Burden of disease and treatment patterns in patients with vitiligo: findings from a national longitudinal retrospective study in the UK.

BACKGROUND: UK studies examining vitiligo burden and vitiligo-related healthcare resource utilization (HCRU) are lacking. OBJECTIVE: To describe the incidence and prevalence of vitiligo, the demographic and clinical characteristics of patients with vitiligo, vitiligo burden, HCRU, incidence of mental health comorbidities and management strategies, including treatment patterns. METHODS: This retrospective study used UK Clinical Practice Research Datalink and Hospital Episode Statistics databases to analyse patients with vitiligo from 1 January 2010 to 31 December 2021. RESULTS: Among 17 239 incident patients, mean incidence of vitiligo was 0.16 (2010-2021) per 1000 person-years [PY; range 0.10 (2020-COVID-19) to 0.19 (2010/2013/2018)]; among 66 217 prevalent patients, prevalence increased from 0.21% (2010) to 0.38% (2021). The most common comorbidities recorded after vitiligo diagnosis were diabetes (19.4%), eczema (8.9%), thyroid disease (7.5%) and rheumatoid arthritis (6.9%). Mental health diagnoses recorded at any time included depression and/or anxiety (24.6%), depression (18.5%), anxiety (16.0%) and sleep disturbance (12.7%), and recorded after vitiligo diagnosis in 6.4%, 4.4%, 5.5% and 3.9%, respectively. Mental health comorbidities were more common in White (e.g. depression and/or anxiety 29.0%) than in Black (18.8%) and Asian (16.1%) patients. In adolescents, depression and/or anxiety was most commonly diagnosed after a vitiligo diagnosis than before (7.4% vs. 1.8%). Healthcare resources were used most frequently in the first year after vitiligo diagnosis (incident cohort), typically dermatology-related outpatient appointments (101.9/100 PY) and general practitioner consultations (97.9/100 PY). In the year after diagnosis, 60.8% of incident patients did not receive vitiligo-related treatment (i.e. topical corticosteroids, topical calcineurin inhibitors, oral corticosteroids or phototherapy), increasing to 82.0% the next year; median time from diagnosis to first treatment was 34.0 months (95% confidence interval 31.6-36.4). Antidepressants and/or anxiolytics were recorded for 16.7% of incident patients in the year after diagnosis. In 2019, 85.0% of prevalent patients did not receive vitiligo-related treatments. CONCLUSION: Most patients were not on vitiligo-related treatments within a year of diagnosis, with the time to first treatment exceeding 2 years, suggesting that vitiligo may be dismissed as unimportant. New effective treatments, early initiation and psychological intervention and support are needed to reduce the vitiligo burden on patients.

Vitiligo is a chronic disease in which cells that produce the skin pigment called melanin are attacked, resulting in white or pale patches of skin. It is diagnosed in an estimated 0.2­0.8% of people in Europe. This study aimed to describe how many new cases of vitiligo were recorded between 2010 and 2021 in the UK and the overall percentage of people with vitiligo. Linked national general practitioner (GP) and hospital-based records containing information on medical diagnoses, admissions and hospital visits were used. Records of other diseases and conditions, including mental health conditions, in combination with healthcare service use and treatment prescribed to patients with vitiligo, were studied to describe the impact of living with vitiligo. It was found that 0.16 new cases of vitiligo were recorded per 1000 person-years (for example, 0.16 new cases would have been recorded if 1000 people were followed for 1 year or if 100 people were all followed for 10 years) between 2010 and 2021. In 2021, 0.4% of the population studied had vitiligo. In the 5 years after a new diagnosis of vitiligo, the most common other diseases recorded were diabetes (19%), eczema (9%), thyroid disease (8%) and rheumatoid arthritis (7%), and the most common mental health conditions were depression and/or anxiety (25%). In the year after diagnosis, GP and dermatology outpatient visits were the most common type of medical services used. In 2019, 85% of all individuals with vitiligo were not receiving any vitiligo-related treatment (such as creams or phototherapy). It took approximately 34 months from diagnosis of vitiligo to the start of first treatment. The results suggest that new effective treatments and psychological interventions are needed to reduce the burden of vitiligo.

Drug discovery for heart failure targeting myosin-binding protein C.

