Elevated intrinsic cortical curvature in treatment-resistant schizophrenia: Evidence of structural deformation in functional connectivity areas and comparison with alternate indices of structure.

BACKGROUND: Research suggests structural and connectivity abnormalities in patients with treatment-resistant schizophrenia (TRS) compared to first-line responders and healthy-controls. However, measures of these abnormalities are often influenced by external factors like nicotine and antipsychotics, limiting their clinical utility. Intrinsic-cortical-curvature (ICC) presents a millimetre-scale measure of brain gyrification, highly sensitive to schizophrenia differences, and associated with TRS-like traits in early stages of the disorder. Despite this evidence, ICC in TRS remains unexplored. This study investigates ICC as a marker for treatment resistance in TRS, alongside structural indices for comparison. METHODS: We assessed ICC in anterior cingulate, dorsolateral prefrontal, temporal, and parietal cortices of 38 first-line responders, 30 clozapine-resistant TRS, 37 clozapine-responsive TRS, and 52 healthy-controls. For comparative purposes, Fold and Curvature indices were also analyzed. RESULTS: Adjusting for age, sex, nicotine-use, and chlorpromazine equivalence, principal findings indicate ICC elevations in the left hemisphere dorsolateral prefrontal (p < 0.001, η2partial = 0.142) and temporal cortices (LH p = 0.007, η2partial = 0.060; RH p = 0.011, η2partial = 0.076) of both TRS groups, and left anterior cingulate cortex of clozapine-resistant TRS (p = 0.026, η2partial = 0.065), compared to healthy-controls. Elevations that correlated with reduced cognition (p = 0.001) and negative symptomology (p < 0.034) in clozapine-resistant TRS. Fold and Curvature indices only detected group differences in the right parietal cortex, showing interactions with age, sex, and nicotine use. ICC showed interactions with age. CONCLUSION: ICC elevations were found among patients with TRS, and correlated with symptom severity. ICCs relative independence from sex, nicotine-use, and antipsychotics, may support ICC's potential as a viable marker for TRS, though age interactions should be considered.

Evaluation of the Glymphatic System in Schizophrenia Spectrum Disorder Using Proton Magnetic Resonance Spectroscopy Measurement of Brain Macromolecule and Diffusion Tensor Image Analysis Along the Perivascular Space Index.

BACKGROUND AND HYPOTHESIS: The glymphatic system (GS), a brain waste clearance pathway, is disrupted in various neurodegenerative and vascular diseases. As schizophrenia shares clinical characteristics with these conditions, we hypothesized GS disruptions in patients with schizophrenia spectrum disorder (SCZ-SD), reflected in increased brain macromolecule (MM) and decreased diffusion-tensor-image-analysis along the perivascular space (DTI-ALPS) index. STUDY DESIGN: Forty-seven healthy controls (HCs) and 103 patients with SCZ-SD were studied. Data included 135 proton magnetic resonance spectroscopy (1H-MRS) sets, 96 DTI sets, with 79 participants contributing both. MM levels were quantified in the dorsal-anterior cingulate cortex (dACC), dorsolateral prefrontal cortex, and dorsal caudate (point resolved spectroscopy, echo-time = 35ms). Diffusivities in the projection and association fibers near the lateral ventricle were measured to calculate DTI-ALPS indices. General linear models were performed, adjusting for age, sex, and smoking. Correlation analyses examined relationships with age, illness duration, and symptoms severity. STUDY RESULTS: MM levels were not different between patients and HCs. However, left, right, and bilateral DTI-ALPS indices were lower in patients compared with HCs (P < .001). In HCs, age was positively correlated with dACC MM and negatively correlated with left, right, and bilateral DTI-ALPS indices (P < .001). In patients, illness duration was positively correlated with dACC MM and negatively correlated with the right DTI-ALPS index (P < .05). In the entire population, dACC MM and DTI-ALPS indices showed an inverse correlation (P < .01). CONCLUSIONS: Our results suggest potential disruptions in the GS of patients with SCZ-SD. Improving brain's waste clearance may offer a potential therapeutic approach for patients with SCZ-SD.

