Orphan drugs

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Monitoring Appropriate Monoclonal Antibodies Prescribing via Administrative Data: An Application to Psoriasis

: The Italian Medicines Agency (AIFA) and the Italian Regional Health Systems have implemented measures together with data collection and analysis to improve medicines' appropriate prescription. Administrative databases represent rich Real-World Evidence (RWE) sources that may be leveraged for research purposes. Thus, such heritage may allow for appropriate prescription studies to be carried out on complex pharmaceutical molecules, as the appropriateness of prescriptions is essential both for patients' treatment and to ensure healthcare systems' sustainability. This study analyzed the appropriate monoclonal antibodies (mAbs) prescribed in psoriasis treatment across Tuscany, Italy. Data were extracted from several large administrative databases collected by the Tuscan Regional Healthcare System through record linkages. The analysis showed that over 30% of the 2020 cohort of psoriatic patients could be regarded as potentially inappropriate treated, signaling that mAbs are often prescribed as first-line treatment contrary to guidelines. Variation was observed in the appropriate prescription of mAbs, across different types of mAbs and areas. The study revealed potential inappropriate prescription, and its geographic variation should raise awareness among managers about the appropriate use of resources. Despite limitations, this could represent a pilot for future studies to evaluate the appropriate prescription of mAbs in other clinic conditions and across time

Transcranial direct current stimulation: A novel approach in the treatment of vascular depression.

Background: Despite the impact of depression in terms of personal suffering and socioeconomic burden, most currently available treatment options are often ineffective. A particularly difficult-to-treat depressive disorder characteristic of the elderly is vascular depression, a late-life depressive syndrome related to a variety of potential vascular mechanisms. Transcranial Direct Current Stimulation (tDCS), a non-invasive and effective somatic approach to depression, also showed positive effects on cognitive deficits. Aim: We performed a double-blind randomized study to investigate the efficacy of tDCS as augmentation strategy to sertraline in the treatment of vascular depression, hypothesizing a positive effect in both depressive symptoms and cognitive functions. Methods: We enrolled 93 inpatients over 60 years of age with a diagnosis of vascular depression. Depressive symptoms were weekly assessed (T0, T1, T2) with the 21-items Hamilton depression rating scale (HDRS). Cognitive functioning was evaluated with the Milan Overall Dementia Assessment (MODA) at baseline and after the treatment protocol. All patients were randomly assigned into three groups, Group I: one tDCS stimulation per day, Group II: two tDCS stimulations per day, Sham group: one sham tDCS stimulation per day. Stimulation was performed for 10 consecutive working days. Results: A significant interaction time∗treatment was observed on HDRS scores (F = 14, p < 0.001). All groups improved at T1 but whereas Group II significantly differed from the Sham group (p < 0.001) we observed no difference between Sham and Group I. At T2 all groups improved but Group II showed the greater improvement (vs. Sham p < 0.001; vs. Group I p < 0.001) and the Sham group the smallest (vs. Group I p = 0.005). A significant interaction time∗treatment was also observed on MODA scores (F = 3.31, p = 0.04). Only subjects treated with tDCS improved at T2 (Group I: p < 0.001; Group II: p = 0.007). However, no difference between Group I and II was shown. Conclusion: tDCS as augmentation treatment of an adequate pharmacotherapy is a potential strategy in the management of vascular depression, a disease known to be often unresponsive to antidepressants only. Non-invasiveness, the absence of severe side effects and the possibility of administering it to outpatients at an affordable price make tDCS an important tool in clinical practice

Stem-Skilled Parents and Autism Spectrum Disorder in Offspring: A Case-Control Study