Cardiac MyBP-C (cMyBP-C) interacts with actin and myosin to fine-tune cardiac muscle contractility. Phosphorylation of cMyBP-C, which reduces the binding of cMyBP-C to actin and myosin, is often decreased in patients with heart failure (HF) and is cardioprotective in model systems of HF. Therefore, cMyBP-C is a potential target for HF drugs that mimic its phosphorylation and/or perturb its interactions with actin or myosin. We labeled actin with fluorescein-5-maleimide (FMAL) and the C0-C2 fragment of cMyBP-C (cC0-C2) with tetramethylrhodamine (TMR). We performed two complementary high-throughput screens (HTS) on an FDA-approved drug library, to discover small molecules that specifically bind to cMyBP-C and affect its interactions with actin or myosin, using fluorescence lifetime (FLT) detection. We first excited FMAL and detected its FLT, to measure changes in fluorescence resonance energy transfer (FRET) from FMAL (donor) to TMR (acceptor), indicating binding. Using the same samples, we then excited TMR directly, using a longer wavelength laser, to detect the effects of compounds on the environmentally sensitive FLT of TMR, to identify compounds that bind directly to cC0-C2. Secondary assays, performed on selected modulators with the most promising effects in the primary HTS assays, characterized the specificity of these compounds for phosphorylated versus unphosphorylated cC0-C2 and for cC0-C2 versus C1-C2 of fast skeletal muscle (fC1-C2). A subset of identified compounds modulated ATPase activity in cardiac and/or skeletal myofibrils. These assays establish the feasibility of the discovery of small-molecule modulators of the cMyBP-C-actin/myosin interaction, with the ultimate goal of developing therapies for HF.

The effectiveness of mindfulness-based cognitive therapy for social anxiety symptoms in people living with alopecia areata: a single-group case-series design.

BACKGROUND: Alopecia areata (AA) is an immunological disorder characterised by hair loss. Individuals with AA report high levels of social anxiety. One intervention that holds potential for reducing social anxiety in individuals with AA is mindfulness-based cognitive therapy (MBCT). AIMS: Our key aim was to investigate whether MBCT reduces social anxiety in individuals with AA. The study also investigated whether MBCT reduces depression, general anxiety, and increases quality of life and increases trait mindfulness in individuals with AA. METHOD: Five participants with AA took part in an 8-session in-person MBCT intervention. A multiple-baseline single-group case series design was adopted. Idiographic measures of social anxiety were measured each day from baseline, through intervention, to follow-up. Standardised questionnaires of trait mindfulness, social anxiety, depression, anxiety, and quality of life were completed at baseline, post-intervention, and at 4-week follow-up. RESULTS: All participants completed the MBCT course, but one participant was excluded from the idiographic analysis due to a high amount of missing data. The remaining four participants demonstrated reductions in idiographic measures of social anxiety from baseline to follow-up. These effects were larger between baseline and follow-up, than between baseline and post-intervention. Two participants demonstrated significant improvement in standardised measures of wellbeing from baseline to follow-up - they also practised mindfulness most regularly at home between sessions. CONCLUSION: MBCT may be effective in reducing social anxiety and improving wellbeing in individuals with AA, although this might be dependent on the extent to which participants regularly practise mindfulness exercises.

Parent and child experience of skin conditions: relevance for the provision of mindfulness-based interventions.

BACKGROUND: Managing a skin condition can be difficult, and there is a lack of psychological support for children and their families. OBJECTIVES: To identify issues surrounding caring for a child with a skin condition, investigate experiences of current psychological support to gain a sense of what is needed, and determine the relevance of offering mindfulness-based interventions for children and families. MATERIALS AND METHODS: This study employed a mixed inductive and deductive form of qualitative inquiry to understand the experiences and needs of children and families. Twenty-three participants (12 parents/carers: 11 females, 1 male; 11 children: 6 females, 5 males, aged 8-11 years) were recruited with an advert posted on social media. In-depth data were collected from semi-structured interviews. Interviews were recorded, transcribed and analysed with a descriptive form of thematic analysis. RESULTS: Systematic analysis of the data led to five themes being developed: (i) caregiver burden of childhood skin conditions; (ii) skin condition overshadowing childhood; (iii) battling for recognition and lack of support; (iv) naturalistic use and understanding of mindfulness in everyday coping: and (v) openness and relevance of offering mindfulness-based interventions. CONCLUSIONS: Living with a skin condition was reported as being associated with mood disturbance, with impacts on schooling, sleep and daily life. Parents and children expressed a desire for short/accessible interventions that could fit with daily routines and might provide the opportunity to connect with other families. The findings indicate that mindfulness-based interventions may be likely to be accepted, as many participants had experience of using mindful techniques in school, and described that they were naturalistically using 'mindfulness' to manage itch and stress. However, the findings indicate that a number of misconceptions exist about the fundamental nature and aims of mindfulness. Addressing misconceptions related to mindfulness needs to be considered when planning both future studies and service delivery.

