Expanding the phenotypic spectrum of Chromosome 16p13.11 microduplication: A multicentric analysis of 206 patients.

INTRODUCTION: Recurrent chromosome 16p13.11 microduplication has been characterised in the literature as a cause of developmental delay, learning difficulties and behavioural abnormalities. It is a neurosusceptibility locus and has incomplete penetrance and variable expression. Other clinical features, such as cardiac abnormalities have also been reported. The duplicated region contains the MYH11 gene, which encodes the protein myosin-11 and is a component of the myosin heavy chain in smooth muscle. Recent literature has suggested 16p13.11 microduplication as one of the possible risk factors for thoracic aortic aneurysms and dissection (TAAD). Therefore, we studied the detailed phenotype of cases of chromosome 16p13.11 microduplication from seven centres in the United Kingdom (UK) to expand the phenotype, focusing on the cardiac abnormalities. METHODS: All individuals with a chromosome 16p13.11 microduplication seen in Clinical Genetics prior to June 2017 in 6 centres (prior to 2018 in the seventh centre) were identified through the regional genetics laboratory databases. A Microsoft Excel® proforma was created and clinical data was collected retrospectively from clinical genetics databases from the seven genetics services in the UK. The data was collated and analysed collectively. RESULTS: The majority of the individuals presented with (72%) developmental delay and (62%) behavioural abnormalities, in keeping with the published literature. 27% had some dysmorphic features, 14% had visual impairment and 8% had congenital cardiac abnormalities. Echocardiograms were performed in 50% of patients, and only 3.8% patients had aortic dilatation and no one had aortic dissection. 9.7% of patients were found to have a second genetic/chromosomal diagnosis, especially where there were additional phenotypic features. CONCLUSION: 16p13.11 microduplication is a neurosusceptibility locus and is associated with variable expression. It may be helpful to refer children with 16p13.11 microduplication for a cardiac review for congenital cardiac abnormalities and also for ophthalmological assessment. Further prospective studies with cardiac assessments are recommended in this cohort of patients to determine whether ongoing aortic surveillance is indicated. Guidelines about the frequency of surveillance are indicated, especially in individuals with normal cardiac findings. We also highlight the importance of considering a second diagnosis if the phenotype is inconsistent with that reported.

'It's Hard to Make Good Choices and It Costs More': Adolescents' Perception of the External School Food Environment.

Research on the impact of school and community food environments on adolescent food choice is heavily reliant on objective rather than subjective measures of food outlets around schools and homes. Gaining the perspective of adolescents and how they perceive and use food environments is needed. The aim of this study was to explore adolescent's perception and use of the food environment surrounding their schools. Purposive sampling was used to recruit schools. Mapping exercises and discussion groups were facilitated with 95 adolescents from six schools. Thematic analysis showed that adolescents are not loyal to particular shops but are attracted to outlets with price discounts, those with 'deli' counters and sweets. Cost, convenience and choice are key factors influencing preference for food outlets and foods. Quality, variety and health were important factors for adolescents but these features, especially affordable healthy food, were hard to find. Social factors such as spending time with friends is also an important feature of food environments that deserves further attention. Adolescents' perceptions of their food environment provide insights into features that can be manipulated to enable healthy choices.

Neuronal antibody prevalence in children with seizures under 3 years: A prospective national cohort.

OBJECTIVE: To report the prevalence of anti-neuronal antibodies in a prospective whole-nation cohort of children presenting with seizures before their third birthday. METHODS: This was a prospective population-based national cohort study involving all children presenting with new-onset epilepsy or complex febrile seizures before their third birthday over a 3-year period. Patients with previously identified structural, metabolic, or infectious cause for seizures were excluded. Serum samples were obtained at first presentation and tested for 7 neuronal antibodies using live cell-based assays. Clinical data were collected with structured proformas at recruitment and 24 months after presentation. In addition, patients with seizures and clinically suspected autoimmune encephalitis were independently identified by a review of the case records of all children <3 years of age in Scotland who had undergone EEG. RESULTS: Two hundred ninety-eight patients were identified and recruited and underwent autoantibody testing. Antibody positivity was identified in 18 of 298 (6.0%). The antibodies identified were GABA receptor B (n = 8, 2.7%), contactin-associated protein 2 (n = 4, 1.3%), glycine receptor (n = 3, 1.0%), leucine-rich glioma inactivated 1 (n = 2, 0.7%), NMDA receptor (n = 1, 0.3%), and GABA receptor A (n = 1, 0.3%). None of these patients had a clinical picture of autoimmune encephalitis. Seizure classification and clinical phenotype did not correlate with antibody positivity. CONCLUSIONS: Autoimmune encephalitis is very rare in early childhood. However serum neuronal antibodies are identified in 6.4% of children presenting with seizures at <3 years of age. Antibody testing should not be a routine clinical test in early childhood-onset epilepsy because, in the absence of other features of autoimmune encephalitis, antibody positivity is of doubtful clinical significance. Antibody testing should be reserved for patients with additional features of encephalitis.

