Showing papers by "Princess Margaret Hospital for Children published in 2012"

Long-term differences in language and cognitive function after childhood exposure to anesthesia.

Abstract: BACKGROUND: Over the past decade, the safety of anesthetic agents in children has been questioned after the discovery that immature animals exposed to anesthesia display apoptotic neurodegeneration and long-term cognitive deficiencies. We examined the association between exposure to anesthesia in children under age 3 and outcomes in language, cognitive function, motor skills, and behavior at age 10. METHODS: We performed an analysis of the Western Australian Pregnancy Cohort (Raine) Study, which includes 2868 children born from 1989 to 1992. Of 2608 children assessed, 321 were exposed to anesthesia before age 3, and 2287 were unexposed. RESULTS: On average, exposed children had lower scores than their unexposed peers in receptive and expressive language (Clinical Evaluation of Language Fundamentals: Receptive [CELF-R] and Expressive [CELF-E]) and cognition (Colored Progressive Matrices [CPM]). After adjustment for demographic characteristics, exposure to anesthesia was associated with increased risk of disability in language (CELF-R: adjusted risk ratio [aRR], 1.87; 95% confidence interval [CI], 1.20–2.93, CELF-E: aRR, 1.72; 95% CI, 1.12–2.64), and cognition (CPM: aRR, 1.69; 95% CI, 1.13–2.53). An increased aRR for disability in language and cognition persisted even with a single exposure to anesthesia (CELF-R aRR, 2.41; 95% CI, 1.40–4.17, and CPM aRR, 1.73; 95% CI, 1.04–2.88). CONCLUSIONS: Our results indicate that the association between anesthesia and neuropsychological outcome may be confined to specific domains. Children in our cohort exposed to anesthesia before age 3 had a higher relative risk of language and abstract reasoning deficits at age 10 than unexposed children.

International consensus on (ICON) pediatric asthma

Abstract: Asthma is the most common chronic lower respiratory disease in childhood throughout the world. Several guidelines and/or consensus documents are available to support medical decisions on pediatric asthma. Although there is no doubt that the use of common systematic approaches for management can considerably improve outcomes, dissemination and implementation of these are still major challenges. Consequently, the International Collaboration in Asthma, Allergy and Immunology (iCAALL), recently formed by the EAACI, AAAAI, ACAAI, and WAO, has decided to propose an International Consensus on (ICON) Pediatric Asthma. The purpose of this document is to highlight the key messages that are common to many of the existing guidelines, while critically reviewing and commenting on any differences, thus providing a concise reference. The principles of pediatric asthma management are generally accepted. Overall, the treatment goal is disease control. To achieve this, patients and their parents should be educated to optimally manage the disease, in collaboration with healthcare professionals. Identification and avoidance of triggers is also of significant importance. Assessment and monitoring should be performed regularly to re-evaluate and fine-tune treatment. Pharmacotherapy is the cornerstone of treatment. The optimal use of medication can, in most cases, help patients control symptoms and reduce the risk for future morbidity. The management of exacerbations is a major consideration, independent of chronic treatment. There is a trend toward considering phenotype-specific treatment choices; however, this goal has not yet been achieved.

Emergency department overcrowding, mortality and the 4-hour rule in Western Australia.

Abstract: OBJECTIVE To assess whether emergency department (ED) overcrowding was reduced after the introduction of the 4-hour rule in Western Australia and whether any changes in overcrowding were associated with significant changes in patient mortality rates. DESIGN, SETTING AND PATIENTS Quasi-experimental intervention study using dependent pretest and post-test samples. Hospital and patient data were obtained for three tertiary hospitals and three secondary hospitals in Perth, WA, for 2007-08 to 2010-11. MAIN OUTCOME MEASURES Mortality rates; overcrowding rates. RESULTS No change was shown in mortality from 2007-08 to 2010-11 for the secondary hospitals and from 2007-08 to 2009-10 for the tertiary hospitals. ED overcrowding (as measured by 8-hour access block) at the tertiary hospitals improved dramatically, falling from above 40% in July 2009 to around 10% by early 2011, and presentations increased by 10%, while the mortality rate fell significantly (by 13%; 95% CI, 7%-18%; P < 0.001) from 1.12% to 0.98% between 2009-10 and 2010-11. Monthly mortality rates decreased significantly in two of the three tertiary hospitals concurrently with decreased access block and an increased proportion of patients admitted in under 4 hours. CONCLUSION Introduction of the 4-hour rule in WA led to a reversal of overcrowding in three tertiary hospital EDs that coincided with a significant fall in the overall mortality rate in tertiary hospital data combined and in two of the three individual hospitals. No reduction in adjusted mortality rates was shown in three secondary hospitals where the improvement in overcrowding was minimal.

