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1.  Alberta Provincial Pediatric EnTeric Infection TEam (APPETITE): epidemiology, emerging organisms, and economics 
BMC Pediatrics  2015;15:89.
Each year in Canada there are 5 million episodes of acute gastroenteritis (AGE) with up to 70 % attributed to an unidentified pathogen. Moreover, 90 % of individuals with AGE do not seek care when ill, thus, burden of disease estimates are limited by under-diagnosing and under-reporting. Further, little is known about the pathogens causing AGE as the majority of episodes are attributed to an “unidentified” etiology. Our team has two main objectives: 1) to improve health through enhanced enteric pathogen identification; 2) to develop economic models incorporating pathogen burden and societal preferences to inform enteric vaccine decision making.
This project involves multiple stages: 1) Molecular microbiology experts will participate in a modified Delphi process designed to define criteria to aid in interpreting positive molecular enteric pathogen test results. 2) Clinical data and specimens will be collected from children aged 0–18 years, with vomiting and/or diarrhea who seek medical care in emergency departments, primary care clinics and from those who contact a provincial medical advice line but who do not seek care. Samples to be collected will include stool, rectal swabs (N = 2), and an oral swab. Specimens will be tested employing 1) stool culture; 2) in-house multiplex (N = 5) viral polymerase chain reaction (PCR) panel; and 3) multi-target (N = 15) PCR commercially available array. All participants will have follow-up data collected 14 days later to enable calculation of a Modified Vesikari Scale score and a Burden of Disease Index. Specimens will also be collected from asymptomatic children during their well child vaccination visits to a provincial public health clinic. Following the completion of the initial phases, discrete choice experiments will be conducted to enable a better understanding of societal preferences for diagnostic testing and vaccine policy. All of the results obtained will be integrated into economic models.
This study is collecting novel samples (e.g., oral swabs) from previously untested groups of children (e.g., those not seeking medical care) which are then undergoing extensive molecular testing to shed a new perspective on the epidemiology of AGE. The knowledge gained will provide the broadest understanding of the epidemiology of vomiting and diarrhea of children to date.
PMCID: PMC4521468  PMID: 26226953
Vomiting; Diarrhea; Gastroenteritis; Norovirus; Rotavirus; Polymerase Chain reaction; Rectal swabs; Discrete choice experiments; Economic analysis; Vaccine
2.  U-shaped relationship between early blood glucose and mortality in critically ill children 
BMC Pediatrics  2015;15:88.
The aims of this study are to evaluate the relationship between early blood glucose concentrations and mortality and to define a ‘safe range’ of blood glucose concentrations during the first 24 h after pediatric intensive care unit (PICU) admission with the lowest risk of mortality. We further determine whether associations exist between PICU mortality and early hyperglycemia and hypoglycemia occurring within 24 h of PICU admission, even after adjusting for illness severity assessed by the pediatric risk of mortality III (PRISM III) score.
This retrospective cohort study included patients admitted to PICU between July 2008 and June 2011 in a tertiary teaching hospital. Both the initial admission glucose values and the mean glucose values over the first 24 h after PICU admission were analyzed.
Of the 1349 children with at least one blood glucose value taken during the first 24 h after admission, 129 died during PICU stay. When analyzing both the initial admission and mean glucose values during the first 24 h after admission, the mortality rate was compared among children with glucose concentrations ≤65, 65-90, 90–110, 110–140, 140–200, and >200 mg/dL (≤3.6, 3.6–5.0, 5.0–6.1, 6.1–7.8, 7.8–11.1, and >11.1 mmol/L). Children with glucose concentrations ≤65 mg/dL (3.6 mmol/L) and >200 mg/dL (11.1 mmol/L) had significantly higher mortality rates, indicating a U-shaped relationship between glucose concentrations and mortality. Blood glucose concentrations of 110–140 mg/dL (6.1–7.8 mmol/L), followed by 90–110 mg/dL (5.0–6.1 mmol/L), were associated with the lowest risk of mortality, suggesting that a ‘safe range’ for blood glucose concentrations during the first 24 h after admission in critically ill children exists between 90 and 140 mg/dL (5.0 and 7.8 mmol/L). The odds ratios of early hyperglycemia (>140 mg/dL [7.8 mmol/L]) and hypoglycemia (≤65 mg/dL [3.6 mmol/L]) being associated with increased risk of mortality were 4.13 and 15.13, respectively, compared to those with mean glucose concentrations of 110–140 mg/dL (6.1–7.8 mmol/L) (p <0.001). The association remained significant after adjusting for PRISM III scores (p <0.001).
There was a U-shaped relationship between early blood glucose concentrations and PICU mortality in critically ill children. Both early hyperglycemia and hypoglycemia were associated with mortality, even after adjusting for illness severity.
PMCID: PMC4513674  PMID: 26204931
Critically ill children; Glucose; Hyperglycemia; Hypoglycemia; Intensive care; Mortality; Pediatric; Pediatric risk of mortality III
3.  How are children with HIV faring in Nigeria?- a 7 year retrospective study of children enrolled in HIV care 
BMC Pediatrics  2015;15:87.
To review the pediatric care and treatment program at Massey Street Children Hospital, in Lagos, Nigeria a retrospective analysis of medical records focusing on health services, survival and retention in care.
The analysis covered a cohort of children initiated on antiretroviral therapy (ART) from 2005 to 2011. In this population, pediatric HIV care was defined as initiating ART between ages 0 and 14 years. Treatment initiation and follow-up were according to the Nigerian national guidelines for pediatric ART, which are based on World Health Organization guidelines adapted to our local context. The primary endpoint was mortality measured as cumulative survival. Other outcomes of interest included “loss to follow-up”, “transferred out”, and “stopped treatment”.
Mean (SD) age at ART initiation was 51 (39) months in female children and 52 (42) months in male children. After seven years of ART care, 64 % of the 660 study children were retained in care and on treatment, 16 % were lost to follow-up, 10 % were dead, and 9 % had discontinued HIV care at this facility for other reasons. World Health Organization disease stage, CD4 count, age, and year of ART initiation were highly predictive of mortality, while anemia at baseline was not statistically significantly associated.
