Research by staff affiliated to Our Lady's Children's Hospital Crumlin

Recent Submissions

  • Novel clinical and genetic insight into CXorf56-associated intellectual disability.

    Rocha, Maria Eugenia; Silveira, Tainá Regina Damaceno; Sasaki, Erina; Sás, Daíse Moreno; Lourenço, Charles Marques; Kandaswamy, Krishna K; Beetz, Christian; Rolfs, Arndt; Bauer, Peter; Reardon, Willie; et al. (2019-12-10)
    Intellectual disability (ID) is one of most frequent reasons for genetic consultation. The complex molecular anatomy of ID ranges from complete chromosomal imbalances to single nucleotide variant changes occurring de novo, with thousands of genes identified. This extreme genetic heterogeneity challenges the molecular diagnosis, which mostly requires a genomic approach. CXorf56 is largely uncharacterized and was recently proposed as a candidate ID gene based on findings in a single Dutch family. Here, we describe nine cases (six males and three females) from three unrelated families. Exome sequencing and combined database analyses, identified family-specific CXorf56 variants (NM_022101.3:c.498_503del, p.(Glu167_Glu168del) and c.303_304delCTinsACCC, p.(Phe101Leufs*20)) that segregated with the ID phenotype. These variants are presumably leading to loss-of-function, which is the proposed disease mechanism. Clinically, CXorf56-related disease is a slowly progressive neurological disorder. The phenotype is more severe in hemizygote males, but might also manifests in heterozygote females, which showed skewed X-inactivation patterns in blood. Male patients might present previously unreported neurological features such as epilepsy, abnormal gait, tremor, and clonus, which extends the clinical spectrum of the disorder. In conclusion, we confirm the causative role of variants in CXorf56 for an X-linked form of intellectual disability with additional neurological features. The gene should be considered for molecular diagnostics of patients with ID, specifically when family history is suggestive of X-linked inheritance. Further work is needed to understand the role of this gene in neurodevelopment and intellectual disability.
  • Protocol for a prospective, observational, longitudinal study in paediatric patients with moderate-to-severe atopic dermatitis (PEDISTAD): study objectives, design and methodology.

    Paller, Amy S; Guttman-Yassky, Emma; Irvine, Alan D; Baselga, Eulalia; de Bruin-Weller, Marjolein; Jayawardena, Shyamalie; Zhang, Annie; Mina-Osorio, Paola; Rizova, Elena; Ozturk, Zafer E (2020-03-24)
    Introduction: Atopic dermatitis (AD) is a chronic inflammatory skin disease often associated with atopic comorbidities and has significant impact on children and their families. There is a lack of robust and longitudinal long-term data on disease characteristics and typical clinical practice with currently available treatments in children with moderate-to-severe AD. Hence, an observational study is needed to evaluate AD characteristics and progression in paediatric patients with moderate-to-severe AD. Methods and analysis: Pediatric Study in Atopic Dermatitis (PEDISTAD) is a prospective, observational, longitudinal study in paediatric patients with moderate-to-severe AD who are currently receiving systemic or topical treatment and whose disease is not adequately controlled by topical prescription therapies or for whom those therapies are not medically advisable. 1300 children at 100-150 sites in approximately 20 countries worldwide will be enrolled and followed for 5 years. AD therapy is at the discretion of the investigator. Data collected will include: AD disease characteristics and comorbidities; current therapy for AD and initiation of new treatments/changes in current treatment; patient-reported/caregiver-reported outcomes; days missed from school/work for the patient/caregiver; healthcare professional visits; safety and biomarkers. Ethics and dissemination: This study is conducted in accordance with the principles established by the 18th World Medical Assembly and all subsequent amendments and the guidelines for Good Epidemiology Practice. Each individual country assures that ethics approval has been received and local regulatory requirements are met. Ethics approval has been obtained in all countries currently participating in PEDISTAD. Study data will be disseminated in manuscripts submitted to peer-reviewed medical journals as well as in abstracts submitted to congresses and in the resulting posters and presentations.
  • Heart University: a new online educational forum in paediatric and adult congenital cardiac care. The future of virtual learning in a post-pandemic world?

