The Brescia Internationally Validated European Guidelines on Minimally Invasive Pancreatic Surgery (EGUMIPS).

OBJECTIVE: To develop and update evidence-based and consensus-based guidelines on laparoscopic and robotic pancreatic surgery. SUMMARY BACKGROUND DATA: Minimally invasive pancreatic surgery (MIPS), including laparoscopic and robotic surgery, is complex and technically demanding. Minimizing the risk for patients requires stringent, evidence-based guidelines. Since the International Miami Guidelines on MIPS in 2019, new developments and key publications have been reported, necessitating an update. METHODS: Evidence-based guidelines on 22 topics in 8 domains were proposed: terminology, indications, patients, procedures, surgical techniques and instrumentation, assessment tools, implementation and training, and artificial intelligence. The Brescia Internationally Validated European Guidelines on Minimally Invasive Pancreatic Surgery (EGUMIPS, September 2022) used the Scottish Intercollegiate Guidelines Network (SIGN) methodology to assess the evidence and develop guideline recommendations, the Delphi method to establish consensus on the recommendations among the Expert Committee, and the AGREE II-GRS tool for guideline quality assessment and external validation by a Validation Committee. RESULTS: Overall, 27 European experts, 6 international experts, 22 international Validation Committee members, 11 Jury Committee members, 18 Research Committee members, and 121 registered attendees of the 2-day meeting were involved in the development and validation of the guidelines. In total, 98 recommendations were developed, including 33 on laparoscopic, 34 on robotic, and 31 on general MIPS, covering 22 topics in 8 domains. Out of 98 recommendations, 97 reached at least 80% consensus among the experts and congress attendees, and all recommendations were externally validated by the Validation Committee. CONCLUSIONS: The EGUMIPS evidence-based guidelines on laparoscopic and robotic MIPS can be applied in current clinical practice to provide guidance to patients, surgeons, policy-makers, and medical societies.

Virtual Reality Combined With Psychoeducation to Improve Emotional Well-Being in Informal Caregivers of Alzheimer's Disease Patients: Rationale and Study Design of a Randomized Controlled Trial.

OBJECTIVES: Care for community-dwelling people with dementia is frequently delegated to relatives, who find themselves in the role of informal caregivers with no practical management knowledge. This situation exposes caregivers to increased risk for emotional wellbeing. The current study aims to test whether the integration of the efficacy of an immersive virtual reality (VR) experience into an online psychoeducational program impacts caregiver empathy and therefore emotional wellbeing. METHODS: One-hundred informal caregivers of mild-to-moderate Alzheimer's disease (AD) patients will be enrolled and randomly assigned to (i) an online psychoeducational program (control arm); or (ii) an online psychoeducational program integrated with VR (experimental arm). VR will consist of 360-degree videos involving the caregivers to an immersive experience of dementia symptoms from the patient's perspective. Before, after the intervention and after 2 months, all participants will complete validated clinical scales for caregiver burden and anxiety (primary outcomes) and sense of competence and dispositional empathy (secondary outcomes). A subsample of 50 participants will also undergo MRI exam, including structural and functional (resting-state and task-functional MRI [fMRI]) sequences. The fMRI task paradigm will use emotional stimuli to evaluate the neural correlate of empathy, by stressing its cognitive and affective components. The main outcome will be the change in the clinical assessment; the secondary outcome will be the change in brain connectivity of networks subserving the empathic and emotional functioning. RESULTS: We expect that the psychoeducational program will decrease anxiety and stress, enabling caregivers to perceive themselves capable of managing AD patients at home, educating them on symptom handling and boosting their cognitive empathy. In the experimental intervention, the VR-based experience will act as an add-on to psychoeducation, leading to greater improvement in the assessed clinical dimensions. VR should, in fact, enable a deeper understanding of disease symptoms and improve caregivers' cognitive empathy. We expect that the experimental intervention will result in deeper comprehension of disease symptoms and further strengthen caregivers' cognitive empathy. At the neural level, we expect to observe increased activation in circuits subserving cognitive empathy and decreased activation in circuits underlying affective empathy. CONCLUSIONS: To the best of our knowledge, this will be the first randomized controlled trial assessing the effect of combining psychoeducational interventions with VR-based experience in caregivers, and assessing both clinical and imaging outcomes. TRIAL REGISTRATION: Registered in ClinicalTrials.gov (NCT05780476).

