School of child & adolescent health

Title: Treatment of Infants with epilepsy: Common practice across the world
Authors: JM Wilmshurst¹, RJ Burman¹, WD Gaillard ², JH Cross.³
Affiliation: ¹Department of Pediatric Neurology, Red Cross War Memorial Children’s Hospital, University of Cape Town, South Africa, ²Center for Neuroscience, Children's National Medical Center, George Washington University, Washington, District of Columbia, USA, ³UCL-Institute of Child health, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom


Purpose: 

There is currently a lack of high quality data to guide the development of treatment recommendations for infants with epilepsy. The aim of this study was to develop global understanding of the preferred use of treatment interventions and to identify inter-regional differences.

Method: 

An electronic survey was distributed to chapters of various global and regional child neurology associations. Questions were focused on current clinical practice including drug and non-drug treatment interventions. Inter-regional comparisons were then identified and analysed using the relevant statistical analysis.

Results: 

733 unique responses were captured from 96 different countries. The survey found that overall that there was significant variability between regions (p <0.001, X² test). Furthermore, the North American region is more likely to use Levetiracetam in focal, generalized and myoclonic seizures compared to all other regions (p <0.001, X² test).

Looking at the use of alternative therapies, overall previous experience with vagal nerve stimulation and epilepsy surgery significantly increases the preferred use of these therapies once seizures have been diagnosed as medically refractory (p <0.001, X² test).
Conclusion: 

The results from this survey highlight the lack of global consistency in the management of infants with epilepsy. The identified differences in global prescribing practices may provide a useful platform for further investigation into the issues surrounding the management of infants with epilepsy.

Title: RESOLVED LOWER LIMB MUSCLE TONE ABNORMALITIES IN CHILDREN WITH HIV ENCEPHALOPATHY RECEIVING STANDARD ANTIRETROVIRAL THERAPY
Authors: Theresa N. Mann^1,2, Kirsten A. Donald³, Kathleen G. Walker⁴, Nelleke G. Langerak¹
Affiliation: ¹ Division of Neurosurgery, Department of Surgery, University of Cape Town, Cape Town, South Africa ² Division of Orthopedic Surgery, Department of Surgical Sciences, Stellenbosch University, Tygerberg, Cape Town, South Africa ³ Division of Developmental Pediatrics, Department of Pediatrics and Child Health, University of Cape Town and Red Cross War Memorial Children’s Hospital, Cape Town, South Africa ⁴ Division of Pediatric Neurology, Department of Pediatrics and Child Health, University of Cape Town and Red Cross War Memorial Children’s Hospital, Cape Town, South Africa
Objective:

This short report describes clinical observations that arose during a follow-up examination of children previously diagnosed with Human Immunodeficiency Virus (HIV) encephalopathy and increased lower limb muscle tone. It is among the first to describe that increased lower limb muscle tone in children with a confirmed HIV encephalopathy diagnosis may resolve over time in some cases.

Methods:

Children potentially eligible for a study investigating the natural history of spastic diplegia in children with HIV encephalopathy were identified using a database of patients seen at the Red Cross War Memorial Children’s Hospital HIV Neurology clinic between 2008 and 2014. The database included each child’s medical history and the findings of a physical examination. Children diagnosed with HIV encephalopathy and recorded as having increased lower limb muscle tone were invited to the hospital for further screening, including a follow-up physical exam. During screening, it was found that lower limb muscle tone abnormalities had resolved in some children. Possible explanations for this unexpected finding including i) age and follow up time, ii) severity of the initial neurological findings and iii) age at the start of anti-retroviral treatment were subsequently investigated.

Results:

Of 19 children previously diagnosed with HIV encephalopathy and increased lower limb muscle tone, some were found to have resolved muscle tone abnormalities during a follow-up physical examination (Resolved group, n=13, median age 9y7mo [interquartile range 7y3mo-10y9mo]) whereas others continued to show increased lower limb muscle tone at follow-up (Unresolved group, n=6 median age 8y6mo [interquartile range 7y9mo-9y7mo])). A review of clinical records showed no significant differences in age or follow-up time between the Resolved and Unresolved groups. However, children in the Resolved group had less severe neurological signs at the initial assessment and tended to commence antiretroviral treatment later compared to children in the Unresolved group (median age at start of treatment 2y3mo [interquartile range 7mo-5y3mo] vs. 8mo [interquartile range 6mo-12mo], p=0.08).