Assessing past suicidal behaviour in schizophrenia spectrum disorders using the Columbia-Suicide Severity Rating Scale and the Beck Scale for Suicide Ideation: Analysis across the life-span.

Assessing the number of past suicide attempts is vital in clinical and research settings, as it is a significant variable in assessing suicide risk. This study sought to compare the accuracy of the C-SSRS and the BSS in reporting past suicide attempts in schizophrenia spectrum disorders . Six hundred participants were recruited from the Centre for Addiction and Mental Health in Toronto, and completed the BSS and C-SSRS. A medical chart review was performed to determine the number of past suicide attempts. In addition, receiver operating characteristic curves were generated to compare the accuracy of both tests under various stratifications. Based on our findings, there were no significant differences (P = 0.8977) between the BSS and CSSRS in detecting a history of past suicide attempts. The BSS exhibited a sensitivity of 0.847 and a specificity of 0.841, while the C-SSRS had a slightly lower sensitivity of 0.795 and a slightly higher specificity of 0.889. Additionally, repeating the analysis to determine the accuracy of detecting multiple past suicide attempts, the BSS demonstrated a sensitivity of 0.704 and a specificity of 0.959, whereas the C-SSRS had a sensitivity of 0.787 and a specificity of 0.927. We further contrasted the two scales, stratified by different demographic variables such as age and sex. The accuracy of both tools, which is defined as the ability to identify true positive cases while minimizing false positives, increased as age increased, but these differences were not statistically significant. Therefore, both tools show a high level of accuracy in reporting past suicide attempt history and should be utilized to fit the specific needs of the research or clinical teams. These findings can inform clinical practice and future research, highlighting the importance of selecting assessment tools that fit the population's needs and context.

Disease Progression Patterns of Brain Morphology in Schizophrenia: More Progressed Stages in Treatment Resistance.

BACKGROUND AND HYPOTHESIS: Given the heterogeneity and possible disease progression in schizophrenia, identifying the neurobiological subtypes and progression patterns in each patient may lead to novel biomarkers. Here, we adopted data-driven machine-learning techniques to identify the progression patterns of brain morphological changes in schizophrenia and investigate the association with treatment resistance. STUDY DESIGN: In this cross-sectional multicenter study, we included 177 patients with schizophrenia, characterized by treatment response or resistance, with 3D T1-weighted magnetic resonance imaging. Cortical thickness and subcortical volumes calculated by FreeSurfer were converted into z scores using 73 healthy controls data. The Subtype and Stage Inference (SuStaIn) algorithm was used for unsupervised machine-learning analysis. STUDY RESULTS: SuStaIn identified 3 different subtypes: (1) subcortical volume reduction (SC) type (73 patients), in which volume reduction of subcortical structures occurs first and moderate cortical thinning follows, (2) globus pallidus hypertrophy and cortical thinning (GP-CX) type (42 patients), in which globus pallidus hypertrophy initially occurs followed by progressive cortical thinning, and (3) cortical thinning (pure CX) type (39 patients), in which thinning of the insular and lateral temporal lobe cortices primarily happens. The remaining 23 patients were assigned to baseline stage of progression (no change). SuStaIn also found 84 stages of progression, and treatment-resistant schizophrenia showed significantly more progressed stages than treatment-responsive cases (P = .001). The GP-CX type presented earlier stages than the pure CX type (P = .009). CONCLUSIONS: The brain morphological progressions in schizophrenia can be classified into 3 subtypes, and treatment resistance was associated with more progressed stages, which may suggest a novel biomarker.

Copy Number Variation Analysis of Aggressive Behaviour in Schizophrenia.

