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Background Poverty is associated with increased morbidity related to multiple child and adult health conditions and increased risk of premature death. Despite robust evidence linking income and health, and some recommendations for universal screening, poverty screening is not routinely conducted in clinical care. Methods We conducted an exploratory study of implementing universal poverty screening and intervention in family medicine and a range of pediatric care settings (primary through tertiary). After attending a training session, health care providers (HCPs) were instructed to perform universal screening using a clinical poverty tool with the question “Do you ever have difficulty making ends meet at the end of the month?” for the three-month implementation period. HCPs tracked the number of patients screened and a convenience sample of their patients were surveyed regarding the acceptability of being screened for poverty in a healthcare setting. HCPs participated in semi-structured focus groups to explore barriers to and facilitators of universal implementation of the tool. Results Twenty-two HCPs (10 pediatricians, 9 family physicians, 3 nurse practitioners) participated and 150 patients completed surveys. Eighteen HCPs participated in focus groups. Despite the self-described motivation of the HCPs, screening rates were low (9% according to self-reported numbers). The majority of patients either supported (72%) or were neutral (22%) about the appropriateness of HCPs screening for and intervening on poverty. HCPs viewed poverty as relevant to clinical care but identified time constraints, physician discomfort, lack of expertise and habitual factors as barriers to implementation of universal screening. Conclusions Poverty screening is important and acceptable to clinicians and patients. However, multiple barriers need to be addressed to allow for successful implementation of poverty screening and intervention in health care settings.

BackgroundA high maternal prepregnancy body mass index has been associated with lower offspring IQ, but it is unclear if the relationship is causal. To explore this, our objectives were to compare maternal and paternal estimates and to assess whether certain factors mediate the association.MethodsWe analysed data from the Avon Longitudinal Study of Parents and Children, which initially recruited 14 541 women residing in Avon, UK, with an expected date of delivery in 1991–1992. Data were collected during and after pregnancy by questionnaire, medical record abstraction and clinical assessment. At approximately 8 years of age, psychologists administered an abbreviated form of the Wechsler Intelligence Scale for Children-III. We fit multivariable logistic regression models to estimate parental prepregnancy obesity and overweight–offspring IQ associations. Counterfactually defined indirect (mediated) effects of maternal prepregnancy obesity on offspring IQ were estimated through path analysis.ResultsAmong 4324 mother–father–child triads and using normal weight as the referent, we observed consistently stronger associations for maternal prepregnancy obesity and offspring performance IQ (eg, adjusted β (95% CI)=−3.4 (−5.7 to −1.2) vs −0.97 (−2.9 to 0.96) for paternal obesity). The indirect effects of maternal obesity on offspring IQ through pathways involving gestational weight gain and duration of breastfeeding were small but significant.ConclusionOur findings are consistent with a weak biologic effect of maternal adiposity in pregnancy on offspring performance IQ. Given the growing prevalence of obesity worldwide, more evidence is needed to resolve the correlation versus causation debate in this area.

Background: Selective neonatal left mainstem bronchial intubation to treat right lung disease is typically achieved with elaborate maneuvers, instrumentation and devices. This is often attributed to bronchial geometry which favors right mainstem entry of an endotracheal tube deliberately advanced beyond the carina. Case summary: A neonate with severe bullous emphysema affecting the right lung required urgent non-ventilation of that lung. We achieved left mainstem bronchial intubation by turning the endotracheal tube 180° such that the Murphy's eye faced the left instead of the right, and simulated a left-handed intubation by slightly orientating the endotracheal tube such that its concavity faced the left instead of the right as in a conventional right-handed intubation. Conclusion: Urgent intubation of the left mainstem bronchus with an endotracheal tube can be easily achieved by recognizing that it is the position of the endotracheal tube tip and the direction of its concavity that are the chief determinants of which bronchus an endotracheal tube goes when advanced. This is important in critically ill neonates as the margin of safety and time window are small, and the absence of double-lumen tubes. Use of fiberoptic bronchoscope and blockers should be reserved as backup plans. Resumo: Justificativa: A intubação seletiva neonatal do brônquio principal esquerdo para tratar a doença pulmonar direita é tipicamente realizada com elaboradas manobras, instrumentação e dispositivos. Isso é frequentemente atribuído à geometria brônquica que favorece a entrada principal direita de um tubo endotraqueal (TET) deliberadamente avançado para além da carina. Resumo do caso: Recém-nascido com enfisema bolhoso grave afetando o pulmão direito que precisou com urgência da não ventilação desse pulmão. Conseguimos a intubação brônquica esquerda fazendo uma rotação de 180° do TET, de forma que o olho de Murphy ficasse voltada para a esquerda e não para a direita, e simulamos uma intubação à esquerda orientando ligeiramente o TET, de modo que sua concavidade virasse para a esquerda em vez de para a direita, como em uma intubação convencional à direita. Conclusão: A intubação urgente do brônquio principal esquerdo com um TET pode ser facilmente obtida reconhecendo-se que é a posição da ponta do TET e a direção de sua concavidade que determinam para qual brônquio o TET irá quando avançado. Isso é importante em neonatos criticamente doentes diante da margem de segurança e janela de tempo pequenas e na ausência de tubos de duplo lúmen. O uso de broncofibroscópio e bloqueadores deve ser considerado como planos de segurança. Keywords: Bullous emphysema, Endobronchial intubation, Neonate, Palavras-chave: Enfisema bolhoso, Intubação endobrônquica, Recém-nascido

