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Abstract BackgroundDisruptive behavior disorders are among the most common disorders of childhood, and evidence-based parenting programs are the first-line treatment. Digital microinterventions have been proposed as one possible means of supporting parenting style change by giving parents in-the-moment advice about how to respond to challenging behavior. Until now, no digital microintervention supporting evidence-based parenting skills programs has been evaluated. ObjectiveThe aim of this study is to evaluate the subjective experience of parents using a digital microintervention to support evidence-based parenting skills, with particular attention to acceptability, usability, family relationships, and parents’ values. MethodsWe conducted serial interviews with 11 parents of 33 children before and after spending 3 weeks using an app including 3 digital microinterventions. Parents were recruited via local authorities in the Midlands region of the United Kingdom. Previous participation in a parenting program was an inclusion criterion. Interviews explored family composition; child behavior problems; and experience of using the mobile app, including barriers to use. Thematic analysis was conducted from a user-centered design perspective, and illustrative case vignettes were produced. ResultsMany parents used the app in ways that helped them rather than strictly following the instructions they were given. Parents described a range of barriers to using the app including practical problems and failure to change child behavior. Parents and children responded in a variety of ways to the use of the phone, with many wholeheartedly embracing the convenience of technology. Case vignettes illustrate the uniqueness of each family’s experience. ConclusionsParents’ use of a mobile app supporting evidence-based parenting skills is difficult to predict due to the unique challenges each family encounters. Many parents found it an acceptable and helpful addition to family life, but increased personalization is likely to be key to supporting parents. Future digital microintervention developers should keep in mind that parents are likely to use the app pragmatically rather than following instructions, may struggle to use a complex app under pressure, and are likely to hold complex feelings about parenting with an app.

Maintaining a well-functioning mitochondrial network through the mitochondria quality control (MQC) mechanisms, including biogenesis, dynamics and mitophagy, is crucial for overall health. Mitochondrial dysfunction caused by oxidative stress and further exacerbated by impaired quality control can trigger inflammation through the release of the damage-associated molecular patterns (mtDAMPs). mtDAMPs act by stimulating the cyclic GMP-AMP synthase (cGAS) stimulator of interferon genes (STING) pathway. Recently, aberrant signalling of the cGAS-STING axis has been recognised to be closely associated with several sterile inflammatory diseases (e.g. non-alcoholic fatty liver disease, obesity). This may fit the pathophysiology of hypothyroidism, an endocrine disorder characterised by the reduction of thyroid hormone production associated with impaired metabolic fluxes, oxidative balance and inflammatory status. Both 3,5,3’-triiodo-L-tyronine (T3) and its derivative 3,5-diiodo-L-thyronine (3,5-T2), are known to mitigate processes targeting mitochondria, albeit the underlying mechanisms are not yet fully understood. Therefore, we used a chemically induced hypothyroidism rat model to investigate the effect of 3,5-T2 or T3 administration on inflammation-related factors (inflammatory cytokines, hepatic cGAS-STING pathway), oxidative stress, antioxidant defence enzymes, mitochondrial DNA (mtDNA) damage, release and repair, and the MQC system in the liver. Hypothyroid rats showed: i) increased oxidative stress, ii) accumulation of mtDNA damage, iii) high levels of circulating cytokines, iv) hepatic activation of cGAS-STING pathways and v) impairment of MQC mechanisms and autophagy. Both iodothyronines restored oxidative balance by enhancing antioxidant defence, preventing mtDNA damage through the activation of mtDNA repair mechanisms (OGG1, APE1, and POLγ) and promoting autophagy progression. Concerning MQC, both iodothyronines stimulated mitophagy and dynamics, with 3,5-T2 activating fusion and T3 modulating both fusion and fission processes. Moreover, only T3 enhanced mitochondrial biogenesis. Notably, 3,5-T2, but not T3, reversed the hypothyroidism-induced activation of the cGAS-STING inflammatory cascade. In addition, it is noteworthy that 3,5-T2 seems more effective than T3 in reducing circulating pro-inflammatory cytokines IL-6 and IL-1B and in stimulating the release of IL-10, a known anti-inflammatory cytokine. These findings reveal novel molecular mechanisms of hepatic signalling pathways involved in hypothyroidism, which could be targeted by natural iodothyronines, particularly 3,5-T2, paving the way for the development of new treatment strategies for inflammatory diseases.