Unsupervised [18F]Flortaucipir cutoffs for tau positivity and staging in Alzheimer's disease.

PURPOSE: Several [18F]Flortaucipir cutoffs have been proposed for tau PET positivity (T+) in Alzheimer's disease (AD), but none were data-driven. The aim of this study was to establish and validate unsupervised T+ cutoffs by applying Gaussian mixture models (GMM). METHODS: Amyloid negative (A-) cognitively normal (CN) and amyloid positive (A+) AD-related dementia (ADRD) subjects from ADNI (n=269) were included. ADNI (n=475) and Geneva Memory Clinic (GMC) cohorts (n=98) were used for validation. GMM-based cutoffs were extracted for the temporal meta-ROI, and validated against previously published cutoffs and visual rating. RESULTS: GMM-based cutoffs classified less subjects as T+, mainly in the A- CN (<3.4% vs >28.5%) and A+ CN (<14.5% vs >42.9%) groups and showed higher agreement with visual rating (ICC=0.91 vs ICC<0.62) than published cutoffs. CONCLUSION: We provided reliable data-driven [18F]Flortaucipir cutoffs for in vivo T+ detection in AD. These cutoffs might be useful to select participants in clinical and research studies.

A multinational case-control study comparing forensic and non-forensic patients with schizophrenia spectrum disorders: the EU-VIORMED project.

BACKGROUND: The relationship between schizophrenia and violence is complex. The aim of this multicentre case-control study was to examine and compare the characteristics of a group of forensic psychiatric patients with a schizophrenia spectrum disorders and a history of significant interpersonal violence to a group of patients with the same diagnosis but no lifetime history of interpersonal violence. METHOD: Overall, 398 patients (221 forensic and 177 non-forensic patients) were recruited across five European Countries (Italy, Germany, Poland, Austria and the United Kingdom) and assessed using a multidimensional standardised process. RESULTS: The most common primary diagnosis in both groups was schizophrenia (76.4%), but forensic patients more often met criteria for a comorbid personality disorder, almost always antisocial personality disorder (49.1 v. 0%). The forensic patients reported lower levels of disability and better social functioning. Forensic patients were more likely to have been exposed to severe violence in childhood. Education was a protective factor against future violence as well as higher levels of disability, lower social functioning and poorer performances in cognitive processing speed tasks, perhaps as proxy markers of the negative syndrome of schizophrenia. Forensic patients were typically already known to services and in treatment at the time of their index offence, but often poorly compliant. CONCLUSIONS: This study highlights the need for general services to stratify patients under their care for established violence risk factors, to monitor patients for poor compliance and to intervene promptly in order to prevent severe violent incidents in the most clinically vulnerable.

Precuneus magnetic stimulation for Alzheimer's disease: a randomized, sham-controlled trial.

Repetitive transcranial magnetic stimulation (rTMS) is emerging as a non-invasive therapeutic strategy in the battle against Alzheimer's disease. Alzheimer's disease patients primarily show alterations of the default mode network for which the precuneus is a key node. Here, we hypothesized that targeting the precuneus with TMS represents a promising strategy to slow down cognitive and functional decline in Alzheimer's disease patients. We performed a randomized, double-blind, sham-controlled, phase 2, 24-week trial to determine the safety and efficacy of precuneus stimulation in patients with mild-to-moderate Alzheimer's disease. Fifty Alzheimer's disease patients were randomly assigned in a 1:1 ratio to either receive precuneus or sham rTMS (mean age 73.7 years; 52% female). The trial included a 24-week treatment, with a 2-week intensive course in which rTMS (or sham) was applied daily five times per week, followed by a 22-week maintenance phase in which stimulation was applied once weekly. The Clinical Dementia Rating Scale-Sum of Boxes was selected as the primary outcome measure, in which post-treatment scores were compared to baseline. Secondary outcomes included score changes in the Alzheimer's Disease Assessment Scale-Cognitive Subscale, Mini-Mental State Examination and Alzheimer's Disease Cooperative Study-Activities of Daily Living scale. Moreover, single-pulse TMS in combination with EEG was used to assess neurophysiological changes in precuneus cortical excitability and oscillatory activity. Our findings show that patients that received precuneus repetitive magnetic stimulation presented a stable performance of the Clinical Dementia Rating Scale-Sum of Boxes score, whereas patients treated with sham showed a worsening of their score. Compared with the sham stimulation, patients in the precuneus stimulation group also showed also significantly better performances for the secondary outcome measures, including the Alzheimer's Disease Assessment Scale-Cognitive Subscale, Mini-Mental State Examination and Alzheimer's Disease Cooperative Study-Activities of Daily Living scale. Neurophysiological results showed that precuneus cortical excitability remained unchanged after 24 weeks in the precuneus stimulation group, whereas it was significantly reduced in the sham group. Finally, we found an enhancement of local gamma oscillations in the group treated with precuneus stimulation but not in patients treated with sham. We conclude that 24 weeks of precuneus rTMS may slow down cognitive and functional decline in Alzheimer's disease. Repetitive TMS targeting the default mode network could represent a novel therapeutic approach in Alzheimer's disease patients.

