Supporting self-management: development and evaluation of a digital resource for adults with asthma

The problem: Around 300 million people worldwide have asthma and prevalence is increasing. Support for optimal self-management can be effective in improving a range of outcomes and is cost effective, but is underutilised as a treatment strategy. Supporting optimum self-management using digital technology shows promise, but how best to do this is not clear. Aim: The purpose of this project was to explore the potential role of a digital intervention in promoting optimum self-management in adults with asthma. Methods: Following the MRC Guidance on the Development and Evaluation of Complex Interventions which advocates using theory, evidence, user testing and appropriate modelling and piloting, this project had 3 phases. Phase 1: Examination of the literature to inform phases 2 and 3, using systematic review methods and focussed literature searching. Phase 2: Developing the Living Well with Asthma website. A prototype (paper-based) version of the website was developed iteratively with input from a multidisciplinary expert panel, empirical evidence from the literature (from phase 1), and potential end users via focus groups (adults with asthma and practice nurses). Implementation and behaviour change theories informed this process. The paper-based designs were converted to the website through an iterative user centred process (think aloud studies with adults with asthma). Participants considered contents, layout, and navigation. Development was agile using feedback from the think aloud sessions immediately to inform design and subsequent think aloud sessions. Phase 3: A pilot randomised controlled trial over 12 weeks to evaluate the feasibility of a Phase 3 trial of Living Well with Asthma to support self-management. Primary outcomes were 1) recruitment & retention; 2) website use; 3) Asthma Control Questionnaire (ACQ) score change from baseline; 4) Mini Asthma Quality of Life (AQLQ) score change from baseline. Secondary outcomes were patient activation, adherence, lung function, fractional exhaled nitric oxide (FeNO), generic quality of life measure (EQ-5D), medication use, prescribing and health services contacts. Results: Phase1: Demonstrated that while digital interventions show promise, with some evidence of effectiveness in certain outcomes, participants were poorly characterised, telling us little about the reach of these interventions. The interventions themselves were poorly described making drawing definitive conclusions about what worked and what did not impossible. Phase 2: The literature indicated that important aspects to cover in any self-management intervention (digital or not) included: asthma action plans, regular health professional review, trigger avoidance, psychological functioning, self-monitoring, inhaler technique, and goal setting. The website asked users to aim to be symptom free. Key behaviours targeted to achieve this include: optimising medication use (including inhaler technique); attending primary care asthma reviews; using asthma action plans; increasing physical activity levels; and stopping smoking. The website had 11 sections, plus email reminders, which promoted these behaviours. Feedback during think aloud studies was mainly positive with most changes focussing on clarification of language, order of pages and usability issues mainly relating to navigation difficulties. Phase 3: To achieve our recruitment target 5383 potential participants were invited, leading to 51 participants randomised (25 to intervention group). Age range 16-78 years; 75% female; 28% from most deprived quintile. Nineteen (76%) of the intervention group used the website for an average of 23 minutes. Non-significant improvements in favour of the intervention group observed in the ACQ score (-0.36; 95% confidence interval: -0.96, 0.23; p=0.225), and mini-AQLQ scores (0.38; -0.13, 0.89; p=0.136). A significant improvement was observed in the activity limitation domain of the mini-AQLQ (0.60; 0.05 to 1.15; p = 0.034). Secondary outcomes showed increased patient activation and reduced reliance on reliever medication. There was no significant difference in the remaining secondary outcomes. There were no adverse events. Conclusion: Living Well with Asthma has been shown to be acceptable to potential end users, and has potential for effectiveness. This intervention merits further development, and subsequent evaluation in a Phase III full scale RCT.

