Monoallelic variation in DHX9, the gene encoding the DExH-box helicase DHX9, underlies neurodevelopment disorders and Charcot-Marie-Tooth disease.

DExD/H-box RNA helicases (DDX/DHX) are encoded by a large paralogous gene family; in a subset of these human helicase genes, pathogenic variation causes neurodevelopmental disorder (NDD) traits and cancer. DHX9 encodes a BRCA1-interacting nuclear helicase regulating transcription, R-loops, and homologous recombination and exhibits the highest mutational constraint of all DDX/DHX paralogs but remains unassociated with disease traits in OMIM. Using exome sequencing and family-based rare-variant analyses, we identified 20 individuals with de novo, ultra-rare, heterozygous missense or loss-of-function (LoF) DHX9 variant alleles. Phenotypes ranged from NDDs to the distal symmetric polyneuropathy axonal Charcot-Marie-Tooth disease (CMT2). Quantitative Human Phenotype Ontology (HPO) analysis demonstrated genotype-phenotype correlations with LoF variants causing mild NDD phenotypes and nuclear localization signal (NLS) missense variants causing severe NDD. We investigated DHX9 variant-associated cellular phenotypes in human cell lines. Whereas wild-type DHX9 was restricted to the nucleus, NLS missense variants abnormally accumulated in the cytoplasm. Fibroblasts from an individual with an NLS variant also showed abnormal cytoplasmic DHX9 accumulation. CMT2-associated missense variants caused aberrant nucleolar DHX9 accumulation, a phenomenon previously associated with cellular stress. Two NDD-associated variants, p.Gly411Glu and p.Arg761Gln, altered DHX9 ATPase activity. The severe NDD-associated variant p.Arg141Gln did not affect DHX9 localization but instead increased R-loop levels and double-stranded DNA breaks. Dhx9-/- mice exhibited hypoactivity in novel environments, tremor, and sensorineural hearing loss. All together, these results establish DHX9 as a critical regulator of mammalian neurodevelopment and neuronal homeostasis.

'Eczema shouldn't control you; you should control eczema': qualitative process evaluation of online behavioural interventions to support young people and parents/carers of children with eczema.

BACKGROUND: There is a lack of well-conducted randomized controlled trials evaluating the effectiveness of theory-based online interventions for eczema. To address these deficiencies, we previously developed and demonstrated the effectiveness of two online behavioural interventions: Eczema Care Online for parents/carers of children with eczema, and Eczema Care Online for young people with eczema. OBJECTIVES: To explore the views and experiences of people who have used the Eczema Care Online interventions to provide insights into how the interventions worked and identify contextual factors that may impede users' engagement with the interventions. METHODS: Qualitative semistructured interviews were conducted with 17 parents/carers of children with eczema and 17 young people with eczema. Participants were purposively sampled from two randomized controlled trials of the interventions and recruited from GP surgeries in England. Transcripts were analysed using inductive thematic analysis, and intervention modifications were identified using the person-based approach table of changes method. RESULTS: Both young people and parents/carers found the interventions easy to use, relatable and trustworthy, and perceived that they helped them to manage their eczema, thus suggesting that Eczema Care Online may be acceptable to its target groups. Our analysis suggested that the interventions may reduce eczema severity by facilitating empowerment among its users, specifically through improved understanding of, and confidence in, eczema management, reduced treatment concerns, and improved treatment adherence and management of irritants/triggers. Reading about the experiences of others with eczema helped people to feel 'normal' and less alone. Some (mainly young people) expressed firmly held negative beliefs about topical corticosteroids, views that were not influenced by the intervention. Minor improvements to the design and navigation of the Eczema Care Online interventions and content changes were identified and made, ready for wider implementation. CONCLUSIONS: People with eczema and their families can benefit from reliable information, specifically information on the best and safest ways to use their eczema treatments early in their eczema journey. Together, our findings from this study and the corresponding trials suggest wider implementation of Eczema Care Online (EczemaCareOnline.org.uk) is justified.

Efficacy, Use, and Acceptability of a Web-Based Self-management Intervention Designed to Maximize Sexual Well-being in Men Living With Prostate Cancer: Single-Arm Experimental Study.