Genome-Wide Association Studies of Asthma in Population-Based Cohorts Confirm Known and Suggested Loci and Identify an Additional Association near HLA

Abstract: Rationale: Asthma has substantial morbidity and mortality and a strong genetic component, but identification of genetic risk factors is limited by availability of suitable studies. Objectives: To t ...

Newly Emerging Clones of Bordetella pertussis Carrying prn2 and ptxP3 Alleles Implicated in Australian Pertussis Epidemic in 2008–2010

Abstract: Australia is experiencing a prolonged epidemic of pertussis that began in 2008. A total of 194 Bordetella pertussis isolates collected from 2008 through 2010 were typed by single-nucleotide polymorphism (SNP) analysis, by multilocus variable number tandem repeats analysis, and by fim3, prn, and ptxP sequence analyses. Strains with 2 closely related SNP profiles carrying prn2 and ptxP3 from the recently emerged SNP cluster I predominated. The data suggest increasing selection among the B. pertussis population in Australia in favor of strains carrying prn2 and ptxP3 under the pressure of acellular vaccine-induced immunity.

Incidence of vitamin D deficiency rickets among Australian children: an Australian Paediatric Surveillance Unit study.

Abstract: OBJECTIVE To determine the incidence of and factors associated with vitamin D deficiency rickets in Australian children. DESIGN 18-month questionnaire-based prospective observational study, using Australian Paediatric Surveillance Unit (APSU) data. SETTING Australian paediatricians and child health workers, January 2006 - July 2007. PARTICIPANTS Children aged ≤ 15 years with vitamin D deficiency rickets (25-hydroxyvitamin D [25OHD] ≤ 50 nmol/L, and elevated alkaline phosphatase levels [> 229 IU/L] and/or radiological rickets). MAIN OUTCOME MEASURES Incidence of vitamin D deficiency rickets. Description of demographics, clinical presentation, identification and further analysis of overrepresented groups, and treatment regimens compared with best-practice guidelines. RESULTS We identified 398 children with vitamin D deficiency (55% male; median age, 6.3 years [range, 0.2-15 years]). The overall incidence in children ≤ 15 years of age in Australia was 4.9/100 000/year. All had a low 25OHD level (median, 28 nmol/L [range, 5-50 nmol]) and an elevated alkaline phosphatase level (median, 407 IU/L [range, 229-5443 IU/L]), and 48 (12%) were hypocalcaemic. Ninety-five children had wrist x-rays, of whom 67 (71%) had rachitic changes. Most (98%) had dark or intermediate skin colour and 18% of girls were partially or completely veiled. Most children were born in Africa (252; 63%) and 75% of children were refugees. Duration of exclusive breastfeeding was inversely related to serum vitamin D levels in children < 3 years of age. Empirical vitamin D treatment was given to 4% of children before diagnosis. CONCLUSIONS Vitamin D deficiency rickets is a significant problem in Australia among known high-risk groups. Public health campaigns to prevent, identify and tre@vitamin D deficiency, especially in high-risk groups, are essential.

Histologic chorioamnionitis is associated with reduced risk of late-onset sepsis in preterm infants.

Abstract: BACKGROUND: Histologic chorioamnionitis (HCA) is implicated in the onset of preterm labor and delivery. Chorioamnionitis is a known risk factor for early-onset sepsis and may modulate postnatal immunity. Preterm infants are at greatly increased risk of late-onset sepsis (LOS), particularly with coagulase-negative staphylococci (CoNS), but the impact of HCA on the risk of LOS is unknown. METHODS: Eight hundred thirty-eight preterm infants born at <30 weeks gestational age at a single tertiary center were included. Histologic examination of placenta and extraplacental membranes was performed, and clinical data were extracted from hospital databases. The influence of HCA on the incidence of early-onset sepsis and LOS was examined using logistic regression analysis and Cox proportional hazards regression. RESULTS: Mean gestational age was 26.9 ± 1.9 weeks, and mean birth weight was 936 ± 277 g. Two hundred and seventy-six (33%) of 838 infants developed LOS. The presence of fetal or maternal HCA, or maternal HCA and fetal HCA alone, was associated with a significantly decreased risk of LOS with any organism. Histologic chorioamnionitis correlated with a significantly decreased risk of CoNS LOS. CONCLUSIONS: HCA is associated with a significantly reduced risk of acquiring LOS, both with CoNS and other bacteria. Perinatal inflammation may enhance the functional maturation of the preterm immune system and provide protection against LOS in high-risk preterm infants. * Abbreviations: BW — : birth weight CI — : confidence interval CLD — : chronic lung disease CoNS — : coagulase-negative staphylococci EOS — : early-onset sepsis GA — : gestational age HCA — : histologic chorioamnionitis HR — : hazard ratio LOS — : late-onset sepsis OR — : odds ratio TLR — : Toll -like receptor

