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Background The prescription of antipsychotics outside overt psychotic conditions remains controversial, especially in youth where it is relatively widespread. Furthermore, some studies seem to indicate that antipsychotic exposure in individuals at ultra-high-risk (UHR) for psychosis is associated with higher conversion rates. This study was set up to test whether the inter-current prescription of antipsychotics in UHR patients was related to the psychometric threshold for a diagnosis of psychosis. Methods The 24-item Brief Psychiatric Rating Scale (BPRS) was used to quantify treatment response up to 2 years in 125 UHR participants. Standard psychometric criteria were used to quantify conversion to psychosis. Kaplan-Mayer and Cox proportional hazard survival analysis were applied to determine the impact of having or not received the prescription of an antipsychotic drug. Results Over the study period 30 (24%) subjects received the prescription of an antipsychotic. In the sample, there were 31 participants (25%) who had reached the psychometric threshold for conversion to psychosis after 2 years of treatment. UHR people who received a prescription of antipsychotics during the first 2 years of treatment were statistically more likely to reach the psychometric threshold for conversion to psychosis on the BPRS: Hazard ratio = 3.03 (95%CI: 1.49-6.16); p = .003. Conclusion This finding supports the hypothesis that the prescription of antipsychotics within UHR cohorts is to be considered a red flag for higher incipient risk of conversion to psychosis.

BACKGROUND Ultra-high risk (UHR) people are a heterogeneous group with variable outcomes. This study aimed at (a) estimating trajectories of response to treatment to identify homogeneous subgroups; (b) establishing the impact on these trajectories of known predictors of outcome in UHR subjects. METHODS Mixed models of growth curves and latent class growth analysis (LCGA) were applied to the 24-item brief psychiatric rating scale (BPRS) to measure the response to treatment over 2 years in 125 UHR participants. Group differences were tested on sociodemographic variables and clinical indicators that are known to affect the outcome in UHR people. RESULTS BPRS scores decreased across all tested models, with a greater decrease for affective and positive symptoms than for all other dimensions of BPRS. Past admissions to the hospital for psychiatric reasons other than psychosis and the presence of a decline in premorbid functioning before the episode were associated with a slower decrease of BPRS score. LCGA identified three classes, one (82% of participants) with a progressive decrease in the BPRS scores, a second class with a moderate improvement (10%), and a third with no improvement (8%). Those in the 'no improvement' class had a higher chance of receiving a diagnosis of psychosis within the spectrum of schizophrenia. CONCLUSION Most UHR individuals that are treated within a specialized service undergo substantial improvement in their psychopathology, but some seem resistant to the protocol of treatment and need close reevaluation within the first 12 months of treatment.

Background: Additional extrinsic muscles of the tongue are reported in literature and one of them is the myloglossus muscle (MGM). Since MGM is nowadays considered as anatomical variant, the aim of this study is to clarify some open questions by evaluating and describing the myloglossal anatomy (including both MGM and its ligamentous counterpart) during human cadaver dissections. Materials and methods: Twenty-one regions (including masticator space, sublingual space and adjacent areas) were dissected and the presence and appearance of myloglossus were considered, together with its proximal and distal insertions, vascularisation and innervation. Results: The myloglossus was present in 61.9% of cases with muscular, ligamentous or mixed appearance and either bony or muscular insertion. Facial artery provided myloglossal vascularisation in the 84.62% and lingual artery in the 15.38%; innervation was granted by the trigeminal system (buccal nerve and mylohyoid nerve), sometimes (46.15%) with hypoglossal component. Conclusions: These data suggest us to not consider myloglossus as a rare anatomical variant.

Aim: The aim of this study was to evaluate the differences between teachers' knowledge about early psychosis among three different Italian cities and a UK sample. Methods: The sample consisted of 556 secondary school teachers from three different cities in Italy (Milan, Rome and Lamezia Terme) and London (UK). The research was based on the Knowledge and Experience of Social Emotional Difficulties Among Young People Questionnaire. The Italian version of the questionnaire was used in Italy. Results: Overall, 67.6% of English teachers, 58.5% of Milan's teachers, 41.8% of Rome’s teachers and 33.3% of Lamezia Terme’s teachers were able to recognise psychotic symptoms from a case vignette. Logistic regression analysis showed that 'city' was the only independent variable significantly related to the correct/wrong answer about diagnosis. Conclusions: We found statistically significant differences between the three Italian samples and the UK sample regarding teachers' knowledge about first signs of psychosis. English teachers showed a better knowledge than Italian teachers in general. Teachers from Milan, where a specific early detection program was established in 2000, seemed to be more familiar with early signs of psychosis than teachers in the other two Italian towns.

Treatment in early intervention services (EIS) seems superior to treatment as usual on several outcomes, but the extent of heterogeneity in response is unclear. In this study, treatment response trajectories up to 2 years in first-episode psychosis (FEP) patients enrolled in an Italian early intervention service (EIS) have been quantified. The 24-item Brief Psychiatric Rating Scale (BPRS) was used to quantify treatment response up to 2 years in 129 participants. Conditional growth modeling and latent class growth analysis were used to test changes over time in the BPRS and separation into independent classes over time. Group differences were tested on socio-demographic and clinical variables known to be related to outcome in psychosis. Scores on the BPRS showed a statistically significant decrease in overall scores across all tested models. Four trajectories were identified across 2 years. Most patients showed a progressive decrease in the BPRS scores; a scant fraction showed a more stepped decrease from very high levels of psychopathology. No potential predictor was statistically related to the time course of BPRS scores. Most patients that undergo treatment within an EIS are characterized by amelioration, but patients that have higher baseline scores of psychopathology require more intensive treatment.

