Late effects of treatment in survivors of childhood acute lymphoblastic leukaemia

Long-term survival and probable cure have become norms in acute lymphoblastic leukaemia of childhood. The adverse effects of treatment for leukaemia are diverse and complex. In many cases, treatment effects come to light 1 ong after the end of therapy. These so-ca 11 ed 1 ate effects (which are yet obscure and incompletely understood) have become increasingly important as the number of children surviving leukaemia increases. This thesis describes a comprehensive study of leukaemia survivors attending the Oncology Clinic of the Red Cross War Memorial Children's Hospital. The study sample consisted of all leukaemia survivors in long-term remission, disease free and off treatment up to January 1st, 1984. The study is introduced by a chapter which describes acute lymphoblastic leukaemia and pays particular attention to the effects of the primary disease on organs which may subsequently exhibit late effects of treatment. Treatment of acute lymphoblastic leukaemia is described in some detail and the reasons for current treatment strategies are outlined. Individual modalities of treatment are then discussed with reference to their mechanisms of action and potential for damage to non-neoplastic tissue. The study then examines all systems likely to have been damaged during therapy, in order to achieve a comprehensive impression of the late effects of leukaemia treatment. In each chapter, pertinent literature was reviewed up to January 1987. Growth is a major task of childhood. Many chronic diseases are potential causes of growth failure. A longitudinal retrospective study showed that statured growth in leukaemia survivors was stunted during treatment. Catch-up growth did not occur at the end of treatment, although normal growth velocity was resumed. Adult height was expected to be reduced as a result. In addition to temporary stunting of statured growth, leukaemia survivors showed a progressive increase in weight-for-height during treatment. This trend continued after treatment had ended. These changes in weight and height were peculiar to leukaemia survivors. Control groups of children with solid tumours in long term remission showed less stunting during treatment and had catch-up growth after treatment, except when they had undergone spinal i rradi ati on. Normal endocrine function is a prerequisite for normal growth and development. Although growth hormone responses to insulin-induced hypoglycaemia were frequently and significantly abnormal in survivors of childhood leukaemia, these children grew normally once treatment had stopped. Impaired growth hormone secretion appeared to be a marker of hypothalamic damage caused by leukaemia therapy. Testicular and ovarian function was normal in the absence of irradiation of these organs. Thyroid function was normal in leukaemia survivors although a minority showed evidence of hypothalamic damage in their response to thyrotropin releasing hormone. Normal prolactin levels in children showing other hormonal evidence of hypothalamic damage were thought to indicate the selectivity of damage caused by leukaemia treatment. Adrenal control and function were normal in leukaemia survivors. In the absence of a growth disorder, only thyroid status may need long-term assessment in leukaemia survivors. Intellectual development is a further major task of childhood. A sibling-controlled study of intellectual function indicated an intelligence deficit in children surviving leukaemia and its treatment. This deficit was thought to be the consequence of therapy, since children surviving solid tumours showed no such deficit in comparison with their sibling controls. Survivors of childhood leukaemia also had an increased incidence of visual perceptual difficulty and more school prob 1 ems than survivors of solid tumours, particularly in early primary grades. Intellectual outcome and school performance in leukaemia survivors may be improved by early visual perceptual training. Children surviving acute lymphoblastic leukaemia had significantly more minor motor abnormalities than children surviving solid tumours. Minor motor abnormalities were frequently and significantly associated with abnormalities of the brain visualized by computerized tomography. Neurophysiologic measurement (EEG, VER, BAER) did not contribute to the assessment of neurological outcome and correlated poorly with clinical and CT scan findings. A functional assessment of neurological outcome in leukaemia survivors should include a clinical examination for minor motor dysfunction. Some children manifested other organ-specific damage due to chemotherapy or radiotherapy. These isolated cases are discussed in the form of case reports and literature reviews. Patients have received treatment with cytotoxic drugs in addition to standard leukaemia therapy need to be followed for treatment-specific late effects. The psychological outcome of leukaemia survivors was assessed by means of parent interviews and teacher questionnaires. In terms of a low frequency of behaviour problems reported by these observers, psychosocial adaptation in leukaemia survivors vas surprisingly good. Children surviving solid tumours and healthy school children from the same community (the latter from a literature report) had similar frequencies of behavioural problems. In both leukemic children ana solid tumour control patients, certain patterns of family behaviour ~ere predictive of a poor psychological outcome. It appears that an early family assessment may identify families 'at risk'. If needs to be shewn whether such families would benefit from professional psychological support. In the final chapter a 'functional deficit score' is offered as a measure of overall outcome in terms of late effects of therapy. Patients were rated in five categories (growth, intellectual outcome, neurological status, miscellaneous organ damage and psychosocial adaptation) according to the severity of persistent late effects. Children surviving acute lymphoblastic leukaemia were shown to have been more seriously damaged by their treatment than children surviving solid tumours. The difference in overall damage was the consequence of central nervous system injury. Available evidence indicates that this central nervous system injury is caused by radiotherapy (with or ·thought a synergistic effect with i intrathecal 1 methotrexate) given as central nervous system 'prophylaxis'. With few exceptions, leukaemia survivors in this study had received L400 rads of deep x-ray therapy as cranial irradiation. This dosage has since been reduced world-wide. Current cranial irradiation 'prophylaxis' consists of 1800 rad of megavoltage radiotherapy. Fa 11 ow-up studies of survivor cohorts given such radiotherapy should include the measures embodied in the 'functional deficit score' described above