Background: Aging implies changes in terms of lung function, immune system, and respiratory and extra-respiratory comorbidities. Few studies have specifically addressed the relevance of age on severe asthma burden and control. We aimed to evaluate whether age acts as an independent determinant of asthma severity, in terms of clinical, functional, and inflammatory profile, and to explore potential cofactors that contribute to a more difficult disease control in different age groups. Methods: Patients from Severe Asthma Network Italy (SANI) registry were retrospectively divided in subgroups according to their age. Cutoffs for age were established according to quartiles in order to obtain a comparable number of patients for each group, and then rounded for the sake of simplicity. Results: Overall, 1805 severe asthma patients were analyzed. Lung function represented the most important age-related variable. On the opposite the level of asthma control was not differently distributed among age ranges. In young people the presence of atopy-related comorbidities (allergic rhinitis, atopic dermatitis) predominated, whilst systemic-metabolic and degenerative comorbidities such as diabetes, cardiovascular diseases, anxious-depressive syndrome, and osteoporosis prevailed in elderly. Bronchiectasis and sleep disturbances were significantly associated with age. Conclusions: Despite that it cannot be considered a treatable trait, our study suggests that age should be evaluated within a personalized approach to severe asthma patients, in order to provide a better clinical profiling and a more tailored treatment strategy.

Abstract The small muscle protein, X-linked (SMPX) gene encodes a cytoskeleton-associated protein, highly expressed in the inner ear hair cells (HCs), possibly regulating auditory function. In the last decade, several mutations in SMPX have been associated with X-chromosomal progressive non syndromic hearing loss in humans and, in line with this, Smpx-deficient animal models, namely zebrafish and mouse, showed significant impairment of inner ear HCs development, maintenance, and functioning. In this work, we uncovered smpx expression in the neuromast mechanosensory HCs of both Anterior and Posterior Lateral Line (ALL and PLL, respectively) of zebrafish larvae and focused our attention on the PLL. Smpx was subcellularly localized throughout the cytoplasm of the HCs, as well as in their primary cilium. Loss-of-function experiments, via both morpholino-mediated gene knockdown and CRISPR/Cas9 F0 gene knockout, revealed that the lack of Smpx led to fewer properly differentiated and functional neuromasts, as well as to a smaller PLL primordium (PLLp), the latter also Smpx-positive. In addition, the kinocilia of Smpx-deficient neuromast HCs appeared structurally and numerically altered. Such phenotypes were associated with a significant reduction in the mechanotransduction activity of the neuromast HCs, in line with their positivity for Smpx. In summary, this work highlights the importance of Smpx in lateral line development and, specifically, in proper HCs differentiation and/or maintenance, and in the mechanotransduction process carried out by the neuromast HCs. Because lateral line HCs are both functionally and structurally analogous to the cochlear HCs, the neuromasts might represent an invaluable—and easily accessible—tool to dissect the role of Smpx in HCs development/functioning and shed light on the underlying mechanisms involved in hearing loss.