Background Platelet concentrates represent a new approach to improve tissue regeneration and can be used alone or together with autogenous bone, recombinant human growth factors, and/or other biomaterials, to enhance tissue regeneration. Among platelet concentrates, concentrated growth factors (CGFs) exhibit an interesting clinical and biotechnological application potential. Objective The aim of this study was to evaluate the in vitro release of 4 growth factors (bone morphogenetic proteins [BMP] -2, BMP-7, transforming growth factor [TGF] -β1, and insulin-like growth factor [IGF] -1) by the enzyme-linked immunosorbent assay (ELISA) technique, in CGFs mixed or not with β-tricalcium phosphate (β-TCP), using or not the Round-up device, at different times. Methods CGFs were obtained from healthy volunteers, mixed or not with β-TCP, using or not the Round-up device. The release of 4 growth factors from these CGFs was then measured at 5 hours, 1, 3, 6, and 8 days, using the ELISA assay. Results Comparison of the results obtained with those achieved for CGFs alone showed that BMP2 and BMP-7 release, significantly increased in CGFs mixed with Round-up and β-TCP, TGF-β1 release was similar to CGFs alone, whereas IG-1 release was lower compared with CGFs alone. Conclusion The present data suggest that β-TCP addition to CGF could enhance and improve tissue regeneration, especially bone regeneration, increasing the release of some growth factors that play an important role in osteogenesis.

Aim This is the first comprehensive, nationwide survey aimed at collecting evidence about the process of implementation and development of early intervention in psychosis (EIP) services (EIPs) in Italy, following the establishment of the pilot program ‘Programma 2000’ in 1999 and the publishing of the Italian National Guidelines in 2007. This survey covers all the Departments of Mental Health (DMHs) operating in Italy in 2013. Methods Using a purpose-designed form to assess EIP implementation, all directors of public mental health services for adults throughout Italy (n = 216) were asked to provide information about the activities of EIP-relevant local services. The initial delivery was followed by a request for a prompt response. Results Out of 216 enquired DMHs, 103 provided computable answers to the survey (response rate = 48%). Among responders, 45 (44%) reported the implementation of EIP (one out of five DMHs operating in Italy). About a half of the active EIPs also targeted patients at ultra-high risk of psychosis (n = 27). Strict application of guidelines related to drug prescription was reported in 35% of EIPs. Conversely, 90% provided some kind of structured psychotherapy and psychoeducation. Among EIPs, a minority reported willingness to provide initial assessment/contact at the patient's home. Conclusion Albeit slowly, the implementation of EIP is spreading throughout the Italian public network of mental health. There is still a wide variability in the distribution of EIP services across the Italian territory. Further efforts are necessary to stimulate policy endorsement and resource allocation, as well as to support the poorest zones.

Aim In November 2005 the Italian Center on Control of Maladies, a department operating under the Ministry of Health, financed a project aimed at evaluating the feasibility of a protocol of intervention based on the early intervention in psychosis (EIP) model within the Italian public mental health-care network. Methods The study was carried out between March 2007 and December 2009. It involved five centres operating under the Departments of Mental Health of Milan (Programma 2000), Rome (area D), Grosseto, Salerno (Nocera) and Catanzaro (Soverato). Results Enrolment lasted 12 months, at the end of which 43 patients were enrolled as first-episode psychosis (FEP), and 24 subjects as ultra high-risk (UHR) patients. Both FEP and UHR samples included a preponderance of male patients. A family history of psychosis was rarely reported in both samples. The FEP incidence rate was lower than expected on the basis of international estimates of the incidence of schizophrenia but within the expected figure for the estimated Italian rates in three centres out of five. Conclusions Overall, the study proved that an EIP centre can be established within the public Department of Mental Health to reach a good fraction of the cases in need of treatment. Since then, several studies have been set up to assess the feasibility of EIP in the Italian public mental health sector in Lombardy and Tuscany, and in 2012 the Emilia-Romagna Regional Authority started an educational plan aimed at implementing the EIP model in all the Mental Health Departments in the region.

L’insorgenza in giovane eta di sintomi potenzialmente prodromici di evoluzione psicotica, la necessita di riconoscerli in contesti e con programmi di valutazione non stigmatizzanti, la necessita altrettanto ineludibile di approcci di supporto o francamente terapeutici, sono temi che in questo momento vengono dibattuti in un clima di grande fervore scientifico e clinico dalla comunita internazionale. Gli Autori, rifacendosi all’esperienza di un centro per l’individuazione e l’intervento precoce nelle psicosi attivo da 15 anni (Programma 2000, Milano), che sin dall’avvio si e rivolto oltre che agli esordi (FEP) anche alle situazioni ad alto rischio di evoluzione psicotica (UHR), sviluppano alcune riflessioni di natura pratica sulla necessita per i Servizi di porre l’attenzione a tale popolazione di giovani. La convinzione che tale percorso, in un’ottica di prevenzione mirata, possa contribuire ad arginare o scongiurare la transizione in malattia, sostiene la ragionevole speranza che il futuro di molti giovani possa essere migliore di quanto non accada usualmente. Cio richiede curiosita, interesse e determinazione da parte degli operatori oltre che una chiara aspirazione a sperimentare innovazioni e cambiamenti nella struttura del proprio lavoro, fondandoli sulle evidenze attualmente disponibili.

The underlying structures of clinical caseness and need of care in prodromal (i.e., at-risk) and early phases of schizophrenia remain poorly characterized in their essential psycho-behavioral coherence. To identify the schizophrenia proneness-related subtypes within a population of young help-seekers referred to a dedicated, community-based early detection program (Programma 2000). A sample of consecutive referrals (n = 168) for suspected psychosis or first-episode schizophrenia spectrum psychosis received a detailed clinical assessment, including the early recognition inventory for the retrospective assessment of the onset of schizophrenia checklist. We used exploratory factor analysis (EFA) to determine the underlying dimensional structure and latent class analysis (LCA) to identify putative vulnerability subtypes. EFA identified four factors: dysphoria (irritability tension), paranoid autocentrism, introversive withdrawal, and disturbed subjective experience. LCA distinguished three classes, interpretable as carrying different degrees of "proneness to schizophrenia psychosis," which best captured the underlying continuum of clinical severity. The validity of the three classes was supported by distinct patterns of association with major clinical variables (i.e., diagnostic staging at referral). Vulnerability to schizophrenia psychosis in young help-seekers may manifest in three major clinical prototypes, presenting common levels of dysphoria and social withdrawal but different degrees of paranoid autocentrism and disturbed subjective experience. Overall, the results provide the empirical background to dissect shared features of clinical caseness from more schizophrenia-specific vulnerability components. This is of value for the refinement of the clinical staging model as well as for the pragmatic implementation of multiple-gate screening programs.