BACKGROUND: Sexual dysfunction is a frequent side effect associated with different prostate cancer treatment approaches. It can have a substantial impact on men and their partners and is associated with increased psychological morbidity. Despite this, sexual concerns are often not adequately addressed in routine practice. Evidence-based web-based interventions have the potential to provide ongoing information and sexual well-being support throughout all stages of care. OBJECTIVE: The aim of this study is to examine the efficacy of a web-based self-management intervention designed to maximize sexual well-being in men living with prostate cancer and explore user perspectives on usability and acceptability. METHODS: We used a single-arm study design, and participants were provided with access to the 5-step intervention for a period of 3 months. The intervention content was tailored based on responses to brief screening questions on treatment type, relationship status, and sexual orientation. Efficacy was assessed by using two-tailed, paired sample t tests for comparing the mean differences between pre- and postintervention measurements for exploring the participants' self-reported knowledge and understanding, sexual satisfaction, and comfort in discussing sexual issues. Usability and acceptability were determined based on the program use data and a postintervention survey for exploring perceived usefulness. RESULTS: A total of 109 participants were recruited for this study. Significant postintervention improvements at follow-up were observed in the total scores (out of 20) from the survey (mean 12.23/20 points, SD 2.46 vs mean 13.62/20, SD 2.31; t88=9.570; P=.001) as well as in individual item scores on the extent to which the participants agreed that they had sufficient information to manage the impact that prostate cancer had on their sex life (mean 2.31/4 points, SD 0.86 vs mean 2.57/4, SD 0.85; t88=3.660; P=.001) and had the potential to have a satisfying sex life following treatment (mean 2.38/4 points, SD 0.79 vs mean 3.17/4, SD 0.78; t88=7.643; P=.001). The median number of intervention sessions was 3 (range 1-11), and intervention sessions had a median duration of 22 minutes (range 8-77). Acceptable usability scores were reported, with the highest result observed for the question on the extent to which the intervention provided relevant information. CONCLUSIONS: This study provides evidence on the efficacy of a tailored web-based intervention for maximizing sexual well-being in men living with prostate cancer. The results indicate that the intervention may improve one's self-perceived knowledge and understanding of how to manage sexual issues and increase self-efficacy or the belief that a satisfactory sex life could be achieved following treatment. The findings will be used to refine the intervention content before testing as part of a larger longitudinal study for examining its effectiveness.

Development and implementation of an online intervention and embedded decision aid to support self-management of acne vulgaris: qualitative interviews with healthcare professionals.

BACKGROUND: Acne is common and has a significant impact on quality of life. Topical treatments are first-line and effective, but non-adherence is common due to slow onset of action, or lack of advice on how to manage side effects. AIM: The Acne Care Online programme is developing an online intervention to support acne self-management and help-seeking. This project aims to explore experiences and views of healthcare professionals (HCPs) treating acne to assess the acceptability and feasibility of implementing this intervention and embedded decision aid in practice. METHOD: This qualitative study recruited HCPs working in general practice. Email invitations were sent to eight research-active practices in Southwest England, and snowball sampling was used. Purposive sampling was used to seek diverse participants. Semi-structured virtual interviews were conducted, audio-recorded, and transcribed. Data were explored using thematic analysis. RESULTS: Nine interviews were conducted, including seven GPs, one nurse, and one pharmacist. Findings highlighted challenges faced by HCPs managing acne in time-limited consultations, particularly around patients' limited understanding of effective treatments, frequent requests from patients for non-first-line treatments, treatment non-adherence, and addressing psychosocial impact. The intervention and embedded decision aid were perceived as beneficial in addressing these challenges, improving shared decision making, and providing a reliable resource for patients. Interviewees suggested integrating the intervention into electronic practice templates for effective implementation. CONCLUSION: HCPs were positive about the potential for the intervention to be implemented as a useful tool in practice. Potential implementation barriers need to be considered, such as making the intervention quick to access in time-limited consultations.

White matter microstructure of children with sensory over-responsivity is associated with affective behavior.