Bullying victimization: time trends and the overlap between traditional and cyberbullying across countries in Europe and North America.

OBJECTIVES: This study explores recent cross-national trends over time (2002-2014) in the occurrence of victimization by bullying; then it documents the overlap between cybervictimization and traditional bullying in 2014 among adolescents in 37 countries. METHODS: Data from four cycles (2002, 2006, 2010, and 2014) of the cross-national Health Behavior in School-Aged Children study were included (N = 764,518). Trends in traditional victimization were evaluated using logistic regression models in 37 countries. Prevalence of cybervictimization and the overlap between cybervictimization and traditional victimization were estimated. RESULTS: Linear decreases in bullying victimization were observed in 21 countries among boys, and in 12 countries among girls. The prevalence of cybervictimization was systematically lower than traditional victimization. Overall across all countries, 45.8% of those who reported cybervictimization also reported traditional victimization (46.5% for boys and 45.3% for girls), but wide country variations were observed. CONCLUSIONS: These indicate the need for a more holistic perspective to intervention and prevention that considers all expressions of bullying, traditional or online. Public health programs and policies could focus on addressing bullying more broadly, rather than focusing on behaviors that happen in a particular context.

Amniotic band sequence in paternal half-siblings with vascular Ehlers-Danlos syndrome.

Familial amniotic band sequence (ABS) is rare but has been reported in the offspring of mothers with connective tissue disorders. We present a family of two half-siblings with ABS who share the same biological father. Following a serious vascular event a de novo pathogenic variant in COL3A1 was detected in the father, confirming a diagnosis of vascular Ehlers-Danlos syndrome (vEDS). The same variant was found in both his ABS-affected children but not in his unaffected child. The amniotic membrane is derived from fetal tissue, type III collagen being a component. As the affected children are paternal half-siblings, ABS was less likely due to maternal factors. Rather, the amniotic bands may have resulted from decreased type III collagen production as seen in people with vEDS, causing fragility of the amniotic membrane. Consequently, it is important to consider vEDS in patients with ABS.

Incidence and phenotypes of childhood-onset genetic epilepsies: a prospective population-based national cohort.

Epilepsy is common in early childhood. In this age group it is associated with high rates of therapy-resistance, and with cognitive, motor, and behavioural comorbidity. A large number of genes, with wide ranging functions, are implicated in its aetiology, especially in those with therapy-resistant seizures. Identifying the more common single-gene epilepsies will aid in targeting resources, the prioritization of diagnostic testing and development of precision therapy. Previous studies of genetic testing in epilepsy have not been prospective and population-based. Therefore, the population-incidence of common genetic epilepsies remains unknown. The objective of this study was to describe the incidence and phenotypic spectrum of the most common single-gene epilepsies in young children, and to calculate what proportion are amenable to precision therapy. This was a prospective national epidemiological cohort study. All children presenting with epilepsy before 36 months of age were eligible. Children presenting with recurrent prolonged (>10 min) febrile seizures; febrile or afebrile status epilepticus (>30 min); or with clusters of two or more febrile or afebrile seizures within a 24-h period were also eligible. Participants were recruited from all 20 regional paediatric departments and four tertiary children's hospitals in Scotland over a 3-year period. DNA samples were tested on a custom-designed 104-gene epilepsy panel. Detailed clinical information was systematically gathered at initial presentation and during follow-up. Clinical and genetic data were reviewed by a multidisciplinary team of clinicians and genetic scientists. The pathogenic significance of the genetic variants was assessed in accordance with the guidelines of UK Association of Clinical Genetic Science (ACGS). Of the 343 patients who met inclusion criteria, 333 completed genetic testing, and 80/333 (24%) had a diagnostic genetic finding. The overall estimated annual incidence of single-gene epilepsies in this well-defined population was 1 per 2120 live births (47.2/100 000; 95% confidence interval 36.9-57.5). PRRT2 was the most common single-gene epilepsy with an incidence of 1 per 9970 live births (10.0/100 000; 95% confidence interval 5.26-14.8) followed by SCN1A: 1 per 12 200 (8.26/100 000; 95% confidence interval 3.93-12.6); KCNQ2: 1 per 17 000 (5.89/100 000; 95% confidence interval 2.24-9.56) and SLC2A1: 1 per 24 300 (4.13/100 000; 95% confidence interval 1.07-7.19). Presentation before the age of 6 months, and presentation with afebrile focal seizures were significantly associated with genetic diagnosis. Single-gene disorders accounted for a quarter of the seizure disorders in this cohort. Genetic testing is recommended to identify children who may benefit from precision treatment and should be mainstream practice in early childhood onset epilepsy.

