Real-World Apremilast Use for Treatment of Plaque Psoriasis in Italy: Patient Perspective, Characteristics, and Clinical Outcomes from the DARWIN Study

IntroductionWhile several european studies have reported real-world apremilast use, patient-perceived benefits, and treatment satisfaction, local reimbursement criteria for apremilast vary and data from Italy are limited.methodsThe cross-sectional DARWIN study enrolled consecutive patients who had initiated apremilast for plaque psoriasis 6 (+/- 1) months prior to enrolment at a single visit across 24 Italian dermatological sites. disease severity was assessed using body surface area (BSA) and physician global assessment (PGA). patient-reported outcomes assessed 6 (+/- 1) months after apremilast initiation were dermatology life quality Index (DLQI), patient benefit Index (PBI), and 9-item treatment satisfaction questionnaire for medication (TSQM-9).ResultsOf 184 patients enrolled between July 2019 and January 2021, 180 were included in the analysis. at apremilast initiation, median (25th-75th percentile) time since psoriasis diagnosis was 8.6 (3.2-22.2) years; median BSA, 10.0% (5.0-16.0); mean (standard seviation, SD) DLQI total score, 13.5 (8.0). over half (54.9%) of patients with available data reported psoriasis had a very or extremely large effect on their quality of life (QoL); half reported itching (50.6%) and/or special areas involvement (50.0%). most (73.9%) had comorbidities and were biologic-naive (81.5%). the most common reasons for initiating apremilast were lack of efficacy of previous treatment (56.7%) and contraindications to other treatments (44.4%). At 6 (+/- 1) months, most patients were continuing apremilast and/or reported a global PBI score >= 1 (minimum clinical benefit) (86.1% and 90.0%, respectively); approximately half achieved BSA <= 3% and/or DLQI total score <= 5 (47.1% and 48.5%); 18.8% achieved PGA = 0; mean (SD) TSQM-9 global treatment satisfaction score was 59.0 (24.8). apremilast was well tolerated; no new safety signals were identified .conclusions patients treated with apremilast for 6 months in Italian clinical practice reported improved QoL, clinically relevant improvements in symptoms, high treatment satisfaction, and high treatment persistence. our data indicate apremilast is a valuable treatment option for moderate plaque psoriasis. study registration clinical trials.gov identifier, NCT04031027

Long-Term Drug Survival and Effectiveness of Secukinumab in Patients with Moderate to Severe Chronic Plaque Psoriasis: 42-Month Results from the SUPREME 2.0 Study

Purpose: SUPREME, a phase IIIb study conducted in Italy, demonstrated safety and high efficacy of secukinumab for up to 72 weeks in patients with moderate-to-severe plaque-type psoriasis. SUPREME 2.0 study aimed to provide real-world data on the long-term drug survival and effectiveness of secukinumab beyond 72 weeks.Patients and Methods: SUPREME 2.0 is a retrospective observational chart review study conducted in patients previously enrolled in SUPREME study. After the end of the SUPREME study, eligible patients continued treatment as per clinical practice, and their effectiveness and drug survival data were retrieved from medical charts.Results: Of the 415 patients enrolled in the SUPREME study, 297 were included in SUPREME 2.0; of which, 210 (70.7%) continued secukinumab treatment throughout the 42-month observation period. Patients in the biologic-naive cohort had higher drug survival than those in the biologic-experienced cohort (74.9% vs 61.7%), while HLA-Cw6-positive and HLA-Cw6-negative patients showed similar drug survival (69.3% and 71.9%). After 42 months, Psoriasis Area and Severity Index (PASI) 90 was achieved by 79.6% of patients overall; with a similar proportion of biologic-naive and biologic-experienced patients achieving PASI90 (79.8% and 79.1%). The mean absolute PASI score reduced from 21.94 to 1.38 in the overall population, 21.90 to 1.24 in biologic-naive and 22.03 to 1.77 in biologic-experienced patients after 42 months. The decrease in the absolute PASI score was comparable between HLA-Cw6-positive and HLA-Cw6-negative patients. The baseline Dermatology Life Quality Index scores also decreased in the overall patients (10.5 to 2.32) and across all study sub-groups after 42 months. Safety was consistent with the known profile of secukinumab, with no new findings. Conclusion: In this real-world cohort study, secukinumab showed consistently high long-term drug survival and effectiveness with a favourable safety profile

Understanding sex/gender differences in intelligence profiles of children with Autism: A comprehensive WISC meta-analysis

Background: Intelligence assessment in children with autism spectrum disorders (ASD) often sparks debates about sex/gender differences. Specifically, the question arises whether girls exhibit lower performance on intelligence scales compared to boys. This meta-analysis examines nine studies (N=1105; 809 boys and 296 girls) to quantify sex/gender differences on the Wechsler Intelligence Scale for Children (WISC) in children with ASD, comparing their results to typically developing children. Method and procedures: Random-effects meta-analyses on WISC indices and subtests were conducted to address the heterogeneity across effect sizes. Results for children with ASD were compared to those of typically developing children. Outcomes and results: Findings revealed no significant differences in general intellectual functioning (full-scale IQ), verbal comprehension, working memory, or processing speed between boys and girls in children with ASD. Boys showed an advantage only in the perceptual reasoning index. At the subtest level, boys outperformed on certain tasks, while girls excelled in others. Conclusions and implications: The observed pattern of differences in the ASD population aligns quantitatively with those in typically developing populations. Differences, if present, are specific to certain indices rather than general intelligence. These insights contribute to a nuanced understanding of gender-related cognitive variations in the context of ASD

The impact of math anxiety and self-efficacy in middle school STEM choices: A 3-year longitudinal study