    Tretter, Justin T; Windram, Jonathan; Faulkner, Theresa; Hudgens, Michelle; Sendzikaite, Skaiste; Blom, Nico A; Hanseus, Katarina; Loomba, Rohit S; McMahon, Colin J; Zheleva, Bistra; et al. (2020-04-13)
    Online learning has become an increasingly expected and popular component for education of the modern-day adult learner, including the medical provider. In light of the recent coronavirus pandemic, there has never been more urgency to establish opportunities for supplemental online learning. Heart University aims to be "the go-to online resource" for e-learning in CHD and paediatric-acquired heart disease. It is a carefully curated open access library of paedagogical material for all providers of care to children and adults with CHD or children with acquired heart disease, whether a trainee or a practising provider. In this manuscript, we review the aims, development, current offerings and standing, and future goals of Heart University.
  • Recombinant factor VIII Fc fusion protein for the treatment of severe haemophilia A: Final results from the ASPIRE extension study.

    Nolan, Beatrice; Mahlangu, Johnny; Pabinger, Ingrid; Young, Guy; Konkle, Barbara A; Barnes, Chris; Nogami, Keiji; Santagostino, Elena; Pasi, K John; Khoo, Liane; et al. (2020-03-30)
    Introduction: The efficacy and safety of recombinant factor VIII Fc fusion protein (rFVIIIFc) as an extended half-life treatment for severe haemophilia A were demonstrated in the Phase 3 A-LONG and Kids A-LONG studies. Eligible subjects who completed A-LONG and Kids A-LONG could enrol in ASPIRE (NCT01454739), an open-label extension study. Aim: To report the long-term safety and efficacy of rFVIIIFc in subjects with severe haemophilia A who enrolled in ASPIRE. Methods: Previously treated subjects received one or more of the following regimens: individualized prophylaxis (IP), weekly prophylaxis, modified prophylaxis or episodic treatment. Subjects could switch treatment regimen at any time. The primary endpoint was inhibitor development. Results: A total of 150 subjects from A-LONG and 61 subjects from Kids A-LONG enrolled in ASPIRE. Most subjects received the IP regimen (A-LONG: n = 110; Kids A-LONG: n = 59). Median (range) treatment duration in ASPIRE for subjects from A-LONG and Kids A-LONG was 3.9 (0.1-5.3) years and 3.2 (0.3-3.9) years, respectively. No inhibitors were observed (0 per 1000 subject-years; 95% confidence interval, 0-5.2) and the overall rFVIIIFc safety profile was consistent with prior studies. For subjects on the IP regimen, annualized bleed rates (ABR) remained low (median overall ABR for adults and adolescents was <1.0) and extended-dosing intervals were maintained (median of 3.5 days) for the majority of subjects in ASPIRE. Conclusion: ASPIRE results, which include up to 5 years of follow-up data, confirm earlier reports on the consistent and well-characterized safety and efficacy of rFVIIIFc treatment for severe haemophilia A.
  • Dendritic Cell-Based Therapy Using LY6E Peptide with a Putative Role Against Colorectal Cancer.

    Tokhanbigli, Samaneh; Asadirad, Ali; Baghaei, Kaveh; Piccin, Andrea; Yarian, Fatemeh; Parsamanesh, Gilda; Hashemi, Seyed Mahmoud; Asadzadeh Aghdaei, Hamid; Zali, Mohammad Reza (2020-05-22)
    Introduction: Albeit early stage gastrointestinal (GI) carcinomas have a good prognosis if treated with surgery, diagnosis is often confirmed at a late stage and efficacious drugs are lacking. Recent progress in immune-based therapies has focused on dendritic cells (DCs), aiming to elicit tumor-specific responses by inducing immunological memory. Our previous microarray study indicated that a biomarker, termed lymphocyte antigen-6E (LY6E), is commonly overexpressed in two potentially lethal GI cancers: those of colon and stomach. In this study, we examined the antigenic potency of LY6E in stimulating DCs. Methods: Following isolation, differentiation, and maturation of mononuclear cells, DCs were pulsed with LY6E peptide, a protein related to major histocompatibility complex (MHC) class I/II. Subsequently, DCs were co-cultured with mouse splenocytes to assess antigen-specific T-cell proliferation. Elucidated cytotoxic T-lymphocyte responses were assessed using subcutaneous colorectal murine tumor models. Results: Our in vitro results suggest that DCs loaded with LY6E peptide antigen are capable of stimulating and inducing proliferation of murine T-cells. Furthermore, our in vivo results demonstrate that LY6E peptide has a substantial impact on provoking immune responses against induced colon cancer in mice. Discussion: In conclusion, based on the overexpression of LY6E in colorectal, gastric, and pancreatic cancers, the role of this peptide should be further investigated with a goal of developing new therapies for these challenging diseases.
  • International randomised controlled trial for the treatment of newly diagnosed EWING sarcoma family of tumours - EURO EWING 2012 Protocol.