Paolo Cameli,1 Maria Aliani,2 Elena Altieri,3 Pietro Bracciale,4 Luisa Brussino,5 Maria Filomena Caiaffa,6 Giorgio Walter Canonica,7,8 Cristiano Caruso,9 Stefano Centanni,10 Maria D’Amato,11 Fausto De Michele,12 Stefano Del Giacco,13 Fabiano Di Marco,14 Girolamo Pelaia,15 Paola Rogliani,16,17 Micaela Romagnoli,18 Pietro Schino,19 Jan Walter Schroeder,20 Gianenrico Senna,21 Alessandra Vultaggio,22 Marco Benci,23 Silvia Boarino,24 Francesco Menzella25 1Respiratory Diseases Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy; 2UO Pneumologia e Pneumologia Riabilitativa, ICS Maugeri, IRCCS Bari, Bari, Italy; 3Reparto di Pneumologia, P.O. Garbagnate Milanese, Garbagnate Milanese (MI), Italy; 4Reparto di Pneumologia, Ospedale Ostuni, Ostuni (BR), Italy; 5Dipartimento di Scienze Mediche, Università degli Studi di Torino; SCDU Immunologia e Allergologia, AO Ordine Mauriziano Umberto I, Torino, Italy; 6Cattedra e Scuola di Allergologia e Immunologia Clinica, Dipartimento di Scienze Mediche, Università di Foggia, Foggia, Italy; 7Department of Biomedical Sciences, Humanitas University, Pieve Emanuele (MI), Italy; 8Personalized Medicine Center: Asthma and Allergology, Humanitas Research Hospital, Rozzano (MI), Italy; 9Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico A. Gemelli, IRCCS, Università Cattolica del Sacro Cuore, Roma, Italy; 10Respiratory Unit ASST Santi Paolo e Carlo, Department of Health Sciences Universita’ degli Studi di Milano, Milano, Italy; 11UOSD Malattie Respiratorie “Federico II”, Ospedale Monaldi, AO Dei Colli, Napoli, Italy; 12UOC Pneumologia e Fisiopatologia Respiratoria, AORN A. Cardarelli, Napoli, Italy; 13Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy; 14Department of Health Sciences, Università Degli Studi Di Milano, Pneumologia, ASST Papa Giovanni XXIII, Bergamo, Italy; 15Dipartimento di Scienze della Salute, Università Magna Graecia, Catanzaro, Italy; 16Division of Respiratory Medicine, University Hospital “Tor Vergata”, Roma, Italy; 17Unit of Respiratory Medicine, Department of Experimental Medicine, University of Rome “Tor Vergata”, Roma, Italy; 18UOC Pneumologia, AULSS 2 Marca Trevigiana, Treviso, Italy; 19Fisiopatologia Respiratoria, Ospedale Generale Regionale, Ente Ecclesiastico “F. Miulli”, Acquaviva delle Fonti (BA), Italy; 20Allergy and Clinical Immunology, ASST Grande Ospedale Metropolitano Niguarda, Milano, Italy; 21Allergy Unit and Asthma Center, Verona University Hospital, Verona, Italy; 22Dipartimento di Medicina Sperimentale e Clinica, Università degli Studi di Firenze, Firenze, Italy; 23Medical Affairs R&I, AstraZeneca, Milano, Italy; 24Medical Evidence R&I, AstraZeneca, Milano, Italy; 25Pulmonology Unit, Ospedale “S. Valentino”, AULSS 2 Marca Trevigiana, Montebelluna (TV), ItalyCorrespondence: Paolo Cameli, Respiratory Diseases Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy, Email paolo.cameli@unisi.itPurpose: Severe eosinophilic asthma (SEA) patients often present overlapping inflammatory features rendering them eligible for multiple biologic therapies; switching biologic treatment is a strategy adopted to optimize asthma control when patients show partial or no response to previous biologics.Patients and Methods: ANANKE is a retrospective, multicenter Italian study (NCT04272463). Here, we outline the characteristics and long-term clinical outcomes in naïve-to-biologics and biologics-experienced patients treated with benralizumab for up to 96 weeks. Bio-experienced patients were split into omalizumab and mepolizumab subsets according to the type of biologic previously used.Results: A total of 124 (76.5%) naïve and 38 (23.5%) bio-experienced patients were evaluated at index date; 13 patients (34.2%) switched from mepolizumab, 21 patients (55.3%) switched from omalizumab, and four patients (10.5%) received both biologics. The mepolizumab subset was characterized by the longest SEA duration (median of 4.6 years), the highest prevalence of chronic rhinosinusitis with nasal polyposis (CRSwNP) (76.5%), and the greatest oral corticosteroid (OCS) daily dosage (median of 25 mg prednisone equivalent). The omalizumab group showed the highest severe annual exacerbation rate (AER) (1.70). At 96 weeks, treatment with benralizumab reduced any and severe AER by more than 87% and 94%, respectively, across all groups. Lung function was overall preserved, with major improvements observed in the mepolizumab group, which also revealed a 100% drop of the median OCS dose. Asthma Control Test (ACT) score improved in the naïve group while its increment was more variable in bio-experienced patients; among these, a marked difference was noticed between omalizumab and mepolizumab subsets (median ACT score of 23.5 and 18, respectively).Conclusion: Benralizumab promotes durable and profound clinical benefits in naïve and bio-experienced groups, indicating that a nearly complete depletion of eosinophils is highly beneficial in the control of SEA, independently of previous biologic use.Keywords: benralizumab, asthma, eosinophils, switch, long-term

