Patient and health professional views on risk-stratified monitoring of immune-suppressing treatment in adults with inflammatory diseases.

OBJECTIVE: To explore the acceptability of an individualised risk-stratified approach to monitoring for target-organ toxicity in adult patients with immune-mediated inflammatory diseases established on immune-suppressing treatment(s). METHODS: Adults (≥18 years) taking immune-suppressing treatment(s) for at-least six months, and healthcare professionals (HCPs) with experience of either prescribing and/or monitoring immune-suppressing drugs were invited to participate in a single, remote, one-to-one, semi-structured interview. Interviews were conducted by a trained qualitative researcher and explored their views and experiences of current monitoring and acceptability of a proposed risk-stratified monitoring plan. Interviews were transcribed verbatim and inductively analysed using thematic analysis in NVivo. RESULTS: Eighteen patients and 13 HCPs were interviewed. While participants found monitoring of immune-suppressing drugs with frequent blood-tests reassuring, the current frequency of these was considered burdensome by patients and HCPs alike, and to be a superfluous use of healthcare resources. Given abnormalities rarely arose during long-term treatment, most felt that monitoring blood-tests were not needed as often. Patients and HCPs found it acceptable to increase the interval between monitoring blood-tests from three-monthly to six-monthly or annually depending on the patients' risk profiles. Conditions of accepting such a change included: allowing for clinician and patient autonomy in determining an individuals' frequency of monitoring blood-tests, the flexibility to change monitoring frequency if someone's risk profile changed, and endorsement from specialist societies and healthcare providers such as the National Health Service. CONCLUSION: A risk-stratified approach to monitoring was acceptable to patients and HCPs. Guideline groups should consider these findings when recommending blood-test monitoring intervals.

Fatigue during the COVID-19 pandemic - prevalence and predictors: findings from a prospective cohort study.

The COVID-19 pandemic and consequent lockdowns had a substantial impact on mental health. Distress and fatigue are highly correlated. However, little is known about the determinants of fatigue in the general population during the pandemic. This study aimed to examine the prevalence and predictors of fatigue during the COVID-19 pandemic in the UK population. Online surveys were completed by a UK community cohort in April 2020 (wave 1), July-September 2020 (wave 2) and November-December 2020 (wave 3). In total, 3097 participants completed the wave 1 survey, and 1385 and 1087 participants (85.4% women) completed wave 2 and 3 surveys respectively. Fatigue was assessed using the Chalder Fatigue Scale at waves 2 and 3. Hair samples were provided by 827 participants (90.6% women) at wave 1 and wave 2, which were analyzed to indicate HairE (stress hormone). The mean total fatigue score during wave 2 was 14.7 (SD = 4.7), significantly higher than pre-pandemic levels observed in the community (mean difference 0.50, p = .003). At wave 2, 614 (44.3%) participants met the case definition for fatigue, only 15.6% of whom indicated that fatigue lasted for more than 6 months (suggesting it had started prior to the pandemic). Predictors of fatigue at wave 3 included being in a risk group, depression and belief in having COVID-19, which explained 23.8% of the variability in fatigue scores. Depression at wave 1 was the only significant predictor of remaining a fatigue case at wave 3. Fatigue was highly prevalent in the UK community during the COVID-19 pandemic and limited people's daily function. Depression and sociodemographic variables were significant predictors of fatigue.

Fatigue levels between July-December 2020 were higher compared to pre-pandemic levels.Predictors of fatigue levels 7-8 months later included being a clinical risk group, depression and belief in having had COVID-19.HairE was not associated with fatigue.Depression was the only significant predictor of remaining a fatigue case.

Humoral and cellular immunity in patients with rare autoimmune rheumatic diseases following SARS-CoV-2 vaccination.