INTRODUCTION: An increased proclivity towards violence is often associated with those diagnosed with schizophrenia (SCZ), despite contradictory findings from prior studies exploring the association between violence and SCZ. Evidence has shown that certain comorbidities, specifically the presence of a substance use disorders, can result in increased aggression in those with SCZ. Copy number variation (CNV) load has also previously been implicated in the genetic vulnerability of individuals with SCZ. For this study, we aimed to determine whether CNV load correlates with increased violence in SCZ. METHODS: Community-dwelling patients diagnosed with SCZ spectrum disorders (n = 203) were recruited from a non-forensic population. The assessment for aggression was completed using a cross-sectional and retrospective design, and CNV analysis was conducted analysing genomic DNA using the Illumina Omni 2.5 array. RESULTS: No correlation between the number of CNV events (either deletion or duplication) and the severity of the physical violence episode index was found. However, there was a significant association between larger deletion events across the violent behaviours under investigation. DISCUSSION: These results need to be confirmed in more extensive studies using standardized tools developed for non-forensic populations, such as the Brown-Goodwin Scale of Aggression.

Clinical outcomes of a digitally supported approach for self-management of type 2 diabetes mellitus.

Background: Self-management of Type 2 diabetes mellitus (T2D) is challenging. Regular self-monitoring of blood glucose and healthy lifestyles are required to improve glycometabolic control, thus delaying diabetes complications, and reducing hospitalizations. Digital technologies can empower patients in their disease management promoting self-management and motivation to change behaviors. We report the results of an exploratory trial aimed at evaluating the metabolic outcomes of using digital solutions for T2D self-management developed in the ProEmpower project, a European Commission funded Pre-Commercial Procurement. Methods: Two digital solutions, DM4All and DiaWatch, which were codesigned with providers, patients, and caregivers, enabled the collection of clinical parameters by the patient using a smartphone integrated with the medical devices (glucometer, sphygmomanometer, scale, smart watch for heart rate monitoring and step counter). Data were automatically sent to the shared care plan allowing professionals to monitor adherence to treatment, set goals, and communicate more effectively with patients. At baseline and after an average follow-up of 8 months, glycosylated hemoglobin (HbA1c), body weight, blood pressure, and blood lipids were measured in 100 T2D patients using the ProEmpower solutions across different diabetes centers in Campania Region, age 45-79 years, both genders, and compared with a Control cohort of T2D patients (n = 100) with similar clinical characteristics and followed for a comparable period of observation in the same centers. Results: At baseline, the ProEmpower participants and the Control subjects were on average overweight, with a similar BMI in the two cohorts, and mean HbA1c was at acceptable levels (around 7.0%). After the 8 month exploratory trial, body weight, HbA1c, systolic and diastolic blood pressure, and plasma and LDL-cholesterol significantly decreased in the ProEmpower participants compared to baseline (p < 0.05 for all). The changes in systolic and diastolic blood pressure, and plasma and LDL-cholesterol were significantly different from those observed in the Control cohort (p < 0.05 for all). Conclusion: This pilot study showed positive effects on metabolic outcomes relevant to cardiovascular risk in T2D of adopting digital telemedicine self-monitoring solutions based on automation of measurements and coaching on healthy lifestyles promotion.

Characterization and prediction of individual functional outcome trajectories in schizophrenia spectrum disorders (PREDICTS study): Study protocol.

Schizophrenia spectrum disorders (SSDs) are associated with significant functional impairments, disability, and low rates of personal recovery, along with tremendous economic costs linked primarily to lost productivity and premature mortality. Efforts to delineate the contributors to disability in SSDs have highlighted prominent roles for a diverse range of symptoms, physical health conditions, substance use disorders, neurobiological changes, and social factors. These findings have provided valuable advances in knowledge and helped define broad patterns of illness and outcomes across SSDs. Unsurprisingly, there have also been conflicting findings for many of these determinants that reflect the heterogeneous population of individuals with SSDs and the challenges of conceptualizing and treating SSDs as a unitary categorical construct. Presently it is not possible to identify the functional course on an individual level that would enable a personalized approach to treatment to alter the individual's functional trajectory and mitigate the ensuing disability they would otherwise experience. To address this ongoing challenge, this study aims to conduct a longitudinal multimodal investigation of a large cohort of individuals with SSDs in order to establish discrete trajectories of personal recovery, disability, and community functioning, as well as the antecedents and predictors of these trajectories. This investigation will also provide the foundation for the co-design and testing of personalized interventions that alter these functional trajectories and improve outcomes for people with SSDs.