BACKGROUND: Sensory processing dysfunction (SPD) is linked to altered white matter (WM) microstructure in school-age children. Sensory over-responsivity (SOR), a form of SPD, affects at least 2.5% of all children and has substantial deleterious impact on learning and mental health. However, SOR has not been well studied using microstructural imaging such as diffusion MRI (dMRI). Since SOR involves hypersensitivity to external stimuli, we test the hypothesis that children with SOR require compensatory neuroplasticity in the form of superior WM microstructural integrity to protect against internalizing behavior, leaving those with impaired WM microstructure vulnerable to somatization and depression. METHODS: Children ages 8-12 years old with neurodevelopmental concerns were assessed for SOR using a comprehensive structured clinical evaluation, the Sensory Processing 3 Dimensions Assessment, and underwent 3 Tesla MRI with multishell multiband dMRI. Tract-based spatial statistics was used to measure diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) metrics from global WM and nineteen selected WM tracts. Correlations of DTI and NODDI measures with measures of somatization and emotional disturbance from the Behavioral Assessment System for Children, 3rd edition (BASC-3), were computed in the SOR group and in matched children with neurodevelopmental concerns but not SOR. RESULTS: Global WM fractional anisotropy (FA) is negatively correlated with somatization and with emotional disturbance in the SOR group but not the non-SOR group. Also observed in children with SOR are positive correlations of radial diffusivity (RD) and free water fraction (FISO) with somatization and, in most cases, emotional disturbance. These effects are significant in boys with SOR, whereas the study is underpowered for girls. The most affected white matter are medial lemniscus and internal capsule sensory tracts, although effects of SOR are observed in many cerebral, cerebellar, and brainstem tracts. CONCLUSION: White matter microstructure is related to affective behavior in children with SOR.

Online behavioural interventions for children and young people with eczema: a quantitative evaluation.

BACKGROUND: Two online behavioural interventions (one website for parents/carers of children with eczema; and one for young people with eczema) have been shown in randomised controlled trials to facilitate a sustained improvement in eczema severity. AIM: To describe intervention use and examine potential mediators of intervention outcomes and contextual factors that may influence intervention delivery and outcomes. DESIGN AND SETTING: Quantitative process evaluation in UK primary care. METHOD: Parents/carers and young people were recruited through primary care. Intervention use was recorded and summarised descriptively. Logistic regression explored sociodemographic and other factors associated with intervention engagement. Mediation analysis investigated whether patient enablement (ability to understand and cope with health issues), treatment use, and barriers to adherence were mediators of intervention effect. Subgroup analysis compared intervention effects among pre-specified participant subsets. RESULTS: A total of 340 parents/carers and 337 young people were recruited. Most parents/carers (87%, n = 148/171) and young people (91%, n = 153/168) in the intervention group viewed the core introduction by 24 weeks. At 24 weeks, users had spent approximately 20 minutes on average on the interventions. Among parents/carers, greater intervention engagement was associated with higher education levels, uncertainty about carrying out treatments, and doubts about treatment efficacy at baseline. Among young people, higher intervention use was associated with higher baseline eczema severity. Patient enablement (the ability to understand and cope with health issues) accounted for approximately 30% of the intervention effect among parents/carers and 50% among young people. CONCLUSION: This study demonstrated that positive intervention outcomes depended on a modest time commitment from users. This provides further support that the wider implementation of Eczema Care Online is justified.

Cost-effectiveness of two online interventions supporting self-care for eczema for parents/carers and young people.

