Azienda Socio Sanitaria Territoriale Lariana

To compare two sodium hyaluronate formulations (HYMOVIS® ONE and MONOVISC®) for single intra-articular (IA) injection in patients with knee osteoarthritis pain. This randomized, controlled study included 347 subjects allocated to two treatment arms: HYMOVIS® ONE (n = 175) and MONOVISC® (n = 172). The primary endpoint assessed non-inferiority of HYMOVIS® ONE versus MONOVISC® based on change from baseline in the WOMAC LK3.1 A1 Pain subscale. Secondary outcomes evaluated patient response using OMERACT-OARSI criteria, changes in WOMAC stiffness and function scores, health-related quality of life (SF-12), global assessments by patients and clinicians, and rescue medication use. The mean WOMAC LK3.1 A1 walking pain subscale score decreased significantly from baseline at week 12 in both groups, with reductions of 65 % for HYMOVIS® ONE and 66 % for MONOVISC®. At week 26, reductions were 73 % for HYMOVIS® ONE and 69 % for MONOVISC®. The non-inferiority test yielded a p-value of 0.0003. Clinically significant change from baseline was observed for all secondary endpoints. For the WOMAC LK3.1 Function subscale, the comparison between groups at week 26 showed a statistically significant difference (p = 0.0367) favoring HYMOVIS® ONE. Both treatments were well tolerated. A single injection of HYMOVIS® ONE was well tolerated and non-inferior to MONOVISC®, with improvements across all study endpoints maintained through 26 weeks, indicating sustained symptomatic relief of knee OA. NCT06528600 (www.clinicaltrials.gov).

Direct current stimulation (DCS) -i.e., the application of a static electric field to the brain through surface scalp electrodes- emerged as a novel therapy for neuropsychiatric disorders. In this study, DCS-induced changes in gene expression were assessed on Botryllus schlosseri, a ubiquitous simple colonial chordate living in temperate seas and sharing genetic remarkable similarities with mammals. Colonies underwent either sham or real DCS stimulation. Behavioral assessments, including the Siphon Stimulation Test and heart-rate measurements, were conducted before and at three intervals post-stimulation (3, 24, and 48h). Gene expression was analyzed with sequencing reads via Trimmomatic®. Analysis of heart rate frequency revealed post-treatment differences between the groups immediately after stimulation (p=0.001), with the effect decreasing over time. Real DCS differentially expressed 191 genes at three h post-DCS, 104 at 24h, and 529 at 48h. Our study introduces a novel pre-clinical model for DCS application demonstrating for the first in vivo time an after-effect on gene expression related to inflammation, human development, and neurodegeneration. To the best of our knowledge, this is the first paper addressing DCS effects on gene expression in a living animal model.