Conclusions:

It is anticipated that this information may be of immediate value to those involved in the treatment of children with HIV encephalopathy and increased lower limb muscle tone whilst awaiting the outcome of future controlled clinical trials.

HREC REF 447/2012

Title: Review of liver injuries in young children
Authors: Van As AB, Fester A, Banderker E, Millar AJ, Numanoglu A
Affiliation: Trauma Unit, Department of Paediatric Surgery, Red Cross War Memorial Children’s Hospital in Cape Town, University of Cape Town


Purpose:

This study on the management of blunt liver injury in children is based on the authors’ experience of 409 patients over a 32-year period.

Materials and Methods:

All children presenting to our institution with confirmed blunt liver trauma were studied retrospectively. Hospital folders of 409 patients were analysed. Information was gathered about the clinical presentation, associated injuries, grade of injury, transfusion requirements and haemodynamic stability to examine factors influencing outcome.

Results:

The age of patients ranged between 3 weeks and 13 years (mean of 7 years). Overall, most injuries were motor vehicle related, 303 pedestrian and 47 passenger, followed by 26 falls, 17 non-accidental injury cases, 3 bicycle injuries, 3 crush injuries and 1 unknown cause. One-hundred-and-sixty-three (163) patients sustained an isolated hepatic injury and 246 had multiple injuries. Associated injuries included 160 head injuries, 163 fractures, 102 thoracic and 191 intra-abdominal (96 spleen, 70 renal, 5 pancreatic and 5 hollow viscus). A total of 368 patients were managed non-operatively, while 30 underwent laparotomy and 2 died very briefly after arrival. The total number of fatalities was three, one due to severe head injury and two due to injuries sustained by the liver. A total of 146 patients required a transfusion, 31% of the non-operative group (mean 17ml/kg) and 100% of the operative group (mean 30.4ml/kg). There were 13 complications in the non-operative group and in addition to the aforementioned avulsion include 2 ruptured subcapsular haematomas, 7 abscesses, 1 pancreatic pseudocyst and one fat embolism syndrome.

Conclusion:

The vast majority (93%) was successfully treated non-operatively with only 4% coming to liver related laparotomy, complications were lower, transfusions less and the in-hospital occupancy was shorter. Complication rate was 8% and mortality was 1%. We confirm the success selective non-operative management of blunt liver trauma as adopted by our institution 32 years ago.

Title: THE EFFECTS ON PRONING ON REGIONAL VENTILATION IN CHILDREN WITH ACUTE RESPIRATORY DISTRESS SYNDROME (ARDS) OR ACUTE LUNG INJURY (ALI) - A PILOT STUDY
Authors: Morrow BM¹; Lupton-Smith AR¹; Rimensberger PC²; Argent AC¹
Affiliation: ¹School of Child and Adolescent Health, University of Cape Town; Paediatric Intensive Care Unit, Red Cross War Memorial Children’s Hospital; ²University Hospital of Geneva, Switzerland

Introduction:

Prone positioning is commonly used in ALI/ARDS to improve oxygenation. Improved oxygenation is thought to occur due to the recruitment of collapsed dorsal lung regions and improved ventilation homogeneity in the lung.

Aim:

To determine the effect of turning children with ALI/ARDS from the supine to prone position on regional ventilation.

Methods:

Thoracic electrical impedance tomography (EIT) measurements were taken lying in the supine position (baseline) and 5, 20 and 60 minutes after being turned into the prone position. Arterial blood gas measurements were obtained at baseline and after 60 minutes of being in the prone position.

Repeated measures ANOVA was used to determine the difference in mean relative dorsal impedance change between responders and non-responders. Global inhomogeneity indices were calculated. Regional filling characteristics of dorsal and ventral regions were also calculated from regional vs. global tidal volume tracings. Polynomial co-efficients above 0.2 indicate initial low regional tidal volume change compared to normal (recruitable lung). A negative co-efficient, < -0.2, indicates late low regional tidal volume change (over-inflation). Co-efficients between –0.2 and +0.2 indicates regional tidal volume changes occurring homogenously over the whole of inspiration (optimal, protective ventilation).
Results:

Preliminary data on the first 11 patients (9 male, median (interquartile range) age 11 (20.6) months) are presented. Median (interquartile range) baseline PaO2 was 9.43 (4) kPa. Six (55%) children demonstrated an improvement in PaO2 of 1.9 (1.8) kPa in the prone position (responders). Five (45%) children demonstrated a reduction of 1.5 (1.3) kPa in PaO2 in the prone position (non-responders).