Resumo Justificativa A intubacao seletiva neonatal do bronquio principal esquerdo para tratar a doenca pulmonar direita e tipicamente feita com elaboradas manobras, instrumentacao e dispositivos. Isso e frequentemente atribuido a geometria bronquica que favorece a entrada principal direita de um tubo endotraqueal (TET) deliberadamente avancado para alem da carina. Resumo do caso Recem‐nascido com enfisema bolhoso grave que afetava o pulmao direito e precisou com urgencia da nao ventilacao desse pulmao. Para conseguir a intubacao bronquica esquerda fizemos uma rotacao de 180° do TET, de forma que o olho de Murphy ficasse voltado para a esquerda, e nao para a direita, e para simular uma intubacao a esquerda orientamos ligeiramente o TET, de modo que sua concavidade virasse para a esquerda em vez de para a direita, como em uma intubacao convencional a direita. Conclusao A intubacao urgente do bronquio principal esquerdo com um TET pode ser facilmente obtida se reconhecermos que e a posicao da ponta do TET e a direcao de sua concavidade que determinam para qual bronquio o TET ira quando avancado. Isso e importante em neonatos criticamente doentes diante da margem de seguranca e janela de tempo pequenas e na ausencia de tubos de duplo lumen. O uso de broncofibroscopio e bloqueadores deve ser considerado como planos de seguranca.

BACKGROUND AND OBJECTIVES: Hypoglycemia monitoring is not recommended for most full-term newborns. We wished to determine the incidence, presentation and case characteristics of hypoglycemia in low-risk newborns. METHODS: With the assistance of the Canadian Paediatric Surveillance Program, we conducted a national study of severe hypoglycemia in apparently low-risk full-term newborns. Paediatricians who reported a case were sent a detailed questionnaire and the data were analyzed. RESULTS: All 93 confirmed cases were singletons, 56% were first-borns and 65% were male. An 8% rate of First Nations cases was twofold the population rate. Maternal hypertension rate was 23%, fourfold the general pregnancy rate. Maternal obesity was double the general pregnancy rate at 23%. Concerning signs or feeding issues were noted in 98% at the time of diagnosis. Median time to diagnosis was 4.1 hours. Mean blood glucose at intravenous (IV) start was 1.4 ± 0.5 hours (SD). Seventy-eight per cent had at least one of four potential stress indicators and were more likely to have early diagnosis (P=0.03). Major signs were present in 20%. Those cases presented later and had lower glucose levels (median=0.8 mmol/L versus 1.6 mmol/L, [P

The aim of this study was to assess the efficacy of a visual noise feedback system and "quiet time" in reducing noise levels in the neonatal intensive care unit (NICU).A prospective cross-sectional study was performed in a combined level II/III NICU at a Canadian tertiary care hospital. Noise levels were recorded continuously for three weeks without and then three weeks with visual noise feedback system. Noise levels were compared after one year of using visual feedback, and subsequently with the addition of two "quiet times."Visual feedback reduced noise levels from 54.2 dB (95% CI 53.8-54.7 dB) to 49.4 dB (95% CI 48.9-49.8 dB; P 0.0001) and increased the amount of time spent under 45 dB from 0 to 25% (P 0.0001) after three weeks of use. However, this effect was not sustained at one year of visual feedback, with noise levels at 54.7 dB (95% CI 54.5-55.0 dB, P = 0.55). Quiet Time did not further reduce daily noise in the NICU (average noise levels 54.7, 95% CI 54.4-55.0 dB, P = 0.836).While visual noise feedback system reduced noise levels in the short term, these effects were not sustainable at one year and could not be remediated with the addition of a Quiet Time initiative. Continuing education regarding the detrimental effects of noise is paramount to ensure persistent noise reduction in the NICU.

Background The rapid expansion of genetic knowledge, and the implications for healthcare has resulted in an increased role for Primary Care Providers (PCPs) to incorporate genetics into their daily practice. The objective of this study was to explore the self-identified needs, including educational needs, of both urban and rural Primary Care Providers (PCPs) in order to provide genetic care to their patients. Methods Using a qualitative grounded theory approach, ten key informant interviews, and one urban and two rural PCP focus groups (FGs) (n = 19) were conducted. All PCPs practiced in Southeastern Ontario. Data was analyzed using a constant comparative method and thematic design. The data reported here represent a subset of a larger study. Results Participants reported that PCPs have a responsibility to ensure patients receive genetic care. However, specific roles and responsibilities for that care were poorly defined. PCPs identified a need for further education and resources to enable them to provide care for individuals with genetic conditions. Based on the findings, a progressive stepped model that bridges primary and specialty genetic care was developed; the model ranged from PCPs identifying patients with genetic conditions that they could manage alone, to patients who they could manage with informal or electronic consultation to those who clearly required specialist referral. Conclusions PCPs identified a need to integrate genetics into primary care practice but they perceived barriers including a lack of knowledge and confidence, access to timely formal and informal consultation and clearly defined roles for themselves and specialists. To address gaps in PCP confidence in providing genetic care, interventions that are directed at accessible just-in-time support and consultation have the potential to empower PCPs to manage patients’ genetic conditions. Specific attention to content, timing, and accessibility of educational interventions is critical to address the needs of both urban and rural PCPs. A progressive framework for bridging primary to specialty care through a ‘stepped’ model for providing continuing medical education, and genetic care can was developed and can be used to guide future design and delivery of educational interventions and resources.

