Tolerability of vortioxetine compared to selective serotonin reuptake inhibitors in older adults with major depressive disorder (VESPA): a randomised, assessor-blinded and statistician-blinded, multicentre, superiority trial.

BACKGROUND Major depressive disorder (MDD) is prevalent and disabling among older adults. Standing on its tolerability profile, vortioxetine might be a promising alternative to selective serotonin reuptake inhibitors (SSRIs) in such a vulnerable population. METHODS We conducted a randomised, assessor- and statistician-blinded, superiority trial including older adults with MDD. The study was conducted between 02/02/2019 and 02/22/2023 in 11 Italian Psychiatric Services. Participants were randomised to vortioxetine or one of the SSRIs, selected according to common practice. Treatment discontinuation due to adverse events after six months was the primary outcome, for which we aimed to detect a 12% difference in favour of vortioxetine. The study was registered in the online repository clinicaltrials.gov (NCT03779789). FINDINGS The intention-to-treat population included 179 individuals randomised to vortioxetine and 178 to SSRIs. Mean age was 73.7 years (standard deviation 6.1), and 264 participants (69%) were female. Of those on vortioxetine, 78 (44%) discontinued the treatment due to adverse events at six months, compared to 59 (33%) of those on SSRIs (odds ratio 1.56; 95% confidence interval 1.01-2.39). Adjusted and per-protocol analyses confirmed point estimates in favour of SSRIs, but without a significant difference. With the exception of the unadjusted survival analysis showing SSRIs to outperform vortioxetine, secondary outcomes provided results consistent with a lack of substantial safety and tolerability differences between the two arms. Overall, no significant differences emerged in terms of response rates, depressive symptoms and quality of life, while SSRIs outperformed vortioxetine in terms of cognitive performance. INTERPRETATION As opposed to what was previously hypothesised, vortioxetine did not show a better tolerability profile compared to SSRIs in older adults with MDD in this study. Additionally, hypothetical advantages of vortioxetine on depression-related cognitive symptoms might be questioned. The study's statistical power and highly pragmatic design allow for generalisability to real-world practice. FUNDING The study was funded by the Italian Medicines Agency within the "2016 Call for Independent Drug Research"

Comorbilit\ue0 in bambini e adolescenti con Disturbo da Deficit di Attenzione con Iperattivit\ue0/Impulsivit\ue0 in regione Lombardia

Nei pazienti ADHD \ue8 importante valutare e monitorare sistematicamente l'intero spettro delle possibili comorbilit\ue0 psicopatologiche associate, anche tenendo conto della loro evoluzione, comparsa e associazione con particolari tappe cronologiche e psicologiche dello sviluppo

Differences between centers in functional outcome of patients with ADHD after 1 year from the time of diagnosis

Abstract Although the pharmacological therapy of ADHD has been widely studied, little has been done to compare the different therapeutic approaches (e.g., drug therapy vs. psychological treatments) and even less has been done to compare the outcome of the therapy between centers. This multicenter observational study aims to assess between-center variation in functional outcome of ADHD patients one year after the diagnosis, according to the treatment received. We used the Regional ADHD Registry data on 1429 patients enrolled in 16 ADHD centers in the 2011–2022 period. To evaluate the effectiveness of the therapy we used a generalized linear mixed model with the center as the random effect, including patient condition at diagnosis and center characteristics, weighting by the inverse of the propensity score of the treatment received by the patient. Between-center variation was expressed as the relative difference in odds-ratios between the observed and the expected number of patients whose condition improved, using the Clinical Global Impressions—Improvement Scale (CGI-I), and the relative 95% CI. Patients who received combined treatment were significantly more likely to improve compared to other treatment groups (65.5% vs 54.4% for methylphenidate alone, 53.4% for psychological treatment alone, or 40.5% for no therapy). Adjusted for patients and center characteristics, the log-odds ratio ranged from 0.85 (0.29–1.55 95% CI) to − 0.64 (− 1.17–− 0.18 95% CI). The mean expected probability of improvement after one year of therapy for an average patient with ADHD for each center was 47.7% in a center at the 25th percentile and 61.2% in a center at the 75th percentile of the outcome distribution after adjustments. The wide between-center variation in patient functional improvement one year after the diagnosis of ADHD could be largely explained by center-specific therapeutic approaches or attitudes. More careful and stringent work is needed to reduce differences in responses between centers, as could formal and periodic audit programs within and between centers

MOESM1 of Italian regional health service costs for diagnosis and 1-year treatment of ADHD in children and adolescents

Additional file 1. Additional tables

IOEASMA: an integrated clinical and educational pathway for managing asthma in children and adolescents

