Prognosis of Children with HIV-1 Infection Starting Antiretroviral Therapy in Southern Africa: A Collaborative Analysis of Treatment Programs

BACKGROUND: Prognostic models for children starting antiretroviral therapy (ART) in Africa are lacking. We developed models to estimate the probability of death during the first year receiving ART in Southern Africa. METHODS: We analyzed data from children ≤10 years old who started ART in Malawi, South Africa, Zambia or Zimbabwe from 2004-2010. Children lost to follow-up or transferred were excluded. The primary outcome was all-cause mortality in the first year of ART. We used Weibull survival models to construct two prognostic models: one with CD4%, age, WHO clinical stage, weight-for-age z-score (WAZ) and anemia and one without CD4%, because it is not routinely measured in many programs. We used multiple imputation to account for missing data. RESULTS: Among 12655 children, 877 (6.9%) died in the first year of ART. 1780 children were lost to follow-up/transferred and excluded from main analyses; 10875 children were included. With the CD4% model probability of death at 1 year ranged from 1.8% (95% CI: 1.5-2.3) in children 5-10 years with CD4% ≥10%, WHO stage I/II, WAZ ≥-2 and without severe anemia to 46.3% (95% CI: 38.2-55.2) in children <1 year with CD4% <5%, stage III/IV, WAZ< -3 and severe anemia. The corresponding range for the model without CD4% was 2.2% (95% CI: 1.8-2.7) to 33.4% (95% CI: 28.2-39.3). Agreement between predicted and observed mortality was good (C-statistics=0.753 and 0.745 for models with and without CD4% respectively). CONCLUSION: These models may be useful to counsel children/caregivers, for program planning and to assess program outcomes after allowing for differences in patient disease severity characteristics.

Blood glucose and prognosis in children with presumed severe malaria: is there a threshold for 'hypoglycaemia'?

OBJECTIVES: Hypoglycaemia (glucose <2.2 mmol/l) is a defining feature of severe malaria, but the significance of other levels of blood glucose has not previously been studied in children with severe malaria. METHODS: A prospective study of 437 consecutive children with presumed severe malaria was conducted in Mali. We defined hypoglycaemia as <2.2 mmol/l, low glycaemia as 2.2-4.4 mmol/l and hyperglycaemia as >8.3 mmol/l. Associations between glycaemia and case fatality were analysed for 418 children using logistic regression models and a receiver operator curve (ROC). RESULTS: There was a significant difference between blood glucose levels in children who died (median 4.6 mmol/l) and survivors (median 7.6 mmol/l, P < 0.001). Case fatality declined from 61.5% of the hypoglycaemic children to 46.2% of those with low glycaemia, 13.4% of those with normal glycaemia and 7.6% of those with hyperglycaemia (P < 0.001). Logistic regression showed an adjusted odds ratio (AOR) of 0.75 (0.64-0.88) for case fatality per 1 mmol/l increase in baseline blood glucose. Compared to a normal blood glucose, hypoglycaemia and low glycaemia both significantly increased the odds of death (AOR 11.87, 2.10-67.00; and 5.21, 1.86-14.63, respectively), whereas hyperglycaemia reduced the odds of death (AOR 0.34, 0.13-0.91). The ROC [area under the curve at 0.753 (95% CI 0.684-0.820)] indicated that glycaemia had a moderate predictive value for death and identified an optimal threshold at glycaemia <6.1 mmol/l, (sensitivity 64.5% and specificity 75.1%). CONCLUSIONS: If there is a threshold of blood glucose which defines a worse prognosis, it is at a higher level than the current definition of 2.2 mmol/l.

Duplication of the sodium channel gene cluster on 2q24 in children with early onset epilepsy

Sodium channel gene aberrations are associated with a wide range of seizure disorders, particularly Dravet syndrome. They usually consist of missense or truncating gene mutations or deletions. Duplications involving multiple genes encoding for different sodium channels are not widely known. This article summarizes the clinical, radiologic, and genetic features of patients with 2q24 duplication involving the sodium channel gene cluster.

A simple asthma prediction tool for preschool children with wheeze or cough

BACKGROUND Many preschool children have wheeze or cough, but only some have asthma later. Existing prediction tools are difficult to apply in clinical practice or exhibit methodological weaknesses. OBJECTIVE We sought to develop a simple and robust tool for predicting asthma at school age in preschool children with wheeze or cough. METHODS From a population-based cohort in Leicestershire, United Kingdom, we included 1- to 3-year-old subjects seeing a doctor for wheeze or cough and assessed the prevalence of asthma 5 years later. We considered only noninvasive predictors that are easy to assess in primary care: demographic and perinatal data, eczema, upper and lower respiratory tract symptoms, and family history of atopy. We developed a model using logistic regression, avoided overfitting with the least absolute shrinkage and selection operator penalty, and then simplified it to a practical tool. We performed internal validation and assessed its predictive performance using the scaled Brier score and the area under the receiver operating characteristic curve. RESULTS Of 1226 symptomatic children with follow-up information, 345 (28%) had asthma 5 years later. The tool consists of 10 predictors yielding a total score between 0 and 15: sex, age, wheeze without colds, wheeze frequency, activity disturbance, shortness of breath, exercise-related and aeroallergen-related wheeze/cough, eczema, and parental history of asthma/bronchitis. The scaled Brier scores for the internally validated model and tool were 0.20 and 0.16, and the areas under the receiver operating characteristic curves were 0.76 and 0.74, respectively. CONCLUSION This tool represents a simple, low-cost, and noninvasive method to predict the risk of later asthma in symptomatic preschool children, which is ready to be tested in other populations.

