Search

Andrea Spini,1 Luca L’Abbate,2 Ylenia Ingrasciotta,1 Giorgia Pellegrini,1 Massimo Carollo,1 Valentina Ientile,2 Olivia Leoni,3 Martina Zanforlini,4 Domenica Ancona,5 Paolo Stella,5 Anna Cavazzana,6 Angela Scapin,6 Sara Lopes,7 Valeria Belleudi,7 Gianluca Trifirò1 1Department of Diagnostics and Public Health, University of Verona, Verona, Italy; 2Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Messina, Italy; 3Lombardy Regional Centre of Pharmacovigilance and Regional Epidemiologic Observatory, Milan, Italy; 4Azienda Regionale per l’Innovazione e gli Acquisti, S.p.A, Milan, Italy; 5Apulian Regional Health Department, Bari, Italy; 6Azienda Zero, Regione Veneto, Italy; 7Department of Epidemiology, Lazio Regional Health Service, Rome, ItalyCorrespondence: Gianluca Trifirò, Department of Diagnostics and Public Health, University of Verona, P. le L.A. Scuro 10, Verona, 37134, Italy, Tel +39 045 802 7679, Email gianluca.trifiro@univr.itPurpose: This research aimed to develop and validate a META-algorithm combining individual immune-mediated inflammatory disease (IMID)-specific algorithms to identify the exact IMID indications for incident biological drug users from claims data within the context of the Italian VALORE project.Methods and Patients: All subjects with at least one dispensing of TNF-alpha inhibitors, anti-interleukin agents, and selective immunosuppressants approved for IMIDs were identified from claims databases of Latium region in Italy (observation period: 2010– 2020). Validated coding algorithms for identifying individual IMIDs from claims databases were found from published literature and combined into a META-algorithm. Positive predictive value (PPV), sensitivity (Se), negative predictive value (NPV), specificity (Sp), and accuracy (Acc) were estimated for each indication against the electronic therapeutic plans (ETPs) of the Latium region as the reference standard. Lastly, the frequency of the indication of use across individual biologic drugs was compared with that reported in three other Italian regions (Lombardy, Apulia, and the Veneto region).Results: In total, 9755 incident biological drug users with a single IMID indication were identified. Using the newly developed META-algorithm, an indication of use was detected in 95% (n=9255) of the total cohort. The estimated Acc, Se, Sp, PPV, and NPV, against the reference standard were as follows: 0.96, 0.86, 0.97, 0.82, and 0.98 for Crohn’s disease, 0.96, 0.80, 0.98, 0.85, and 0.97 for ulcerative colitis, 0.93, 0.76, 0.99, 0.95, and 0.92 for rheumatoid arthritis, 0.97, 0.75, 0.99, 0.85, and 0.98 for spondylarthritis, and 0.91, 0.92, 0.91, 0.88, and 0.94 for psoriatic arthritis/psoriasis, respectively. Additionally, no substantial difference was observed in the frequency of indication of use by active ingredient among Latium and the other three Italian regions included in the study.Conclusion: The newly developed META-algorithm demonstrated high validity estimates in the Italian claims data and was capable of discriminating with good performance among the most frequent IMID indications.Plain Language Summary: In the claims database, the lack of information on the indication of use represents a well-known limitation for the conduct of observational studies. This study was conducted to develop and validate a META-algorithm that accurately identifies the exact indication for the use of biological drugs in treating various immune-mediated inflammatory diseases. Using claims databases from the Latium region, we developed and validated a META-algorithm. The META-algorithm combines disease-specific algorithms for different immune-mediated inflammatory diseases (ie, Crohn’s disease, ulcerative colitis, rheumatoid arthritis, spondyloarthritis, psoriasis, and psoriatic arthritis) and was tested against a reference standard (electronic therapeutic plans of the Lazio region). The META-algorithm reported high validity estimates and was able to distinguish with a good performance among the most frequent IMIDs as indications for use. Applying this META-algorithm may facilitate post-marketing surveillance of biological drugs such as TNF-alpha inhibitors, anti-interleukin, and selective immunosuppressants in specific therapeutic areas in an Italian setting.Keywords: immune-mediated inflammatory diseases, biological drugs, validation, claims data, META-algorithm, indication for use

Te paper reconstructs the profound intellectual connection between Piero Calamandrei and the brothers Carlo and Nello Rosselli, which began in the 1920s with the foundation of the Circolo di Cultura in Florence, and prosecuted through the collaboration with the underground newspaper Non Mollare, until the establishment of the Partito d’Azione that inherited the legacy of the Giustizia e Libertà movement founded by Carlo Rosselli in 1929. Particular attention is paid to the commemorative plaques dedicated by Calamandrei to the Rosselli brothers and to the ideas of liberal socialism, actively cultivated by the Florentine jurist in the Constituent Assembly.