The ophthalmic artery has an anomalous origin in 2-3 % of cases and rarely arises from the anterior cerebral artery. Herein, we provide the first anatomical, radiological, and histological description of such an anomalous origin, together with a literature review. During the anatomical dissection of an 81-year-old Caucasian male, the absence of the right ophthalmic artery in its usual location was evident from an endonasal transsphenoidal perspective. The specimen was then studied in detail, through multiple dissections, corrosion casting, high-resolution CT, and histological analysis. The English literature on anomalous origins of the ophthalmic artery was reviewed, together with reported associated pathologies. Anatomo-radiological analysis documented that the right ophthalmic artery arose from the inferior surface of A1 tract of the anterior cerebral artery (A1) and passed over the optic nerve in its subarachnoid tract. A meningo-ophthalmic artery was evident on the same side and reached the orbit through the superior orbital fissure. Histological examination of both internal carotid artery (ICA) walls documented a significantly decreased thickness of the tunica media and adventitia on the side of the anomalous ophthalmic artery, with a significantly different content of collagen types I and III. The literature review documented an association of aneurysms and anomalous ophthalmic arteries. To the best of our knowledge, this is the first anatomical report that includes a radiological and arterial wall analysis of a persistent ventral ophthalmic artery. The latter provides histological data that support the clinical evidence of a higher association of aneurysms with anomalous origins of the ophthalmic artery.

Aim: Duration of untreated psychosis (DUP) can influence the prognosis of schizophrenia. Previous studies have suggested that gender may influence the length of DUP. This study reports the result of the first systematic literature review and meta-analysis on the role of gender in influencing DUP in first-episode psychosis. Method: Systematic literature search in PubMed/Medline and Ovid/PsychINFO. Twenty-seven studies presenting data on 4721 patients diagnosed with psychosis at their first episode (2834 males and 1887 females) were included in the analysis. Results: Samples had a higher proportion of males: odds ratio = 2.5 (95% confidence interval: 1.8–3.3). Mean age at first contact was 25.4 for males and 27.5 for females. Patients from non-Western countries were older at first contact than patients from Western countries. Average DUP in schizophrenia was 64 weeks and did not differ between genders but was shorter in Western compared with non-Western countries. Conclusion: Earlier age at first contact and larger incidence in males support the existence of specific gender differences in first-episode psychosis; however, these are not associated with DUP length.

Aim: So far, no study has assessed the validity of the Health of the Nation Outcome Scales (HoNOS) in patients enrolled in early intervention programmes, nor has any study evaluated the validity of the HoNOS in people at ultra high-risk (UHR) of psychosis. This study set out to assess the validity and reliability of the HoNOS as a measure of outcome in the patients enrolled in an early intervention programme. Methods: The concurrent, discriminant and predictive validity, and the reliability of the HoNOS as a measure of outcome in an early intervention programe were assessed in 87 first-episode psychosis (FEP) patients, and in 81 patients at UHR of psychosis. Results: Reliability indexes were good in the FEP sample, and less good in the UHR sample. HoNOS total scores differentiated between FEP and UHR patients, and the HoNOS subscales proved able to assess a specific profile of symptoms in the two samples, demonstrating a helpful adjunctive measure of health status without complete overlap with other scales. Sensitivity to change was also very good, again with differences between FEP and UHR patients. HoNOS scores at intake did not predict failure to attain remission in FEP patients. There were too few cases of transition to psychosis (n = 2) to assess predictive validity of HoNOS in the UHR sample. Conclusion: HoNOS possesses satisfactory sensitivity and validity to be used in the routine assessment in early intervention programmes.

Purpose of review.In this review, we provide an update of recent studies on the age of onset (AOO) of the major mental disorders, with a special focus on the availability and use of services providing prevention and early intervention.Recent findings.The studies reviewed here confirm previous reports on the AOO of the major mental disorders. Although the behaviour disorders and specific anxiety disorders emerge during childhood, most of the high-prevalence disorders (mood, anxiety and substance use) emerge during adolescence and early adulthood, as do the psychotic disorders. Early AOO has been shown to be associated with a longer duration of untreated illness, and poorer clinical and functional outcomes.Summary.Although the onset of most mental disorders usually occurs during the first three decades of life, effective treatment is typically not initiated until a number of years later. There is increasing evidence that intervention during the early stages of disorder may help reduce the severity and/or the persistence of the initial or primary disorder, and prevent secondary disorders. However, additional research is needed on effective interventions in early-stage cases, as well as on the long-term effects of early intervention, and for an appropriate service design for those with emerging mental disorders. This will mean not only the strengthening and re-engineering of existing systems, but is also crucial the construction of new streams of care for young people in transition to adulthood.

Suicidality is high in schizophrenia, particularly in first-episode patients. Little is known about patients with prodromal symptoms of psychosis or otherwise high-risk persons. In a sample enrolled in an early intervention program implemented in Milan (Italy), a history of attempted suicide before enrollment was found in 6 first-episode schizophrenia (out of 87, 6.9%), and 7 high-risk of psychosis (out of 81, 8.6%) patients. In the first-episode group, a history of suicide attempts was related to a shorter duration of untreated psychosis. In the high-risk group, a family psychiatric history in first/second degree relatives of patients and a personal history of substance abuse were both associated with an enhanced risk of attempted suicide before enrollment. During the first year of treatment, 3 new attempted suicides were recorded among 57 (5.3%) high-risk patients, and none among first-episode patients (n=58) (no dropout in the sample). The levels of suicide ideation on the BPRS did not differ by group at assessment, and significantly declined from assessment at entry to 1-year follow-up, except in seven HRP patients who become positive for core symptoms of schizophrenia, as measured on the BPRS. At enrollment, patients at high risk of psychosis had the same prevalence of past suicide attempts than first-episode schizophrenia patients: since suicide attempt is the most important predictor of a future suicidal attempt, the assessment of suicide risk should be given a privileged role in patients at high risk of psychosis as well.