    Anderton, Jennifer; Moroz, Veronica; Marec-Bérard, Perrine; Gaspar, Nathalie; Laurence, Valerie; Martín-Broto, Javier; Sastre, Ana; Gelderblom, Hans; Owens, Cormac; Kaiser, Sophie; et al. (2020-01-17)
    Background: Although there have been multiple randomised trials in newly diagnosed Ewing sarcoma family of tumours (ESFT) and these have been conducted over many years and involved many international cooperative groups, the outcomes for all stages of disease have plateaued. Internationally, the standard treatment of ESFT is not defined, and there is a need to add new agents other than conventional chemotherapy to improve outcomes. This trial will compare two different induction/consolidation chemotherapy regimens: (1) vincristine, ifosfamide, doxorubicin and etoposide (VIDE) induction and vincristine, actinomycin D, ifosfamide or cyclophosphamide, or busulfan and mephalan (VAI/VAC/BuMel) consolidation and (2) vincristine, doxorubicin, cyclophosphamide, ifosfamide and etoposide (VDC/IE) induction and ifosfamide and etoposide, vincristine and cyclophosphamide, vincristine, actinomycin D and ifosfamide, or busulfan and mephalan (IE/VC/VAI/BuMel) consolidation (randomisation 1, or R1). A second randomisation (R2) will determine whether the addition of zoledronic acid to consolidation chemotherapy, as assigned at R1, is associated with improved clinical outcome. Methods: EURO EWING 2012 is an international, multicentre, phase III, open-label randomised controlled trial. There are two randomisations: R1 and R2. Patients are randomly assigned at two different time points: at entry to the trial (R1) and following local control therapy (R2). The primary outcome measure is event-free survival. The secondary outcome measures include overall survival, adverse events and toxicity, histological response of the primary tumour, response of the primary tumour, regional lymph nodes or metastases (or both), and achievement of local control at the end of treatment. Discussion: This study will establish which is the "standard regimen" of chemotherapy, taking into account both clinical outcomes and toxicity. This will form the chemotherapy backbone for future interventional studies where we may want to add new targeted agents. It will also determine the role of zoledronic acid in conjunction with the separate EE2008 trial. Any trial in ESFT needs to take into account the rarity of the tumour and consider that international cooperation is needed to provide answers in a timely manner.
  • Investigation of the Role of Dinutuximab Beta-Based Immunotherapy in the SIOPEN High-Risk Neuroblastoma 1 Trial (HR-NBL1).

    Ladenstein, Ruth; Pötschger, Ulrike; Valteau-Couanet, Dominique; Luksch, Roberto; Castel, Victoria; Ash, Shifra; Laureys, Genevieve; Brock, Penelope; Michon, Jean Marie; Owens, Cormac; et al. (2020-01-28)
    To explore the effects of immunotherapy in the International Society of Paediatric Oncology Europe Neuroblastoma Group SIOPEN high-risk neuroblastoma 1 trial (HR-NBL1 trial), two cohorts were studied: one prior to and one after the introduction of dinutuximab beta. All patients received standard induction and high-dose therapy (HDT) with autologous stem cell rescue (ASCR); the local control comprised surgery and radiotherapy to the primary tumour site, followed by isotretinoin. A landmark timepoint of 109 days, resulting from the median time between ASCR and initiation of immunotherapy, was used to define patients' eligibility in the pre-immunotherapy analysis cohort. Median follow-up was 5.8 years (inter-quartile range (IQR): 4.2-8.2 years) for 844 eligible patients balanced for risk factors, such as age, sex, stage 4, MYCN amplification and response prior to HDT. The five-year event-free and overall survival (95% confidence interval (CI) of 466 patients not receiving immunotherapy was 42% (38-47%) and 50% (46-55%) but was 57% (51-62%) and 64% (59-69%) for 378 patients receiving immunotherapy (p < 0.001). A multivariate analysis identified absence of immunotherapy (p = 0.0002, hazard ratio (HR) 1.573); type of HDT (p = 0.0029, HR 1.431); less than complete response prior to maintenance therapy (p = 0.0043, HR 1.494) and >1 metastatic compartment at diagnosis (p < 0.001, HR 2.665) as risk factors for relapse or progression. Results suggest an important role for dinutuximab beta-based immunotherapy within the treatment concepts applied in HR-NBL1/SIOPEN.
  • The complex genetic landscape of familial MDS and AML reveals pathogenic germline variants.