Background: Participatory architecture can promote dialogue across cultures while working together to create physical outputs. A team of academics with a background in architecture, psychology and health sciences evaluated a participatory architecture workshop in Southern Italy as part of the Crossing Cultures project. The goal was to explore participants' experiences and perceived benefits. In the context of situated learning, the workshop brought together architecture students, local citizens and asylum seekers, who by working together and learning from each other formed a community of practice (CoP). Objective: The aim of this study was to explore the experiences of members of the CoP, their beliefs about the benefits of the project and ways to improve it. Setting: Data collection took place in 2019 during a participatory architecture workshop in Belmonte, Italy. Method: Twenty-five asylum seekers, locals and students took part in in-depth interviews, which were later subjected to thematic analysis. Results: Participants reported experiences relating to 'living together', 'working together', 'making home', 'making locals comfortable to be involved' and 'understanding and respecting differences'. Perceived benefits were 'creating a space for connection', 'revitalising local communities', 'promoting development of towns', 'broadening horizons', 'gaining or practising skills', 'having your ideas heard' and 'creating lasting things'. Conclusion: Findings suggest that creating a CoP not only fulfils individual goals but also addresses common concerns. Participatory architecture workshops in an area with high immigration can create connections between asylum seekers and local people, and promote intercultural dialogue while helping to reactivate an economically and socially deprived area.

BackgroundConduct disorder increases risks of educational dropout, future mental illness, and incarceration if untreated. First-line treatment of conduct disorder involves evidence-based parenting skills programs. Time-outs, a frequent tool in these programs, can be effective at improving behavior, and recent apps have been developed to aid this process. However, these apps promote the use of time-outs in inconsistent or developmentally inappropriate ways, potentially worsening behavior problems. Digital microinterventions like these apps could guide parents through high-quality time-outs in the moment, but current time-out apps lack features promoting adherence to the evidence-based best practice. Agile scrum is a respected approach in the software development industry. ObjectiveWe aimed to explore the feasibility of using the agile scrum approach to build a digital microintervention to help parents deliver an evidence-based time-out. MethodsThe agile scrum methodology was used. Four sprints were conducted. Figma software was used for app design and wireframing. Insights from 42 expert stakeholders were used during 3 sprint reviews. We consulted experts who were identified from councils around the Midlands region of the United Kingdom and charities through personal contacts and a snowballing approach. ResultsOver 4 development sprints from August 2022 to March 2023, the app was iteratively designed and refined based on consultation with a diverse group of 42 experts who shared their knowledge about the content of common parenting programs and the challenges parents commonly face. Modifications made throughout the process resulted in significant app enhancements, including tailored timer algorithms and enhanced readability, as well as an onboarding zone, mindfulness module, and pictorial information to increase inclusivity. By the end of the fourth sprint, the app was deemed ready for home use by stakeholders, demonstrating the effectiveness of our agile scrum development approach. ConclusionsWe developed an app to support parents to use the evidence-based time-out technique. We recommend the agile scrum approach to create mobile health apps. Our experience highlights the valuable role that frontline health and social care professionals, particularly those working with vulnerable families, can play as experts in scrum reviews. There is a need for research to both evaluate the impact of digital microinterventions on child behavioral change and also create digital microinterventions that cater to non–English speakers and individuals who participate in parenting programs in settings outside the United Kingdom.

Abstract Rationale It is unclear how each individual asthma symptom is associated with asthma diagnosis or control. Objectives To assess the performance of individual asthma symptoms in the identification of patients with asthma and their association with asthma control. Methods In this cross‐sectional study, we assessed real‐world data using the MASK‐air® app. We compared the frequency of occurrence of five asthma symptoms (dyspnea, wheezing, chest tightness, fatigue and night symptoms, as assessed by the Control of Allergic Rhinitis and Asthma Test [CARAT] questionnaire) in patients with probable, possible or no current asthma. We calculated the sensitivity, specificity and predictive values of each symptom, and assessed the association between each symptom and asthma control (measured using the e‐DASTHMA score). Results were validated in a sample of patients with a physician‐established diagnosis of asthma. Measurement and Main Results We included 951 patients (2153 CARAT assessments), with 468 having probable asthma, 166 possible asthma and 317 no evidence of asthma. Wheezing displayed the highest specificity (90.5%) and positive predictive value (90.8%). In patients with probable asthma, dyspnea and chest tightness were more strongly associated with asthma control than other symptoms. Dyspnea was the symptom with the highest sensitivity (76.1%) and the one consistently associated with the control of asthma as assessed by e‐DASTHMA. Consistent results were observed when assessing patients with a physician‐made diagnosis of asthma. Conclusions Wheezing and chest tightness were the asthma symptoms with the highest specificity for asthma diagnosis, while dyspnea displayed the highest sensitivity and strongest association with asthma control.

