A harmonized and efficient clinical research environment would benefit patients and enhance European competitiveness

Background. Implementation of the EU Regulation No. 536/2014 through national guidelines is a great opportunity to make sponsors reconsider Europe as a prime location for clinical trials. Methods. In November 2014, a Panel of clinical researchers and representatives of the pharmaceutical industry, patient organisations and Italian regulatory agency discussed potential advances fostering Italian competitiveness in terms of clinical research. As a case study, this analysis of the Italian situation can be representative of the average European situation. Results. Features characterising Italian clinical research patterns were analysed. Considerable engagement and cooperation by all stakeholders is required in addition to a well-structured interaction between National Authorities and ethical committees to comply with the strict timeframes mandated by the new Regulation. Conclusions. In the Panel’s view, harmonisation of the approval process and strengthening of clinical site performance are mandatory to provide a good return on investment in Europe for the pharmaceutical industry, access for patients to innovative treatments and new resources for clinical sites.                                                                                                                                                                 

Insight in cognitive impairment assessed with the Cognitive Assessment Interview in a large sample of patients with schizophrenia

The Cognitive Assessment Interview (CAI) is an interview-based scale measuring cognitive impairment and its impact on functioning in subjects with schizophrenia (SCZ). The present study aimed at assessing, in a large sample of SCZ (n = 601), the agreement between patients and their informants on CAI ratings, to explore patients' insight in their cognitive deficits and its relationships with clinical and functional indices. Agreement between patient- and informant-based ratings was assessed by the Gwet's agreement coefficient. Predictors of insight in cognitive deficits were explored by stepwise multiple regression analyses. Patients reported lower severity of cognitive impairment vs. informants. A substantial to almost perfect agreement was observed between patients' and informants' ratings. Lower insight in cognitive deficits was associated to greater severity of neurocognitive impairment and positive symptoms, lower severity of depressive symptoms, and older age. Worse real-life functioning was associated to lower insight in cognitive deficit, worse neurocognitive performance, and worse functional capacity. Our findings indicate that the CAI is a valid co-primary measure with the interview to patients providing a reliable assessment of their cognitive deficits. In the absence of informants with good knowledge of the subject, the interview to the patient may represent a valid alternative

Accuracy of self-assessment of real-life functioning in schizophrenia

A consensus has not yet been reached regarding the accuracy of people with schizophrenia in self-reporting their real-life functioning. In a large (n=618) cohort of stable, community-dwelling schizophrenia patients we sought to: (1) examine the concordance of patients' reports of their real-life functioning with the reports of their key caregiver; (2) identify which patient characteristics are associated to the differences between patients and informants. Patient-caregiver concordance of the ratings in three Specific Level of Functioning Scale (SLOF) domains (interpersonal relationships, everyday life skills, work skills) was evaluated with matched-pair t tests, the Lin's concordance correlation, Somers' D, and Bland-Altman plots with limits of agreement (LOA). Predictors of the patient-caregiver differences in SLOF ratings were assessed with a linear regression with multivariable fractional polynomials. Patients' self-evaluation of functioning was higher than caregivers' in all the evaluated domains of the SLOF and 17.6% of the patients exceeded the LOA, thus providing a self-evaluation discordant from their key caregivers. The strongest predictors of patient-caregiver discrepancies were caregivers' ratings in each SLOF domain. In clinically stable outpatients with a moderate degree of functional impairment, self-evaluation with the SLOF scale can become a useful, informative and reliable clinical tool to design a tailored rehabilitation program

The interplay among psychopathology, personal resources, context-related factors and real-life functioning in schizophrenia: stability in relationships after 4 years and differences in network structure between recovered and non-recovered patients

Improving real-life functioning is the main goal of the most advanced integrated treatment programs in people with schizophrenia. The Italian Network for Research on Psychoses previously explored, by using network analysis, the interplay among illness-related variables, personal resources, context-related factors and real-life functioning in a large sample of patients with schizophrenia. The same research network has now completed a 4-year follow-up of the original sample. In the present study, we used network analysis to test whether the pattern of relationships among all variables investigated at baseline was similar at follow-up. In addition, we compared the network structure of patients who were classified as recovered at follow-up versus those who did not recover. Six hundred eighteen subjects recruited at baseline could be assessed in the follow-up study. The network structure did not change significantly from baseline to follow-up, and the overall strength of the connections among variables increased slightly, but not significantly. Functional capacity and everyday life skills had a high betweenness and closeness in the network at follow-up, as they had at baseline, while psychopathological variables remained more peripheral. The network structure and connectivity of non-recovered patients were similar to those observed in the whole sample, but very different from those in recovered subjects, in which we found few connections only. These data strongly suggest that tightly coupled symptoms/dysfunctions tend to maintain each other's activation, contributing to poor outcome in schizophrenia. Early and integrated treatment plans, targeting variables with high centrality, might prevent the emergence of self-reinforcing networks of symptoms and dysfunctions in people with schizophrenia

