MissForest - nonparametric missing value imputation for mixed-type data

Modern data acquisition based on high-throughput technology is often facing the problem of missing data. Algorithms commonly used in the analysis of such large-scale data often depend on a complete set. Missing value imputation offers a solution to this problem. However, the majority of available imputation methods are restricted to one type of variable only: continuous or categorical. For mixed-type data the different types are usually handled separately. Therefore, these methods ignore possible relations between variable types. We propose a nonparametric method which can cope with different types of variables simultaneously. We compare several state of the art methods for the imputation of missing values. We propose and evaluate an iterative imputation method (missForest) based on a random forest. By averaging over many unpruned classification or regression trees random forest intrinsically constitutes a multiple imputation scheme. Using the built-in out-of-bag error estimates of random forest we are able to estimate the imputation error without the need of a test set. Evaluation is performed on multiple data sets coming from a diverse selection of biological fields with artificially introduced missing values ranging from 10% to 30%. We show that missForest can successfully handle missing values, particularly in data sets including different types of variables. In our comparative study missForest outperforms other methods of imputation especially in data settings where complex interactions and nonlinear relations are suspected. The out-of-bag imputation error estimates of missForest prove to be adequate in all settings. Additionally, missForest exhibits attractive computational efficiency and can cope with high-dimensional data.Comment: Submitted to Oxford Journal's Bioinformatics on 3rd of May 201

Perinatale Betreuung an der Grenze der Lebensfähigkeit zwischen 22 und 26 vollendeten Schwangerschaftswochen

Die ersten Empfehlungen zur Betreuung von Frühgeborenen an der Grenze der Lebensfähigkeit in der Schweiz wurden im Jahre 2002 veröffentlicht1). Als Grundlage dienten damals unter anderem Empfehlungen europäischer2), 3) und kanadischer Fachgruppen4), sowie die relevanten edizinischethischen Richtlinien der Schweizerischen Akademie der Medizinischen Wissenschaften (SAMW)5), 6). Revidierte Empfehlungen aus Nordamerika und Europa7)–11), neue Empfehlungen aus weiteren Ländern12)–17) und neue Daten zu Mortalität und Morbidität18)– 22), insbesondere auch aus der Schweiz23), 24), haben Anlass dazu gegeben, die Empfehlungen für die Schweiz zu überarbeiten

Catch-up growth up to ten years of age in children born very preterm or with very low birth weight

BACKGROUND: Improved survival due to advances in neonatal care has brought issues such as postnatal growth and development more to the focus of our attention. Most studies report stunting in children born very preterm and/or small for gestational age. In this article we study the growth pattern of these children and aim to identify factors associated with postnatal catch-up growth. METHODS: 1338 children born with a gestational age <32 weeks and/or a birth weight of <1500 grams were followed during a Dutch nationwide prospective study (POPS). Subgroups were classified as appropriate for gestational age and <32 weeks (AGA) or small for gestational age (<32 wks SGA and ≥32 wks SGA). Data were collected at different intervals from birth until 10 years for the 962 survivors and compared to reference values. The correlation between several factors and growth was analysed. RESULTS: At 10 years the AGA children had attained normal height, whereas the SGA group demonstrated stunting, even after correction for target height (AGA: 0.0 SDS; SGA <32 wks: -0.29SDS and ≥32 wks: -0.13SDS). Catch-up growth was especially seen in the SGA children with a fast initial weight gain. BMI was approximately 1 SD below the population reference mean. CONCLUSION: At 10 years of age, children born very preterm AGA show no stunting. However, many children born SGA, especially the very preterm, show persistent stunting. Early weight gain seems an important prognostic factor in predicting childhood growth

Long-term outcome of preterm infants treated with nasal continuous positive airway pressure

This study's aim was to assess neurodevelopmental and growth outcome until the age of 4 years of premature infants placed on early nCPAP, in the setting of the neonatal intensive care unit (NICU) and follow-up program of the Division of Neonatology of the Department of Pediatrics of the University Hospital, Lausanne, Switzerland. All consecutive inborn infants weighing &lt;1500 g or &lt;32 weeks of gestational age admitted to the NICU during two periods of 12 months-7.1996-6.1997 and 7.1998-6.1999-were compared before and after the systematic application of early nCPAP. Of 172 infants admitted to the NICU, 150 (87%) survived. 126 (84%) were tested at 6 months' corrected age, 121 (81%) at 18 months' corrected age, and 117 (78%) at the age of 4 years. Detailed perinatal data were collected. Follow-up included neurological examination, developmental testing and measurement of growth parameters. Statistical analyses were performed. Early application of nCPAP and avoidance of mechanical ventilation showed no adverse effects on neurodevelopment and growth. A significantly higher developmental quotient was found in the nCPAP group at 18 months' corrected age. Several trends were also noted in the nCPAP group with a decrease of intraventricular hemorrhage and in "abnormal neurodevelopment" at 6 months corrected age, a bigger head circumference at all different tested ages and a greater height at 6 and 18 months corrected ages. In conclusion, our study of developmental outcome documents the absence of any harmful effect of early application of nCPAP to treat respiratory failure in very low birthweight infants