Validation of the Italian Version of the Daily Spiritual Experience Scale Among Psychiatric Patients.

Spiritual experience can represent an important aspect of mental health. The purpose of the current study was to validate the Italian version of the Daily Spiritual Experience Scale (DSES-IT) in a population of patients with different psychiatric disorders. It involved 209 patients enrolled in four facilities within the network of IRCCS Centro San Giovanni di Dio Fatebenefratelli Research Institute in Italy. The exploratory factor analysis (EFA) indicated two domains. Internal consistency was very good (Cronbach's Alpha = .93). Scale stability across time assessed by test-retest reliability showed a good performance (Pearson's correlation r > 0.9 for all items). Convergent reliability was assessed by Pearson's correlation between the DSES-IT and the WHOQOL-SRPB scales (r = - .63, p = 0.001). Diagnostic group comparison revealed a statistically significant difference among the patient groups (ANOVA test p = 0.01). The results confirm good psychometric properties of the Italian version of the DSES scale.

Responsiveness to left-prefrontal tDCS varies according to arousal levels.

Over the past two decades, the postulated modulatory effects of transcranial direct current stimulation (tDCS) on the human brain have been extensively investigated. However, recent concerns on reliability of tDCS effects have been raised, principally due to reduced replicability and to interindividual variability in response to tDCS. These inconsistencies are likely due to the interplay between the level of induced cortical excitability and unaccounted structural and state-dependent functional factors. On these grounds, we aimed at verifying whether the behavioural effects induced by a common tDCS montage (F3-rSOA) were influenced by the participants' arousal levels, as part of a broader mechanism of state-dependency. Pupillary dynamics were recorded during an auditory oddball task while applying either a sham or real tDCS. The tDCS effects were evaluated as a function of subjective and physiological arousal predictors (STAI-Y State scores and pre-stimulus pupil size, respectively). We showed that prefrontal tDCS hindered task learning effects on response speed such that performance improvement occurred during sham, but not real stimulation. Moreover, both subjective and physiological arousal predictors significantly explained performance during real tDCS, with interaction effects showing performance improvement only with moderate arousal levels; likewise, pupil response was affected by real tDCS according to the ongoing levels of arousal, with reduced dilation during higher arousal trials. These findings highlight the potential role of arousal in shaping the neuromodulatory outcome, thus emphasizing a more careful interpretation of null or negative results while also encouraging more individually tailored tDCS applications based on arousal levels, especially in clinical populations.

Chromoendoscopy Is Not Superior to White Light Endoscopy in Improving Adenoma Detection in Lynch Syndrome Cohort Undergoing Surveillance with High-Resolution Colonoscopy: A Real-World Evidence Study.