OBJECTIVES: Coronavirus 2019 vaccine responses in rare autoimmune rheumatic diseases (RAIRDs) remain poorly understood; in particular there is little known about whether people develop effective T cell responses. We conducted an observational study to evaluate the short-term humoral and cell-mediated T cell response after the second severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination in RAIRD patients compared with healthy controls (HCs). METHODS: Blood samples were collected after the second dose and anti-spike, anti-nucleocapsid antibody levels and SARS-CoV-2-specific T cell responses were measured and compared with those of HCs. Activation-induced marker and deep phenotyping assays were used to identify differences in T cells between high and no/low antibody groups, followed by multidimensional clustering. RESULTS: A total of 50 patients with RAIRDs were included (31 with AAV, 4 with other systemic vasculitis, 9 with SLE and 6 with myositis). The median anti-spike levels were significantly lower in RAIRD patients compared with HCs (P < 0.0001). Fifteen (33%) patients had undetectable levels and 26 (57%) had levels lower than the lowest HC. Rituximab in the last 12 months (P = 0.003) was associated with reduced immunogenicity compared with a longer pre-vaccination period. There was a significant difference in B cell percentages (P = 0.03) and spike-specific CD4+ T cells (P = 0.02) between no/low antibody vs high antibody groups. Patients in the no/low antibody group had a higher percentage of terminally differentiated (exhausted) T cells. CONCLUSIONS: Following two doses, most RAIRD patients have lower antibody levels than the lowest HC and lower anti-spike T cells. RAIRD patients with no/low antibodies have diminished numbers and poor quality of memory T cells that lack proliferative and functional capacities.

The facilitators and barriers to improving functional activity and wellbeing in people with dementia: a qualitative study from the process evaluation of Promoting Activity, Independence and Stability in Early Dementia (PrAISED).

BACKGROUND: The PRomoting Activity, Independence and Stability in Early Dementia (PrAISED) study delivered an exercise and functional activity programme to participants living with dementia. A Randomised Controlled Trial showed no measurable benefits in activities of daily living, physical activity or quality of life. OBJECTIVE: To explore participants' responses to PrAISED and explain why an intervention that might be expected to have produced measurable health gains did not do so. METHODS: A process evaluation using qualitative methods, comprising interviews and researcher notes. SETTING: Data were collected in participants' homes or remotely by telephone or videoconferencing. SAMPLE: A total of 88 interviews were conducted with 44 participants living with dementia (n = 32 intervention group; n = 12 control group) and 39 caregivers. A total of 69 interviews were conducted with 26 therapists. RESULTS: Participants valued the intervention as proactively addressing health issues that were of concern to them, and as a source of social contact, interaction, information and advice. Facilitators to achieving positive outcomes included perceiving progress towards desired goals, positive expectations, therapists' skills and rapport with participants, and caregiver support. Barriers included: cognitive impairment, which prevented independent engagement and carry-over between sessions; chronic physical health problems and intercurrent acute illness and injury; 'tapering' (progressively infrequent supervision intended to help develop habits and independent activity); and the COVID-19 pandemic. CONCLUSIONS: Self-directed interventions may not be appropriate in the context of dementia, even in the mild stages of the condition. Dementia-specific factors affected outcomes including caregiver support, rapport with therapists, availability of supervision, motivational factors and the limitations of remote delivery. The effects of cognitive impairment, multimorbidity and frailty overwhelmed any positive impact of the intervention. Maintenance of functional ability is valued, but in the face of inevitable progression of disease, other less tangible outcomes become important, challenging how we frame 'health gain' and trial outcomes.

Adherence to limiting weight-bearing activity in patients with diabetic foot ulcers: A qualitative study.

Patients with diabetic foot ulcers are advised to limit weight-bearing activity for ulcers to heal. Patients often disregard this advice although the reasons are not yet fully understood. This study explored (1) patients' experiences of receiving the advice and (2) factors influencing adherence to the advice. Semi-structured interviews were conducted with 14 patients with diabetic foot ulcers. Interviews were transcribed and analysed using inductive thematic analysis. Advice regarding limiting weight-bearing activity was described by patients as directive, generic and conflicting with other priorities. Rapport, empathy and rationale supported receptivity to the advice. Barriers and facilitators to limiting weight-bearing activity included demands of daily living, enjoyment of exercise, sick/disabled identity and burden, depression, neuropathy/pain, health benefits, fear of negative consequences, positive feedback, practical support, weather and active/passive role in recovery. It is important that healthcare professionals pay attention to how limiting weight-bearing activity advice is communicated. We propose a more person-centred approach in which advice is tailored to individuals' specific needs with discussion around patient priorities and constraints.

Relationship Between Anxiety, Depression, and Susceptibility to Severe Acute Respiratory Syndrome Coronavirus 2 Infection: Proof of Concept.