Objective: This paper describes the structure and the organization of the single Italian programme specifically targeted at the early detection of and interventions for subjects at onset of or at high risk of psychosis, Programma 2000. Methods: Programma 2000 is a comprehensive multi-modal protocol of early intervention in psychosis, set up in Milan in 1999. The service has been very active since its opening, and at the time of writing (spring (April) 2008), more than 300 young patients have been evaluated through a detailed protocol that embraces Health of the Nation Outcome Scale (HoNOS), Brief Psychiatric Rating Scale (BPRS), Cognitive Behavioural Assessment 2.0, Disability Assessment Schedule, Camberwell Family Interview, Wechsler Adult Intelligence Scale and the Early Recognition Inventory Retrospective Assessment of Symptoms. The treatment includes psychoeducation, cognitive behavioural therapy (CBT), both structured and unstructured psychosocial interventions and pharmacotherapy, when necessary. Results: The programme focuses on young people aged 17–30 years: to date, a total of 132 subjects with definite psychosis or within the high-risk category have been enrolled in treatment after assessment. Patients with first-episode psychosis were, on average and expectedly, more severe than those in the at-risk group, and were more likely to be prescribed antipsychotic drugs. A large majority of patients in both groups received tailored CBT; individual sessions of skills training were provided to two-thirds of patients. In both groups, improvement was found in both the BPRS and HoNOS, and in the level of global functioning as assessed on Global Assessment of Functioning at 6 month and 1 year follow up. Global functioning was more sensitive to change than symptom severity, reflecting the intensive and personalized efforts to improve social and role functioning in patients. Conclusions: Programma 2000 is still in development but it has already gained the support of therapists and other relevant people involved in the life of subjects at onset, or at high risk of psychosis.

To date, the pathogenesis of abdominal aortic aneurism (AAA) still remains unclear. As such, the aim of this study was to evaluate changes of the aortic structure during AAA. We analysed the microscopic frame of vessels sections, starting from the primum movens leading to abnormal dilatation. AAA samples were collected and processed through various staining methods (Verhoeff-Van Gieson, Masson Goldner, Sirius Red). Subsequently, the vessel morphology and collagenic web of the tunica media and adventitia were determined and the amount of type I and type III collagen was measured. We also applied immune-histochemistry markers for CD34 and PGP 9.5 in order to identify vascular and nerve structures in the aorta. Immune-positivity quantification was used to calculate the percentage of the stained area. We found increasing deposition of type I collagen and reduced type III collagen in both tunica media and adventitia of AAA. The total amount of vasa vasorum, marked with CD34, and nerva vasorum, marked with PGP 9.5, was also higher in AAA samples. Cardiovascular risk factors (blood pressure, dyslipidemia, cigarette smoking) and radiological data (maximum aneurism diameter, intra-luminal thrombus, aortic wall calcification) increased these changes. These results suggest that the tunica adventitia may have a central role in the pathogenesis of AAA as clearly there are major changes characterized by rooted inflammatory infiltration. The presence of immune components could explain these modifications within the framework of the aorta.

Scientific background: Platelet concentrates are nowadays widely applied in different clinical fields to improve soft tissue and bone regeneration. “Concentrated Growth Factors” (CGF) is a new generation of platelet concentrate products, which exhibits an interesting clinical and biotechnological application potential. Aim of the study: The aim of this study is to assess the biological rationale for the use of CGF, by evaluating blood cell localization, the in vitro cumulative release of seven growth factors (PDGF-AB, VEGF, TNF-α, TGF-β1, BDNF, BMP- 2 and IGF-1), its in vitro effects on cell proliferation and its mechanical behavior. Methods: CGFs were obtained from volunteer donors. Blood cell localization was evaluated after properly morphological staining and immunohistochemistry. The amount of growth factors release was measured at 5 hours, 1, 3, 6, 7 and 8 days, using ELISA assay. Cells were cultured with and without CGF and their proliferation were evaluated after 72 hours, performing the quantification of Ki-67, using flow cytometry (FACS). The mechanical response of CGF under compression was also attempted. Results: The results showed that platelets and leukocytes were found in a very thin space called “buffy coat”, localized between the white and red part of CGF. Each growth factor evaluated, had a specific kinetic release with a great variability among subjects. The in vitro cell proliferation was stimulated. CGF showed an “apparent plasticity” and its mechanical response was influenced by fibrin network structure. Conclusion: These findings support the CGF’s clinical use and will allow us to better understand and improve the clinical outcomes.

The aim of the current study was to review the use of fresh frozen bone (FFB) in oral and maxillofacial surgery. We performed a review of the articles published in the literature between 1976 and May 2014 analyzing three medical databases (PubMed, Cochrane Library, and Embase) and using specific search terms. Literature analysis on FFB applications in oral and maxillofacial surgery revealed 47 articles between 1976 and May 2014. There are 46 clinical articles and one review. Clinical articles are represented by 22 case reports and case series and 24 retrospective studies. Classifying the scientific production by year of publication, it is evident that especially during the last 6 years there was an increase of FFB graft use in oral and maxillofacial approaches. The literature analysis on FFB's use shows that its application in oral and maxillofacial surgery began slowly in 1992 with Perrott and since 2006 it had a real development. The recent significant increase emphasizes the importance of FFB for bone regeneration in oral and maxillofacial surgery. This review found consistent evidence of FFB's use increase in oral and maxillofacial surgery suggesting a valid instrument for bone regeneration. To date, risks connected to the infections' transmission and to the immunogenic potential are extremely low and could be considered practically absent. So, this is an important alternative in the preimplant reconstructive surgery.

Integrated multi-element psychosocial interventions have been suggested to improve the outcomes of first-episode psychosis (FEP) patients, but they have been studied primarily in experimental settings and in nonepidemiologically representative samples. Thus, we performed a cluster-randomized controlled trial, comparing an integrated multi-element psychosocial intervention, comprising cognitive behavioral therapy, family intervention, and case management, with treatment as usual (TAU) for FEP patients in 117 community mental health centers (CMHCs) in a large area of northern Italy (10 million inhabitants). The randomized units (clusters) were the CMHCs, and the units of observation the patients (and, when available, their family members). The primary hypotheses were that add-on multicomponent intervention: (1) results in greater improvements in symptoms, as assessed with positive and negative syndrome scale and (2) reduces in-hospital stay, based on days of hospitalization over the 9-month follow-up. Four hundred and forty-four FEP patients received the intervention or TAU and were assessed at baseline and 9 months. Based on the retention rates of patients (and families) in the experimental arm, multi-element psychosocial interventions can be implemented in routine mental health services. Regarding primary outcomes, patients in the experimental arm showed greater reductions in overall symptom severity, while no difference could be found for days of hospitalization. Among the secondary outcomes, greater improvements were detected in the experimental arm for global functioning, emotional well-being, and subjective burden of delusions. No difference could be found for service disengagement and subjective burden of auditory hallucinations. These findings support feasibility and effectiveness of early interventions for psychosis in generalist mental health services.