Identifying health inequalities in individuals with major mental illness (MMI) using routine data

Abstract and Summary of Thesis: Background: Individuals with Major Mental Illness (such as schizophrenia and bipolar disorder) experience increased rates of physical health comorbidity compared to the general population. They also experience inequalities in access to certain aspects of healthcare. This ultimately leads to premature mortality. Studies detailing patterns of physical health comorbidity are limited by their definitions of comorbidity, single disease approach to comorbidity and by the study of heterogeneous groups. To date the investigation of possible sources of healthcare inequalities experienced by individuals with Major Mental Illness (MMI) is relatively limited. Moreover studies detailing the extent of premature mortality experienced by individuals with MMI vary both in terms of the measure of premature mortality reported and age of the cohort investigated, limiting their generalisability to the wider population. Therefore local and national data can be used to describe patterns of physical health comorbidity, investigate possible reasons for health inequalities and describe mortality rates. These findings will extend existing work in this area. Aims and Objectives: To review the relevant literature regarding: patterns of physical health comorbidity, evidence for inequalities in physical healthcare and evidence for premature mortality for individuals with MMI. To examine the rates of physical health comorbidity in a large primary care database and to assess for evidence for inequalities in access to healthcare using both routine primary care prescribing data and incentivised national Quality and Outcome Framework (QOF) data. Finally to examine the rates of premature mortality in a local context with a particular focus on cause of death across the lifespan and effect of International Classification of Disease Version 10 (ICD 10) diagnosis and socioeconomic status on rates and cause of death. Methods: A narrative review of the literature surrounding patterns of physical health comorbidity, the evidence for inequalities in physical healthcare and premature mortality in MMI was undertaken. Rates of physical health comorbidity and multimorbidity in schizophrenia and bipolar disorder were examined using a large primary care dataset (Scottish Programme for Improving Clinical Effectiveness in Primary Care (SPICE)). Possible inequalities in access to healthcare were investigated by comparing patterns of prescribing in individuals with MMI and comorbid physical health conditions with prescribing rates in individuals with physical health conditions without MMI using SPICE data. Potential inequalities in access to health promotion advice (in the form of smoking cessation) and prescribing of Nicotine Replacement Therapy (NRT) were also investigated using SPICE data. Possible inequalities in access to incentivised primary healthcare were investigated using National Quality and Outcome Framework (QOF) data. Finally a pre-existing case register (Glasgow Psychosis Clinical Information System (PsyCIS)) was linked to Scottish Mortality data (available from the Scottish Government Website) to investigate rates and primary cause of death in individuals with MMI. Rate and primary cause of death were compared to the local population and impact of age, socioeconomic status and ICD 10 diagnosis (schizophrenia vs. bipolar disorder) were investigated. Results: Analysis of the SPICE data found that sixteen out of the thirty two common physical comorbidities assessed, occurred significantly more frequently in individuals with schizophrenia. In individuals with bipolar disorder fourteen occurred more frequently. The most prevalent chronic physical health conditions in individuals with schizophrenia and bipolar disorder were: viral hepatitis (Odds Ratios (OR) 3.99 95% Confidence Interval (CI) 2.82-5.64 and OR 5.90 95% CI 3.16-11.03 respectively), constipation (OR 3.24 95% CI 3.01-3.49 and OR 2.84 95% CI 2.47-3.26 respectively) and Parkinson’s disease (OR 3.07 95% CI 2.43-3.89 and OR 2.52 95% CI 1.60-3.97 respectively). Both groups had significantly increased rates of multimorbidity compared to controls: in the schizophrenia group OR for two comorbidities was 1.37 95% CI 1.29-1.45 and in the bipolar disorder group OR was 1.34 95% CI 1.20-1.49. In the studies investigating inequalities in access to healthcare there was evidence of: under-recording of cardiovascular-related conditions for example in individuals with