Understanding low acuity emergency department presentations in infancy: A cohort study.

OBJECTIVE: Low acuity presentations (LAPs) contribute to large numbers of ED presentations and carry numerous consequences. The present study sought to improve the understanding of regional infant LAPs by analysing temporal patterns of presentation, discharge diagnoses and potential predictive factors. METHODS: This retrospective observational study examined ED presentations among children less than 12 months old (infants) to the Royal Prince Alfred Hospital between 2017 and 2019. Descriptive statistics were used to identify temporal patterns of presentation and common discharge diagnoses among LAPs. Multivariable logistic regression was used to determine the association between early life, demographic and perinatal factors and low acuity presenters. RESULTS: Of 6881 infant ED presentations, 19.8% were LAPs, occurring disproportionately on weekdays (82.2%) and during hours of 08.00-17.00 (69.9%). Respiratory tract infections and gastrointestinal complaints were most common overall, though non-allergic rash, feeding difficulties, eczema and developmental concerns contributed substantially among LAPs. Socio-economic status (SES) (odds ratio [OR] 1.71), overseas maternal nationality (OR 1.25) and Medicare ineligible maternal financial class (OR 0.49) were associated with low acuity presenters. Low appearance, pulse, grimace, activity and respiration score (OR 3.53), low SES (OR 3.26), complicated delivery (OR 1.64), maternal multiparity (OR 0.50), maternal partner presence (OR 0.40) and obstetric complications (OR 0.37) were associated with repeat, multi-low acuity presenters (multi-LAPs). CONCLUSION: A substantial minority of infant ED presentations are LAPs. Targeted interventions may benefit from focusing on families with a background of socioeconomic disadvantage, social isolation, cultural and linguistic diversity and perinatal complications, with a view to strengthening engagement with community-based services among these groups.

Diagnosing X-Linked Adrenoleukodystrophy after Implementation of Newborn Screening: A Reference Laboratory Perspective.

Adrenoleukodystrophy (ALD) is caused by pathogenic variants in the ABCD1 gene, encoding for the adrenoleukodystrophy protein (ALDP), leading to defective peroxisomal ß-oxidation of very long-chain and branched-chain fatty acids (VLCFA). ALD manifests in both sexes with a spectrum of phenotypes, but approximately 35% of affected males develop childhood cerebral adrenoleukodystrophy (CCALD), which is lethal without hematopoietic stem cell transplant performed before symptoms start. Hence, ALD was added to the Recommended Uniform Screening Panel after the successful implementation in New York State (2013-2016). To date, thirty-five states have implemented newborn screening (NBS) for ALD, and a few programs have reported on the successes and challenges experienced. However, the overall impact of NBS on early detection of ALD has yet to be fully determined. Here, we conducted a retrospective analysis of VLCFA testing performed by our reference laboratory (ARUP Laboratories, Salt Lake City, UT, USA) over 10 years. Rate of detection, age at diagnosis, and male-to-female ratio were evaluated in patients with abnormal results before and after NBS implementation. After NBS inclusion, a significant increase in abnormal results was observed (471/6930, 6.8% vs. 384/11,670, 3.3%; p < 0.0001). Patients with ALDP deficiency identified via NBS were significantly younger (median age: 30 days vs. 21 years; p < 0.0001), and males and females were equally represented. ALD inclusion in NBS programs has increased pre-symptomatic detection of this disease, which is critical in preventing adrenal crisis as well as the severe cerebral form.

Distinct Places to Address Intimate Partner Violence.

The concept of place can be used to address intimate partner violence (IPV). Place, to geographers, is a concept that helps explain how human experiences shape a sense of meaning surrounding locations. Using a grounded theory approach and qualitative interviews with service providers, we present a case study exploring how Brantford social service agencies apply placemaking strategies and take advantage of the elements of place to reduce the harm associated with IPV. Six themes arose in the interviews. Home, the women's shelter, courts, and schools were found to represent unique areas where placemaking strategies help to reduce harm. Hair salons emerged as a unique place to reach victims, whereas prison was a place that encouraged offenders to make changes. These themes show the concept of place has the potential to add insights into how IPV can be reduced and the traumas facing victims addressed.

Role of technology in improving knowledge and confidence in asthma management in school staff.

