The Effect of Surgical Gastronomy for People Diagnosed with RTT - Research Proposal Example

Name: Unit: Health and social care Title: Health Research Proposal on the effect of surgical gastronomy for people diagnosed with RTT Literature review Rett syndrome (RTT) is a severe neurodevelopment disorder mostly in females and leads to a rigourous intellectual disability. The main cause of the disorder is mutations in MECP2, but there are also some cases in CDKL5 mutations. Mutations in MECP2 lead to disadvantages in growth in lymphoblast as well as neuronal cells. This results to inactivation of X which can easily result to a variation of phenotypic in large scale.1 Originally, before extensive research was done, MECP2 was mostly seen as a transcriptional repressor. However, with more research, MECP2 have a role in specific genes which is regulation of neuronal activity dependent expression, for instance Bdnf in mouse.2 According to Christodoulou3 the estimated RTT cumulative incidence in Australia in females is about 1 in every 10 females by the age of 12. This has been regarded as among the common causes of severe mental retardation. Characteristics of RTT include progressive loss of communicative abilities, as well as deceleration of head growth among others after a normal developmental period.4 Christodoulou5 also notes that in girls, RTT usually lead development of seizures, a disturbed pattern of breathing with periodic apnoea and hyperventilation, retardation of growth, as well as gait apraxia. Patients with RTT also exhibit significant autonomic involvement which leads to gastrointestinal abnormalities as well as peripheral vasomotor instability. Common infections that are associated with RTT include dysphgia, gastroesophageal reflux disease (GERD), feeding impairment which later result to constipation and failure to thrive.6 According to Naidu et al7, patients who experience mutations that are related to MECP2 amino-terminus have the greatest number of gastrointestinal problems. These patients usually require early gastronomy as a result of severe malnutrition. With characteristics of special developmental profile, the diagnosis of RTT is based on use of established criteria and constellation of consistent clinical features. The diagnostic criteria include normal prenatal as well as perinatal period where in the first 5-6 months, there is normal developmental progress. However, between 3months and 3 years, acquired skills are reduced for instance, communication skills and purposeful functioning of the hands among others.8 Hagberg et al9 state that RTT characteristic is intense and sometimes stereotypic movement of hands that develop due to loss of movements of purposeful hand. The pattern consists of tortuous hand wringing, patting, as well as other bizarre automatisms of hands during waking hours. Another prominent feature is gait ataxia where supportive criteria of diagnosis include EEG abnormalities, problem in breathing, growth retardation, peripheral vasomotor and spasticity. RTT clinical diagnosis should not be included in case of presence of signs of cataract, storage disorder, or optic atrophy, an identifiable neurodegenerative or metabolic disorder, evidence of postnatal brain injury or acquired neurological disorder.10 Although this disorder was initially known to be exclusively for females, cases of Rett-like phenotype have been reported occasionally in males including those with 47XXY karyotype. Males with mosaic for severe mutations, milder mutations as well as other non-RTT phenotypes have been attributed to MECP2 mutations.11 RTT growth trajectory in children with chronic illnesses or other chromosomal disorders moves away from the pattern of the failure of growth. Early head growth deceleration followed by deceleration in the gain in height and weight may be a good indication of early RTT diagnosis. Growth abnormalities are associated with multiple factors. Difficulties in feeding lead to inadequate dietary intake and are associated with gastroesophageal dysmotility and oral motor dysfunction. The patterns of how the weight of the subjects has reduced in relation to height as well as the reduction in height in relation to age are consistent with chronic and acute under-nutrition.12 The purpose of this research is to study the effect of surgical gastronomy on growth in RTT. Research questions: What is the effect of surgical gastronomy on progressive decline in weight, height and BMI? Does surgical gastronomy improve the weight, height as well as body mass index at an earlier age? Does surgical gastronomy result in reversal of under nutrition for patients with RTT? We hypothesise that surgical gastronomy will reverse the progressive reduction in weight, height as well as BMI; lead to better improvement in weight, height and body mass index at an earlier age; and it contributes the reversal of under nutrition for patients with RTT. Study design This will be observational by looking back at the medical records of the subjects. The information that will be acquired includes, birth and growth measurements as well as anthropometric measurements before and after surgical gastronomy and use of medications after surgery. This will be very important as it will address the questions of what was done to which