Does social cognition change? Evidence after 4 years from the Italian Network for Research on Psychoses

Background Deficits in social cognition (SC) are significantly related to community functioning in schizophrenia (SZ). Few studies investigated longitudinal changes in SC and its impact on recovery. In the present study, we aimed: (a) to estimate the magnitude and clinical significance of SC change in outpatients with stable SZ who were assessed at baseline and after 4 years, (b) to identify predictors of reliable and clinically significant change (RCSC), and (c) to determine whether changes in SC over 4 years predicted patient recovery at follow-up. Methods The reliable change index was used to estimate the proportion of true change in SC, not attributable to measurement error. Stepwise multiple logistic regression models were used to identify the predictors of RCSC in a SC domain (The Awareness of Social Inference Test [TASIT]) and the effect of change in TASIT on recovery at follow-up. Results In 548 participants, statistically significant improvements were found for the simple and paradoxical sarcasm of TASIT scale, and for the total score of section 2. The reliable change index was 9.8. A cut-off of 45 identified patients showing clinically significant change. Reliable change was achieved by 12.6% and RCSC by 8% of participants. Lower baseline TASIT sect. 2 score predicted reliable improvement on TASIT sect. 2. Improvement in TASIT sect. 2 scores predicted functional recovery, with a 10-point change predicting 40% increase in the probability of recovery. Conclusions The RCSC index provides a conservative way to assess the improvement in the ability to grasp sarcasm in SZ, and is associated with recovery

The association between insight and depressive symptoms in schizophrenia: Undirected and Bayesian network analyses

Background. Greater levels of insight may be linked with depressive symptoms among patients with schizophrenia, however, it would be useful to characterize this association at symptom-level, in order to inform research on interventions. Methods. Data on depressive symptoms (Calgary Depression Scale for Schizophrenia) and insight (G12 item from the Positive and Negative Syndrome Scale) were obtained from 921 community-dwelling, clinically-stable individuals with a DSM-IV diagnosis of schizophrenia, recruited in a nationwide multicenter study. Network analysis was used to explore the most relevant connections between insight and depressive symptoms, including potential confounders in the model (neurocognitive and social-cognitive functioning, positive, negative and disorganization symptoms, extrapyramidal symptoms, hostility, internalized stigma, and perceived discrimination). Bayesian network analysis was used to estimate a directed acyclic graph (DAG) while investigating the most likely direction of the putative causal association between insight and depression. Results. After adjusting for confounders, better levels of insight were associated with greater self-depreciation, pathological guilt, morning depression and suicidal ideation. No difference in global network structure was detected for socioeconomic status, service engagement or illness severity. The DAG confirmed the presence of an association between greater insight and self-depreciation, suggesting the more probable causal direction was from insight to depressive symptoms. Conclusions. In schizophrenia, better levels of insight may cause self-depreciation and, possibly, other depressive symptoms. Person-centered and narrative psychotherapeutic approaches may be particularly fit to improve patient insight without dampening self-esteem

The interplay among psychopathology, personal resources, context-related factors and real-life functioning in schizophrenia: stability in relationships after 4 years and differences in network structure between recovered and non-recovered patients

Improving real-life functioning is the main goal of the most advanced integrated treatment programs in people with schizophrenia. The Italian Network for Research on Psychoses previously explored, by using network analysis, the interplay among illness-related variables, personal resources, context-related factors and real-life functioning in a large sample of patients with schizophrenia. The same research network has now completed a 4-year follow-up of the original sample. In the present study, we used network analysis to test whether the pattern of relationships among all variables investigated at baseline was similar at follow-up. In addition, we compared the network structure of patients who were classified as recovered at follow-up versus those who did not recover. Six hundred eighteen subjects recruited at baseline could be assessed in the follow-up study. The network structure did not change significantly from baseline to follow-up, and the overall strength of the connections among variables increased slightly, but not significantly. Functional capacity and everyday life skills had a high betweenness and closeness in the network at follow-up, as they had at baseline, while psychopathological variables remained more peripheral. The network structure and connectivity of non-recovered patients were similar to those observed in the whole sample, but very different from those in recovered subjects, in which we found few connections only. These data strongly suggest that tightly coupled symptoms/dysfunctions tend to maintain each other's activation, contributing to poor outcome in schizophrenia. Early and integrated treatment plans, targeting variables with high centrality, might prevent the emergence of self-reinforcing networks of symptoms and dysfunctions in people with schizophrenia

Clinical Features, Cardiovascular Risk Profile, and Therapeutic Trajectories of Patients with Type 2 Diabetes Candidate for Oral Semaglutide Therapy in the Italian Specialist Care