Background Carers of people who are involuntarily admitted to hospital report feeling isolated and unsupported by services. The Independent Review of the Mental Health Act (MHA) recommended that carers be supported. However, no research has directly explored what type of support carers would find most helpful when a relative/friend is involuntary admitted. Aims To explore carers’ experiences and views around the support they want to receive when their relative/friend is involuntarily admitted under the MHA. Method A total of 22 one-to-one interviews with carers were conducted online at three sites across England. Audio recordings of the interviews were transcribed, and data were analysed with thematic analysis. Results Four main themes were identified: (a) heterogeneity in the current support for carers, (b) information about mental health and mental health services, (c) continuous support, and (d) peer support and guidance. Carers reported receiving support from professionals, peers and relatives, but this was unstructured, and the extent of support varied across carers. Carers reported wanting more information about mental health services, and for this information to be consistent. Carers also reported wanting emotional support from a single, continuous person, helping them establish a more personal and sincere connection. Peers were also identified as important in the provision of carer support, allowing carers to feel reassured and understood in their experience. Conclusions The support received by carers is currently unstructured. To meet the MHA review recommendations, carers of patients who are involuntarily admitted should be allocated a named contact person, ideally with lived experience, to offer information and personal continuity of support.

Introduction In England, a national Mental Health Act (MHA) review was carried out, providing recommendation for policy and practice changes. One of these recommendations was to provide support to family members (FMs) of patients who have been involuntarily hospitalised. In response to this review, the National Institute for Health and Care Research (NIHR) provided funding for research to address policy questions, for example what support may be most relevant to FMs during their patients’ treatment. The study presented here was funded as part of this initiative and has explored what support FMs wish to receive. Objectives To explore FMs’ experiences and views around support they would have liked during their patients’ involuntary hospitalisation and wider stakeholder views on what a family support programme in England should involve. This information can be used to develop a support programme for FMs. Methods One-to-one interviews were conducted online as part of two work packages. The first work package explored FMs’ experiences and views of support. The second work package explored views on what should be included in a family support programme in England from FMs, patients and professionals. Interviews took place at three sites across England. Audio recordings of the interviews were transcribed, and data were analysed using thematic analysis. Results 22 FMs were recruited to the first work package, where four key themes were identified: (1) heterogeneity in the current support for families; (2) information about mental health and mental health services; (3) continuous support; and (4) peer support and guidance. FMs reported receiving support from professionals, peers and relatives, but the extent of this support varied. FMs consistently reported wanting a named contact to provide information and personal continuity of support. 5 FMs, 4 patients and 10 professionals took part in the second work package, where four main themes were also identified: (1) development of a support programme; (2) delivery of a support programme; (3) factors limiting accessibility or engagement; and (4) benefits of a support programme. Information about the MHA and strategies to promote effective communication between FMs and professionals were identified as important to include in the programme and its delivery should include a combination of face-to-face, written and online methods. Potential benefits of the programme include improved FM knowledge and wellbeing. Conclusions FMs of involuntarily hospitalised patients should receive information around the MHA and strategies to promote effective communication with professionals. FMs should also be allocated a named contact person to offer information and personal continuity of support through various methods, for example through online, face-to-face or written contact. Disclosure of Interest None Declared