There was no difference between responders and non-responders in the change in regional ventilation in the dorsal lung after prone turning (p = 0.2). Five responders (83.3%) demonstrated notable heterogeneity of ventilation at baseline, with either or both the ventral and dorsal lung regions being hyperinflated and/or recruitable on regional filling characteristics, with a mean correlation coefficient of 0.8 between regional and global ventilation. After prone turning, the filling characteristics changed notably, with polynomial coefficients in the optimal ventilation range for both ventral and dorsal regions, and increased mean correlation coefficients of 1.

In contrast, five (100%) non-responders demonstrated optimal ventilation in both ventral and dorsal regions at baseline, with high mean correlation coefficients of 1, which was unchanged after turning.

The coefficient of variation in the global homogeneity indices changed from 87.0% to 18.4% in responders and from 15.7% to 8.1% in non-responders (p = 0.02) after proning, indicating improved homogeneity of ventilation following prone turning in responders.
Conclusions:

Preliminary data suggests that improved oxygenation as a result of being turned prone may be related to improved homogeneity of ventilation and not due to improved dorsal lung ventilation

UCT HREC 269/2008

Title: CHEST RADIOGRAPHIC ABNORMALITIES IN HIV-INFECTED AFRICAN CHILDREN – A LONGITUDINAL STUDY
Authors: Richard D. Pitcher, Carl J. Lombard, Mark F. Cotton, Stephen J. Beningfield, Lesley Workman, Heather J. Zar

Objective:

To investigate the natural history of chest radiographic abnormalities in HIV-infected African children and the impact of anti-retroviral therapy (ART).

Methods:

Prospective longitudinal study of the association of chest radiographic findings with clinical and immunological parameters. Chest radiographs were performed at enrolment, 6-monthly, when initiating ART and if indicated clinically. Radiographic abnormalities were classified as normal, mild or moderate severity and considered persistent if present for 6 consecutive months or longer. An ordinal multiple logistic regression model assessed the association of enrolment and time-dependent variables with temporal radiographic findings.

Results:

258 children [median(IQR) age: 28 (13-51) months; median CD4+%: 21 (15-24)] were followed for a median of 24 (18-42) months. 70 (27%) were on ART at enrolment; 130(50%) [median age: 33(18-56) months] commenced ART during the study. 154 (60%) had persistent severe radiographic abnormalities, with median duration 18 (6-24) months. Amongst children on ART, 69% of radiographic changes across all 6-month transition periods were improvements, compared to 45% in those not on ART. Radiographic severity was associated with previous radiographic severity (OR=120.80; 95%CI = 68.71–212.38), lack of ART (OR=1.72; 95%CI = 1.29–2.27), enrolment age <18months (OR=1.39; 95% CI = 1.06–1.83), diffuse, severe radiographic abnormality at enrolment (OR = 2.18; 95% CI = 1.33–3.56), hospitalization for respiratory infection during the previous 6 months (OR=1.88; 95% CI=1.06–3.30) and length of follow-up: at 18-24months (OR = 0.66; 95% CI= 0.49–0.90), and at 30-54 months (OR= 0.42; 95% CI = 0.32-0.56).

Conclusion:

Most children had severe radiographic abnormalities persisting for at least 18 months. ART was beneficial, reducing the risk of radiographic deterioration or increasing the likelihood of radiological improvement.