Objective:This study aimed at defining the characteristics of a population of patients diagnosed with first-episode psychosis (FEP), and accessing for the first time a center for early intervention in psychosis in the health district of Milan and its surroundings.Methods:Patients were included in the study from January 2007 to December 2008; criteria: first contact with any public mental health service of the catchment area for a first episode of schizophrenia or related syndromes according to the ICD-10 criteria. Cluster analysis was used to divide patients into groups based on the main socio-demographic and clinical characteristics at presentation.Results:Overall, 91 FEP patients were enrolled in the study. Two clusters were identified, which differed principally by symptom profile. Patients in cluster 1 (n=36) had severe agitation, and a history of alcohol and/or substance abuse at presentation more often than those in cluster 2 (n=55), who were more likely to suffer at presentation from severe depression or apathy, anxiety, poor self-care, functional or work impairment and severe social withdrawal. After six months of treatment patients improved on almost all symptomatic dimensions on the Health of the Nation Outcome Scale and the Brief Psychiatric Rating Scale, with greater improvement in cluster 1 than in cluster 2.Conclusions:The findings of this study need replication in larger samples and on a wider severity scale. Nevertheless, the heterogeneity of patients with FEP might impact on treatment. Policymakers should recognize the importance of the diagnostic and outcome assessment in the treatment of severe mental disorders.

RIASSUNTOScopo – L'analisi del rapporto tra costi di trattamento e gravità dei pazienti psichiatrici, raggruppati in classi omogenee. Disegno – Rilevazione prospettica dei costi e della gravità di 1371 pazienti psichiatrici adulti, in carico presso 2 Unità Operative di Psichiatria, osservati per un periodo medio di circa 9 mesi. I dati raccolti riguardano tutti i servizi psichiatrici delle Unità Operative, che comprendono quelli ambulatoriali, quelli residenziali e semi-residenziali e i Servizi Psichiatrici di Diagnosi e Cura degli ospedali per acuti. Setting – Le Unità Operative Psichiatriche di Magenta (MI) e di Desio (MI). Metodo – La gravità di ogni paziente è stata misurata attraverso la scheda HoNOS. La compilazione di questa scheda è stata effettuata al momento del reclutamento e in seguito con una cadenza mediamente trimestrale. Oltre alle schede trimestrali sono state previste compilazioni al momento dell'ammissione e della dimissione dai reparti ospedalieri di psichiatria, dai Centri Residenziali di Terapie psichiatriche e di risocializzazione e dalle Comunità Protette. Tutti i pazienti osservati sono stati raggruppati in base alla diagnosi principale (ICD-10) e al livello massimo di gravità dei problemi presentati durante l'intero periodo di osservazione. I costi presi in considerazione sono i soli costi diretti sostenuti dai servizi psichiatrici pubblici. La loro attribuzione ai singoli pazienti è avvenuta sulla base di costi standard o di tariffe (procedure diagnostiche), applicati alle quantità rilevate prospetticamente attraverso il Registro regionale, integrato con apposite schede. Risultati – Il costo complessivo realizzato dai 1371 pazienti osservati è risultato pari a 9771.1 milioni di lire, con un costo medio per paziente di 7127000 lire (ds 19499400). Il costo totale per giornat'a di osservazione è risultato pari a 27172 lire (ds 68358) e non risulta correlato alia durata del periodo di osservazione. La gravità media dei pazienti risulta pari a 4.26 punti (ds 3.73) al momento dell'arruolamento e pari a 3.19 punti (ds 3.26) al termine dello studio. Quella media, misurata attraverso i valori massimi della HoNOS osservati sull'intero periodo, risulta pari a 6.00 punti (ds 4.64). Gravità e costo del trattamento per singolo caso risultano direttamente correlati (r = 0.626, p = 0.0001). II raggruppamento dei pazienti ha portato a definire delle classi che presentano un punteggio medio di gravità complessivamente diverso (p = 0.0001). Diversi nel loro insieme risultano anche i costi medi di trattamento per classe (p = 0.0001). Conclusioni Tutti i pazienti psichiatrici adulti possono essere raggruppati in classi relativamente omogenee rispetto alia gravità e con costi di trattamento almeno in parte diversi. Uno studio più ampio forse potrebbe migliorare i risultati ottenuti e fornire la base per una diversa modalità di finanziamento dei servizi psichiatrici.

The continuously growing segment of the geriatric population with the high incidence and prevalence of comorbidity and disability suggests that enhanced preventive and rehabilitative programs will be mandatory. The early arrangement of comprehensive assessment and rehabilitation services is extremely important not only in preventing the decline of patients in the acute care settings and successive prolonged care before discharge, but also in improving functional status at discharge. We have considered the effectiveness of a rehabilitation program in acute medical care of the elderly. This article discusses a pilot project being carried out at Catholic University Hospital "A. Gemelli" of Rome.

In November 2005 the Italian Center on Control of Maladies, a department operating under the Ministry of Health, financed a project aimed at evaluating the feasibility of a protocol of intervention based on the early intervention in psychosis (EIP) model within the Italian public mental health-care network.The study was carried out between March 2007 and December 2009. It involved five centres operating under the Departments of Mental Health of Milan (Programma 2000), Rome (area D), Grosseto, Salerno (Nocera) and Catanzaro (Soverato).Enrolment lasted 12 months, at the end of which 43 patients were enrolled as first-episode psychosis (FEP), and 24 subjects as ultra high-risk (UHR) patients. Both FEP and UHR samples included a preponderance of male patients. A family history of psychosis was rarely reported in both samples. The FEP incidence rate was lower than expected on the basis of international estimates of the incidence of schizophrenia but within the expected figure for the estimated Italian rates in three centres out of five.Overall, the study proved that an EIP centre can be established within the public Department of Mental Health to reach a good fraction of the cases in need of treatment. Since then, several studies have been set up to assess the feasibility of EIP in the Italian public mental health sector in Lombardy and Tuscany, and in 2012 the Emilia-Romagna Regional Authority started an educational plan aimed at implementing the EIP model in all the Mental Health Departments in the region.

