Understanding distress in women at increased risk of breast cancer: the effects of experience of breast cancer in the family and illness perceptions

The aim of the current work was to improve understanding of factors associated with distress in women at increased risk of breast cancer because of their family history of the disease. Levels of distress have been described in this population although few studies have attempted to investigate causes of variation in distress. A number of anecdotal reports and qualitative studies have highlighted that women's experiences of breast cancer in their family is related to distress. The first study in this thesis aimed to assess women's experiences in a quantitative manner and demonstrated associations with general and cancer specific distress.Applying theoretical perspectives from health psychology enables us to consider how these experiences may influence psychological response to genetic risk. Using Leventhal's SelfRegulatory Model (SRM) (Leventhal et al. 1980) a theoretical model was developed for use in this thesis. This model proposed that perceptions of breast cancer mediate the impact of experiences of the disease in the family on psychological well-being. A large cross-sectional questionnaire study of women at increased risk of breast cancer and women in the general population was conducted in order to systematically explore this model. As there were no measures available to assess perceptions of breast cancer in healthy populations an existing generic measure was adapted and evaluated in the current samples. The mediation model was then systematically explored in a series of analyses.The results confirmed a number ofhypotheses. Women at increased risk of breast cancer showed higher levels of cancer specific distress and held different perceptions ofbreast cancer than women with no experience of the disease. Analysis indicated that experience of breast cancer in the family was associated with levels of distress and perceptions of the disease and that both experience ofbreast cancer and illness perceptions predicted distress in women at increased risk. Some support for the mediation model was found.This thesis has shown that the SRM can be successfully applied to women at increased risk of breast cancer. Further work is required to explore additional aspects xvi of illness perceptions in healthy individuals at increased risk of disease and to test the causality of relations revealed in this thesis. Utilising theoretical models to understand response to risk in this clinical context is likely to provide implications for the development and evaluation of interventions aimed at improving psychological well-being

De Grey Hours

Treasured amongst the holdings of the National Library of Wales is the little-known manuscript which is the subject of this dissertation. It is an example of a Book of Hours, which was one of the most popular genres of manuscript production during the middle ages, and was named for a previous owner, a member of the De Grey family. This manuscript has received very little attention previously. The first objective of the dissertation was to investigate as far as is possible at this stage the origins and original ownership of the manuscript. To this end, the family history of the De Greys was researched and an outline of the results forms a substantial part of the dissertation. This research into the background of the De Grey Hours revealed some intriguing possibilities as regards its original ownership and a new proposition based on contextual evidence and evidence within the manuscript is set out for consideration. The other objective of this dissertation has been to investigate the structure and organization of this book of hours taking into account its textual contents and its extensive and rich programme of illustrations. The investigation of the illuminations produced evidence that points to what is probably the origin of the De Grey Hours, that is, the atelier or school that was responsible for its production

Illness Cognitions and Coping Self-Efficacy in Depression Among Persons With Low Vision.

PURPOSE: To investigate the mediating role of coping self-efficacy (CSE) between two types of illness cognitions (i.e., acceptance and helplessness) and depressive symptoms in persons with low vision. METHODS: This was a single-group, cross-sectional study. Patients with visual acuity \u3c 6/12 in the better eye and at least minimal depressive symptoms (≥5 on the Patient Health Questionnaire-9 [PHQ-9]) were recruited from vision rehabilitation services and participated in telephone-administered structured interviews at one time point. Measures were the PHQ-9, CSE Scale, and Illness Cognition Questionnaire. Structural equation modeling (SEM) devised the causal flow of illness cognitions and their observed indirect effects on depressive symptoms via the CSE mediators: problem focused, emotion focused, and social support. RESULTS: The study comprised 163 patients (mean age 62 years; 61% female), most with age-related macular degeneration (26%) and moderate vision impairment (44%, \u3c6/18-6/60). Structural equation modeling indices indicated a perfect fit (χ2 \u3c 0.001, P = 1.00), accounting for 55% of the variance in depressive symptoms. Lower levels of acceptance and higher levels of helplessness illness cognitions were associated with lower self-efficacy in problem-focused coping (β = 0.38, P \u3c 0.001, β = -0.28, P \u3c 0.01, respectively), which in turn was associated with greater depressive symptom severity (β = -0.54, P \u3c 0.001). CONCLUSIONS: Lack of acceptance and greater helplessness relating to low vision led to a lack of perceived capability to engage in problem-focused coping, which in turn promoted depressive symptoms. Third-wave cognitive-behavioral treatments that focus on acceptance may be efficacious in this population

A tailored intervention to promote uptake of retinal screening among young adults with type 2 diabetes - an intervention mapping approach

