Fifteen-minute consultation: The prepubescent gender-diverse child: how to answer parents' questions

Parents and caregivers may seek help with different questions or concerns on how to handle the diverse gender expressions of their children. Sometimes the issue may be evident while seeking medical advice for other concerns. Because of the many uncertainties around this topic, clinicians need to know what to say and what can be done to provide the best possible care for gender-diverse children

Variability of cardiac troponin levels in normal subjects and in patients with cardiovascular diseases: analytical considerations and clinical relevance

: In accordance with all the most recent international guidelines, the variation of circulating levels of cardiac troponins I and T, measured with high-sensitivity methods (hs-cTnI and hs-cTnT), should be used for the detection of acute myocardial injury. Recent experimental and clinical evidences have demonstrated that the evaluation of hs-cTnI and hs-cTnT variations is particularly relevant: a) for the differential diagnosis of Acute Coronary Syndromes (ACS) in patients admitted to the Emergency Department (ED); b) for the evaluation of cardiovascular risk in patients undergoing major cardiac or non-cardiac surgery, and in asymptomatic subjects of the general population aged >55 years and with co-morbidities; c) for the evaluation of cardiotoxicity caused by administration of some chemotherapy drugs in patients with malignant tumors. The aim of this document is to discuss the fundamental statistical and biological considerations on the intraindividual variability of hs-cTnI and hs-cTnT over time in the same individual. Firstly, it will be discussed in detail as the variations of circulating levels strictly depend not only on the analytical error of the method used but also on the intra-individual variability of the biomarker. Afterwards, the pathophysiological interpretation and the clinical relevance of the determination of the variability of the hs-cTnI and hs-cTnT values ​​ in patients with specific clinical conditions are discussed. Finally, the evaluation over time of the variation in circulating levels of hs-cTnI and hs-cTnT is proposed for a more accurate estimation of cardiovascular risk in asymptomatic subjects from the general population

Group B Streptococcus early-onset disease and observation of well-appearing newborns

Background International guidelines lack a substantial consensus regarding management of asymptomatic full-term and late preterm neonates at risk for early-onset disease (EOS). Large cohorts of newborns are suitable to increase the understanding of the safety and efficacy of a given strategy. Methods This is a prospective, area-based, cohort study involving regional birth facilities of Emilia-Romagna (Italy). We compared cases of EOS (at or above 35 weeks\u2019 gestation) registered in 2003\u20132009 (baseline period: 266,646 LBs) and in 2010\u20132016, after introduction of a new strategy (serial physical examinations, SPEs) for managing asymptomatic neonates at risk for EOS (intervention period: 265,508 LBs). Results There were 108 cases of EOS (baseline period, n = 60; intervention period, n = 48). Twenty-two (20.4%) remained asymptomatic through the first 72 hours of life, whereas 86 (79.6%) developed symptoms, in most cases (52/86, 60.5%) at birth or within 6 hours. The median age at presentation was significantly earlier in the intrapartum antibiotic prophylaxis (IAP)exposed than in the IAP-unexposed neonates (0 hours, IQR 0.0000\u20130.0000 vs 6 hours, IQR 0.0000\u201315.0000, p<0.001). High number of neonates (n = 531) asymptomatic at birth, exposed to intrapartum fever, should be treated empirically for each newborn who subsequently develops sepsis. IAP exposed neonates increased (12% vs 33%, p = 0.01), age at presentation decreased (median 6 vs 1 hours, p = 0.01), whereas meningitis, mechanical ventilation and mortality did not change in baseline vs intervention period. After implementing the SPEs, no cases had adverse outcomes due to the strategy, and no cases developed severe disease after 6 hours of life. Conclusions Infants with EOS exposed to IAP developed symptoms at birth in almost all cases, and those who appeared well at birth had a very low chance of having EOS. The risk of EOS in neonates (asymptomatic at birth) exposed to intrapartum fever was low. Although definite conclusions on causation are lacking, our data support SPEs of asymptomatic newborns at risk for EOS. SPEs seems a safe and effective alternative to laboratory screening and empirical antibiotic therapy