DNA Methylation Profiles of Airway Epithelial Cells and PBMCs from Healthy, Atopic and Asthmatic Children

Abstract: Background Allergic inflammation is commonly observed in a number of conditions that are associated with atopy including asthma, eczema and rhinitis. However, the genetic, environmental or epigenetic factors involved in these conditions are likely to be different. Epigenetic modifications, such as DNA methylation, can be influenced by the environment and result in changes to gene expression.

The effectiveness of a standardised preoperative preparation in reducing child and parent anxiety: a single-blind randomised controlled trial.

Abstract: Aims: To evaluate the effect of a structured preoperative preparation on child and parent state anxiety, child behavioural change and parent satisfaction.

Sexual dimorphism in multiple aspects of 3D facial symmetry and asymmetry defined by spatially dense geometric morphometrics

Abstract: Accurate measurement of facial sexual dimorphism is useful to understanding facial anatomy and specifically how faces influence, and have been influenced by, sexual selection. An important facial aspect is the display of bilateral symmetry, invoking the need to investigate aspects of symmetry and asymmetry separately when examining facial shape. Previous studies typically employed landmarks that provided only a sparse facial representation, where different landmark choices could lead to contrasting outcomes. Furthermore, sexual dimorphism is only tested as a difference of sample means, which is statistically the same as a difference in population location only. Within the framework of geometric morphometrics, we partition facial shape, represented in a spatially dense way, into patterns of symmetry and asymmetry, following a two-factor anova design. Subsequently, we investigate sexual dimorphism in symmetry and asymmetry patterns separately, and on multiple aspects, by examining (i) population location differences as well as differences in population variance-covariance; (ii) scale; and (iii) orientation. One important challenge in this approach is the proportionally high number of variables to observations necessitating the implementation of permutational and computationally feasible statistics. In a sample of gender-matched young adults (18-25 years) with self-reported European ancestry, we found greater variation in male faces than in women for all measurements. Statistically significant sexual dimorphism was found for the aspect of location in both symmetry and asymmetry (directional asymmetry), for the aspect of scale only in asymmetry (magnitude of fluctuating asymmetry) and, in contrast, for the aspect of orientation only in symmetry. Interesting interplays with hypotheses in evolutionary and developmental biology were observed, such as the selective nature of the force underpinning sexual dimorphism and the genetic independence of the structural patterns of fluctuating asymmetry. Additionally, insights into growth patterns of the soft tissue envelope of the face and underlying skull structure can also be obtained from the results.

The Use of an Automated, Portable, Glucose Control System for Overnight Glucose Control in Adolescents and Young Adults With Type 1 Diabetes

Abstract: OBJECTIVE A key milestone in progress towards providing an efficacious and safe closed-loop artificial pancreas system for outpatient use is the development of fully automated, portable devices with fault detection capabilities to ensure patient safety. The ability to remotely monitor the operation of the closed-loop system would facilitate future physician–supervised home studies. RESEARCH DESIGN AND METHODS This study was designed to investigate the efficacy and safety of a fully automated, portable, closed-loop system. The Medtronic Portable Glucose Control System (PGCS) consists of two subcutaneous glucose sensors, a control algorithm based on proportional-integral-derivative with insulin feedback operating from a BlackBerry Storm smartphone platform, Bluetooth radiofrequency translator, and an off-the-shelf Medtronic Paradigm Veo insulin pump. Participants with type 1 diabetes using insulin pump therapy underwent two consecutive nights of in-clinic, overnight, closed-loop control after a baseline open-loop assessment. RESULTS Eight participants attended for 16 overnight studies. The PGCS maintained mean overnight plasma glucose levels of 6.4 ± 1.7 mmol/L (115 ± 31 mg/dL). The proportion of time with venous plasma glucose 8 mmol/L was 7, 78, and 15%, respectively. The proportion of time the sensor glucose values were maintained between 3.9 and 8 mmol/L was greater for closed-loop than open-loop (84.5 vs. 46.7%; P P CONCLUSIONS These results suggest that the PGCS, an automated closed-loop device, is safe and effective in achieving overnight glucose control in patients with type 1 diabetes.

