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Recent years have seen an exponential increase in the variety of healthcare data captured across numerous sources. However, mechanisms to leverage these data sources to support scientific investigation have remained limited. In 2013 the Pediatric Heart Network (PHN), funded by the National Heart, Lung, and Blood Institute, developed the Integrated CARdiac Data and Outcomes (iCARD) Collaborative with the goals of leveraging available data sources to aid in efficiently planning and conducting PHN studies; supporting integration of PHN data with other sources to foster novel research otherwise not possible; and mentoring young investigators in these areas. This review describes lessons learned through the development of iCARD, initial efforts and scientific output, challenges, and future directions. This information can aid in the use and optimisation of data integration methodologies across other research networks and organisations.
Approximately 32,000 infants are born with CHDs each year in the United States of America. Of every 1000 live births, 2.3 require surgical or transcatheter intervention in the first year of life. There are few more stressful times for parents than when their neonate receives a diagnosis of complex CHD requiring surgery. The stress of caring for these infants is often unrelenting and may last for weeks, months, and often years, placing parents at risk for developing post-traumatic stress disorder, as well as a drastic decrease in quality of life. Anxiety often peaks in the days and weeks after discharge from the hospital as families no longer have immediate access to nursing and medical staff. The purpose of this paper is to describe the methods of a randomised controlled trial that was designed to determine whether REACH would favourably affect parental and infant outcomes by decreasing parental stress, improve parental quality of life, increase infant stability, and decrease resource utilisation in infants with complex CHD.
Despite improvements in the medical and surgical management of infants with CHD, growth failure before surgery in many infants continues to be a significant concern. A nutritional pathway was developed, the aim of which was to provide a structured approach to nutritional care for infants with CHD awaiting surgery.
Materials and methods
The modified Delphi process was development of a nutritional pathway; initial stakeholder meeting to finalise draft guidelines and develop questions; round 1 anonymous online survey; round 2 online survey; regional cardiac conference and pathway revision; and final expert meeting and pathway finalisation.
Paediatric Dietitians from all 11 of the paediatric cardiology surgical centres in the United Kingdom contributed to the guideline development. In all, 33% of participants had 9 or more years of experience working with infants with CHD. By the end of rounds 1 and 2, 76 and 96% of participants, respectively, were in agreement with the statements. Three statements where consensus was not achieved by the end of round 2 were discussed and agreed at the final expert group meeting.
Nutrition guidelines were developed for infants with CHD awaiting surgery, using a modified Delphi process, incorporating the best available evidence and expert opinion with regard to nutritional support in this group.
In May 2016 a Norovirus (NoV) gastroenteritis outbreak involved a high school class visiting a seaside resort near Taormina (Mascali, Sicily). Twenty-four students and a teacher were affected and 17 of them showed symptoms on the second day of the journey, while the others got ill within the following 2 days. Symptoms included vomiting, diarrhoea and fever, and 12 students required hospitalisation. Stool samples tested positive for NoV genome by Real-Time polymerase chain reaction assay in all 25 symptomatic subjects. The GII.P2/GII.2 NoV genotype was linked to the outbreak by ORF1/ORF2 sequence analysis. The epidemiological features of the outbreak were consistent with food/waterborne followed by person-to-person and/or vomit transmission. Food consumed at a shared lunch on the first day of the trip was associated to illness and drinking un-bottled tap water was also considered as a risk factor. The analysis of water samples revealed the presence of bacterial indicators of faecal contamination in the water used in the resort as well as in other areas of the municipal water network, linking the NoV gastroenteritis outbreak to tap water pollution from sewage leakage. From a single water sample, an amplicon whose sequence corresponded to the capsid genotype recovered from patients could be obtained.
Norwood palliation for patients with single ventricle heart disease is associated with a significant risk for acute kidney injury, which portends a worse prognosis. We sought to investigate the impact of hybrid stage I palliation (Hybrid) on acute kidney injury risk.
This study is a single-centre prospective case–control study of seven consecutive neonates with single ventricle undergoing Hybrid palliation. Levels of serum creatinine and four novel urinary biomarkers, namely neutrophil gelatinase-associated lipocalin, interleukin-18, liver fatty acid-binding protein, and kidney injury molecule-1, were obtained before and after palliation. Acute kidney injury was defined as a ⩾50% increase in serum creatinine within 48 hours after the procedure. Data were compared with a contemporary cohort of 12 neonates with single ventricle who underwent Norwood palliation.