Overall study results suggest a viable pediatric HIV program exists at the study facility. Retention rates were lowest for the earliest cohort of infected children, which implies long-term challenges. Mother-to-child transmission programs need to be dynamic to stem the scourge of pediatric HIV in Nigeria.
PMCID: PMC4510895  PMID: 26198439
4.  Evaluating reporting and process quality of publications on UNHS: a systematic review of programmes 
BMC Pediatrics  2015;15:86.
Congenital hearing loss is one of the most frequent birth defects, and Early Detection and Intervention has been found to improve language outcomes. The American Academy of Pediatrics (AAP) and the Joint Committee on Infant Hearing (JCIH) established quality of care process indicators and benchmarks for Universal Newborn Hearing Screening (UNHS). We have aggregated some of these indicators/benchmarks according to the three pillars of universality, timely detection and overreferral. When dealing with inter-comparison, relying on complete and standardised literature data becomes crucial.
The purpose of this paper is to verify whether literature data on UNHS programmes have included sufficient information to allow inter-programme comparisons according to the indicators considered.
We performed a systematic search identifying UNHS studies and assessing the quality of programmes.
The identified 12 studies demonstrated heterogeneity in criteria for referring to further examinations during the screening phase and in identifying high-risk neonates, protocols, tests, staff, and testing environments. Our systematic review also highlighted substantial variability in reported performance data. In order to optimise the reporting of screening protocols and process performance, we propose a checklist. Another result is the difficulty in guaranteeing full respect for the criteria of universality, timely detection and overreferral.
Standardisation in reporting UNHS experiences may also have a positive impact on inter-program comparisons, hence favouring the emergence of recognised best practices.
Electronic supplementary material
The online version of this article (doi:10.1186/s12887-015-0404-x) contains supplementary material, which is available to authorized users.
PMCID: PMC4511235  PMID: 26198353
Neonatal screening; Process assessment (Health Care); Quality indicators; Health care; Benchmarking; Checklist
5.  Clinical features and outcomes of invasive pneumococcal disease in a pediatric intensive care unit 
BMC Pediatrics  2015;15:85.
Invasive pneumococcal disease (IPD) results in high morbidity and mortality globally each year, although it is a vaccine-preventable disease. This study aimed to characterize the clinical features of IPD in a pediatric intensive care unit (PICU) in Taiwan. The seven-valent pneumococcal conjugate vaccine (PCV7) was introduced in the private sector in October 2005. The estimated coverage rate of PCV7 vaccination in 2010 was 45.5 % among children <5 years of age.
We conducted a retrospective study at a single center in northern Taiwan for invasive pneumococcal disease in a PICU from 2009 to 2013. Demographic characteristics, clinical courses, serotype, antibiotic susceptibility, and outcomes were analyzed.
Over the 5-year study period, 2167 patients were admitted to the PICU; 48 (2.2 %) had IPD. There were 29 female and 19 male patients. Their mean age was 3.7 years (range 0.7–12.5 years, with the peak age at 2–5 years; n = 30, 63 %). Pneumonia was the most frequent type (n = 38, 79 %), followed by meningitis (n = 10, 21 %). In total, three patients died, all within 72 h after admission; the final diagnoses were all meningitis. Thirty-four children with pneumonia received chest tube insertion for pleural effusion drainage. Of them, 22 (65 %) finally still underwent video-assisted thoracoscopic surgery. Eight (17 %) children had hemolytic uremic syndrome, and seven of them underwent hemodialysis. In total, 37 serotypes were detected; 95 % were covered by PCV13. Serotype 19A was most common (54 %) overall; however, in those with meningitis, serotype 19 F was most common.
Meningitis is the most severe type of invasive pneumococcal disease in our pediatric intensive care unit. It may progress rapidly even when subjects are given antibiotics promptly. The most common serotype in meningitis is 19 F, which is vaccine preventable. Thus, universal mass pneumococcal vaccination is still needed.
PMCID: PMC4504450  PMID: 26184113
Hemolytic uremic syndrome (HUS); herd immunity; invasive pneumococcal disease; mortality; pediatric intensive care unit; pneumococcal conjugate vaccine; serotype 19 F; Streptococcus pneumoniae
6.  Comparing three short questionnaires to detect psychosocial problems among 3 to 4-year olds 
BMC Pediatrics  2015;15:84.
Validated questionnaires help community pediatric services to identify psychosocial problems. Our aim was to assess which of three short questionnaires was most suitable for this identification among pre-school children.
We included 1,650 children (response 64 %) aged 3–4 years undergoing routine well-child health assessments in 18 services across the Netherlands. Child healthcare professionals (CHPs) interviewed and examined children and parents. Parents were randomized regarding filling out the Strengths and Difficulties Questionnaire (SDQ) or the KIPPPI, a Dutch-origin questionnaire. In addition, all filled out the Ages and Stages Questionnaires: Social-Emotional (ASQ:SE) and the Child Behavior Checklist (CBCL). We assessed the internal consistency and validity of each questionnaire, with CBCL and treatment status as criteria, and the degree to which each questionnaire could improve identification based solely on clinical assessment.
The internal consistency of the total problems scale of each questionnaire was satisfactory, Cronbach's alphas varied between 0.75 and 0.98. Only the SDQ discriminated sufficiently between children with and without problems as measured by the CBCL (sensitivity = 0.76 at a cut-off point with specificity = 0.90), in contrast to the other two questionnaires (with sensitivity indices varying between 0.51–0.63). Similar results were found for the treatment status criterion, although sensitivity was lower for all questionnaires. The SDQ seemed to add most to the identification of psychosocial problems by CHPs, but the differences between the SDQ and the ASQ:SE were not statistically significant.
The SDQ is the best tool for the identification of psychosocial problems in pre-school children by community paediatric services.
PMCID: PMC4502948  PMID: 26178201
7.  A pilot study to determine the short-term effects of milk with differing glycaemic properties on sleep among toddlers: a randomised controlled trial 
BMC Pediatrics  2015;15:79.
Sleep is important for children as it directly impacts their mental and physical development. Sleep is not only influenced by the timing but also the macronutrient (carbohydrate and protein) content of meals. Glycaemic index (GI) and glycaemic load (GL) describe the quality of carbohydrates in a food and the burden of these foods on the body’s blood glucose response. Diets with a high GI/GL may increase the risk of developing obesity and type 2 diabetes mellitus in adulthood. The present study is piloted to evaluate the short-term impact of milk products with differing glycaemic properties on the sleep patterns of toddlers.