Objective: To investigate the effectiveness of technology enabled learning in improving asthma first aid knowledge and self-confidence in providing asthma first aid to children in staff within a school setting. Study Design: A prospective randomized parallel study using a pre and post test design was conducted across Metropolitan schools of New South Wales (NSW), Australia. School staff in selected schools were randomly assigned to receive first aid asthma management training via a self-directed multimedia eBook learning resource or standard face-to-face training. Staff completed a 14 item validated Asthma First Aid Knowledge Questionnaire and a 4 item, 10-point Likert-scale asthma management self-confidence questionnaire immediately pre and post training. Results: 148 school staff from 46 schools were recruited with a total of 59 (78%) staff completing the eBook training and 62 (86%) completing face-to-face training. The mean asthma first aid knowledge score and self-confidence score in managing asthma increased significantly (p < 0.0001) in the eBook training group post training. There was no significant difference in the increase in the mean scores post training between the eBook and face-to-face training groups (p = 0.11). Conclusion: Asthma management knowledge and self-confidence increased in school staff following the eBook training. In school settings where human resources for health education are limited, technology enabled learning may be substituted to provide a self-directed approach to asthma first aid management training.

Correction to: International experience in the development of patient-derived xenograft models of diffuse intrinsic pontine glioma.

There are two errors and one omission in the original article. Author Gottardo's correct name is Nicholas G. Gottardo, author Hulleman's correct affiliation is no. 3 (VUMC, Amsterdam), and the Acknowledgements should include the following sentence: "We would like to thank Dr Angel Montero Carcaboso (Hospital Sant Joan de Deu, Barcelona, Spain) for generously supplying the HSJD-DIPG007 cells."

International experience in the development of patient-derived xenograft models of diffuse intrinsic pontine glioma.

PURPOSE: Diffuse intrinsic pontine glioma is the most aggressive form of high grade glioma in children with no effective therapies. There have been no improvements in survival in part due poor understanding of underlying biology, and lack of representative in vitro and in vivo models. Recently, it has been found feasible to use both biopsy and autopsy tumors to generate cultures and xenograft models. METHODS: To further model development, we evaluated the collective international experience from 8 collaborating centers to develop DIPG pre-clinical models from patient-derived autopsies and biopsies. Univariate and multivariate analysis was performed to determine key factors associated with the success of in vitro and in vivo PDX development. RESULTS: In vitro cultures were successfully established from 57% of samples (84.2% of biopsies and 38.2% of autopsies). Samples transferred in DMEM media were more likely to establish successful culture than those transported in Hibernate A. In vitro cultures were more successful from biopsies (84.2%) compared with autopsies (38.2%) and as monolayer on laminin-coated plates than as neurospheres. Primary cultures successfully established from autopsy samples were more likely to engraft in animal models than cultures established from biopsies (86.7% vs. 47.4%). Collectively, tumor engraftment was more successful when DIPG samples were directly implanted in mice (68%), rather than after culturing (40.7%). CONCLUSION: This multi-center study provides valuable information on the success rate of establishing patient-derived pre-clinical models of DIPG. The results can lead to further optimization of DIPG model development and ultimately assist in the investigation of new therapies for this aggressive pediatric brain tumor.

High prevalence of developmental concern amongst infants at 12 months following hospitalised parechovirus infection.

AIM: The human parechovirus (HPeV) is an increasingly recognised cause of sepsis and central nervous system infection in young infants for which there are limited long-term outcome data. We aimed to assess neurodevelopmental outcome and quality of life in infants following hospitalised HPeV infection. METHODS: This cohort study was a 12-month follow-up of infants who were hospitalised with confirmed HPeV infection at the Sydney Children's Hospitals Network during an outbreak in Sydney in 2013. Telephone interviews were conducted with parents/guardians. We administered standardised questionnaires, including: Ages and Stages Questionnaire (ASQ), Liverpool Outcome Score-follow-up, Pediatric Quality of Life Inventory(PedsQL) Infant scales and Short-Form health survey (SF-12). RESULTS: We followed up 46 of 79 infants (58%) aged between 12 and 16 months who had been hospitalised with HPeV infection; 19% showed significant concern in developmental attainment (ASQ3 score <2 standard deviation below population mean), and 50% showed some concern (<1 standard deviation below mean). ASQ3 developmental outcome was associated with the presence of neurodevelopmental sequelae (lower total Liverpool Outcome Score) and poorer health-related quality of life (HRQOL) in physical functioning (PedsQL physical component score), but not overall HRQOL (total PedsQL score) or parental HRQOL (SF-12 scores). No significant associations were identified between clinical or laboratory features during acute hospitalisation and adverse outcome on ASQ3. CONCLUSIONS: A high proportion of infants show developmental concern at 12-month follow-up post-hospitalisation with HPeV infection. Clinical features during hospitalisation were not associated with adverse outcomes at 12 months. These results suggest that careful follow-up of young infants hospitalised with HPeV disease may be warranted.