Adalimumab and ABP 501 in the Treatment of a Large Cohort of Patients with Inflammatory Arthritis: A Real Life Retrospective Analysis

The recent introduction of ABP 501, an adalimumab biosimilar, in the treatment of rheumatic diseases was supported by a comprehensive comparability exercise with its originator. On the other hand, observational studies comparing adalimumab and ABP 501 in inflammatory arthritis are still lacking. The main aim of this study is to compare the clinical outcomes of the treatment with adalimumab, both the originator and ABP 501, in a large cohort of patients affected by autoimmune arthritis in a real life setting. We retrospectively analysed the baseline characteristics and the retention rate in a cohort of patients who received at least a course of adalimumab (originator or ABP 501) from January 2003 to December 2020. We stratified the study population according to adalimumab use: naive to original (oADA), naive to ABP 501 (bADA) and switched from original to ABP 501 (sADA). The oADA, bADA and sADA groups included, respectively, 724, 129 and 193 patients. In each group, the majority of patients had a diagnosis of rheumatoid arthritis. The total observation period was 9805.6 patient-months. The 18-month retentions rate in oADA, bADA and sADA was, respectively, 81.5%, 84.0% and 88.0% (p > 0.05). The factors influencing the adalimumab retention rate were an axial spondylarthritis diagnosis (Hazard Ratio (HR) 0.70; p = 0.04), switch from oADA to ABP 501 (HR 0.53; p = 0.02) and year of prescription (HR 1.04; p = 0.04). In this retrospective study, patients naive to the adalimumab originator and its biosimilar ABP 501 showed the same retention rate. Patients switching from the originator to biosimilar had a higher retention rate, even though not statistically significant, when compared to naive

Apremilast retention rate in clinic practice:observations from an Italian multi-center study

Objective There are few real-world setting studies focused on apremilast efectiveness (i.e., retention rate) in psoriatic arthritis (PsA). The main aim of this retrospective observational study is the assessment of apremilast 3-year retention ratein real-world PsA patients. Moreover, the secondary objective is to report the reasons of apremilast discontinuation and thefactors related to treatment persistence. Methods In ffteen Italian rheumatological referral centers, all PsA consecutive patients who received apremilast were enrolled. Anamnestic data, treatment history, and PsA disease activity (DAPSA) at baseline were recorded. The Kaplan–Meier curve and the Coxanalysis computed the apremilast retention rate and treatment persistence-related risk factors. A p-value<0.05 was considered statistically signifcant. Results The 356 enrolled patients (median age 60 [interquartile range IQR 52–67] yrs; male prevalence 42.7%) median observation period was 17 [IQR 7–34] months (7218 patients-months). The apremilast retention rate at 12, 24, and 36 months was, respectively, 85.6%, 73.6%, and 61.8%. The main discontinuation reasons were secondary inefcacy (34% of interruptions), gastro-intestinal intolerance (24%), and primary inefcacy (19%). Age and oligo-articular phenotype were related to treatment persistence (respectively hazard ratio 0.98 IQR 0.96–0.99; p=0.048 and 0.54 IQR 0.31–0.95; p=0.03). Conclusion Almost three-ffths of PsA patients receiving apremilast were still in treatment after 3 years. This study confrmed its efectiveness and safety profle. Apremilast appears as a good treatment choice in all oligo-articular PsA patients and in those ones burdened by relevant comorbiditi