Background and objectives Universal hypoglycaemia monitoring of newborns is not recommended. We wished to determine the incidence, presentation and case characteristics of hypoglycaemic newborns that were not being monitored. Methods Through the Canadian Paediatric Surveillance Program we conducted a national study of severe hypoglycaemia in apparently low-risk full-term newborns. Inclusion criteria were: an otherwise healthy infant less than 96 hours old; gestational age 37–42 weeks; birth weight 2500–3999 grams; whole blood or serum glucose less than 2.0 mmol/L and IV dextrose used to treat the hypoglycaemia. Data were managed and analysed using IBM SPSS Statistics for Windows, Version 24.0 (Armonk, NY: IBM Corp.). Results From April 2014 to March 2016, 177 cases were reported. There were 5 duplicates, 33 cases did not meet inclusion criteria and 46 questionnaires were not returned, leaving 93 confirmed cases. The estimated incidence was 1 in 8378 births. All cases were singletons, 56% were first-borns and 65% were male. An 8% rate of First Nations cases was 3-fold the population rate. Maternal hypertension was present in 23%, 4-fold the overall pregnancy rate. Maternal obesity was double the overall pregnancy rate at 23%. Concerning signs or feeding issues were present at diagnosis in 98%. Median time to diagnosis was 4.1 hours. Mean blood glucose was 1.4±0.5 hours (SD). Seventy eight percent had at least one of 4 potential perinatal stress indicators (emergency Caesarean Section, meconium at delivery, requiring resuscitation or cord artery pH Conclusion While acknowledging the study’s limitations, the impact of First Nations origin, maternal obesity, maternal hypertension and perinatal stress indicators warrant further study and possible incorporation into glucose monitoring guidelines. The data further supports adoption of norm-based standards to identify and monitor all SGA infants. Funding Supported by grants from Queen’s University Faculty of Health Sciences and the Public Health Agency of Canada.

To effectively translate genetic advances into practice, engagement of primary care providers (PCPs) is essential. Using a qualitative, phenomenological methodology, we analyzed key informant interviews and focus groups designed to explore perspectives of urban and rural PCPs. PCPs endorsed a responsibility to integrate genetics into their practices and expected advances in genetic medicine to expand. However, PCPs reported limited knowledge and difficulties accessing resources, experts, and continuing education. Rural practitioners’ additional concerns included cost, distance, and poor patient engagement. PCPs’ perspectives are crucial to develop relevant educational and systems-based interventions to further expand genetic medicine in primary care.

We report a case of severe respiratory distress in a neonate who was not endotracheally intubated soon after esophageal atresia/tracheoesophageal fistula (EA/TEF) repair. In this serious situation, any form of emergency respiratory support or definitive airway management may compromise the esophageal anastomosis and fistula repair. The cause of respiratory distress in the early postoperative period after EA/TEF is multifactorial, and in this case, included symptomatic tracheomalacia, which is commonly associated with EA/TEF.

Selective neonatal left mainstem bronchial intubation to treat right lung disease is typically achieved with elaborate maneuvers, instrumentation and devices. This is often attributed to bronchial geometry which favors right mainstem entry of an endotracheal tube deliberately advanced beyond the carina.A neonate with severe bullous emphysema affecting the right lung required urgent non-ventilation of that lung. We achieved left mainstem bronchial intubation by turning the endotracheal tube 180° such that the Murphy's eye faced the left instead of the right, and simulated a left-handed intubation by slightly orientating the endotracheal tube such that its concavity faced the left instead of the right as in a conventional right-handed intubation.Urgent intubation of the left mainstem bronchus with an endotracheal tube can be easily achieved by recognizing that it is the position of the endotracheal tube tip and the direction of its concavity that are the chief determinants of which bronchus an endotracheal tube goes when advanced. This is important in critically ill neonates as the margin of safety and time window are small, and the absence of double-lumen tubes. Use of fiberoptic bronchoscope and blockers should be reserved as backup plans.

Objective To examine the association between the interpregnancy interval (IPI) and preterm birth, low birth weight, and SGA birth in a developed country with universal health coverage. Methods We conducted a secondary analysis of data housed at the Manitoba Centre for Health Policy. All live births in Manitoba hospitals over a 29-year period were identified and consecutive births to the same mother were grouped into sibling pairs to calculate the IPI for the younger siblings. Logistic regression models were fit to examine the association between the IPI and adverse perinatal outcomes, adjusted for potentially confounding sociodemographic and clinical factors. Results In a cohort of more than 171 000 births and relative to IPIs of 18 to 23 months, IPIs shorter than 12 and longer than 23 months were associated with significantly increased odds of preterm birth overall and both medically indicated and spontaneous preterm births, low birth weight, and SGA birth. The strongest association observed was for intervals shorter than 6 months and spontaneous preterm birth (adjusted OR 1.83, 95% CI 1.65-2.03). When the outcome was modelled as GA categories, the strongest association observed was for intervals shorter than 6 months and early preterm birth ( Conclusion If the associations observed between the IPI and adverse perinatal outcomes in this large, population-based cohort are causal, birth spacing could form an important target of public health messaging in Canada.