This study set out to investigate the patterns of referral in a sample (n = 206) of patients having first-time access to an Italian comprehensive program that targets the early detection of and early intervention on subjects at the onset of psychosis. The primary goal of the study was to investigate the duration of untreated illness (DUI) and/or the duration of untreated psychosis (DUP) in the sample since the implementation of the program.Data on pathways of referrals prospectively collected over a 11-year period, from 1999 to 2010; data referred to patients from a defined catchment area, and who met ICD-10 criteria for a first episode of a psychotic disorder (FEP) or were classified to be at ultra-high risk of psychosis (UHR) according to the criteria developed by the Personal Assessment and Crisis Evaluation (PACE) Clinic in Melbourne. Changes over time in the DUI and DUP were investigated in the sample.Referrals increased over time, with 20 subjects enrolled per year in the latter years of the study. A large majority of patients contacted a public or private mental health care professional along their pathway to treatment, occurring more often in FEP than in UHR patients. FEP patients who had contact with a non-psychiatric health care professional had a longer DUP. Over time, DUP and DUI did not change in FEP patients, but DUI increased, on average, in UHR patients.The establishment of an EIP in a large metropolitan area led to an increase of referrals from people and agencies that are not directly involved in the mental health care system; over time, there was an increase in the number of patients with longer DUI and DUP than those who normally apply for psychiatric services.

RIASSUNTOScopo - Lo studio è stato condotto con l'obiettivo di descrivere le linee di tendenza manifestatesi nel periodo 1983-1993 nei Servizi psichiatrici pubblici lombardi relativamente a indicatori di struttura, personale e attività. Setting - Sono stati utilizzati dati relativi a tutti i presidi facenti capo, secondo quanto previsto dal Progetto Obiettivo Regionale, alle Unità Operative di Psichiatria della Regione Lombardia, ovvero Centri Psico-sociali, Ambulatori, Strutture Intermedie Non Residenziali, Servizi Psichiatrici di Diagnosi e Cura, Centri Residenziali di Terapie Psichiatriche e di Risocializzazione e Comunita Protette. Non sono stati inclusi nello studio i dati relativi all'attivita svolta dagli ex Ospedali Psichiatrici e dalle strutture private. Disegno - I dati sono stati forniti dal Sistema Informativo Psichiatrico Regionale che dal 1983 rileva in maniera omogenea e sistematica su tutto il territorio regionale informazioni relative alle strutture, al personale e alle prestazioni erogate dalle Unita Operative di Psichiatria. Sui dati relativi al periodo 1983-1993 e stata condotta un'analisi grafica della dinamica dei servizi con descrizione delle tendenze evidenziatesi nel periodo in oggetto e delle interazioni tra le variabili considerate. Principali misure utilizzate - Variabili di risorse e di prestazioni relative all'attivita degenziale e a quella non residenziale dei servizi. Formulazione di indicatori che permettano l'analisi delle relazioni tra le variabili stesse. Risultati - Nel periodo considerato si assiste globalmente a un aumento consistente del volume di attivita (residenziale e non) spiegabile solo parzialmente attraverso l'aumento delle risorse a disposizione. L'incremento quantitative dell'assistenza fornita pare infatti legato da un lato a una sempre maggiore utilizzazione delle risorse allocate e a un aumento della produttivita dei servizi, dall'altro alia pressione crescente della domanda. I dati a disposizione, inoltre, evidenziano come il baricentro della organizzazione dei servizi pubblici si sia spostato sempre piú negli anni sul momento di trattamento non residenziale, anche se l'assenza di una analoga documentazione per quanto attiene alle strutture private rende questa conclusione parziale. Conclusioni - L'analisi condotta testimonia l'importanza del Sistema Informativo per monitorare i cambiamenti nella organizzazione dei servizi e per fornire i dati necessari alia attivazione di indagini ad hoc (per es. studi di esito).

RIASSUNTOScopo - Lo scopo di questo lavoro è la classificazione delle USSL lombarde in gruppi, ognuno dei quali omogeneo, per quanto possibile, rispetto alle modalitá di funzionamento dei servizi psichiatrici territoriali; il fine è valutare il mix di servizi psichiatrici offerti dalla Regione attraverso le USSL. Disegno - Sono stati analizzati i dati raccolti nel 1992 e 1993 dal Sistema Informativo Psichiatrico Regionale lombardo relativi alle strutture, il personale e le attività delle Unitá Operative di Psichiatria ed ai ricoveri nelle strutture private nelle 83 USSL lombarde. Tramite l'analisi delle componenti principali sono state selezionate sette variabili sulle quali basare la classificazione; per formare i gruppi e stata utilizzata la Cluster Analysis secondo il metodo di Ward. Risultati - Sono stati selezionati 5 cluster. Nel primo i servizi sono focalizzati sull'attivitá di ricovero (a cui ricorrono anche in ambito privato), mentre le équipe territoriali sembrano riflettere un certo «grigiore» nella loro composizione e nella varietà di interventi offerti. Il secondo è caratterizzato da un tasso estremamente ridotto di interventi nelle strutture territoriali (svolti prevalentemente in sede) e da una loro scarsa diversificazione; è ridotta anche l'attività di ricovero. Nel terzo le USSL sono in grado di offrire una «ricca» attività territoriale (in termini sia di quantità che di varietà), ma tendono delegare al ricovero in strutture private la risoluzione di una parte rilevante dei loro problemi, forse anche a causa della limitata dotazione di strutture riabilitative. Il quarto cluster è composto da servizi,con una ricca dotazione di strutture e soprattutto di personale,che utilizzano al massimo le risorse disponibili per l'attivita di ricovero (sia in SPDC che in CRT-CP), mentre a livello territoriale offrono un servizio adeguato sia in termini di quantita che di varieta degli interventi offerti. Nelle USSL che compongono il quinto cluster gli elementi caratterizzanti sono la ricca dotazione di strutture riabilitative e la accentuata differenziazione delle équipe territoriali, la cui attività quantitativamente molto rilevante (anche se poco diversificata) viene svolta soprattutto all'esterno della struttura. Conclusioni - L'analisi proposta ha consentito di osservare rilevanti disomogeneità nell'offerta dei servizi psichiatrici lombardi e di individuare 5 differenti modelli sintetizzabili nelle tipologie sopradescritte. Il metodo utilizzato permette di monitorare, nel tempo e nello spazio, lo sviluppo dei diversi modelli, utilizzando dati forniti routinariamente dai servizi, senza la necessità di indagini ad hoc.