Living With Physical Health Conditions: A Systematic Review of Mindfulness-Based Interventions for Children, Adolescents, and Their Parents.

OBJECTIVES: This systematic review aimed to identify and appraise studies investigating the efficacy of mindfulness-based interventions (MBIs) for improving depression, anxiety and parental stress in families affected by childhood physical illnesses, as well as feasibility and acceptability. METHODS: Embase, PsycINFO, Scopus, Medline, and PubMed were searched between February 2 and 17, 2021, and updated on August 5, 2022. Studies investigating MBIs with children and adolescents (<18 years) with physical health conditions were included, and results are presented with narrative synthesis. RESULTS: Eighteen studies met eligibility criteria. Studies included children and adolescents with chronic pain, headaches, cancer, heart conditions, esophageal atresia, inflammatory bowel disease, and polycystic ovary syndrome. Most studies reported mindfulness was feasible and acceptable, although findings for different health conditions were mixed. Some studies encountered difficulties with attrition, resulting in findings being underpowered. CONCLUSIONS: MBIs show promise for improving anxiety and depression in children with physical health conditions, but there is limited support for reducing stress in the family unit. A potential direction for future research might be the inclusion of parents. However, because of the heterogeneity of studies included in this review, findings must be cautiously interpreted.

Mindful parenting intervention for parents of children with skin conditions: a single group experimental cases series.

BACKGROUND: Parents of children with eczema or psoriasis experience high levels of parenting stress, which can negatively impact their child's mental and physical health. AIMS: We aimed to investigate the effectiveness, feasibility and acceptability of a mindful parenting intervention for parents of children with eczema or psoriasis. METHOD: Seven parents of children (4-12 years old) with eczema or psoriasis took part in an 8-week mindful parenting group intervention. A single-case experimental design was adopted, whereby parents completed daily idiographic measures of parenting stress related to their child's skin condition. Parents also completed standardised questionnaires measuring their parenting stress, depression, anxiety and quality of life, and children completed a quality of life measure, at four time points: baseline, pre-intervention, post-intervention and 6-week follow-up. Parents provided qualitative feedback after the intervention. RESULTS: All parents completed the intervention and showed improvements in idiographic measures of parenting stress from baseline to follow-up. Improvements in parenting stress were larger at follow-up than post-intervention, suggesting the benefits of intervention continue beyond the intervention. Six of seven parent-child dyads showed improvement in at least one of the wellbeing measures, from pre-intervention to post-intervention or follow-up. Feasibility was demonstrated through good participant retention, adherence to home practice, and treatment fidelity. Acceptability was demonstrated through positive parent evaluations of the intervention. CONCLUSIONS: Mindful parenting can be an effective, feasible and acceptable intervention for parents of children with eczema or psoriasis. Future studies should attempt to replicate the findings through randomised controlled trials.

A randomized controlled feasibility trial of online compassion-focused self-help for psoriasis.

BACKGROUND: People with psoriasis can experience psychological distress that might be amenable to psychosocial self-help. OBJECTIVES: This study tested the feasibility and acceptability of two theoretically developed self-help interventions designed to reduce feelings of shame and improve quality of life. METHODS: A randomized controlled feasibility trial was conducted comprising 130 participants with psoriasis who were randomly allocated to receive either compassion-based self-help (n = 65) or mindfulness-based self-help (n = 65), over a 4-week period. Both interventions were provided online. RESULTS: The interventions were found to be acceptable, with over 70% of study completers reporting that they found the materials helpful. Of the 130 participants, 92 completed the study, with attrition at 29%. Both interventions showed modest yet statistically significant reductions in shame (Cohen's d = 0.20) and improvements in quality of life (Cohen's d = 0.40). CONCLUSIONS: Self-help based on compassion and mindfulness is acceptable to users, and can reduce feelings of shame and improve quality of life for people living with psoriasis. What is already known about this topic? Psoriasis can be associated with psychological distress. Various forms of psychological intervention have been tested; however, few compassion based interventions have been developed or trialled. What does this study add? This study demonstrates that compassion-based self-help is acceptable to people with psoriasis. This study provides provisional evidence of effectiveness of compassion based self-help in reducing feelings of shame and improving quality of life for people living with psoriasis.