BACKGROUND: Psychological factors can influence susceptibility to viral infections. We examined whether such influences are evident in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS: Participants (n = 102) completed measures of anxiety, depression, positive mood, and loneliness and provided a blood sample for the measurement of antibodies to the SARS-CoV-2 spike and nucleocapsid proteins. RESULTS: SARS-CoV-2 was significantly negatively associated with anxiety and depression. The model remained significant after adjustment for age and gender, although anxiety and depression were no longer significant independent predictors. CONCLUSIONS: These findings offer early support for the hypothesis that psychological factors may influence susceptibility to SARS-CoV-2 infection.

Psychological Predictors of Self-reported COVID-19 Outcomes: Results From a Prospective Cohort Study.

BACKGROUND: Previous research has shown that psychological factors, such as stress and social support, are associated with greater susceptibility to viral respiratory illnesses and more severe symptoms. During the COVID-19 pandemic there has been a well-documented deterioration in psychological well-being and increased social isolation. This raises questions as to whether those experiencing psychological adversity during the pandemic are more at risk of contracting and/or experiencing COVID-19 symptoms. PURPOSE: To examine the relationship between psychological factors and the risk of COVID-19 self-reported infection and the symptomatic experience of SARS-CoV-2 (indicated by the number and severity of symptoms). METHODS: As part of a longitudinal prospective observational cohort study, 1,087 adults completed validated measures of psychological well-being during April 2020 and self-reported incidence of COVID-19 infection and symptom experience across the pandemic through to December 2020. Regression models were used to explore these relationships controlling for demographic and occupational factors. RESULTS: Greater psychological distress during the early phase of the pandemic was significantly associated with subsequent self-reported SARS-CoV-2 infection as well as the experience of a greater number and more severe symptoms. CONCLUSIONS: COVID-19 infection and symptoms may be more common among those experiencing elevated psychological distress. Further research to elucidate the mechanisms underlying these associations is needed.

Stress and Health: A Review of Psychobiological Processes.

The cumulative science linking stress to negative health outcomes is vast. Stress can affect health directly, through autonomic and neuroendocrine responses, but also indirectly, through changes in health behaviors. In this review, we present a brief overview of (a) why we should be interested in stress in the context of health; (b) the stress response and allostatic load; (c) some of the key biological mechanisms through which stress impacts health, such as by influencing hypothalamic-pituitary-adrenal axis regulation and cortisol dynamics, the autonomic nervous system, and gene expression; and (d) evidence of the clinical relevance of stress, exemplified through the risk of infectious diseases. The studies reviewed in this article confirm that stress has an impact on multiple biological systems. Future work ought to consider further the importance of early-life adversity and continue to explore how different biological systems interact in the context of stress and health processes.

Earlier diagnosis of lung cancer in a randomised trial of an autoantibody blood test followed by imaging.

The EarlyCDT-Lung test is a high-specificity blood-based autoantibody biomarker that could contribute to predicting lung cancer risk. We report on the results of a phase IV biomarker evaluation of whether using the EarlyCDT-Lung test and any subsequent computed tomography (CT) scanning to identify those at high risk of lung cancer reduces the incidence of patients with stage III/IV/unspecified lung cancer at diagnosis compared with the standard clinical practice at the time the study began.The Early Diagnosis of Lung Cancer Scotland (ECLS) trial was a randomised controlled trial of 12 208 participants at risk of developing lung cancer in Scotland in the UK. The intervention arm received the EarlyCDT-Lung test and, if test-positive, low-dose CT scanning 6-monthly for up to 2 years. EarlyCDT-Lung test-negative and control arm participants received standard clinical care. Outcomes were assessed at 2 years post-randomisation using validated data on cancer occurrence, cancer staging, mortality and comorbidities.At 2 years, 127 lung cancers were detected in the study population (1.0%). In the intervention arm, 33 out of 56 (58.9%) lung cancers were diagnosed at stage III/IV compared with 52 out of 71 (73.2%) in the control arm. The hazard ratio for stage III/IV presentation was 0.64 (95% CI 0.41-0.99). There were nonsignificant differences in lung cancer and all-cause mortality after 2 years.ECLS compared EarlyCDT-Lung plus CT screening to standard clinical care (symptomatic presentation) and was not designed to assess the incremental contribution of the EarlyCDT-Lung test. The observation of a stage shift towards earlier-stage lung cancer diagnosis merits further investigations to evaluate whether the EarlyCDT-Lung test adds anything to the emerging standard of low-dose CT.

Effects of Brief Mood-Improving Interventions on Immunity: A Systematic Review and Meta-Analysis.

