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(2022)ThesisAcute kidney injury (AKI) occurs commonly in hospitalised children and carries an increased risk of morbidity and mortality. This thesis investigates the relationship between AKI and baseline kidney function, as this has not been well explored. We studied children exposed to acyclovir, and children with cancer, as these groups both have an increased risk of AKI. Children with cancer have been shown to have high baseline kidney function, known as glomerular hyperfiltration (GH), which is poorly understood. GH is a glomerular filtration rate above normal, which we define as a measured glomerular filtration rate (NMGFR) ³160mL/min/1.73m2. In a retrospective review of 150 children treated with acyclovir, 27 (18%) developed AKI. The only factor associated with AKI on multivariable analysis in this cohort was higher baseline estimated GFR (p=0.013). We reviewed the records of 202 children who underwent allogeneic haematopoietic stem cell transplant (HSCT) for haematological malignancy. In the first 100 days post-HSCT, 173 (85.6%) children developed AKI and stage 3 AKI occurred in 58 (28.7%). Factors significantly associated with stage 3 AKI on multivariable analysis were use of ciclosporin (vs. tacrolimus) (p=0.02), total body irradiation (p=0.01), early AKI on or before day 10 post-HSCT (p=0.001), ³10% creatinine increase 24 hours after AKI onset (p=0.001), and higher pre-HSCT NMGFR (p=0.03). At 1-year, patients with stage 3 AKI had greater reduction in estimated GFR than other children (-53.9 vs -18.8mL/min/1.73m2; p=0.0002). Analysis of the above cohort combined with the records of 91 children who underwent NMGFR at time of solid organ cancer diagnosis revealed that 16% had GH. GH was more common in young children (p=0.0055) and those with acute myeloid leukaemia (p=0.02), and was associated with higher weight gain (a surrogate for fluid accumulation) post-HSCT (p=0.02). Most children with GH pre-HSCT returned to a normal GFR. Development of GH at 1-year post-HSCT was associated with prior acute GVHD. This research is among the first to demonstrate that GH is associated with an increased risk of AKI. Our results suggest that GH occurring before HSCT may have a different underlying cause to hyperfiltration occurring post-HSCT and warrants further investigation.
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(2022)ThesisAddressing antimicrobial resistance (AMR) as a purely medical problem fails to recognise the sociological factors that drive the misuse of antimicrobials. Antimicrobial use is shaped by the local social, cultural, political and economic context. There is now widespread recognition that addressing AMR requires an understanding of the social factors that underpin our use and prescription of antimicrobials. Sociological and anthropological explorations of the global antimicrobial crisis have thus far disproportionately focused on economically wealthier nations. This is despite the recognition of economically poorer nations as sites of considerable, escalating, and often unregulated, antimicrobial use. This thesis examines the social dynamics of antimicrobial use in the Indian context through ethnographic observations and 100 qualitative interviews with doctors, community health practitioners, pharmacists, pharmacy employees and community members in Hyderabad, India. Using a constructivist grounded theory approach to data collection and analysis, the focus is on gaining an understanding of how enduring and emerging inequalities, infective risk and uncertainty, labour risks and precarious work, improvisation and self-medication, and informal and formal pharmaceutical economies shape antimicrobial use in India. Using a critical sociological lens, I explore: the dynamics of biopolitics and risk; the pharmaceuticalisation of everyday life and the vested interests therein; the economies of healthcare and antimicrobial use, including commodification and privatisation; and the vulnerability and structural violence associated with the use of antimicrobials. Knowledge of the social dynamics driving antimicrobial use can then in the future be used to inform policies and programs aimed at optimising antimicrobial use in India, appropriately tailoring them to context, rather than continuing with pan-national approaches that do little to accommodate considerations of the Global South.