INTRODUCTION:Benzylpenicillin has long been included in treatment protocols for amatoxin poisoning based on experimental evidence suggesting inhibition of hepatocellular amatoxin uptake via OATP1B3. However, no human pharmacokinetic data have confirmed whether therapeutic regimens achieve serum concentrations sufficient to inhibit this transporter in vivo. METHODS:We retrospectively analyzed serum benzylpenicillin concentrations in 16 patients with confirmed amatoxin poisoning treated at the Florence Poison Control Center between 2020 and 2024. All patients received continuous intravenous benzylpenicillin infusion (500,000 IU/kg/day for 48 h, followed by 250,000 IU/kg/day for 48 h) as part of a standardized multimodal protocol. Serum samples (n = 44) were collected during routine care and analyzed using LC-MS/MS. Concentrations were expressed in micromolar (µM) and compared with the reported OATP1B3 inhibitory concentration (IC50 = 25 µM). RESULTS:During the first 48h, all serum samples exceeded the IC50 threshold, with mean concentrations of 265 ± 87 µM at 24 h and 241 ± 74 µM at 48 h. Across all samples, the median concentration was 176 µM (range 45-430 µM), and 93% exceeded 25 µM. Following dose reduction, mean concentrations declined but remained above the IC50 in 66% of samples. No adverse events attributable to benzylpenicillin were observed, and all patients survived to discharge without liver transplantation. DISCUSSION:Although benzylpenicillin's clinical efficacy has yielded conflicting results across retrospective series, variability in dosing regimens and timing likely accounts for much of this inconsistency. The present findings demonstrate that continuous infusion maintains pharmacologically relevant exposure throughout the critical window of amatoxin hepatocellular uptake, supporting target engagement in vivo. The reduced-dose regimen sustained inhibitory concentrations in most samples, suggesting dose optimization is feasible without compromising pharmacological activity. CONCLUSION:Continuous intravenous infusion of benzylpenicillin achieves serum concentrations exceeding the in vitro OATP1B3 inhibitory threshold in patients with amatoxin poisoning, providing human pharmacokinetic support for its proposed antidotal mechanism and its continued inclusion in multimodal treatment protocols.

Introduction Termination of pregnancy for fetal anomaly is associated with profound psychological distress for parents and can be emotionally demanding for healthcare professionals. Evidence on professionals' knowledge, practices, and support needs in Italy remains limited. We aimed to examine Italian healthcare professionals' knowledge of legal aspects, bereavement care practices, and emotional experiences related to care in the context of termination of pregnancy (ToP) for fetal anomaly, and to explore factors associated with supportive behaviors. Methods A cross-sectional web-based survey was conducted among healthcare professionals between September 2022 and December 2023. The survey included sociodemographic and professional characteristics, knowledge of Italian law, bereavement care practices, and professionals' emotional experiences. Results A total of 552 respondents participated of which 84.8% were midwives; 99.4% correctly identified when termination of pregnancy can be performed, while 19.5% were aware that no legally fixed gestational threshold exists; younger and less experienced respondents showed lower levels of legal knowledge (p<0.001). Feelings of inadequacy were reported by 51.4% of respondents, and 71.2% reported the need for debriefing after assisting with a termination of pregnancy. The presence of a shared emotional support protocol was significantly associated with supportive behaviors (p <= 0.003). Routine use of memory boxes was reported by 53.0% of respondents, whereas follow-up care was least consistently ensured (37.4%); 97.2% recognized the need for lactation management after termination of pregnancy for fetal anomaly. Conclusions The RESPeC-ToP Study highlights gaps in legal knowledge and uneven implementation of key bereavement care components. Training and shared emotional support protocols emerge as actionable strategies to standardize supportive practices and strengthen both quality of care and staff support within maternity services.