BACKGROUND: Young adults (18-39 years) with type 2 diabetes are at risk of early development and rapid progression of diabetic retinopathy, a leading cause of vision loss and blindness in working-age adults. Retinal screening is key to the early detection of diabetic retinopathy, with risk of vision loss significantly reduced by timely treatment thereafter. Despite this, retinal screening rates are low among this at-risk group. The objective of this study was to develop a theoretically-grounded, evidence-based retinal screening promotion leaflet, tailored to young adults with type 2 diabetes. METHODS: Utilising the six steps of Intervention Mapping, our multidisciplinary planning team conducted a mixed-methods needs assessment (Step 1); identified modifiable behavioural determinants of screening behaviour and constructed a matrix of change objectives (Step 2); designed, reviewed and debriefed leaflet content with stakeholders (Steps 3 and 4); and developed program implementation and evaluation plans (Steps 5 and 6). RESULTS: Step 1 included in-depth qualitative interviews (N = 10) and an online survey that recruited a nationally-representative sample (N = 227), both informed by literature review. The needs assessment highlighted the crucial roles of knowledge (about diabetic retinopathy and screening), perception of personal risk, awareness of the approval of significant others and engagement with healthcare team, on retinal screening intentions and uptake. In Step 2, we selected five modifiable behavioural determinants to be targeted: knowledge, attitudes, normative beliefs, intention, and behavioural skills. In Steps 3 and 4, the "Who is looking after your eyes?" leaflet was developed, containing persuasive messages targeting each determinant and utilising engaging, cohort-appropriate imagery. In Steps 5 and 6, we planned Statewide implementation and designed a randomised controlled trial to evaluate the leaflet. CONCLUSIONS: This research provides an example of a systematic, evidence-based approach to the development of a simple health intervention designed to promote uptake of screening in accordance with national guidelines. The methods and findings illustrate how Intervention Mapping can be employed to develop tailored retinal screening promotion materials for specific priority populations. This paper has implications for future program planners and is intended to assist those wishing to use Intervention Mapping to create similar theoretically-driven, tailored resources

Problem-solving therapy for adults with diabetic retinopathy and diabetes-specific distress: a pilot randomized controlled trial

OBJECTIVE: To provide preliminary evidence for the impact of problem-solving therapy for diabetes (PST-D) in adults with diabetic retinopathy (DR) and diabetes distress. RESEARCH DESIGN AND METHODS: In a pilot randomized controlled trial, 40 participants with DR and diabetes distress were allocated to the PST-D or control groups. Diabetes distress (DDS), depressive symptoms (PHQ-9), self-care activities (SDSCA), and HbA1c were assessed at baseline, and 3 and 6-month follow-ups. RESULTS: At the 6-month follow-up, the PST-D group showed significant improvements relative to the control group, in \u27regimen-related distress\u27 (PST-D: -1.3&plusmn;1.4; control: -0.4&plusmn;1.1), depressive symptoms (PST-D: -4.3&plusmn;6.1; control: -0.3&plusmn;4.6), and HbA1c (PST-D: -1.2%&plusmn;1.01; control: 0.2%&plusmn;1.2%) (all p&lt;0.05). In multiple regression analysis, adjusting for baseline values and sociodemographic factors, PST-D was associated with significant improvement in \u27regimen-related distress\u27, depressive symptoms, and HbA1c at the 6-month follow-up (p&lt;0.05). CONCLUSIONS: PST-D is a promising intervention for improving psychological outcomes and glycemic control. A fully powered study is required to confirm these findings and examine mechanisms of change in HbA1c.<br /

Experiences of using the Theoretical Domains Framework across diverse clinical environments: a qualitative study

This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License. The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. Permissions beyond the scope of the License are administered by Dove Medical Press Limited. Information on how to request permission may be found at: http://www.dovepress.com/permissions.phpBACKGROUND: The Theoretical Domains Framework (TDF) is an integrative framework developed from a synthesis of psychological theories as a vehicle to help apply theoretical approaches to interventions aimed at behavior change. PURPOSE: This study explores experiences of TDF use by professionals from multiple disciplines across diverse clinical settings. METHODS: Mixed methods were used to examine experiences, attitudes, and perspectives of health professionals in using the TDF in health care implementation projects. Individual interviews were conducted with ten health care professionals from six disciplines who used the TDF in implementation projects. Deductive content and thematic analysis were used. RESULTS: Three main themes and associated subthemes were identified including: 1) reasons for use of the TDF (increased confidence, broader perspective, and theoretical underpinnings); 2) challenges using the TDF (time and resources, operationalization of the TDF) and; 3) future use of the TDF. CONCLUSION: The TDF provided a useful, flexible framework for a diverse group of health professionals working across different clinical settings for the assessment of barriers and targeting resources to influence behavior change for implementation projects. The development of practical tools and training or support is likely to aid the utility of TDF

Detection of motor changes in huntington's disease using dynamic causal modeling

Deficits in motor functioning are one of the hallmarks of Huntington's disease (HD), a genetically caused neurodegenerative disorder. We applied functional magnetic resonance imaging (fMRI) and dynamic causal modeling (DCM) to assess changes that occur with disease progression in the neural circuitry of key areas associated with executive and cognitive aspects of motor control. Seventy-seven healthy controls, 62 pre-symptomatic HD gene carriers (preHD), and 16 patients with manifest HD symptoms (earlyHD) performed a motor finger-tapping fMRI task with systematically varying speed and complexity. DCM was used to assess the causal interactions among seven pre-defined regions of interest, comprising primary motor cortex, supplementary motor area (SMA), dorsal premotor cortex, and superior parietal cortex. To capture heterogeneity among HD gene carriers, DCM parameters were entered into a hierarchical cluster analysis using Ward's method and squared Euclidian distance as a measure of similarity. After applying Bonferroni correction for the number of tests, DCM analysis revealed a group difference that was not present in the conventional fMRI analysis. We found an inhibitory effect of complexity on the connection from parietal to premotor areas in preHD, which became excitatory in earlyHD and correlated with putamen atrophy. While speed of finger movements did not modulate the connection from caudal to pre-SMA in controls and preHD, this connection became strongly negative in earlyHD. This second effect did not survive correction for multiple comparisons. Hierarchical clustering separated the gene mutation carriers into three clusters that also differed significantly between these two connections and thereby confirmed their relevance. DCM proved useful in identifying group differences that would have remained undetected by standard analyses and may aid in the investigation of between-subject heterogeneity

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p&lt;0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p&lt;0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p&lt;0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP &gt;5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification