published: October 2021

AbstractTrimethyl glycine, or betaine, is an amino acid derivative found in diverse organisms, from bacteria to plants and animals. It can function as an osmolyte to protect cells against osmotic stress, and building evidence suggests betaine may also play important functional roles in the nervous system. However, despite growing interest in betaine’s roles in the nervous system, few molecular mechanisms have been elucidated. Here we identify the expression of betaine synthesis pathway genes in the nervous system of the nematode worm, C. elegans. We show that betaine, produced in a single pair of interneurons, the RIMs, can control complex behavioural states. Moreover, we also identify and characterise a new betaine-gated inhibitory ligand gated ion channel, LGC-41, which is required for betaine related behavioural changes. Intriguingly we observed expression of LGC-41 in punctate structures across several sensory and interneurons, including those synaptically connected to the RIMs. Our data presents a neuronal molecular mechanism for the action of betaine, via a specific receptor, in the control of complex behaviour within the nervous system of C. elegans. This may suggest a much broader role for betaine in the regulation of animal nervous systems than previously recognised.