Publications by authors named "Dominic Fitzgerald"

180 Publications

Sudden Unexpected Death in Infancy [SUDI]: What the clinician, pathologist, coroner and researchers want to know.

Paediatr Respir Rev 2021 Aug 13. Epub 2021 Aug 13.

Department of Respiratory Medicine, The Children's Hospital at Westmead, Sydney, NSW 2145, Australia; Discipline of Child & Adolescent Health, Sydney Medical School, Faculty of Health Sciences, University of Sydney, Westmead, NSW 2145, Australia.

The loss of an apparently healthy infant is confronting for any family, puzzling for a clinician and challenging for the pathologist charged with the task of demonstrating a cause for death. The term "cot death" evolved to "sudden infant death syndrome" [SIDS] and now "sudden unexpected death in infancy [SUDI]" as the epidemiology and pathology of infant death changed. Community interventions were successful in changing sleep practices for young babies. The current research focus is on understanding genetic predispositions to unexpected death in early childhood. Whilst much has been achieved in reducing the infant mortality rate from SUDI by between 50%, and 80% in some countries, over the last 30 years, there remain challenges for improving rates of accurate diagnosis and reaching out to more vulnerable families with clearly modifiable risk factors for SUDI. These challenges directly involve the clinician through taking a systematic and detailed history and better standardised death scene evaluations with specifically accredited assessors. Better knowledge regarding circumstances of SUDI cases will help Coroners and researchers provide answers for grieving families now, and in the future contribute to further reductions in the rate of SUDI in communities across the world.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.prrv.2021.08.002DOI Listing
August 2021

Somatic, psychological and economic benefits of regular physical activity beginning in childhood.

J Paediatr Child Health 2022 Jan 6. Epub 2022 Jan 6.

Department of Respiratory Medicine, The Children's Hospital at Westmead, Sydney, New South Wales, Australia.

Physical activity is a natural part of a healthy life-style, which should be nurtured from early childhood. Regular physical activity mitigates against the global problems of overweight and obesity, hypertension, anxiety and depression. It lowers the morbidity and mortality from cardiovascular disease and provides hope for sustainable economics to support an ageing population into their retirement. This is preventative health economics that can be achieved with integrated support from families, communities, health-care professionals and governments at all levels. At present, children lack the support of those responsible for them at a societal level to adequately protect them from the physical and emotional consequences of reduced physical activity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jpc.15879DOI Listing
January 2022

Whole-genome analysis of Nigerian patients with breast cancer reveals ethnic-driven somatic evolution and distinct genomic subtypes.

Nat Commun 2021 11 26;12(1):6946. Epub 2021 Nov 26.

Center for Clinical Cancer Genetics and Global Health, Department of Medicine, The University of Chicago, Chicago, IL, 60637, USA.

Black women across the African diaspora experience more aggressive breast cancer with higher mortality rates than white women of European ancestry. Although inter-ethnic germline variation is known, differential somatic evolution has not been investigated in detail. Analysis of deep whole genomes of 97 breast cancers, with RNA-seq in a subset, from women in Nigeria in comparison with The Cancer Genome Atlas (n = 76) reveal a higher rate of genomic instability and increased intra-tumoral heterogeneity as well as a unique genomic subtype defined by early clonal GATA3 mutations with a 10.5-year younger age at diagnosis. We also find non-coding mutations in bona fide drivers (ZNF217 and SYPL1) and a previously unreported INDEL signature strongly associated with African ancestry proportion, underscoring the need to expand inclusion of diverse populations in biomedical research. Finally, we demonstrate that characterizing tumors for homologous recombination deficiency has significant clinical relevance in stratifying patients for potentially life-saving therapies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-021-27079-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8626467PMC
November 2021

Gaming the future.

Paediatr Respir Rev 2021 Oct 19. Epub 2021 Oct 19.

Discipline of Child & Adolescent Health, Faculty of Medicine & Health Sciences, University of Sydney, Camperdown, NSW 2050, Australia; Department of Respiratory Medicine, The Children's Hospital at Westmead, NSW 2145, Australia. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.prrv.2021.10.001DOI Listing
October 2021

Paediatric pneumonia: deriving a model to identify severe disease.