BACKGROUND: Endoscopic surveillance in patients with Lynch syndrome (LS) is crucial due to a genetically based high risk of colorectal cancer (CRC). We aimed to compare the adenoma detection rate (ADR) between high-resolution white light endoscopy (WLE) alone and WLE plus dye chromoendoscopy (CE) in a cohort of LS patients. METHODS: In a context of real-world data, we retrospectively enrolled 50 LS patients who had non-randomly undergone WLE versus CE surveillance examinations from 2007 to 2019. The 2 groups were compared at baseline (BL) in terms of the rate of patients with lesions and the number of lesions, and at follow-up (FU), to evaluate a possible enhanced detection rate. Longitudinal analysis of the effect of the endoscopy type on the main outcomes was performed by generalized linear mixed models. RESULTS: Forty-two patients had undergone at least one diagnostic colonoscopy. At BL and at FU analysis, we found no significant differences in detection rates and clinical-pathological features between WLE and CE groups. At the longitudinal analysis, an increase in the endoscopy rank (i.e., the position of each colonoscopy for all the colonoscopies that a patient had undergone) was associated with an increase in polyp detection rate (p = 0.006) and ADR (p = 0.005), while a trend toward significance (p = 0.069) was found for endoscopy type (CE vs. WLE) in the detection of serrated lesions. CONCLUSIONS: CE is not superior to high-resolution WLE in increasing the ADR. Even under standard WLE, an active and careful endoscopic surveillance of LS patients can prevent CRC.

Cognitive and biological effects of citrus phytochemicals in subjective cognitive decline: a 36-week, randomized, placebo-controlled trial.

BACKGROUND: Auraptene (AUR) and naringenin (NAR) are citrus-derived phytochemicals that influence several biological mechanisms associated with cognitive decline, including neuronal damage, oxidative stress and inflammation. Clinical evidence of the efficacy of a nutraceutical with the potential to enhance cognitive function in cohorts at risk of cognitive decline would be of great value from a preventive perspective. The primary aim of this study is to determine the cognitive effects of a 36-week treatment with citrus peel extract standardized in levels of AUR and NAR in older adults experiencing subjective cognitive decline (SCD). The secondary aim is to determine the effects of these phytochemicals on blood-based biomarkers indicative of neuronal damage, oxidative stress, and inflammation. METHODS: Eighty older persons with SCD will be recruited and randomly assigned to receive the active treatment (400 mg of citrus peel extract containing 0.1 mg of AUR and 3 mg of NAR) or the placebo at a 1:1 ratio for 36 weeks. The primary endpoint is a change in the Repeatable Battery for the Assessment of Neuropsychological Status score from baseline to weeks 18 and 36. Other cognitive outcomes will include changes in verbal and nonverbal memory, attention, executive and visuospatial functions. Blood samples will be collected from a consecutive subsample of 60 participants. The secondary endpoint is a change in interleukin-8 levels over the 36-week period. Other biological outcomes include changes in markers of neuronal damage, oxidative stress, and pro- and anti-inflammatory cytokines. CONCLUSION: This study will evaluate whether an intervention with citrus peel extract standardized in levels of AUR and NAR has cognitive and biological effects in older adults with SCD, facilitating the establishment of nutrition intervention in people at risk of cognitive decline. TRIAL REGISTRATION: The trial is registered with the United States National Library of Medicine at the National Institutes of Health Registry of Clinical Trials under the code NCT04744922 on February 9th, 2021 ( https://www. CLINICALTRIALS: gov/ct2/show/NCT04744922 ).

Positive and negative syndrome scale in forensic patients with schizophrenia spectrum disorders: a systematic review and meta-analysis.

Among forensic patients with schizophrenia spectrum disorders, the association between symptomatology and violence is still not entirely clear in literature, especially because symptoms shift both during the acute phase of the illness and after. The aims were to investigate the level of symptomatology in forensic patients and to evaluate if there are differences in the level of symptoms between forensic and non-forensic patients. According to PRISMA guidelines, a systematic search was performed in PubMed, Web of Science, and ProQuest, using the following key words: "forensic" AND "Positive and Negative Syndrome Scale" OR "PANSS". A total of 27 studies were included in the systematic review, while only 23 studies in the meta-analysis. The overall sample included a total of 1702 participants, most commonly male and inpatients in forensic settings. We found that studies with an entirely male sample had significantly lower Positive PANSS ratings than studies with mixed samples. Although both forensic and non-forensic patients were affected by mild psychopathological symptoms, forensic patients presented higher ratings in all four PANSS scales. This meta-analysis shows that forensic patients reported a mild level of symptomatology, as assessed with the PANSS, and therefore might be considered as patients in partial remission. Among patients with schizophrenia, the association between symptoms and violence is very complex: many factors might be considered as key mediators and thus should be taken into account to explain this association. Further studies are needed.Trial registration all materials and data can be found on the OSF framework: https://osf.io/5ceja (date of registration: 8 September 2021).