The census system in the region of Lombardy provides no direct information on day-care centers (DCs) since the regional law of 31 December 1984 No. 67 does not distinguish them as autonomous structures, but assigns their therapeutic and rehabilitative functions to the OPUs as a whole, particularly to some of their subdivisions, primarily the psychosocial center (PSC). Analytic information on these facilities will be available after 1995 once a system for monitoring rehabilitative activities has begun to function. The DCs came into being as part of experimental initiatives financed through allocated budgets and specific projects, and were developed as deemed fitting and desirable by their operators, who, after noting the need for them, attempted to meet that need in accordance with local resources and local orientations. Thus, the initiative for the Lombardy Region has been given permission to develop psychiatric day care on the basis of many different organizational models. Information on the DCs in Lombardy gathered by means of the "activity sheets" currently used in psychiatric facilities enables us to sketch a general picture of the activities available to a patient over the course of a day, but only on a quantitative scale. The data accumulated measure the volume of services that may, in general terms, be labeled rehabilitative so long as the physical premises allow for realization of individual activities: PSCs; non

(1996). Day Centers: Proposals for Developing Guidelines. International Journal of Mental Health: Vol. 25, Day Centers in Psychiatry: Problems, Achievements, and Prospects 1. General Problems, pp. 5-12.

Sex-related differences in the clinical expression and outcome of schizophrenia have long been recognized; this study set out to evaluate whether they extend to those subjects who are at high risk of developing psychosis. In a sample enrolled in two early intervention programs in northern Italy, patients with first-episode psychosis (FEP; n=152) were compared to patients at ultra-high risk of psychosis (UHR; n=106) on a series of sex-related clinical characteristics of schizophrenia. In both the FEP and the UHR samples, males outnumbered females. In FEP patients, women had been referred at an older age than men and had a shorter duration of untreated illness (DUI) and of untreated psychosis. In UHR patients no sex differences were found in age of onset or DUI. There was no diagnosis by sex interaction on symptoms severity or level of functioning at presentation. The limited number of women in both samples, and the exclusion of people who were older than 30 and of those with substance dependence may have reduced the extent of sex-related differences in this study. Sex differences of precipitating factors for psychosis might be worthy of further investigation.

Nitric oxide (NO) is a gaseous molecule implicated both in vascular tone and nociceptive transmission. The capillary blood supply to the dorsal root ganglia (DRG) is unique because it is highly permeable to several low and high molecular-weight compounds. This anatomical situation leads to a potential role of endothelial nitric oxide synthase (eNOS) in inflammatory nociception, which is not well established. Therefore, we examined the role of eNOS in DRG in a murine chronic inflammatory pain model induced by complete Freund’s adjuvant using L-N5-(1-iminoethyl)ornithine (L-NIO), a potent inhibitor of eNOS activity. Pain state was examined using a behavioral test. The expression of eNOS, platelet endothelial cell adhesion molecule-1 (CD31) and vascular endothelial growth factor (VEGF) was examined by immunofluorescence. In control animals, CD31 was detected in vessels; VEGF was localized both in vessels and neurons while a weak eNOS immunopositivity was detected in both vessels and in neurons. Under inflammatory pain conditions, eNOS, CD31 and VEGF immunopositivity increased. Administration of L-NIO significantly attenuated thermal hyperalgesia by 24 h and decreased eNOS activity and CD31 immunopositivity by 7 days. VEGF was unaffected. Our results show that eNOS plays a nociceptive role in the early phases of inflammation while in the later phases it may be involved in neurotrophic support.

Duration of untreated psychosis (DUP) can influence the prognosis of schizophrenia. Previous studies have suggested that gender may influence the length of DUP. This study reports the result of the first systematic literature review and meta-analysis on the role of gender in influencing DUP in first-episode psychosis.Systematic literature search in PubMed/Medline and Ovid/PsychINFO. Twenty-seven studies presenting data on 4721 patients diagnosed with psychosis at their first episode (2834 males and 1887 females) were included in the analysis.Samples had a higher proportion of males: odds ratio = 2.5 (95% confidence interval: 1.8-3.3). Mean age at first contact was 25.4 for males and 27.5 for females. Patients from non-Western countries were older at first contact than patients from Western countries. Average DUP in schizophrenia was 64 weeks and did not differ between genders but was shorter in Western compared with non-Western countries.Earlier age at first contact and larger incidence in males support the existence of specific gender differences in first-episode psychosis; however, these are not associated with DUP length.

So far, no study has assessed the validity of the Health of the Nation Outcome Scales (HoNOS) in patients enrolled in early intervention programmes, nor has any study evaluated the validity of the HoNOS in people at ultra high-risk (UHR) of psychosis. This study set out to assess the validity and reliability of the HoNOS as a measure of outcome in the patients enrolled in an early intervention programme.The concurrent, discriminant and predictive validity, and the reliability of the HoNOS as a measure of outcome in an early intervention programe were assessed in 87 first-episode psychosis (FEP) patients, and in 81 patients at UHR of psychosis.Reliability indexes were good in the FEP sample, and less good in the UHR sample. HoNOS total scores differentiated between FEP and UHR patients, and the HoNOS subscales proved able to assess a specific profile of symptoms in the two samples, demonstrating a helpful adjunctive measure of health status without complete overlap with other scales. Sensitivity to change was also very good, again with differences between FEP and UHR patients. HoNOS scores at intake did not predict failure to attain remission in FEP patients. There were too few cases of transition to psychosis (n = 2) to assess predictive validity of HoNOS in the UHR sample.HoNOS possesses satisfactory sensitivity and validity to be used in the routine assessment in early intervention programmes.