Ethics No: 2002/C073
Title: CLINICAL PREDICTORS OF CULTURE CONFIRMED PULMONARY TUBERCULOSIS (PTB) IN A HIGH TB AND HIV PREVALENCE AREA
Abbreviated Title: Clinical Predictors of Culture confirmed TB
Authors: Lisa Frigati (MBBCh, MMed, FCPaeds, MScTMIH, Cert PaedID) ^a, Mhairi Maskew (MBBCh, PhD) ^b, Lesley Workman (MPH) ^c, Jacinta Munro (matric) ^d, Savvas Andronikou (MBBCh, PhD) ^e, Mark P Nicol ⁽MBBCh, MMed, PhD) ^f, Heather J Zar (MBBCh, FCPaeds, PhD) ^g
Affiliation: ^a Department of Pediatrics and Child Health, University of Cape Town and Tygerberg Children’s Hospital, Cape Town, South Africa; ^b Health Economics and Epidemiology Research Office, Department of Internal Medicine, School of Clinical Medicine, University of the Witwatersrand; ^c Division of Clinical Pharmacology, Department of Medicine and Child Health University of Cape Town, Cape Town, South Africa; ^d Department of Pediatrics and Child Health, University of Cape Town, Cape Town, South Africa and Red Cross War Memorial Children’s Hospital, Cape Town, South Africa; ^e Department of Radiology, Faculty of Health Sciences, University of Cape Town; ^f Division of Medical Microbiology, Department of Clinical Laboratory Sciences, Institute for Infectious Diseases and Molecular Medicine, University of Cape Town and National Health Laboratory Service of South Africa; ^g Department of Paediatrics and Child Health, Red Cross Childrens Hospital, University of Cape Town, South Africa and MRC unit on Child and Adolescent Lung Health

Background:

The burden of childhood tuberculosis (TB) remains significant especially in areas of high HIV prevalence. Clinical diagnosis predominates, despite advances in molecular and microbiological diagnostics

Aim:

To identify clinical features associated with culture-confirmed pulmonary TB (PTB) in children.

Methods:

Children admitted to hospital were enrolled in a study of novel diagnostics for PTB in South Africa. Standardized clinical, radiological and microbiological data were collected. Definite TB was defined by culture of M. tuberculosis from a respiratory specimen. Adjusted odds ratios for definite TB were calculated using a multivariate logistic regression model.

Results:

Adjusted odds ratio (AOR) for definite TB increased with a history of fever for more than 1 week (AOR 8.54, CI 2.37-30.74), with a chest radiograph (CXR) suggestive of PTB (AOR 10.0, CI 3.22 -31.2) and with a positive tuberculin skin test (TST) (AOR 64.4, CI 14.3 -290.5). The likelihood ratio of having definite TB if 2 of these factors (CXR and TST) were present compared with having none of them was 17.7. Cough, household contact with TB, HIV status and wheezing were not significantly associated with definite TB.

Conclusions:

Prolonged fever, CXR suggestive of TB or a positive TST were predictive of definite TB and should be considered in composite scoring systems for TB diagnosis in high HIV prevalence settings. Other commonly associated symptoms were not associated with definite TB.

Key Words: tuberculosis, diagnosis, children, clinical factors

Corresponding author: Dr Lisa Frigati: [e-mail]

Title: MICROBIOLOGICAL YIELD FROM INDUCED SPUTUM COMPARED TO OROPHARYNGEAL SWAB IN YOUNG CHILDREN WITH CYSTIC FIBROSIS
Authors: Marco Zampoli¹; Komala Pillay²; Henri Carrara³; Heather J Zar⁴ and Brenda Morrow¹
Background: 

Standard respiratory sampling in young children with cystic fibrosis (CF) is by oropharyngeal swab (OPS) as they can’t spontaneously expectorate. Sputum induction (IS) has been poorly investigated in this population. We aimed to compare the bacteriological yield of OPS vs. IS in young children with CF.

Methods: 

Sequentially paired OPS followed by IS samples were collected in children <5 years of age attending a CF clinic in Cape Town, South Africa. 

Results:

IS was successfully paired with OPS in 98/113 (85%) attempts in 32 children (mean ± SD 19±16 months), with no serious adverse events. IS Culture yield for any CF-associated bacteria from IS was 46% vs. 28% from OPS (p=0.01). The sensitivity, specificity, PPV and NPV of OPS compared to IS in isolating CF-associated bacteria was 56%, 96%, 93%, and 72% respectively. 

Conclusion:

Sputum induction is feasible, safe and superior to oropharyngeal swab for detecting CF-associated bacteria in young children with CF.