Introduction: This study aimed to address therapeutic inertia in the management of type 2 diabetes (T2D) by investigating the potential of early treatment with oral semaglutide. Methods: A cross-sectional survey was conducted between October 2021 and April 2022 among specialists treating individuals with T2D. A scientific committee designed a data collection form covering demographics, cardiovascular risk, glucose control metrics, ongoing therapies, and physician judgments on treatment appropriateness. Participants completed anonymous patient questionnaires reflecting routine clinical encounters. The preferred therapeutic regimen for each patient was also identified. Results: The analysis was conducted on 4449 patients initiating oral semaglutide. The population had a relatively short disease duration (42%  60% of patients, and more often than sitagliptin or empagliflozin. Conclusion: The study supports the potential of early implementation of oral semaglutide as a strategy to overcome therapeutic inertia and enhance T2D management

LA DIAGNOSI DI IPOTIROIDISMO CONGENITO AI TEMPI DELLA PANDEMIA DA SARS-CoV-2: L’ESPERIENZA DELLA CLINICA PEDIATRICA DI PALERMO

Obiettivi La pandemia da SARS-CoV-2 ha severamente compromesso i programmi di assistenza sanitaria, specie in casi in cui l’accesso alle cure ha richiesto tempi brevi, non programmabili. Lo screening neonatale per l’ipotiroidismo congenito (IC) rientra fra queste necessità assistenziali, con cooperazione fra componenti di un team multi-specialistico. E’ indispensabile l’integrazione fra medici e infermieri professionali, con competenze ed esperienza in ambito neonatologico. Metodi Abbiamo valutato l’attività integrata diagnostico-terapeutica del nostro centro di Endocrinologia Pediatrica, nel periodo gennaio 2020–aprile 2021, corrispondente alla diffusione del SARS-CoV-2 in Italia. Risultati Su un totale di 21300 neonati sottoposti a screening neonatale, sono stati screenati 1122 neonati con un TSH > 6. Fra questi, 75 neonati (7%) avevano un incremento del TSH sul secondo spot e/o su siero (48 M, 27 F, età gestazionale: 38.3 ± 1.3 w; p.c. neonatale: 3154 ± 121 gr). Il TSH al primo screening era 12.5 ± 21; il TSH su siero all’accesso presso il nostro centro, prima di un eventuale terapia con L-tiroxina, era 37.1 ± 77.5. Fra questi, 25 (33%) hanno presentato la normalizzazione di TSH, fT3 e fT4, valutati su siero al momento della valutazione presso il nostro centro e, pertanto, non hanno iniziato la terapia con L-tiroxina. I neonati ai quali è stato confermato un livello di TSH, fT3, fT4 patologico, avevano un’età all’inizio della terapia sostitutiva con L-tiroxina di 17 ± 3 gg. Fra questi pazienti, 2 con agenesia tiroidea; 3 con ipoplasia tiroidea, 25 con tiroide in situ. 4 hanno iniziato terapia oltre 22 gg ma non in relazione al lockdown: 1 proveniva da altra provincia, tutti e 4, comunque, con TSH < 10 al primo screening, e solo successivamente hanno presentato livelli di TSH francamente patologici. Conclusioni Il follow-up terapeutico è stato realizzabile, nonostante le limitazioni numeriche relative agli accessi in ospedale, grazie ad un programma di telemedicina, coordinato con i pediatri di famiglia. La strategia del team multi-specialistico, costruito attorno alle esigenze del piccolo paziente sottoposto a screening neonatale, ha garantito tempistica, coordinazione dei ruoli e affidabilità di una presa in carico efficace ai fini terapeutici e del follow-up

Participatory environmental health research: A tool to explore the socio-exposome in a major european industrial zone

ObjectivesWe show that participatory research approaches can be a useful tool across disciplines and data collection methods to explore the socio-exposome near one of the largest industrial harbors in Europe. We analyzed resident involvement in each project and their capacity to affect structural changes.MethodsLongitudinal participatory environmental monitoring studies on lichens, petunias, aquatic systems and groundwater were conducted under the program VOCE (Volunteers for the Citizens' Observation of the Environment), which mobilized nearly 100 volunteers to collect and report data. A community-based participatory health survey, Fos EPSEAL was also carried out during the same period. We describe citizens' involvement in each study following Davis and Ramirez-Andreotta's (2021) ‘best practice’ grid. We also use residents' insights to refine understanding of the socio-exposome.ResultsThe region is significantly impacted by industrial pollution and fenceline communities are disproportionately exposed. The community-based participatory health survey documented negative health outcomes among the residents, including a higher prevalence of chronic symptoms and diabetes (e.g., 11.9%) in the Fos-Berre Lagoon region than in other communities. This methodology shows the benefits of the co-production of knowledge in environmental health: not only does it enable epistemological transformations favorable to the vulnerable population, but it also triggered public action (i.e., media and public authorities’ attention leading to official expertise reports, filing of collective complaints before the courts).ConclusionThis body of multiple participatory research studies over time is a useful approach to better understand the socio-exposome and health issues in an industrial zone