Early Loss of the Glucagon Response to Hypoglycemia in Adolescents With Type 1 Diabetes

Abstract: OBJECTIVE To assess the glucagon response to hypoglycemia and identify influencing factors in patients with type 1 diabetes compared with nondiabetic control subjects. RESEARCH DESIGN AND METHODS Hyperinsulinemic hypoglycemic clamp studies were performed in all participants. The glucagon response to both hypoglycemia and arginine was measured, as well as epinephrine, cortisol, and growth hormone responses to hypoglycemia. Residual β-cell function was assessed using fasting and stimulated C-peptide. RESULTS Twenty-eight nonobese adolescents with type 1 diabetes (14 female, mean age 14.9 years [range 11.2–19.8]) and 12 healthy control subjects (6 female, 15.3 years [12.8–18.7]) participated in the study. Median duration of type 1 diabetes was 0.66 years (range 0.01–9.9). The glucagon peak to arginine stimulation was similar between groups ( P = 0.27). In contrast, the glucagon peak to hypoglycemia was reduced in the group with diabetes (95% CI): 68 (62–74) vs. 96 (87–115) pg/mL ( P R = −0.41, P 1c . Epinephrine, cortisol, and growth hormone responses to hypoglycemia were present in both groups. CONCLUSIONS The glucagon response to hypoglycemia in adolescents with type 1 diabetes is influenced by the duration of diabetes and can be lost early in the course of the disease.

Autosomal-Recessive Congenital Cerebellar Ataxia Is Caused by Mutations in Metabotropic Glutamate Receptor 1

Abstract: Autosomal-recessive congenital cerebellar ataxia was identified in Roma patients originating from a small subisolate with a known strong founder effect. Patients presented with global developmental delay, moderate to severe stance and gait ataxia, dysarthria, mild dysdiadochokinesia, dysmetria and tremors, intellectual deficit, and mild pyramidal signs. Brain imaging revealed progressive generalized cerebellar atrophy, and inferior vermian hypoplasia and/or a constitutionally small brain were observed in some patients. Exome sequencing, used for linkage analysis on extracted SNP genotypes and for mutation detection, identified two novel (i.e., not found in any database) variants located 7 bp apart within a unique 6q24 linkage region. Both mutations cosegregated with the disease in five affected families, in which all ten patients were homozygous. The mutated gene, GRM1, encodes metabotropic glutamate receptor mGluR1, which is highly expressed in cerebellar Purkinje cells and plays an important role in cerebellar development and synaptic plasticity. The two mutations affect a gene region critical for alternative splicing and the generation of receptor isoforms; they are a 3 bp exon 8 deletion and an intron 8 splicing mutation (c.2652_2654del and c.2660+2T>G, respectively [RefSeq accession number NM_000838.3]). The functional impact of the deletion is unclear and is overshadowed by the splicing defect. Although ataxia lymphoblastoid cell lines expressed GRM1 at levels comparable to those of control cells, the aberrant transcripts skipped exon 8 or ended in intron 8 and encoded various species of nonfunctional receptors either lacking the transmembrane domain and containing abnormal intracellular tails or completely missing the tail. The study implicates mGluR1 in human hereditary ataxia. It also illustrates the potential of the Roma founder populations for mutation identification by exome sequencing.