schizophrenia: OR for Atrial Fibrillation (AF) was 0.62 95% CI 0.52 - 0.73, for hypertension 0.71 95% CI 0.67 - 0.76, for Coronary Heart Disease (CHD) 0.76 95% CI 0.69 - 0.83 and for peripheral vascular disease (PVD) 0.83 95% CI 0.72 - 0.97. Similarly in individuals with bipolar disorder OR for AF was 0.56 95% CI 0.41-0.78, for hypertension 0.69 95% CI 0.62 - 0.77 and for CHD 0.77 95% CI 0.66 - 0.91. There was also evidence of less intensive prescribing for individuals with schizophrenia and bipolar disorder who had comorbid hypertension and CHD compared to individuals with hypertension and CHD who did not have schizophrenia or bipolar disorder. Rate of prescribing of statins for individuals with schizophrenia and CHD occurred significantly less frequently than in individuals with CHD without MMI (OR 0.67 95% CI 0.56-0.80). Rates of prescribing of 2 or more anti-hypertensives were lower in individuals with CHD and schizophrenia and CHD and bipolar disorder compared to individuals with CHD without MMI (OR 0.66 95% CI 0.56-0.78 and OR 0.55 95% CI 0.46-0.67, respectively). Smoking was more common in individuals with MMI compared to individuals without MMI (OR 2.53 95% CI 2.44-2.63) and was particularly increased in men (OR 2.83 95% CI 2.68-2.98). Rates of ex-smoking and non-smoking were lower in individuals with MMI (OR 0.79 95% CI 0.75-0.83 and OR 0.50 95% CI 0.48-0.52 respectively). However recorded rates of smoking cessation advice in smokers with MMI were significantly lower than the recorded rates of smoking cessation advice in smokers with diabetes (88.7% vs. 98.0%, p<0.001), smokers with CHD (88.9% vs. 98.7%, p<0.001) and smokers with hypertension (88.3% vs. 98.5%, p<0.001) without MMI. The odds ratio of NRT prescription was also significantly lower in smokers with MMI without diabetes compared to smokers with diabetes without MMI (OR 0.75 95% CI 0.69-0.81). Similar findings were found for smokers with MMI without CHD compared to smokers with CHD without MMI (OR 0.34 95% CI 0.31-0.38) and smokers with MMI without hypertension compared to smokers with hypertension without MMI (OR 0.71 95% CI 0.66-0.76). At a national level, payment and population achievement rates for the recording of body mass index (BMI) in MMI was significantly lower than the payment and population achievement rates for BMI recording in diabetes throughout the whole of the UK combined: payment rate 92.7% (Inter Quartile Range (IQR) 89.3-95.8 vs. 95.5% IQR 93.3-97.2, p<0.001 and population achievement rate 84.0% IQR 76.3-90.0 vs. 92.5% IQR 89.7-94.9, p<0.001 and for each country individually: for example in Scotland payment rate was 94.0% IQR 91.4-97.2 vs. 96.3% IQR 94.3-97.8, p<0.001. Exception rate was significantly higher for the recording of BMI in MMI than the exception rate for BMI recording in diabetes for the UK combined: 7.4% IQR 3.3-15.9 vs. 2.3% IQR 0.9-4.7, p<0.001 and for each country individually. For example in Scotland exception rate in MMI was 11.8% IQR 5.4-19.3 compared to 3.5% IQR 1.9-6.1 in diabetes. Similar findings were found for Blood Pressure (BP) recording: across the whole of the UK payment and population achievement rates for BP recording in MMI were also significantly reduced compared to payment and population achievement rates for the recording of BP in chronic kidney disease (CKD): payment rate: 94.1% IQR 90.9-97.1 vs.97.8% IQR 96.3-98.9 and p<0.001 and population achievement rate 87.0% IQR 81.3-91.7 vs. 97.1% IQR 95.5-98.4, p<0.001. Exception rates again were significantly higher for the recording of BP in MMI compared to CKD (6.4% IQR 3.0-13.1 vs. 0.3% IQR 0.0-1.0, p<0.001). There was also evidence of differences in rates of recording of BMI and BP in MMI across the UK. BMI and BP recording in MMI were significantly lower in Scotland compared to England (BMI:-1.5% 99% CI -2.7 to -0.3%, p<0.001 and BP: -1.8% 99% CI -2.7 to -0.9%, p<0.001). While rates of BMI and BP recording in diabetes and CKD were similar in Scotland compared to England (BMI: -0.5 99% CI -1.0 to 0.05, p=0.004 and BP: 0.02 99% CI -0.2 to 0.3, p=0.797). Data from the PsyCIS cohort showed an increase in Standardised Mortality Ratios (SMR) across the lifespan for individuals with MMI compared to the local Glasgow and wider Scottish populations (Glasgow SMR 1.8 95% CI 1.6-2.0 and Scotland SMR 2.7 95% CI 2.4-3.1). Increasing socioeconomic deprivation was associated with an increased overall rate of death in MMI (350.3 deaths/10,000 population/5 years in the least deprived quintile compared to 794.6 deaths/10,000 population/5 years in the most deprived