Autism spectrum disorder (ASD) is a neurodevelopment disorder characterised by a range of deficits in two specific domains: social communication and social interaction and repetitive patterns of behaviour. Several studies have explored the link between ASD and STEM (science, technology, engineering and mathematics, or other mathematics-grounded disciplines), but results are still uncertain. Objective of the study was to estimate the potential role of systemising abilities in parents as a risk factor for ASD in the offspring, using the achievement of a degree in STEM disciplines as a proxy characteristic of the exposure. There were 1,316 participants overall. There were 658 incident consecutive cases of definite ASD, diagnosed in a Reference Centre for ASD in Italy, from 2001 to 2020. The main exposure variable was parental education level. The risk of ASD in the offspring associated with the main exposure variable and the exposure covariates (e.g. use of neurotropic drugs during the first trimester of the mother’s pregnancy, perinatal outcomes of participants and/or preterm birth) was studied by using conditional logistic regression analysis. In addition, we carried out a mediation analysis to investigate whether and the extent to which covariates significantly associated with ASD risk mediate the relationship between parental education level and ASD in offspring. A STEM degree in parents was significantly associated with risk of ASD in offspring (OR 1.43, 95% CI 1.03-2.54). Familiarity was weakly associated with the risk of ASD (OR 1.33, 95% CI 1.00-1.66) and is the stronger mediator (PME 28%). Sensitivity analysis did not show deviations related to gender or ASD level. Our study moves in the direction of confirming the risk of occurrence of ASD in the offspring of parents with elevated systemising abilities

Local characterization of ferromagnetic properties in ferromagnet/superconductor bilayer by Point Contact Andreev Reflection Spectroscopy

We realized point contact spectroscopy experiment on ferromagnet/superconductor bilayers. Differential conductance curves show several features that we explained within Bogoliubov-de Gennes formalism considering the presence of two interfaces in the normal-metal-tip/ferromagnet/superconductor device. We demonstrate that such configuration is suitable as local probe of the spin polarization and thickness of ferromagnetic layer, directly on bilayer areas. This is due to the high sensitivity of the Andreev surface states to the physical properties of the ferromagnetic interlayer

A Morphological and Ultrastructural Study of the Anterior Digestive Tract of Adult Nile Tilapia Oreochromis niloticus

Among the most-used fish species in aquaculture is the Nile tilapia, due to its rapid growth rate and its adaptation to a wide range of farming conditions. A careful description of the morphology of the digestive tract, particularly the esophagus and stomach, allows a better understanding of the relationship between structure and function. Combining scanning and light microscopy we highlighted the presence of five different zones in the stomach (1: esophagus-gastric lumen passage; 2: descending glandular portion; 3: fundic portion; 4: ascending glandular portion; 5: gastric-pyloric transition portion). Histochemical investigation showed a secretion of carboxylates mucopolysaccharides along the esophagus and sulphated complex carbohydrates in the stomach. These results suggest that mucins play a protective role of the epithelial lining, which is essential for a correct digestive process. Finally, the characterization of the main cellular structures may be inspiring for more advanced studies aiming to decipher the role of specific molecules, such as neuropeptides, involved in the physiological digestive process

Yield of diagnosis and risk of stroke with screening strategies for atrial fibrillation: a comprehensive review of current evidence.

Atrial fibrillation (AF) is the most prevalent arrhythmia worldwide. The presence of AF is associated with increased risk of systemic thromboembolism, but with the uptake of oral anticoagulant (OAC) and implementation of a holistic and integrated care management, this risk is substantially reduced. The diagnosis of AF requires a 30-s-long electrocardiographic (ECG) trace, irrespective of the presence of symptoms, which may represent the main indication for an ECG tracing. However, almost half patients are asymptomatic at the time of incidental AF diagnosis, with similar risk of stroke of those with clinical AF. This has led to a crucial role of screening for AF, to increase the diagnosis of population at risk of clinical events. The aim of this review is to give a comprehensive overview about the epidemiology of asymptomatic AF, the different screening technologies, the yield of diagnosis in asymptomatic population, and the benefit derived from screening in terms of reduction of clinical adverse events, such as stroke, cardiovascular, and all-cause death. We aim to underline the importance of implementing AF screening programmes and reporting about the debate between scientific societies' clinical guidelines recommendations and the concerns expressed by the regulatory authorities, which still do not recommend population-wide screening. This review summarizes data on the ongoing trials specifically designed to investigate the benefit of screening in terms of risk of adverse events which will further elucidate the importance of screening in reducing risk of outcomes and influence and inform clinical practice in the next future