Nutritional screening in a cancer prehabilitation programme: A cohort study.

BACKGROUND: Cancer patients are often malnourished pre-operatively. The present study aimed to establish whether current screening was appropriate for use in prehabilitation and investigate any association between nutritional risk, functionality and quality of life (QoL). METHODS: This cohort study used routinely collected data from September 2020 to August 2021 from patients in a Prehab4cancer programme. Included patients were aged ≥ 18 years, had colorectal, lung or oesophago-gastric cancer and were scheduled for surgery. Nutritional assessment included Patient-Generated Subjective Global Assessment (PG-SGA) Short-Form and QoL with a sit-to-stand test. Association between nutritional risk and outcomes was analysed using adjusted logistic regression. RESULTS: From 928 patients referred to Prehab4Cancer service over 12 months, data on nutritional risk were collected from 526 patients. Pre-operatively, 233 out of 526 (44%) patients were at nutritional risk (score ≥ 2). During prehabilitation, 31% of patients improved their PG-SGA and 74% of patients maintained or improved their weight. Odds ratios (OR) with confidence intervals (CI) showed that patients with better QoL using EuroQol-5 Dimensions (OR = 0.05, 95% CI = 0.01, 0.45, p = 0.01), EuroQol Visual Analogue Scale (OR = 0.96, 95% CI = 0.93, 1.00, p = 0.04) or sit-to-stand (OR = 0.96, 95% 0.93, 1.00, p = 0.04) were less likely to be nutritional at risk. CONCLUSIONS: Almost half of patients in Prehab4Cancer programme assessed using PG-SGA were at risk of malnutrition. However, almost half of the sample did not have their risk assessed. Patients at risk of malnutrition were more likely to have a poorer QoL and sit-to-stand test than those who were not at risk.

Malignant extracranial germ cell tumours: A first national report by the South African Children's Cancer Study Group.

OBJECTIVE: To determine the overall survival (OS) and prognostic factors influencing outcomes in children and adolescents with malignant extracranial germ cell tumours (MEGCTs) in preparation for the development of a harmonised national treatment protocol. METHODS: A retrospective folder review was undertaken at nine South African paediatric oncology units to document patient profiles, tumour and treatment-related data and outcomes for all children with biopsy-proven MEGCTs from birth up to and including 16 years of age. RESULTS: Between 1 January 2000 and 31 December 2015, 218 patients were diagnosed with MEGCTs. Female sex (hazard ratio [HR] 0.284, p = .037) and higher socio-economic status (SES) (HR 0.071, p = .039) were associated with a significantly lower risk of death. Advanced clinical stage at diagnosis significantly affected 5-year OS: stage I: 96%; stage II: 94.3%; stage III: 75.5% (p = .017) and stage IV (60.1%; p < .001). There was a significant association between earlier stage at presentation and higher SES (p = .03). Patients with a serum alpha-fetoprotein (AFP) level of more than 33,000 ng/ml at diagnosis had significantly poorer outcomes (p = .002). The use of chemotherapy significantly improved survival, irrespective of the regimen used (p < .001). CONCLUSIONS: The cohort demonstrated a 5-year OS of 80.3% with an event-free survival (EFS) of 75.3%. Stage, the use of chemotherapy and an elevated serum AFP level of more than 33,000 ng/ml were independently predictive of outcome. The relationship between SES and outcome is important as the implementation of the new national protocol hopes to standardise care across the socio-economic divide.

Sex Cord Stromal Tumors in Children and Adolescents: A First Report by The South African Children's Cancer Study Group (1990-2015).

