Therapeutic Strategies for Restoring Linear Growth in Children with Crohn’s Disease.

MD(Res)Linear growth retardation affects up to 40% of children with Crohn’s disease (CD). It is caused by a combination of under\nutrition, and by a direct effect of cytokines on the axis linking human growth hormone (GH), insulin like growth factor\1 (IGF\1) and the growth plate of growing bones. In particular,the inflammation causes a functional insensitivity to GH, resulting in low circulating IGF\1. Current management is synonymous with the optimal management of childhood CD:to eliminate inflammation,and maintain remission. However, there is currently no consensus as to how to treat growth failure in patients whose inflammation remains intractable to treatment. This thesis examined the hypothesis that successful treatment of inflammation would improve linear growth in children with CD. We performed a series of retrospective studies examining a cohort of children aged ≤17 years with CD treated at Bart’s and The London Children Hospital. We determined the height standard deviation scores (SDS) of patients at diagnosis and investigated growth outcomes following treatments used to induce and maintain remission. These were:exclusive enteral nutrition (EEN), thiopurines and infliximab. Finally, as a potential new therapy, we considered the use of exogenously administered recombinant human IGF\1 (rhIGF\1) to restore plasma IGF\1 levels. We performed an open\labelled pharmacokinetic (PK) study of rhIGF\1 in 8 children with CD and growth failure. 9% of our patients had height SDS of \2 SDS at diagnosis; a four\fold increase compared to the normal age matched population. In addition, symptom duration negatively correlated with height SDS at diagnosis (r=\0.06; p=0.02). From 89 5 patients receiving EEN for primary induction of remission, 62.9% (56/89) of patients achieved complete remission. Over the course of 5 years, responders to EEN grew significantly better than non\responders (change in height SDS +0.18 [0.12] vs to \ 0.37 [0.13] respectively; p=0.005). This occurred despite no differences in duration of remission or treatment escalation between groups. 51% (26/51) patients treated with thiopurines were in remission at 12 months. These patients had improved growth (median change height SDS [IQR] 0.08 [\0.06 – 0.19] vs \0.24 [\0.61 \ \0.07] in non\responders; p=0.001). 39.2% (20/51) of these patients started anti\TNF therapy. However, over 12 months, we found that this conferred no improvement in growth (median [IQR] at 0 months\0.38 [\1.73 to \0.10] as compared to \0.61 [\ 1.72 to \0.09] at 12 months; p=0.43), irrespective of response to treatment. Subcutaneous treatment with 120 μg/kg twice daily rhIGF\1 restored plasma levels of IGF\1 in our patients, albeit it in some to high levels (median [range] concentration +2.09 [\1.27 to +5.21]). We were able to develop a PK mathematical model from these results to determine a more appropriate dosage. We found that in addition to patient’s age and weight, PCDAI also needs to be taken into consideration when determining dose. In summary, growth retardation is very common finding in paediatric CD. Response to EEN and thiopurines seems to result in beneficial effects upon growth. However, a number of children continued to have poor growth despite treatment. Our results show it is possible to increase circulating IGF\1 concentrations with exogenous injections, and develop a mathematical model to devise a dose to use in further trials

Analytical Approaches to Music of South Asia, Volume 1 (2023)

Contents: 1. Editors’ Introduction to the AAMSA journal 2. A Novel Generative Paradigm for Carnatic Rhythmic Composition Jagdish A. Krishnaswamy and Robert Wells 3. The Musical Journeys of a Goddess Paolo Pacciolla 4. Suḷādi Songs of Haridāsa Composers Arati Ra

The Virtual Sociality of Rights: The Case of Women\u27s Rights are Human Rights

This essay traces the relationship between activists and academics involved in the campaign for women\u27s rights as human rights as a case study of the relationship between different classes of what I call knowledge professionals self-consciously acting in a transnational domain. The puzzle that animates this essay is the following: how was it that at the very moment at which a critique of rights and a reimagination of rights as rights talk proved to be such fertile ground for academic scholarship did the same rights prove to be an equally fertile ground for activist networking and lobbying activities? The paper answers this question with respect to the work of self-reflexivity in creating a virtual sociality of rights

Right in the Home: Feminist Theoretical Perspective on International Human Rights

The author explores some of the conceptual limitations of international human rights in adequately protecting women\u27s rights, particularly, in adequately protecting women from physical and sexual violence within the family. Relying on the insights of feminist theory, Rao argues that the public\private distinction on which liberal human rights discourse is premised operates to obscure and negate the sphere in which women are physically and sexually abused as a valid sphere of inquiry and protection. Rao argues that international human rights must be informed by a more complex understanding of the dispersion and operation of power, which breaks down the artificial distinction between public and private realms. (Editor’s abstract.

Droits de «l’homme» et vie «privée» : Perspectives théoriques féministes sur les conventions internationales traitant des droits de l’homme

Rao Arati, Bonis Oristelle. Droits de «l’homme» et vie «privée» : Perspectives théoriques féministes sur les conventions internationales traitant des droits de l’homme. In: Projets féministes, n°3, Octobre 1994. Droit, culture, pouvoirs. pp. 17-39

Geriatric assessment and comorbidity

Elderly persons, a rapidly growing population segment, have an increased incidence of cancer. The older cancer patient’s clinical evaluation and treatment is influenced by conditions such as disabilities, comorbidity, and functional status, along with tumor type and stage. These conditions and other geriatric syndromes can be identified by comprehensive geriatric assessment to guide therapy and affect prognosis and quality of life. Comprehensive geriatric assessment involves the medical, functional, affective, social, spiritual, and environmental assessments. The medical assessment, which includes a nutrition, vision, hearing, continence, gait and balance, and cognition evaluation, can provide additional information to performance status and comorbidity. Although there are many assessment domains using several instruments, comprehensive geriatric assessment can be focused and efficient, especially with a multidisciplinary team of nurses, social workers, pharmacists, and other personnel. Comorbid illnesses may have complex interactions, with the underlying cancer influencing cancer diagnosis, disease course, treatment-related side effects, and mortality. Many instruments are available for comorbidity measurement, and retrospective studies in elderly cancer cohorts have shown comorbidity to influence survival. However, the ultimate aim would be to use comorbidity and comprehensive geriatric assessments prospectively in the older cancer patient to help predict the suitability and success of treatment with various antineoplastic modalities

The need for an aging and cancer curriculum for hematology/oncology trainees

There has long been recognition for the need of education and training in aging and cancer. As the proportion of older individuals in the United States increases, with 20% being over 65 by 2030, it will become increasingly important for hematology–oncology trainees to have directed curriculum in geriatric-oncology. In order to better define the best way to meet the need for educational material specific to the special population of older patients for Oncology Training Programs, a survey was developed and administered to Hematology–Oncology Program Directors, in order to perform an educational needs assessment. The survey was administered during the 2008 Annual Meeting to 54 attendees at the Program Director's Breakfast. The survey asked questions regarding general program characteristics, as well as the importance of geriatric-oncology curriculum, a description of such current curriculum, the most important topics to cover in the curriculum, and recommendations for the format of the curriculum. The survey showed that 32% of training programs had a formal curriculum that covered topics in geriatric-oncology, 56% had an informal curriculum, and 2% had no curriculum. Most used a multimodality approach including clinical experience, journal clubs and lectures. Most hematology–oncology fellowship directors believe curriculum in geriatric-oncology is important; have faculty with either training or interest in geriatric-oncology that could facilitate curriculum delivery; and would use a curriculum if it were readily available. Investment in developing content and curriculum in geriatric-oncology would be very valuable and well-received