Dynamic change in genome-wide methylation in response to increased suicidal ideation in schizophrenia spectrum disorders.

Suicide is a significant public health crisis, with 800,000 people dying annually. Most people completing suicide have previous psychiatric conditions, and those with psychotic and mood disorders are particularly vulnerable. Unfortunately, there are currently no biomarkers available for accurately detecting suicidal ideation. Given the genetic and environmental factors that play a role in suicidal ideation, we attempted to determine epigenetic modifications, specifically DNA methylation, in response to changes in suicidal ideation. Using a longitudinal study design, 31 participants with schizophrenia spectrum disorders were interviewed at a baseline visit and again at a follow-up visit 3-12 months later. Current suicidal ideation was recorded at both visits with the Columbia Suicide Severity Rating Scale and the Beck Scale for Suicide Ideation, and whole blood was collected for methylation analysis. Our analysis shows a significant negative correlation between cg26910920 methylation and increasing Columbia Suicide Severity Rating Scale scores and a positive correlation between cg13673029 methylation and increasing Beck Scale for Suicide Ideation scores. This pilot study indicates that there is  the possibility  that DNA methylation can respond to changes in suicidal ideation over time and potentially be used as a biomarker of suicidal ideation in the future.

Biosynthesis of kratom opioids.

Mitragynine, an analgesic alkaloid from the plant Mitragyna speciosa (kratom), offers a safer alternative to clinical opioids such as morphine, owing to its more favorable side effect profile. Although kratom has been traditionally used for stimulation and pain management in Southeast Asia, the mitragynine biosynthesis pathway has remained elusive. We embarked on a search for mitragynine biosynthetic genes from the transcriptomes of kratom and other members of the Rubiaceae family. We studied their functions in vitro and in vivo. Our investigations led to the identification of several reductases and an enol methyltransferase that forms a new clade within the SABATH methyltransferase family. Furthermore, we discovered a methyltransferase from Hamelia patens (firebush), which catalyzes the final step. With the tryptamine 4-hydroxylase from the psychedelic mushroom Psilocybe cubensis, we accomplished the four-step biosynthesis for mitragynine and its stereoisomer, speciogynine in both yeast and Escherichia coli when supplied with tryptamine and secologanin. Although we have yet to pinpoint the authentic hydroxylase and methyltransferase in kratom, our discovery completes the mitragynine biosynthesis. Through these breakthroughs, we achieved the microbial biosynthesis of kratom opioids for the first time. The remarkable enzyme promiscuity suggests the possibility of generating derivatives and analogs of kratom opioids in heterologous systems.

GWAS of biological aging to find longevity genes in schizophrenia.

Schizophrenia (SCZ) is a severe psychotic disorder associated with premature mortality and aging. Moreover, the symptoms and progression of psychiatric disorders in general are associated with decreased lifespan, biological aging, and poorer medical outcomes. In this study, we investigated the relationship between several epigenetic clocks and scanned the entire genome for association in a cohort of SCZ individuals (n = 107). Biological age was computed from blood DNA methylation (DNAm) and tested for association against  common  variants across the genome using general linear models. Genes affecting epigenetic age acceleration in our cohort were found mainly when using the telomeric length clock rather than the other biological clocks. These findings pair with existing evidence that there are some genes associated with longevity and suggest further investigations of  putative biological mechanisms for morbidity and premature mortality, not only in patients with SCZ but also in the general population.