Cancer and changes in facial appearance: A meta-ethnography of qualitative studies.

INTRODUCTION: Living with an altered facial appearance as a result of treatment for cancer requires considerable psychological adjustment. As such it is essential that health care professionals understand the lived experience of people affected. This systematic review provides a meta-ethnography of studies that have explored the experience of changed facial appearance as a result of cancer. METHODS: A search of four databases (Web of Science, CINAHL, PsycInfo, and Scopus) took place using terms relating to qualitative research, cancer, and changed facial appearance. Thirteen studies were identified, appraised, and included in the synthesis. The findings and interpretations within the studies were subject to meta-ethnography procedures so as to elicit novel cross-cutting themes. FINDINGS: The experience of changed facial appearance after cancer was clustered into three contexts. In the context of the disease, subthemes were the primacy of survival, the changing relationship with the disease, and the impact of the care team on the experience of changed appearance. In the context of the social world, subthemes were positive reactions, negative reactions, and coping strategies. In the context of the self, subthemes were the self under attack, self-to-self relating, the self in the world, and rebuilding the self. CONCLUSIONS: The findings indicate that health care professionals must conduct holistic assessments, so as to fully recognize and where necessary address the impact upon self. The meta-ethnography shows that the experience of facial appearance change following cancer is complex and requires awareness of a number of theoretical areas including identity construction, social support, stigmatization, and the specific literature on visible difference. Statement of contribution What is already known on this subject? Changed facial appearance after cancer can cause significant social difficulties and impact on the sense of self. The experience of managing the specific dual challenges of cancer and altered facial appearance is not clearly understood. Recent studies that have focused specifically on the experience of changes in appearance after cancer have been limited in scope and transferability. What does this study add? To our knowledge, this is the first meta-ethnography to bring together the literature on the impact of altered facial appearance following cancer. Patients may feel unable to talk about appearance with health care professionals because it is seen as a frivolous issue. Clinicians should facilitate open, person-centred opportunities for patients to discuss the impact of changed appearance and where necessary facilitate access to support.

Atomistic Models from Orientation and Distance Constraints Using EPR of a Bifunctional Spin Label.

We have used high-resolution orientation and distance measurements derived from electron paramagnetic resonance of a bifunctional spin label (BSL) to build and refine atomistic models of protein structure. We demonstrate this approach by investigating the effects of nucleotide binding on the structure of myosin's catalytic domain while myosin is in complex with actin. Constraints for orientation of individual helices were obtained in a previous study from continuous-wave electron paramagnetic resonance of myosin labeled at specific sites with BSLs in oriented muscle fibers. In this study, new distance constraints were derived from double electron-electron resonance on myosin constructs labeled with a BSL specifically at two sites. Using these complementary constraints together, we thoroughly characterize the BSL's rigid, highly stereoselective attachment to protein α-helices, which permits accurate measurements of orientation and distance. We also leverage these measurements to derive a novel, to our knowledge, structural model for myosin-II in complex with actin and MgADP and compare our model to other recent actomyosin structures. The described approach is applicable to any orientable complex (e.g., membranes or filaments) in which site-specific di-Cys mutation is feasible.

The role of psychological flexibility in appearance anxiety in people who have experienced a visible burn injury.