Objective The primary objective of this study was to determine the feasibility of using diffusion-weighted magnetic resonance imaging (DWMRI) to assess white matter changes in high-risk neonates. Secondary objectives were to determine if exposure to chorioamnionitis (clinical or histopathologic) is associated with DWMRI findings in the neonatal brain, and to calculate the sample size required for a more definitive prospective cohort study. Methods Seventeen women with PPROM (preterm premature rupture of the membranes) who delivered 18 infants not requiring ventilatory support were recruited to participate in this case series. When stable, infants underwent DWMRI scanning. All placentas were examined for evidence of histopathologic chorioamnionitis (HCA). Results There was histopathologic evidence of chorioamnionitis in seven of the 18 placentas examined; three of these patients had clinical chorioamnionitis. Diffusion MRI revealed changes in both the diffusion-weighted imaging and the apparent diffusion coefficient in three of the seven infants confirmed to have HCA (43%), while only one of the 11 infants with normal placentas (9%) showed similar findings. Routine head ultrasound examination demonstrated abnormal cortical findings that would normally prompt further investigation in only one of these infants. Conclusion Exposure to HCA may be associated with abnormal DWMRI findings on imaging of the neonatal brain within 96 hours of delivery. Further study is required to delineate the association of chorioamnionitis and white matter changes with long-term neurodevelopmental sequelae.

Objectives:To determine whether a novel method and device, called a variable attenuation plate (VAP), which equalizes chest radiographic appearance and allows for synchronization of manual image windowing with comparison studies, would improve consistency in interpretation.Materials and Methods:Research ethics board approved the prospective cohort pilot study, which included 50 patients in the intensive care unit (ICU) undergoing two serial chest radiographs with a VAP placed on each one of them. The VAP allowed for equalization of density and contrast between the patients’ serial chest radiographs. Three radiologists interpreted all the studies with and without the use of VAP. Kappa and percent agreement was used to calculate agreement between radiologists’ interpretations with and without the plate.Results:Radiologist agreement was substantially higher with the VAP method, as compared to that with the non-VAP method. Kappa values between Radiologists A and B, A and C, and B and C were 46%, 55%, and 51%, respectively, which improved to 73%, 81%, and 66%, respectively, with the use of VAP. Discrepant report impressions (i.e., one radiologist's impression of unchanged versus one or both of the other radiologists stating improved or worsened in their impression) ranged from 24 to 28.6% without the use of VAP and from 10 to 16% with the use of VAP (χ2= 7.454,P< 0.01). Opposing views (i.e., one radiologist's impression of improved and one of the others stating disease progression or vice versa) were reported in 7 (12%) cases in the non-VAP group and 4 (7%) cases in the VAP group (χ2= 0.85,P= 0.54).Conclusion:Numerous factors play a role in image acquisition and image quality, which can contribute to poor consistency and reliability of portable chest radiographic interpretations. Radiologists’ agreement of image interpretation can be improved by use of a novel method consisting of a VAP and associated software and has the potential to improve patient care.

Altered tissue plasminogen activator (tPA) expression may influence the fate of neurons after cerebral ischemia. We determined the changes in tPA and plasminogen activator inhibitor (PAI-I) expression in adult rat brain after transient middle cerebral artery (MCA) occlusion. Immunohistology revealed tPA staining in ipsilateral but not contralateral cortex and striatum 6 h after occlusion. This pattern was maintained at 24 h. Staining data was supported by Western blot data which showed no tPA protein in contralateral cortex at 3 h but abundant protein in ipsilateral cortex which increased further at 6 h and 24 h. In contrast there was prominent PAI-I immunostaining and protein expression in control tissue after MCA occlusion but it diminished progressively at 3, 6 and 24 h in the lesioned cortex.

OBJECTIVES: Two studies reported an increased risk of autistic disorder in children conceived less than 12 months after a previous birth. Our objective was to examine the association between the interpregnancy interval (IPI) and autism spectrum disorder (ASD) in a Canadian cohort. METHODS: Using administrative datasets housed at the Manitoba Centre for Health Policy, we identified pairs of first- and second-born singleton siblings born between 1988 and 2005. Diagnoses of ASD were ascertained by searching physician billing claims, hospital discharge abstracts, education data, and a database containing information on individuals identified for a 2002–2007 ASD surveillance program in Manitoba. Logistic regression models were fit to examine the association between the IPI and ASD in 41,050 second-born siblings where the first-borns did not have ASD, using IPIs of ≥36 months as the reference category and specifying three case groups. Case Group 1 included individuals with at least one ASD code ( n = 490); Case Group 2 included those with two or more ASD codes ( n = 375); and Case Group 3 comprised individuals with a record in the ASD surveillance program database ( n = 141). RESULTS: The adjusted odds ratios (ORs) for IPIs shorter than 12 months ranged from 1.22 (95% CI: 0.91–1.63) for Case Group 1 to 1.72 (95% CI: 0.96–3.06) for Case Group 3. When the case groups were restricted to individuals with more severe ASD, the ORs increased and were significant for Case Groups 1 and 2. CONCLUSION: Our findings also support an association between short IPIs and more severe ASD.