Harmonizing neuropsychological assessment for mild neurocognitive disorders in Europe.

INTRODUCTION: Harmonized neuropsychological assessment for neurocognitive disorders, an international priority for valid and reliable diagnostic procedures, has been achieved only in specific countries or research contexts. METHODS: To harmonize the assessment of mild cognitive impairment in Europe, a workshop (Geneva, May 2018) convened stakeholders, methodologists, academic, and non-academic clinicians and experts from European, US, and Australian harmonization initiatives. RESULTS: With formal presentations and thematic working-groups we defined a standard battery consistent with the U.S. Uniform DataSet, version 3, and homogeneous methodology to obtain consistent normative data across tests and languages. Adaptations consist of including two tests specific to typical Alzheimer's disease and behavioral variant frontotemporal dementia. The methodology for harmonized normative data includes consensus definition of cognitively normal controls, classification of confounding factors (age, sex, and education), and calculation of minimum sample sizes. DISCUSSION: This expert consensus allows harmonizing the diagnosis of neurocognitive disorders across European countries and possibly beyond.

The impact of artifact removal approaches on TMS-EEG signal.

Transcranial magnetic stimulation (TMS)-evoked potentials (TEPs) allow one to assess cortical excitability and effective connectivity in clinical and basic research. However, obtaining clean TEPs is challenging due to the various TMS-related artifacts that contaminate the electroencephalographic (EEG) signal when the TMS pulse is delivered. Different preprocessing approaches have been employed to remove the artifacts, but the degree of artifact reduction or signal distortion introduced in this phase of analysis is still unknown. Knowing and controlling this potential source of uncertainty will increase the inter-rater reliability of TEPs and improve the comparability between TMS-EEG studies. The goal of this study was to assess the variability in TEP waveforms due to of the use of different preprocessing pipelines. To accomplish this aim, we preprocessed the same TMS-EEG data with four different pipelines and compared the results. The dataset was obtained from 16 subjects in two identical recording sessions, each session consisting of both left dorsolateral prefrontal cortex and left inferior parietal lobule stimulation at 100% of the resting motor threshold. Considerable differences in TEP amplitudes and global mean field power (GMFP) were found between the preprocessing pipelines. Topographies of TEPs from the different pipelines were all highly correlated (ρ>0.8) at latencies over 100 ms. By contrast, waveforms at latencies under 100 ms showed a variable level of correlation, with ρ ranging between 0.2 and 0.9. Moreover, the test-retest reliability of TEPs depended on the preprocessing pipeline. Taken together, these results take us to suggest that the choice of the preprocessing approach has a marked impact on the final TEP, and that further studies are needed to understand advantages and disadvantages of the different approaches.

Impact of SARS-CoV-2 Pandemic on Colorectal Cancer Screening Delay: Effect on Stage Shift and Increased Mortality.

BACKGROUND & AIMS: The SARS-CoV-2 pandemic had a sudden, dramatic impact on healthcare. In Italy, since the beginning of the pandemic, colorectal cancer (CRC) screening programs have been forcefully suspended. We aimed to evaluate whether screening procedure delays can affect the outcomes of CRC screening. METHODS: We built a procedural model considering delays in the time to colonoscopy and estimating the effect on mortality due to up-stage migration of patients. The number of expected CRC cases was computed by using the data of the Italian screened population. Estimates of the effects of delay to colonoscopy on CRC stage, and of stage on mortality were assessed by a meta-analytic approach. RESULTS: With a delay of 0-3 months, 74% of CRC is expected to be stage I-II, while with a delay of 4-6 months there would be a 2%-increase for stage I-II and a concomitant decrease for stage III-IV (P = .068). Compared to baseline (0-3 months), moderate (7-12 months) and long (> 12 months) delays would lead to a significant increase in advanced CRC (from 26% to 29% and 33%, respectively; P = .008 and P < .001, respectively). We estimated a significant increase in the total number of deaths (+12.0%) when moving from a 0-3-months to a >12-month delay (P = .005), and a significant change in mortality distribution by stage when comparing the baseline with the >12-months (P < .001). CONCLUSIONS: Screening delays beyond 4-6 months would significantly increase advanced CRC cases, and also mortality if lasting beyond 12 months. Our data highlight the need to reorganize efforts against high-impact diseases such as CRC, considering possible future waves of SARS-CoV-2 or other pandemics.

