UAB Pre And Post-Doctoral Training Program In Biostatistics
Gary Cutter, Professor And Director
Biostatisticsuniversity Of Alabama At Birmingham
Grant 5T32NS054584-03 from National Institute Of Neurological Disorders And Stroke IRG: NST
Project start date: 2007-07-01
Project end date: 2012-06-30
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Grants awarded to Gary Cutter
Gary Cutter
Institution:
Grant 5P50DE011147-030001 from National Institute Of Dental And Craniofacial Research
Abstract: Project 1 seeks to evaluate the effect of an antimicrobial agent applied to the mother s with the aim of reducing her levels of mutans streptococci M(MS) which, in turn, will decrease the likelihood of vertical transmission of MS to her infant. Our experience from a five year randomized trial (MITS) suggests the optimum time period for the applications of an agent so as to have an impact on the vertical transmission of MS. Previous studies provide sufficient information on the optimal concentration of chlorhexidine, an effective method of its delivery, and its efficacy in reducing oral MS levels. Total elimination or reduction of maternal oral MS over a time period should result in either; 1) a complete prevention of MS transmission or, 2) a lower degree of MS transmission or, 3) a delayed transmission of MS from mother to child. This in turn could result in a lower caries incidence in the child. In order to test the above hypotheses, a randomized active versus no treatment controlled clinical trial is proposed. Assuming the proportion of children with detectable levels of MS at 2 years of age is 16% in the treatment group, a total of 51 children are needed per group. To account for potential losses, a total of 64 infants will be included in each group. The trial will test the following two hypotheses 1) The application of the treatment agent to the mothers dentition at 3 months intervals from six months (generally prior to the time of the child s first tooth emergence) until the second birthday of the child will result in having a larger proportion of children with undetectable levels of oral MS in saliva samples in the treatment group compared to the untreated control group, and 2) The application of the treatment agent to the mothers dentition at 3 months intervals from the time of the child s first tooth emergence until the third birthday of the child will result in a decrease incidence of dental caries in children in the treatment group compared to the untreated control group. The treatment agent we will use is a combination of chlorhexidine and Sumatara benzoin. A layer of this varnish applied to all surfaces of teeth after a dental prophylaxis will be covered by another layer of polyurethane sealant in order to achieve sustained release and to prevent the bitter taste of chlorhexidine. Treatment mothers will be given new tooth brushes after each treatment to prevent a possible source of re- colonization, namely the old tooth brushes. Precautions will be taken to prevent lactating or pregnant mothers from being exposed to these agents. Basic demographic, oral bacteriological, medical, dental, and prenatal and post natal nutritional data will be collected and immunological profiles of mother-child pairs will be evaluated. These data would be analyzed to study the natural history of MS colonization as well as to evaluate the effectiveness of the therapeutic intervention. The proposed study is conducted among a group of subjects who belong to a population sub group who is at high risk for caries or who suffer the consequences of caries most. Despite one hundred years of research, dental caries still impact heavily on the nation and its economy, and if the proposed approach of preventing tooth decay succeeds, it would have major implications.
Keywords: Streptococcus mutans, antibacterial agent, chemoprevention, perinatal, preschool child (1-5), preventive dentistry, vertical transmission, chlorhexidine, dental caries inhibitor, human therapy evaluation, local antiinfective agent, mother child interaction, human subject
Thymectomy In Non-Thymomatous MG Patients On Prednisone
Gary Cutter, Professor And Director
Biostatisticsuniversity Of Alabama At Birmingham
Grant 5U01NS042685-05 from National Institute Of Neurological Disorders And Stroke IRG: NSD
Abstract: Myasthenia gravis (MG) is an autoimmune disease involving the thymus in which 85% of patients have antibodies to muscle acetylcholine receptors (AchR-Ab) that interfere with neuromuscular transmission and can cause severe, sometimes life-threatening, weakness. Thymectomy has been used world-wide to treat non-thymomatous MG, based on retrospective non-randomized studies. Prednisone (a corticosteroid) is also frequently used to treat MG. Both therapies are often employed together and both have adverse effects. Whether thymectomy benefits those who are also receiving prednisone is not known. To investigate the safety while comparing efficacy, we propose a multicenter, multiracial, international, single-blinded, 3-year duration clinical trial in which patients aged 18-60 years with generalized AchR-Ab positive non- thymomatous MG are randomized to receive extended transsternal thymectomy (ETTX) or no thymectomy. Both groups will receive prednisone administered by a ´blind´ evaluator according to the same set protocol aimed at establishing the minimum dose needed to achieve and maintain Minimal Manifestation (MM) status. The primary endpoint will comprise response and toxicity using a composite measuring clinical course, short and long term toxicities based on (a) clinical efficacy of therapy evaluated by the QMG weakness score (b) frequency of serious adverse events (c) the total dose of prednisone (Area under the Dose time Curve, AUDTC). A significant difference favoring ETTX would establish its clinical benefits in this patient population, and provide indirect evidence of the possible benefits of ETTX in patients not receiving prednisone medication. Conversely, failure to demonstrate a significant difference in the global or individual components of the primary endpoint would suggest that thymectomy is an unnecessary procedure in the population studied. Subgroup analysis may show whether benefits are confined to those who are prednisone naive at entry or in a particular age group. Thus the results will impact on current clinical practice
Project start date: 2005-09-23
Project end date: 2010-08-31
3U01NS042685-05S1 (2009): $75000
3U01NS042685-04S1 (2009): $1349862