quintile). No significant difference in rate of death for individuals with schizophrenia compared with bipolar disorder was reported (6.3% vs. 4.9%, p=0.086), but primary cause of death varied: with higher rates of suicide in individuals with bipolar disorder (22.4% vs. 11.7%, p=0.04). Discussion: Local and national datasets can be used for epidemiological study to inform local practice and complement existing national and international studies. While the strengths of this thesis include the large data sets used and therefore their likely representativeness to the wider population, some limitations largely associated with using secondary data sources are acknowledged. While this thesis has confirmed evidence of increased physical health comorbidity and multimorbidity in individuals with MMI, it is likely that these findings represent a significant under reporting and likely under recognition of physical health comorbidity in this population. This is likely due to a combination of patient, health professional and healthcare system factors and requires further investigation. Moreover, evidence of inequality in access to healthcare in terms of: physical health promotion (namely smoking cessation advice), recording of physical health indices (BMI and BP), prescribing of medications for the treatment of physical illness and prescribing of NRT has been found at a national level. While significant premature mortality in individuals with MMI within a Scottish setting has been confirmed, more work is required to further detail and investigate the impact of socioeconomic deprivation on cause and rate of death in this population. It is clear that further education and training is required for all healthcare staff to improve the recognition, diagnosis and treatment of physical health problems in this population with the aim of addressing the significant premature mortality that is seen. Conclusions: Future work lies in the challenge of designing strategies to reduce health inequalities and narrow the gap in premature mortality reported in individuals with MMI. Models of care that allow a much more integrated approach to diagnosing, monitoring and treating both the physical and mental health of individuals with MMI, particularly in areas of social and economic deprivation may be helpful. Strategies to engage this “hard to reach” population also need to be developed. While greater integration of psychiatric services with primary care and with specialist medical services is clearly vital the evidence on how best to achieve this is limited. While the National Health Service (NHS) is currently undergoing major reform, attention needs to be paid to designing better ways to improve the current disconnect between primary and secondary care. This should then help to improve physical, psychological and social outcomes for individuals with MMI.

Investigation of multisensory processing and structural brain differences in Autism Spectrum Disorder

This thesis is an investigation of structural brain abnormalities, as well as multisensory and unisensory processing deficits in autistic traits and Autism Spectrum Disorder (ASD). To achieve this, structural and functional magnetic resonance imaging (fMRI) and psychophysical techniques were employed. ASD is a neurodevelopmental condition which is characterised by the social communication and interaction deficits, as well as repetitive patterns of behaviour, interests and activities. These traits are thought to be present in a typical population. The Autism Spectrum Quotient questionnaire (AQ) was developed to assess the prevalence of autistic traits in the general population. Von dem Hagen et al. (2011) revealed a link between AQ with white matter (WM) and grey matter (GM) volume (using voxel-based-morphometry). However, their findings revealed no difference in GM in areas associated with social cognition. Cortical thickness (CT) measurements are known to be a more direct measure of cortical morphology than GM volume. Therefore, Chapter 2 investigated the relationship between AQ scores and CT in the same sample of participants. This study showed that AQ scores correlated with CT in the left temporo-occipital junction, left posterior cingulate, right precentral gyrus and bilateral precentral sulcus, in a typical population. These areas were previously associated with structural and functional differences in ASD. Thus the findings suggest, to some extent, autistic traits are reflected in brain structure - in the general population. The ability to integrate auditory and visual information is crucial to everyday life, and results are mixed regarding how ASD influences audiovisual integration. To investigate this question, Chapter 3 examined the Temporal Integration Window (TIW), which indicates how precisely sight and sound need to be temporally aligned so that a unitary audiovisual event can be perceived. 