Patients who underwent Hybrid were more likely to be high-risk candidates (86 versus 25%, p=0.01) compared with those who underwent Norwood. Despite similar preoperative serum creatinine levels, there was a trend towards higher levels of postoperative peak serum creatinine (0.7 [0.63, 0.94] versus 0.56 [0.47, 0.74], p=0.06) and rate of acute kidney injury (67 versus 29%, p=0.17) in the Norwood cohort. Preoperative neutrophil gelatinase-associated lipocalin (58.4 [11, 86.3] versus 6.3 [5, 16.2], p=0.07) and interleukin-18 (30.6 [9.6, 167.2] versus 6.3 [6.3, 16.4], p=0.03) levels were higher in the Hybrid cohort. Nevertheless, longitudinal mixed-effect models demonstrated Hybrid palliation to be a protective factor against increased postoperative levels of neutrophil gelatinase-associated lipocalin (estimate −1.8 [−3.0, −9.0], p<0.001) and liver fatty acid-binding protein (−49.3 [−89.7, −8.8], p=0.018).
In this single-centre case–control study, postoperative acute kidney injury risk did not differ significantly by single ventricle stage I treatment strategy; however, postoperative elevation in novel urinary biomarkers, consistent with subclinical kidney injury, was encountered in the Norwood cohort but not in the Hybrid cohort.
Children with hypoplastic left heart syndrome are at a risk for neurodevelopmental delays. Current guidelines recommend systematic evaluation and management of neurodevelopmental outcomes with referral for early intervention services. The Single Ventricle Reconstruction Trial represents the largest cohort of children with hypoplastic left heart syndrome ever assembled. Data on life events and resource utilisation have been collected annually. We sought to determine the type and prevalence of early intervention services used from age 1 to 4 years and factors associated with utilisation of services.
Data from 14-month neurodevelopmental assessment and annual medical history forms were used. We assessed the impact of social risk and geographic differences. Fisher exact tests and logistic regression were used to evaluate associations.
Annual medical history forms were available for 302 of 314 children. Greater than half of the children (52–69%) were not receiving services at any age assessed, whereas 20–32% were receiving two or more therapies each year. Utilisation was significantly lower in year 4 (31%) compared with years 1–3 (with a range from 40 to 48%) (p<0.001). Social risk factors were not associated with the use of services at any age but there were significant geographic differences. Significant delay was reported by parents in 18–43% of children at ages 3 and 4.
Despite significant neurodevelopmental delays, early intervention service utilisation was low in this cohort. As survival has improved for children with hypoplastic left heart syndrome, attention must shift to strategies to optimise developmental outcomes, including enrolment in early intervention when merited.
Cerebrovascular reactivity monitoring has been used to identify the lower limit of pressure autoregulation in adult patients with brain injury. We hypothesise that impaired cerebrovascular reactivity and time spent below the lower limit of autoregulation during cardiopulmonary bypass will result in hypoperfusion injuries to the brain detectable by elevation in serum glial fibrillary acidic protein level.
We designed a multicentre observational pilot study combining concurrent cerebrovascular reactivity and biomarker monitoring during cardiopulmonary bypass. All children undergoing bypass for CHD were eligible. Autoregulation was monitored with the haemoglobin volume index, a moving correlation coefficient between the mean arterial blood pressure and the near-infrared spectroscopy-based trend of cerebral blood volume. Both haemoglobin volume index and glial fibrillary acidic protein data were analysed by phases of bypass. Each patient’s autoregulation curve was analysed to identify the lower limit of autoregulation and optimal arterial blood pressure.
A total of 57 children had autoregulation and biomarker data for all phases of bypass. The mean baseline haemoglobin volume index was 0.084. Haemoglobin volume index increased with lowering of pressure with 82% demonstrating a lower limit of autoregulation (41±9 mmHg), whereas 100% demonstrated optimal blood pressure (48±11 mmHg). There was a significant association between an individual’s peak autoregulation and biomarker values (p=0.01).
Individual, dynamic non-invasive cerebrovascular reactivity monitoring demonstrated transient periods of impairment related to possible silent brain injury. The association between an impaired autoregulation burden and elevation in the serum brain biomarker may identify brain perfusion risk that could result in injury.
