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Background Biological drugs have improved the management of immune-mediated inflammatory diseases (IMIDs) despite being associated with important safety issues such as immunogenicity, infections, and malignancies in real-world settings. Objective The aim of this study was to explore the potential of a large Italian multi-database distributed network for use in the postmarketing surveillance of biological drugs, including biosimilars, in patients with IMID. Methods A retrospective cohort study was conducted using 13 Italian regional claims databases during 2010–2019. A tailor-made R-based tool developed for distributed analysis of claims data using a study-specific common data model was customized for this study. We measured the yearly prevalence of biological drug users and the frequency of switches between originator and biosimilars for infliximab, etanercept, and adalimumab separately and stratified them by calendar year and region. We then calculated the cumulative number of users and person-years (PYs) of exposure to individual biological drugs approved for IMIDs. For a number of safety outcomes (e.g., severe acute respiratory syndrome coronavirus 2 [SARS-COV-2] infection), we conducted a sample power calculation to estimate the PYs of exposure required to investigate their association with individual biological drugs approved for IMIDs, considering different strengths of association. Results From a total underlying population of almost 50 million inhabitants from 13 Italian regions, we identified 143,602 (0.3%) biological drug users, with a cumulative exposure of 507,745 PYs during the entire follow-up. The mean age ± standard deviation of biological drug users was 49.3 ± 16.3, with a female-to-male ratio of 1.2. The age-adjusted yearly prevalence of biological drug users increased threefold from 0.7 per 1000 in 2010 to 2.1 per 1000 in 2019. Overall, we identified 40,996 users of biosimilars of tumor necrosis factor (TNF)-α inhibitors (i.e., etanercept, adalimumab, and infliximab) in the years 2015–2019. Of these, 46% (N = 18,845) switched at any time between originator and biosimilars or vice versa. To investigate a moderate association (incidence rate ratio 2) between biological drugs approved for IMIDs and safety events of interest, such as optic neuritis (lowest background incidence rate 10.4/100,000 PYs) or severe infection (highest background incidence rate 4312/100,000 PYs), a total of 43,311 PYs and 104 PYs of exposure to individual biological drugs, respectively, would be required. As such, using this network, of 15 individual biological drugs approved for IMIDs, the association with those adverse events could be investigated for four (27%) and 14 (93%), respectively. Conclusion The VALORE project multi-database network has access to data on more than 140,000 biological drug users (and > 0.5 million PYs) from 13 Italian regions during the years 2010–2019, which will be further expanded with the inclusion of data from other regions and more recent calendar years. Overall, the cumulated amount of person-time of exposure to biological drugs approved for IMIDs provides enough statistical power to investigate weak/moderate associations of almost all individual compounds and the most relevant safety outcomes. Moreover, this network may offer the opportunity to investigate the interchangeability of originator and biosimilars of several TNFα inhibitors in different therapeutic areas in real-world settings. Supplementary Information The online version contains supplementary material available at 10.1007/s40259-021-00498-3.

Cannabis use during adolescence is associated with an increased risk of developing psychosis. According to a current hypothesis, this results from detrimental effects of early cannabis use on brain maturation during this vulnerable period. However, studies investigating the interaction between early cannabis use and brain structural alterations hitherto reported inconclusive findings. We investigated effects of age of cannabis initiation on psychosis using data from the multicentric Personalized Prognostic Tools for Early Psychosis Management (PRONIA) and the Cannabis Induced Psychosis (CIP) studies, yielding a total sample of 102 clinically-relevant cannabis users with recent onset psychosis. GM covariance underlies shared maturational processes. Therefore, we performed source-based morphometry analysis with spatial constraints on structural brain networks showing significant alterations in schizophrenia in a previous multisite study, thus testing associations of these networks with the age of cannabis initiation and with confounding factors. Earlier cannabis initiation was associated with more severe positive symptoms in our cohort. Greater gray matter volume (GMV) in the previously identified cerebellar schizophrenia-related network had a significant association with early cannabis use, independent of several possibly confounding factors. Moreover, GMV in the cerebellar network was associated with lower volume in another network previously associated with schizophrenia, comprising the insula, superior temporal, and inferior frontal gyrus. These findings are in line with previous investigations in healthy cannabis users, and suggest that early initiation of cannabis perturbs the developmental trajectory of certain structural brain networks in a manner imparting risk for psychosis later in life.

In schizophrenia, neurocognitive subtypes can be distinguished based on cognitive performance and they are associated with neuroanatomical alterations. We investigated the existence of cognitive subtypes in shortly medicated recent onset psychosis patients, their underlying gray matter volume patterns and clinical characteristics. We used a K-means algorithm to cluster 108 psychosis patients from the multi-site EU PRONIA (Prognostic tools for early psychosis management) study based on cognitive performance and validated the solution independently (N = 53). Cognitive subgroups and healthy controls (HC; n = 195) were classified based on gray matter volume (GMV) using Support Vector Machine classification. A cognitively spared (N = 67) and impaired (N = 41) subgroup were revealed and partially independently validated (Nspared = 40, Nimpaired = 13). Impaired patients showed significantly increased negative symptomatology (pfdr = 0.003), reduced cognitive performance (pfdr pfdr p = 0.01) separating impaired patients from HC revealed increases and decreases across several fronto-temporal-parietal brain areas, including basal ganglia and cerebellum. Cognitive and functional disturbances alongside brain morphological changes in the impaired subgroup are consistent with a neurodevelopmental origin of psychosis. Our findings emphasize the relevance of tailored intervention early in the course of psychosis for patients suffering from the likely stronger neurodevelopmental character of the disease.