Individuals with inflammatory bowel diseases (IBDs) have an increased risk of developing psychiatric comorbidities, including eating disorders (EDs). We aimed to investigate the potential association between key disease characteristics, including psychological features, and the development of EDs in a clinical sample of adolescents with IBDs. We enrolled 52 adolescents with IBDs, 83% of whom were in clinical remission, and systematically collected additional information on disease duration, the total number of relapses, the use of steroids, and the number of hospital admissions. All participants completed a validated psychometric battery assessing psychological symptoms (Symptom Checklist-90–Revised, SCL-90-R), alexithymia (Toronto Alexithymia Scale-20, TAS-20), and ED symptomatology (Eating Disorders Inventory-3rd edition, EDI-3). About one in ten patients (9.6%) reported Eating Disorder Risk scores higher than the cut-off on the EDI-3 subscale, specifically addressing the risk of developing EDs. According to the EDI-3 scores, the risk of developing EDs directly correlated with the number of total relapses of IBDs (p < 0.05). The TAS-total scores also correlated with the number of total relapses (p < 0.01), as well as with the number of steroid cycles (p < 0.05), the number of hospital admissions (p < 0.05), and overall disease duration (p < 0.05). Our findings suggest that disease relapses increase the risk of developing both EDs and alexithymia in adolescents with IBDs. The recurrence of disease relapses should be identified and screened early on to prevent the onset of psychiatric disorders, including EDs. Research should be conducted on larger samples with different IBD phenotypes to further investigate the characteristics of patients with IBDs at risk of developing EDs.

Andrea Spini,1 Luca L’Abbate,2 Ylenia Ingrasciotta,1 Giorgia Pellegrini,1 Massimo Carollo,1 Valentina Ientile,2 Olivia Leoni,3 Martina Zanforlini,4 Domenica Ancona,5 Paolo Stella,5 Anna Cavazzana,6 Angela Scapin,6 Sara Lopes,7 Valeria Belleudi,7 Gianluca Trifirò1 1Department of Diagnostics and Public Health, University of Verona, Verona, Italy; 2Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Messina, Italy; 3Lombardy Regional Centre of Pharmacovigilance and Regional Epidemiologic Observatory, Milan, Italy; 4Azienda Regionale per l’Innovazione e gli Acquisti, S.p.A, Milan, Italy; 5Apulian Regional Health Department, Bari, Italy; 6Azienda Zero, Regione Veneto, Italy; 7Department of Epidemiology, Lazio Regional Health Service, Rome, ItalyCorrespondence: Gianluca Trifirò, Department of Diagnostics and Public Health, University of Verona, P. le L.A. Scuro 10, Verona, 37134, Italy, Tel +39 045 802 7679, Email gianluca.trifiro@univr.it

To date, no population-based studies have specifically explored the external validity of pivotal randomized clinical trials (RCTs) of biologics simultaneously for a broad spectrum of immuno-mediated inflammatory diseases (IMIDs). The aims of this study were, firstly, to compare the patients’ characteristics and median treatment duration of biologics approved for IMIDs between RCTs’ and real-world setting (RW); secondly, to assess the extent of biologic users treated for IMIDs in the real-world setting that would not have been eligible for inclusion into pivotal RCT for each indication of use. Using the Italian VALORE distributed database (66,639 incident biologic users), adult patients with IMIDs treated with biologics in the Italian real-world setting were substantially older (mean age ± SD: 50 ± 15 years) compared to those enrolled in pivotal RCTs (45 ± 15 years). In the real-world setting, certolizumab pegol was more commonly used by adult women with psoriasis/ankylosing spondylitis (F/M ratio: 1.8–1.9) compared to RCTs (F/M ratio: 0.5–0.6). The median treatment duration (weeks) of incident biologic users in RW was significantly higher than the duration of pivotal RCTs in almost all indications for use and most biologics (4–100 vs. 6–167). Furthermore, almost half (46.4%) of biologic users from RW settings would have been ineligible for inclusion in the respective indication-specific pivotal RCTs. The main reasons were: advanced age, recent history of cancer and presence of other concomitant IMIDs. These findings suggest that post-marketing surveillance of biologics should be prioritized for those patients.