The people classified as being at ultra-high risk (UHR) of developing psychosis are expected to share many risk factors for psychosis with the patients diagnosed with schizophrenia, including an enhanced incidence of obstetric complications (OCs). This study set out to investigate the incidence and correlates of OCs in a sample of patients accessing an early intervention center. Patients' mothers were asked whether they had suffered from any somatic complication during pregnancy from a list of OCs with potential direct relevance to the physical wellbeing of the offspring. Out of 86 patients diagnosed with first-episode psychosis, 20 (23%) cases were positive for the occurrence of severe OCs, as reported by their mothers during an interview; out of 83 UHR patients, 21 (25%) cases were positive for OCs. OCs were more common in individuals with a family history of psychosis than in those without such a history. OCs might interact with genetic vulnerability to increase the risk of psychosis. Lack of comparison to healthy controls is a limitation that decreases the value of these findings.

Expressed emotion (EE) was examined in a large sample of families of patients with either first-episode psychosis (FEP) within the schizophrenia spectrum, or who met the criteria for ultra high-risk (UHR) of psychosis. The aim of our study was to determine the patterns and relationship of EE with the duration of untreated illness (DUI) or of untreated psychosis (DUP), as well as with illness severity. The sample used in our study included 77 FEP and 66 UHR families. The Camberwell Family Interview was used to assess EE. In both samples, about one-third of patients’ families were classified as high EE, with emotional over-involvement (EOI) being the most frequent reason for a family to be classified as high EE. In FEP, higher EE correlated with longer DUI, and higher paternal EOI with longer DUP. DUI, however, was not found to correlate to EE in UHR patients. Severity of illness at the initial assessment did not relate to EE in either FEP or UHR families. Families of FEP and UHR patients were not found to differ in terms of the prevalence of a high EE rating, or of any of its subcomponents. The results of this study only partially support the hypothesis that high EE develops as a reaction to patient status. Patients from families with high EE could possibly benefit from interventions that are targeted at improving their resilience when dealing with problematic family environments.

Aim: The aim of this study was to describe a service operating in Milan, Italy, that provides early intervention for young people aged 17–30 years at the onset and at high risk of psychosis. Method: Following 2 years of preliminary study and organization, Programma2000 was launched in Milan in 1999. This programme was targeted at early detection and intervention in subjects at the onset of, at risk of, or showing ‘prodromal’ signs of psychosis. This paper contains data on the organization and activities of Programma2000. Results: The service has been active since its launch and has received 378 referrals as of March 2009, 342 of which were thoroughly evaluated. At entry, patients undergo a detailed evaluation of their psychopathology, personal and social role functioning, and cognitive status, with repeated testing over time in order to multidimensionally assess outcome. Treatment involves cognitive–behavioural psychotherapy, structured and unstructured psychosocial interventions, and pharmacotherapy when deemed necessary. Treatment appears effective in reducing morbidity and improving social functioning. Conclusion: A team dedicated to the early identification and treatment of young people with early psychosis is a feasible and sustainable extension of the traditional methods of care for people with mental disorders in Italy.

Introduction A large body of research has shown that Oxytocin (OXT) is an important prosocial peptide and there is also initial evidence that the central OXT system is altered in several mental disorders that are characterized by severe social disturbances and deficits, such as anxiety disorders disorders with prominent social dysfunction (e.g., schizophrenia) mood disorders and borderline personality disorder. In particular, Feifel et al. (2010) and Pedersen et al (2011) recently conducted two randomized, placebo-controlled study of intranasal oxytocin in schizophrenia patients to test the hypothesis that oxytocin can reduce symptoms of this disorder. Their results support the hypothesis that oxytocin may reduce psychotic symptoms and may diminish certain social cognition deficits that are not improved by current antipsychotic medications. Aims to review the main studies conducted on oxytocin and its relation with mental disorders. Methods We will present a systematic review on the studies conducted on oxytocin and mental disorder, both in non-clinical and in clinical samples. In order to overcome some of the limitations of the previous studies, we will present a study which is going to be run, aimed at testing whether the intranasal administration of the neuropeptide oxytocin as adjunct to antipsychotic treatment improves positive and negative symptoms its effect on social cognition, social functioning and empathy in patients with schizophrenia.

This article considers the importance of rehabilitation in the medical care of elderly patients. It discusses a pilot project being carried out at ‘Policlinico Gemelll’ hospital of Rome, which enables patients to achieve the maximum level of independence and a satisfactory quality of life. The article is published as part of the College of Occupational Therapists' current focus on ‘Equalising Opportunities’.

Background Multi-element interventions for first-episode psychosis (FEP) are promising, but have mostly been conducted in non-epidemiologically representative samples, thereby raising the risk of underestimating the complexities involved in treating FEP in ‘real-world’ services. Methods/Design The Psychosis early Intervention and Assessment of Needs and Outcome (PIANO) trial is part of a larger research program (Genetics, Endophenotypes and Treatment: Understanding early Psychosis - GET UP) which aims to compare, at 9 months, the effectiveness of a multi-component psychosocial intervention versus treatment as usual (TAU) in a large epidemiologically based cohort of patients with FEP and their family members recruited from all public community mental health centers (CMHCs) located in two entire regions of Italy (Veneto and Emilia Romagna), and in the cities of Florence, Milan and Bolzano. The GET UP PIANO trial has a pragmatic cluster randomized controlled design. The randomized units (clusters) are the CMHCs, and the units of observation are the centers’ patients and their family members. Patients in the experimental group will receive TAU plus: 1) cognitive behavioral therapy sessions, 2) psycho-educational sessions for family members, and 3) case management. Patient enrolment will take place over a 1-year period. Several psychopathological, psychological, functioning, and service use variables will be assessed at baseline and follow-up. The primary outcomes are: 1) change from baseline to follow-up in positive and negative symptoms’ severity and subjective appraisal; 2) relapse occurrences between baseline and follow-up, that is, episodes resulting in admission and/or any case-note records of re-emergence of positive psychotic symptoms. The expected number of recruited patients is about 400, and that of relatives about 300. Owing to the implementation of the intervention at the CMHC level, the blinding of patients, clinicians, and raters is not possible, but every effort will be made to preserve the independency of the raters. We expect that this study will generate evidence on the best treatments for FEP, and will identify barriers that may hinder its feasibility in ‘real-world’ clinical settings, patient/family conditions that may render this intervention ineffective or inappropriate, and clinical, psychological, environmental, and service organization predictors of treatment effectiveness, compliance, and service satisfaction. Trial registration ClinicalTrials.gov Identifier NCT01436331