Sponsorship: Astra Zeneca Respiratory Research Grant; South African Thoracic Society

Conflicts of interest: non declared
Title: THE EFFECT OF BODY POSITION ON REGIONAL DISTRIBUTION OF VENTILATION AND MUSCLE ACTIVITY IN MECHANICALLY VENTILATED INFANTS AND CHILDREN 

Authors: Lupton-Smith AR¹; Argent AC¹; Rimensberger PC²; Morrow BM¹

Affiliation: ¹School of Child and Adolescent Health, University of Cape Town; Paediatric Intensive Care Unit, Red Cross War Memorial Children’s Hospital; ²University Hospital of Geneva, Switzerland

Introduction:

Recent studies have questioned the pattern of ventilation distribution (VD) in the paediatric population.  There are no recent studies examining the effect of body position in older mechanically ventilated children. In addition, there are few studies reporting muscle activity in relation to body position in this population.

Aim:

To determine the effect of body positions on regional VD and respiratory muscle activity in mechanically ventilated children.

Methods:

Thoracic electrical impedance tomography (EIT) and surface electromyography (sEMG) measurements were taken in left and right side lying in mechanically ventilated infants and children. Functional EIT images were produced offline and total regional relative tidal impedance (ΔZ) in the left and right lungs was calculated for each patient in each position. Activity (µV) of the left and right hemidiaphragm was examined in each position.

Results:

Preliminary data on the first 17 patients aged from six months to 6 years are presented.  11 (65%) children demonstrated varied patterns of VD between left and right side lying. No significant differences were found between left and right lungs in left (p=0.61) and right (p=0.77) side lying.  No significant difference was found in diaphragm activity between in either position.

Conclusions:

The paediatric pattern of ventilation is not predictable in mechanically ventilated infants and children, as previously described.  Muscle activity may not be affected by body position.

UCT HREC 126/2012

Title:  Adenoviral PNEUMONIA at Red Cross War Memorial Children’s Hospital: a retrospective descriptive study reviewing The PRESENTATION, clinical course and outcomes of laboratory- confirmed adenovirus associated pneumonia at RCWMCH

Authors: Zakira M-Sablay; Marco Zampoli 

Affiliation:  Department of Paediatrics and Child Health, University of Cape Town

Background: 

Pneumonia is an important cause of morbidity and mortality in children. Viruses have emerged as important aetiological agents in childhood pneumonia. The aim of this study was to document the clinical presentation, severity and outcome of adenoviral-associated pneumonia (AVP) at RCWMCH in children below 5 years of age and identify risk factors associated with poor outcome.

Methods: 

A retrospective study of laboratory-confirmed AVP cases was conducted between 1 January and 31 December 2011. The medical records of adenovirus PCR positive respiratory tract samples identified through the National Health Laboratory Service (NHLS) database were retrieved. Demographic, clinical and outcomes data of children with AVP was extracted and analysed. Outcome measures were death and development of chronic lung disease (CLD).

Results: 

1910 respiratory samples were submitted to the NHLS from which 206/1910 (11%) AVP cases were identified. The median age was 12 months (IQR 6-24), 70 (34%) children were malnourished and 14 (7%) HIV-infected. Fever was the commonest presenting symptom occurring in 159 (77%) of cases. Seventy six (37%) required ICU admission. There was a high prevalence of co-morbid conditions with 98 (47%) having at least one; cardiac disease was the most common (48 (23%) of which 35 (17%) had congenital heart disease. Twenty nine (14%) developed CLD which was associated with hypoxia at presentation (26/29, 90%, p = 0.01) and admission to ICU (18/29, 62%, p < 0.01). Eighteen (9%) children died. Mortality was associated with hypoxia at presentation (17/18, 94%, p =0.02), admission to ICU (14/18, 78%, p < 0.01), blood stream infection (4/18, 22%, p=0.01) and underlying cardiac disease (8/18, 44%, p =0.02). ICU admission (OR 8.3, 95% CI 2.3- 29.0) and blood stream infection (OR 11.2; 95% CI 2.3-54.1) were independent risk factors for mortality. 

Conclusion:

Adenoviral-associated pneumonia is an important cause of pneumonia and CLD in children less than 5 years of age. Underlying cardiac disease, hypoxia, blood stream infection and ICU admission were associated with poor outcome.

Funding: Department of Paediatrics and Child Health, UCT.
Conflicts of interest: none declared