Genome-Wide Association Study to Identify the Genetic Determinants of Otitis Media Susceptibility in Childhood

Abstract: Background: Otitis media (OM) is a common childhood disease characterised by middle ear inflammation and effusion. Susceptibility to recurrent acute OM (rAOM; ≥3 episodes of AOM in 6 months) and chronic OM with effusion (COME; MEE ≥3 months) is 40-70% heritable. Few underlying genes have been identified to date, and no genome-wide association study (GWAS) of OM has been reported. Methods and Findings: Data for 2,524,817 single nucleotide polymorphisms (SNPs; 535,544 quality-controlled SNPs genotyped by Illumina 660W-Quad; 1,989,273 by imputation) were analysed for association with OM in 416 cases and 1,075 controls from the Western Australian Pregnancy Cohort (Raine) Study. Logistic regression analyses under an additive model undertaken in GenABEL/ProbABEL adjusting for population substructure using principal components identified SNPs at CAPN14 (rs6755194: OR = 1.90; 95%CI 1.47-2.45; Padj-PCA = 8.3×10-7) on chromosome 2p23.1 as the top hit, with independent effects (rs1862981: OR = 1.60; 95%CI 1.29-1.99; Padj-PCA = 2.2×10-5) observed at the adjacent GALNT14 gene. In a gene-based analysis in VEGAS, BPIFA3 (PGene = 2×10-5) and BPIFA1 (PGene = 1.07×10-4) in the BPIFA gene cluster on chromosome 20q11.21 were the top hits. In all, 32 genomic regions show evidence of association (Padj-PCA<10-5) in this GWAS, with pathway analysis showing a connection between top candidates and the TGFβ pathway. However, top and tag-SNP analysis for seven selected candidate genes in this pathway did not replicate in 645 families (793 affected individuals) from the Western Australian Family Study of Otitis Media (WAFSOM). Lack of replication may be explained by sample size, difference in OM disease severity between primary and replication cohorts or due to type I error in the primary GWAS. Conclusions: This first discovery GWAS for an OM phenotype has identified CAPN14 and GALNT14 on chromosome 2p23.1 and the BPIFA gene cluster on chromosome 20q11.21 as novel candidate genes which warrant further analysis in cohorts matched more precisely for clinical phenotypes.

Topical 0.1% rapamycin for angiofibromas in paediatric patients with tuberous sclerosis: a pilot study of four patients.

Abstract: Tuberous sclerosis complex (TSC) is an autosomal dominant genodermatosis characterised by the development of hamartomatous tumours in multiple organs including the brain, skin, kidneys, heart and lungs. Facial angiofibromas are the most visible and unsightly of the cutaneous manifestations of TSC, often resulting in stigmatisation for both the affected individuals and their families. Current treatments include vascular laser, ablative lasers and other destructive techniques such as shave excision and electrodessication. For the best outcome these treatments have to be repeated throughout childhood and teenage years, necessitating multiple general anaesthetics. We report a pilot study of topical rapamycin in four children with TSC and facial angiofibromas. Two patients were trialled on 0.1% rapamycin in petrolatum and the other two patients with 0.1% rapamycin solution (Rapamune) applied topically. Both preparations were rapidly and equally effective, however the 0.1% in petrolatum was much better tolerated. Younger patients with smaller angiofibromas had the best response with near complete clearance. Both preparations were more cost effective than pulsed dye laser under general anaesthesia. Although larger studies are needed, this treatment shows a potential to be a first-line management for facial angiofibromas in TSC and appears safe to start in early childhood.

Antibiotic-impregnated catheters for the prevention of CSF shunt infections: a systematic review and meta-analysis.

Abstract: Context. CSF infections are a serious complication of CSF shunts and external ventricular drains (EVDs). Antibiotic-impregnated catheters (AIC) have been tried in order to minimise the risk of such infections. Objectives. To conduct a systematic review and a meta-analysis comparing AICs versus non-AICs used as ventriculo-peritoneal (VP) shunts or external ventricular drains (EVDs) in the neonatal population. The secondary aim was to include data from a paediatric and adult population if insufficient information was available from neonatal studies. Data sources. PubMed (March 2011), EMBASE (March 2011), CENTRAL (1980–March 2011), and CINAHL (March 2011) were searched. Study selection. Both randomised controlled trials (RCTs) and observational studies were included. Results. Only three observational studies reported on the use of AI-VP shunt catheters in the neonatal population. Meta-analysis found a statistically significant difference favouring AI shunts (RR: 0.37; CI: 0.16, 0.86; p = 0.02). Twelv...

The normal and the challenging pediatric airway.