    Rio-Machin, Ana; Vulliamy, Tom; Hug, Nele; Walne, Amanda; Tawana, Kiran; Cardoso, Shirleny; Ellison, Alicia; Pontikos, Nikolas; Wang, Jun; Tummala, Hemanth; et al. (2020-02-25)
    he inclusion of familial myeloid malignancies as a separate disease entity in the revised WHO classification has renewed efforts to improve the recognition and management of this group of at risk individuals. Here we report a cohort of 86 acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) families with 49 harboring germline variants in 16 previously defined loci (57%). Whole exome sequencing in a further 37 uncharacterized families (43%) allowed us to rationalize 65 new candidate loci, including genes mutated in rare hematological syndromes (ADA, GP6, IL17RA, PRF1 and SEC23B), reported in prior MDS/AML or inherited bone marrow failure series (DNAH9, NAPRT1 and SH2B3) or variants at novel loci (DHX34) that appear specific to inherited forms of myeloid malignancies. Altogether, our series of MDS/AML families offer novel insights into the etiology of myeloid malignancies and provide a framework to prioritize variants for inclusion into routine diagnostics and patient management.
  • Global Retinoblastoma Presentation and Analysis by National Income Level.

    Fabian, Ido Didi; Abdallah, Elhassan; Abdullahi, Shehu U; Abdulqader, Rula A; Adamou Boubacar, Sahadatou; Ademola-Popoola, Dupe S; Adio, Adedayo; Afshar, Armin R; Aggarwal, Priyanka; Aghaji, Ada E; et al. (2020-05)
    Importance: Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale. Objectives: To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis. Design, setting, and participants: A total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017. Main outcomes and measures: Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. Results: The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4%) were female. Most patients (n = 3685 [84.7%]) were from low- and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 [62.8%]), followed by strabismus (n = 429 [10.2%]) and proptosis (n = 309 [7.4%]). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 [95% CI, 12.94-24.80], and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 [95% CI, 4.30-7.68]). Conclusions and relevance: This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs.
  • Risk Factors for Respiratory Syncytial Virus Bronchiolitis Admissions

    Meenaghan, Samantha; Breatnach, C.; Smith, H. (Irish Medical Journal, 2020-01)
    AimDetermine the seasonal incidence of hospital Respiratory Syncytial Virus (RSV) bronchiolitis and explore the variables associated with admission to ward versus the Paediatric Intensive Care Unit (PICU).MethodRetrospective case-control study. Children, aged ≤2 years, between November and March, over a 3 year period with a positive RSV nasopharyngeal aspirate test.ResultsA total of 557 children were included; 19% (n=106) required PICU admission. Children admitted to the PICU were younger in age, median (IQR) 6.93 (3.96, 11.89) weeks compared to children who remained on the wards 11.00 (5.86, 24.14) weeks. Being underweight at the point of admission (adjusted odds ratio 3.15, 95% 1.46, 6.70, p=0.003) was associated with a PICU admission.ConclusionNumber of RSV bronchiolitis hospitalisations are increasing each year. Age, weight and the use of HFNC were independent predictors for PICU admission.
  • Musculoskeletal anomalies in children with Down syndrome: an observational study.