Does being accompanied make a difference in communication during breast cancer consultations? Results from a multi-centered randomized controlled trial.

OBJECTIVES: This study is based on a multi-centered RCT conducted on breast cancer patients during their first consultation with an oncologist. The main aim was to evaluate whether the introduction of a communication tool (i.e., the Question Prompt Sheet or Question Listing), with or without a companion, impacted the number of questions asked by patients during the consultation, and subsequent psychological and relational outcomes. METHODS: The sample consisted of 324 breast cancer patients who were randomly placed into one of the two intervention groups: Question Prompt Sheet or Question Listing. Before and after the consultation, patients completed a set of standardized instruments: Satisfaction with decisions made during the consultation (SWD), Shared Decision Making Questionnaire (SDMQ-9), Patient Enablement Instrument (PEI), Patient Health Questionnaire Depression scale (PHQ-9), General Health Questionnaire (GHQ-12). RESULTS: The results indicate that the number of questions asked during the consultation was higher when a Question Listing was provided and when the patient was unaccompanied. Unaccompanied patients asked more questions in both groups and had significantly lower scores than accompanied on the GHQ-12 and on the PHQ-9, indicating lower clinical symptomatology. CONCLUSIONS: Results are in contrast with previous literature, indicating that being unaccompanied help patients to interact more with the oncologist. Further studies are needed to evaluate how the presence or not of a companion really impacts breast cancer patients during their first consultation with an oncologist. TRIAL REGISTRATION: ClinicalTrials.gov NCT01510964.

Investigating the Endo-Lysosomal System in Major Neurocognitive Disorders Due to Alzheimer's Disease, Frontotemporal Lobar Degeneration and Lewy Body Disease: Evidence for SORL1 as a Cross-Disease Gene.

Dysfunctions in the endo-lysosomal system have been hypothesized to underlie neurodegeneration in major neurocognitive disorders due to Alzheimer's disease (AD), Frontotemporal Lobar Degeneration (FTLD), and Lewy body disease (DLB). The aim of this study is to investigate whether these diseases share genetic variability in the endo-lysosomal pathway. In AD, DLB, and FTLD patients and in controls (948 subjects), we performed a targeted sequencing of the top 50 genes belonging to the endo-lysosomal pathway. Genetic analyses revealed (i) four previously reported disease-associated variants in the SORL1 (p.N1246K, p.N371T, p.D2065V) and DNAJC6 genes (p.M133L) in AD, FTLD, and DLB, extending the previous knowledge attesting SORL1 and DNAJC6 as AD- and PD-related genes, respectively; (ii) three predicted null variants in AD patients in the SORL1 (p.R985X in early onset familial AD, p.R1207X) and PPT1 (p.R48X in early onset familial AD) genes, where loss of function is a known disease mechanism. A single variant and gene burden analysis revealed some nominally significant results of potential interest for SORL1 and DNAJC6 genes. Our data highlight that genes controlling key endo-lysosomal processes (i.e., protein sorting/transport, clathrin-coated vesicle uncoating, lysosomal enzymatic activity regulation) might be involved in AD, FTLD and DLB pathogenesis, thus suggesting an etiological link behind these diseases.

DAily time use, Physical Activity, quality of care and interpersonal relationships in patients with Schizophrenia spectrum disorders (DiAPASon): an Italian multicentre study.