Arch Dis Child 2021 Nov 10. Epub 2021 Nov 10.

Respiratory Medicine, Children's Hospital at Westmead, Sydney, New South Wales, Australia.

Background: Community-acquired pneumonia (CAP) is a leading cause of childhood hospitalisation. Limited data exist on factors predicting severe disease with no paediatric-specific predictive tools.

Methods: Retrospective cohort (2011-2016) of hospitalised CAP cases. We analysed clinical variables collected at hospital presentation against outcomes. Stratified outcomes were mild (hospitalised), moderate (invasive drainage procedure, intensive care) or severe (mechanical ventilation, vasopressors, death).

Results: We report 3330 CAP cases, median age 2.0 years (IQR 1-5 years), with 2950 (88.5%) mild, 305 (9.2%) moderate and 75 (2.3%) severe outcomes. Moderate-severe outcomes were associated with hypoxia (SaO <90%; OR 6.6, 95% CI 5.1 to 8.5), increased work of breathing (severe vs normal OR 5.8, 95% CI 4.2 to 8.0), comorbidities (4+ comorbidities vs nil; OR 8.8, 95% CI 5.5 to 14) and being indigenous (OR 4.7, 95% CI 2.6 to 8.4). Febrile children were less likely than afebrile children to have moderate-severe outcomes (OR 0.57 95% CI 0.44 to 0.74). The full model receiver operating characteristic (ROC) area under the curve (AUC) was 0.78. Sensitivity analyses showed similar results with clinical or radiological CAP definitions. We derived a clinical tool to stratify low, intermediate or high likelihood of severe disease (AUC 0.72). High scores (≥5) had nearly eight times higher odds of moderate-severe disease than those with a low (≤1) score (OR 7.7 95% CI 5.6 to 10.5).

Conclusions: A clinical risk prediction tool is needed for child CAP. We have identified risk factors and derived a simple clinical tool using clinical variables at hospital presentation to determine a child's risk of invasive or intensive care treatment with an ROC AUC comparable with adult pneumonia tools.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/archdischild-2021-322665DOI Listing
November 2021

Regional oxygenation, perfusion and body and/or head position: Are preterm infants adversely impacted? A systematic review.

Paediatr Respir Rev 2021 Sep 23. Epub 2021 Sep 23.

Westmead Hospital, Department of Neonatology, Westmead, Australia; The University of Sydney, Sydney, Australia.

This review addresses regional oxygenation and perfusion changes for preterm infants and changes with body position, with or without head rotation. Future directions for improving neurodevelopmental and clinical outcomes are suggested. The MEDLINE, Embase and Scopus databases were searched up to July 2021. Fifteen out of 470 studies met the inclusion criteria. All were prospective, observational studies with a moderate risk of bias. Significant variation was found for the baseline characteristics of the cohort, postnatal ages, and respiratory support status at the time of monitoring. When placed in a non-supine position, preterm infants showed a transient reduction in cardiac output and stroke volume without changes to heart rate or blood pressure. No studies reported on long-term neurodevelopmental outcomes. Overall, side lying or prone position does not appear to adversely affect regional, and specifically cerebral, oxygenation or cerebral perfusion. The effect of head rotation on regional oxygenation and perfusion remains unclear.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.prrv.2021.09.004DOI Listing
September 2021

Medicine and law: The odd couple no more?

Paediatr Respir Rev 2021 Aug 14. Epub 2021 Aug 14.

Paediatric Respiratory and Sleep Physician, Department of Respiratory Medicine, The Children's Hospital at Westmead, Locked Bag 4001, Westmead, New South Wales 2145, Australia. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.prrv.2021.08.003DOI Listing
August 2021

Update in management of paediatric primary spontaneous pneumothorax.

Paediatr Respir Rev 2021 Aug 10. Epub 2021 Aug 10.

