Early detection of delirium in older medical inpatients: prodrome, predictors and motor subtyping

Background Delirium is highly prevalent, especially in older patients. It independently leads to adverse outcomes, but remains under-detected, particularly hypoactive forms. Although early identification and intervention is important, delirium prevention is key to improving outcomes. The delirium prodrome concept has been mooted for decades, but remains poorly characterised. Greater understanding of this prodrome would promote prompt identification of delirium-prone patients, and facilitate improved strategies for delirium prevention and management. Methods Medical inpatients of ≥70 years were screened for prevalent delirium using the Revised Delirium Rating Scale (DRS--‐R98). Those without prevalent delirium were assessed daily for delirium development, prodromal features and motor subtype. Survival analysis models identified which prodromal features predicted the emergence of incident delirium in the cohort in the first week of admission. The Delirium Motor Subtype Scale-4 was used to ascertain motor subtype. Results Of 555 patients approached, 191 patients were included in the prospective study. The median age was 80 (IQR 10) and 101 (52.9%) were male. Sixty-one patients developed incident delirium within a week of admission. Several prodromal features predicted delirium emergence in the cohort. Firstly, using a novel Prodromal Checklist based on the existing literature, and controlling for confounders, seven predictive behavioural features were identified in the prodromal period (for example, increasing confusion; and being easily distractible). Additionally, using serial cognitive tests and the DRS-R98 daily, multiple cognitive and other core delirium features were detected in the prodrome (for example inattention; and sleep-wake cycle disturbance). Examining longitudinal motor subtypes in delirium cases, subtypes were found to be predominantly stable over time, the most prevalent being hypoactive subtype (62.3%). Discussion This thesis explored multiple aspects of delirium in older medical inpatients, with particular focus on the characterisation of the delirium prodrome. These findings should help to inform future delirium educational programmes, and detection and prevention strategies.

Development of a novel probe integrated with a micro-structured impedance sensor for the detection of breast cancer

The work described in this thesis focuses on the development of an innovative bioimpedance device for the detection of breast cancer using electrical impedance as the detection method. The ability for clinicians to detect and treat cancerous lesions as early as possible results in improved patient outcomes and can reduce the severity of the treatment the patient has to undergo. Therefore, new technology and devices are continually required to improve the specificity and sensitivity of the accepted detection methods. The gold standard for breast cancer detection is digital x-ray mammography but it has some significant downsides associated with it. The development of an adjunct technology to aid in the detection of breast cancers could represent a significant patient and economic benefit. In this project silicon substrates were pattern with two gold microelectrodes that allowed electrical impedance measurements to be recorded from intact tissue structures. These probes were tested and characterised using a range of in vitro and ex vivo experiments. The end application of this novel sensor device was in a first-in-human clinical trial. The initial results of this study showed that the silicon impedance device was capable of differentiating between normal and abnormal (benign and cancerous) breast tissue. The mean separation between the two tissue types 4,340 Ω with p < 0.001. The cancer type and grade at the site of the probe recordings was confirmed histologically and correlated with the electrical impedance measurements to determine if the different subtypes of cancer could each be differentiated. The results presented in this thesis showed that the novel impedance device demonstrated excellent electrochemical recording potential; was biocompatible with the growth of cultured cell lines and was capable of differentiating between intact biological tissues. The results outlined in this thesis demonstrate the potential feasibility of using electrical impedance for the differentiation of biological tissue samples. The novelty of this thesis is in the development of a new method of tissue determination with an application in breast cancer detection.