Dupilumab in the treatment of severe uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP): A multicentric observational Phase IV real-life study (DUPIREAL)

Background Chronic rhinosinusitis with nasal polyps (CRSwNP) is associated with significant morbidity and reduced health-related quality of life. Findings from clinical trials have demonstrated the effectiveness of dupilumab in CRSwNP, although real-world evidence is still limited. Methods This Phase IV real-life, observational, multicenter study assessed the effectiveness and safety of dupilumab in patients with severe uncontrolled CRSwNP (n = 648) over the first year of treatment. We collected data at baseline and after 1, 3, 6, 9, and 12 months of follow-up. We focused on nasal polyps score (NPS), symptoms, and olfactory function. We stratified outcomes by comorbidities, previous surgery, and adherence to intranasal corticosteroids, and examined the success rates based on current guidelines, as well as potential predictors of response at each timepoint. Results We observed a significant decrease in NPS from a median value of 6 (IQR 5–6) at baseline to 1.0 (IQR 0.0–2.0) at 12 months (p < .001), and a significant decrease in Sino-Nasal Outcomes Test-22 (SNOT-22) from a median score of 58 (IQR 49–70) at baseline to 11 (IQR 6–21; p < .001) at 12 months. Sniffin' Sticks scores showed a significant increase over 12 months (p < .001) compared to baseline. The results were unaffected by concomitant diseases, number of previous surgeries, and adherence to topical steroids, except for minor differences in rapidity of action. An excellent-moderate response was observed in 96.9% of patients at 12 months based on EPOS 2020 criteria. Conclusions Our findings from this large-scale real-life study support the effectiveness of dupilumab as an add-on therapy in patients with severe uncontrolled CRSwNP in reducing polyp size and improving the quality of life, severity of symptoms, nasal congestion, and smell

Off-label long acting injectable antipsychotics in real-world clinical practice: a cross-sectional analysis of prescriptive patterns from the STAR Network DEPOT study

Introduction Information on the off-label use of Long-Acting Injectable (LAI) antipsychotics in the real world is lacking. In this study, we aimed to identify the sociodemographic and clinical features of patients treated with on- vs off-label LAIs and predictors of off-label First- or Second-Generation Antipsychotic (FGA vs. SGA) LAI choice in everyday clinical practice. Method In a naturalistic national cohort of 449 patients who initiated LAI treatment in the STAR Network Depot Study, two groups were identified based on off- or on-label prescriptions. A multivariate logistic regression analysis was used to test several clinically relevant variables and identify those associated with the choice of FGA vs SGA prescription in the off-label group. Results SGA LAIs were more commonly prescribed in everyday practice, without significant differences in their on- and off-label use. Approximately 1 in 4 patients received an off-label prescription. In the off-label group, the most frequent diagnoses were bipolar disorder (67.5%) or any personality disorder (23.7%). FGA vs SGA LAI choice was significantly associated with BPRS thought disorder (OR = 1.22, CI95% 1.04 to 1.43, p = 0.015) and hostility/suspiciousness (OR = 0.83, CI95% 0.71 to 0.97, p = 0.017) dimensions. The likelihood of receiving an SGA LAI grew steadily with the increase of the BPRS thought disturbance score. Conversely, a preference towards prescribing an FGA was observed with higher scores at the BPRS hostility/suspiciousness subscale. Conclusion Our study is the first to identify predictors of FGA vs SGA choice in patients treated with off-label LAI antipsychotics. Demographic characteristics, i.e. age, sex, and substance/alcohol use co-morbidities did not appear to influence the choice towards FGAs or SGAs. Despite a lack of evidence, clinicians tend to favour FGA over SGA LAIs in bipolar or personality disorder patients with relevant hostility. Further research is needed to evaluate treatment adherence and clinical effectiveness of these prescriptive patterns