Department of Respiratory Medicine, The Children's Hospital at Westmead, Westmead, New South Wales, Australia; Discipline of Paediatrics and Child Health, University of Sydney, Sydney, New South Wales, Australia. Electronic address:

Paediatric spontaneous pneumothorax (PSP) management continues to lack paediatric-specific guideline recommendations. There have been increasing reports of paediatric retrospective case studies supplemented by important well designed RCT (predominantly) adult studies. Taken together, these suggest that conservative management may have an increasing role to play in the management of PSP and that aspiration may have limited utility as a first line intervention. Our local experience, as part of a multicentre retrospective analysis and subsequent audit of management since, corroborates recent published data: it highlights an increasing trend towards conservative management in spontaneous pneumothorax with similar rates of recurrence, compared to intervention, and low use of aspiration with similarly low success rates. We have therefore updated our local practice guidelines and share these with readers. Specifically, we have removed aspiration in the management of primary spontaneous pneumothorax and reserved intervention for children who are clinically unstable or show evidence of increasing air leak irrespective of pneumothorax size. Whilst the success of this change in clinical practice will need to be reviewed in the next 5-10 years, the overall low incidence of the condition, demands a multicentre, and probably multinational, collaborative approach to allow the best chance of obtaining definitive evidence to guide clinical paediatric management.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.prrv.2021.08.001DOI Listing
August 2021

The accumulating consequences of COVID-19 in children.

Paediatr Respir Rev 2021 09 29;39:1-2. Epub 2021 Jul 29.

Department of Respiratory Medicine, The Children's Hospital at Westmead, Sydney, New South Wales 2145, Australia; Discipline of Child & Adolescent Health, Sydney Medical School, Faculty of Health Sciences, University of Sydney, Camperdown, New South Wales 2050, Australia. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.prrv.2021.07.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8319046PMC
September 2021

Blended and e-learning in pediatric education: harnessing lessons learned from the COVID-19 pandemic.

Eur J Pediatr 2021 Jul 29. Epub 2021 Jul 29.

Children's Hospital of Richmond at Virginia Commonwealth University, Richmond, VA, 23298, USA.

Face-to-face education as the traditional basis for medical education was disrupted by the COVID-19 pandemic as learners and educators were moved online with little time for preparation. Fortunately, as online learning has grown, together with medical education shifting to problem-based and team-centered learning over the last three decades, existing resources have been adapted and improved upon to meet the challenges. Effective blended learning has resulted in innovative synchronous and asynchronous learning platforms. Clearly, to do this well requires time, effort, and adjustment from clinicians, educators, and learners, but it should result in an engaging change in teaching practice. Its success will rely on an evaluation of learning outcomes, educator and learner satisfaction, and long-term retention of knowledge. It will be important to maintain ongoing assessment of all aspects of the medical education process, including how to best teach and assess theory, physiology, pathology, history-taking, physical examination, and clinical management.Conclusion: The COVID-19 pandemic triggered emergency transitional processes for teaching and assessment in medical education which built upon existing innovations in teaching medicine with the use of technology. These strategies will continue to evolve so as to provide the basis for an enduring hybrid teaching model involving blended and e-learning in medical education.. What is Known: • Most pediatricians provide clinical teaching to medical students and residents, but few have had formal training in online educational approaches and techniques. • Being able to adapt to new and innovative integrated teaching methods is of key importance when becoming a competent teacher. What is New: • This review presents an up-to-date summary of best practice in blended and e-learning and how it may be optimally delivered. • Knowledge of the principles of e-learning, and how people learn more generally, helps pediatricians shape their clinical teaching and facilitates better interaction with medical students and residents.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00431-021-04149-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8318775PMC
July 2021

What we have learnt about trauma, loss and grief for children in response to COVID-19.

Paediatr Respir Rev 2021 Sep 31;39:16-21. Epub 2021 May 31.

Discipline of Child and Adolescent Health, Sydney Medical School, Faculty of Health Sciences, University of Sydney, NSW 2006, Australia; Department of Infectious Diseases, The Children's Hospital at Westmead, Westmead, NSW 2145, Australia.