This study examines the use of Beatrice Alemagna’s picture book ‘What is a Child?’ as a tool for understanding and implementing nurturing care principles in perinatal healthcare settings. Through mixed-methods analysis of forum discussions among 42 perinatal professionals, including psychologists, midwives, physicians, nurses, pharmacists and early childhood educators, we explored how engagement with the book’s metaphorical and visual elements facilitated professional reflection and development. Qualitative analysis revealed four primary themes: the power of metaphors in conveying complex caregiving concepts, the importance of collective care and community support, understanding the temporality of care and fostering transformative dialogue. Quantitative analysis showed significant differences in thematic engagement across professional groups, with medical professionals emphasising physical health (20.8%) and nutrition (32.1%), while psychologists focused more on early learning opportunities (28.3%) and responsive caregiving (21.0%). However, the picture book’s narrative framework encouraged professionals to transcend their domain-specific perspectives, fostering a more holistic appreciation of nurturing care principles. These findings suggest that carefully selected picture books can serve as sophisticated tools for professional development in perinatal care, particularly in translating abstract theoretical concepts into actionable insights while honouring different professional perspectives and expertise.

Idarucizumab and andexanet alfa are licensed for the emergency reversal of the antithrombotic effect of direct oral anticoagulants (DOAC). Given their recent commercialization and rare use in clinical practice, current evidence on rare thromboembolic adverse events following idarucizumab or andexanet alfa administration is insufficient to draw definitive conclusions. The aim of this study was to perform a signal detection analysis based on data from a large spontaneous reporting database to identify possible safety signals concerning rare, serious and unexpected thromboembolic events reported following the administration of idarucizumab and andexanet alfa, respectively. A disproportionality analysis was performed based on Individual Case Safety Reports (ICSRs) submitted from any US or non-US country between 2004 and 2022 to the FDA Adverse Event Reporting System (FAERS). A case/non-case approach was applied: cases were ICSRs containing the event of interest, non-cases were the remaining reports. The odds of exposure to idarucizumab and andexanet alfa, respectively, in cases versus non-cases was measured. Reporting odds ratio (ROR) and 95

Problem. Guidelines ask that a woman whose baby has died be cared for away from the sights and sounds of newborns, but they do not say where she should be cared for instead. Background. One common way to move a bereaved woman away from newborns is to admit her to a gynaecology ward, although this could undermine midwifery care. To date, no study assessed the impact of bereavement space on grief or mental health. Aim. To test whether separate accommodation is associated with better outcomes and reported care, and whether achieving separation in a gynaecology ward rather than an obstetric ward is associated with a difference in midwifery care. Methods. Cross-sectional analysis of the Italian OPALE observatory. Of 2601 women reporting a perinatal loss, 1662 reported both their ward and whether they shared accommodation, giving four care configurations. Measures were the Perinatal Grief Scale, the NSESSS, satisfaction with accommodation, respectful care, ratings of the midwife and the nurse, and an indicator of no midwifery care, adjusted for type of loss, gestational age, maternal age, time since loss and geographical area. Findings. Overall, 35.7% of women shared accommodation with mothers and newborns, falling from 47.1% of losses before 2015 to 26.9% from 2023 onwards. Sharing was associated with higher grief (adjusted difference 3.22, 95% CI 0.81 to 5.63), more post-traumatic stress symptoms (1.13, 0.17 to 2.09), lower satisfaction with accommodation (−30.05, −33.08 to −27.02) and less respectful care (−0.51 on 0 to 4, −0.64 to −0.37). Among women for whom separation had been achieved, those in a gynaecology ward were more satisfied with their accommodation (7.33, 3.85 to 10.82) but reported lower midwifery presence (−7.13, −11.18 to −3.09) and three times the odds of receiving no midwifery care (OR 3.05, 1.49 to 6.23), with no difference in respectful care or satisfaction. Discussion. Relocation to gynaecology delivers the room the guidelines ask for but erodes the midwifery care they assume will accompany it, a deficit invisible in the woman's global satisfaction. Conclusion. Guidance requiring separate accommodation should add that separation must not remove the woman from midwifery care. A separate room within the obstetric ward satisfies both, and provided the better care in our sample.

