Risperidone for disruptive behaviour in children and adolescents with learning disability

MSc (Med) (Child Health Neurodevelopment), Faculty of Health Sciences, University of the WitwatersrandBackground Disruptive behaviour is the most commonly reported mental health problem in individuals with learning disability. Pharmacotherapy is part of a multidisciplinary approach to the treatment of disruptive behaviour. Risperidone, an atypical antipsychotic drug, is the most commonly used treatment for symptom improvement. It is therefore important to establish the efficacy and safety of risperidone therapy in this dependent, vulnerable and young population, given the well documented adverse effects and the potential for long term treatment. Objectives To assess the effects of risperidone for disruptive behaviour in children and adolescents with learning disability. Search strategy The following electronic databases were searched: CENTRAL (Cochrane Central Register of Controlled Trials); MEDLINE; PsycINFO; CINAHL; Clinicaltrials.gov; National Research Register (NRR). In addition, reference lists of relevant publications and narrative reviews were checked; handsearches were done; authors of published trials and pharmaceutical manufacturer of risperidone (Risperdal) were contacted. Selection criteria All randomised or quasi-randomised controlled trials of risperidone versus placebo (or no treatment) for children and adolescents (age less than 18 years) with a diagnosis of learning disability and disruptive behaviour were considered. Data collection and analysis Trial eligibility and data quality were evaluated and analysed by the author and independently verified by an additional reviewer. Unpublished data were considered for inclusion and relevant authors were contacted in the case of incomplete data. Results Four randomised controlled trials involving 279 children and adolescents were identified. The majority of the children were living at home and not institutionalised. Meta-analyses of the primary outcome scales (Nisonger Child Behaviour Rating Form, Aberrant Behaviour Checklist, Behaviour Problem Inventory) measuring several core symptoms of disruptive behaviour, namely conduct problems, self-injury, irritability, aggressive / destructive behaviours and stereotypy suggest statistically significant improvement in disruptive type behaviours in children treated with risperidone compared to placebo. Adverse event data showed that the prevalence of adverse effects viz. weight gain, sedation / somnolence and raised prolactin levels were significantly higher in the children receiving risperidone. Conclusions In the studies included in this review, risperidone treatment for disruptive behaviour in learning disabled children and adolescents appears to have a beneficial effect on certain symptoms of disruptive behaviour. However, the applicability of these findings to wider clinical practice remains unclear, due to poor methodological quality, inadequate study sample size and short duration of treatment of the included studies. Long term safety has not been established and serious adverse effects, affecting growth, are of concern. Further research is required to establish the efficacy and safety of risperidone for disruptive behaviour in learning disabled children and adolescents in clinical practice

Malignant peripheral nerve sheath tumours and neurofibromatosis 1: A case series and recommendations for care

Background: The incidence of malignant peripheral nerve sheath tumours (MPNST) in patients with neurofibromatosis 1 (NF1) is significantly higher than that of the general population. NF1-associated MPNST occur at a younger age and carry a worse prognosis than sporadic MPNST. Aim: This case series describes four cases of MPNST in patients with NF1. Setting: The study was performed in a public academic hospital in the Western Cape province of South Africa. Method: Demographics, disease status, histopathology, treatment and outcome data were collected retrospectively from medical charts and through review of histological slides. Results: The median age was 36.5 years. All tumours were > 5 cm at presentation and located on the trunk. One patient presented with metastatic disease. There was a mean delay of 3.5 months from presentation to initiation of treatment. Three patients underwent wide excision, with one receiving adjuvant chemotherapy and radiotherapy. At a median follow-up of 20 months from histological diagnosis only one patient was alive in clinical remission. Two patients had succumbed to progressive disease at 8 and 16 months from diagnosis and one patient with terminal metastatic disease was lost to follow-up. Conclusion: In this series the patients presented with advanced, often unresectable lesions for which single modality therapy was not curative. An adult NF1 health surveillance guideline for resource-constrained environments could lead to early diagnosis and treatment of MPNST and other complications in NF1 patients

The continuum of fetal alcohol spectrum disorders in a community in South Africa: Prevalence and characteristics in a fifth sample