The disruption of daily life resulting from COVID-19 and its precautions has taken an enormous emotional toll on children and families. The consequences of disrupted schooling, changed social interactions and altered family dynamics has had some unanticipated positives such as improved on-line educational upskilling and personal resilience. However, the potential longer term implications for educational outcomes, economic impacts of job loss and prolonged financial insecurity, physical wellbeing and mental health remain unclear. The potential for post-traumatic stress disorders from what is experienced by children with imposed isolation from friends and extended family, domestic violence and death of relatives remains concerning. Confronting images and stories relayed through social media and the popular press will challenge children's views of safety, security, trust and potentially rob them of much of the innocence of youth. In an overwhelming global response to the "adult" problems of the COVID-19 pandemic, this article reflects on the consequences of trauma, loss and grief through the perspective of children and how they may alter their view of the world.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.prrv.2021.05.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8437675PMC
September 2021

Chronic sleep deprivation in teenagers: Practical ways to help.

Paediatr Respir Rev 2021 Dec 12;40:73-79. Epub 2021 May 12.

Department of Respiratory Medicine, The Children's Hospital at Westmead, Locked Bag 4001, Westmead, NSW 2145, Australia; Speciality of Child & Adolescent Health, Sydney Medical School, Faculty of Health Sciences, University of Sydney, Camperdown, NSW 2050, Australia.

Teenagers of today sleep less than previous generations. Technology is largely to blame for keeping people perpetually connected in the digital world which is in turn driven by changing social demands for immediacy as a form of intimacy. The consequences for teenagers are later bed times, reduced total sleep time and a degree of sleep catch up on weekends. This is termed chronic sleep deprivation or "social jetlag". The consequences of chronic sleep deprivation are underappreciated in the medical setting. They include altered mood, more somatic and psychological symptomatology, greater anxiety, more school absenteeism, reduced educational results and compromised vocational aspirations. Engagement with reluctant teenagers and their parents may be challenging and at times frustrating for all concerned. Much of the art of improving outcomes involves developing a rapport with the teenager, assisting them to gain insight into the problems associated with chronic sleep deficiency and fostering commitment from all family members to implement unpopular boundaries on the use of technology.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.prrv.2021.05.001DOI Listing
December 2021

The practicalities of providing expert evidence for the court.

Paediatr Respir Rev 2021 Apr 22. Epub 2021 Apr 22.

Senior Counsel, Greenway Chambers in Sydney, NSW, Australia.

The role of the expert witness is clear in the eyes of the court but that understanding is less consistent for the medical professionals who may be called on in this capacity. The fundamental key is the clinician's purpose in using their experience, knowledge and training as they provide the court with an unbiased assessment of the clinical issues that have arisen in the case. Using the Australian context, this article provides guidance for clinicians who are asked to provide the court with their expertise through written and spoken representations, drawing upon experience and the use of the "Expert Witness Code of Conduct".
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.prrv.2021.04.001DOI Listing
April 2021

Covid-19 and the impact on young athletes.

Paediatr Respir Rev 2021 Sep 1;39:9-15. Epub 2021 May 1.

Jessie Ball duPont Distinguished Professor, Dept. of Pediatrics Professor of Biomedical Engineering Virginia Commonwealth University School of Medicine Virginia Eminent Scholar in Pediatrics 1000 East Broad St.Richmond, VA 23298 USA. Electronic address:

The Covid-19 pandemic has disrupted organised sport in the community as authorities cancelled, greatly modified or postponed sporting participation as part of a strategy to reduce transmission of the virus. This had a significant impact on young athletes and their families in relation to their psycho-social, physical and career progression considerations. The disruption is likely to continue for some years, considering the constraints of lockdowns, the need to overcome dysfunctional national logistics for delivery of medical care, fund and implement an efficacious vaccine programme locally, nationally and worldwide, develop sufficient herd immunity and create an environment of confidence in the safety of returning to sports for participants, coaches, umpires, administrators and observers. This article will consider the interim challenges regarding the physical and psychosocial importance of maintaining an active sporting programme for young athletes, reflect on safety measures for modifying sporting equipment and environmental protections to allow safest participation in training and competition and provide advice on protocols for a gradual return to sport for the young athlete after infection with Covid-19.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.prrv.2021.04.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087861PMC
September 2021

Survey of the practices of neonatologists in managing neonates believed to be at high risk of sleep disordered breathing.