Abstract Background Due to the lack of real life clinical and educational studies, “Io e l’Asma” Centre performed this implementation research (IR). Evaluate long-term effectiveness on bronchial asthma control of an integrated clinical and educational pathway for asthmatic children and adolescents. Methods An observational retrospective pre-post intervention IR study was conducted among 262 children with asthma, ages 6-15 yrs. The intervention protocol included three clinical visits 8 weeks apart; an educational course at visit 1, post intervention consisted in two follow-up visits 6 months apart. The primary outcome was to verify the percentage of children who achieved bronchial asthma control at each visit. Secondary outcomes were based on daily therapy modulation, hospital admissions and the number of school days missed. An economic assessment was also included. Results Two hundred sixty two children with bronchial asthma completed the pathway and were included in the analysis. The percentage of children who obtained disease control increased from 44% at visit 1 to 79% at visit 3 and at 1-year follow-up was 83%. Hospital admissions represent 11% of children: 8% before the intervention, 2% during the intervention, and 1% before and during the intervention; no hospitalizations related to bronchial asthma exacerbations were reported during the 2 follow-up visits. Conclusions The therapeutic-educational pathway was adapted according to the international guidelines and the primary performance indicators. Our findings confirmed that the clinical plus educational approach, shared between specialists and family physicians, is an effective template for asthma management. These findings also demonstrated a strong economic advantage

Pediatrician and parental evaluation of child neurodevelopment at 2 years of age

Abstract Background The early identification of infants with a risk for neurodevelopmental disorders in the first few years of life is essential for better developmental outcomes. Screenings should be carried out by combining the family pediatricians’ and parents’ perspectives, the two fundamental sources of information on children’s health. The present study has three aims: (a) to test the feasibility of parent-report instruments to detect warning signs in their children’s development; (b) to ascertain whether there is an agreement between the family pediatricians’ (FP) clinical judgments of warning signs and the parental perceptions; (c) to determine whether there is a link between parents’ distress and child development. Methods Within the NASCITA birth cohort, in addition to the family pediatrician’s clinical evaluation with routine tools, the Modified Checklist for Autism in Toddlers, Revised (M-CHAT-R) was completed by parents to assess the child’s language, social skills, behavior, and sensory areas. Parents were also asked to complete the Parenting Stress Index, Short Form (PSI-SF) to verify the magnitude of stress in the parent-child system. Univariate and multivariate analyses were performed to evaluate the association between child and parental characteristics and the presence of warning signs. Results The follow-up assessment was completed for 435 infants: 69 (15.8%) presented warning signs: 43 in the pediatrician’s assessment and 36 in the M-CHAT-R (10 in both). A total of 16 children (14 with warning signs) received a diagnosis after a specialist evaluation. Being male (OR 2.46, 95%CI: 1.23–4.91) and having sleep disorders (OR 2.43, 95% CI 1.17–5.04) was associated with a greater likelihood of warning signs in the multivariate analysis, while reading aloud was a protective factor (not exposed versus exposed (OR = 3.14; 95% CI 1.60–6.17). For 73 children (18.4%), at least one parent tested positive for PSI-SF. An increased prevalence of parental distress was observed in children with warning signs (OR 2.36, 95% CI 1.27–4.37). Conclusions Integrating physician and parental perspectives during well-child visits and in clinical practice appears feasible and can improve the identification of children at risk of developmental disorders

Comorbidity prevalence and treatment outcome in children and adolescents with ADHD

Although ADHD comorbidity has been widely studied, some issues remain unsolved. This multicenter observational study aims to examine comorbid psychiatric disorders in a clinical sample of newly diagnosed, treatment na\uc3\uafve children and adolescents with and without ADHD and, to compare treatment efficacy based on the type of comorbidity. We performed an analysis of the medical records of patients identified from the Regional ADHD Registry database, enrolled in 18 ADHD centers in the 2011\ue2\u80\u932016 period. 1919 of 2861 subjects evaluated (67%) met the diagnostic criteria for ADHD: 650 (34%) had only ADHD, while 1269 (66%) had at least one comorbid psychiatric disorder (learning disorders, 56%; sleep disorders, 23%; oppositional defiant disorder, 20%; anxiety disorders, 12%). Patients with ADHD of combined type and with severe impairment (CGI-S \ue2\u89\ua55) were more likely to present comorbidity. 382 of 724 (53%) followed up patients improved after 1 year of treatment. ADHD with comorbidity showed greater improvement when treated with combined interventions or methylphenidate alone. Specifically, combined treatment showed significant superiority for ADHD with learning disorders (ES 0.66) and ODD (ES 0.98), lower for ADHD with sleep or anxiety disorders. Training intervention alone showed only medium efficacy (ES 0.50) for ADHD and learning disorders. This study was the first describing comorbidity patterns of ADHD in Italy, confirming, in a multicenter clinical setting, that ADHD is more often a complex disorder. Findings highlight important diagnostic, therapeutic, and service organization aspects that should be broadly extended to ensure an appropriate and homogenous ADHD management