During the COVID-19 pandemic, there have been multiple reports about an unforeseen surge in adolescents and young adults exhibiting sudden onset functional tic-like behaviors. This phenomenon has been mainly associated with the female gender and occasionally after exposure to social media content featuring similar patterns of functional tic-like behaviors. A significant portion of these individuals have been directed to specialist clinics for movement disorders with initial misdiagnoses of late-onset refractory Tourette syndrome. Distinguishing between rapid onset functional tic-like behaviors and neurodevelopmental tics as part of Tourette syndrome can be challenging; however, the differential diagnosis is facilitated by focusing on specific clinical and demographic factors, which we have explored in a systematic literature review. Compared to neurodevelopmental tics, functional tic-like behaviors typically present with a more abrupt and intense manifestation of symptoms, onset at a later age, higher prevalence among females, inability to suppress tics, coexisting anxiety and depression, and sometimes a history of exposure to social media content portraying tic-like behaviors of a similar nature. This novel manifestation of a functional neurological disorder may thus be viewed as an emerging neuropsychiatric condition potentially triggered/exacerbated by the psychosocial repercussions of the COVID-19 crisis.

Individuals with inflammatory bowel diseases (IBDs) have an increased risk of developing psychiatric comorbidities, including eating disorders (EDs). We aimed to investigate the potential association between key disease characteristics, including psychological features, and the development of EDs in a clinical sample of adolescents with IBDs. We enrolled 52 adolescents with IBDs, 83% of whom were in clinical remission, and systematically collected additional information on disease duration, the total number of relapses, the use of steroids, and the number of hospital admissions. All participants completed a validated psychometric battery assessing psychological symptoms (Symptom Checklist-90–Revised, SCL-90-R), alexithymia (Toronto Alexithymia Scale-20, TAS-20), and ED symptomatology (Eating Disorders Inventory-3rd edition, EDI-3). About one in ten patients (9.6%) reported Eating Disorder Risk scores higher than the cut-off on the EDI-3 subscale, specifically addressing the risk of developing EDs. According to the EDI-3 scores, the risk of developing EDs directly correlated with the number of total relapses of IBDs (p < 0.05). The TAS-total scores also correlated with the number of total relapses (p < 0.01), as well as with the number of steroid cycles (p < 0.05), the number of hospital admissions (p < 0.05), and overall disease duration (p < 0.05). Our findings suggest that disease relapses increase the risk of developing both EDs and alexithymia in adolescents with IBDs. The recurrence of disease relapses should be identified and screened early on to prevent the onset of psychiatric disorders, including EDs. Research should be conducted on larger samples with different IBD phenotypes to further investigate the characteristics of patients with IBDs at risk of developing EDs. [ABSTRACT FROM AUTHOR]

This study aims to investigate changes in the income–health gradient over the later life course. We test the age-as-leveler, the cumulative advantage/disadvantage, and the persistent inequality pattern for physical and cognitive health domains, and analyze whether these patterns are gendered. We used HRS data (1992–2016) and Poisson growth curve models to predict multimorbidity (33,860 participants) as an indicator of physical health and memory (25,291 participants) as an indicator of cognitive health. We disentangled the within-participant from the between-participant effects. For multimorbidity, the income–health gradient weakened as individuals aged; whereas for memory, the income–health gradient strengthened as individuals aged. The cumulative advantage/disadvantage of higher/lower income on memory may be more pronounced among women than men. Findings were confirmed by sensitivity analyses. Findings suggest that the support for the age-as-leveler or cumulative advantage/disadvantage pattern may depend on health domains and the effect strength may depend on gender. [ABSTRACT FROM AUTHOR]

Background: Worldwide, three million deaths each year are reported due to the harmful use of alcohol. To date, only a few drugs have been approved for the treatment of Alcohol Use Disorder (AUD). This systematic review and meta-analysis aim to assess the long-term efficacy and safety of sodium oxybate (SMO) treatment in patients with AUD., Methods: We followed the PRISMA statement guidelines and searched PubMed and ISI Web of Science to retrieve the studies of interest. In total, 13 studies on long-term (>12 weeks) SMO administra- tion in patients with AUD were included in this systematic review, and 7 were included in the meta- analysis., Results: Overall, the abstinence rate after 12 weeks of treatment was similar in the SMO and placebo groups, while it was significantly in favour of SMO compared to Naltrexone (NTX). The completion rate was similar in all three conditions. Mean corpuscular volume (MCV) levels favoured SMO over NTX, while Alcohol Craving Scale (ACS) scores did not favour SMO. The incidence of adverse reactions varied widely between studies., Conclusion: SMO in the chronic treatment of patients with AUD showed no superiority to placebo in our analysis of published RCTs, although many observational studies reported its beneficial effect in the long term. On the contrary, SMO was superior to NTX treatment on abstinence. The rate of study completion was similar in the three groups. Safety was not an issue in any of the studies included. Further studies are needed to better assess SMO efficacy and safety in the long term.