BMJ Paediatr Open 2021 19;5(1):e000979. Epub 2021 Feb 19.

Neonatology, Children's Hospital at Westmead, Westmead, New South Wales, Australia.

Objective: To determine the practices of neonatologists in managing high-risk neonates believed to be at risk of sleep disordered breathing (SDB).

Design: An electronic web-based questionnaire assessing awareness of and current practices for managing neonates predisposed to SDB with conditions like craniofacial anomalies, neuromuscular disorders or airway problems was emailed to 232 neonatologists and neonatal fellows working in Australia and New Zealand (NZ). Additionally, neonatologists were approached directly during the annual Australia and NZ perinatal conference in 2019.

Results: 93 neonatologists (40%) responded to the survey. The majority (85%) of the respondents stated that there were no written protocols/criteria for sleep consultation in their unit. We found considerable variations in the threshold for performing tests including oximetry or referring for polysomnography. Most respondents would perform oximetry before referring for a sleep consultation. However, the duration of oximetry varied from 6 to 24 hours and there was no consensus about what is considered abnormal on an oximetry study.

Conclusion: Management of SDB is gaining importance in neonatal care because of prolonged length of hospital stay and possible long-term effects of SDB. Responses received suggest a lack of clarity regarding thresholds for referral for treatment of SDB. Likely contributory factors are concerns regarding a lack of long-term outcome data from treatment perceived to be onerous for the family, unsettling to some infants and delaying hospital discharge. To overcome inconsistencies in practice, standardised guidelines for assessing and managing SDB in neonates are needed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmjpo-2020-000979DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7898842PMC
February 2021

Respiratory outcomes post nusinersen in spinal muscular atrophy type 1.

Pediatr Pulmonol 2021 05 14;56(5):807-808. Epub 2020 Dec 14.

Department of Respiratory Medicine, The Children's Hospital at Westmead, Sydney, New South Wales, Australia.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ppul.25209DOI Listing
May 2021

STARRPeaker: uniform processing and accurate identification of STARR-seq active regions.

Genome Biol 2020 12 8;21(1):298. Epub 2020 Dec 8.

Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT, 06520, USA.

STARR-seq technology has employed progressively more complex genomic libraries and increased sequencing depths. An issue with the increased complexity and depth is that the coverage in STARR-seq experiments is non-uniform, overdispersed, and often confounded by sequencing biases, such as GC content. Furthermore, STARR-seq readout is confounded by RNA secondary structure and thermodynamic stability. To address these potential confounders, we developed a negative binomial regression framework for uniformly processing STARR-seq data, called STARRPeaker. Moreover, to aid our effort, we generated whole-genome STARR-seq data from the HepG2 and K562 human cell lines and applied STARRPeaker to comprehensively and unbiasedly call enhancers in them.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13059-020-02194-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7722316PMC
December 2020

Pulmonary Manifestations of Gastrointestinal, Pancreatic, and Liver Diseases in Children.

Pediatr Clin North Am 2021 02;68(1):41-60

Department of Respiratory Medicine, The Children's Hospital at Westmead, Locked Bag 4001, Westmead, New South Wales 2145, Australia; Faculty Health Sciences, University of Sydney, Sydney, New South Wales, Australia. Electronic address:

Pulmonary manifestations of gastrointestinal (GI) diseases are often subtle, and underlying disease may precede overt symptoms. A high index of suspicion and a low threshold for consultation with a pediatric pulmonologist is warranted in common GI conditions. This article outlines the pulmonary manifestations of different GI, pancreatic, and liver diseases in children, including gastroesophageal reflux disease, inflammatory bowel disease, pancreatitis, alpha1-antitrypsin deficiency, nonalcoholic fatty liver disease, and complications of chronic liver disease (hepatopulmonary syndrome and portopulmonary hypertension).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.pcl.2020.09.002DOI Listing
February 2021

Erratum to Childhood asthma in 2015: The Fuss and the Future: [Paediatric Respiratory Reviews 16/2 (2015) 81-82].