OBJECTIVE: To estimate the cost-effectiveness of online behavioral interventions (EczemaCareOnline.org.uk) designed to support eczema self-care management for parents/carers and young people from an NHS perspective. METHODS: Two within-trial economic evaluations, using regression-based approaches, adjusting for baseline and pre-specified confounder variables, were undertaken alongside two independent, pragmatic, parallel group, unmasked randomized controlled trials, recruiting through primary care. Trial 1 recruited 340 parents/carers of children aged 0-12 years and Trial 2 337 young people aged 13-25 years with eczema scored ≥ 5 on Patient-Oriented Eczema Measure (POEM). Participants were randomized (1:1) to online intervention plus usual care or usual care alone. Resource use, collected via medical notes review, was valued using published unit costs in UK £Sterling 2021. Quality-of-life was elicited using proxy CHU-9D in Trial 1 and self-report EQ-5D-5L in Trial 2. RESULTS: The intervention was dominant (cost saving and more effective) with a high probability of cost-effectiveness (> 68%) in most analyses. The exception was the complete case cost-utility analysis for Trial 1 (omitting participants with children aged < 2), with adjusted incremental cost savings of -£34.15 (95% CI - 104.54 to 36.24) and incremental QALYs of - 0.003 (95% CI - 0.021 to 0.015) producing an incremental cost per QALY of £12,466. In the secondary combined (Trials 1 and 2) cost-effectiveness analysis, the adjusted incremental cost was -£20.35 (95% CI - 55.41 to 14.70) with incremental success (≥ 2-point change on POEM) of 10.3% (95% CI 2.3-18.1%). CONCLUSION: The free at point of use online eczema self-management intervention was low cost to run and cost-effective. TRIAL REGISTRATION: This trial was registered prospectively with the ISRCTN registry (ISRCTN79282252). URL www.EczemaCareOnline.org.uk .

Patient perceptions of empathy in primary care telephone consultations: A mixed methods study.

OBJECTIVE: Clinical empathy can enhance patient outcomes. This study examined patients' perceptions of empathy in primary care consultations delivered by telephone. METHODS: A mixed methods study was nested in a larger feasibility study conducted May-October 2020. Adults reporting a UK primary care consultation in the previous 2 weeks completed an online survey. A sample of survey respondents participated in a semi-structured qualitative interview. Interviews were analysed thematically. RESULTS: Survey respondents (n = 359) rated practitioners as between 'good' and 'very good' at established patient-reported indicators of clinical empathy. Telephone consultations were rated slightly lower than face-to-face or other consultations. 30 survey respondents were interviewed. Three qualitative themes identified how telephone consultations can shape clinical empathy: setting for an empathic encounter; feeling connected; being acknowledged. CONCLUSION: Primary care patients typically perceive good levels of clinical empathy in telephone consultations; specific features of telephone consultations may facilitate and/or hinder clinical empathy. PRACTICE IMPLICATIONS: To ensure patients feel listened to, acknowledged and understood, practitioners may need to increase their empathic verbalisations in telephone consultations. By using verbal responses to demonstrate active listening and by clearly describing and/or implementing next steps in management, practitioners may be able to enhance clinical empathy in telephone consultations.

A randomised controlled trial of a digital intervention (Renewed) to support symptom management, wellbeing and quality of life in cancer survivors.

BACKGROUND: Many cancer survivors following primary treatment have prolonged poor quality of life. AIM: To determine the effectiveness of a bespoke digital intervention to support cancer survivors. DESIGN: Pragmatic parallel open randomised trial. SETTING: UK general practices. METHODS: People having finished primary treatment (<= 10 years previously) for colo-rectal, breast or prostate cancers, with European-Organization-for-Research-and-Treatment-of-Cancer QLQ-C30 score <85, were randomised by online software to: 1)detailed 'generic' digital NHS support ('LiveWell';n=906), 2) a bespoke complex digital intervention ('Renewed';n=903) addressing symptom management, physical activity, diet, weight loss, distress, or 3) 'Renewed-with-support' (n=903): 'Renewed' with additional brief email and telephone support. RESULTS: Mixed linear regression provided estimates of the differences between each intervention group and generic advice: at 6 months (primary time point: n's respectively 806;749;705) all groups improved, with no significant between-group differences for EORTC QLQ-C30, but global health improved more in both intervention groups. By 12 months there were: small improvements in EORTC QLQ-C30 for Renewed-with-support (versus generic advice: 1.42, 95% CIs 0.33-2.51); both groups improved global health (12 months: renewed: 3.06, 1.39-4.74; renewed-with-support: 2.78, 1.08-4.48), dyspnoea, constipation, and enablement, and lower NHS costs (generic advice £265: in comparison respectively £141 (153-128) and £77 (90-65) lower); and for Renewed-with-support improvement in several other symptom subscales. No harms were identified. CONCLUSION: Cancer survivors quality of life improved with detailed generic online support. Robustly developed bespoke digital support provides limited additional short term benefit, but additional longer term improvement in global health enablement and symptom management, with substantially lower NHS costs.