Informed consent for voluntary counselling and testing for HIV infection in South African mothers and children: An assessment of burdens and consequences and an argument for a modification in the process of informed consent

The HIV / AIDS epidemic is devastating Africa. The continent lacks the material resources to treat infected persons or to support those affected by the epidemic. One great resource in Africa is the cohesive strength of families. Because of a fear of stigma, HIV infected persons tend not to disclose their diagnosis to their families. This non-disclosure perpetuates stigma, because ordinary people do not discover that their own family may be affected by the epidemic. Non-disclosure also results in the loss of specific family support to infected individuals and the loss of general family support as a national resource. The standard method of taking informed consent prior to HIV testing of pregnant mothers has the effect of enhancing non-disclosure, because of its inherent focus on the patient as an isolated, autonomous decision maker. This dissertation advances the thesis that an alteration in the process of informed consent, to involve the family in deliberation prior to consent, will facilitate disclosure of an HIV-positive diagnosis to the family. Disclosure will have the positive effects firstly of giving the mother access to the emotional support of her family and secondly of serving to educate the family, and through the family society as a whole, that ordinary, virtuous women can be infected with HIV

National Autism Indicators Report: Vocational Rehabilitation 2016

Employment is about more than simply earning a paycheck - it influences quality of life, independence, and wellness. Historically, employment outcomes for adults with autism are poor. The U.S. Vocational Rehabilitation system (VR) is designed to provide support to states for implementation of services to assist people with disabilities to prepare for, find, and keep employment. VR data allow us to examine some outcomes for those with autism compared to their peers.To make a difference, research must reach those who need it. The National Autism Indicators Report series presents our research findings in a clearly communicated, open-access, online format to speed the delivery of information to decision-makers while maintaining very high standards of scientific credibility

Paediatric arthritides

No Abstract. South African Family Practice Vol. 47(6) 2005: 14-2

National Autism Indicators Report: Transition into Young Adulthood

There is very little research published concerning how people with autism do in the adult portion of their lifespans. We analyzed data from "The National Longitudinal Transition Study-2" and "The Survey of Pathways to Diagnosis and Services" to examine the service needs and life outcomes of adolescents and young adults on the autism spectrum. This report describes the prevalence of a wide variety of indicators related to transition planning, services access, unmet needs, employment, postsecondary education, living arrangements, social participation, and safety and risk