    Foley, Charlene; Killeen, Orla G (2018-11-24)
    Background: Musculoskeletal complications of Down syndrome (DS) are common but infrequently reported. The combination of ligamentous laxity and low muscle tone contributes to increased risk of a number of musculoskeletal disorders and a delay in acquisition of motor milestones. The primary aim of this study was to describe musculoskeletal anomalies reported in a national cohort of children with DS. Methods: This was an observational study. Children with DS, aged 0-21 years, were invited to attend a musculoskeletal assessment clinic conducted by a paediatric physician. Relevant musculoskeletal history and clinical findings were documented. Results: Over an 18-month period, 503 children with DS were examined (56% male). The median age was 8.1 years (0.6-19.2). Pes planus was almost universal, occurring in 91% of the cohort. A range of other musculoskeletal anomalies were observed, with inflammatory arthritis (7%) and scoliosis (4.8%) occurring most frequently after pes planus. Delay in ambulation was common; the median age to walk was 28 months (12-84). Conclusion: Children with DS are at increased risk of a number of potentially debilitating musculoskeletal problems. These conditions can present in variable manners or be completely asymptomatic. Pes planus is common; therefore, early consideration of orthotics and lifelong appropriate supportive footwear should be considered. Delayed ambulation is frequently noted. A significant proportion of children with DS have arthritis; however, despite a high prevalence, it is often missed, leading to delayed diagnosis. An annual musculoskeletal assessment for all children with DS could potentially enable early detection of problems, allowing for timely multidisciplinary team intervention and better clinical outcomes.
  • KAT6A Syndrome: genotype-phenotype correlation in 76 patients with pathogenic KAT6A variants.

    Kennedy, Joanna; Goudie, David; Blair, Edward; Chandler, Kate; Joss, Shelagh; McKay, Victoria; Green, Andrew; Armstrong, Ruth; Lees, Melissa; Kamien, Benjamin; et al. (2018-09-24)
    Purpose: Pathogenic variants in KAT6A have recently been identified as a cause of syndromic developmental delay. Within 2 years, the number of patients identified with pathogenic KAT6A variants has rapidly expanded and the full extent and variability of the clinical phenotype has not been reported. Methods: We obtained data for patients with KAT6A pathogenic variants through three sources: treating clinicians, an online family survey distributed through social media, and a literature review. Results: We identified 52 unreported cases, bringing the total number of published cases to 76. Our results expand the genotypic spectrum of pathogenic variants to include missense and splicing mutations. We functionally validated a pathogenic splice-site variant and identified a likely hotspot location for de novo missense variants. The majority of clinical features in KAT6A syndrome have highly variable penetrance. For core features such as intellectual disability, speech delay, microcephaly, cardiac anomalies, and gastrointestinal complications, genotype- phenotype correlations show that late-truncating pathogenic variants (exons 16-17) are significantly more prevalent. We highlight novel associations, including an increased risk of gastrointestinal obstruction. Conclusion: Our data expand the genotypic and phenotypic spectrum for individuals with genetic pathogenic variants in KAT6A and we outline appropriate clinical management.
  • Circumcision Rates after the Release of Preputial Adhesions

    Aworanti, O.M; Rasheed, F.; Aldiab, A; Mortell, A. (Irish Medical Journal, 2019-07)
    The non-retractile foreskin in children is one of the most frequent indication for referral to a paediatric surgeon in Ireland. This is probably due to parental concerns when children complain of related symptoms coupled with a misperception among some general practitioners (GP) of the natural separation process of the inner surface of the prepuce from the glans surface1,2,3. Phimosis from the Greek word ‘Ψιμoσισ’ (muzzling) generally describes the non-retractile foreskin. Phimosis is best classified as either pathological or physiological. Pathological phimosis is either due to balanitis xerotica obliterans (BXO) or due to a constricting phimotic ring that hinders retraction, both usually in the older boy. Physiological phimosis is simply the non-retractile or incompletely retractile state of the foreskin in usually asymptomatic young boys. Foreskin retraction has been established to be complete by the age of 3 years in 90% 1 and by the age of 16 years in 99% 2 of boys. During this preputial separation process, complaints such as local discomfort, ballooning of the foreskin during micturition and smegma retention cysts are common and require simple reassurance only 3. No pathologic sequelae have been attributed to these physiologic processes on assessing urine flow rates, post-void residual bladder volumes and bladder wall thickness in young boys with physiologic phimosis 3. Furthermore, as partial separation of the foreskin ensues, young boys can suffer from episodes of balanoposthitis1,3. This inflammation of the glans and prepuce (or prepuce only - termed posthitis) generally resolves with antibiotic treatment and can be prevented with improved local hygiene. Therefore, absolute and strong indications for a medical circumcision are limited to pathological phimosis due to BXO and prevention of recurrent urinary tract infections (UTI) usually in children with vesicoureteric reflux or posterior urethral valves respectively4,5
  • Varicella Related Hospital Admissions in Ireland