Developments of the k0-NAA measurement model implemented in k0-INRIM software

The k0-INRIM software is a computer program that was recently developed to automatically evaluate combined uncertainty while performing mass fraction measurements adopting the k0-standardization method of Neutron Activation Analysis. In this paper, significant developments of the adopted measurement model, following a complete revision of the detector characterization procedure, are reported. In particular, the efficiency ratio between monitor and analyte γ-emissions accounts for conversions between counting positions, extended sample geometry and self-absorption. In addition, true-coincidence summing, neutron flux gradient, moisture and blank corrections are included in the model. The developed measurement model is implemented in the latest k0-INRIM release; this greatly improves flexibility of the software in most of the common situations encountered in routine analysis without losing its inherent characteristic focused on uncertainty evaluation through propagation of covariances via sensitivity coefficients. A performance test was carried out by measuring the Au mass fraction of a cylindrical sample prepared from electronic waste material. Results obtained by counting the sample at different positions with respect to the detector end-cap are presented

Studying Income Inequality of Immigrant Communities in Italy

This article deals with the issue of economic integration of immigrants in Italy. Ethnic inequality and economic stratification are analysed based both on the European Survey on Income and Living Conditions (EU-SILC) and the ad-hoc survey on households with foreign people conducted by the National Institute of Statistics in 2009. With reference to the native group and the groups identified by the largest ethnic communities living in Italy, through the Analysis of Gini decomposition technique, the article highlights that the between-group inequality accounts for a barely four percent of the overall inequality, the largest share being due to the inequalities within the groups. The policy prescription suggested is the adoption of ‘‘peculiar’’ policies on specific subgroups of immigrants aimed at reducing the disparities within the subgroups

The 31Si half-life

Half-life values are of paramount importance in analytical techniques based on radioactivity to rescale the measured activity to a reference time. An in depth analysis of the papers reporting the results used to calculate the recommended values discloses a broad lack of information on the performed experiments and, occasionally, an almost complete absence of uncertainty budgets [1]. This was the case for 31Si, the radionuclide produced via (n, γ) reaction adopted to quantify the 30Si mole fraction of the 28Si-enriched material manufactured to determine the Avogadro constant [2]. The now recommended 157.36(26) min 31Si half-life is the average of ten data accepted without a detailed discussion of the uncertainty budget [3]. Aiming at improving the reliability of the 31Si half-life value we carried out an experiment based on repeated observations of the 31Si decay via neutron activation and γ-counting. The resulting value, 157.16 (20) min, was recently published together with the evaluation of the uncertainty [4]. Details of the experiments, including the measurement model and the corrections applied to achieve the declared 0.13% relative standard uncertainty will be discussed during the presentation

VERIFICATION OF k0-NAA ANALYTICAL METHOD IN PAVIA LABORATORY AND DETAILED UNCERTAINTY EVALUATION

The topic of the talk involves the application of k0-NAA analytical method in the laboratory of the INRIM’s radiochemistry and spectroscopy unit located at the University of Pavia. As knowledge of flux parameters is a key step to set-up k0-NAA, f and were first evaluated in three channels of the 250 kW TRIGA Mark II reactor of Pavia, with use of Cd-covered and Cd-ratio approaches on a similar flux monitor set composed by Au, Rb, Zr and Co. Obtained values of f and  were 15.6(3) and -0.036(6), 15.7(4) and -0.041(7), 17.4(4) and -0.016(6) in Central Channel (CC), Rabbit and Lazy Susan channels, respectively [1]. Standard uncertainty is indicated in parenthesis and refers to the last digit. The verification of the applied k0-NAA method, including the assessment of flux parameters, was finally performed by irradiating standards and a reference material in CC and calculating the mass of target element from counting of -emissions using a monitor of Co. The ratio between the experimentally evaluated mass and the expected value for the same target element a, referred as a, was calcuated for each of 15 standard elements and for the 15 certified elements that were quantified in the reference material. All results appear to be in good agreement and no severe deviations from unity were registered in the experiment performed with standards confirming both the correct application of method and flux parameters evaluation. Moreover, a detailed uncertainty budget was carried out with particular focus on the major contributors (Q0 values and efficiency-related uncertainty mainly) having care to deal with all the occurring correlations among parameters. The aim was accomplished with calculation of sensitivity coefficients for each input value and with aid of the covariance matrix to resolve correlations