Abstract: Management of a child's airway is one of the main sources of stress for anesthetists who do not routinely anesthetize children. Unfortunately, trainees are gaining less experience in pediatric airway management than in the past, which is particularly difficult at a time when some beliefs about airway management are being challenged and airway management is less standardized. Fortunately, most children have an easily managed, normal airway. Nevertheless, it is of vital importance to teach our trainees the basic airway skills that are probably the most important skill in an anesthetists' repertoire when it comes to a difficult airway situation. This review focuses on the airway management in children with a normal and a challenging airway. Different choices of airway management in children, and their advantages and disadvantages are discussed. Furthermore, the three broad causes of a challenging airway in children and infants are highlighted - the difficulty obtaining a mask seal, difficulty visualizing the vocal cords, and the third cause in which the larynx can be visualized but the difficulty lies at or beyond that level. Guidelines are given how to deal with these patients as well as with the feared but rare scenario of 'cannot ventilate, cannot intubate' in children.

Tertiary paediatric refugee health clinic in Western Australia: Analysis of the first 1026 children

Abstract: Aim: Children account for approximately half of the humanitarian refugees currently resettled in Australia. A multidisciplinary refugee health clinic (RHC) was established at the tertiary paediatric hospital in Western Australia to address burgeoning referrals of refugee children following voluntary post-resettlement health assessment. The aim of this study is to describe the epidemiology of common conditions in resettled paediatric refugees attending a tertiary multidisciplinary RHC. Methods: Standardised clinical and demographic data were routinely collected during first visit clinical assessment at the RHC. Descriptive analyses of the first 1026 children are presented. Results: One thousand twenty-six refugee children from 475 families and over 30 different ethnicities were described. Nine hundred twenty-seven (90.4%) children were referred following post-resettlement health assessment. Median age was 7.8 years. Common reasons for referral were: vitamin D deficiency (400, 39%), iron deficiency (226, 22%), positive Helicobacter pylori serology (206, 21%), poor appetite (175, 17.1%), and schistosomiasis (170, 16.6%). Comorbidities identified by the RHC included tinea capitis and corporis (297, 28.9%), and dental disease (228, 22.2%). Two-thirds of children (680, 66.3%) had at least one abnormal finding on clinical examination that identified pathologies that were not evident from the history. Three hundred eighty children (37%) were referred to sub-specialty services. Conclusions: A multidisciplinary paediatric RHC facilitated and strengthened the management of refugee children with multiple and complex health needs. Evidenced–based culturally appropriate methods to identify developmental delay, psychological morbidity and quantify social needs of this vulnerable population remain uncertain. These findings are relevant to the continuing evolution of paediatric refugee health care in Australia and other high income countries.

Use of data linkage to investigate the aetiology of acute lower respiratory infection hospitalisations in children

Abstract: Aim: To document the aetiology of acute lower respiratory infection (ALRI) hospitalisations in Western Australian children by linking population-based laboratory data with hospital morbidity data. Methods: Data from all ALRI hospitalisations and laboratory records related to respiratory pathogens between 2000 and 2005 were extracted and linked through a population-based record linkage system. The proportion of specimens that were positive for each respiratory viral or bacterial pathogen was documented. Results: Eight thousand nine hundred and eighty (45.2%) ALRI hospitalisations were linked to a laboratory record. Admissions to a private hospital and admissions from non-metropolitan areas were less likely to have a linked laboratory record. In 57.9% of linked hospitalisations, a respiratory virus and/or a bacterial pathogen was identified. Frequently identified viral pathogens included respiratory syncytial virus (RSV; n= 3226; 39.5% of those tested), influenza viruses (n= 664; 8.5%), parainfluenza virus type 3 (n= 348; 4.6%), picornaviruses (n= 292; 22.3%) and adenoviruses (n= 211; 2.7%). RSV was identified in 63.7% of bronchiolitis admissions in those aged under 6 months and 33.1% of pneumonia admissions in those aged under 12 months. Influenza viruses were identified in 81.6% of influenza-coded admissions. When a test was requested, Bordetella pertussis was identified in 21.2% of ALRI hospitalisations (n= 354), including 86.8% of whooping cough-coded admissions. Conclusions: This is the first report of population-based data linkage between statewide laboratory data and hospitalisation records and demonstrates proof of principle. RSV continues to be an important pathogen in ALRI. As pathogens were identified across all diagnoses, relying on hospital diagnosis coding alone may not accurately estimate the burden of different categories of ALRI.

Solitary, multifocal and generalized myofibromas: clinicopathological and immunohistochemical features of 114 cases.