Patient-reported quality of life outcomes for children with serious congenital heart defects

Objective To compare patient-reported, health-related quality of life (QoL) for children with serious congenital heart defects (CHDs) and unaffected classmates and to investigate the demographic and clinical factors influencing QoL. Design Retrospective cohort study. Setting UK National Health Service. Patients UK-wide cohort of children with serious CHDs aged 10–14 years requiring cardiac intervention in the first year of life in one of 17 UK paediatric cardiac surgical centres operating during 1992–1995. A comparison group of classmates of similar age and sex was recruited. Main outcome measures Child self-report of healthrelated QoL scores (Pediatric Quality of Life Inventory, PedsQL) and parental report of schooling and social activities. Results Questionnaires were completed by 477 children with CHDs (56% boys; mean age 12.1 (SD 1.0) years) and 464 classmates (55%; 12.0 (SD 1.1) years). Children with CHDs rated QoL significantly lower than classmates (CHDs: median 78.3 (IQR 65.0–88.6); classmates: 88.0 (80.2–94.6)) and scored lower on physical (CHDs: 84.4; classmates: 93.8; difference 9.4 (7.8 to 10.9)) and psychosocial functioning subscales (CHDs: 76.7, classmates: 85.0; difference 8.3 (6.0 to 10.6)). Cardiac interventions, school absence, regular medications and non-cardiac comorbidities were independently associated with reduced QoL. Participation in sport positively influenced QoL and was associated with higher psychosocial functioning scores. Conclusions Children with serious CHDs experience lower QoL than unaffected classmates. This appears related to the burden of clinical intervention rather than underlying cardiac diagnosis. Participation in sports activities is positively associated with increased emotional well-being. Child self-report measures of QoL would be a valuable addition to clinical outcome audit in this age group.RLK was awarded an MRC Special Training Fellowship in Health of the Public and Health Services Research (reference G106/1083). TD was supported by an NIHR Academic Clinical Fellowship. This work was supported by a British Heart Foundation project grant (reference PG/02/065/13934). The Centre for Paediatric Epidemiology and Biostatistics benefits from funding support from the Medical Research Council in its capacity as the MRC Centre of Epidemiology for Child Health (reference G04005546). Great Ormond St Hospital for Children NHS Trust and the UCL Institute of Child Health receives a proportion of funding from the Department of Health’s NIHR Biomedical Research Centres schem

Self-reported health experiences of children living with congenital heart defects: Including patient-reported outcomes in a national cohort study

Background: Understanding children’s views about living with congenital heart defects (CHDs) is fundamental to supporting their successful participation in daily life, school and peer relationships. As an adjunct to a health and quality of life outcomes questionnaire, we asked school-age children who survived infant heart procedures to describe their experiences of living with CHDs. Methods: In a UK-wide cohort study, children aged 10 to 14 years with CHDs self-completed postal questionnaires that included an open question about having a ‘heart problem’. We compared the characteristics of children with more and less severe cardiac diagnoses and, through collaborative inductive content analysis, investigated the subjective experiences and coping strategies described by children in both clinical severity groups. Results: Text and/or drawings were returned by 436 children (246 boys [56%], mean age 12.1 years [SD 1.0; range 10–14]); 313 had less severe (LS) and 123 more severe (MS) cardiac diagnoses. At the most recent hospital visit, a higher proportion of the MS group were underweight (more than two standard deviations below the mean for age) or cyanosed (underweight: MS 20.0%, LS 9.9%; cyanosed: MS 26.2%, LS 3.5%). Children in the MS group described concerns about social isolation and feeling ‘different’, whereas children with less severe diagnoses often characterised their CHD as ‘not a big thing’. Some coping strategies were common to both severity groups, including managing health information to avoid social exclusion, however only children in the LS group considered their CHD ‘in the past’ or experienced a sense of survivorship. Conclusions: Children’s reported experiences were not dependent on their cardiac diagnosis, although there were clear qualitative differences by clinical severity group. Children’s concerns emphasised social participation and our findings imply a need to shift the clinical focus from monitoring cardiac function to optimising participation. We highlight the potential for informing and evaluating clinical practice and service provision through seeking patient-reported outcomes in paediatric care