    McCarthy, K.N.; Ó Maoldomhnaigh, C.; Butler, K.M.; Gavin, P.J. (Irish Medical Journal, 2019-07)
    Aim The aim of this study was to evaluate trends in admissions for patients with primary varicella infection in Irish hospitals. Methods The Hospital Inpatient Enquiry System was evaluated from Irish hospitals from 2005-2016 for patients with primary varicella infection. Results There were 2717 admissions with primary varicella infection. The average annual number of admissions was 226 for an incidence of 4.87/100,000. Average length of stay (ALOS) was 5-days. Sixty-two (2.5%) patients required intensive-care with an ALOS of 26-days. The most common secondary diagnoses were cellulitis, volume-depletion and streptococcal infection. The number of admissions due to streptococcal infection and cellulitis significantly increased over the period. Conclusion Chickenpox places a consistent burden on Irish healthcare, accounting for in excess of 1100 acute and 160 intensive-care bed days annually. This study adds weight to the argument that universal varicella vaccine should be considered and provides baseline epidemiology to determine vaccine effectiveness in the future.
  • The Prevalence of Pseudomonas Aeruginosa Infection Over a Ten-Year Period in Children with Cystic Fibrosis

    Al Shidhani, K; O’Reilly, R; Javadpour, S; O’Sullivan, N; McNally, P; Cox, D.W (Irish Medical Journal, 2019-06)
    A retrospective observational study was performed at Our Lady’s Children’s Hospital, Crumlin (OLCHC), Dublin, the largest paediatric tertiary CF referral centre in Ireland. Patient’s case notes, microbiology laboratory results and data from the Cystic Fibrosis Registry of Ireland (CFRI) database were used as sources for the data collection. We compared the prevalence of PA infection in 2014 with 2004. PA infection was defined as one positive culture on an airway sample (either a sputum, throat swab or broncho-alveolar lavage sample). The modified Leed’s criteria was used to classify PA infection into never infected, free of infection (negative PA culture for > 12 months), intermittent infection ( positive PA culture for < 6 months) and chronic infection ( positive PA culture for > 6 months).
  • Congenital Atrial Haemangioma

    Daly, A; Franklin, O; Nölke, L (Irish Medical Journal, 2019-04)
    Cardiac hemangioma is a rare form of primary cardiac tumor. Only small a number of cardiac hemangioma cases have been reported in the literature and therefore appreciation of the best management strategies for primary cardiac tumors in neonates is somewhat lacking. We present the rare case of a neonate who presented with symptoms arising from a congenital atrial haemangioma on day three of life. This report serves to remind the paediatric medical community of the rare diagnosis of primary cardiac tumours, diagnostic clues and therapeutic interventions used to address this unusual diagnosis.
  • An Audit of Paediatric Organ and Tissue Donation in Ireland

    Marshall, L; Hennessey, I; Lynch, C; Gibbons, C; Crowe, S; 1. Our Lady’s Children’s Hospital Crumlin 2. Temple Street Children’s University Hospital 3. Organ Donation and Transplant Ireland. 4. School of Medicine, University of Dublin, Trinity College, Dublin (Irish Medical Journal, 2018-11)
    Organ donation may be considered in children who die in paediatric intensive care units if certain criteria are met and if their families wish for organ donation. In general organs are donated after death has been confirmed using neurological criteria to diagnose brainstem death (BSD). Donation of organs can also occur in certain circumstances after death has been confirmed using circulatory criteria (DCD). The Intensive Care Society of Ireland has published guidelines on organ donation after brainstem death and more recently on donation after circulatory death1,2. The American College of Critical Care Medicine, The Academy of Royal Medical Colleges and The Australian & New Zealand Intensive Care Society have all also published specific guidelines on the determination of brainstem death in infants and children
  • Children's complex care needs: a systematic concept analysis of multidisciplinary language.