Toddlers were recruited from various day care centres. Informed consent was obtained from both the mothers and the centres. A double-blind randomised controlled trial with a between-subjects design was adopted. The toddlers were randomised to either one of two types of milk with a differing GI (“Low” = 23 and “High = 65”) for a period of 3.5 days. There were no other dietary restrictions imposed except that the enrolled child did not consume any other milk during the study period. The sleep patterns were recorded using a Phillips Actiwatch-2, which was worn on the wrist for 24 h over 4 days. The parameters used to measure the sleep pattern were sleep-onset latency (SOL), total sleep time (TST), wake after sleep onset (WASO) and sleep efficiency (SE).
A total of 56 toddlers completed the study. The toddlers had a mean age of 19.9 ± 4.3 months. There were no significant differences (p > 0.05) between the two GI groups for SOL, TST, WASO and SE at the end of the feeding period.
Sleep patterns of toddlers on low-GI milk did not differ from those with high-GI milk consumed over a short period. Future studies should consider the glycaemic effects of other foods, along with milk with differing GI, consumed for a longer feeding duration.
Trial registration NCT01589003.
PMCID: PMC4502465  PMID: 26174581
Glycaemic index; Toddlers; Sleep; Milk
8.  Adverse drug events in hospitalized children at Ethiopian University Hospital: a prospective observational study 
BMC Pediatrics  2015;15:83.
The nature and magnitude of adverse drug events (ADEs) among hospitalized children in low-income countries is not well described. The aim of this study was thus, to assess the incidence and nature of ADEs in hospitalized children at a teaching hospital in Ethiopia.
We used prospective observational method to study children that were hospitalized to Jimma University Specialized Hospital between 1 February and 1 May 2011. ADEs were identified using review of treatment charts, interview of patient and care-giver, attendance at ward rounds and/or meetings and voluntary staff reports. Two senior pediatric residents evaluated the severity and preventability of ADEs using preset criteria. Logistic regression analysis was employed to determine predictors of ADEs.
There were 634 admissions with 6182 patient-days of hospital stay. There were 2072 written medication orders accounting for 35,117 medication doses. Fifty eight ADEs were identified with an incidence of 9.2 per 100 admissions, 1.7 per 1000 medication doses and 9.4 per 1000 patient-days. One-third of ADEs were preventable; 47 % of these were due to errors in the administration stage of medication use process. Regarding the severity of ADEs, 91 % caused temporary harms and 9 % resulted in permanent harm/death. Anti-infective drugs were the most common medications associated with ADEs. The occurrence of ADEs increased with age, length of hospital stay, and use of CNS, endocrine and antihistamine medicines.
ADEs are common in hospitalized children in low-income settings; however, one-third deemed preventable. A strategy to prevent the occurrence and consequences of ADEs including education of nurses/physicians is of paramount importance.
Electronic supplementary material
The online version of this article (doi:10.1186/s12887-015-0401-0) contains supplementary material, which is available to authorized users.
PMCID: PMC4502527  PMID: 26173560
Adverse drug events; Ethiopia; Hospitalized children; Incidence; Risk factors
9.  Blood pressure tracking in urban black South African children: birth to twenty cohort 
BMC Pediatrics  2015;15:78.
Hypertension is an emerging public health problem in South Africa. Recent evidence from longitudinal studies has shown that hypertension in adulthood can be traced back to childhood. There is scarcity of longitudinal data on paediatric blood pressure (BP) particularly in African populations. The objective of this study is to assess the prevalence of hypertension and evaluate BP tracking between childhood and late adolescence among South African black Children.
This study utilized data from the Birth to Twenty cohort, which is comprised of children born in Soweto, Johannesburg in 1990 (N = 3273, 78.5 % black). Data on BP and anthropometry were collected at six follow-up periods between ages 5 and 18 years. Blood pressure status was classified using the Fourth report on National High Blood pressure program in children and adolescents. Pearson correlation coefficients and relative risk ratios (RR) were used to describe tracking of BP between childhood and late adolescence.
The overall point prevalence ranged from 9.2 to 16.4 % for prehypertension and 8.4 to 24.4 % for hypertension. Tracking coefficients ranged from 0.20 to 0.57 for SBP and 0.17- 0.51 for DBP in both sexes over the 14 years of measurement. The proportion of children who maintained an elevated BP status between childhood, adolescence and age 18 years ranged from 36.1 % at age 5 years to 56.3 % at age 13 years. Risk of having elevated BP at 18 years ranged from; RR: 1.60 (95 % CI: 1.29–2.00) at 5 years to RR: 2.71 (95 % CI: 2.32–3.17) at 14 years of age.
This study reports high prevalence of elevated BP which tracks from early childhood into late adolescence. These findings emphasize the importance of early identification of children at risk of developing elevated BP and related risk factors plus timely intervention to prevent hypertension in adulthood.
PMCID: PMC4502542  PMID: 26173634
Paediatric; Blood pressure; Hypertension; Tracking
10.  Predictors of caregiver depression and family functioning after perinatal stroke 
BMC Pediatrics  2015;15:75.
Perinatal stroke is a leading cause of cerebral palsy and lifelong neurological morbidity. Studies on perinatal stroke outcomes are increasing, although examinations of its broader impact on parents and families have been limited. A recent study found that parents of children with moderate and severe outcomes have increased risk for psychosocial concerns, including depressive symptoms and poor family functioning. Other parents adapt remarkably well, but how this occurs is unknown. The primary aim of this study was to examine predictors of parent and family outcomes, namely caregiver depression and family functioning. The secondary aim was to explore potential mediators and moderators of the relationship between condition severity and parent and family outcomes.
Parents were recruited from a large, population-based perinatal stroke research cohort, and they completed measures assessing their demographics, social supports, stress levels, marital quality, feelings of guilt and blame, psychological well-being, and family functioning. Bivariate analyses compared these variables. Predictor variables, mediators, and moderators were chosen according to the strength of their relationship with the outcome variables (i.e., caregiver depression and family functioning) and theory. Hierarchical regression, mediator, and moderator analyses were conducted accordingly.