OBJECTIVE: Positive mood has been associated with enhanced immune function. Interventions that improve mood could therefore provide a mechanism for optimizing immune-related health outcomes. Brief interventions that improve mood, also known as mood inductions, potentially offer a pragmatic approach to enhancing immune function for finite periods where this would be beneficial to health (e.g., in advance of vaccination or surgery). This review sought to systematically examine the evidence regarding the effects of brief, single-session positive mood interventions on immunity. METHODS: Systematic searches of electronic databases were performed from earliest records to July 25, 2018. We identified 42 interventions suitable for inclusion, 6 of which were tested in multiple subpopulations. Random-effects meta-analyses were performed for pre-post experimental group immune outcomes measured in at least five intervention studies. RESULTS: Although interventions were heterogeneous, 81% resulted in a statistically significant change in at least one immune parameter after the positive mood intervention for one or more of the subpopulations examined. However, studies were, in general, of low-to-moderate quality with small sample sizes (median n = 32) and did not examine the persistence or clinical relevance of the immune changes observed. Random-effects meta-analyses showed a significant medium-sized effect of interventions on increasing secretory IgA concentration (g = 0.65), a small but statistically significant effect for increased Interleukin-6 production (g = 0.12), and nonsignificant effects on natural killer cell activity (g = 0.15). CONCLUSIONS: The current literature suggests that improvements in mood resulting from brief interventions can influence some immune parameters in ways indicative of enhanced immune function. However, there is a need for higher-quality research in this area that focuses on clinically relevant immune outcomes and mechanisms.

Physical activity engagement strategies in people with mild cognitive impairment or dementia - a focus group study.

Objective: This focus group study aimed to explore how to motivate people with mild cognitive impairment (MCI) or dementia and their carers to engage in exercise and physical activity.Methods: Four focus groups were conducted with six people with MCI or dementia, three carers and four clinicians (nurse, occupational therapist, physiotherapists). A thematic analysis of the data was undertaken.Results: Five main themes were identified: 'memory problems', 'self-motivation', 'external motivation', 'design of activities' and 'barriers'. Participants viewed exercise positively but emphasised that it needed to fit into their daily routine. Goal-setting was seen as helpful by some participants but others saw this as a source of potential failure. Enjoyment was seen as key to engagement.Conclusion: Exercise and physical activity interventions need an individualised approach to engage people with MCI or dementia, with a positive emphasis on enjoyment. Goal-setting should be used with caution in this group of people.

Young people, mental health and COVID-19 infection: the canaries we put in the coal mine.

OBJECTIVES: The number of people testing positive for Severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) in the UK, particularly among young adults, is increasing. We report here on the mental health of young adults and related psychological and behavioural responses to the pandemic and consider the role of these factors in fuelling the increase in coronavirus disease 2019 (COVID-19) in this group. METHODS: An online survey was completed during the first six weeks of the first UK-wide lockdown by 3097 respondents, including data for 364 respondents aged 18-24 years. The survey included measures of mental health and indices capturing related psychological and behavioural responses to the pandemic. RESULTS: The mental health of 18- to 24-years-olds in the first 6 weeks of lockdown was significantly poorer than that of older respondents and previously published norms: with 84% reporting symptoms of depression and 72% reporting symptoms of anxiety. Young adults also reported significantly greater loneliness and reduced positive mood, both of which were also associated with greater mental health difficulties. CONCLUSIONS: We contend that the combination of mental health, social and economic considerations may have contributed to the rise of COVID-19 infections in young adults, and ascribing blame to this group will not aid our efforts to regain control of the disease.

Lung cancer screening: does pulmonary nodule detection affect a range of smoking behaviours?

BACKGROUND: Lung cancer screening can reduce lung cancer mortality by 20%. Screen-detected abnormalities may provide teachable moments for smoking cessation. This study assesses impact of pulmonary nodule detection on smoking behaviours within the first UK trial of a novel auto-antibody test, followed by chest x-ray and serial CT scanning for early detection of lung cancer (Early Cancer Detection Test-Lung Cancer Scotland Study). METHODS: Test-positive participants completed questionnaires on smoking behaviours at baseline, 1, 3 and 6 months. Logistic regression compared outcomes between nodule (n = 95) and normal CT groups (n = 174) at 3 and 6 months follow-up. RESULTS: No significant differences were found between the nodule and normal CT groups for any smoking behaviours and odds ratios comparing the nodule and normal CT groups did not vary significantly between 3 and 6 months. There was some evidence the nodule group were more likely to report significant others wanted them to stop smoking than the normal CT group (OR across 3- and 6-month time points: 3.04, 95% CI: 0.95, 9.73; P = 0.06). CONCLUSION: Pulmonary nodule detection during lung cancer screening has little impact on smoking behaviours. Further work should explore whether lung cancer screening can impact on perceived social pressure and promote smoking cessation.