OBJECTIVES: Pediatric sex cord stromal tumors (SCSTs) are extremely rare and there are no reported data from Africa. The authors evaluated the outcomes of children and adolescents with biopsy-proven SCSTs in preparation for the introduction of a national protocol. MATERIALS AND METHODS: Retrospective data were collated from 9 South African pediatric oncology units from January 1990 to December 2015. Kaplan-Meier analysis was performed to estimate overall survival (OS) and event-free survival. RESULTS: Twenty-three patients were diagnosed with SCSTs, 3 male and 20 female individuals, during the study period. Histologies included 1 thecoma, 9 Sertoli-Leydig cell tumors, and 13 juvenile granulosa cell tumors. Stage I tumors predominated (n=14; 60.9%), with 2 stage II (8.7%), 5 stage III (21.7%), and 2 stage IV tumors (8.7%). The upfront resection rate was 91.3% with no reported surgical morbidity or mortality and an OS of 82.1%. Chemotherapy approaches were not standardized. Most children (81.8%), except 2, had recognized platinum-based regimens. Chemotherapy-related toxicity was minimal and acceptable. Assessment of glomerular filtration rate and audiology assessments were infrequent and not standardized. Three patients were lost to follow-up. CONCLUSIONS: Although the numbers in this cohort are small, this study represents the first national cohort in Africa. The 5-year OS of 82.1% was encouraging. Standardized management of rare tumors like SCSTs is critical to improve ensure OS and address potential long-term sequelae.

Maltreatment in childhood and intimate partner violence: A latent class growth analysis in a South African pregnancy cohort.

Intimate partner violence (IPV) is a significant global problem, prevalent in low and middle-income countries (LMICs). IPV is particularly problematic during the perinatal and early postnatal period, where it is linked with negative maternal and child health outcomes. There has been little examination of profiles of IPV and early life adversity in LMIC contexts. We aimed to characterize longitudinal IPV and to investigate maternal maltreatment in childhood as a predictor of IPV exposure during pregnancy and postnatally in a low resource setting. This study was nested in the Drakenstein Child Health Study, a longitudinal birth cohort. Maternal IPV (emotional, physical and sexual) was measured at six timepoints from pregnancy to two years postpartum (n = 832); sociodemographic variables and maternal maltreatment in childhood were measured antenatally at 28-32 weeks' gestation. Associations between maternal maltreatment in childhood and IPV latent class membership (to identify patterns of maternal IPV exposure) were estimated using multinomial and logistic regression. We observed high levels of maternal maltreatment during childhood (34%) and IPV during pregnancy (33%). In latent class analysis separating by IPV sub-type, two latent classes of no/low and moderate sexual IPV and three classes of low, moderate, and high emotional and physical IPV (separately) were detected. In combined latent class analysis, including all IPV sub-types together, a low, moderate and high exposure class emerged as well as a high antenatal/decreasing postnatal class. Moderate and high classes for all IPV sub-types and combined analysis showed stable intensity profiles. Maternal childhood sexual abuse, physical abuse and neglect, and emotional abuse predicted membership in high IPV classes, across all domains of IPV (aORs between 1.99 and 5.86). Maternal maltreatment in childhood was associated with increased probability of experiencing high or moderate intensity IPV during and around pregnancy; emotional neglect was associated with decreasing IPV class for combined model. Intervening early to disrupt this cycle of abuse is critical to two generations.

NeuroAIDS in children.

The human immunodeficiency virus-1 (HIV-1) enters the central nervous system compartment within the first few weeks of systemic HIV infection and may cause a spectrum of neurologic complications. Without combination antiretroviral therapy (cART), 50-90% of all HIV-infected infants and children develop some form of neuroAIDS. Of the estimated 2.3 million children less than 15 years of age who were living in sub-Saharan Africa at the end of 2014, only 30% were receiving cART, suggesting that there is a large burden of neuroAIDS among HIV-infected children in sub-Saharan Africa. There is complex interplay between the disease process itself, the child's immune reaction to the disease, the secondary complications, the side-effects of antiretroviral drugs, and inadequate antiretroviral drug uptake into the central nervous system. In addition there is the layering effect from the multiple socioeconomic challenges for children living in low- and middle-income countries. Adolescents may manifest with a range of neurocognitive sequelae from mild neurocognitive disorder through to severe neurocognitive impairment. Neuroimaging studies on white-matter tracts have identified dysfunction, especially in the frontostriatal networks needed for executive function. Psychiatric symptoms of depression, attention deficit hyperactivity disorder, and behavioral problems are also commonly reported in this age group. Antiretroviral drugs may cause treatment-limiting neurologic and neuropsychiatric adverse reactions. The following chapter addresses the neurologic complications known to be, and suspected of being, associated with HIV infection in children and adolescents.