26 adult males with ASD and 26 age and IQ-matched typically developed males were presented with flash-beep (BF), point-light drummer, and face-voice (FV) displays with varying degrees of asynchrony and asked to make Synchrony Judgements (SJ) and Temporal Order Judgements (TOJ). Analysis of the data included fitting Gaussian functions as well as using an Independent Channels Model (ICM) to fit the data (Garcia-Perez & Alcala-Quintana, 2012). Gaussian curve fitting for SJs showed that the ASD group had a wider TIW, but for TOJ no group effect was found. The ICM supported these results and model parameters indicated that the wider TIW for SJs in the ASD group was not due to sensory processing at the unisensory level, but rather due to decreased temporal resolution at a decisional level of combining sensory information. Furthermore, when performing TOJ, the ICM revealed a smaller Point of Subjective Simultaneity (PSS; closer to physical synchrony) in the ASD group than in the TD group. Finding that audiovisual temporal processing is different in ASD encouraged us to investigate the neural correlates of multisensory as well as unisensory processing using functional magnetic resonance imaging fMRI. Therefore, Chapter 4 investigated audiovisual, auditory and visual processing in ASD of simple BF displays and complex, social FV displays. During a block design experiment, we measured the BOLD signal when 13 adults with ASD and 13 typically developed (TD) age-sex- and IQ- matched adults were presented with audiovisual, audio and visual information of BF and FV displays. Our analyses revealed that processing of audiovisual as well as unisensory auditory and visual stimulus conditions in both the BF and FV displays was associated with reduced activation in ASD. Audiovisual, auditory and visual conditions of FV stimuli revealed reduced activation in ASD in regions of the frontal cortex, while BF stimuli revealed reduced activation the lingual gyri. The inferior parietal gyrus revealed an interaction between stimulus sensory condition of BF stimuli and group. Conjunction analyses revealed smaller regions of the superior temporal cortex (STC) in ASD to be audiovisual sensitive. Against our predictions, the STC did not reveal any activation differences, per se, between the two groups. However, a superior frontal area was shown to be sensitive to audiovisual face-voice stimuli in the TD group, but not in the ASD group. Overall this study indicated differences in brain activity for audiovisual, auditory and visual processing of social and non-social stimuli in individuals with ASD compared to TD individuals. These results contrast previous behavioural findings, suggesting different audiovisual integration, yet intact auditory and visual processing in ASD. Our behavioural findings revealed audiovisual temporal processing deficits in ASD during SJ tasks, therefore we investigated the neural correlates of SJ in ASD and TD controls. Similar to Chapter 4, we used fMRI in Chapter 5 to investigate audiovisual temporal processing in ASD in the same participants as recruited in Chapter 4. BOLD signals were measured while the ASD and TD participants were asked to make SJ on audiovisual displays of different levels of asynchrony: the participants’ PSS, audio leading visual information (audio first), visual leading audio information (visual first). Whereas no effect of group was found with BF displays, increased putamen activation was observed in ASD participants compared to TD participants when making SJs on FV displays. Investigating SJ on audiovisual displays in the bilateral superior temporal gyrus (STG), an area involved in audiovisual integration (see Chapter 4), we found no group differences or interaction between group and levels of audiovisual asynchrony. The investigation of different levels of asynchrony revealed a complex pattern of results indicating a network of areas more involved in processing PSS than audio first and visual first, as well as areas responding differently to audio first compared to video first. These activation differences between audio first and video first in different brain areas are constant with the view that audio leading and visual leading stimuli are processed differently.