The prevalence and characteristics of the continuum of diagnoses within fetal alcohol spectrum disorders (FASD) were researched in a fifth sample in a South African community

A South African mixed race lip/philtrum guide for diagnosis of fetal alcohol spectrum disorders

The adverse effects of maternal alcohol use during pregnancy represent a spectrum of growth restriction, facial dysmorphology, and neurocognitive challenges in the offspring. The continuum of diagnoses is referred to as fetal alcohol spectrum disorders (FASD). Short palpebral fissures, a smooth philtrum, and a thin vermilion border of the upper lip comprise the three cardinal facial features of FASD. Early attempts to define a smooth philtrum and thin vermilion border of the upper lip were subjective. Astley and colleagues introduced a 5-point Likert-scaled lip/philtrum guide based on Caucasian North American subjects as an objective tool for the evaluation of the facial dysmorphology in FASD. This Caucasian guide has been incorporated into all current diagnostic schemes for FASD. However, broad international clinical experience with FASD indicates racial and ethnic differences with respect to the facial morphology. Because of the substantial number of children with FASD in South Africa among the Cape Coloured (mixed race) population in the Western Cape Province, we developed a specific lip/philtrum guide for that population. The guide incorporates a 45-degree view of the philtrum that enables an enhanced 3-dimensional evaluation of philtral height not possible with a frontal view alone. The guide has proven to be a more specific and sensitive tool for evaluation of the facial dysmorphology of FASD in the Cape Coloured population than the use of the previous North American Caucasian guide and points to the utility of racial and ethnic-specific dysmorphology tools in the evaluation of children with suspected FASD

Prenatal diagnosis and outcomes of congenital Lower Urinary Tract Obstruction (LUTO) at Tygerberg Hospital Fetal Medicine Unit: an audit of 12 years