Promoting smoking cessation during pregnancy: A feasibility and pilot trial of a digital storytelling intervention delivered via text-messaging.

OBJECTIVE: Smoking during pregnancy causes risks to mother and infant health. We investigated the feasibility and likely success of SKIP-IT, a narrative and picture-based smoking cessation intervention delivered via text messages. METHODS: A feasibility and pilot trial. We aimed to recruit 70 pregnant women who smoked, randomised to usual care alone, or usual care and the SKIP-IT intervention, between 12 weeks of pregnancy and 6 weeks post due-date. Outcomes assessed were recruitment, retention, acceptability of, and engagement with the intervention, smoking behaviour, intentions, perceived risk, and self-efficacy. RESULTS: Of 312 women initially approached by smoking cessation services only 54 (17%) agreed to be contacted by the research team. Twenty were then either ineligible or uncontactable and 28 (82%) participated. Most women reported texts to be entertaining and helpful. The proportion of women not smoking at follow-up was lower in the intervention group, but numbers were too small to draw conclusions about effectiveness. CONCLUSION: The intervention was acceptable, but difficulty in making initial and follow-up contacts meant our methods were unfeasible for a larger trial. PRACTICE IMPLICATIONS: Digital Storytelling interventions could help women quit smoking, but further research is required to identify alternative methods for studies with pregnant women who smoke.

Brief Report: Characterization of Sensory Over-Responsivity in a Broad Neurodevelopmental Concern Cohort Using the Sensory Processing Three Dimensions (SP3D) Assessment.

Sensory Over-Responsivity (SOR) is an increasingly recognized challenge among children with neurodevelopmental concerns (NDC). To investigate, we characterized the incidence of auditory and tactile over-responsivity (AOR, TOR) among 82 children with NDC. We found that 70% of caregivers reported concern for their child's sensory reactions. Direct assessment further revealed that 54% of the NDC population expressed AOR, TOR, or both - which persisted regardless of autism spectrum disorder (ASD) diagnosis. These findings support the high prevalence of SOR as well as its lack of specificity to ASD. Additionally, AOR is revealed to be over twice as prevalent as TOR. These conclusions present several avenues for further exploration, including deeper analysis of the neural mechanisms and genetic contributors to sensory processing challenges.

Eczema Care Online: development and qualitative optimisation of an online behavioural intervention to support self-management in young people with eczema.

OBJECTIVES: To describe the development of Eczema Care Online (ECO), an online behaviour change intervention for young people with eczema (phase I); and explore and optimise the acceptability of ECO among this target group using think-aloud interviews (phase II). METHODS: Theory-based, evidence-based and person-based approaches to intervention development were used. In phase I, a qualitative systematic review and qualitative interviews developed an in-depth understanding of the needs and challenges of young people with eczema. Guiding principles highlighted key intervention design objectives and features to address the needs of this target group to maximise user engagement. Behavioural analysis and logic modelling developed ECO's hypothesised programme theory. In phase II, qualitative think-aloud interviews were carried out with 28 young people with eczema and the intervention was optimised based on their feedback. RESULTS: The final intervention aimed to reduce eczema severity by supporting treatment use (emollients, topical corticosteroids/topical calcineurin inhibitors), management of irritants/triggers, emotional management and reducing scratching. Generally, young people expressed positive views of intervention content and design in think-aloud interviews. Quotes and stories from other young people with eczema and ECO's focus on living with eczema (not just topical treatments) were valuable for normalising eczema. Young people believed ECO addressed knowledge gaps they had from childhood and the safety information about topical corticosteroids was reassuring. Negative feedback was used to modify ECO. CONCLUSIONS: A prototype of the ECO intervention was developed using rigorous and complementary intervention development approaches. Subsequent think-aloud interviews helped optimise the intervention, demonstrated ECO is likely to be acceptable to this target group, and provided support for our guiding principles including key design objectives and features to consider when developing interventions for this population. A randomised controlled trial and process evaluation of the intervention is underway to assess effectiveness and explore user engagement with the intervention's behavioural goals.