BACKGROUND: Schizophrenia spectrum disorders (SSD) are ranked among the leading causes of disabilities worldwide. Many people with SSD spend most of their daily time being inactive, and this is related to the severity of negative symptoms. Here, we present the 3-year DiAPAson project aimed at (1) evaluating the daily time use among patients with SSD living in Residential Facilities (RFs) compared to outpatients with SSD and to the general population (Study 1); (2) evaluating the quality of staff-patient relationships, its association with specific patient outcomes and the quality of care provided in RFs (Study 2); and (3) assessing daily activity patterns in residential patients, outpatients with SSD and healthy controls using real-time methodologies (Study 3). METHODS: Study 1 will include 300 patients with SSD living in RFs and 300 outpatients; data obtained in these clinical populations will be compared with normative data obtained by the National Institute of Statistics (ISTAT) in the national survey on daily time use. Time use assessments will consist of daily diaries asking participants to retrospectively report time spent in different activities. In Study 2, a series of questionnaires will be administered to 300 residential patients (recruited for Study 1) to evaluate the quality of care and staff-patient relationships, level of well-being and burnout of RFs' staff, and quality of RFs using a European standardized questionnaire (QuIRC-SA). In Study 3, the daily time use will be evaluated in a subgroup of 50 residential patients, 50 outpatients and 50 healthy controls using the Experience Sampling Method approach (participants will complete a brief questionnaire -about time use, mood and perceived energy- on a smartphone 8 times a day for 1 week) to compare retrospective and real-time reports. Moreover, their level of physical activity, sleep patterns, and energy expenditure will be monitored through a multi-sensor device. DISCUSSION: This project is highly innovative because it combines different types of assessments (i.e., retrospective and real-time reports; multi-sensor monitoring) to trace an accurate picture of daily time use and levels of physical activity that will help identify the best therapeutic options promoting daily activities and physical exercise in patients with SSD. TRIAL REGISTRATION: ISRCTN registry ID ISRCTN21141466.

Substance use disorders and violent behaviour in patients with severe mental disorders: A prospective, multicentre study.

OBJECTIVE: The relationship between alcohol and substance use and the risk of violence exhibited by patients with mental disorders is under-researched. This prospective cohort study aims to compare patients with severe mental disorders and with different substance use behaviors in terms of sociodemographic and clinical characteristics, hostility, impulsivity and aggressive behaviors. Furthermore, this study aims to assess differences in violent behaviors during a 1-year monitoring follow-up. METHODS: A total of 378 participants with severe mental disorders from Italian residential facilities and from four Departments of Mental Health (244 outpatients and 134 residential patients) were enrolled. Participants were categorized as Persons with Current Substance Use, Persons with Former Substance Use and Persons with Non-Substance Use. All these patients underwent a complex multidimensional assessment, including the lifetime and current substance use; a subsample of outpatients was also assessed with a laboratory substance assay including the testing for specific substances. We assessed the differences among these three groups in hostility, impulsivity and aggressive behaviors. RESULTS: The results of the close 1-year monitoring show a significantly higher risk of violence for patients with severe mental disorders Persons with Current Substance Use compared to Persons with Former Substance Use and Persons with Non-Substance Use. Persons with Current Substance Use showed significantly higher scores for irritability, negativism and verbal assault compared to Persons with Non-Substance Use. Persons with Former Substance Use showed significantly higher scores for lifetime history of aggressive behaviors compared with patients with Persons with Non-Substance Use. CONCLUSION: These findings suggest that patients with comorbid mental illness and substance use disorders should be referred for specific interventions to reduce aggressive behavior and ensure patient well-being and community safety.

Randomized controlled trial on the efficacy of a multilevel non-pharmacologic intervention in older adults with subjective memory decline: design and baseline findings of the E.Mu.N.I. study.