A total of 103 parents participated in this study (76 mothers, 27 fathers; mean age of 39.2 years; mean child age of 7.46 years). Condition severity, anxiety, social support, and blame independently predicted caregiver depression while condition severity, stress levels, and marital quality independently predicted family functioning. Blame regarding the cause of their child’s condition also mediated the relationship between condition severity and caregiver depression.
Adverse parental outcomes can be predicted in perinatal stroke populations. Moreover, anxiety and stress management techniques, marital support, and psychoeducation regarding the unpreventable nature of perinatal stroke may be utilized in the future to enhance family outcomes.
PMCID: PMC4502550  PMID: 26174779
11.  Determinants and processes of HIV status disclosure to HIV - infected children aged 4 to 17 years receiving HIV care services at Baylor College of Medicine Children’s Foundation Tanzania, Centre of Excellence (COE) in Mbeya: a cross-sectional study 
BMC Pediatrics  2015;15:81.
Disclosure of HIV sero-status to HIV-infected children is associated with reduced risk of death and better adherence to antiretroviral drugs. However, caregivers find it difficult to determine when and how they should disclose the HIV sero-positive status to HIV-infected children. In this study, we assessed the determinants and processes of HIV status disclosure to HIV-infected children aged 4 to 17 years receiving HIV care services at the Baylor College of Medicine Children's Foundation Tanzania, Centre of Excellence (COE) in Mbeya.
This was a cross-sectional study conducted among 334 caregivers of HIV positive children attending the Baylor COE in Mbeya, Tanzania. Data were collected using quantitative and qualitative research methods. Quantitative data were collected on socio-demographic characteristics of children and caregivers using an interviewer-administered questionnaire. Data were entered into Epi-Info version 3.5.1 and analyzed using STATA version10. Univariable and multivariable logistic regression analyses were conducted to obtain odds ratios (OR) and 95 % confidence intervals (95 % CI) associated with disclosing HIV positive status to HIV-infected children. Qualitative data were collected on the processes used in accomplishing the HIV status disclosure event using case histories and key informant interviews and analyzed manually using latent analysis techniques.
About one-third of the caregivers (32.6 %) disclosed the children’s HIV sero-positive status to them. Disclosure was more likely among children 10 years or older (adjusted OR [AOR] = 8.8; 95 % CI: 4.7, 16.5), caregivers with knowledge about HIV disclosure (AOR = 5.7; 95 % CI: 2.3, 13.7) and those earning more than Tsh 99,999 (US $62.5) per month (AOR = 2.4; 95 % CI: 1.3, 4.5). Qualitative findings showed that caregivers used a diversity of approaches to complete the HIV status disclosure event including direct, third-party, event-driven and use of drawings.
Our study shows that disclosure is common among older children and is largely driven by the caregivers’ knowledge about HIV status disclosure and monthly earnings. HIV status disclosure was accomplished through a variety of approaches. These findings suggest a need to provide caregivers with knowledge about HIV status disclosure approaches to improve HIV status disclosure to HIV-infected children.
Electronic supplementary material
The online version of this article (doi:10.1186/s12887-015-0399-3) contains supplementary material, which is available to authorized users.
PMCID: PMC4502565  PMID: 26173426
Disclosure; HIV- infected children; Determinants, Processes
12.  Diabetes IN develOpment (DINO): the bio-psychosocial, family functioning and parental well-being of youth with type 1 diabetes: a longitudinal cohort study design 
BMC Pediatrics  2015;15:82.
Strict glycemic control during adolescence decreases the risk of developing complications later in life, even if this level of control is not maintained afterwards. However, the majority of adolescents with type 1 diabetes (T1D) are in poor control and so far medical or psychological interventions have shown limited success. Adolescence is characterized by major biological, psychosocial, cognitive and parent–child relationship changes and the complex interaction between these developmental trajectories, and its impact on health outcomes is still poorly understood. A specific topic of interest in this context is the timing of diagnosis. The longitudinal study DINO (Diabetes IN develOpment) aims to examine:If and how the onset of T1D before vs. during puberty results in different outcomes of glycemic control, self-management, psychological functioning and diabetes-related quality of life.The timing of onset of disturbed eating behavior, its risk factors and its prospective course in relation to glycemic and psychological consequences.If and how the onset of T1D before vs. during puberty results in different family functioning and parental well-being.If and how the cognitive development of youth with T1D relates to glycemic control and diabetes self-management.
DINO, a longitudinal multi-center cohort study is conducted in youth with T1D in the age range 8–15 years at baseline. Participants will be divided into two subgroups: pre-pubertal and pubertal. Both groups will be followed for 3 years with assessments based on a bio-psychosocial model of diabetes, scheduled at baseline, 12 months, 24 months and 36 months examining the biological, psychosocial -including disturbed eating behaviors- and cognitive development, family functioning and parental well-being.
A better understanding of how the different trajectories affect one another will help to gain insight in the protective and risk factors for glycemic outcomes and in who needs which support at what moment in time. First results are expected in 2016.
Electronic supplementary material
The online version of this article (doi:10.1186/s12887-015-0400-1) contains supplementary material, which is available to authorized users.
PMCID: PMC4502615  PMID: 26173476
Type 1 diabetes; Development; Youth; Quality of life; Well-being; Adolescence; Cognition; HbA1c; Psychosocial; Parents
13.  Prediction of outcomes by early treatment responses in childhood T-cell acute lymphoblastic leukemia: a retrospective study in China 
BMC Pediatrics  2015;15:80.
Early treatment responses are important prognostic factors in childhood T-cell acute lymphoblastic leukemia (T-ALL) patients. The predictive values of early treatment responses in Chinese childhood T-ALL patients were still unknown.
From January 2003 to December 2012, 74 consecutive patients aged ≤15 years with newly diagnosed T-ALL were treated with BCH-2003 protocol or CCLG-2008 protocol in the Department of Pediatric, Institute of Hematology and Blood Diseases Hospital in China. Predictive values of early treatment responses, including prednisone response, bone marrow morphology at day 15 and day 33 during induction chemotherapy, and minimal residual disease (MRD) monitored by flow cytometry after induction therapy (time point 1, TP1) and before consolidation therapy (time point 2, TP2), were analyzed.