Abstract: Oudijk L, den Bakker M A, Hop W C J, Cohen M, Charles A K, Alaggio R, Coffin C M & de Krijger R R (2012) Histopathology 60, E1–E11 Solitary, multifocal and generalized myofibromas: clinicopathological and immunohistochemical features of 114 cases Aims: To report a large series of solitary and multiple myofibromas with systematic clinicopathological correlations. Methods and results: We report on 114 patients with myofibromas, 97 of which were solitary and 17 multifocal. The age at presentation ranged from newborn to 70 years. All multifocal myofibromas and 91% of solitary myofibromas occurred in children. The head and neck region was the most common site (n = 43), followed by the trunk (n = 24), lower limbs (n = 14), upper limbs (n = 11), and viscera (n = 4). Solitary and multifocal myofibromas stained positively for smooth muscle actin (SMA) in 95% and 92% of cases, muscle-specific actin (MSA) in 75% and 50% of cases, and desmin in 10% and 14% of cases, respectively. Regressive features were seen in 34 solitary myofibromas and in nine multifocal myofibromas. Most patients were treated with complete excision (n = 79) or partial excision (n = 12). There were no recurrences after treatment. Conclusions: Solitary and multiple myofibromas are benign tumours that predominantly occur in infancy and childhood. Myofibromas occur especially in the head and neck region, and are characterized by SMA and, to a lesser extent, MSA expression. The clinical course is self-limiting, and local excision appears to be sufficient.

Factors associated with the performance of a blood-based interferon-γ release assay in diagnosing tuberculosis

Abstract: Background: Indeterminate results are a recognised limitation of interferon-γ release assays (IGRA) in the diagnosis of latent tuberculosis (TB) infection (LTBI) and TB disease, especially in children. We investigated whether age and common co-morbidities were associated with IGRA performance in an unselected cohort of resettled refugees. Methods: A retrospective cross-sectional study of refugees presenting for their post-resettlement health assessment during 2006 and 2007. Refugees were investigated for prevalent infectious diseases, including TB, and for common nutritional deficiencies and haematological abnormalities as part of standard clinical screening protocols. Tuberculosis screening was performed by IGRA; QuantiFERON-TB Gold in 2006 and QuantiFERON-TBGold In-Tube in 2007. Results: Complete data were available on 1130 refugees, of whom 573 (51%) were children less than 17 years and 1041 (92%) were from sub-Saharan Africa. All individuals were HIV negative. A definitive IGRA result was obtained in 1004 (89%) refugees, 264 (26%) of which were positive; 256 (97%) had LTBI and 8 (3%) had TB disease. An indeterminate IGRA result was obtained in 126 (11%) refugees (all failed positive mitogen control). In multivariate analysis, younger age (linear OR = 0.93 [95% CI 0.91-0.95], P<0.001), iron deficiency anaemia (2.69 [1.51-4.80], P = 0.001), malaria infection (3.04 [1.51-6.09], P = 0.002), and helminth infection (2.26 [1.48-3.46], P<0.001), but not vitamin D deficiency or insufficiency, were associated with an indeterminate IGRA result. Conclusions: Younger age and a number of common co-morbidities are significantly and independently associated with indeterminate IGRA results in resettled predominantly African refugees.

Analysis of Glucose Responses to Automated Insulin Suspension With Sensor-Augmented Pump Therapy

Abstract: OBJECTIVE The advent of sensor-augmented pump therapy with a low-glucose suspend (LGS) function (Medtronic Paradigm Veo System), allowing insulin to be automatically suspended for up to 2 h when sensor glucose falls below a preset threshold, has the potential to reduce the duration of hypoglycemia. In this report, we analyzed blood glucose profiles following a full 2-h insulin suspension activated by the LGS function, as well as examined different patterns of use among patients. RESEARCH DESIGN AND METHODS Data from a cohort of participants using the Veo system for up to 6 months were analyzed to determine the time and duration of insulin suspension activated by the LGS function. We further evaluated overnight suspend events with no patient response occurring prior to 3:00 a.m., which allowed us to determine the pattern of sensor glucose values with no patient intervention during and after the period of insulin suspension. RESULTS There were 3,128 LGS events during the 2,493 days evaluated. The median duration was 11.2 min, and 36% of events occurred overnight. There were 126 full 2-h suspend events that occurred overnight with no patient response, occurring before 3:00 a.m. For these events, the mean sensor glucose at the end of the 2-h suspend period was 99 ± 6 mg/dL ([means ± SE] 5.5 ± 0.3 mmol/L). The mean sensor glucose 2 h after insulin delivery resumed was 155 ± 10 mg/dL (8.6 ± 0.6 mmol/L). There were no episodes of severe hypoglycemia or diabetic ketoacidosis. CONCLUSIONS Analyses of sensor glucose patterns following insulin suspension activated by LGS suggest that this technology is safe and unlikely to be associated with adverse outcomes.