Bullying and bystander behaviour and health outcomes among adolescents in Ireland.

BACKGROUND: Little is known about the impact of being a bystander to bullying. This study compared health outcomes among bullies, victims and bystanders, and investigated actions taken by bystanders when they saw bullying. METHOD: Participants included 7522 students aged 12-18 years that completed self-report questionnaires in the 2013/2014 Health Behaviour in School-aged Children survey. Binary logistic regression models (controlled for bully, victim, bystander status and demographic variables) were used to investigate the associations between participation in bullying as a bully, victim and bystander and health outcomes. RESULTS: Overall, 13.3% of adolescents reported being a bully, 25.1% reported being a victim and 30.5% reported that they saw bullying, in the last couple of months. Bystanders were significantly more likely to experience psychological symptoms (OR 1.355), somatic symptoms (OR 1.392) and low life satisfaction (OR 1.268) than those who were not bystanders. Helping the victim was significantly associated with experiencing psychological symptoms (OR 1.240), somatic symptoms (OR 1.251) and low life satisfaction (OR 1.198). Being a bully was significantly associated with experiencing psychological symptoms (OR 1.382) and not having excellent health (OR 1.252). Victims were significantly more likely to experience psychological symptoms (OR 2.437), somatic symptoms (OR 2.364), low life satisfaction (OR 2.564) and not having excellent health (OR 1.559). CONCLUSION: In Ireland, being a bystander to bullying is more prevalent in schools than bullying perpetration or victimisation. The impact of being a bystander to bullying needs to be highlighted and included in intervention development.

The relationship between cyberbullying and friendship dynamics on adolescent body dissatisfaction: A cross-sectional study.

The relationship between cyberbullying and friendship dynamics on adolescent body dissatisfaction was examined. Data from the Irish contribution to the international cross-sectional 2013/2014 Health Behaviour in School-aged Children study were used. Results showed that girls were three times more likely than boys to report that their body is too fat, and adolescents who were cyberbullied were almost twice as likely as adolescents who were not cyberbullied to consider themselves too fat. Stronger friendship dynamics were associated with decreased levels of body dissatisfaction, and friendship dynamics were found to partially mediate the relationship between cyberbullying and body dissatisfaction.

Cross-national time trends in bullying victimization in 33 countries among children aged 11, 13 and 15 from 2002 to 2010.

BACKGROUND: Bullying among children and adolescents is a public health concern; victimization is associated with psychological and physical health problems. The purpose of this study is to examine temporal trends in bullying victimization among school-aged children in Europe and North America. METHODS: Data were obtained from cross-sectional self-report surveys collected as part of the Health Behaviour in School-aged Children (HBSC) study from nationally representative samples of 11-, 13- and 15-year-olds, from 33 countries and regions which participated in the 2001-02, 2005-06 and 2009-10 surveys. Responses from 581 838 children were included in the analyses. Binary logistic regression was used for the data analyses. RESULTS: The binary logistic regression models showed significant decreasing trends in occasional and chronic victimization between 2001-02 and 2009-10 across both genders in a third of participating countries. One country reported significant increasing trends for both occasional and chronic victimization. Gender differences in trends were evident across many countries. CONCLUSION: Overall, while still common in many countries, bullying victimization is decreasing. The differences between countries highlight the need to further investigate measures undertaken in countries demonstrating a downward trend.

The burden of mucosal barrier injury laboratory-confirmed bloodstream infection among hematology, oncology, and stem cell transplant patients.

OBJECTIVE: To evaluate the impact and burden of the new National Healthcare Safety Network surveillance definition, mucosal barrier injury laboratory-confirmed bloodstream infection (MBI-LCBI), in hematology, oncology, and stem cell transplant populations. DESIGN: Retrospective cohort study. SETTING: Two hematology, oncology, and stem cell transplant units at a large academic medical center. METHODS: Central line-associated bloodstream infections (CLABSIs) identified during a 14-month period were reviewed and classified as MBI-LCBI or non-MBI-LCBI (MBI-LCBI criteria not met). During this period, interventions to improve central line maintenance were implemented. Characteristics of patients with MBI-LCBI and non-MBI-LCBI were compared. Total CLABSI, MBI-LCBI, and non-MBI-LCBI rates were compared between baseline and postintervention phases of the study period. RESULTS: Among 66 total CLABSI cases, 47 (71%) met MBI-LCBI criteria. Patients with MBI-LCBI and non-MBI-LCBI were similar in regard to most clinical and demographic characteristics. Between the baseline and postintervention study periods, the overall CLABSI rate decreased from 3.37 to 3.21 infections per 1,000 line-days (incidence rate ratio, 0.95; 4.7% reduction, P=.84), the MBI-LCBI rate increased from 2.08 to 2.61 infections per 1,000 line-days (incidence rate ratio, 1.25; 25.3% increase, P=.44), and the non-MBI-LCBI rate decreased from 1.29 to 0.60 infections per 1,000 line-days (incidence rate ratio, 0.47; 53.3% reduction, P=.12). CONCLUSIONS: Most CLABSIs identified among hematology, oncology, and stem cell transplant patients met MBI-LCBI criteria, and CLABSI prevention efforts did not reduce these infections. Further review of the MBI-LCBI definition and impact is necessary to direct future definition changes and reporting mandates.