subject, why it was done and how well were the outcomes of the surgical gastronomy in regard to each subject. In addition, it will address whether the objectives are fulfilled based on the following aspects; effectiveness, efficiency and acceptability. That is, the benefits of surgical gastronomy to the patient in regard to improvements in health (growth), the outputs or the benefits obtained, as well as the ethical, psychological and social acceptability in regard to the treatment of patients in relation to healthcare (intervention). Conduction of extensive literature review in regard to development in subjects with RTT will corroborate the need for this research. Preliminary activities were important in assisting in identification of issues related with growth in subjects with RTT, and also incorporated the researcher’s knowledge about standards of development into the study design. The study design will also assist in collecting data that is sufficient in addressing all research questions. Methodology Girls as well as young women that will meet the criteria of clinical diagnosis of RTT and had surgical gastronomy will be included. All the subjects will be females because males with MEPC2 mutations rarely meet the criteria of diagnosis of RTT and have different phenotype. In addition, the syndrome consensus criteria will be based on: normal perinatal history; postnatal head growth deceleration; psychomotor development where it will be largely normal in the first six months; loss of achieved purposeful skills of the hands between six months and two and half years; cognitive impairment, communication dysfunction; and failing or impaired locomotion. Complete sets of data sets will be on hand for a variable number of subjects. This is due to accessibility to the medical records of each patient. Standard stadiometric as well as anthropometric measures will be obtained in order to derive the weight, height as well as BMI scores in subjects with RTT before surgical gastronomy and after surgical gastronomy. MECP2 mutations will be recorded. However, parents will be required to give their daughters permission in order to participate in the study. In addition, due to cognitive impairment of the subjects, assent will be waived for them. The heights and weights of individuals will be obtained through direct measurement during physical examination as well as indirectly based on the medical records, that is, if surgical gastronomy occurred before evaluation. Wall-mounted stadiometer consisting of a movable headpiece will be used to measure standing heights. For the subjects that will not be able to stand, measurements will be done horizontally using a measuring board with a movable perpendicular foot piece. Measurements of heights or lengths will exclude orthotics, shoes. Measurement of weight will be done using electronic balance where the recordings will be to the nearest 0.1kg. Orthotics, heavy clothes and shoes will be removed before weighing. BMI will be calculated in regard to the ratio of weight over the squared height for the subjects (BMI, kg/m2). Where there will be characteristics of sequence and deletion analysis in MEPC2 mutations the recording will be based on records provided by the parents of the subjects. The weights and length during birth and medication indications after surgical gastronomy will be recorded using medical record or parent recall. Parents of each subject will be provided with standard questionnaire to provide information associated with RTT. There will be a performance of a matched analysis by use of multiple logistic regressions in order to control potential cofounders. Statistical analysis Statistical analysis will be crucial and t-test will be applied for detecting the differences in weight, height as well as the body mass index between RTT before and after surgical gastronomy and reference population. Weight, height, and body mass index slopes will be calculated from the difference between these measures before surgical gastronomy (that is, from birth to pre-gastronomy) and after surgical gastronomy (that is post-gastronomy). In addition, paired t-tests will be used in detection of differences in weight, heights as well as BMI score slope before and after surgical gastronomy. Furthermore, linear regression will be applied in detecting the differences between the weight, height as well as BMI score slope before surgical gastronomy and after surgical gastronomy. This will be as a function of the age at which surgical gastronomy was done. Analysis of variance will be applied for the detection of the differences in weight, height as well as BMI score slopes before and after surgical gastronomy among gene mutation classes. Chi squire (X2) analysis will be very essential in detecting differences in medication between the subjects with fundoplication or without it13. There will be a need for a systematic design in order to guide the research. The design will focus on multiple data and appropriate analysis of data. Throughout the research, data collection and analysis will be documented with clear indication on the source of data, its management, preparation and analysis. This will provide accountability on how the research will be carried out. In regard to the outcome, the important variables will be the