PURPOSE OF REVIEW:Biosimilars are increasingly shaping the management of pediatric allergic diseases and offering cost-effective alternatives to originator biology. This review summarizes the scientific and regulatory principles of biosimilars and examines the role of biosimilars in pediatric allergology, focusing on their clinical applications, opportunities, and challenges. RECENT FINDINGS:Biosimilars were developed through a stepwise comparability process, including analytical, pharmacokinetic, pharmacodynamic, and clinical evaluations, to ensure equivalence with reference products. Among pediatric allergies, biologics targeting type 2 inflammation have significantly improved outcomes in several diseases, including asthma, atopic dermatitis, chronic spontaneous urticaria, and food allergies. Omalizumab is currently the only biologic drug with an approved biosimilar that has demonstrated comparable efficacy, safety, and immunogenicity, even after switching. However, concerns remain regarding limited availability of long-term pediatric data. SUMMARY:Biosimilars represent a promising and sustainable opportunity to broaden access to advanced pediatric allergology therapies. Their integration into clinical practice, supported by growing evidence and appropriate clinical governance, has the potential to optimize treatment outcomes and improve long-term disease management. Further evidence on their risk-benefit profiles will help support their effective and informed use in the pediatric population.

Real-world data on adverse drug reactions (ADRs) associated with idarucizumab and andexanet alfa are limited. This study aimed to assess the frequency, the characteristics and clinical and demographic factors associated with ADRs related to their use. This is a retrospective analysis of ADR reports collected in Vigibase® until May 31, 2023. Multivariable logistic regression estimated reporting odds ratios (RORs) for serious ADRs, death, and thromboembolic events according to demographical and clinical covariates. A total of 1095 Individual Case Safety Reports (ICSRs) reporting idarucizumab (72

Background: Pregnancies following perinatal loss present emotional and clinical challenges that require individualized care. While awareness of the psychological vulnerability of bereaved parents is increasing, the perspectives and preparedness of healthcare professionals (HCPs) are still under-investigated. Methods: The UNSURENESS study involved a national cross-sectional web-based survey conducted between August 2023 and February 2024. The questionnaire explored sociodemographic data, professional experience, training in perinatal loss care, communication approaches, and clinical decision making. Results: Two hundred female HCPs participated (midwives 78.0%). One-third had received specific training on managing pregnancies after perinatal loss. On a 0-4 Likert scale, participants emphasized the importance of addressing the previous loss (M = 3.82; SD = 0.03) and building a trusting relationship with parents (M = 3.78; SD = 0.04). Providing comprehensive information (M = 3.59; SD = 0.05) and promoting shared decision making (M = 3.72; SD = 0.04) followed closely. The most challenging tasks included responding to parental fears (M = 3.37; SD = 0.75) and offering reassurance (M = 3.06; SD = 1.06). Clinical decisions were primarily driven by continuity of care (M = 3.70; SD = 0.56) and parental preferences (M = 3.63; SD = 0.57), rather than national guidelines (M = 3.16; SD = 0.82) or research evidence (M = 2.86; SD = 0.94). Conclusions: HCPs are aware of the psychosocial complexity involved in these pregnancies but often lack specific training. There is a clear need for trauma-informed interventions and national guidelines to better support both professionals and bereaved families.

INTRODUCTION:In the aftermath of perinatal loss, the physiologic onset of lactation presents a complex array of emotional responses for women, including grief and despair. Effective lactation management is essential for maternal health, yet it is often inadequately addressed by health care professionals, potentially compromising the physical and psychological recovery of the bereaved mother. The aim of this study was to investigate how Italian health care providers support women in managing lactation after a perinatal loss. METHODS:This study employed a web-based, cross-sectional design. Participants involved in perinatal bereavement care were asked to answer a survey consisting of 3 areas: sociodemographic information, knowledge and experience of perinatal loss, and lactation after perinatal loss. RESULTS:A total of 1227 health care professionals participated in this study. A significant majority (60.2%) had received formal training on perinatal loss care, expressing high satisfaction with an average score of 4.7 out of 5. However, less than half (42.5%) reported having a guideline for bereavement care in their workplace. Despite the opportunity, 25% of the respondents did not provide lactation information. Discussions predominantly centered on pharmacologic suppression of lactation in cases of stillbirth (89.5%) and neonatal death (83.8%), as well as complications associated with these events. Postdischarge follow-up was reported as lacking by 78.2% of the sample. CONCLUSIONS:The discrepancy between the training of health care professionals and their practice highlights a critical need to enhance the implementation of bereavement care guidelines and follow-up support, underscoring the importance of integrating lactation management into the perinatal loss care continuum.