Introduction Peer support has been identified as successful in improving patient wellbeing and empowerment and there is evidence that peer support can also help their family members (FMs). A peer support programme for FMs, developed in Germany, significantly improved FMs’ quality of life. We have worked to adapt this support programme for delivery in England. We will report the results of this adaptation process and of the implementation of peer support for FMs. Objectives To examine the feasibility of the peer support programme developed and assess whether it can be delivered using a “train-the-trainer” approach. Methods The peer support programme is being implemented in two stages. In stage one, FMs with experience of supporting an involuntarily hospitalised patient (family peer supporters (FPSs)) receive an online training programme consisting of four sessions. These sessions, provided by the research team and FMs with lived experience of caring for an involuntarily hospitalised patient, teach FPSs skills in communication, reflection, coping and trialogue (promotion of equal communication between FMs, professionals and patients). FPSs then use these skills to deliver support to FMs of patients who are currently involuntarily hospitalised. This support is delivered for up to three months. The impact of this programme is assessed through one-to-one interviews with FPSs and FMs. Questionnaires are also provided to FMs measuring their quality of life, caregiving burden and psychological wellbeing before and after receiving support from FPSs. In stage two, a modified version of the training programme (based on FPS feedback) is provided to a new group of FPSs. This training will be delivered by FPSs from stage one. After receiving the training programme, stage two FPSs will deliver support to other FMs as described for stage one. Assessment of the modified programme will mirror stage one. Results Provision of the stage one training programme is complete, and delivery of support is in progress with modifications being made for stage two. Eight FPSs and six out of a target of 12 FMs have been recruited for stage one. FPSs reported the training programme to be a positive experience, highlighting that it was engaging, easy to understand and gave them the confidence to support other FMs. Technical difficulties and an overload of information were cited as areas to improve for the next stage. Conclusions FPSs described the peer support training programme as a positive experience overall. However, improvements need to be made for stage two which is in progress. A more comprehensive report of our findings, including the impact of this peer support programme and the feasibility of implementing it in England, will be provided as the programme progresses. Disclosure of Interest None Declared

Introduction Digital technologies and interventions (defined as patient-facing or self-administered interventions delivered through a digital platform) have an increasing role in mental health care. It is key to ensure that appropriate patient and public involvement (PPI) is not overlooked when developing new digital mental health interventions (DMHIs). The unique perspective offered by those with lived experience can improve study conduct and design as well as ensure that interventions meet the needs of users, which may improve their quality and acceptability. Objectives To develop guidance for the involvement of people with lived experience of severe mental illness in designing and conducting research on DMHIs. Methods Four co-production workshops were arranged online with people who have lived experience of severe mental illness. Initial ideas were formulated in the first workshop and were then prioritised in the second workshop using the nominal group technique. The prioritised ideas were then refined in workshops three and four. Minutes were generated from each workshop and were validated by the those who took part. These minutes were analysed using thematic analysis. Results Nineteen people with lived experience participated in the co-production workshops overall. Six people took part in one workshop only and 13 took part in multiple workshops. Two main themes were identified in this study: why do people become and remain involved in PPI?; and what areas should be discussed within PPI consultations? Three subthemes associated with the second theme were also identified. These are: areas related to specific types of DMHI; areas related to any type of DMHI; and what can make a difference within DMHIs? To ensure that people become and remain interested in PPI around DMHIs, it is important to provide a non-judgemental space for people with lived experience to discuss any concerns and ensure they feel valued during consultations. Aspects to consider discussing in PPI consultations around the development of DMHIs include the provision of safety and security within DMHIs, issues around digital exclusion and the potential impact of people’s symptoms on DMHI use. Finally, points that were identified as important to consider when developing DMHIs include offering encouragement throughout the DMHI, accommodating for individual and collective needs within DMHIs and developing a structure within the DMHI which includes adding in attainable goals. Conclusions If used, the information provided from this study can generate positive and productive PPI consultations where those with lived experience can make significant contributions to the development of DMHIs. Such contributions will increase the acceptability and efficacy of the DMHIs developed. Disclosure of Interest None Declared