Paediatr Respir Rev 2020 Nov 2;36:159. Epub 2015 May 2.

Paediatric Respiratory and Sleep Physician, Clinical Professor, Sydney Medical School, Discipline of Paediatrics and Child Health, University of Sydney. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.prrv.2015.04.004DOI Listing
November 2020

Paediatric pneumonia in high-income countries: Defining and recognising cases at increased risk of severe disease.

Paediatr Respir Rev 2021 Sep 17;39:71-81. Epub 2020 Oct 17.

Department of Respiratory Medicine, The Children's Hospital at Westmead, Sydney, NSW 2145, Australia; Discipline of Child & Adolescent Health, Children's Hospital Westmead Clinical School, Faculty of Medicine and Health, The University of Sydney, NSW 2145, Australia.

World Health Organisation definitions of pneumonia severity are routinely used in research. In high income health care settings with high rates of pneumococcal vaccination and low rates of mortality, malnutrition and HIV infection, these definitions are less applicable. National guidelines from leading thoracic and infectious disease societies describe 'severe pneumonia' according to criteria derived from expert consensus rather than a robust evidence base. Contemporary cohort studies have used clinical outcomes such as intensive care therapy or invasive procedures for complicated pneumonia, to define severe disease. Describing severe pneumonia in such clinically relevant terms facilitates the identification of risk factors associated with worsened disease and the subsequently increased morbidity, and need for tertiary level care. The early recognition of children at higher risk of severe pneumonia informs site of care decisions, antibiotic treatment decisions as well as guiding appropriate investigations. Younger age, malnutrition, comorbidities, tachypnoea, and hypoxia have been identified as important associations with 'severe pneumonia' by WHO definition. Most studies have been performed in low-middle income countries and whilst they provide some insight into those at risk of mortality or treatment failure, their generalisability to the high-income setting is limited. There is a need to determine more precise definitions and criteria for severe disease in well-resourced settings and to validate factors associated with intensive care admission or invasive procedures to enhance the early recognition of those at risk.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.prrv.2020.10.004DOI Listing
September 2021

E-cigarettes, e-toxicity and e-commerce: a continuing public health emergency.

Paediatr Respir Rev 2020 Nov 11;36:73-74. Epub 2020 Oct 11.

University of Sydney, Faculty of Health Sciences, University of Sydney, New South Wales 2050, Australia; Department of Respiratory Medicine, Concord Hospital, Concord, Sydney, New South Wales, 2137, Australia.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.prrv.2020.10.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7548115PMC
November 2020

Real-world respiratory and bulbar comorbidities of SMA type 1 children treated with nusinersen: 2-Year single centre Australian experience.

Paediatr Respir Rev 2021 Sep 22;39:54-60. Epub 2020 Sep 22.

School of Women's and Children's Health, UNSW Medicine, UNSW Sydney, Australia; Sydney Children's Hospital, Randwick, Australia. Electronic address:

Aim: To describe the respiratory and nutritional supportive care and hospitalisations required in the real-world scenario in children with SMA type 1 treated with nusinersen.

Methods: Single-centre observational cohort study of children with SMA1 commencing nusinersen from November 2016 to September 2018. Motor, respiratory and nutritional clinical characteristics and management are described from initiation of nusinersen for a minimum of two years.

Results: Nine children (5 females, 4 males), median age 10.7 months (range 2.7-181.2) commenced treatment with nusinersen and outcomes were assessed over a total of 270.5 patient months and 209 hospital admissions. Supportive care in newly-diagnosed patients (n = 7) included gastrostomy insertion (n = 4) and commencement of noninvasive ventilation (n = 4) at an average of 8.3 and 4.5 months after diagnosis, respectively. The annualised hospitalisation rate was 9.3/patient/year, average length of stay (LOS) of 3.3 days (SD = 5.6). Children with two SMN2 copies required more gastrostomies (p < 0.05) and had more frequent admissions (p < 0.05). Number of total admissions halved from the first to the second year of treatment in all patients (p < 0.005).