Thesis (MMed)--Stellenbosch University, 2015.ENGLISH ABSTRACT: Objective: To determine the frequency, etiology, survival and associated morbidity of prenatally detected Lower Urinary Tract Obstruction (LUTO) to predict outcome and guide prenatal counselling and management. Methods: Retrospective record review of prenatal LUTO cases at the Tygerberg Hospital Fetal Medicine Unit between January 2003 and June 2014. Results: A total of 75 prenatal LUTO cases were detected in 12 years, giving an approximate frequency of 1.2 per 10,000 births calculated over a 3 year period. The median gestation at diagnosis was 22.4 weeks. Prenatally 39 (52%) were classified as ‘Isolated’, 16 (21%) as ‘Isolated with marker’ and 20 (27%) as ‘Complex’. Gender difference observed with predominance of males (60/68) (88%), male:female ratio 7.5:1. Males had predominantly ‘Isolated LUTO’ (n=36, 60%), and females ‘Complex LUTO’ (n=5, 63%). Survival outcomes included: TOP 26 (35%), IUD 1 (1%), Stillbirths 8 (11%), NND 12 (16%), Infant deaths 4 (5%), alive >1 year 16 (21%), Lost to follow-up/Unknown 8 (11%). The most common etiology was PUV (51%). Chromosomal aneuploidy was found in 9.3% (7/75), all in males, with Trisomy 21 the most common anomaly (4/7) (57%). Prenatal findings shown to be significantly associated with a ‘Poor outcome’ are bilateral renal cortex echogenic/cystic changes (p=0.029), anhydramnios (p=0.011) and pulmonary hypoplasia (p=0.003). Morbidity measures showed survivors beyond 1 year of age (n=16) had renal impairment (n=6, 37%), bladder dysfunction (n=4, 25%), recurrent UTI’’s (n=9, 56%). Conclusion: This study adds novel data on the burden and impact of congenital LUTO in a South African, developing country setting. It confirms high mortality and significant morbidity, and supports the predictive value of specific antenatal ultrasound findings. Recommendations for clinical practice include; systematic ultrasound examination for other major anomalies, including soft markers to better define the risk of underlying chromosomal anomalies, determination of gender and karyotyping. The overall poor prognosis makes extensive counselling of the parents essential, especially if detected late in pregnancy, and supports the development of standardised guidelines for congenital anomalies.AFRIKAANSE OPSOMMING: Doel: Om die frekwensie, etiologie, oorlewing en geassosieerde morbiditeit van voorgeboorte Laer Urinêre Obstruksie (LUO) te bepaal ten einde die finale uitkoms te voorspel en inligting vir voorgeboorte berading en hantering te bepaal. Metode: Retrospektiewe rekord oorsig van voorgeboorte LUO gevalle by Tygerberg Hospitaal Fetale Medisyne Afdeling tussen Januarie 2003 en Junie 2014. Resultate: Vyf en sewentig prenatale LUO gevalle is gediagnoseer in ‘n 12 jaar tydperk, met ‘n berekende frekwensie van 1.2 per 10,000 oor ‘n 3 jaar periode. Die mediane gestasie van diagnose was 22.4 weke. In die voorgeboorte tydperk is 39 (52%) gevalle as ‘Geisoleerd’ geklassifiseerd, 16 (21%) as ‘Geisoleerd met merker’ en 20 (27%) as ‘Kompleks’. Manlike geslag was die algemeenste waargeneem (60/68) (88%), met ‘n manlik:vroulik verhouding van 7.5:1. Manlike geslag het veral ‘Geisoleerde’ LUO’ gehad (n=36, 60%), en vroulike geslag ‘Kompleks’ (n=5, 63%). Uitkomste rakende oorlewing sluit in: Terminasies 26 (35%), Intrauteriene sterftes 1 (1%), Stilgeboortes 8 (11%), Neonatale sterftes 12 (16%), Baba sterftes 4 (5%), Oorleef>1 jaar 16 (21%), Onbekend 8 (11%). Die algemeenste etiologie was Pelviese Urethra Kleppe (51%). Chromosomale aneuploidie was gevind in 9.3% (7/75), almal manlik, met Trisomie 21 die mees algemeen (4/7) (57%). Voorgeboorte bevindings wat statisties geasosieerd was met ‘n ‘Swak uitkoms’ is bilaterale renale korteks egogene of sistiese veranderinge (p=0.029), anhidramnios (p=0.011), en pulmonale hipoplasie (p=0.003). Morbiditeit in oorlewendes> 1 jaar (n=16) sluit in; abnormale nier funksie n=6 (37%), enurese n=4 (25%), herhaalde blaasinfeksies n=9 (56%). Gevolgtrekking: Die studie dra nuwe kennis by tot die bestaande literatuur aangaande die las en impak van kongenitale LUO in Suid Afrika, ‘n ontwikkelende land. Dit bevestig die hoë mortaliteit en morbiditeit, en steun die voorspellende waarde van spesifieke prenatale ultraklank bevindinge. Praktiese aanbevelings vir kliniese praktyk behels die volgende; sistematiese ultraklank ondersoek om ander major kongenitale afwykings uit te skakel, insluitende sagte merkers om die risiko vir ‘n onderliggende chromosomale afwyking te bepaal, asook geslag bepaling en kariotipering. Aangesien die prognose van LUO swak is, is berading van die ouers belangrik, veral as die diagnose laat in swangerskap gemaak word, en daarom moet daar gestandardiseerde riglyne rakende hantering van kongenitale afwykings ontwikkel word.Master

Malignant peripheral nerve sheath tumours and neurofibromatosis 1 : a case series and recommendations for care