Gastrointestinal bezoars: Review of the literature and report of a rare case of pumpkin seed rectal impaction.

In science, bezoar is a mass of hair or undigested vegetable matter, found in a human or animal's intestines, similar to a hairball. Usually, it is found trapped in every part of the gastrointestinal system and must be distinguished by pseudobezoar which is an indigestive object voluntarily introduced into the digestive tract. The term Bezoar is from Arabic bazahr, "bezoar" or ultimately from Middle Persian p'tzhl padzahr, "antidote, bezoar"ægagropile o egagropile It should be a universal antidote that works against any poison, and could neutralize any poison. Otherwise, the name could derive from a kind of Turkish goat whose name is just bezoar. Authors report a case of fecal impaction by pumpkin seeds bezoar with abdominal pain: a difficulty to void with subsequent rectal inflammation and hemorrhoid enlargement was observed. The patient underwent a successful manual disimpaction. Guidelines do not require IRB approval Authors examined the literature about occlusion from bezoar The most common causes of occlusion from bezoar are: a previous gastric surgery such as a gastric band (for weight loss) or gastric bypass, a reduced stomach acid (hypochlorhydria) or decreased stomach size, a delayed gastric emptying, typically due to diabetes, autoimmune disorders, or mixed connective tissue disease. Seed bezoars are usually found in the rectum of patients without predisposing factors, causing constipation and pain. Rectal impaction is common after ingestion of seeds while a true occlusion is rare. Although several cases of phytobezoars composed of various types of seeds are reported in literature, bezoars of pumpkin seeds have rarely been reported.

Cortical thinning in relation to impaired insight into illness in patients with treatment resistant schizophrenia.

Impaired insight into illness is a common element of schizophrenia that contributes to treatment nonadherence and negative clinical outcomes. Previous studies suggest that impaired insight may arise from brain abnormalities. However, interpretations of these findings are limited due to small sample sizes and inclusion of patients with a narrow range of illness severity and insight deficits. In a large sample of patients with schizophrenia, the majority of which were designated as treatment-resistant, we investigated the associations between impaired insight and cortical thickness and subcortical volumes. A total of 94 adult participants with a schizophrenia spectrum disorder were included. Fifty-six patients (60%) had treatment-resistant schizophrenia. The core domains of insight were assessed with the VAGUS insight into psychosis scale. We obtained 3T MRI T1-weighted images, which were analysed using CIVET and MAGeT-Brain. Whole-brain vertex-wise analyses revealed impaired insight, as measured by VAGUS average scores, was related to cortical thinning in left frontotemporoparietal regions. The same analysis in treatment-resistant patients showed thinning in the same regions, even after controlling for age, sex, illness severity, and chlorpromazine antipsychotic dose equivalents. No association was found in non-treatment-resistant patients. Region-of-interest analyses revealed impaired general illness awareness was associated with cortical thinning in the left supramarginal gyrus when controlling for covariates. Reduced right and left thalamic volumes were associated with VAGUS symptom attribution and awareness of negative consequences subscale scores, respectively, but not after correction for multiple testing. Our results suggest impaired insight into illness is related to cortical thinning in left frontotemporoparietal regions in patients with schizophrenia, particularly those with treatment resistance where insight deficits may be more chronic.

Polygenic Risk Score Effect on Violent Behavior in Schizophrenia.

Previous studies aiming to establish a correlation between schizophrenia (SCZ) and aggressive behavior have resulted in contradictory results. Despite this, a certain degree of evidence suggests a potential underlying genetic component to aggression in SCZ. Polygenic risk score (PRS) analysis is a novel technique to estimate the combined effect of multiple genetic influences on aggression. Our objective was to investigate whether PRS could determine a proclivity toward aggressive behavior in patients with SCZ. Community-dwelling patients diagnosed with a schizophrenia spectrum disorder (n = 205) were recruited from a nonforensic outpatient sample. Participants were assessed for aggression using a cross-sectional and retrospective design, and PRS was calculated using genomic DNA and the Illumina Omni 2.5 array. We did not detect any associations between lifetime physical aggression (P = 32), verbal aggression (P = 24), or aggression against property (P = 24) and the PRS for SCZ risk. There may be several reasons to explain our null findings. We recommend that future interaction analyses of PRSs in SCZ that investigate violence focus on forensic psychiatric patients with higher base rates of violence and use participant interviews to assess aggression.