In this study, we isolate and analyse a new set of microsatellite loci for Cattleya walkeriana. Twenty-two primer pairs were screened for C. walkeriana (n = 32) and assessed for their transferability to Cattleya loddigesii (n = 12) and Cattleya nobilior (n = 06). All loci amplified for C. walkeriana; however, for C. loddigesii and C. nobilior, four and five primers, respectively, did not present amplification. The polymorphic loci presented between 2 and 13 alleles per locus for both C. walkeriana and C. loddigesii, with respective averages of 5.1 and 4.2. For C. nobilior, we found between two and five alleles per locus, with an average of 2.6. For C. walkeriana, observed heterozygosity varied from 0.100 to 0.966, whereas expected heterozygosity ranged from 0.097 to 0.900. The observed and expected heterozygosity for C. loddigesii and C. nobilior were also estimated. We found no significant linkage disequilibrium between any pair of loci, and evidence of null alleles at four loci (Cw16, Cw24, Cw30 and Cw31) for C. walkeriana. The combined power to exclude the first parent and combined non-exclusion probability of identity were 0.999 and 2.3 × 10−20, respectively. These new loci can be used in studies of germplasm resources, and assessments of genotypic and genetic diversity and population structure, thus improving the accuracy of such analyses and their applicability in the conservation and protection of these endangered species.
There is a known high prevalence of genetic and clinical syndrome diagnoses in the paediatric cardiac population. These disorders often have multisystem effects, which may have an important impact on neurodevelopmental outcomes. Taken together, these facts suggest that patients and families may benefit from consultation by genetic specialists in a cardiac neurodevelopmental clinic.
This study assessed the burden of genetic disorders and utility of genetics evaluation in a cardiac neurodevelopmental clinic.
A retrospective chart review was conducted of patients evaluated in a cardiac neurodevelopmental clinic from 6 December, 2011 to 16 April, 2013. All patients were seen by a cardiovascular geneticist with genetic counselling support.
A total of 214 patients were included in this study; 64 of these patients had a pre-existing genetic or syndromic diagnosis. Following genetics evaluation, an additional 19 were given a new clinical or laboratory-confirmed genetic diagnosis including environmental such as teratogenic exposures, malformation associations, chromosomal disorders, and single-gene disorders. Genetic testing was recommended for 112 patients; radiological imaging to screen for congenital anomalies for 17 patients; subspecialist medical referrals for 73 patients; and non-genetic clinical laboratory testing for 14 patients. Syndrome-specific guidelines were available and followed for 25 patients with known diagnosis. American Academy of Pediatrics Red Book asplenia guideline recommendations were given for five heterotaxy patients, and family-based cardiac screening was recommended for 23 families affected by left ventricular outflow tract obstruction.
Genetics involvement in a cardiac neurodevelopmental clinic is helpful in identifying new unifying diagnoses and providing syndrome-specific care, which may impact the patient’s overall health status and neurodevelopmental outcome.
Fontan survivors have depressed cardiac index that worsens over time. Serum biomarker measurement is minimally invasive, rapid, widely available, and may be useful for serial monitoring. The purpose of this study was to identify biomarkers that correlate with lower cardiac index in Fontan patients.
Methods and results
This study was a multi-centre case series assessing the correlations between biomarkers and cardiac magnetic resonance-derived cardiac index in Fontan patients ⩾6 years of age with biochemical and haematopoietic biomarkers obtained ±12 months from cardiac magnetic resonance. Medical history and biomarker values were obtained by chart review. Spearman’s Rank correlation assessed associations between biomarker z-scores and cardiac index. Biomarkers with significant correlations had receiver operating characteristic curves and area under the curve estimated. In total, 97 cardiac magnetic resonances in 87 patients met inclusion criteria: median age at cardiac magnetic resonance was 15 (6–33) years. Significant correlations were found between cardiac index and total alkaline phosphatase (−0.26, p=0.04), estimated creatinine clearance (0.26, p=0.02), and mean corpuscular volume (−0.32, p<0.01). Area under the curve for the three individual biomarkers was 0.63–0.69. Area under the curve for the three-biomarker panel was 0.75. Comparison of cardiac index above and below the receiver operating characteristic curve-identified cut-off points revealed significant differences for each biomarker (p<0.01) and for the composite panel [median cardiac index for higher-risk group=2.17 L/minute/m2 versus lower-risk group=2.96 L/minute/m2, (p<0.01)].
Higher total alkaline phosphatase and mean corpuscular volume as well as lower estimated creatinine clearance identify Fontan patients with lower cardiac index. Using biomarkers to monitor haemodynamics and organ-specific effects warrants prospective investigation.
Observations of five cepheids in Crux are described and annual epochs of maxima presented. The O–C diagram of S Crucis shows changes between two alternative periods. The observing method appears suited to sites with only a limited number of hours available.
Lower semi-continuity results for polyconvex functionals of the calculus of variations along sequences of maps u: Ω ⊂ ℝn → ℝm in W1,m, 2 ⩽ m⩽ n, weakly converging in W1,m-1, are established. In addition, for m = n + 1, we also consider the autonomous case for weakly converging maps in W1,n-1.