Major depressive disorder (MDD) is a leading cause of disability worldwide and contributes significantly to the global burden of disease. Recent data show an increasing prevalence of treatment-resistant depression (TRD). Patients with autism spectrum disorder (ASD) often exhibit MDD as a comorbidity and it is often resistant to conventional treatments. ASD determines emotional dysregulation and a reduced ability to understand mental states (mentalization). These features can lead to suicidal ideation and/or behavior. Intranasal esketamine may offer a novel therapeutic option for this population. This case series focuses on the clinical response to intranasal esketamine in patients with autism and TRD; esketamine is approved in Italy as an add-on therapy in TRD, so our case study is based on an in-label treatment. Three young patients (n = 3, F/M 2:1, age range 20-25 y) with light to moderate autism (Level 1 or 2) were treated. Esketamine was administered in augmentation with selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs) in accordance with EMA/AIFA guidelines. A structured follow-up protocol was set to monitor depressive symptoms, social cognition, and mentalization. Follow-up during treatment was maintained for six months, and psychometric evaluations were performed at six time points: baseline (T0), 1 week (T1), 1 month (T2), 2 months (T3), 3 months (T4), and 6 months (T5). Also, subjective quality of life was investigated before and after the observation period. Despite differences in clinical profile, all patients showed good efficacy of esketamine in reducing depressive symptoms: two patients experienced clinical remission at T5 (MADRS < 10), one patient showed partial response (dMADRS = 43.24%). No major side effects were reported. Significant improvements were observed after the first week of treatment (P1: MADRS_T0 = 37, MADRS_T1 = 12; P2: MADRS_T0 = 32, MADRS_T1 = 21; P3: MADRS_T0 = 25, MADRS_T1 = 12). Depressive relapses occurred (e.g., P1, T3-T4), but they were not associated with hospitalizations and/or suicidal attempts. Suicidal ideation, when present, decreased by the end of the follow-up period. Lack of mentalization and in social cognition was noted, with just mild improvements during therapy. Subjective quality of life improved significantly for all patients (P1: 28% at T0, 73% at T5. P2: 25% at T0, 71% at T5. P3: 35% at T0, 80% at T5). Intranasal esketamine showed a favorable efficacy and safety in these three cases of TRD in comorbidity with ASD (at six months: total remission = 66.66%, partial remission = 33.33%, inefficacy = 0%, drop-out = 0, severe adverse events = 0). Besides improvements in depressive symptoms, esketamine was associated with a constant decrease in suicidal thoughts. A case series is unfit to form statistical conclusions; preliminary data warrant further investigation in randomized controlled studies to validate the therapeutic potential of esketamine in this population.

Despite continuous improvements in neonatal resuscitation and stabilization in the last decades, thermal management immediately after birth remains an unresolved issue in preterm infants. To compare 2 strategies of thermal management (plastic wrapping with or without drying) for preventing heat loss at birth in very preterm infants. This multicenter, unblinded, randomized clinical trial was conducted among very preterm infants (birth weight <1500 g and/or gestational age ≤30 weeks 6 days) at 21 tertiary care hospitals in Italy from February 21, 2023, to July 18, 2024. Eligible neonates were randomly allocated to either drying before plastic wrapping in the delivery room (intervention arm) or plastic wrapping without drying (control arm). The primary outcome was the proportion of participants with normothermia (36.5-37.5 °C) at admission to the neonatal intensive care unit (NICU). The secondary outcomes included hypothermia (<36.5 °C), moderate to severe hypothermia (<36.0 °C), and hyperthermia (>37.5 °C) at NICU admission, temperature at 1 hour after NICU admission, intraventricular hemorrhage, respiratory distress syndrome, late-onset sepsis, bronchopulmonary dysplasia, and mortality before hospital discharge. Overall, 354 very preterm infants were randomized (180 [50.8%] female; mean [SD] gestational age, 28.6 [2.5] weeks); all received the allocated intervention and were included in the analysis. Normothermia at NICU admission was achieved in 81 of 177 dried infants (45.8%) and 82 of 177 undried infants (46.3%; risk ratio, 0.99; 95% CI, 0.79-1.24). The mean (SD) neonatal temperature at NICU admission was 36.4 °C (0.8 °C) in dried neonates and 36.5 °C (0.7 °C) in undried neonates (mean difference, -0.1 °C; 95% CI, -0.2 °C to 0.1 °C). In-hospital mortality included 26 of 177 dried neonates (14.7%) and 10 of 177 undried neonates (5.6%) (unadjusted risk ratio, 2.60; 95% CI, 1.29-5.23). The other secondary outcome measures were not different between the 2 arms. In this multicenter randomized clinical trial, drying before plastic wrapping provided no benefit to very preterm infants in maintaining normothermia at NICU admission. Most deaths could be expected due to the compromised profile of the neonates, with no pathophysiological explanation related to the trial interventions. Approximately half of the infants were outside the normal thermal range at NICU admission; hence, thermal management remains a challenge requiring further investigations. ClinicalTrials.gov Identifier: NCT05740072.