The 5-year event free survival (EFS) and overall survival (OS) rates for these patients were 62.5 % (SE, 6.4) and 62.7 % (SE, 6.6), respectively. Prednisone poor responder was strongly associated with increased chance of induction failure (14.8 %) and decreased survival rate (5 year EFS rate, 51.1 % (SE, 10.5)). Patients with ≥25 % blast cells in bone marrow at day 15 were more likely to have an inferior outcome. 93.2 % of the T-ALL patients achieved complete remission at day 33 while patients with resistant disease all died of disease progression. MRD ≥10−2 at TP1 or MRD ≥10−3 at TP2 was significantly related to dismal prognosis. Risk groups classified by MRD at two time points could stratify patients into different groups: 29.0 % of the patients were MRD standard risk (MRD < 10−4 at both time points) with 3-year EFS rate of 100 %, 29.0 % were MRD high risk (MRD ≥10−2 at TP1 or MRD ≥10−2 at TP2) with 3-year EFS rate of 55.6 % (SE, 16.6) , and the rest of patients were defined as MRD intermediate risk with 3-year EFS rate of 85.7 % (SE, 13.2).
Our study demonstrated that MRD was the most powerful predictor of treatment outcome in childhood T-ALL patients and conventional morphological assessments of treatment response still played important roles in predicting treatment outcome and tailoring treatment intensity especially in countries with inadequate skills or financial resources for MRD monitoring.
Electronic supplementary material
The online version of this article (doi:10.1186/s12887-015-0390-z) contains supplementary material, which is available to authorized users.
PMCID: PMC4502910  PMID: 26174476
Childhood; T-cell acute lymphoblastic leukemia; Prednisone response; Minimal residual disease; Prognosis
14.  Survival status and predictors of mortality in severely malnourished children admitted to Jimma University Specialized Hospital from 2010 to 2012, Jimma, Ethiopia: a retrospective longitudinal study 
BMC Pediatrics  2015;15:76.
Although community based treatment of severe acute malnutrition has been advocated for in recent years, facility based treatment of severe acute malnutrition is still required. Therefore, information on the treatment outcomes of malnutrition and potential predictors of mortality among severely malnourished children admitted to hospitals is critical for the improvement of quality care. Thus, the aim of this study was to assess survival status and predictors of mortality in severely malnourished children admitted to Jimma University Specialized Hospital from September 11, 2010 to September 10, 2012.
Retrospective longitudinal study was conducted at Jimma University Specialized Hospital. From September 11, 2010 to September 10, 2012 available data from severely malnourished children admitted to the hospital were reviewed. Data were analyzed using SPSS version 20 for windows. Bivariate and multivariable analyses were performed by Kaplan-Meier and Cox regression to identify clinical characteristics associated with mortality.
A total of 947 children were enrolled into the study. An improvement, death and abscond rate were 77.8, 9.3 and 12.9 % respectively. The median duration from admission to death was 7 days. The average length of stay in the hospital and average weight gain were 17.4 days and 10.4 g/kg/day respectively. The main predictors of earlier hospital deaths were age less than 24 months (AHR = 1.9, 95 % CI [1.2–2.9]), hypothermia (AHR = 3.0, 95 % CI [1.4–6.6]), impaired consciousness level (AHR = 2.6, 95 % CI [1.5–4.5]), dehydration (AHR = 2.3, 95 % CI [1.3–4.0]), palmar pallor (AHR = 2.1, 95 % CI [1.3–3.3]) and co-morbidity/complication at admission (AHR = 3.7, 95 % CI [1.9–7.2]).
The treatment outcomes (improvement rate, death rate, average length of stay in the hospital and average weight gain) were better than most reports in the literatures and in agreement with minimum international standard set for management of severe acute malnutrition. Intervention to further reduce earlier deaths should focus on young children with hypothermia, altered mental status, dehydration, anemia and comorbidities.
PMCID: PMC4502938  PMID: 26174805
Survival status; Predictors of mortality; Severe malnutrition; Children; Hospital
15.  Fragile X syndrome screening in Chinese children with unknown intellectual developmental disorder 
BMC Pediatrics  2015;15:77.
Fragile X syndrome is the most common genetic disorder of intellectual developmental disorder/mental retardation (IDD/MR). The prevalence of FXS in a Chinese IDD children seeking diagnosis/treatment in mainland China is unknown.
Patients with unknown moderate to severe IDD were recruited from two children’s hospitals. Informed consent was obtained from the children's parents. The size of the CGG repeat was identified using a commercial TP-PCR assay. The influence of AGG interruptions on the CGG expansion during maternal transmission was analyzed in 24 mother-son pairs (10 pairs with 1 AGG and 14 pairs with 2 AGGs).
553 unrelated patients between six months and eighteen years of age were recruited. Specimens from 540 patients (male:female = 5.2:1) produced high-quality TP-PCR data, resulting in the determination of the FMR1 CGG repeat number for each. The most common repeat numbers were 29 and 30, and the most frequent interruption pattern was 2 or 3 AGGs. Five full mutations were identified (1 familial and 4 sporadic IDD patients), and size mosaicism was apparent in 4 of these FXS patients (4/5 = 80 %). The overall yield of FXS in the IDD cohort was 0.93 % (5/540). Neither the mean size of CGG expansion (0.20 vs. 0.79, p > 0.05) nor the frequency of CGG expansion (2/10 vs. 9/14, p > 0.05) was significantly different between the 1 and 2 AGG groups following maternal transmission.
The FMR1 TP-PCR assay generates reliable and sensitive results across a large number of patient specimens, and is suitable for clinical genetic diagnosis. Using this assay, the prevalence of FXS was 0.93 % in Chinese children with unknown IDD.
Electronic supplementary material
The online version of this article (doi:10.1186/s12887-015-0394-8) contains supplementary material, which is available to authorized users.
PMCID: PMC4502947  PMID: 26174701
Chinese children; Intellectual developmental disorder; FMR1; Fragile X syndrome; Triplet repeat primed (TP)-PCR
16.  Subcutaneous fat necrosis in neonates with hypoxic ischaemic encephalopathy registered in the Swiss National Asphyxia and Cooling Register 
BMC Pediatrics  2015;15:73.
Neonates with hypoxic ischaemic encephalopathy (HIE) are routinely treated with therapeutic hypothermia (TH) for 72 h in order to improve neurological outcome. Subcutaneous fat necrosis (SCFN) is an adverse event occurring in neonates with HIE.