Clinical characteristics and neurodevelopmental outcomes of children with tuberculous meningitis and hydrocephalus.

AIM: Tuberculous meningitis (TBM) is a lethal and commonly occurring form of extra-pulmonary tuberculosis in children, often complicated by hydrocephalus which worsens outcome. Despite high mortality and morbidity, little data on the impact on neurodevelopment exists. We examined the clinical characteristics, and clinical and neurodevelopmental outcomes of TBM and hydrocephalus. METHOD: Demographic and clinical data (laboratory and radiological findings) were prospectively collected on children treated for probable and definite TBM with hydrocephalus. At 6 months, clinical outcome was assessed using the Paediatric Cerebral Performance Category Scale and neurodevelopmental outcome was assessed with the Griffiths Mental Development Scale - Extended Version. RESULTS: Forty-four patients (median age 3y 3mo, range 3mo-13y 1mo, [SD 3y 5mo]) were enrolled. The mortality rate was 16%, three patients (6.8%) were in a persistent vegetative state, two were severely disabled (4.5%), and 11 (25%) suffered mild-moderate disability. All cases demonstrated neurodevelopmental deficits relative to controls. Multiple or large infarcts were prognostic of poor outcome. INTERPRETATION: Neurological and neurodevelopmental deficits are common after paediatric TBM with hydrocephalus, and appear to be related to ongoing cerebral ischaemia and consequent infarction. The impact of TBM on these children is multidimensional and presents short- and long-term challenges.

Preliminary Validation of a New Developmental Screening Tool for Neurodevelopmental Delay in HIV-Infected South African Children.

Screening for developmental delays among HIV-infected children is not routine in most pediatric HIV clinics in Africa because of the lack of locally adaptable, simple, sensitive and rapid screening tools. The Division of Developmental Pediatrics of the Red Cross War Memorial Children's Hospital developed a tool for rapid screening of moderate to severe global developmental delays among HIV-infected children aged 9 to 36 months. The diagnostic accuracy of the novel screening tool was evaluated. Forty-seven HIV-infected children aged 9 to 36 months were screened using the Red Cross War Memorial Children's Hospital developmental screening tool. Full developmental assessments of same children were performed using the Bayley Scales of Infant and Toddler Development, Third Edition. The Red Cross War Memorial Children's Hospital tool's sensitivity was 78.5%, specificity 54.6%, positive predictive value was 42.6%, and negative predictive value was 85.4%. The Red Cross War Memorial Children's Hospital screening tool was adequately sensitive and therefore recommended for screening of moderate to severe developmental delays among HIV-infected children.

White matter integrity and cognitive performance in children with prenatal methamphetamine exposure.

There is emerging evidence on the harmful effects of prenatal methamphetamine (MA) exposure on the structure and function of the developing brain. However, few studies have assessed white matter structural integrity in the presence of prenatal MA exposure, and results are inconsistent. This investigation thus used diffusion tensor imaging (DTI) to investigate white matter microstructure and cognitive performance in a group of prenatal MA exposed (or MA) children and controls of similar age. Seventeen MA children and 15 healthy controls (aged 6-7 years) underwent DTI and assessment of motor function and general cognitive ability. Whole brain analyses of white matter structure were performed using FSL's tract-based spatial statistics comparing fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and axial diffusivity (AD). Mean diffusion values were extracted from white matter regions shown to differ across groups to determine whether variations in FA predicted cognitive performance. Analyses were controlled for maternal nicotine use. MA children showed significantly lower FA as well as higher MD, RD and AD in tracts that traverse striatal, limbic and frontal regions. Abnormal FA levels in MA children were significantly associated with poorer motor coordination and general cognitive ability sub-items that relate to aspects of executive function. Our findings suggest that, consistent with previous studies in older children, there are disruptions of white matter microstructural integrity in striatal, limbic and frontal regions of young MA exposed children, with prominent cognitive implications. Future longitudinal studies may clarify how prenatal MA exposure affects white matter structural connectivity at different stages of brain maturation.