We have previously shown that tissue plasminogen activator (tPA) participates in the neurotoxicity of microglial conditioned medium (MgCM). Killing of hippocampal neurons by MgCM was prevented by both plasminogen activator inhibitor-1 (PAI-1) and anti-tPA antibody. An N-methyl-D-aspartate (NMDA) receptor blocker protected neurons from MgCM, suggesting that this subtype of glutamate receptor is involved. Whereas glutamate receptor-mediated events are important in cerebral ischemia and tPA has previously been shown to enhance excitotoxicity in hippocampus, we hypothesized that tPA would exaggerate oxygen glucose deprivation (OGD) injury in cultures of hippocampal neurons. Dissociated rat hippocampal cells were grown under conditions designed to optimize neuronal growth while minimizing glial replication. At 7--10 days, cultures were subjected to OGD for 2.5 hr. Recombinant human tPA (1,000 IU) was added immediately after OGD. Viability was assessed 24 hr later. Viable, apoptotic, and necrotic cells were classified and quantified based on staining patterns of acridine orange and ethidium bromide under fluorescence microscopy. tPA alone did not alter neuronal integrity. OGD produced significant neuronal death (viability reduced by 45%, P < 0.001). tPA completely protected OGD-exposed cultures. Potential mechanisms of tPA protection were explored. Whereas tPA antibody abolished the protective effect of tPA, its proteolytic inhibitor PAI-1 did not alter the effect. The effect of tPA was tested in separate free radical and excitatory amino acid insults. It did not protect neurons from hydrogen peroxide (1 microM), S-nitro-acetylpenicillamine (10 microM), glutamate (50 microM), or NMDA (10 microM) damage but significantly attenuated injury caused by 250 microM kainate. We conclude that tPA is capable of protecting hippocampal neurons from OGD by a nonproteolytic action. The mechanism of protection was not defined, although attenuation of AMPA/kainate glutamate receptors may play a role.

Selective vulnerability of hippocampal neurons to ischemia is felt to relate to intense glutamatergic input and glutamate receptor expression. Since astrocytes are thought to have a neuroprotective role we speculated that hippocampal astrocyte sensitivity to insult could also contribute to this regional vulnerability. The purpose of the study was to determine if there is a differential sensitivity of cultured hippocampal and cortical astrocytes to oxygen-glucose deprivation (OGD). Hippocampal and cortical astrocytes were grown to confluence at matching cell density. Cultures were exposed to OGD for 2, 4, 6, 8 and 10 h. Progressive reduction in viability occurred in hippocampal astrocytes beginning at 2 h OGD. Reduction in cortical astrocyte viability was not observed until 4 h OGD. Death of hippocampal astrocytes was significantly greater than that of cortical astrocytes at each period of OGD. Based on acid phosphatase activity data the LD(50) for OGD duration in hippocampal astrocytes was 2 h compared to 8 h in cortical astrocytes. Regional differences in sensitivity of astrocytes to OGD implies that this may contribute to regional differences in neuronal vulnerability to ischemia.

Several CNS disorders feature microglial activation. Microglia are known to have both restorative and cytotoxic capabilities. Neuronal apoptosis has been noted after an acute insult such as ischemia. Microglia may participate in this event. We previously showed that conditioned medium (CM) harvested from peritoneal macrophages or from activated microglia triggered apoptosis in rat hippocampal neurons in culture. We wished to characterize the factor responsible for triggering neuronal death. Quiescent microglia produced CM that did not disrupt hippocampal neurons. Lipopolysaccharide-activated microglia produced CM which resulted in neuronal death. This effect was blocked by plasminogen activator inhibitor-1, by tPA STOP, and by co-incubation with tPA antibody. Recombinant human tPA exaggerated the neurotoxic effects of microglial CM, while tPA alone was toxic only at very high concentrations. This in vitro system, which probably excludes any significant impact of microglial free radicals, suggests that microglial tPA may contribute significantly to hippocampal neuronal death.

We recently demonstrated that conditioned medium (CM) from peritoneal macrophages or activated microglia triggers a predominantly apoptotic death in hippocampal neurons in culture. We tested the effects of propentofylline (ppf), an agent that is neuroprotective in focal ischemia and is also associated with reduced microglial antigen expression after insult. Ppf had no impact on the secretion of neurotoxin from microglia. However, ppf significantly attenuated the effects of macrophage and microglial conditioned medium on neurons. Ppf did not attenuate neuronal hypoxic injury but did reverse the exaggeration of hypoxic injury exerted by subsequent addition of macrophage CM. A1 and A2 adenosine receptor inhibitors and an inhibitor of adenosine uptake each mimicked the effect of ppf. Neither ATP nor a deaminase inhibitor blocked the effect of microglial CM. These findings may be relevant to the neuroprotective effects of ppf in ischemia and dementia. J. Neurosci. Res. 56:54–59, 1999. © 1999 Wiley-Liss, Inc.