Abnormal small airways function in children with mild asthma

BACKGROUND Small airways disease is a hallmark in adults with persistent asthma, but little is known about small airways function in children with mild asthma and normal spirometry. We assessed ventilation heterogeneity, a marker of small airways function, with an easy tidal breath single-breath washout (SBW) technique in school-aged children with mild asthma and normal FEV1 and healthy age-matched control subjects. METHODS The primary outcome was the double-tracer gas phase III slope (SDTG), an index of ventilation heterogeneity in acinar airways derived from the tidal double-tracer gas SBW test. The second outcome was the nitrogen phase III slope (SN2), an index of global ventilation heterogeneity derived from the tidal nitrogen SBW test using pure oxygen. Triplicate SBW and spirometry tests were performed in healthy children (n = 35) and children with asthma (n = 31) at baseline and in children with asthma after bronchodilation. RESULTS Acinar (SDTG) but not global (SN2) ventilation heterogeneity was significantly increased in asthma despite normal FEV1. Of the 31 children with asthma, abnormal results were found for SDTG (≤ -2 z scores) in 11; forced expiratory flow, midexpiratory phase (FEF25%-75%) in three; and FEV1 in zero. After bronchodilation, SDTG, SN2, FEF25%-75%, and FEV1 significantly changed (mean [95% CI] change from baseline, 36% [15%-56%], 38% [18%-58%], 17% [9-25%], and 6% [3%-9%], respectively). CONCLUSIONS Abnormal acinar ventilation heterogeneity in one-third of the children suggests that small airways disease may be present despite rare and mild asthma symptoms and normal spirometry. The easy tidal SBW technique has considerable potential as a clinical and research outcome in children with asthma.

Cognitive Interventions with Children with Special Needs - Transfer effects and multidisciplinary perspectives

Our last study with regularly developed children demonstrated a positive effect of working memory training on cognitive abilities. Building upon these findings, the aim of this multidisciplinary study is to investigate the effects of training of core functions with children who are suffering from different learning disabilities, like AD/HD, developmental dyslexia or specific language impairment. In addition to working memory training (BrainTwister), we apply a perceptual training, which concentrates on auditory-visual matching (Audilex), as well as an implicit concept learning task. We expect differential improvements of mental capacities, specifically of executive functions (working memory, attention, auditory and visual processing), scholastic abilities (language and mathematical skills), as well as of problem solving. With that, we hope to find further directions regarding helpful and individually adapted interventions in educational settings. Interested parties are invited to discuss and comment the design, the research question, and the possibilities in recruiting the subjects.

Which clinical signs predict hypoxaemia in young Senegalese children with acute lower respiratory tract disease?

BACKGROUND Acute lower respiratory tract diseases are an important cause of mortality in children in resource-limited settings. In the absence of pulse oximetry, clinicians rely on clinical signs to detect hypoxaemia. OBJECTIVE To assess the diagnostic value of clinical signs of hypoxaemia in children aged 2 months to 5 years with acute lower respiratory tract disease. METHODS Seventy children with a history of cough and signs of respiratory distress were enrolled. Three experienced physicians recorded clinical signs and oxygen saturation by pulse oximetry. Hypoxaemia was defined as oxygen saturation <90%. Clinical predictors of hypoxaemia were evaluated using adjusted diagnostic odds ratios (aDOR). RESULTS There was a 43% prevalence of hypoxaemia. An initial visual impression of poor general status [aDOR 20·0, 95% CI 3·8-106], severe chest-indrawing (aDOR 9·8, 95% CI 1·5-65), audible grunting (aDOR 6·9, 95% CI 1·4-25) and cyanosis (aDOR 26·5, 95% CI 1·1-677) were significant predictors of hypoxaemia. CONCLUSION In children under 5 years of age, several simple clinical signs are reliable predictors of hypoxaemia. These should be included in diagnostic guidelines.

Use of Complementary and Alternative Medicine in Children with Cancer: A Study at a Swiss University Hospital

Background Though complementary and alternative medicine (CAM) are frequently used by children and adolescents with cancer, there is little information on how and why they use it. This study examined prevalence and methods of CAM, the therapists who applied it, reasons for and against using CAM and its perceived effectiveness. Parent-perceived communication was also evaluated. Parents were asked if medical staff provided information on CAM to patients, if parents reported use of CAM to physicians, and what attitude they thought physicians had toward CAM. Study Design All childhood cancer patients treated at the University Children’s Hospital Bern between 2002–2011 were retrospectively surveyed about their use of CAM. Results Data was collected from 133 patients (response rate: 52%). Of those, 53% had used CAM (mostly classical homeopathy) and 25% of patients received information about CAM from medical staff. Those diagnosed more recently were more likely to be informed about CAM options. The most frequent reason for choosing CAM was that parents thought it wouldimprove the patient’s general condition. The most frequent reason for not using CAM was lack of information. Of those who used CAM, 87% perceived positive effects. Conclusions Since many pediatric oncology patients use CAM, patients’ needs should be addressed by open communication between families, treating oncologists and CAM therapists, which will allow parents to make informed and safe choices about using CAM.