Effects of prenatal methamphetamine exposure: a review of cognitive and neuroimaging studies.

Prenatal methamphetamine exposure (PME) is a significant problem in several parts of the world and poses important health risks for the developing fetus. Research on the short- and long-term outcomes of PME is scarce, however. Here, we summarize present knowledge on the cognitive and behavioral outcomes of PME, based on a review of the neuroimaging, neuropsychology, and neuroscience literature published in the past 15 years. Several studies have reported that the behavioral and cognitive sequelae of PME include broad deficits in the domains of attention, memory, and visual-motor integration. Knowledge regarding brain-behavior relationships is poor, however, in large part because imaging studies are rare. Hence, the effects of PME on developing neurocircuitry and brain architecture remain speculative, and are largely deductive. Some studies have implicated the dopamine-rich fronto-striatal pathways; however, cognitive deficits (e.g., impaired visual-motor integration) that should be associated with damage to those pathways are not manifested consistently across studies. We conclude by discussing challenges endemic to research on prenatal drug exposure, and argue that they may account for some of the inconsistencies in the extant research on PME. Studies confirming predicted brain-behavior relationships in PME, and exploring possible mechanisms underlying those relationships, are needed if neuroscience is to address the urgency of this growing public health problem.

A diffusion tensor imaging and neurocognitive study of HIV-positive children who are HAART-naïve "slow progressors".

There are few neuropsychological or neuroimaging studies of HIV-positive children with "slow progression". "Slow progressors" are typically defined as children or adolescents who were vertically infected with HIV, but who received no or minimal antiretroviral therapy. We compared 12 asymptomatic HIV-positive children (8 to 12 years) with matched controls on a neuropsychological battery as well as diffusion tensor imaging in a masked region of interest analysis focusing on the corpus callosum, internal capsule and superior longitudinal fasciculus. The "slow progressor" group performed significantly worse than controls on the Wechsler Abbreviated Scale of Intelligence Verbal and Performance IQ scales, and on standardised tests of visuospatial processing, visual memory and executive functioning. "Slow progressors" had lower fractional anisotropy (FA), higher mean diffusivity (MD) and radial diffusivity (RD) in the corpus callosum (p= <0.05), and increased MD in the superior longitudinal fasciculus, compared to controls. A correlation was found between poor performance on a test of executive function and a test of attention with corpus callosum FA, and a test of executive function with lowered FA in the superior longitudinal fasiculus. These data suggest that demyelination as reflected by the increase in RD may be a prominent disease process in paediatric HIV infection.

The usefulness of electroencephalograms in a survey of children from the Western cape of South Africa.

There are few dedicated pediatric neurophysiology services in Africa. Optimizing the efficiency of these units is essential for the large populations they serve. Two hundred eighty-seven electroencephalogram (EEG) studies, performed in a sub-Saharan neurophysiology unit, were analyzed for referral sources, appropriateness of referral, reporting consistency, and use in confirming epilepsy or a neurologic process. Pediatric neurologists requested 24% of the electroencephalogram studies and pediatricians 45%. Pediatric neurologists requested more appropriate referrals than pediatricians or nonspecialists. The electroencephalogram studies assisted management in 40% of cases. Electroencephalogram studies for nonepileptic indications, such as syncope, were highly predictable and typically normal. Education and training in the management of children with epilepsy could improve requesting practice and the subsequent usefulness of electroencephalograms in the diagnosis of epilepsy syndromes. This is especially important in the context of a resource-poor country.