Effect of vitamin D supplementation on bone status, glucose homeostasis and immune function in children with vitamin D deficiency

Background: Between 1961-1971 vitamin D deficiency was recognized as a public health issue in the UK, because of the lack of effective sunlight and the population mix [1, 2]. In recent years, health care professionals have cited evidence suggesting a re-emergence of the vitamin D deficiency linked to a number of health consequences as a concern [3-6]. Evidence from observational studies has linked low vitamin D status with impairment in glucose homeostasis and immune dysfunction [7-9]. However, interventional studies, particularly those focused on paediatric populations, have been limited and inconsistent. There is a need for detailed studies, to clarify the therapeutic benefits of vitamin D in these important clinical areas. Objective: The aims of this PhD thesis were two-fold. Firstly, to perform preliminary work assessing the association between vitamin D deficiency and bone status, glucose homeostasis and immune function, and to explore any changes in these parameters following short term vitamin D3 replacement therapy. Secondly, to assess the effectiveness of an electronic surveillance system (ScotPSU) as a tool to determine the current incidence of hospital-based presentation of childhood vitamin D deficiency in Scotland. Methods: Active surveillance was performed for a period of two years as a part of an electronic web-based surveillance programme performed by the Scottish Paediatric Surveillance Unit (ScotPSU). The validity of the system was assessed by identifying cases with profound vitamin D deficiency (in Glasgow and Edinburgh) from the regional laboratory. All clinical details were checked against those identified using the surveillance system. Thirty-seven children aged 3 months to 10 years, who had been diagnosed with vitamin D deficiency, were recruited for the bone, glucose and immunity studies over a period of 24 months. Twenty-five samples were analysed for the glucose and bone studies; of these, 18 samples were further analysed for immune study. Treatment consisted of six weeks taking 5000 IU units cholecalciferol orally once a day. At baseline and after completion of treatment, 25 hydroxyvitamin D (25(OH)D), parathyroid hormone (PTH), alkaline phosphatase (ALP), collagen type 1 cross-linked C-telopeptide (CTX), osteocalcin (OCN), calcium, phosphate, insulin, glucose, homeostasis model assessment index, estimated insulin resistance (HOMA IR), glycated hemoglobin (HbA1c), sex hormone binding globulin (SHBG), lipids profiles, T helper 1 (Th1) cytokines (interleukin-2 ( IL-2), tumor necrosis factors-alpha (TNF-α), interferon-gamma (INF-γ)), T helper 2 (Th2) cytokines (interleukin-4 (IL-4), interleukin-5 (IL-5), interleukin-6 (IL-6)), T helper 17 (Th17) cytokine (interleukin-17 (IL-17)), Regulatory T (Treg) cytokine (interleukin-10 (IL-10)) and chemokines/cytokines, linked with Th1/Th2 subset balance and/or differentiation (interleukin-8 (IL-8), interleukin-12 (IL-12), eosinophil chemotactic protein ( EOTAXIN), macrophage inflammatory proteins-1beta (MIP-1β), interferon-gamma-induced protein-10 (IP-10), regulated on activation, normal T cell expressed and secreted (RANTES), monocyte chemoattractant protein-1(MCP-1)) were measured. Leukoocyte subset analysis was performed for T cells, B cells and T regulatory cells and a luminex assay was used to measure the cytokiens. Results: Between September 2009 and August 2011, 163 cases of vitamin D deficiency were brought to the attention of the ScotPSU, and the majority of cases (n = 82) were reported in Glasgow. The cross-validation checking in Glasgow and Edinburgh over a one-year period revealed only 3 (11%) cases of clearly symptomatic vitamin D deficiency, which had been missed by the ScotPSU survey in Glasgow. While 16 (67%) symptomatic cases had failed to be reported through the ScotPSU survey in Edinburgh. For the 23 children who are included in bone and glucose studies, 22 (96%) children had basal serum 25(OH)D in the deficiency range (< 50 nmol/l) and one (4%) child had serum 25(OH)D in the insufficiency range (51-75 nmol/l). Following vitamin D3 treatment, 2 (9%) children had final serum 25(OH)D lower than 50 nmol/l, 6 (26%) children had final serum 25(OH)D between >50-75 nmol/l, 12 (52%) children reached a final serum 25(OH)D >75-150 nmol/l and finally 3 (13%) exceeded the normal reference range with a final 25(OH)D >150 nmol/l. Markers for remodelling ALP and PTH had significantly decreased (p = 0.001 and <0.0001 for ALP and PTH respectively). In 17 patients for whom insulin and HOMA IR data were available and enrolled in glucose study, significant improvements in insulin resistance (p = 0.04) with a trend toward a reduction in serum insulin (p = 0.05) was observed. Of those 14 children who had their cytokines profile data analysed and enrolled in the immunity study, insulin and HOMA IR data were missed in one child. A significant increase in the main Th2 secreted cytokine IL-4 (p = 0.001) and a tendency for significant increases in other Th2 secreted cytokines IL-5 (p = 0.05) and IL-6 (p = 0.05) was observed following vitamin D3 supplementation. Conclusion: An electronic surveillance system can provide data for studying the epidemiology of vitamin D deficiency. However, it may underestimate the number of positive cases. Improving vitamin D status in vitamin D deficient otherwise healthy children significantly improved their vitamin D deficient status, and was associated with an improvement in bone profile, improvements in insulin resistance and an alteration in main Th2 secreting cytokines.