Use it or lose it: a qualitative study of the maintenance of physical activity in older adults.

BACKGROUND: Lack of physical activity (PA) is a recognised global public health problem, which is increasing in prevalence with a detrimental impact on the pattern of disease worldwide. In the UK, older adults comprise the most sedentary group, with only 57% of males and 52% of females aged 65-74 years and 43% of males and 21% of females aged 75-84 years meeting PA recommendations. PA confers multiple health benefits including increased stamina, muscle, bone and joint strength, increased independence and reduced risk of falls in old age. Despite benefits experienced during time-limited PA programmes, increased PA is not always continued. This study aimed to provide a better understanding of PA maintenance behaviours in older people. METHODS: Face to face semi-structured interviews were conducted with adults who completed one of two strength and balance exercise programmes as part of the ProAct65+ trial: group (FaME) and home based (OTAGO) exercises. Five GP practices in Nottingham and Derby were recruited and invited people aged 65 years and older who met eligibility criteria. Interviews were conducted in participants' homes. Interviews explored PA levels pre and post intervention, perceived health benefits, facilitators, barriers and use of technology for PA maintenance. The interviews were transcribed verbatim and analysed using framework analysis and the software NVivo10. RESULTS: Fifteen participants from each intervention group were interviewed. The FaME group consisted of 10 females and 5 males, age range of 70-88 years. The OTAGO group consisted of 12 females and 3 males aged 72-95 years. Important themes identified were physical, social, psychological and environmental facilitators and barriers. These included increased physical autonomy, enjoyment, positive evaluation of the activity and physical benefits, importance of social interaction, positive feedback, development of behaviour considered normal or habitual, motivation and self-efficacy. Some participants used technologies not included in the original interventions, like pedometers and smart phones to motivate themselves. CONCLUSIONS: A range of modifiable factors influence continued participation in PA at the end of exercise programmes. The findings from this study will inform the commissioning and quality improvement of future PA programmes and development of an intervention to enhance continuation of PA after exercise interventions in older adults.

Positive mood on the day of influenza vaccination predicts vaccine effectiveness: A prospective observational cohort study.

Influenza vaccination is estimated to only be effective in 17-53% of older adults. Multiple patient behaviors and psychological factors have been shown to act as 'immune modulators' sufficient to influence vaccination outcomes. However, the relative importance of such factors is unknown as they have typically been examined in isolation. The objective of the present study was to explore the effects of multiple behavioral (physical activity, nutrition, sleep) and psychological influences (stress, positive mood, negative mood) on the effectiveness of the immune response to influenza vaccination in the elderly. A prospective, diary-based longitudinal observational cohort study was conducted. One hundred and thirty-eight community-dwelling older adults (65-85years) who received the 2014/15 influenza vaccination completed repeated psycho-behavioral measures over the two weeks prior, and four weeks following influenza vaccination. IgG responses to vaccination were measured via antigen microarray and seroprotection via hemagglutination inhibition assays at 4 and 16weeks post-vaccination. High pre-vaccination seroprotection levels were observed for H3N2 and B viral strains. Positive mood on the day of vaccination was a significant predictor of H1N1 seroprotection at 16weeks post-vaccination and IgG responses to vaccination at 4 and 16weeks post-vaccination, controlling for age and gender. Positive mood across the 6-week observation period was also significantly associated with post-vaccination H1N1 seroprotection and IgG responses to vaccination at 16weeks post-vaccination, but in regression models the proportion of variance explained was lower than for positive mood on the day of vaccination alone. No other factors were found to significantly predict antibody responses to vaccination. Greater positive mood in older adults, particularly on the day of vaccination, is associated with enhanced responses to vaccination.

Determinants of motivation to quit in smokers screened for the early detection of lung cancer: a qualitative study.