We analyzed risk factors for SCFN regarding demographic factors, cooling methods and deviation from target temperature range during hypothermia therapy. Data of all neonates registered in the National Asphyxia and Cooling Register in Switzerland between 2011 and 2013 were analyzed.
2.8 % of all cooled neonates with HIE developed SCFN. Perinatal and neonatal characteristics did not differ between neonates with and without SCFN. Applied cooling methods did not correlate with the occurrence of SCFN. In neonates with SCFN 83.3 % of all noted temperatures were within the target temperature range versus 77.5 % in neonates without SCFN. Neonates with SCFN showed 3.6 % of all measured temperatures below target temperature range compared to 12.7 % in neonates without SCFN.
Subcutaneous fat necrosis in the neonate with HIE undergoing TH is a potential adverse event that seems to occur independently from the whole-body cooling method applied and proportion of temperature measurements outside target temperature range. In this cohort, moderate overcooling associated with moderate hypothermia (33.0–34.0 °C) does not seem to be an independent risk factor for SCFN. There is no correlation between the severity of HIE and incidence of SCFN.
Electronic supplementary material
The online version of this article (doi:10.1186/s12887-015-0395-7) contains supplementary material, which is available to authorized users.
PMCID: PMC4496817  PMID: 26156857
Hypoxic ischaemic encephalopathy; Subcutaneous fat necrosis; Register; Hypothermia therapy
17.  Predictors of treatment failure for non-severe childhood pneumonia in developing countries – systematic literature review and expert survey – the first step towards a community focused mHealth risk-assessment tool? 
BMC Pediatrics  2015;15:74.
Improved referral algorithms for children with non-severe pneumonia at the community level are desirable. We sought to identify predictors of oral antibiotic failure in children who fulfill the case definition of World Health Organization (WHO) non-severe pneumonia. Predictors of greatest interest were those not currently utilized in referral algorithms and feasible to obtain at the community level.
We systematically reviewed prospective studies reporting independent predictors of oral antibiotic failure for children 2–59 months of age in resource-limited settings with WHO non-severe pneumonia (either fast breathing for age and/or lower chest wall indrawing without danger signs), with an emphasis on predictors not currently utilized for referral and reasonable for community health workers. We searched PubMed, Cochrane, and Embase and qualitatively analyzed publications from 1997–2014. To supplement the limited published evidence in this subject area we also surveyed respiratory experts.
Nine studies met criteria, seven of which were performed in south Asia. One eligible study occurred exclusively at the community level. Overall, oral antibiotic failure rates ranged between 7.8-22.9 %. Six studies found excess age-adjusted respiratory rate (either WHO-defined very fast breathing for age or 10–15 breaths/min faster than normal WHO age-adjusted thresholds) and four reported young age as predictive for oral antibiotic failure. Of the seven predictors identified by the expert panel, abnormal oxygen saturation and malnutrition were most highly favored per the panel’s rankings and comments.
This review identified several candidate predictors of oral antibiotic failure not currently utilized in childhood pneumonia referral algorithms; excess age-specific respiratory rate, young age, abnormal oxygen saturation, and moderate malnutrition. However, the data was limited and there are clear evidence gaps; research in rural, low-resource settings with community health workers is needed.
Electronic supplementary material
The online version of this article (doi:10.1186/s12887-015-0392-x) contains supplementary material, which is available to authorized users.
PMCID: PMC4496936  PMID: 26156710
integrated Community Case Management (iCCM); Community health workers; Childhood pneumonia; Pediatrics; Developing countries; Predictors; Treatment failure; mHealth
18.  Neonatal respiratory distress syndrome revealing a cervical bronchogenic cyst: a case report 
BMC Pediatrics  2015;15:72.
Bronchogenic cyst is a congenital malformation, rarely located in the cervical region and almost never involved in a neonate with acute respiratory distress in the delivery room.
Case presentation
A female newborn with respiratory distress syndrome caused by a large left cervical mass. Intubation was difficult due to tracheal deviation. Magnetic resonance imaging confirmed a left cervical cyst displacing the trachea and esophagus laterally. Surgical excision was performed via a cervical approach on the 5th day, and pathological examination revealed a bronchogenic cyst. The patient's course was complicated by left vocal cord paralysis and necrotic lesions in the glottic and subglottic regions; she required a tracheostomy on the 13th day. Inflammatory stenosis in the subglottic region required balloon dilation once, 20 days later. Proximal esophageal stenosis induced transient upper airway obstruction with salivary stasis. Decannulation was performed at 2 months and the patient was discharged 10 days later.
A bronchogenic cyst can exceptionally obstruct the airways in the neonatal period. Surgical excision is necessary, but postoperative complications may occur if the cyst is in close contact with the trachea and esophagus, including necrotic and stenotic lesions of the upper aerodigestive tract. In those situations, tracheostomy may be necessary for mechanical ventilation weaning and the initiation of oral feeding.
PMCID: PMC4491209  PMID: 26112048
Cervical bronchogenic cyst; Neonatal respiratory distress syndrome; Tracheostomy
19.  Evaluation of an educational program for essential newborn care in resource-limited settings: Essential Care for Every Baby 
BMC Pediatrics  2015;15:71.
Essential Care for Every Baby (ECEB) is an evidence-based educational program designed to increase cognitive knowledge and develop skills of health care professionals in essential newborn care in low-resource areas. The course focuses on the immediate care of the newborn after birth and during the first day or until discharge from the health facility. This study assessed the overall design of the course; the ability of facilitators to teach the course; and the knowledge and skills acquired by the learners.
Testing occurred at 2 global sites. Data from a facilitator evaluation survey, a learner satisfaction survey, a multiple choice question (MCQ) examination, performance on two objective structured clinical evaluations (OSCE), and pre- and post-course confidence assessments were analyzed using descriptive statistics. Pre-post course differences were examined. Comments on the evaluation form and post-course group discussions were analyzed to identify potential program improvements.