Digital Health Service for Identification of Frailty Risk Factors in Community-Dwelling Older Adults: The SUNFRAIL+ Study Protocol.

This article reports the study protocol of a nationwide multicentric study in seven Italian regions aimed at assessing the effectiveness of a digitally supported approach for the early screening of frailty risk factors in community-dwelling older adults. SUNFRAIL+ is a prospective observational cohort study aimed at carrying out a multidimensional assessment of community-dwelling older adults through an IT platform, which allows to connect the items of the SUNFRAIL frailty assessment tool with a cascading multidimensional in-depth assessment of the bio-psycho-social domains of frailty. Seven centers in seven Italian regions will administer the SUNFRAIL questionnaire to 100 older adults. According to the answers provided by older adults, they will be subjected to one or more validated in-depth scale tests in order to perform further diagnostic or dimensional evaluations. The study aims to contribute to the implementation and validation of a multiprofessional and multistakeholder service model for the screening of frailty in community-dwelling older adult population.

Exploratory Factor Analysis (EFA) of the Short Functional Geriatric Evaluation (SFGE) to Assess the Multidimensionality of Frailty in Community-Dwelling Older Adults.

The Short Functional Geriatric Evaluation (SFGE) is a multidimensional and short questionnaire to assess biopsychosocial frailty in older adults. This paper aims to clarify the latent factors of SFGE. Data were collected from January 2016 to December 2020 from 8800 community-dwelling older adults participating in the "Long Live the Elderly!" program. Social operators administered the questionnaire through phone calls. Exploratory factor analysis (EFA) was carried out to identify the quality of the structure of the SFGE. Principal component analysis was also performed. According to the SFGE score, 37.7% of our sample comprised robust, 24.0% prefrail, 29.3% frail, and 9.0% very frail individuals. Using the EFA, we identified three main factors: psychophysical frailty, the need for social and economic support, and the lack of social relationships. The Kaiser-Meyer-Olkin measure of sampling adequacy was 0.792, and Bartlett's test of sphericity had a statistically significant result (p-value < 0.001). The three constructs that emerged explain the multidimensionality of biopsychosocial frailty. The SFGE score, 40% of which is social questions, underlines the crucial relevance of the social domain in determining the risk of adverse health outcomes in community-dwelling older adults.

Mediating effect of genome-wide DNA methylation on suicidal ideation induced by stressful events.

OBJECTIVE: Schizophrenia is a debilitating disease that is associated with higher rates of death by unnatural causes including suicide. Exposure to stressful events is an important risk factor for suicidal ideation (SI); however, the mechanisms that link stress, SI, and suicide remain unclear. Epigenetic processes are involved in both vulnerability to suicidal behavior and stress. Therefore, we sought to study the relationship between epigenetic modifications and suicidal behavior and stress. METHODS: This pilot study was conducted on 39 patients diagnosed with schizophrenia (54% men and age 45.5 ± 12.7). We analyzed the effects of (a) stress exposure and (b) the mediation of DNA methylation [via an epigenetic wide association study (EWAS) of more than 450 000 CpG sites across the genome] on SI severity. RESULTS: The top CpG site mediating the effect of global stress exposure on SI was cg27660192 located in an intergenic region on chromosome 11, exerting a facilitating effect on worsening SI through DNA hypomethylation. CONCLUSION: These preliminary results indicate that DNA methylation in peripheral tissues can shed light on the complex relationship between stress and SI in schizophrenia.

Genome-wide methylation analysis of treatment resistant schizophrenia.