While written action plans are standard in the treatment and management of asthma, significant variability exists in the content and format among plans. This variability results in inconsistent educational messages that lend themselves to patient confusion and suboptimal health outcomes.To assess the content of Canadian paediatric written action plans for consistency in format, layout, zone-defining symptoms, suggested treatment options and adherence to current Canadian asthma care guidelines.Written action plans were sought from Canadian paediatric hospitals, major teaching hospitals associated with academic centres and three national organizations, for a total of 17 plans. An analysis was performed to assess the similarities and differences among plans.Of all the Canadian paediatric written action plans, 76% were found to consist of three zones and 82% incorporated a traffic light-style design. The plans were divided between symptom-based (59%) and combined symptom- and peak-flow rate approaches (41%). Nominal concordance with the 2012 Canadian Thoracic Society guidelines existed with respect to inhaled corticosteroid and oral corticosteroid therapy. Considerable variability existed among the symptom descriptors that defined each zone. Greater consistency existed among treatment strategies, although the suggested treatment was often difficult to ascertain from the plan templates.Canadian written action plans would be improved by nationally clarifying the symptom descriptors for each zone, adding asthma trigger information to the plans, increasing the emphasis of the common cold as a potential harbinger of worsening asthma symptoms and further incorporating national guideline recommendations.Les plans d’action écrits sont la norme pour traiter et prendre en charge l’asthme, mais leur contenu et leur présentation varient énormément. Cette variabilité s’associe à des messages d’éducation non uniformes qui favorisent la confusion des patients et des résultats de santé sous-optimaux.Évaluer le contenu des plans d’action canadiens écrits en pédiatrie pour vérifier l’uniformité de la présentation, de la disposition, des symptômes définissant la zone, des possibilités thérapeutiques suggérées et de l’adhérence aux lignes directrices canadiennes à jour sur l’asthme.Les chercheurs ont obtenu les plans d’action écrits des hôpitaux pédiatriques canadiens, des grands hôpitaux d’enseignement associés à des centres universitaires et de trois organisations internationales, pour un total de 17 plans. Ils ont effectué une analyse pour évaluer les similarités et les différences entre les plans.Il a été établi que 76 % des plans d’action canadiens écrits en pédiatrie se divisaient en trois zones et que 82 % étaient structurés selon le principe des feux de signalisation. Ils étaient répartis entre une approche fondée sur les symptômes (59 %) et une approche combinant les symptômes et le débit de pointe (41 %). Ils présentaient une concordance nominale avec les lignes directrices de la Société canadienne de thoracologie de 2012 à l’égard des corticoïdes inhalés et des corticoïdes oraux. On constatait une importante variabilité quant aux descripteurs des symptômes qui définissaient chaque zone. Les stratégies thérapeutiques étaient plus uniformes, même si le traitement proposé était souvent difficile à déterminer d’après les modèles du plan.On améliorerait les plans d’action canadiens écrits si, sur la scène nationale, on clarifiait les descripteurs des symptômes dans chaque zone, on y ajoutait l’information sur les déclencheurs de l’asthme, on insistait davantage sur le rhume banal comme prédicteur potentiel d’aggravation des symptômes de l’asthme et on intégrait davantage les recommandations sur les lignes directrices nationales.

When macrophage conditioned medium is added to neurons in vitro, there is a loss of cell membrane integrity, a loss of cell processes, and a large increase in apoptotic neurons. We tested the influence of a potent anti-inflammatory steroid on the interaction between macrophages and neurons. Dexamethasone was applied to macrophages in culture for 24 h while the culture was stimulated with lipopolysaccharide and hypoxia. Conditioned medium was collected after dexamethasone was removed. The dexamethasone pretreated medium was not toxic to hippocampal neurons in contrast to medium from stimulated macrophages not treated with steroid. The dexamethasone effect was concentration dependent. Pretreatment of macrophages with indomethacin and transforming growth factor β had similar but less impressive effects when compared to dexamethasone. The effect of dexamethasone may have been mediated by inhibiting the synthesis or release of neurotoxic macrophage protein(s), as a combination of medium from steroid pretreated macrophages with medium from nontreated macrophages was not neuroprotective. The toxin(s) did not appear to be tumor necrosis factor α or arginase. A role for most neutral proteases was also excluded. We also assessed the consequence of stressing neurons with a mild hypoxic exposure immediately prior to conditioned medium application. Medium from dexamethasone-treated macrophages did not exaggerate hypoxic neuronal injury, unlike medium from non-dexamethasone-treated macrophages. It did not, however, block the exaggerating effect when coapplied in equal volume with medium from nontreated macrophages. Dexamethasone at 100 n M had no impact when applied directly to neurons while they were being exposed to conditioned medium. This in vitro protection by dexamethasone may be relevant to the demonstrated benefit of glucocorticoids in selected brain and spinal cord conditions. Suspicion of a potential link between this in vitro finding and in vivo CNS injury justifies an assessment of more specific agents acting on macrophage protein synthesis or secretion.

There is conflicting evidence regarding the impact of glucocorticoid exposure on hypoxic ischemic brain injury. We examined the effects of timing, duration, and concentration of dexamethasone on neuronal injury following in vitro oxygen glucose deprivation (OGD). Dissociated embryonic rat basal forebrain cells were cultured and either preincubated with dexamethasone for 72 h or continuously exposed prior to, during, and after OGD. Injury was assessed by morphology rating and cholineacetyltransferase (ChAT) activity at Day 13 in vitro, 2 days after OGD. Preincubation with nanomolar concentrations of dexamethasone resulted in a dose-dependent exaggeration of injury. Combined glutamate receptor antagonist application negated this deleterious effect, suggesting that dexamethasone may increase glutamate release, decrease uptake, or upregulate glutamate receptor expression. Continuous application of a narrow concentration range of dexamethasone (100 n M and 1 μ M ) prior to, during, and after insult protected neurons. Dose, timing, and duration of glucocorticoid administration may each be critical variables influencing outcome of hypoxic ischemic brain insult.

Glucose depletion increased sensitivity to hypoxic insult in basal forebrain forebrain cultures in a dose-dependent manner as indicated by reduction of choline acetyltransferase (ChAT) activity, increased lactate dehydrogenase (LDH) release and disrupted morphology. The glutamate receptor antagonists 2-amino-5-phosphonovaleric acid (APV) and 6-cyano-2,3-nitroquinoxoline (CNQX) limited the degree of injury in combination and individually. The nitric oxide synthase (NOS) inhibitor N-nitro-L-arginine (NNLA) also either completely protected against mild injury or attenuated severe injury.