Introduction: In today's world, which is progressively oriented towards science and technology and facing a growing demand for skilled professionals, it becomes essential to identify the factors that encourage individuals to pursue careers in STEM fields (Science, Technology, Engineering and Mathematics). Previous research has shown that affective-motivational factors, math performance and gender influence STEM occupational and academic choices in adulthood. However, few studies examined how these factors may influence STEM choices as early as middle school. This study aims to assess how math anxiety, math self-efficacy, math performance and gender influence STEM school choices during middle school. Methods: We longitudinally assessed a group of 109 students (Year 6) over three school years, with measurements taken on three different occasions. Results: Findings indicated that individuals who made an STEM school choice experienced lower math anxiety, higher self-efficacy and math performance and were predominantly male. Furthermore, the results indicated that both math anxiety in Year 7 and self-efficacy in Year 6 made the most substantial unique contributions to the STEM school choice. Conclusion: Math anxiety and math self-efficacy seem to be both crucial in influencing middle school students' STEM choices, offering new perspectives for early interventions aimed at promoting more informed school choices

Muscular damage during telbivudine treatment in a chronic hepatitis B patient

Muscle tissue damage might be related to metabolic and mechanical factors. Certain drugs have been associated with increased blood levels of creatin phospho kinase (CPK) and myoglobin that are biochemical markers of musculoskeletal damage. An increase of CPK plasma levels might suggest severe rhabdomyolysis with possible resulting renal failure. Telbivudine is an antiviral drug indicated for the treatment of chronic hepatitis B (CHB) in adult patients. An increase in CPK plasma levels has been recently described in some telbivudine-treated CHB patients without muscle-skeletal symptoms. In this paper we report a CHB patient that developed a severe increase of CPK plasma levels during telbivudine-treatment. Pharmacological evaluation, using the Naranjo probability scale, indicated a probable relationship between telbivudine and CPK increase, so telbivudine was discontinued and replaced with entecavir with a complete resolution of laboratory findings. In conclusion, telbivudine treatment can induce muscular damage in the absence of skeletal injury, therefore we suggest to closely monitor the muscular function of the patients treated with this drug in order to prevent possible major complications

A comprehensive comparison between GaN MMIC Doherty and combined class-AB power amplifiers for microwave radio links

A combined class-AB and a Doherty power amplifier conceived for microwave backhaul in the 7 GHz frequency band are here presented and compared. They are fabricated in the same GaN monolithic process and have identical total active device periphery. For the given application, the linearity-efficiency trade-off for the two architectures is discussed. The two modules have been thoroughly characterized in linear and non-linear continuous wave conditions. Then, to evaluate linearity under the actual operative conditions, a system level characterization has been carried out, applying a modulated input signal and comparing the spectral responses of the two amplifiers with and without digital predistortion. A saturated output power of 40 dBm has been achieved by both circuits. At 6 dB of output back-off, the Doherty amplifier shows an efficiency of 33%, 10 points higher than that of the class-AB module. On the other hand, system level measurements show that, adopting the same predistorter complexity to comply with the reference standard emission masks, the Doherty amplifier needs at least 1 dB of extra back-off. This negatively affects its efficiency, therefore reducing the advantages it can claim with respect to the class-AB amplifier in continuous wave condition

Truncated reverse isoxazolidinyl nucleosides: a new class of allosteric HIV-1 reverse transcriptase inhibitors

The synthesiso of HEPT-derived tru ncated reversei isoxazolidinyl nucleosides( shown)is reported. These compounds represent the first exampleso f isoxazolidinebse aringa pyrimidine scaffold at the C-3 position usinga glycoside-typeli nkage.B iological evaluation showed that some of the derivativesa ct as non-nucleosidien hibitors of HIV-1r everset ranscriptasew, ith an efficacy comparable to that of Nevirapine but with reduced toxicity

Role of the Insula and Vestibular System in Patients with Chronic Subjective Dizziness: An fMRI Study Using Sound-Evoked Vestibular Stimulation

Chronic subjective dizziness (CSD) is a common vestibular disorder characterized by persistent non-vertiginous dizziness, unsteadiness, and heightened sensitivity to motion stimuli that may last for months to years after events that cause acute vestibular symptoms or disrupt balance. CSD is not associated with abnormalities of basic vestibular or oculomotor reflexes. Rather, it is thought to arise from persistent use of high-threat postural control strategies and greater reliance on visual cues for spatial orientation (i.e., visual dependence), long after triggering events resolve. Anxiety-related personality traits confer vulnerability to CSD. Anomalous interactions between the central vestibular system and neural structures related to anxiety may sustain it. Vestibular- and anxiety-related processes overlap in the brain, particularly in the insula and hippocampus. Alterations in activity and connectivity in these brain regions in response to vestibular stimuli may be the neural basis of CSD. We examined this hypothesis by comparing brain activity from 18 patients with CSD and 18 healthy controls measured by functional magnetic resonance imaging during loud short tone bursts, which are auditory stimuli that evoke robust vestibular responses. Relative to controls, patients with CSD showed reduced activations to sound-evoked vestibular stimulation in the parieto-insular vestibular cortex (PIVC) including the posterior insula, and in the anterior insula, inferior frontal gyrus, hippocampus, and anterior cingulate cortex. Patients with CSD also showed altered connectivity between the anterior insula and PIVC, anterior insula and middle occipital cortex, hippocampus and PIVC, and anterior cingulate cortex and PIVC. We conclude that reduced activation in PIVC, hippocampus, anterior insula, inferior frontal gyrus, and anterior cingulate cortex, as well as connectivity changes among these regions, may be linked to long-term vestibular symptoms in patients with CSD. Furthermore, altered connectivity between the anterior insula and middle occipital cortex may underlie the greater reliance on visual cues for spatial orientation in CSD patients relative to controls