    Brenner, Maria; Kidston, Claire; Hilliard, Carol; Coyne, Imelda; Eustace-Cook, Jessica; Doyle, Carmel; Begley, Thelma; Barrett, Michael J; School of Nursing & Midwifery, Trinity College Dublin (Springer, 2018-11-01)
    Complex care in the arena of child health is a growing phenomenon. Although considerable research is taking place, there remains limited understanding and agreement on the concept of complex care needs (CCNs), with potential for ambiguity. We conducted a systematic concept analysis of the attributes, antecedents, and consequences of children's CCNs from a multidisciplinary perspective. Our data sources included PubMed, Cumulative Index to Nursing and Allied Health Literature, and PsycINFO. Inclusion criteria included publications in peer-reviewed journals between January 1990 and December 2017, written in the English language. One hundred and forty articles were included. We found that children's CCNs refer to multidimensional health and social care needs, in the presence of a recognized medical condition or where there is no unifying diagnosis.Conclusion: Children's CCNs are individual and contextualized, are continuing and dynamic, and are present across a range of settings, impacted by family and healthcare structures. There remain extensive challenges to caring for these children and their families, precluding the possibility that any one profession can possess the requisite knowledge or scope to singularly provide high-quality competent care. What is Known: • Complex care is a growing phenomenon and population prevalence figures show that there is an increasing number of children with complex care needs (CCNs). However, the concept has not been systematically analyzed before, leaving it generally ill-defined and at times confusing. What is New: • This is the first time this concept has been systematically analyzed and this analysis provides a much-needed theoretical framework for understanding the multidimensional nature of CCNs in children. • Children's CCNs refer to multidimensional health and social care needs in the presence of a recognized medical condition or where there is no unifying diagnosis. They are individual and contextualized, are continuing and dynamic, and are present across a range of settings, impacted by family and healthcare structures. It is clear that the very nature of CCNs precludes the possibility that any one profession or discipline can possess the requisite knowledge or scope for high-quality competent care for this population.
  • Cannabis Oil in an Irish Children’s Critical Care Unit

    Fennessy, P; Murphy, L; Crowe, S (Irish Medical Journal, 2018-09)
    We present a case of a five-year-old female admitted postoperatively to the Paediatric Critical Care Unit (PCCU). She had a history of refractory seizures. Her parents had obtained cannabis oil from the United States and were administering it to her at night, in addition to her regular anticonvulsant medication. Her parents reported decreased seizure frequency since its commencement. The child had elective tonsillectomy for management of significant obstructive sleep apnoea (OSA), possibly exacerbated by the sedative properties of cannabis. The admitting surgical and critical care teams were unaware that the child was regularly receiving cannabis until 14 hours after admission to hospital. The PCCU and the hospital do not currently have any guidelines to assist medical and nursing staff with the safe use of this potentially psychogenic preparation. The Irish Health Products Regulatory Authority (HPRA) published a scientific review on the subject in January 20171. After discussion with the child’s parents, we agreed an administration regimen, the timing of which was separate to regular sedative medication in view of the child’s history of OSA. The child’s postoperative course and stay in PCCU was uncomplicated.
  • Astroglial-Mediated Remodeling of the Interhemispheric Midline Is Required for the Formation of the Corpus Callosum.

    Gobius, Ilan; Morcom, Laura; Suárez, Rodrigo; Bunt, Jens; Bukshpun, Polina; Reardon, William; Dobyns, William B; Rubenstein, John L R; Barkovich, A James; Sherr, Elliott H; et al. (CellPress, 2016)
    The corpus callosum is the major axon tract that connects and integrates neural activity between the two cerebral hemispheres. Although ∼1:4,000 children are born with developmental absence of the corpus callosum, the primary etiology of this condition remains unknown. Here, we demonstrate that midline crossing of callosal axons is dependent upon the prior remodeling and degradation of the intervening interhemispheric fissure. This remodeling event is initiated by astroglia on either side of the interhemispheric fissure, which intercalate with one another and degrade the intervening leptomeninges. Callosal axons then preferentially extend over these specialized astroglial cells to cross the midline. A key regulatory step in interhemispheric remodeling is the differentiation of these astroglia from radial glia, which is initiated by Fgf8 signaling to downstream Nfi transcription factors. Crucially, our findings from human neuroimaging studies reveal that developmental defects in interhemispheric remodeling are likely to be a primary etiology underlying human callosal agenesis.

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