Supporting families managing childhood eczema: developing and optimising eczema care online using qualitative research.

BACKGROUND: Childhood eczema is often poorly controlled owing to underuse of emollients and topical corticosteroids (TCS). Parents/carers report practical and psychosocial barriers to managing their child's eczema, including child resistance. Online interventions could potentially support parents/carers; however, rigorous research developing such interventions has been limited. AIM: To develop an online behavioural intervention to help parents/carers manage and co-manage their child's eczema. DESIGN AND SETTING: Intervention development using a theory-, evidence-, and person-based approach (PBA) with qualitative research. METHOD: A systematic review and qualitative synthesis of studies (n = 32) and interviews with parents/carers (n = 30) were used to identify barriers and facilitators to effective eczema management, and a prototype intervention was developed. Think-aloud interviews with parents/carers (n = 25) were then used to optimise the intervention to increase its acceptability and feasibility. RESULTS: Qualitative research identified that parents/carers had concerns about using emollients and TCS, incomplete knowledge and skills around managing eczema, and reluctance to transitioning to co-managing eczema with their child. Think-aloud interviews highlighted that, while experienced parents/carers felt they knew how to manage eczema, some information about how to use treatments was still new. Techniques for addressing barriers included providing a rationale explaining how emollients and TCS work, demonstrating how to use treatments, and highlighting that the intervention provided new, up-to-date information. CONCLUSION: Parents/carers need support in effectively managing and co-managing their child's eczema. The key output of this research is Eczema Care Online for Families, an online intervention for parents/carers of children with eczema, which is being evaluated in a randomised trial.

Eczema Care Online behavioural interventions to support self-care for children and young people: two independent, pragmatic, randomised controlled trials.

OBJECTIVE: To determine the effectiveness of two online behavioural interventions, one for parents and carers and one for young people, to support eczema self-management. DESIGN: Two independent, pragmatic, parallel group, unmasked, randomised controlled trials. SETTING: 98 general practices in England. PARTICIPANTS: Parents and carers of children (0-12 years) with eczema (trial 1) and young people (13-25 years) with eczema (trial 2), excluding people with inactive or very mild eczema (≤5 on POEM, the Patient-Oriented Eczema Measure). INTERVENTIONS: Participants were randomised (1:1) using online software to receive usual eczema care or an online (www.EczemaCareOnline.org.uk) behavioural intervention for eczema plus usual care. MAIN OUTCOME MEASURES: Primary outcome was eczema symptoms rated using POEM (range 0-28, with 28 being very severe) every four weeks over 24 weeks. Outcomes were reported by parents or carers for children and by self-report for young people. Secondary outcomes included POEM score every four weeks over 52 weeks, quality of life, eczema control, itch intensity (young people only), patient enablement, treatment use, perceived barriers to treatment use, and intervention use. Analyses were carried out separately for the two trials and according to intention-to-treat principles. RESULTS: 340 parents or carers of children (169 usual care; 171 intervention) and 337 young people (169 usual care; 168 intervention) were randomised. The mean baseline POEM score was 12.8 (standard deviation 5.3) for parents and carers and 15.2 (5.4) for young people. Three young people withdrew from follow-up but did not withdraw their data. All randomised participants were included in the analyses. At 24 weeks, follow-up rates were 91.5% (311/340) for parents or carers and 90.2% (304/337) for young people. After controlling for baseline eczema severity and confounders, compared with usual care groups over 24 weeks, eczema severity improved in the intervention groups: mean difference in POEM score -1.5 (95% confidence interval -2.5 to -0.6; P=0.002) for parents or carers and -1.9 (-3.0 to -0.8; P<0.001) for young people. The number needed to treat to achieve a 2.5 difference in POEM score at 24 weeks was 6 in both trials. Improvements were sustained to 52 weeks in both trials. Enablement showed a statistically significant difference favouring the intervention group in both trials: adjusted mean difference at 24 weeks -0.7 (95% confidence interval -1.0 to -0.4) for parents or carers and -0.9 (-1.3 to -0.6) for young people. No harms were identified in either group. CONCLUSIONS: Two online interventions for self-management of eczema aimed at parents or carers of children with eczema and at young people with eczema provide a useful, sustained benefit in managing eczema severity in children and young people when offered in addition to usual eczema care. TRIAL REGISTRATION: ISRCTN registry ISRCTN79282252.

