The Quick Mild Cognitive Impairment (Qmci) screen: developing a new screening test for mild cognitive impairment and dementia

Introduction: Identifying mild cognitive impairment (MCI) is challenging. Few short instruments have sufficient sensitivity and specificity for use in busy clinical practice. This thesis explores the development, psychometric evaluation and validation of a new short (3–5 min) cognitive screening instrument, designed to screen for MCI and early dementia, called the Quick Mild Cognitive Impairment (Q

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.

Application of signal detection methods to fisheries management

The abundance of many commercially important fish stocks are declining and this has led to widespread concern on the performance of traditional approach in fisheries management. Quantitative models are used for obtaining estimates of population abundance and the management advice is based on annual harvest levels (TAC), where only a certain amount of catch is allowed from specific fish stocks. However, these models are data intensive and less useful when stocks have limited historical information. This study examined whether empirical stock indicators can be used to manage fisheries. The relationship between indicators and the underlying stock abundance is not direct and hence can be affected by disturbances that may account for both transient and persistent effects. Methods from Statistical Process Control (SPC) theory such as the Cumulative Sum (CUSUM) control charts are useful in classifying these effects and hence they can be used to trigger management response only when a significant impact occurs to the stock biomass. This thesis explores how empirical indicators along with CUSUM can be used for monitoring, assessment and management of fish stocks. I begin my thesis by exploring various age based catch indicators, to identify those which are potentially useful in tracking the state of fish stocks. The sensitivity and response of these indicators towards changes in Spawning Stock Biomass (SSB) showed that indicators based on age groups that are fully selected to the fishing gear or Large Fish Indicators (LFIs) are most useful and robust across the range of scenarios considered. The Decision-Interval (DI-CUSUM) and Self-Starting (SS-CUSUM) forms are the two types of control charts used in this study. In contrast to the DI-CUSUM, the SS-CUSUM can be initiated without specifying a target reference point (‘control mean’) to detect out-of-control (significant impact) situations. The sensitivity and specificity of SS-CUSUM showed that the performances are robust when LFIs are used. Once an out-of-control situation is detected, the next step is to determine how much shift has occurred in the underlying stock biomass. If an estimate of this shift is available, they can be used to update TAC by incorporation into Harvest Control Rules (HCRs). Various methods from Engineering Process Control (EPC) theory were tested to determine which method can measure the shift size in stock biomass with the highest accuracy. Results showed that methods based on Grubb’s harmonic rule gave reliable shift size estimates. The accuracy of these estimates can be improved by monitoring a combined indicator metric of stock-recruitment and LFI because this may account for impacts independent of fishing. The procedure of integrating both SPC and EPC is known as Statistical Process Adjustment (SPA). A HCR based on SPA was designed for DI-CUSUM and the scheme was successful in bringing out-of-control fish stocks back to its in-control state. The HCR was also tested using SS-CUSUM in the context of data poor fish stocks. Results showed that the scheme will be useful for sustaining the initial in-control state of the fish stock until more observations become available for quantitative assessments.

18-Fluorodeoxyglucose positron emission tomography/computed tomography in the management of aggressive non-Hodgkin's B-cell lymphoma

18-Fluorodeoxyglucose (FDG-PET/CT) is an established imaging modality that has been proven to be of benefit in the management of aggressive B-cell non-Hodgkin's lymphoma, such as diffuse large B-cell lymphoma and advanced stage follicular lymphoma. The combination of anatomic and functional imaging afforded by FDG-PET/CT has led to superior sensitivity and specificity in the primary staging, restaging, and assessment of response to treatment of hematological malignancies when compared to FDG-PET and CT alone. The use of FDG-PET/CT for post treatment surveillance imaging remains controversial, and further study is needed to ascertain whether this modality is cost effective and appropriate for use in this setting.