Objective:We sought to determine whether inhaled 3% hypertonic saline (HS) reduces admission to hospital in ambulatory children with moderately severe viral bronchiolitis. Secondary objectives compared changes in respiratory scores before and after treatment and assessed the need for unscheduled medical intervention within 7 days.Methods:Children under the age of 2 years presenting with moderately severe viral bronchiolitis to the emergency department of 4 general hospitals from November 2008 to March 2009 were randomly assigned to receive 3 consecutive 4-mL doses of nebulized 3% HS (treatment group) or 0.9% normal saline (NS; control group) in a double blind fashion, each coadministered with 1 mg salbutamol. Outcome measures included the difference in hospital admission rate and changes in respiratory distress scores.Results:A total of 81 children (mean age 8.9 mo, range 0.7–22 mo) were assessed over 88 visits on an intention-to-treat basis. No statistically significant differences were found between treatment groups. Children in the HS group had a nonsignificant trend toward greater improvement compared with NS controls with a same-day admission rate of 18% (95% confidence interval [CI] 9%–32%) versus 27% (95% CI 16%–42%), respectively. Respiratory Assessment Change Scores (RACS) favoured the HS group over NS controls (mean RACS 4.7 [95% CI 3.6–5.8] v. 3.7 [95% CI 2.5–4.9], respectively), although the CIs overlap and these differences were not statistically significant.Conclusion:The short-term use of nebulized 3% HS did not result in any statistically significant benefits, although a nonsignificant trend toward a decrease in admission rate and improvement in respiratory distress was found. A larger study would be required to determine whether these trends arise from a clinically relevant treatment effect.

Chorioamnionitis, a perinatal infection of the fetal membranes, and maternal fever, which often accompanies infection are both risk factors for cerebral palsy (CP). Inflammation is a typical reaction to infection. Thus the aim of this study was to determine if hyperthermia alters newborn rat brain inflammatory response and oxidant stress after a maternal rat lipopolysaccaharide (LPS) injection. Since chorioamnionitis can predispose the fetus to perinatal hypoxia, we also explored the interaction with postnatal hypoxia. Exposure of newborn pups to brief hypoxia alone significantly increased brain tumor necrosis factor-alpha (TNF-alpha) and slightly increased levels of nitrite/nitrate. When maternal LPS was combined with postnatal hypoxia, the levels of TNF-alpha in were further increased when compared with hypoxia alone. Exposure of newborn pups to hyperthermia at 39 degrees C following maternal LPS and hypoxia caused yet more significant increases in brain TNF-alpha, nitrite/nitrate, and MDA/4-HAD compared to that under normal temperature conditions. This study supports the hypothesis that fever is a significant modifier of brain inflammatory response in developing brain particularly in a setting of hypoxia.

Objective:Variability in image interpretation has been attributed to differences in the interpreters’ knowledge base, experience level, and access to the clinical scenario. Picture archiving and communication system (PACS) has allowed the user to manipulate the images while developing their impression of the radiograph. The aim of this study was to determine the agreement of chest radiograph (CXR) impressions among radiologists and neonatologists and help determine the effect of image manipulation with PACS on report impression.Materials and Methods:Prospective cohort study included 60 patients from the Neonatal Intensive Care Unit undergoing CXRs. Three radiologists and three neonatologists reviewed two consecutive frontal CXRs of each patient. Each physician was allowed manipulation of images as needed to provide a decision of “improved,” “unchanged,” or “disease progression” lung disease for each patient. Each physician repeated the process once more; this time, they were not allowed to individually manipulate the images, but an independent radiologist presets the image brightness and contrast to best optimize the CXR appearance. Percent agreement and opposing reporting views were calculated between all six physicians for each of the two methods (allowing and not allowing image manipulation).Results:One hundred percent agreement in image impression between all six observers was only seen in 5% of cases when allowing image manipulation; 100% agreement was seen in 13% of the cases when there was no manipulation of the images.Conclusion:Agreement in CXR interpretation is poor; the ability to manipulate the images on PACS results in a decrease in agreement in the interpretation of these studies. New methods to standardize image appearance and allow improved comparison with previous studies should be sought to improve clinician agreement in interpretation consistency and advance patient care.

Background In Canada, there are many formal public health programs under development that aim to prevent injuries in the early years (e.g. 0–6). There are paradoxically no population-based studies that have examined patterns of injury by developmental stage among these young children. This represents a gap in the Canadian biomedical literature. The current population-based analysis explores external causes and consequences of injuries experienced by young children who present to the emergency department for assessment and treatment. This provides objective evidence about prevention priorities to be considered in anticipatory counseling and public health planning. Methods Four complete years of data (1999–2002; n = 5876 cases) were reviewed from the Kingston sites of the Canadian Hospitals Injury Reporting and Prevention Program (CHIRPP), an ongoing injury surveillance initiative. Epidemiological analyses were used to characterize injury patterns within and across age groups (0–6 years) that corresponded to normative developmental stages. Results The average annual rate of emergency department-attended childhood injury was 107 per 1000 (95% CI 91–123), with boys experiencing higher annual rates of injury than girls (122 vs. 91 per 1000; p < 0.05). External causes of injury changed substantially by developmental stage. This lead to the identification of four prevention priorities surrounding 1) the optimization of supervision; 2) limiting access to hazards; 3) protection from heights; and 4) anticipation of risks. Conclusion This population-based injury surveillance analysis provides a strong evidence-base to inform and enhance anticipatory counseling and other public health efforts aimed at the prevention of childhood injury during the early years.