Resonance and localization effects at a dipolar organic semiconductor interface.

The image state manifold of the dipolar organic semiconductor vanadyl naphthalocyanine (VONc) on highly oriented pyrolytic graphite is investigated by angle-resolved two-photon photoemission (AR-TPPE) spectroscopy in the 0-1 monolayer regimes. Interfacial charge-transfer from the image potential state of clean graphite populates a near-resonant VONc anion level, identifiable by the graphite image potential state by its distinct momentum dispersion obtained from AR-TPPE. This affinity level is subject to depolarization by the neighboring molecules, resulting in stabilization of this state with coverage. Near a coverage of one monolayer, a hybrid image potential/anion state is also formed, showing progressive localization with coverage. Intensities for all these features develop rather differently with molecular coverage, pointing towards the different types of charge-transfer interactions at play at this interface.

Designing Support Structures Post Sepsis in Children: Perspectives of the Queensland Paediatric Sepsis Program.

Introduction: Paediatric post sepsis syndrome is poorly defined and causes physical, neurocognitive, psychosocial morbidity, and family dysfunction. Families of sepsis survivors report unmet needs during care. Worldwide, the provision of post sepsis care is in its infancy with limited evidence to design clinical support pathways. Perspective: The Queensland Paediatric Sepsis Program (QPSP) developed a family support structure (FSS) to improve care during all stages of childhood sepsis. It was designed in partnership with consumers guided by information from consumers and it is partly delivered by consumers. Key areas include online, multimodal education for families and the ability to connect with other families affected by sepsis. The FSS is delivered by a multidisciplinary team (MDT) acting with clinicians local to the child. Families can join the FSS registry at any stage of their sepsis journey which connects them to our MDT team and opens opportunities to participate in future research and other initiatives. Improving public awareness is a critical outcome for our consumers and they have co-designed media and digital campaigns. Discussion: The ideal FSS for post sepsis syndrome management is a clinical pathway designed in partnership with consumers of interventions proven to improve outcomes from sepsis that meets their requirements. The QPSP FSS is novel as it is co-designed with, and partly delivered by, consumers with interventions aimed to improve the entire spectrum of morbidities suffered by survivors and their families, not just physical sequelae. Evaluation is embedded in the program and outcomes will guide evolution of the FSS.

Harnessing Placebo Effects in Primary Care: Using the Person-Based Approach to Develop an Online Intervention to Enhance Practitioners' Communication of Clinical Empathy and Realistic Optimism During Consultations.

Background: Empathic communication and positive messages are important components of "placebo" effects and can improve patient outcomes, including pain. Communicating empathy and optimism to patients within consultations may also enhance the effects of verum, i.e., non-placebo, treatments. This is particularly relevant for osteoarthritis, which is common, costly and difficult to manage. Digital interventions can be effective tools for changing practitioner behavior. This paper describes the systematic planning, development and optimization of an online intervention-"Empathico"-to help primary healthcare practitioners enhance their communication of clinical empathy and realistic optimism during consultations. Methods: The Person-Based Approach to intervention development was used. This entailed integrating insights from placebo and behavior change theory and evidence, and conducting primary and secondary qualitative research. Systematic literature reviews identified barriers, facilitators, and promising methods for enhancing clinical empathy and realistic optimism. Qualitative studies explored practitioners' and patients' perspectives, initially on the communication of clinical empathy and realistic optimism and subsequently on different iterations of the Empathico intervention. Insights from the literature reviews, qualitative studies and public contributor input were integrated into a logic model, behavioral analysis and principles that guided intervention development and optimization. Results: The Empathico intervention comprises 7 sections: Introduction, Empathy, Optimism, Application of Empathico for Osteoarthritis, Reflection on my Consultations, Setting Goals and Further Resources. Iterative refinement of Empathico, using feedback from patients and practitioners, resulted in highly positive feedback and helped to (1) contextualize evidence-based recommendations from placebo studies within the complexities of primary healthcare consultations and (2) ensure the intervention addressed practitioners' and patients' concerns and priorities. Conclusions: We have developed an evidence-based, theoretically-grounded intervention that should enable practitioners to better harness placebo effects of communication in consultations. The extensive use of qualitative research throughout the development and optimization process ensured that Empathico is highly acceptable and meaningful to practitioners. This means that practitioners are more likely to engage with Empathico and make changes to enhance their communication of clinical empathy and realistic optimism in clinical practice. Empathico is now ready to be evaluated in a large-scale randomized trial to explore its impact on patient outcomes.