Exploring traditional and cyberbullying among Irish adolescents.

OBJECTIVES: This study aimed to explore the associations of traditional and cyberbullying victimisation with self-reported health and life satisfaction, and to examine whether involvement in risk behaviours contributes to these health outcomes. METHODS: We asked questions on involvement in traditional and cyberbullying, risk behaviours, self-reported health and life satisfaction to school children. In total, 318 students aged from 15 to 18 years old in 8 post-primary schools in Ireland completed the survey. RESULTS: Children who were victims of bullying were more likely to report poor health, low life satisfaction and engaging in risky behaviours. Although not statistically significant, we found that cyber victimisation was positively associated with increased reporting of poor health and low life satisfaction. CONCLUSION: Traditional bullying is the most common type of bullying among school children in Ireland, and overall, seems to have a stronger association with poor health. However, a sizable proportion of children are victims of cyberbullying or of both cyberbullying and traditional bullying. It is, therefore, important to acknowledge, identify and address all types of bullying to improve the health outcomes of children.

Assessing Interprofessional Teamwork in Inpatient Medical Oncology Units.

PURPOSE: Teamwork is important to providing safe and effective care for hospitalized patients with cancer; however, few studies have evaluated teamwork in this setting. METHODS: We surveyed all nurses, residents, hospitalists, and oncology physicians in oncology units at a large urban teaching hospital from September to November 2012. Respondents rated teamwork using a validated instrument (Safety Attitudes Questionnaire; scale, 0 to 100) and rated the quality of collaboration they had experienced with other professionals using a 5-point ordinal response scale (1, very low quality; 5, very high quality). Respondents also rated potential barriers to collaboration using a 4-point ordinal response scale (1, not at all a barrier; 4, major barrier). We compared ratings by professionals using analysis of variance (ANOVA). RESULTS: Overall, 129 (67%) of 193 eligible participants completed the survey. Teamwork scores differed across professional types, with nurses providing the lowest ratings (69.7) and residents providing the highest (81.9; ANOVA P = .01). Ratings of collaboration with nurses were high across all types of professionals. Ratings of collaboration with physicians varied significantly by professional type (P ≤ .02), with nurses giving lower ratings of collaboration with all physician types. Similarly, perceived barriers to collaboration differed by professional type, with nurses perceiving the biggest barrier to be negative attitudes regarding the importance of communication. Oncologists did not perceive any of the listed options as major barriers to collaboration. CONCLUSION: In inpatient oncology units, discrepancies exist between nurses' and physicians' ratings of teamwork and collaboration. Oncologists seem to be unaware that teamwork is suboptimal in this setting.

Temporal and spatial distribution of human cryptosporidiosis in the west of Ireland 2004-2007.

BACKGROUND: Cryptosporidiosis is increasingly recognised as a cause of gastrointestinal infection in Ireland and has been implicated in several outbreaks. This study aimed to investigate the spatial and temporal distribution of human cryptosporidiosis in the west of Ireland in order to identify high risk seasons and areas and to compare Classically Calculated (CC) and Empirical Bayesian (EB) incidence rates. Two spatial scales of analysis were used with a view to identifying the best one in assessing geographical patterns of infection. Global Moran's I and Local Moran's I tests of autocorrelation were used to test for evidence of global and local spatial clustering. RESULTS: There were statistically significant seasonal patterns of cryptosporidiosis with peaks in spring and an increasing temporal trend. Significant (p < 0.05) global spatial clustering was observed in CC rates at the Electoral Division (ED) level but not in EB rates at the same level. Despite variations in disease, ED level was found to provide the most accurate account of distribution of cryptosporidiosis in the West of Ireland but required spatial EB smoothing of cases. There were a number of areas identified with significant local clustering of cryptosporidiosis rates. CONCLUSION: This study identified spatial and temporal patterns in cryptosporidiosis distribution. The study also showed benefit in performing spatial analyses at more than one spatial scale to assess geographical patterns in disease distribution and that smoothing of disease rates for mapping in small areas enhances visualisation of spatial patterns. These findings are relevant in guiding policy decisions on disease control strategies.