BACKGROUND: Alzheimer's Disease (AD) is a multifactorial disorder driven by genetic and modifiable lifestyle risk factors. Lifestyle primary prevention initiatives may reduce the prevalence and incidence of dementia in older adults. OBJECTIVES: The E.Mu.N.I study is a randomized controlled trial investigating the effect of multilevel non-pharmacologic interventions on cognitive performances (primary outcome) and structural and vascular brain MRI markers (secondary outcome), as well as markers of brain functional connectivity change (exploratory outcome), in older adults with subjective memory decline (SMD). Here, we present the study design and the baseline features of the sample. METHODS: Cognitively intact older adults with SMD, enrolled between February 2016 and June 2017, were randomly assigned to one of the 3 interventions for 1 year: Active Control Intervention (ACI), i.e., educational lessons; Partial Intervention (PI), i.e., homotaurine administration (100 mg/die) and lessons on the Mediterranean diet; Multilevel Intervention (MI), i.e., PI plus computerized cognitive training and physical exercise training. RESULTS: One-hundred and twenty-eight eligible participants were enrolled (66% female; age: 68 ± 5 years). Eighty-two percent of the sample was composed of volunteers with SMD from the community. Participants were randomly allocated to the interventions as follows: ACI (N = 40), PI (N = 44), MI (N = 44). No significant differences among groups emerged on socio-demographic, clinical-neuropsychological variables and MRI markers at baseline. CONCLUSIONS: The outcomes obtained from the E.Mu.N.I. study will clarify the efficacy of multilevel non-pharmacologic interventions on cognitive and neuroimaging markers in SMD individuals. This is a crucial step forward for the development of cost-effective non-pharmacologic primary prevention initiatives for AD.

Aggressive behavior and metacognitive functions: a longitudinal study on patients with mental disorders.

BACKGROUND: Metacognitive functions play a key role in understanding which psychological variables underlying the personality might lead a person with a severe mental disorder to commit violent acts against others. The aims of this study were to: (a) investigate the differences between patients with poor metacognitive functioning (PM group) and patients with good metacognitive functioning (GM group) in relation to a history of violence; (b) investigate the differences between the two groups in relation to aggressive behavior during a 1-year follow-up; and (c) analyze the predictors of aggressive behavior. METHODS: In a prospective cohort study, patients with severe mental disorders with and without a lifetime history of serious violence were assessed with a large set of standardized instruments and were evaluated bi-monthly with MOAS in order to monitor any aggressive behavior. The total sample included 180 patients: 56% outpatients and 44% inpatients, and the majority were male (75%) with a mean age of 44 (± 9.8) years, and half of them had a history of violence. The sample was split into two groups: poor metacognition (PM) group and good metacognition (GM) group, according to MAI evaluation scores. RESULTS: The PM patients reported a history of violence more frequently than GM patients, during the 1-year follow-up, but no differences between groups in aggressive and violent behavior were found. The strongest predictors of aggressive behavior were: borderline and passive-aggressive personality traits and a history of violence, anger, and hostility. The metacognitive functions alone did not predict aggressive behavior, but metacognitive functions interacted with hostility and angry reactions in predicting aggressive behavior. CONCLUSIONS: This study led to some important conclusions: (a) some aspects closely related to violence are predictive of aggressive behavior only in patients with poor metacognition, thus good metacognition is a protective factor; (b) poor metacognition is associated with a history of violence, which in turn increases the risk of committing aggressive behavior.

European violence risk and mental disorders (EU-VIORMED): a multi-centre prospective cohort study protocol.

BACKGROUND: The link between schizophrenia spectrum disorders (SSD) and violence is a core issue for most forensic psychiatric services. However, the drivers of violence in this population remain unclear, and, to date tools to predict violence risk have a range of limitations. Perhaps because of this uncertainty about the nature of violence risk, treatment programmes and care pathways for mentally disordered offenders vary substantially across the European Union, and differences in legal and policy frameworks are highly relevant. METHODS: The three-year EU-VIORMED project (Grant Number PP-2-3-2016, November 2017-October 2020) involves forensic centres in Italy, Austria, Germany, Poland, and the U.K. It aims to: (a) identify and compare violence risk factors, clinical needs, and decision making capacity in violent (N = 200, "cases") and nonviolent patients with SSD (N = 200; "controls") using a case-control design; (b) test the predictive validity of the HCR-20v3, OxMIS and FoVOx among cases alone (N = 200), using a prospective cohort study; and (c) compare forensic-psychiatric care pathways across the EU, in a continent wide service mapping study. DISCUSSION: Data collection started in September 2018 and continues. By September 2019, 333 participants have been enrolled (201 cases and 132 controls were recruited). Experts from 23 countries provided data for the service mapping exercise. TRIAL REGISTRATION: Retrospectively registered on January 2, 2019 as researchregistry4604 January 2, 2019.