We compared high volume (20 ml/kg) with standard volume (15 ml/kg) packed red blood cell (PRBC) transfusions in a randomized trial. Ten high volume babies received a mean of 2.8 transfusions, while 10 standard volume babies received a mean of 3.4 (p=0.58). No adverse events were attributed to the use of the high volume transfusions.Higher transfusion volumes appear to be well tolerated. The data can be used in the planning of larger controlled trials in VLBW infants.

Afull-term male infant was admitted to the neonatal intensive care unit 30 h after birth for hypoglycemia. A review of the history revealed that the mother was a primagravid 30-year-old woman with obesity (body mass index 35 kg/m 2 ) who had a normal glucose tolerance test at 28 weeks’ gestation. The baby was born by spontaneous vaginal delivery after induction of labour at 41 weeks’ gestation. Apgar scores were 8 at 1 min and 9 at 5 min. Cord blood gases were normal. Birth weight was 2900 g. The mother and newborn were transferred to the postnatal ward. Newborn examination was normal. During the first 24 h, the baby had several breastfeeding attempts with good latch and sustained sucking. The baby had two wet diapers, one small meconium stool and weight was 2800 g at 24 h. At 30 h of life, he had a temperature of 36.3°C and was noted to be jittery, with exaggerated startle, and subsequently experienced a cyanotic episode. A bedside glucose measurement was low. A simultaneous serum glucose measurement was 0.9 mmol/L. The baby was admitted to the neonatal intensive care unit and treated with intravenous dextrose 10% 2 mL/kg slow bolus and 6 mg/kg/min glucose maintenance. Infection was ruled out. There were three additional episodes of low glucose (1.8 mmol/L, 1.9 mmol/L and 2.0 mmol/L). A critical sample obtained during the third hypoglycemic event indicated hyperinsulinism. Hypoglycemia and hyperinsulinism resolved four days later, and he was discharged home feeding well with a normal neurological examination. LEARNING PoINTS

UNLABELLED We compared high volume (20 ml/kg) with standard volume (15 ml/kg) packed red blood cell (PRBC) transfusions in a randomized trial. Ten high volume babies received a mean of 2.8 transfusions, while 10 standard volume babies received a mean of 3.4 (p=0.58). No adverse events were attributed to the use of the high volume transfusions. CONCLUSION Higher transfusion volumes appear to be well tolerated. The data can be used in the planning of larger controlled trials in VLBW infants.

The effect of hypoxia on the neurotransmitter phenotype of rat forebrain cholinergic neurons was analyzed using a dissociated fetal rat culture system. The aims of this study were to examine the feasibility of using choline acetyltransferase (ChAT) activity as a measure of cell injury and/or recovery, to measure the time course of hypoxic effects on ChAT activity, to determine how changes in ChAT activity at 48 h post-injury relate to microscopic changes and LDH release into the medium during that time, and finally to explore the possible mechanisms of hypoxic injury in this model. At exposure to 0.5–1.5% O2 there was a time-dependent decrease in ChAT activity when cells were harvested 48 h after exposure. Forty-eight hours after 8–9 h hypoxic exposure ChAT activity was 50–60% that of controls without any alteration in morphology of neurons. An 8 h exposure to hypoxic conditions caused a post-exposure time-dependent decrease in ChAT activity to 20% of control level at 72 h. Thereafter there was spontaneous recovery of phenotype to 60% of control which remained stable between 5 and 7 days post-exposure. Loss of neurotransmitter phenotype was not well correlated with other measures of cytotoxicity including morphological changes and LDH release. The loss of phenotype observed with hypoxia was mimicked by glutamate and kainate but not by NMDA. Consistent with these observations, neither APV nor AP3 significantly altered the effect of hypoxia on forebrain cholinergic neurons, while the addition of APV and CNQX in combination protected the phenotype of these neurons only if there was 50% or less loss of phenotype following hypoxia. However both APV and CNQX independantly provided significant protection from hypoxia in mixed cortical-basal forebrain cultures supporting a role for afferent input from cortex in both NMDA and non-NMDA receptor mediated injury.

Objective To investigate the use of nebulized 3% hypertonic saline (HS) for treating viral bronchiolitis in moderately ill hospitalized infants by a prospective, randomized, double-blinded, controlled, multicenter trial. Study design A total of 96 infants (mean age, 4.7 months; range, 0.3 to 18 months) admitted to the hospital for treatment of viral bronchiolitis were recruited from 3 regional pediatric centers over 3 bronchiolitis seasons (December 2003 to May 2006). Patients were randomized to receive, in a double-blind fashion, repeated doses of nebulized 3% HS (treatment group) or 0.9% normal saline (NS; control group), in addition to routine therapy ordered by the attending physician. The principal outcome measure was hospital length of stay (LOS). Results On an intention-to-treat basis, the infants in the HS group had a clinically relevant 26% reduction in LOS to 2.6 ± 1.9 days, compared with 3.5 ± 2.9 days in the NS group ( P = .05). The treatment was well tolerated, with no adverse effects attributable to the use of HS. Conclusions The use of nebulized 3% HS is a safe, inexpensive, and effective treatment for infants hospitalized with moderately severe viral bronchiolitis.