Co-administration of multiple vaccines during a single clinical visit is common in pediatric immunization programs, but administering three or more injections simultaneously has raised safety concerns. This systematic review, conducted in 2023, assessed the safety of administering three or more vaccines at the same time compared with giving fewer or the same vaccines across separate sessions. Data from 26 studies were analyzed using random-effects meta-analyses. The risk of any adverse event (AE) was modestly increased (OR ≈ 1.54), mainly due to expected and transient reactions such as fever, irritability and injection-site pain. Importantly, there was no significant increase in serious adverse events (SAEs) (OR 1.07, 95% CI 0.92-1.25). Differences in systemic (OR 1.19, 95% CI 0.95-1.50) or local AEs (OR 1.37, 95% CI 0.85-2.22) were not statistically significant. These findings support the continued co-administration of multiple vaccines in pediatric programs, providing a nuanced safety profile for policymakers and clinicians.

PURPOSE OF REVIEW:Anaphylaxis is a severe allergic reaction characterized by a rapid onset and can be potentially life-threatening. Epinephrine is considered the first-line treatment, and until recently, it was available only for intramuscular injection. A new intranasal epinephrine delivery device has now been approved for use in adults and children, offering a needle-free option for emergency treatment of allergic reactions. This narrative review explores its technical characteristics, along with its pharmacokinetic, pharmacodynamic, and safety profiles based on the results of the most recent clinical trials. RECENT FINDINGS:The key advantages of the intranasal route, including the elimination of needle-length variability, reduced risk of administration errors in obese or underweight patients, and simplified storage requirements, are also discussed. According to recent research, intranasal epinephrine represents an easy-to-use, effective, and well tolerated treatment for severe allergic reactions. Intranasal delivery may offer a painless, easy-to-use, and reliable solution suitable for healthcare professionals, age-appropriate patients and caregivers. SUMMARY:Based on the current evidence, intranasal epinephrine appears to be a promising, well tolerated option that could significantly improve the accessibility and effectiveness of anaphylaxis management in the pediatric setting.

Miscarriage is a traumatic life event that involves over forty thousand Italian women every year. Women affected by this loss can have long-term psychological consequences. For this reason, it is paramount to identify women at risk of developing such complications to ensure they receive proper support. The aim of this study is to perform a translation into Italian and a validation of the Revised Impact of Miscarriage Scale (RIMS), which is a valuable support for healthcare professionals to assess women after a miscarriage. Double-translation technique was performed. A sample of 543 women completed the survey for the validation process which included RIMS, the Perinatal Grief Scale (PGS) and NSESSS. These last two instruments are usually used to assess the impact of perinatal loss on women’s life. The Italian version of RIMS (RIMS-IT) has good internal consistency (Cronbach’s alpha value 0,89). Factor analysis was conducted to confirm the construct validity and three factors were extracted. They reflected the factorial analysis of the original version. Scores of RIMS, PGS, and NSESSS were strongly correlated. RIMS-IT can be a valuable support for clinicians and researchers to identify women at risk of developing psychiatric symptoms and to analyse factors involved in the onset of these complications.

ObjectiveTo develop and assess the GAIA! app, designed to assist pregnant women and healthcare professionals in managing infectious diseases during pregnancy, and to bridge the information gap between health professionals and expectant mothers.Study DesignThis collaborative initiative in Italy involved partnerships with the University of Florence, Careggi University Hospital, and other institutions. The app, built on the Ionic framework, is available on both Apple and Google App Stores. It offers two distinct modes: “healthcare providers” and “patients.” Content for the app was derived from extensive literature reviews and clinical guidelines.ResultsSince its August 2022 launch, the GAIA! app has garnered over 2,500 downloads, indicating its effectiveness and acceptance within the community. The app differentiates itself from others, such as the Sanford Guide, by focusing specifically on the needs of pregnant women. It ensures cross-platform compatibility, a user-friendly interface, and offline functionality.ConclusionsThe GAIA! app has successfully addressed a niche in infectious disease management for pregnant women, gaining significant traction within the community. While it has seen substantial success, challenges like continuous updates and potential language expansion remain. Future endeavors will address these challenges and further evaluate the app’s impact on maternal and child health.