Abstract Background Depressive episodes are common after first-episode psychosis (FEP), affecting more than 40% of people, adding to individual burden, poor outcomes, and healthcare costs. If the risks of developing depression were lower, this could have a beneficial effect on morbidity and mortality, as well as improving outcomes. Sertraline is a selective serotonin reuptake inhibitor and a common first-line medication for the treatment of depression in adults. It has been shown to be safe when co-prescribed with antipsychotic medication, and there is evidence that it is an effective treatment for depression in established schizophrenia. We present a protocol for a multi-centre, double-blind, randomised, placebo-controlled clinical trial called ADEPP that aims to investigate the efficacy and cost-effectiveness of sertraline in preventing depression after FEP. Methods The recruitment target is 452 participants between the ages of 18 and 65 years who are within 12 months of treatment initiation for FEP. Having provided informed consent, participants will be randomised to receive either 50 mg of sertraline daily or matched placebo for 6 months, in addition to treatment as usual. The primary outcome measure will be a comparison of the number of new cases of depression between the treatment and placebo arms over the 6-month intervention phase. Secondary outcomes include suicidal behaviour, anxiety, rates of relapse, functional outcome, quality of life, and resource use. Discussion The ADEPP trial will test whether the addition of sertraline following FEP is a clinically useful, acceptable, and cost-effective way of improving outcomes following FEP. Trial registration ISRCTN12682719 registration date 24/11/2020.

Hypereosinophilic syndrome (HES) encompasses a heterogeneous and complex group of different subtypes within the wider group of hypereosinophilic disorders. Despite increasing research interest, several unmet needs in terms of disease identification, pathobiology, phenotyping, and personalized treatment remain to be addressed. Also, the prospective burden of non-malignant HES and, more in general, HE disorders is currently unknown. On a practical note, shortening the diagnostic delay and the time to an appropriate treatment approach probably represents the most urgent issue, even in light of the great impact of HES on the quality of life of affected patients. The present document represents the first action that the Italian Society of Allergy, Asthma, and Clinical Immunology (SIAAIC) has finalized within a wider project aiming to establish a collaborative national network on HES (InHES—Italian Network on HES) for patients and physicians. The first step of the project could not but focus on defining a common language as well as sharing with all of the medical community an update on the most recent advances in the field. In fact, the existing literature has been carefully reviewed in order to critically integrate the different views on the topic and derive practical recommendations on disease identification and treatment approaches.

The life-long adherence to a dietary pattern able to provide a high amount of polyphenols demonstrating beneficial cardiometabolic effects is demanding for the general population. In this study, red grape pomace (GP) was used as an ingredient to increase the daily polyphenols’ intake. The incorporation of crude crushed GP at 20 and 30% (w/w) in a control (CTR) biscuit formula improved the nutritional profile by increasing the fiber and reducing lipid and energy content while providing up to 540 mgGAE of polyphenols per 100 g. Besides anthocyanins, GP contains flavonoids and grape-seed procyanidins, contributing to the remarkable antioxidant capacity of 20- and 30-GP biscuits. Upon in vitro gastro-duodenal enzymatic digestion, the concentration of reducing sugars for 20-GP and 30-GP compared to the CTR biscuits dropped significantly, meaning that the combined action of GP fibers and polyphenols could delay the intestinal absorption of glucose. Overall, 60 volatiles were detected in biscuits. All in all, the content of Maillard reaction products was lower in GP than in CTR biscuits, possibly due to the free radical scavenging ability of polyphenols. Despite the high rates of GP utilized, the sensorial attributes and the overall liking of the GP biscuits—especially the 20-GP ones—were not substantially affected. These findings will support nutritional studies to assess the potential role as functional foods of GP biscuits, and, afterwards, the large-scale production of a food mainly based on a waste ingredient turned into a resource.

Immunization against COVID-19 is needed in patients with immune-mediated inflammatory diseases (IMIDs). However, data on long-term immunity kinetics remain scarce. This study aimed to compare the humoral and cellular response to COVID-19 in patients with immune-mediated inflammatory diseases (IMIDs) compared to healthy controls. We compared the humoral and cellular response to SARS-Cov-2 elicited by vaccination and/or infection in a prospective cohort of 20 IMID patients compared with a group of 21 healthcare workers (HCWs). We assessed immunity before and after the third and fourth dose of BNT162b2 or after COVID-19 infection using quantitative IgG anti-SARS-CoV-2 Spike antibody (anti-S-IgG), neutralization assay, and specific interferon-gamma (IFN-g) release assay (IGRA). The responses were compared with those of healthy controls. The two groups were similar in age and total exposure, becoming infected for the first time, mainly after the third dose. Neutralizing antibodies and IGRA were negative in 9.5% of IMID patients but not in any HCWs. No significant difference was found between neutralization titers to BA.1 in the IMID and the HCW groups. The study highlights the SARS-CoV-2 immunological responses in healthy controls and IMID patients, suggesting that the combined stimuli of vaccination and infection in IMID patients could promote a more profound immunological response.