Using ECEB course material, master trainers taught 12 facilitators in India and 11 in Kenya who subsequently taught 62 providers of newborn care in India and 64 in Kenya. Facilitators and learners were satisfied with their ability to teach and learn from the program. Confidence (3.5 to 5) and MCQ scores (India: pre 19.4, post 24.8; Kenya: pre 20.8, post 25.0) improved (p < 0.001). Most participants demonstrated satisfactory skills on the OSCEs. Qualitative data suggested the course was effective, but also identified areas for course improvement. These included additional time for hands-on practice, including practice in a clinical setting, the addition of video learning aids and the adaptation of content to conform to locally recommended practices.
ECEB program was highly acceptable, demonstrated improved confidence, improved knowledge and developed skills. ECEB may improve newborn care in low resource settings if it is part of an overall implementation plan that addresses local needs and serves to further strengthen health systems.
Electronic supplementary material
The online version of this article (doi:10.1186/s12887-015-0382-z) contains supplementary material, which is available to authorized users.
PMCID: PMC4479066  PMID: 26105072
20.  Safety and efficacy of a 100 % dimethicone pediculocide in school-age children 
BMC Pediatrics  2015;15:70.
Head lice most commonly affect children, ages 3 to 11. Concerns exist about the safety and efficacy of pesticide-based treatments. Published studies suggest dimethicone is a potentially safe and effective non-toxic treatment, but have not evaluated 100 % dimethicone in a pediatric population. The objectives were to evaluate the efficacy and safety of 100 % dimethicone for the treatment of head lice in children, monitored by school nurses.
This was a multi-site, open-label study of a 100 % dimethicone gel for the treatment of head lice in a pediatric population. Children (ages 3–12) suspected of infestation with head lice were evaluated by school nurses at six schools and daycare programs in New York and New Jersey. Inclusion criteria were presence of at least three live lice, or one live louse and 10 viable eggs (eggs found within 1.27 cm of the scalp) and no use of any head lice treatment within four weeks of enrollment. Counts of live lice and viable eggs found in 58 subjects were tracked at baseline (Day 0) and on Day 1, Day 7, and Day 14 after treatment.
After 1 day of treatment with 100 % dimethicone, 98.30 % of subjects were free of live lice and 55.20 % were free of viable eggs. On day 14, 96.50 % were still free of live lice, and 80.70 % were free of viable eggs. All subjects were monitored by the school nurse at baseline and throughout the study period for adverse effects, including scalp erythema, excoriation, flaking and edema. There was one adverse event of skin irritation lasting 10 min, and no serious adverse events reported. Overall, scalp conditions improved from the baseline: 10 subjects (17.5 %) reported mild to moderate scalp erythema on day 1, compared with only one subject (1.7 %) on day 14; 8 subjects (14.3 %) reported mild scalp excoriation on day 1, with none reporting on day 14.
100 % dimethicone was found to be a safe and highly effective treatment for pediatric head lice. Because dimethicone avoids pesticide exposure and resistance issues, dimethicone should be considered as a first-line treatment for head lice.
Trial Registration
NCT02213055 Date of registration: August 8, 2014
Standards of reporting
The CONSORT 2010 Checklist was consulted during the review of this manuscript. Please note that sections pertaining specifically to randomized controlled trials (RCT’s) were not applicable.
PMCID: PMC4475297  PMID: 26092045
Pediculosis; Pediculus humanus capitis; Pediatrics; Head lice; Dimethicone; Infestation; School; Children
21.  “Having diabetes shouldn’t stop them”: healthcare professionals’ perceptions of physical activity in children with Type 1 diabetes 
BMC Pediatrics  2015;15:68.
Healthcare professionals (HCP) working with children who have Type 1 Diabetes Mellitus (T1DM) have an important role in advising about and supporting the control of blood glucose level in relation to physical activity. Regular physical activity has known benefits for children with T1DM, but children with chronic conditions may face barriers to participation. The perceptions of HCPs were explored in an effort to understand what influences physical activity in children with T1DM and to inform the practice of those working with children who have T1DM.
Semi-structured interviews with 11 HCPs involved in the care of children with T1DM in the UK were conducted. Interviews were recorded, transcribed verbatim and data were analysed using thematic analysis.
The factors perceived to influence participation in physical activity are presented as five major themes and eleven sub-themes. Themes included the positive influence of social support, the child’s motivation to be active, the potential for formal organisations such as school and diabetes clinic to support physical activity, the challenges faced by those who have T1DM and the perceived barriers to HCPs fulfilling their role of promoting physical activity.
Healthcare professionals recognised their role in helping children with T1DM and their parents to incorporate physical activity into diabetes management and everyday life, but perceived barriers to the successful fulfilment of this role. The findings highlight the potential for clinical and non-clinical supportive systems to be sensitive to these challenges and facilitate children’s regular participation in physical activity.
PMCID: PMC4470093  PMID: 26084937
Type 1 diabetes mellitus; Qualitative research; Child; Motor activity; Health personnel
22.  Prevention of peripherally inserted central line-associated blood stream infections in very low-birth-weight infants by using a central line bundle guideline with a standard checklist: a case control study 
BMC Pediatrics  2015;15:69.
Catheter-related infections (CRIs) are one of the severe complications of PICC placement. If treatment is not timely or correct, the incidence of infection and mortality rate can be high. A central line bundle (CLB) guideline was first proposed by the Institute for Healthcare Improvement, and included five key measures. Very low-birth-weight infants (VLBWIs) have a low immune response and indistinct symptoms after infection compared with other populations (Costa P, Kimura AF, de Vizzotto MP, de Castro TE, West A, Dorea E. Prevalence and reasons for non-elective removal of peripherally inserted central catheter in neonates. Rev Gaucha Enferm. 2012;33:126–33). Some reviews have focused on the effect and safety of a CLB in VLBWIs and its preventive effect on bacterial colonization and infection.
Fifty-seven VLBWIs who underwent PICC insertion at a hospital in Qingdao, China, between November 2012 and June 2013, and for whom a CLB guideline and a standard checklist were adopted, were included in the CLB group. In contrast, 53 VLBWIs who underwent PICC insertion, but for whom a CLB guideline and a standard checklist were not adopted, were included in the control group. The incidence of CRIs was compared between before and after the treatment.