Baseline Ultrasound Assessment Improves the Response to Apremilast in Patients with Psoriatic Arthritis: Results from a Multicentre Study

ound: Psoriatic arthritis (PsA) phenotypes show different responses to the many available drugs. For a tailored medicine, it is important to choose the most effective treatment according to patients’ characteristics. Apremilast is recommended in PsA with moderate activity. In clinical practice, the most suitable PsA patients for apremilast are those affected by the peripheral oligoarticular arthritis. However, it is not so straightforward to definitely identify this phenotype. Musculoskeletal ultrasound (MUS) is a good tool for detecting the joints actually involved by PsA. The aim of this study is to verify if MUS assessment is useful in selecting the best PsA responders to apremilast. Methods: The following data of all consecutive PsA patients from 15 centres were recorded: anamnestic data, disease activity, PsA phenotype, apremilast treatment duration and reason of suspension. MUS assessment before apremilast treatment was the criteria which clustered patients in two groups. Apremilast retention rate estimate the drug’s effectiveness. The Cox analysis revealed the risk factors associated with treatment persistence. Mann-Whitney U and Chi-squared tests assessed the intergroup differences. Results: Only 40% of 356 patients (M:F: 152/204; median age 60 yrs) received MUS examination. In MUS group the moderate disease (median DAPSA 22.9 vs 26.9; p=0.0006) and the oligo-articular phenotype (63.6% vs 36.1%, p<0.0001) were more common. The retention rate was higher in MUS group (HR 0.55 IC95% 0.32-0.94; p=0.03). Conclusion: In apremilast treated PsA patients, baseline MUS assessment is related to an increased retention rate. MUS may identify patients’ characteristics favourable to apremilast response

Predictors of DAPSA Response in Psoriatic Arthritis Patients Treated with Apremilast in a Retrospective Observational Multi-Centric Study (2023-02-07)

Background: To date, only a few real-world-setting studies evaluated apremilast effectiveness in psoriatic arthritis (PsA). The aims of this retrospective observational study are to report long-term Disease Activity Index for Psoriatic Arthritis (DAPSA) response of apremilast in PsA patients and to analyze the predictors of clinical response. Methods: All PsA consecutive patients treated with apremilast in fifteen Italian rheumatological referral centers were enrolled. Anamnestic data, treatment history, and PsA disease activity (DAPSA) at baseline, 6 months, and 12 months were recorded. The Mann–Whitney test and chi-squared tests assessed the differences between independent groups, whereas the Wilcoxon matched pairs signed-rank test assessed the differences between dependent samples. Logistic regressions verified if there were factors associated with achievement of DAPSA low disease activity or remission at 6 and 12 months. Results: DAPSA low disease activity or remission rates at 6 and 12 months were observed, respectively, in 42.7% (n = 125) and 54.9% (n = 161) patients. Baseline DAPSA was inversely associated with the odds of achieving low disease activity or remission at 6 months (odds ratio (OR) 0.841, 95% confidence interval (CI) 0.804–0.879; p < 0.01) and at 12 months (OR 0.911, 95% CI 0.883–0.939; p < 0.01). Conclusions: Almost half of the PsA patients receiving apremilast achieved DAPSA low disease activity or remission at 6 and 12 months. The only factor associated with achievement of low disease activity or remission at both 6 and 12 months was baseline DAPSA

Long-Term Retention Rate of Tofacitinib in Rheumatoid Arthritis: An Italian Multicenter Retrospective Cohort Study

Background: Tofacitinib (TOFA) was the first Janus kinase inhibitor (JAKi) to be approved for the treatment of rheumatoid arthritis (RA). However, data on the retention rate of TOFA therapy are still far from definitive. Objective: The goal of this study is to add new real-world data on the TOFA retention rate in a cohort of RA patients followed for a long period of time. Methods: A multicenter retrospective study of RA subjects treated with TOFA as monotherapy or in combination with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) was conducted in 23 Italian tertiary rheumatology centers. The study considered a treatment period of up to 48 months for all included patients. The TOFA retention rate was assessed with the Kaplan–Meier method. Hazard ratios (HRs) for TOFA discontinuation were obtained using Cox regression analysis. Results: We enrolled a total of 213 patients. Data analysis revealed that the TOFA retention rate was 86.5% (95% CI: 81.8–91.5%) at month 12, 78.8% (95% CI: 78.8–85.2%) at month 24, 63.8% (95% CI: 55.1–73.8%) at month 36, and 59.9% (95% CI: 55.1–73.8%) at month 48 after starting treatment. None of the factors analyzed, including the number of previous treatments received, disease activity or duration, presence of rheumatoid factor and/or anti-citrullinated protein antibody, and presence of comorbidities, were predictive of the TOFA retention rate. Safety data were comparable to those reported in the registration studies. Conclusions: TOFA demonstrated a long retention rate in RA in a real-world setting. This result, together with the safety data obtained, underscores that TOFA is a viable alternative for patients who have failed treatment with csDMARD and/or biologic DMARDs (bDMARDs). Further large, long-term observational studies are urgently needed to confirm these results