The optimal perioperative feeding strategies for neonates with CHD are unknown. In the present study, we describe the current feeding practices across a multi-institutional cohort.
Inclusion criteria for this study were as follows: all neonates undergoing cardiac surgery admitted to the cardiac ICU for ⩾24 hours preoperatively between October, 2013 and July, 2014 in the Pediatric Cardiac Critical Care Consortium registry.
The cohort included 251 patients from eight centres. The most common diagnoses included the following: hypoplastic left heart syndrome (17%), coarctation/aortic arch hypoplasia (18%), and transposition of the great arteries (22%); 14% of the patients were <37weeks of gestational age. The median total hospital length of stay was 21 days (interquartile range (IQR) 14–35) and overall mortality was 8%. Preoperative feeding occurred in 133 (53%) patients. The overall preoperative feeding rates across centres ranged from 29 to 79%. Postoperative feeds started on median day 2 (IQR 1–4); for patients with hypoplastic left heart syndrome postoperative feeds started on median day 4. Postoperative feeds were initiated in 89 (35%) patients before extubation (range across centres: 21–61%). The median cardiac ICU discharge feeding volume was 108 cc/kg/day, varying across centres. The mean discharge weight was 280 g above birth weight, ranging from +100 to 430 g across centres. A total of 110 (44%) patients had discharge feeding tubes, ranging from 6 to 80% across centres, and 40/110 patients had gastrostomy/enterostomy tubes placed. In addition, eight (3.2%) patients developed necrotising enterocolitis – three preoperatively and five postoperatively.
In this cohort, neonatal feeding practices and outcomes appear to vary across diagnostic groups and institutions. Only half of the patients received preoperative enteral nutrition; almost half had discharge feeding tubes. Multi-institutional collaboration is necessary to determine feeding strategies associated with best clinical outcomes.
Advancements in paediatric heart failure management have resulted in improved survival and a focus on long-term outcomes including health-related quality of life. We compared health-related quality of life in children with heart failure with healthy patients, children with chronic conditions, and children with cardiovascular disease.
Families (n=63) and children (n=73) aged 2–20 years with heart failure were enrolled and compared with data previously published for healthy patients (n=5480), those with chronic conditions (n=247), and those with cardiovascular disease (n=347). Patients and parents completed the PedsQL 4.0 and the Cardiac 3.0 Module health-related quality-of-life questionnaires. PedsQL scores including Total, Psychosocial Health Summary, and Physical were compared between groups. In general, patients with heart failure had lower scores than the healthy population (p=0.001), and comparable scores with those with chronic conditions. Parents perceived no difference in physical scores for children with heart failure when compared with healthy children, and perceived higher scores for children with heart failure when compared with those with chronic conditions (p⩽0.003). Furthermore, children with heart failure had decremental health-related quality-of-life scores as the American Heart Association stage of heart failure increased, such that patients with stage C heart failure had scores similar to children with severe cardiovascular disease.
Children with heart failure reported significantly impaired health-related quality of life compared with healthy children and similar scores compared with children with chronic conditions. Parental perceptions appear to underestimate these impairments. Children with heart failure appear to have progressive impairment of health-related quality of life with advancing stage of heart failure.
A contact investigation following a case of infectious tuberculosis (TB) reported in a call centre in Milan (Italy) led to the identification of three additional cases that had occurred in employees of the same workplace during the previous 5 years, one of whom was the probable source case. Thirty-three latent infections were also identified. At the time of diagnosis, the source case, because of fear of stigma related to TB, claimed to be unemployed and a contact investigation was not performed in the workplace. Cases were linked through genotyping of Mycobacterium tuberculosis. TB stigma has been described frequently, mainly in high-incidence settings, and is known to influence health-seeking behaviours and treatment adherence. The findings in this report highlight that TB-associated stigma may also lead to incomplete contact investigations. Little is known about the causes and impact of TB-related stigma in low-incidence countries and this warrants further exploration. Research is also needed to evaluate the effectiveness of specific interviewing techniques and training interventions for staff in reducing feelings of stigma in TB patients. Finally, the outbreak emphasizes the importance of integrating routine contact investigations with genotyping.