Interpretation: Children with treated SMA1 experienced considerable respiratory and bulbar comorbidities, necessitating substantial respiratory and nutritional supportive care. Proactive respiratory and nutritional surveillance and management is essential in SMA1 patients treated with nusinersen.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.prrv.2020.09.002DOI Listing
September 2021

Transition to adult care in cystic fibrosis: The challenges and the structure.

Paediatr Respir Rev 2020 Aug 2. Epub 2020 Aug 2.

Department of Respiratory Medicine, The Children's Hospital at Westmead, Sydney, NSW, Australia; Discipline of Child and Adolescent Health, Sydney Medical School, University of Sydney, Sydney, NSW, Australia.

In developed countries, it is projected that there will be a 70% increase in the number of adults living with Cystic Fibrosis (CF) between 2010 and 2025. This shift in demographics highlights the importance of high-quality transition programmes with developmentally appropriate integrated health care services as the individual moves through adolescence to adulthood. Adolescents living with CF face additional and unique challenges that may have long-term impacts on their health, quality of life and life-expectancy. CF specific issues around socially challenging symptoms, body image, reproductive health and treatment burden differentiate people with CF from their peers and require clinicians to identify and address these issues during the transition process. This review provides an overview of the health, developmental and psychosocial challenges faced by individuals with CF, their guardians and health care teams considering the fundamental components and tools that are required to build a transition programme that can be tailored to suit individual CF clinics.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.prrv.2020.07.009DOI Listing
August 2020

COVID-19 changed times shaping the future.

Paediatr Respir Rev 2020 09 27;35:1-2. Epub 2020 Jun 27.

Children's Hospital of Richmond at VCU, USA; Virginia Commonwealth University School of Medicine, Dept. of Pediatrics, Richmond, VA 23298, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.prrv.2020.06.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7319920PMC
September 2020

COVID-19: A tale of two pandemics across the Asia Pacific region.

Paediatr Respir Rev 2020 Sep 27;35:75-80. Epub 2020 Jun 27.

Department of Paediatrics, Prince of Wales Hospital, Hong Kong Special Administrative Region; Faculty of Medicine, Chinese University of Hong Kong, Shatin, Hong Kong Special Administrative Region. Electronic address:

The widely diverse impacts of SAR-CoV-2 infection resulting in the COVID-19 pandemic cannot be held in more stark relief when contrasting the devastating impact upon China, Italy, Great Britain, America and Brazil with the considerably milder course in the geographically isolated countries of Australia and New Zealand and the densely populated Vietnam. Children in the Asia-Pacific region, as with children all over the world to date, have fared better than older adults. Other countries in the Asia-Pacific region, including Indonesia and India have struggled to deal with the pandemic because of a lack of health infrastructure, inability to provide sufficient testing and isolation and widespread poverty. This article will provide a snapshot of the impact of COVID-19 upon countries in the Asia-Pacific region in the six months since the first case of the novel zoonotic coronavirus infection appeared in China.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.prrv.2020.06.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7319925PMC
September 2020

An integrative ENCODE resource for cancer genomics.

Nat Commun 2020 07 29;11(1):3696. Epub 2020 Jul 29.

Program in Computational Biology & Bioinformatics, Yale University, New Haven, CT, 06520, USA.

ENCODE comprises thousands of functional genomics datasets, and the encyclopedia covers hundreds of cell types, providing a universal annotation for genome interpretation. However, for particular applications, it may be advantageous to use a customized annotation. Here, we develop such a custom annotation by leveraging advanced assays, such as eCLIP, Hi-C, and whole-genome STARR-seq on a number of data-rich ENCODE cell types. A key aspect of this annotation is comprehensive and experimentally derived networks of both transcription factors and RNA-binding proteins (TFs and RBPs). Cancer, a disease of system-wide dysregulation, is an ideal application for such a network-based annotation. Specifically, for cancer-associated cell types, we put regulators into hierarchies and measure their network change (rewiring) during oncogenesis. We also extensively survey TF-RBP crosstalk, highlighting how SUB1, a previously uncharacterized RBP, drives aberrant tumor expression and amplifies the effect of MYC, a well-known oncogenic TF. Furthermore, we show how our annotation allows us to place oncogenic transformations in the context of a broad cell space; here, many normal-to-tumor transitions move towards a stem-like state, while oncogene knockdowns show an opposing trend. Finally, we organize the resource into a coherent workflow to prioritize key elements and variants, in addition to regulators. We showcase the application of this prioritization to somatic burdening, cancer differential expression and GWAS. Targeted validations of the prioritized regulators, elements and variants using siRNA knockdowns, CRISPR-based editing, and luciferase assays demonstrate the value of the ENCODE resource.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-020-14743-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7391744PMC
July 2020