Influence of safety warnings on the prescribing attitude of JAK 2inhibitors for rheumatoid arthritis in Italy

The Janus kinase inhibitors (JAKi) tofacitinib (TOFA), baricitinib (BARI), upadacitinib (UPA) and 74 filgotinib (FILGO) are effective drugs for the treatment of rheumatoid arthritis. However, the US 75 Food & Administration (FDA) raised concerns on the safety of TOFA after its approval. This 76 prompted the European Medicines Agency (EMA) to issue two safety warnings for limiting TOFA 77 use then extended in a third warning to all Jaki in patients at high risk of developing serious adverse 78 events (SAE). These included thrombosis, major adverse cardiac events (MACE) and cancer. Thepurpose of this work was to analyze how the first two safety warnings from EMA affected the pre- 80 scribing of Jaki by rheumatologists in Italy. All patients with rheumatoid arthritis who had been 81 prescribed JAKi for the first time in a 36-month period from July 1, 2019, to June 30, 2022 were con- 82 sidered. Data were obtained from the medical records of 29 Italian tertiary referral rheumatology 83 centers. Patients were divided into three groups of 4 months each, depending on whether the JAKi 84 prescription had occurred before the EMA's first safety alert (July 1-October 31, 2019, Group 1), 85 between the first and second alerts (November 1, 2019-February 29, 2020, Group 2), or between the 86 second and third alerts (March 1, 2021-June 30, 2021, Group 3). Percentage and absolute changes in 87 patients prescribed the individual JAKi were analyzed. Differences among the three Groups of pa- 88 tients in demographic and clinical characteristics were also assessed. A total of 864 patients were 89 prescribed a JAKi during the entire period considered. Of these, 343 were identified in Group 1, 233 90 in Group 2 and 288 in Group 3. An absolute reduction of 32% was observed in the number of patients 91 prescribed a JAKi between Group 1 and Group 2 and 16% between Group 1 and Group 3. In contrast, 92 there was a 19% increase in the prescription of a JAKi in patients between Group 2 and Group 3. In 93 the first Group, BARI was the most prescribed drug (227 prescriptions, 66.2% of the total), followed 94 by TOFA (115, 33.5%) and UPA (1, 0.3%). In the second Group, the most prescribed JAKi was BARI 95 (147, 63.1%), followed by TOFA (65, 27.9%) and UPA (33, 11.5%). In the third Group, BARI was still 96 the most prescribed JAKi (104 prescriptions, 36.1%), followed by UPA (89, 30.9%), FILGO (89, 21.5%) 97 and TOFA (33, 11.5%). The number of patients prescribed TOFA decreased significantly between 98 Group 1 and Group 2 and between Group 2 and Group 3 (p ˂ 0.01). Patients who were prescribed 99 BARI decreased significantly between Group 1 and Group 2 and between Group 2 and Group 3 (p 100 ˂ 0.01). In contrast, patients prescribed UPA increased between Group 2 and Group 3 (p ˂ 0.01). 101 These data suggest that the warnings issued for TOFA were followed by a reduction in total JAKi 102 prescriptions. However, the more selective JAKi (UPA and FILGO) were perceived by prescribers 103 as favorable in terms of risk/benefit ratio and their use gradually increased at the expense of the 104 other molecules