CITATION: Burger, H. et al. 2018. Malignant peripheral nerve sheath tumours and neurofibromatosis 1 : a case series and recommendations for care. South African Journal of Oncology, 2:a46, doi:10.4102/sajo.v2i0.46.The original publication is available at https://sajo.org.zaBackground: The incidence of malignant peripheral nerve sheath tumours (MPNST) in patients with neurofibromatosis 1 (NF1) is significantly higher than that of the general population. NF1-associated MPNST occur at a younger age and carry a worse prognosis than sporadic MPNST. Aim: This case series describes four cases of MPNST in patients with NF1. Setting: The study was performed in a public academic hospital in the Western Cape province of South Africa. Method: Demographics, disease status, histopathology, treatment and outcome data were collected retrospectively from medical charts and through review of histological slides. Results: The median age was 36.5 years. All tumours were > 5 cm at presentation and located on the trunk. One patient presented with metastatic disease. There was a mean delay of 3.5 months from presentation to initiation of treatment. Three patients underwent wide excision, with one receiving adjuvant chemotherapy and radiotherapy. At a median follow-up of 20 months from histological diagnosis only one patient was alive in clinical remission. Two patients had succumbed to progressive disease at 8 and 16 months from diagnosis and one patient with terminal metastatic disease was lost to follow-up. Conclusion: In this series the patients presented with advanced, often unresectable lesions for which single modality therapy was not curative. An adult NF1 health surveillance guideline for resource-constrained environments could lead to early diagnosis and treatment of MPNST and other complications in NF1 patients.https://sajo.org.za/index.php/sajo/article/view/46Publisher's versio

Replication of high fetal alcohol spectrum disorders prevalence rates, child characteristics, and maternal risk factors in a second sample of rural communities in South Africa

CITATION: May, Philip A., et al. 2017. Replication of high fetal alcohol spectrum disorders prevalence rates, child characteristics, and maternal risk factors in a second sample of rural communities in South Africa. International Journal of Environmental Research and Public Health, 14(5):522, doi:10.3390/ijerph14050522.The original publication is available at http://www.mdpi.comBackground: Prevalence and characteristics of fetal alcohol syndrome (FAS) and total fetal alcohol spectrum disorders (FASD) were studied in a second sample of three South African rural communities to assess change. Methods: Active case ascertainment focused on children with height, weight and/or head circumference ≤25th centile and randomly-selected children. Final diagnoses were based on dysmorphology, neurobehavioral scores, and maternal risk interviews. Results: Cardinal facial features, head circumference, and total dysmorphology scores differentiated specific FASD diagnostic categories in a somewhat linear fashion but all FASD traits were significantly worse than those of randomly-selected controls. Neurodevelopmental delays were significantly worse for children with FASD than controls. Binge alcohol use was clearly documented as the proximal maternal risk factor for FASD, and significant distal risk factors were: low body mass, education, and income; high gravidity, parity, and age at birth of the index child. FAS rates continue to extremely high in these communities at 89–129 per 1000 children. Total FASD affect 196–276 per 1000 or 20–28% of the children in these communities. Conclusions: Very high rates of FASD persist in these general populations where regular, heavy drinking, often in a binge fashion, co-occurs with low socioeconomic conditions.http://www.mdpi.com/1660-4601/14/5/522Publisher's versio

The continuum of fetal alcohol spectrum disorders in a community in South Africa: Prevalence and characteristics in a fifth sample

BACKGROUND: The prevalence and characteristics of the continuum of diagnoses within fetal alcohol spectrum disorders (FASD) were researched in a fifth sample in a South African community. METHODS: An active case ascertainment approach was employed among all first grade learners in this community (n=862). Following individual examination by clinical geneticists/ dysmorphologists, cognitive/behavioral testing, and maternal interviews, final diagnoses were made in multidisciplinary case conferences. RESULTS: Physical measurements, cardinal facial features of FAS, and total dysmorphology scores clearly differentiated diagnostic categories in a consistent, linear fashion, from severe to mild. Neurodevelopmental delays and behavioral problems were significantly worse for each of the FASD diagnostic categories, although not as consistently linear across diagnostic groups. Alcohol use was documented by direct report from the mother in 71% to 100% of cases in specific diagnostic groups. Significant distal maternal risk factors in this population are: advanced maternal age at pregnancy; low height, weight, and body mass index (BMI); small head circumference; low education; low income; and rural residence. Even when controlling for socioeconomic status, prenatal drinking correlates significantly with total dysmorphology score, head circumference, and five cognitive and behavioral measures. In this community, FAS occurs in 59 – 79 per 1,000 children, and total FASD in 170 – 233 per 1,000 children, or 17% to 23%. CONCLUSIONS: Very high rates of FASD continue in this community where entrenched practices of regular binge drinking co-exist with challenging conditions for childbearing and child development in a significant portion of the population