A comparison of activity, participation and quality of life in children with and without spastic diplegia cerebral palsy

Abstract: Purpose: To measure activity, participation and QoL in children with CP and to determine how these differ from a comparable group of typically developing (TD) children.Method: A total of eleven males and eight females with CP ranging in age from 5 to 12 years (mean age 7 years 10 months, SD 1 year 10 months; GMFCS level I–II) and 19 age and sex matched TD peers were recruited. Activity was measured using Paediatric Activity Card Sort (PACS), 6-Minute Walk Test and Timed Up and Go Test (TUG). Participation was measured using the assessment of Life Habits (LIFE-H) and quality of life was measured using the Cerebral Palsy Quality of Life Questionnaire (CP-QoL).Results: TD children performed more activities of personal care than children with CP, as assessed via the PACS, t(40) = 3.266, p = 0.002. TD children participate in more life habits than children with CP across all the LIFE-H domains except that of relationships. Results from the CP-QoL indicate that TD children experience a greater QoL in the domains...

Does topical lidocaine before tracheal intubation attenuate airway responses in children? An observational audit.

Abstract: Background:? The use of topical lidocaine, applied to the airways with various administration techniques, is common practice in pediatric anesthesia in many institutions. However, it remains unclear whether these practices achieve their intended goal of reducing the risk of perioperative respiratory adverse events (PRAE) in children undergoing elective endotracheal intubation without neuromuscular blockade (NMB). The relative frequency of PRAE (laryngospasm, coughing, desaturation >95%) associated with no use of topical airway lidocaine (TAL), with TAL sprayed directly onto the vocal cords, and TAL administered blindly into the pharynx was assessed. Methods:? This prospective audit involved 1000 patients undergoing general anesthesia with elective endotracheal intubation without NMB. Patients with suspected difficult airways or undergoing airway surgery were excluded. The use of TAL and the mode of administration were recorded. Respiratory adverse events were recorded in the perioperative period. Results:? Two hundred and fifty-four patients had the vocal cords sprayed under direct vision, 236 had lidocaine blindly dripped into the pharynx, and 510 received no TAL. The mean age and known risk factors for PRAE (asthma, recent upper respiratory tract infection (?2?weeks), passive smoking, hayfever, past or present eczema, nocturnal dry cough) were similar among the groups. The proportion of patients with desaturation (>95%) between induction of anesthesia and discharge from the recovery room was higher in the two groups who received TAL (data combined for all patients receiving lidocaine regardless of administration method, P?=?0.01) compared to those who received no TAL. No difference in the rates of laryngospasm (P?=?0.13) or cough (P?=?0.07) was observed among the groups. There was no difference in the rates of PRAE between the groups given TAL directly onto the vocal cords and in those whom received TAL blindly. Conclusions:? The incidence of desaturation was higher in patients receiving TAL compared with children who did not. This association should perhaps be considered when contemplating the use of this technique.

Evaluation of Norepinephrine Transporter Expression and Metaiodobenzylguanidine Avidity in Neuroblastoma: A Report from the Children's Oncology Group

Abstract: Purpose. (123)I-metaiodobenzylguanidine (MIBG) is used for the diagnostic evaluation of neuroblastoma. We evaluated the relationship between norepinephrine transporter (NET) expression and clinical MIBG uptake. Methods. Quantitative reverse transcription PCR (N = 82) and immunohistochemistry (IHC; N = 61) were performed for neuroblastoma NET mRNA and protein expression and correlated with MIBG avidity on diagnostic scans. The correlation of NET expression with clinical features was also performed. Results. Median NET mRNA expression level for the 19 MIBG avid patients was 12.9% (range 1.6-73.7%) versus 5.9% (range 0.6-110.0%) for the 8 nonavid patients (P = 0.31). Median percent NET protein expression was 50% (range 0-100%) in MIBG avid patients compared to 10% (range 0-80%) in nonavid patients (P = 0.027). MYCN amplified tumors had lower NET protein expression compared to nonamplified tumors (10% versus 50%; P = 0.0002). Conclusions. NET protein expression in neuroblastoma correlates with MIBG avidity. MYCN amplified tumors have lower NET protein expression.