The incidence of infection showed a statistically significant reduction from 10.0 to 2.20 per 1000 catheter days in the control group (P < 0.05). The incidence of catheter-related bloodstream infections decreased from 3.1 to 0 per 1000 catheter days, and that of colonization infections decreased from 6.9 to 2.2 per 1000 catheter days (P < 0.05), both of which indicated a statistically significant difference. The indwelling catheter time was 24.8 ± 7.4 days in the control group and 31.9 ± 15.0 days in the study group (P < 0.05), and these values were significantly different.
The use of a CLB guideline with a standard checklist could be effective and feasible for preventing CRIs in VLBWIs and prolonging indwelling catheter time.
PMCID: PMC4470111  PMID: 26084807
Central line bundle; Checklists; Very low birth weight infant; PICC; Catheter related infection
23.  Improving communication and recall of information in paediatric diabetes consultations: a qualitative study of parents’ experiences and views 
BMC Pediatrics  2015;15:67.
Parents of non-adolescent children with type 1 diabetes are responsible for most of their child’s diabetes management tasks. Consultations are used to provide diabetes education, review clinical progress and promote diabetes management tasks. This study explored parents’ experiences of, and views about, their child’s diabetes consultations. The objective was to identify ways in which consultations could be improved to aid communication, understanding and knowledge retention.
In-depth interviews with 54 parents of children (aged ≤12 years) with type 1 diabetes. Data were analysed using an inductive thematic approach.
Parents’ accounts revealed structural and contextual factors which could hinder effective communication and knowledge acquisition during consultations. Most reported feeling anxious going into consultations and worrying about being reprimanded by health professionals if their child’s glycaemic control had not improved. As a consequence, many parents highlighted problems concentrating and assimilating information during consultations. In extreme cases, worries about being reprimanded led parents to omit or fabricate information when discussing their child’s treatment or even to their cancelling appointments. Many parents described wanting opportunities to speak to health professionals alone because young children could be distracting and/or they did not want to raise distressing issues in front of their child. Parents described the benefits of receiving clinical advice from health professionals familiar with their family circumstances and disliking attending busy clinics and seeing different health professionals on each occasion. Parents also highlighted the benefits of receiving treatment recommendations in a written form after the consultation.
Discussion and conclusions
This study has highlighted unrecognised and undocumented aspects of the consultation which may result in parents leaving uncertain about the main issues discussed and with questions unanswered and support needs unaddressed. Structural and contextual changes to consultations are recommended to improve concentration, knowledge acquisition and retention. These include: sending letters/written summaries after consultations highlighting key decisions, providing opportunities for parents to consult health professionals without their child being present, encouraging parents to ask more questions during consultations, having procedures in place to promote continuity of care and providing parents with consistent and non-contradictory advice.
PMCID: PMC4460975  PMID: 26054649
Type 1 diabetes mellitus; Paediatric consultations; Parents; Qualitative research
24.  Growth and health outcomes at school age in HIV-exposed, uninfected Zambian children: follow-up of two cohorts studied in infancy 
BMC Pediatrics  2015;15:66.
Early growth and health of HIV-exposed, uninfected (HEU) children is poorer than that of their HIV-unexposed, uninfected (HUU) counterparts but there is little information about longer term effects of early HIV exposure. We previously recruited two cohorts of HEU and HUU Zambian infants and documented the poorer infant growth and health of the HEU compared to the HUU children. We followed up HEU and HUU children from these cohorts when they were school-aged and compared their growth, health, biochemical markers of acute or chronic disease, and school grades.
We recruited 111 HEU and 279 HUU children aged 6–12 years. We measured anthropometry, determined health by questionnaire and clinical examination, viewed the child’s most recent school report, and measured blood pressure, haemoglobin (Hb), HbA1c, glucose, cholesterol, and C-reactive protein (CRP).
Anthropometric measures were lower among HEU than HUU children, significantly so for hip circumference (age- and sex-adjusted difference −1.74 cm; 95 % confidence interval (CI) -3.24, −0.24; P = 0.023) and mid-upper-arm circumference (adjusted difference −0.63 cm, 95 % CI −1.23, −0.04; P = 0.037) and with borderline effects for body mass index, thigh circumference and subscapular skinfolds. HEU children had significantly lower total, trunk, and limb fat percentages. All anthropometric and body composition differences became non-significant after adjustment for sociodemographic variables which differed between HEU and HUU children. More HEU than HUU children reported minor illnesses and were prescribed medication at the time of visit. There were no differences in biochemical markers between groups. HEU children had lower math grades than HUU children even after adjustment for socioeconomic variables.
Although HEU children were smaller and had lower percent fat than HUU children, this appeared to be due mainly to their poorer socioeconomic status. Reasons for lower school grades require further research.
Electronic supplementary material
The online version of this article (doi:10.1186/s12887-015-0386-8) contains supplementary material, which is available to authorized users.
PMCID: PMC4458018  PMID: 26048411
HIV exposure; Growth; Body composition; School performance
25.  Obesity in school-aged children and its correlation with Gut E.coli and Bifidobacteria: a case–control study 
BMC Pediatrics  2015;15:64.
To determine the correlation between obesity in school-aged children and imbalance of gut microbes by examining the ratio change of intestinal Bifidobacteria and E.coli in obese children compared to non-obese controls.
A hospital-based 1:1 case–control study was performed. Fecal samples of the subjects were collected for DNA extraction and analyzed by quantitative real-time PCR (qPCR) to determine the copy number of Bifidobacteria and E.coli. The ratio of two microbes (B/E) was then calculated and statistically analyzed.
Subjects of the obesity group and control group showed no significant difference in age, gender or height (P > 0.05); whereas they had significant differences in body weight and BMI. Copy numbers of Bifidobacteria and E.coli per gram of wet fecal samples were first determined using qPCR in both obese and normal groups, which were further used for the calculation of B/E ratio. We found that B/E ration in the two groups showed significant difference (P < 0.05). Corrected χ2 test was performed for the two groups against B/E < 1, and it was found that there was a positive correlation (OR = 719.2, OR 95% C.I. = 81.57-6341.18) between B/E ratio decrease with childhood obesity.
The obese children have a lower amount of Bifidobacteria and higher amount of E.coli (smaller B/E ratio) compared to normal non-obese children. It was suggested that obesity in children may be associated with the imbalance of gut microbes.
PMCID: PMC4448301  PMID: 26024884
Obesity; Children; Gut microbes; E.coli; and Bifidobacteria

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