BACKGROUND: The promotion of smoking cessation within lung cancer screening could lead to benefits for smoking-related disease and improve cost-effectiveness of screening. Little is known about how smokers respond to lung cancer screening and how this impacts smoking behaviour. We aimed to understand how lung cancer screening influences individual motivations about smoking, including in those who have stopped smoking since screening. METHODS: Thirty one long-term smokers aged 51-74 took part in semi-structured interviews about smoking. They had been screened with the EarlyCDT-Lung Test (13 positive result; 18 negative) as part of the Early Cancer Detection Test Lung Cancer Scotland Study. They were purposively sampled for interview based on their self-reported post-screening smoking behaviour. Eleven participants had stopped smoking since screening. Verbatim interview transcripts were analysed using thematic analysis. RESULTS: Two key overarching themes were interpretations of screening test results and emotional responses to those interpretations. Participants' understanding of the risk implied by their test result was often inaccurate, for example a negative result interpreted as an 'all-clear' from lung cancer and a positive result as meaning lung cancer would definitely develop. Those interpretations led to emotional responses (fear, shock, worry, relief, indifference) influencing motivations about smoking. Other themes included a wake-up call causing changes in perceived risk of smoking-related disease, a feeling that now is the time to stop smoking and family influences. There was no clear pattern in smoking motivations in those who received positive or negative test results. Of those who had stopped smoking, some cited screening experiences as the sole motivation, some cited screening along with other coinciding factors, and others cited non-screening reasons. Cues to change were experienced at different stages of the screening process. Some participants indicated they underwent screening to try and stop smoking, while others expressed little or no desire to stop. CONCLUSIONS: We observed complex and individualised motivations about smoking following lung cancer screening. To be most effective, smoking cessation support in this context should explore understanding of screening test results and may need to be highly tailored to individual emotional responses to screening.

Stress, Illness Perceptions, Behaviors, and Healing in Venous Leg Ulcers: Findings From a Prospective Observational Study.

OBJECTIVE: The aim of the study was to investigate the impact of stress, illness perceptions, and behaviors on healing of venous leg ulcers. METHODS: A prospective observational study of 63 individuals for 24 weeks investigated possible psychosocial predictors of healing. There were two indices of healing: rate of change in ulcer area and number of weeks to heal. Psychological variables were assessed at baseline using self-report measures (Perceived Stress Scale, Hospital Anxiety and Depression Scale, Revised Illness Perception Questionnaire, adapted Summary of Diabetes Self-Care Activities, Adherence Questionnaire, and Short-Form Health Survey). RESULTS: Controlling for sociodemographic and clinical variables, for the 24 weeks, a slower rate of change in ulcer area was predicted by greater stress (standardized ß = -0.61, p = .008), depression (standardized ß = -0.51, p = .039), and holding negative perceptions or beliefs about the ulcer (standardized ß = -1.4, p = .045). By 24 weeks, 69% of ulcers had closed. A more negative emotional response to the ulcer at baseline (i.e., emotional representation of the ulcer) was associated with a greater number of weeks to heal (hazard ratio [HR] = 0.63, 95% confidence interval [CI] = 0.41-0.95, p = .028). Higher educational attainment (HR = 3.22, 95% CI = 1.37-7.55, p = .007) and better adherence to compression bandaging (HR = 1.41, 95% CI = 1.06-1.88, p = .019) were associated with fewer weeks to heal. No other psychosocial variable (stress, perceptions about the ulcer, health behaviors) predicted weeks to heal. CONCLUSIONS: Alongside ulcer-related predictors, psychological and sociodemographic factors were associated with healing. Future research should explore mediating mechanisms underlying these associations and develop interventions to target these variables.

Detection in blood of autoantibodies to tumour antigens as a case-finding method in lung cancer using the EarlyCDT®-Lung Test (ECLS): study protocol for a randomized controlled trial.