Background: In the context of a comparative study of efficacy and safety of drugs used in rare neuromuscular and neurodegenerative diseases (CAESAR—call AIFA_FV_2012-13-14), we assessed the use patterns of drugs indicated for myasthenia gravis (MG). Methods: A retrospective cohort study was conducted based on administrative healthcare data. For a cohort of MG patients, prevalent and incident use of pyridostigmine (Py) and other indicated drugs in the first year after case identification was evaluated. Prevalent combined use of major therapies (azathioprine (Az), prednisone (Pr), vitamin D (Vd)) stratified by Py use was assessed, and a comparison between therapies at the time of MG identification and during the first year of follow-up was performed. Results: We included 2369 MG patients between 2013 and 2019. Among them, prevalent and incident Py users were 38.4% and 22.0%, respectively. In the first year of follow-up, the use of Pr was observed in 74.5% of Py prevalent users and in 82.0% of Py incident users, respectively; the use of Az was observed in 24.9% and 23.0%, respectively; and the use of Vd was observed in 53.3% and 48.2%, respectively. Among 910 Py prevalent users, 13.1% also used Az, Pr, and Vd, while 15.3% used none of these. Among 938 non-Py users, 2.7% used Az, Pr, and Vd, while 53.8% used none of these. During the first year, an increase in combined therapies was evident in incident Py users. Conclusions: Our results suggest that, for some MG patients, there may be a need for treatments that combine a rapid onset of benefit with long-term and consistent disease control. These issues may be addressed by the new treatments currently being developed. To date, more studies are needed to address the heterogeneity, quality, and generalizability of the existing data and to evaluate patterns of use, efficacy, and safety of new or emerging therapies for MG.

Introduction: In 2021, the European Medicines Agency supported the “Covid Vaccine Monitor (CVM),” an active surveillance project spanning 13 European countries aimed at monitoring the safety of COVID-19 vaccines in general and special populations (i.e., pregnant/breastfeeding women, children/adolescents, immunocompromised people, and people with a history of allergies or previous SARS-CoV-2 infection). Italy participated in this project as a large multidisciplinary network called the “ilmiovaccinoCOVID19 collaborating group.”Methods: The study aimed to describe the experience of the Italian network “ilmiovaccinoCOVID19 collaborating group” in the CVM context from June 2021 to February 2023. Comprising about 30 partners, the network aimed to facilitate vaccinee recruitment. Participants completed baseline and follow-up questionnaires within 48 h from vaccination over a 6-month period. Analyses focused on those who completed both the baseline and the first follow-up questionnaire (Q1), exploring temporal trends, vaccination campaign correlation, and loss to follow-up. Characteristics of recruited vaccinees and vaccinee-reported adverse drug reactions (ADRs) were compared with passive surveillance data in Italy.Results: From June 2021 to November 2022, 22,384,663 first doses and 38,207,452 booster doses of COVID-19 vaccines were administered in Italy. Simultaneously, the study enrolled 1,229 and 2,707 participants for the first and booster doses, respectively. Of these, 829 and 1,879 vaccinees, respectively, completed both baseline and at least Q1 and were included in the analyses, with a significant proportion of them (57.8%/34.3%) belonging to special cohorts. Most vaccinees included in the analyses were women. Comirnaty® (69%) and Spikevax® (29%) were the most frequently administered vaccines. ADR rates following Comirnaty® and Spikevax® were higher after the second dose, particularly following Spikevax®. Serious ADRs were infrequent. Differences were observed in ADR characteristics between CVM and Italian passive surveillance.Conclusion: This study confirmed the favorable safety profile of COVID-19 vaccines, with findings consistent with pivotal clinical trials of COVID-19 vaccines, although different proportions of serious ADRs compared to spontaneous reporting were observed. Continuous evaluation through cohort event monitoring studies provides real-time insights crucial for regulatory responses. Strengthening infrastructure and implementing early monitoring strategies are essential to enhance vaccine safety assessment and prepare for future pandemics.