37th European Photovoltaic Solar Energy Conference and Exhibition; 20-24, In this work, we propose an innovative solution to fabricate a photonic back reflector layer prototype for Cu(In,Ga)(S,Se)2 (CIGS) solar cells that is optically rough, physically flat and electrically associated to molybdenum point contacts. This combination should lead to significant improvement in the efficiency of CIGS solar cells and favor the use of thinner CIGS layers. The nanostructured pattern is obtained using polystyrene beads self-assembly, followed by Ag evaporation and polystyrene beads lift-off. Stacks comprising a nanostructured multilayer of silver, molybdenum and an alumina layer deposited conformally by ALCVD, are successfully stacked. The optical characterization of the samples (in air) during the last steps before polishing, including angular resolved measurements, shows that these layers present very large haze factors (around 50%) over a large region of the solar spectrum. Preliminary attempts to planarize the substrate and to reveal the point contacts by chemical etching are reported.

PURPOSE OF REVIEW: Previous studies suggest an association between depression and increased risk of various type of infections, including acute bacterial skin and skin structure infections (ABSSSI). Here, we review the latest advancement in our understanding of immunity in patients with depression and its relevance to disease management and diagnosis, with a special focus on patients suffering from ABSSSI. RECENT FINDINGS: Recent studies have highlighted the role of hypothalamic-pituitary-adrenal axis, neuro-endocrine stress signaling pathways and behavioral attitudes (substance abuse and homelessness) in the pathogenesis of infections in depressed patients. Furthermore, acute bacterial infections, in turn, have emerged as a possible risk for depression development because of different mechanisms including antibiotic-driven changes in the microbiota. SUMMARY: Recent evidences have emphasized the threat that comanagement of depression and infection pose to infectious disease physician and psychiatrist. Depressed patients with ABSSSI must be closely monitored for drug side-effects, drug-drug interactions, toxicity, and adequate compliance. New management strategies including new long-acting antibiotics (e.g., dalbavancin) are welcome.

35th European Photovoltaic Solar Energy Conference and Exhibition; 878-881, CIGS based solar cells are part of the most popular solar cells developed. Recently, CIGS technology was transferred on flexible substrates with interesting performances. As it was proved that presence of alkali elements in the bulk materials leads to better efficiencies in soda-lime glass substrates, a post-deposition alkali treatment is necessary to achieve high performances when CIGS is deposited on other substrates with no internal alkali source. The control of introduced quantities, localization and distribution of alkali elements (and in certain case, their counter-ions) after post-deposition treatment and ageing is then a crucial information in order to optimize the cells. This study is related to this context and is mainly oriented on alkali reactivity, by considering their evolutions at the surface but also at the sub-surface with Ar+ profiling, thanks to XPS measurements.

Objective: To investigate the capacity and participation restrictions over oneyear in patients treated in community mental health services. Materials and Methods: We recruited 100 consecutive patients with schizophrenia or bipolar I disorder. The assessment instruments included the Mini-ICF-APP, the BPRS and the Clinical Global Impression Scale (CGI). Results: Capacity/participation restrictions and psychopathology levels improved significantly at one year in each diagnostic group. Moreover, changes in Mini-ICF-APP factors (proficiency, relational capacity, autonomy) were significantly higher in patients who were improved or much improved (CGI-Improvement = 1, 2) compared with those observed in patients who were not improved. A higher baseline functional impairment and a higher decrease in psychopathology predicted a higher improvement in total Mini-ICF-APP. After controlling for the effect of these predictors, no difference between diagnostic groups was found. Conclusions: When a community-based treatment is effective in reducing symptom severity, a concurrent improvement is obtained in capacity and participation functioning. The Mini-ICF-APP was sensitive to change in psychopathology and therefore can be used in routine clinical assessments.

Introduction: Major depression is a worldwide problem and often remains undetected and untreated. Given the low rates of detection plus the need to intervene in a short time, it is important to identify factors which are likely to improve treatment outcomes. Methods: STIMA-D was designed to provide the profile of patients with major depression in Italy (focusing on pathway to care, patient characteristics, drug therapy and treatment outcomes). The patients enrolled (M/F, aged between 18 and 65) experienced single/multiple episodes of major depression (DSM-IV-TR). Patients with lifetime or current bipolar syndrome or other mental disorders were excluded. Results: 44 of the 50 invited centers sent data concerning 1 140 patients. The majority of patients were women. Among working individuals, 52.5% of them were absent from work due to depression in the previous 6 months. Recurrent episodes of major depression were very common and were associated with persistence of residual post-episodic symptoms, a family history of mood disorders and presence of anxiety. 59.6% of the patients were treated with monotherapy (SSRI or SNRI), while 19.2% of them were treated with SSRI plus SNRI. Only the 25.5% on monotherapy had a complete response compared to 12.4% of patients on dual therapy. Discussion: Poor outcomes in major depression have profound implications on patients’ quality of life and cost burden. New pharmacological approaches with novel modes of action are therefore urgently needed.