Supporting self-care for eczema: protocol for two randomised controlled trials of ECO (Eczema Care Online) interventions for young people and parents/carers.

INTRODUCTION: Eczema care requires management of triggers and various treatments. We developed two online behavioural interventions to support eczema care called ECO (Eczema Care Online) for young people and ECO for families. This protocol describes two randomised controlled trials (RCTs) aimed to evaluate clinical and cost-effectiveness of the two interventions. METHODS AND ANALYSIS: Design: Two independent, pragmatic, unmasked, parallel group RCTs with internal pilots and nested health economic and process evaluation studies. Setting: Participants will be recruited from general practitioner practices in England. Participants: Young people aged 13-25 years with eczema and parents and carers of children aged 0-12 years with eczema, excluding inactive or very mild eczema (five or less on Patient-Oriented Eczema Measure (POEM)). Interventions: Participants will be randomised to online intervention plus usual care or to usual eczema care alone. Outcome measures: Primary outcome is eczema severity over 24 weeks measured by POEM. Secondary outcomes include POEM 4-weekly for 52 weeks, quality of life, eczema control, itch intensity (young people only), patient enablement, health service and treatment use. Process measures include treatment adherence, barriers to adherence and intervention usage. Our sample sizes of 303 participants per trial are powered to detect a group difference of 2.5 (SD 6.5) in monthly POEM scores over 24 weeks (significance 0.05, power 0.9), allowing for 20% loss to follow-up. Cost-effectiveness analysis will be from a National Health Service and personal social service perspective. Qualitative and quantitative process evaluation will help understand the mechanisms of action and participant experiences and inform implementation. ETHICS AND DISSEMINATION: The study has been approved by South Central Oxford A Research Ethics Committee (19/SC/0351). Recruitment is ongoing, and follow-up will be completed by mid-2022. Findings will be disseminated to participants, the public, dermatology and primary care journals, and policy makers. TRIAL REGISTRATION NUMBER: ISRCTN79282252.

Influence of electrostatic fields on molecular electronic structure: insights for interfacial charge transfer.

Molecular and interfacial electronic structure at organic semiconductor interfaces shows a rich and subtle dependence on short- and long-range electrostatic interactions. Interface dipoles can be controlled making use of the anisotropic charge distribution at the interface, often with direct consequences also for the molecular electronic structure. In this Perspective, we will discuss the emerging understanding of how local and collective electrostatic effects control energy level alignment and molecular electronic structure at organic semiconductor interfaces and highlight some of the ramifications for interfacial charge-transfer dynamics. Attention is paid to the validity of the underlying assumptions inherent to the classical electrostatic approach.

Image states at the interface with a dipolar organic semiconductor.

Image states of the dipolar organic semiconductor vanadyl naphthalocyanine on highly oriented pyrolytic graphite are investigated in the submonolayer to few monolayer regime. The presence of a significant molecular dipole in the organized thin films leads to a strong modification of the image states with coverage. In the 0-1 ML regime, we observe successive stabilization of the image state with increasing coverage. Above 1 ML, a new image state develops, corresponding to the screened interaction at the organic semiconductor/substrate interface. We show that the evolution of the observed image states can be understood on the basis of resonance-enhanced anion formation in the presence of strong electric fields. These data represent a step toward understanding the influence of electrostatic fields on electronic structure at organic semiconductor interfaces.