The evolution of the mHealth era offers the possibility of behavioral interventions to promote changes in lifestyle habits with prevention relevance. These tools are considered digital therapeutics (DTx) and follow the MDR 745/2017 for testing, validation, and certification. In the frame of the ACTIVE3 project, we developed a platform composed of a mobile app, a wearable device, and a cloud backend to support healthy aging intervention in a population of 60–80-year-old subjects. This paper describes the clinical trial protocol and the baseline data of the recruited population. The explored parameters describe the effect of the DTx in the physical, nutritional (and metabolic), and cognitive domains, leveraging the Walking Group initiatives coordinated by ATS Brianza that are active in the Lecco area; in addition, system usability and acceptance were analyzed. The study started on 1 September 2024, and the analyzed baseline data are presented here. With respect to an expected population of 200 subjects, we received interest and consent to participate from 237 subjects: over-enrollment was allowed and all these subjects were accepted into the study. The characterization of the study population at the initial time of the trial was carried out, and the outcomes are presented here. The population is generally more active than Italian people of the same age. According to the outcome of the 6MWT, the population was divided into three groups: trained participants (42 subjects), active participants (142 subjects), and sedentary participants (58 subjects). The tests at month 12 were recently competed, and the final results will be available in winter 2025–2026.

Patient self-care and caregiver contribution to self-care in chronic illnesses should be considered together as a dyadic phenomenon called "dyadic illness management." The possibility of classifying dyadic engagement in chronic conditions care may uncover behavioral patterns useful for improving disease management. Mixed-effects models have been used to obtain dyadic scores, which serve as inputs for latent class analysis. However, the advantages of this approach over simpler synthetic dyadic measures remain unclear. The aim of this study was to compare two methods for obtaining dyadic scores to serve as inputs for identifying distinct patterns of dyadic illness management for type 2 diabetes (T2D) through latent class analysis. This work uses data from a cross-sectional study on 251 patients with T2D and their informal caregivers. Patient self-care and caregiver contribution to self-care were measured by the Self-Care of Diabetes Inventory and the Caregiver Contribution to Self-Care of Diabetes Inventory, respectively. To assess dyadic illness management, we first adopted the incongruence model, a mixed-effects model with a specific codification that enables the estimation of both the average and incongruence in the outcome within each dyad, through random intercepts and random slopes. These estimated coefficients were then used to perform a latent class analysis that was able to identify patterns of dyadic management. As an alternative approach, we calculated the dyadic average and incongruence using the raw means and the difference between patient and caregiver scores. These values were then used as inputs for latent class analysis. The latent class analysis clustered the same dyads into the same classes across both approaches, with identical fit indices. The three-class model showed the best performance in terms of both fit and characterization of the dyads. Mixed-effects models account for interdependence within the dyad and measurement error, returning predicted measures that are shrunk toward the overall mean. However, this approach yielded the same clusters as the simpler method based on observed measures.

ABSTRACTBackgroundNitrous oxide/oxygen (N2O/O2 50%/50%) is an effective and safe technique for procedural sedation in paediatric settings; however, the knowledge, use and perspectives of healthcare professionals regarding N2O/O2 remain limited.AimTo investigate the knowledge, use and perspectives of healthcare professionals regarding N2O/O2 in maternal–infant and emergency units.Study DesignA cross‐sectional study was conducted (March to December 2024) using (i) a sociodemographic information tool and (ii) a 16‐item questionnaire assessing knowledge, clinical use, perceived barriers and willingness to adopt N2O/O2. Descriptive and multivariate analyses were performed.ResultsOf 113 respondents, 40.7% reported currently using N2O/O2 in their clinical units, while 91.0% of non‐users expressed willingness to adopt it. Barriers included lack of equipment (92.9%) and training (84.1%). 91.1% considered N2O/O2 ethically acceptable, consistent with principles of beneficence, non‐maleficence and child comfort. Employment in emergency units and holding a three‐year nursing degree were significant predictors of N2O/O2 use.ConclusionsLimited Use of N2O/O2 in Italian Paediatrics Contrasts With Strong Professional Interest. Improving Training and Resources Could Enhance Access to Safe Paediatric Sedation.Relevance to Clinical PracticeTraining, equipment and guidelines are needed to translate willingness into real clinical practice, improving the safety and consistency of paediatric sedation.