Consequences of physical distancing emanating from the COVID-19 pandemic: An Australian perspective.

Paediatr Respir Rev 2020 Sep 11;35:25-30. Epub 2020 Jun 11.

Discipline of Child and Adolescent Health, Sydney Medial School, Faculty of Health Sciences, University of Sydney, New South Wales 2145, Australia; Department of Infectious Diseases, The Children's Hospital at Westmead, Sydney, New South Wales 2145, Australia.

The sobering reality of the COVID-19 pandemic is that it has brought people together at home at a time when we want them apart in the community. This will bring both benefits and challenges. It will affect people differently based upon their age, health status, resilience, family support structures, and socio-economic background. This article will assess the impact in high income countries like Australia, where the initial wave of infection placed the elderly at the greatest risk of death whilst the protective measures of physical distancing, self-isolation, increased awareness of hygiene practices, and school closures with distance learning has had considerable impact on children and families acutely and may have ramifications for years to come.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.prrv.2020.06.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7289084PMC
September 2020

PRO: Primary Ciliary Dyskinesia: Genes are all you need!

Paediatr Respir Rev 2021 Mar 14;37:32-33. Epub 2020 Apr 14.

Discipline of Child & Adolescent Health, Faculty of Health Sciences, Sydney University, Sydney, New South Wales, Australia. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.prrv.2020.04.005DOI Listing
March 2021

Respiratory management of infants with chronic neonatal lung disease beyond the NICU: A position statement from the Thoracic Society of Australia and New Zealand.

Respirology 2020 08 8;25(8):880-888. Epub 2020 Jun 8.

Discipline of Child and Adolescent Health, Faculty of Medicine and Health, University of Sydney and the Children's Hospital at Westmead, Sydney, New South Wales, Australia.

Chronic neonatal lung disease (CNLD) is defined as continued need for any form of respiratory support (supplemental oxygen and/or assisted ventilation) beyond 36 weeks PMA. Low-flow supplemental oxygen facilitates discharge from hospital of infants with CNLD who are hypoxic in air and is widely used despite lack of evidence on the most appropriate minimum mean target oxygen saturations. Furthermore, there are minimal data to guide the home monitoring, titration or weaning of supplemental oxygen in these infants. The purpose of this position statement is to provide a guide for the respiratory management of infants with CNLD, with special emphasis on role and logistics of supplemental oxygen therapy beyond the NICU stay. Reflecting a variety of clinical practices and infant comorbidities (presence of pulmonary hypertension, retinopathy of prematurity and adequacy of growth), it is recommended that the minimum mean target range for SpO during overnight oximetry to be 93-95% with less than 5% of total recording time to be below 90% SpO . Safety of short-term disconnection from supplemental oxygen should be assessed before discharge, with majority of infants with CNLD not ready for discharge until supplemental oxygen requirement is ≤0.5 L/min. Sleep-time assessment of oxygenation with continuous overnight oximetry is recommended when weaning supplemental oxygen. Palivizumab is considered safe and effective for the reduction of hospital admissions with RSV infection in this group. This statement would be useful for paediatricians, neonatologists, respiratory and sleep physicians and general practitioners managing children with CNLD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/resp.13876DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7496866PMC
August 2020

Broadening our differential diagnosis for anaemia in Aboriginal people.

Aust J Rural Health 2020 06 26;28(3):307-308. Epub 2020 May 26.

Paediatrics Department, Dubbo Base Hospital, Dubbo, NSW, Australia.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ajr.12605DOI Listing
June 2020
-->