Various studies have investigated the relationship between genetic polymorphisms of antipsychotic drug-metabolizing agents and drug response. DNA methylation is a form of epigenetic modification that regulates gene expression. Few studies have analyzed the relationship between genome-wide methylation patterns and treatment resistance schizophrenia. The primary aim of this pilot study is to investigate the association between treatment resistance status and genome-wide DNA methylation in schizophrenia patients. Treatment resistance status was determined for 109 patients with schizophrenia. Treatment resistance was the primary outcome variable in a model, including methylation status of white blood cells using the Illumina 450 array. The genome-wide DNA methylation levels in 109 Schizophrenia subjects did not show that DNA methylation sties were associated with resistance status. From our study, it is evident the importance of continuing to investigate the relationship between DNA methylation and antipsychotic response to personalize treatment in schizophrenia. Future studies require larger prescription databases to build on the results presented in this pilot study.

Trends in Telecare Use among Community-Dwelling Older Adults: A Scoping Review.

A scoping review was conducted to map and analyze the concept of telecare services and the trends in telecare use. This scoping review was conducted according to Arksey and O'Malley's framework. A search was conducted in CINAHL (via EBSCO), ERIC, Academic Search Ultimate, and MEDLINE/PubMed databases. This scoping review considered quantitative (e.g., analytical observational studies, including prospective and retrospective cohort studies, case-control, analytical cross-sectional, and descriptive-observational studies), qualitative (e.g., phenomenology, grounded theory, ethnography, and action research), and mixed-method primary studies. Forty research articles published from 1 January 2012, to 1 January 2022 were included in this review, these studies met the eligibility criteria as all were focused on telecare and targeting older adults over 65 living at home. The reviewers coded the data in an Excel spreadsheet, including the articles' title, year, author, journal information and subject, research methods, sample size, location, and summary. Then, the researchers analyzed the conceptual definitions, measurement techniques, and findings in detail and the findings were grouped into categories. The trends around the concept of telecare are independent living, remote care, aging in place, and safety. Telecare research focuses mainly on service use, chronic illness, ethics, and cost-effectiveness. Technology acceptance among older individuals is a critical factor for telecare use. The results found in the literature about the cost-effectiveness of telecare are inconsistent.

Innovative approaches to service integration addressing the unmet needs of irritable bowel syndrome patients and new approaches for the needs of IBS patients.

Background: Irritable bowel syndrome (IBS) is a common multifactorial condition that affects the large intestine and is characterized by chronic and relapsing abdominal pain and altered bowel habit. IBS is due to a combination of genetic, environmental and dietary factors. It's usually a lifelong problem very frustrating to live with and can have a big impact on quality of life, as single-agent therapy ra. Objective: To analyze the approaches and solutions that address the social and health unmet needs of patients with IBS. Design: A quantitative-qualitative approach was adopted in the current study to identify and specify key digital solution and high impact user scenarios applied to IBS patients, through an adaptation of the "Blueprint on Digital Transformation in Health and Care in an Ageing Society" persona methodology. Settings: Digital health solutions bring the potential of supporting health interventions through mobile apps, wearable devices, telemedicine. Patients: A Survey was administered to a group of patients in an anonymous form, and no need for Medical Ethical Committee approval was identified. Interventions: The theoretical elaboration IBS personas was developed through an interdisciplinary Focus Group, which also mapped the pathway for the patient's management. Main outcome: Three main needs were identified to be met to improve IBS patient's lifestyle: access to psychological support, mHealth solutions supporting diet and adapted physical activity, and home-based digital health support. mHealth intervention has been identified for diet adherence, physical exercise and psychological well-being. The process has been mapped and adapted to integrate the new solutions into the care pathway. Limitation: Further research is needed to evaluate how mHealth services enable IBS patients to manage their conditions and improve their quality of life. Conclusion: The person-centered approach was implemented through a multidisciplinary Focus group that enabled the identification of the need for a mHealth intervention.