BACKGROUND: Lung cancer is the most common cause of cancer related death worldwide. The majority of cases are detected at a late stage when prognosis is poor. The EarlyCDT®-Lung Test detects autoantibodies to abnormal cell surface proteins in the earliest stages of the disease which may allow tumour detection at an earlier stage thus altering prognosis. The primary research question is: Does using the EarlyCDT®-Lung Test to identify those at high risk of lung cancer, followed by X-ray and computed tomography (CT) scanning, reduce the incidence of patients with late-stage lung cancer (III & IV) or unclassified presentation (U) at diagnosis, compared to standard practice? METHODS: A randomised controlled trial of 12 000 participants in areas of Scotland targeting general practices serving patients in the most deprived quintile of the Scottish Index of Multiple Deprivation. Adults aged 50-75 who are at high risk of lung cancer and healthy enough to undergo potentially curative therapy (Performance Status 0-2) are eligible to participate. The intervention is the EarlyCDT®-Lung Test, followed by X-ray and CT in those with a positive result. The comparator is standard clinical practice in the UK. The primary outcome is the difference, after 24 months, between the rates of patients with stage III, IV or unclassified lung cancer at diagnosis. The secondary outcomes include: all-cause mortality; disease specific mortality; a range of morbidity outcomes; cost-effectiveness and measures examining the psychological and behavioural consequences of screening. Participants with a positive test result but for whom the CT scan does not lead to a lung cancer diagnosis will be offered 6 monthly thoracic CTs for 24 months. An initial chest X-ray will be used to determine the speed and the need for contrast in the first screening CT. Participants who are found to have lung cancer will be followed-up to assess both time to diagnosis and stage of disease at diagnosis. DISCUSSION: The study will determine the clinical and cost effectiveness of EarlyCDT®-Lung Test for early lung cancer detection and assess its suitability for a large-scale, accredited screening service. The study will also assess the potential psychological and behavioural harms arising from false positive or false negative results, as well as the potential benefits to patients of true negative EarlyCDT lung test results. A cost-effectiveness model of lung cancer screening based on the results of the EarlyCDT Lung Test study will be developed. TRIAL REGISTRATION: NCT01925625 . August 19, 2013.

The effects of expressive writing before or after punch biopsy on wound healing.

OBJECTIVE: Recent studies have shown that written emotional disclosure (expressive writing) performed in the two weeks prior to wounding improves healing of punch biopsy wounds. In many clinical settings, it would be more practical for patients to perform this intervention after wounding. The aim of this study was to investigate whether expressive writing could speed the healing of punch biopsy wounds if writing was performed after wounds were made. METHODS: One hundred and twenty-two healthy participants aged between 18 and 55years were randomly allocated to one of four groups in a 2 (intervention) by 2 (timing) design. Participants performed either expressive writing or neutral writing, either before or after receiving a 4mm punch biopsy wound. Wounds were photographed on day 10 (primary endpoint) and day 14 after the biopsy to measure epithelisation. Participants also completed questionnaires on stress and affect two weeks prior to the biopsy, on the day of biopsy and two weeks after biopsy. RESULTS: There was a significant difference in healing at day 10 between groups, χ2(3, N=97)=8.84, p=0.032. A significantly greater proportion of participants who performed expressive writing before the biopsy had fully reepithelialised wounds on day 10 compared to participants who performed neutral writing either before or after wounding, with no other significant differences between groups. Amongst people who wrote expressively after wounding, those who finished writing over the first 6days were significantly more likely to be healed at 14days than those who finished writing later. There were significant differences in positive and negative affect over the healing period between the pre and post expressive writing groups. CONCLUSIONS: Expressive writing can improve healing if it is performed prior to wounding. Performing expressive writing after wounding may be able to improve healing depending on the timing of writing and wound assessment. Expressive writing causes affect to worsen followed by subsequent improvement and it is important to consider this in the timing of intervention delivery. Further research with patient groups is required to determine the clinical relevance of these findings.

'What ever I do it's a lost cause.' The emotional and behavioural experiences of individuals who are ulcer free living with the threat of developing further diabetic foot ulcers: a qualitative interview study.

OBJECTIVE: Individuals who have had one diabetic foot ulcer (DFU) are at high risk for developing further DFUs. This study was designed to examine the emotional and behavioural consequences of living with this heightened risk of re-ulceration. PARTICIPANTS AND SETTING: Fifteen women and men living in south-west England were interviewed at home or at the university by an academic psychologist. DESIGN: Interviews were audiotaped and transcribed verbatim. Thematic analysis using the constant comparative method was employed for data analysis. RESULTS: Participants reported having little perceived control in preventing further DFUs. This lack of control was associated with a range of negative emotions including fears and worries about developing further foot ulcers, amputation and guilt for the past neglect. Tensions were present between participants' beliefs and reported behaviours, that is, what they felt they ought to be doing and what they were actually doing to care for their feet; most engaged in 'strategic adherence', that is, conducting a trade-off between living a normal life and following foot-care advice. CONCLUSION: A lack of perceived control appears central to the emotional and behavioural responses of individuals living with the threat of re-ulceration. We propose that these responses may serve to increase individuals' risk of re-ulceration and that these 'risk factors' should be considered part of the management of this patient group.