Photometry of the short-period (P ∼0.285 d) low-mass (M1 ∼0.67, M2 ∼0.48 M⊙) W UMa-type eclipsing binary RW Dor, mainly involving a good series of observations in 1987–88, using standard B and V filters at the Auckland Observatory, is examined. Analysis via light curve fittings alone permits both transit (near main sequence) and occultation (W-type contact binary) solutions. Consideration of proximity or other effects on the relatively small number of measured radial velocities gives rise to a more detailed review of the alternatives, though the (W-type) configuration determined by Hilditch, Hill & Bell (1992) is still confirmed. Further implications of this configuration are examined, given an apparent general trend to period decrease (Δ P/P ∼6 × 10−11), and some light curve asymmetry. This is consistent with the initially low-mass companion, Case-B scenario of Budding (1984). The evidence does suggest irregularity of the period variation however, and further detailed surveillance, including more spectroscopy, is desirable.
To demonstrate the generalisability of the Pediatric Cardiac Quality of Life Inventory in the United Kingdom.
Children and adolescents with heart disease were recruited from three tertiary paediatric cardiac centres in the United Kingdom and completed the Pediatric Cardiac Quality of Life Inventory. Item response option variability, total and subscale scores, patterns of correlation, and internal consistency were compared between the three sites.
A total of 1537 participants – 768 children/adolescents and 769 parents – were evaluated from the three sites. Patterns of item response option variability were similar and acceptable for all samples – child, adolescent, parent of child, and parent of adolescent. Internal consistency was high (0.82–0.96) for all samples from each site, and item–subscale, subscale–subscale, subscale–total, and item–total correlations were moderate to excellent for each centre. Comparisons of patterns of subscale and total score correlations between the three sites revealed no significant differences.
Scores on the Pediatric Cardiac Quality of Life Inventory are generalisable in the United Kingdom, supporting the use of this measure for multi-centre studies of health-related quality of life of children and adolescents with heart disease.
The stellar system ω Centauri (ω Cen) is well known for the large range in elemental abundances among its member stars. Recent work has indicated that the globular cluster M22 (NGC 6656) also possesses an internal abundance range, albeit substantially smallerthan that in ω Cen. Here we compare, as a function of [Fe/H], element-to-iron ratios in the two systems for a number of different elements using data from abundance analyses of red giant branch stars. It appears that the nucleosynthetic enrichment processes were very similar in these two systems despite the substantial difference in total mass.
Syncope is common in children and adolescents and most commonly represents neurocardiogenic syncope. No information has been reported regarding the effect of syncope on health-related quality of life in children.
This was a retrospective cohort study of patients seen in the Heart Institute Syncope Clinic at Cincinnati Children's Hospital Medical Center between July, 2009 and June, 2010. Health-related quality of life was assessed using the PedsQL™ tool. PedsQL™ scores were compared with both healthy historical controls and historical controls with chronic illnesses.
A total of 106 patients were included for analysis. In all, 90% were Caucasian and 63% were girls. The median age was 15.1 years (8.2–21.6). Compared with healthy controls, patients had lower PedsQL™ scores: Total score (75.2 versus 83.8, p < 0.0001); Physical Health Summary (78.8 versus 87.5, p < 0.0001); Psychosocial Health Summary (73.9 versus 81.9, p < 0.001), Emotional Functioning (68.9 versus 79.3, p < 0.001); and School Functioning (66.4 versus 81.1, p < 0.001). No difference was seen in Social Functioning (86.2 versus 85.2, p = 0.81). Patients also had lower PedsQL™ Total scores than patients with diabetes mellitus (p < 0.0001) and similar scores to patients with asthma, end-stage renal disease, obesity, and structural heart disease.
Children with syncope, although typically benign in aetiology, can have low health-related quality of life.
To anglicise an American – that is, English language – disease-specific health-related quality of life measure, using the Paediatric Cardiac Quality of Life Inventory, for children in the age group of 8–12 years and adolescents in the age group of 13–18 years with cardiac disease, and to assess conceptual equivalence of the American and British versions.
A process of forward and backward translation of the measure was undertaken before focus groups and individual interviews with 40 participants – that is, 20 children/adolescents with cardiac disease and 20 parents of children/adolescents with cardiac disease – to determine their understanding of the meaning of the questions.
Interviews established that participants understood the meaning of the questions, although some found it difficult to explain the meaning of questions in which the language was explicit and wanted instead to answer the individual questions as they applied to them/their child. There was agreement that all versions of the questionnaire were relevant and comprehensive, and that the length of the questionnaires was acceptable and practical.
The anglicised version of the Paediatric Cardiac Quality of Life Inventory appears to be a linguistically valid measure of health-related quality of life for children and adolescents with cardiac disease. The psychometric properties of the anglicised Paediatric Cardiac Quality of Life Inventory are now being tested in a multi-centre study in the United Kingdom.