Sepsis-like disease in infants due to human parechovirus type 3 during an outbreak in Australia.

BACKGROUND: Infections with human parechoviruses (HPeVs) are associated with a wide range of clinical presentations in children, ranging from mild or asymptomatic infections to severe sepsis-like presentations or meningoencephalitis. METHODS: We reviewed medical records of infants admitted to 5 hospitals in New South Wales, Australia, during an outbreak of HPeV-3 infection. Data were collected on clinical presentation, laboratory markers, and outcome of infants with HPeV infection confirmed by reverse transcription polymerase chain reaction. RESULTS: We identified 118 infected infants. Most presented with an acute sepsis-like syndrome with high fever, tachycardia, poor perfusion, and severe irritability. Other common features were erythrodermic rash, abdominal distension, edema, and hepatitis. The age range of infants was 4 days to 9.5 months; 75% were <2 months old, including all but 1 of the 30 infants (25%) admitted to intensive care units (ICUs), who as a group, were significantly younger than infants not admitted to ICUs. Only 4% of evaluable cerebrospinal fluid samples had pleocytosis, but HPeV was detected in 95%. Brain magnetic resonance imaging on a small number of children demonstrated white matter changes and diffusion restriction. Sequencing of the VP1 gene confirmed HPeV-3 in all samples tested. All children recovered without ongoing complications at last follow-up. CONCLUSIONS: We report the largest series of HPeV-3 infection in infants, and the first outbreak in Australia. Infants presented with a severe sepsis-like syndrome with a high rate of ICU admissions, but all recovered from the acute infection without complications. Long-term sequelae are unknown.

Safety conferencing: toward a coordinated and inclusive response to safeguard women and children.

To reach out to women from different backgrounds, the battered women's movement needs to place women and their informal supports at the center of a coordinated response. This article shares the views of domestic violence survivors, staff, and supporters on how to create such a coordinated and inclusive response, lays a conceptual foundation for a decision-making forum called safety conferencing, and sets forth guidance for its practice. Safety conferencing is proposed as one means of building the individual and collective strength to reshape connections, make sound choices, and promote the safety of women and children from diverse cultures.

autoregulatory role of endothelium-derived nitric oxide (NO) on Lipopolysaccharide-induced vascular inducible NO synthase expression and function.

Nitric oxide (NO) produced by inducible nitric oxide synthase (iNOS) is responsible for sepsis-induced hypotension and plays a major contributory role in the ensuing multiorgan failure. The present study aimed to elucidate the role of endothelial NO in lipopolysaccharide (LPS)-induced iNOS expression, in isolated rat aortic rings. Exposure to LPS (1 mug/ml, 5 h) resulted in a reversal of phenylephrine precontracted tone in aortic rings (70.7 +/- 3.2%). This relaxation was associated with iNOS expression and NF-kappaB activation. Positive immunoreactivity for iNOS protein was localized in medial and adventitial layers of LPS-treated aortic rings. Removal of the endothelium rendered aortic rings resistant to LPS-induced relaxation (8.9 +/- 4.5%). Western blotting of these rings demonstrated an absence of iNOS expression. However, treatment of endothelium-denuded rings with the NO donor, diethylamine-NONOate (0.1 mum), restored LPS-induced relaxation (61.6 +/- 6.6%) and iNOS expression to levels comparable with arteries with intact endothelium. Blockade of endothelial NOS (eNOS) activation using geldanamycin and radicicol, inhibitors of heat shock protein 90, in endothelium-intact arteries suppressed both LPS-induced relaxation and LPS-induced iNOS expression (9.0 +/- 8.0% and 2.0 +/- 6.2%, respectively). Moreover, LPS treatment (12.5 mg/kg, intravenous, 15 h) of wild-type mice resulted in profound elevation of plasma [NO(x)] measurements that were reduced by approximately 50% in eNOS knock-out animals. Furthermore, LPS-induced changes in vascular reactivity and iNOS expression evident in wild-type tissues were profoundly suppressed in tissues taken from eNOS knockout animals. Together, these data suggest that eNOS-derived NO, in part via activation of NF-kappaB, regulates iNOS-induction by LPS. This study provides the first demonstration of a proinflammatory role of vascular eNOS in sepsis.