BACKGROUND: Individuals with visible differences can experience appearance anxiety that is distressing and disruptive to daily functioning. Understanding psychological factors that maintain appearance anxiety related to scarring is important in developing theoretical understanding of adjustment to injury, and in identifying targets for psychological therapies. This study aimed to investigate whether psychological flexibility, a key element underpinning acceptance and commitment therapy (ACT), was associated with appearance anxiety. It was hypothesised that reduced psychological flexibility (lower acceptance, cognitive defusion, mindfulness, and committed action) would be related to increased appearance anxiety. The role of psychological flexibility in the maintenance of appearance anxiety was investigated using a cross-sectional quantitative questionnaire study. METHOD: Seventy-eight burns patients (47 female, 31 male; M age=45.2years) completed the Derriford Appearance Scale (DAS-24), the Acceptance and Action Questionnaire (AAQ-II), the Cognitive Fusion Questionnaire (CFQ), the Five Facet Mindfulness Questionnaire (FFMQ), and the Committed Action Questionnaire (CAQ-8). RESULTS: As hypothesised, increased appearance anxiety was related to reduced acceptance (rs(76)=0.80, p<0.001, one-tailed) and cognitive defusion (rs(76)=0.76, p<0.001). Reduced levels of mindfully describing (r(72)=-0.39, p<0.001), acting with awareness (r(72)=-0.57, p<0.001), non-judging (r(72)=-0.61, p<0.001) and non-reactivity (r(72)=-0.28, p<0.01) as well as reduced committed action (r(72)=-0.57, p<0.001) were also related to increased appearance anxiety. CONCLUSIONS: Individuals experiencing appearance anxiety associated with a burn injury may struggle with accepting difficult emotions, stepping back from distressing thoughts, being mindful and engaging in valued action. These findings suggest that ACT may be useful in treating appearance related anxiety and concerns associated with conditions causing a visible difference.

Narrative insight in psychosis: The relationship with spiritual and religious explanatory frameworks.

OBJECTIVE: When considering psychosis, the concept of narrative insight has been offered as an alternative to clinical insight in determining individuals' responses to their difficulties, as it allows for a more holistic and person-centred framework to be embraced within professional practice. This study aims to explore the validity of the narrative insight construct within a group of people who have experienced psychosis. DESIGN: Inductive qualitative methods were used to explore how eight participants utilized spiritual or religious explanatory frameworks for their experiences of psychosis and to consider these in relation to the construct of narrative insight. METHODS: Semi-structured interviews were undertaken with individuals who identified themselves as interested in spiritual or religious ideas and whose self-reported experiences which were identified as akin to psychosis by experienced academic clinicians. Transcriptions from these interviews were subject to interpretative phenomenological analysis within a broader research question; a selection of themes and data from the resultant phenomenological structure are explored here for their relevance to narrative insight. RESULTS: Participants discussed spiritual and biological explanations for their experiences and were able to hold alternative potential explanations alongside each other. They were reflective regarding the origins of their explanations and would describe a process of testing and proof in relation to them. CONCLUSIONS: These findings suggest that the narrative insight construct has the potential to be a valid approach to understanding experiences of psychosis, and challenge the dominance of the clinical insight construct within clinical practice. PRACTITIONER POINTS: Clinicians should value the explanatory framework for experiences which are provided by individuals experiencing psychosis, and encourage them to develop a framework which is coherent to their own world view rather than predominantly pursuing a biomedical explanation. Assessments of psychosis should be adapted to include an understanding of the cohesiveness of the individual's explanatory framework and personal value to them, with a reduced focus on their acceptance of biomedical models of 'illness'. Care and care research for individuals experiencing psychosis should consider the value of narrative insight within future developments.

The potential role of mindfulness in psychosocial support for dermatology patients.

While it is widely acknowledged that people living with skin conditions can experience higher levels of psychosocial distress than the general population, access to psychologic support in dermatology is limited. Given the physical and psychosocial consequences of living with skin conditions, interventions used within physical and mental health may be beneficial. Mindfulness, defined as "paying attention in a particular way: on purpose in the present moment and non-judgmentally," has shown promise in improving outcomes in both mental and physical health populations, and studies have implicated a role for mindfulness in improving distress associated with skin conditions. The current review explores the theoretical underpinnings of mindfulness, in particular, the role it may play in reducing physiologic arousal and managing maladaptive thought processes. Although mindfulness interventions offer promise in reducing distress associated with skin conditions, further research is required to fully understand the underlying mechanisms of mindfulness and the active ingredient responsible for improving outcomes in dermatology patients. Mindfulness is one potential psychologic intervention and practitioners should be aware of the range of psychologic support options available. The current review also draws attention to the urgent need for further research into the effectiveness of psychologic interventions for dermatology patients.