Abstract Background The efficacy of benralizumab has been broadly demonstrated in severe eosinophilic asthma (SEA), but only few real-life studies evaluated its long-term effects. Here we present novel data from the ANANKE study in which a large cohort of SEA patients was treated for up to 96 weeks. Methods ANANKE (NCT04272463) is an observational retrospective Italian study investigating the key characteristics of SEA patients (collected during the 12 months prior to benralizumab initiation) and the clinical outcomes during benralizumab treatment (annual exacerbation rate [AER], lung function, asthma control, OCS use, healthcare resource utilization). A post hoc analysis was also conducted in groups of patients based on history of previous biologic therapy (bio-experienced versus naïve patients). Analyses were descriptive only. Results Before benralizumab initiation, evaluable SEA patients (N = 162, 61.1% females, mean age 56.0 ± 12.7) showed a median blood eosinophil count (BEC) of 600 cells/mm3 (IQR: 430–890). Patients experienced frequent exacerbations (annualized exacerbation rate [AER]: 4.10, severe AER: 0.98), with impaired lung function and poor asthma control (median ACT score: 14) despite 25.3% reported oral corticosteroid (OCS) use. Nasal polyposis was present in 53.1% patients; 47.5% patients were atopic. After 96 weeks since the start of benralizumab, nearly 90% patients were still on treatment; benralizumab dramatically decreased exacerbations (AER: − 94.9%; severe AER: − 96.9%), improved respiratory parameters (median increase in pre-bronchodilator forced expiratory volume [pre-BD FEV1]: + 400 mL) and asthma control (median ACT score: 23) while eliminating OCS in 60% patients. Importantly, benralizumab effects were either maintained or progressively improved over time, accompanied by a nearly complete depletion of BEC. Benralizumab reduced AER both in naïve (any AER: − 95.9%; severe AER: − 97.5%) and bio-experienced patients (any AER: − 92.4%; severe AER: − 94.0%). Conclusions Profound and sustained improvements in all asthma outcomes were observed with benralizumab. The correct identification of patients’ eosinophilic-driven asthma phenotype was essential to ensure the achievement of such remarkable results. Trial registration: ClinicalTrials.gov Identifier: NCT04272463.

Abstract Background Leisure activities can improve quality of life in the general population. For people with psychosis, negative symptoms (e.g. being unmotivated, difficulty in sticking with activities) are often a barrier to engaging in social leisure activities. However, we do not know if participation in leisure activities is associated with quality of life in this group and, whether psychosocial interventions should aim to increase leisure activities. Aim This study investigates participation in social leisure activities of people with psychosis and whether their participation is associated with better quality of life. Methods A cross-sectional survey was conducted in 6 NHS mental health trusts. Adults aged 18–65 (N = 533) with a diagnosis of a psychosis-related condition (ICD-10 F20-29) were recruited from outpatient secondary mental health services. Several measures were used including an adapted version of the Time Use Survey (TUS), the Social contacts assessment (SCA) and Manchester Short Assessment of Quality of Life (MANSA). A Structural Equation Model (SEM) was used to explore the relationships between participation in leisure activities and quality of life, and whether social contacts mediated the link. Results Participants attended an average of 2.42 (SD = 1.47) leisure activities in the last 7 days. Their quality of life increased with the number of leisure activities they attended. Participation in leisure activities was positively associated with quality of life in people with psychosis (B = 0.104, SE = 0.051, p = 0.042, 95% CI [0.003 to 0.204]). Leisure activities predicted social contacts, but the link between social contacts and the quality of life was not significant. After controlling for sociodemographic factors, being female and unemployed were negatively linked with quality of life (B = − 0.101, SE = 0.048, p = 0.036, 95% CI [− 0.196 to − 0.006; B = − 0.207, SE = 0.050, p = 0.001, 95% CI [− 0.305 to − 0.108, respectively]. Conclusion People with psychosis who attend more leisure activities have a higher quality of life. Quality of life was lower amongst female and unemployed participants who attended leisure activities. Intervention which helps improve participation in leisure activities may be beneficial for people with psychosis. Trial registration number ISRCTN15815862.