differences between the heights (that is, height after surgical gastronomy less height before surgical gastronomy), weight (weight after less weight before surgical gastronomy), and BMI score slopes (after and before surgical gastronomy). Positive values will mean that surgical gastronomy will reverse decline in regard to weight, height and BMI scores. This will also imply that the progression of under nutrition will be halted due to surgical gastronomy. In general, positive values or results will be an indication of altering the growth failure and under nutrition of the subject with RTT in a favourable way. Data collection tool will be administered using online survey tool and majority of questions will consist of closed-ended questions for instance, multiple-choice questions. For qualitative data collection, open-ended questions will also be used. The objective of the survey will be to elucidate how surgical gastronomy has affected the growth of the participants with RTT. Therefore, questions focused on parents about the how the subject has progressed before gastronomy surgery and after the surgery in regard to weight, height, eating habits among others will be important. Feedback will be collected from the parents who completed the questionnaires14. Sample questionnaire: In what year was your child with Rett syndrome born? In what year was your child diagnosed with Rett syndrome? Please describe the growth of your child with Rett syndrome before gastronomy surgery in regard to: Height: Weight: Size: Eating habits: General development: Would you have considered surgical gastronomy for your child at the time of your child’s diagnosis? o Yes o No o I am unsure Please describe how surgical gastronomy for Rett syndrome affected the growth of your child in regard to: Height: Weight: Size: Eating habits: General development: How important was surgical gastronomy for your child with Rett syndrome? Very important Important Not important Ethical issues In this research respect for parents and the subjects will include respect for autonomous decision making. The most important elements of informed consent in this case will be voluntariness, adequate information and the capacity to understand information. Based on cognitive impairment, the responsibility of consent for the children to participate in this research will be vested in their parents or guardians. These parents and guardians will be assumed to be presenting the best interests of the subjects in their mind. However, in some situations, some of these children may be able to consent during the research. The adequacy of consent may be influenced by various factors such as too complex information or pressures on families or parents which may restrain voluntariness and also, the capacity, in part that is related to nuerocognitive development15. The severity and complexity of the potential outcomes of this research should be though about, in particular, the assessment of the capacity of the child to understand the consequences related to her participation in the study16. Thus, parents will be required to give their daughters permission in order to participate in this study. Assent will be put aside for the subjects in regard to their cognitive impairment References Christodoulou, J. (2004). Western Sydney Genetics Program, Westmead Children’s Hospital Motil, K.J., Morrissey, M., Caeg, E., Barrish, J.O, & Glaze, D.G. (2009). Gastrostomy Placement Improves Height and Weight Gain in Girls with Rett Syndrome, Journal of Paediatric Gastroenterology and Nutrition, 49, 237–242 Weaving, L.S, Ellaway, C.J., Gecz, J., & Christodoulou, J. (2005). Rett syndrome: clinical review and genetic update, Journal of Medical Genetics, 42, 1–7. Hagberg, B., Hanefeld, F., Percy, A., Skjeldal, O. (2002). An update on clinically applicable diagnostic criteria in Rett syndrome. Europian Journal of Paediatrics Neurology, 6, 293–7. Leonard, H., Weaving, L., Eastaugh, P., Smith, L., Delatycki, M., Engerstrom, I. & Christodoulou J. (2004). Trisomy 21 and Rett syndrome: a double burden. Journal of Paediatrics Child Health, 40, 406–9. Topcu, M., Akyerli, C., Sayi, A., Toruner, G.A., Kocoglu, S.R., Cimbis, M., Ozcelik, T. (2002). Somatic mosaicism for a MECP2 mutation associated with classic Rett syndrome in a boy. European Journal Human Genetics, 10, 77–81. Naidu, S., Bibat, G., Kratz, L., et al (2003). Clinical variability in Rett Syndrome. Journal of Child Neurology, 18, 662-668 Guy J, Gan J, Selfridge J, et al (2007). Reversal of neurological defects in a mouse model of Rett syndrome. Science, 23(315), 1143-7 Barfield, R.C., & Church, C. (2005). Informed consent in paediatric clinical trials. Current Opinion of Paediatrics, 17, 20-4. Miller, V.A, Drotar, D., & Kodish, E. (2004). Children’s competence for assent and consent: A review of empirical findings. Ethics Behaviour, 14, 255-95. Mount, R.H., Charman, T., Hastings, R.P., Reilly, S., & Cass, H. (2002). The Rett Syndrome Behaviour Questionnaire (RSBQ): refining the behavioural phenotype of Rett syndrome. Journal of Child Psychology and Psychiatry, 43(8), 1099–1110. U.S. Department of Health and Human Services. National Center for Health Statistics. National Health and Nutrition Examination Survey. Retrieved from: http://www.cdc.gov/growthcharts Read More