Background Nurses are on the frontline in drug treatment of older persons, which impacts on patients’ safety and well-being. Aim of the study was to assess nurses’ confidence and competency in geriatric pharmacotherapy. Methods After literature search, a questionnaire was developed and then refined with a Delphi procedure and cognitive interviews. In a cross-sectional study design, nurses attending an educational event in six Italian cities answered the questionnaire, exploring participants’ general characteristics and scoring confidence (range 0-40) and competency (range 0-100). Satisfactory competency was defined by a score in the top tertile. Results Out of 174 participants, 24, 67, and 83 were from Northern (NI), Central (CI), and Southern Italy (SI), respectively. The mean±SD confidence score was 23.9±4.8. Working in a Geriatrics setting and being employed in a hospital were independent predictors of higher confidence. The competency score (mean: 61.9±11.0) was independent of confidence (r= -0.026; p=0.729). Multivariable predictors of satisfactory competency scoring were: participants’ geographic location in NI (OR 3.3, 95% CI 1.0-10.9) or CI (OR 4.3, 95% CI 1.9-9.9) vs. SI, previous Geriatrics education (OR 2.2, 95% CI 1.0-4.7), and familiarity with bibliographic search engines (OR 1.55, 95% CI 0.99-2.43). Years since graduation were inversely associated with satisfactory scoring (OR 0.95, 95% CI 0.91-0.98). Conclusions This sample of Italian nurses showed moderate confidence and competency in managing drug therapy in older persons. Education, and not experience, was associated with satisfactory scoring. Efforts should be made to enhance training in Geriatrics and the utilization of tools for continuing education.

OBJECTIVES:This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the comparative efficacy and safety of anti-vascular endothelial growth factor (anti-VEGF) agents and their biosimilars for people with neovascular age-related macular degeneration (nAMD), and provide a relative ranking of interventions using network meta-analysis (NMA) methods, considering differences in treatment intensity.

Background Ulcerative colitis (UC) is a chronic inflammatory bowel disease where diagnostic delays can worsen the clinical outcomes and increase the strain on healthcare systems. This study investigated the frequency of potentially missed UC diagnoses in tertiary care and their impact on treatment patterns and healthcare utilization.Methods We conducted a retrospective cohort study using Tuscany's regional healthcare database (2006-2020). Adults newly diagnosed with UC between 2011 and 2018 were included. A "possible missed diagnosis" was defined as a hospital or emergency department (ED) visit for gastrointestinal (GI) symptoms occurring 7-60 months before the UC diagnosis. We assessed the initiation of azathioprine and non-conventional therapies, as well as the rates of ED visits, hospital admissions, and surgery. Survival analyses and Cox regression models were applied.Results Among 3,804 patients with UC, 313 (8.3%) had prior GI-related tertiary care visits suggestive of a missed diagnosis. The mean time to diagnosis was 27.5 months. Compared with those who were timely diagnosed, these patients were not more likely to start azathioprine or non-conventional therapies. However, subjects with a possible missed diagnosis had higher rates of ED visits [adjusted hazard ratio (aHR) = 1.8, 95%CI = 1.5-2.0], hospitalizations (aHR = 1.4, 95%CI = 1.2-1.7), and combined urgent care encounters (aHR = 1.5, 95%CI = 1.3-1.7) compared with other patients.Conclusions Patients with a potentially missed UC diagnosis are more likely to need emergency and inpatient care, despite receiving similar treatments. Promoting earlier recognition of UC symptoms in tertiary care may reduce avoidable hospital use and improve disease management.

Background:Diabetes mellitus is a globally prevalent disease, with an incidence of 5-7 new cases per 1000 person-years and no significant gender disparity. Sodium-glucose co-transporter 2 (SGLT-2) inhibitors are recommended as second-line therapy after metformin in uncomplicated type 2 diabetes, whereas they are recommended as first-line treatment in patients with heart failure or other cardiorenal comorbidities. Given the recent introduction of SGLT-2 inhibitors, their increasing utilization, and the heterogeneity of existing literature, real-world evaluations of these agents are warranted. Objectives:The MANDALORE study, a regional active pharmacovigilance project approved by the Italian Medicines Agency (AIFA), aims primarily to assess the drug utilization of gliflozins in clinical practice. The secondary objective is to analyze safety outcomes and investigate the determinants of treatment switching events. Methods:This retrospective cohort study will analyze medical records of patients who underwent at least one diabetes visit at the Metabolic Diseases and Diabetology/Endocrinology Unit of Pisa University Hospital and the Diabetology and Metabolic Diseases Unit of Livorno Hospital. Inclusion criteria comprise that Tuscan patients receiving their first prescription for a gliflozin (index drug) between 2012 and 2021 (index date). Outcomes to be assessed include treatment switching, time to switching, line of therapy, dose adjustments, and time to dose change. Gliflozin utilization will be investigated, particularly in relation to concomitant interacting or contraindicated medications, and in patients requiring caution as specified by AIFA labeling and relevant tools. Incidence rates will be calculated for secondary safety outcomes, including adverse drug events (ADEs) leading to emergency room visits or hospitalization, non-serious ADEs, and specific ADEs as diabetic ketoacidosis, urinary and genital infections, gangrene, lower limb amputations, and neoplastic events. ADEs and therapeutic effectiveness observed in proximity to switching events will be investigated. Results:The findings from the MANDALORE study are expected to elucidate critical aspects of gliflozin use in routine clinical practice, particularly within the Tuscan regional healthcare context, thereby providing valuable insights from the real-world for clinicians and healthcare systems.

Transthyretin amyloidosis (ATTR) is an infiltrative disease caused by the deposition of misfolded transthyretin (TTR) fibrils in organs and tissues, with incidence and prevalence rapidly increasing worldwide. Current therapeutic strategies fall into two main classes: TTR stabilizers and TTR gene silencers. To date, no comprehensive reviews cover all the available pharmacological treatments for ATTR, both approved and off-label. In addition, previous meta-analyses have often excluded real-world data and have not evaluated safety outcomes. In this Grading of Recommendations Assessment Development and Evaluation (GRADE)-assessed meta-analysis, interventional and observational studies were searched in four databases (MEDLINE, Scopus, Embase, and CENTRAL), and 28 studies were included. The use of TTR stabilizers and gene silencers significantly reduced the risk of all-cause mortality compared with placebo (relative risk, RR: 0.70 [95 % Confidence Interval, CI: 0.60-0.83]) in patients with cardiomyopathy, with no differences between drug classes. In observational studies, TTR stabilizers were associated with an even greater reduction in mortality risk (RR: 0.23 [95 % CI: 0.12-0.44] and an approximately 37 % increase in overall survival probability compared with unexposed patients, estimated using individual patient data from Kaplan-Meier (IPDfromKM) method. These pharmacological treatments also improved nutritional status and quality of life. Overall, they were safe and well tolerated, with no increased risk of adverse events (AEs) or treatment discontinuation due to AEs. In conclusion, this is the first meta-analysis integrating both clinical and real-world data to evaluate efficacy and safety of all available drugs for ATTR, including off-label use. This approach facilitates healthcare decision-making and paves the way for future research.

AimsRefractive lens exchange (RLE) is becoming a popular refractive solution for patients ineligible for corneal surgeries or phakic intraocular lenses. However, concerns regarding retinal detachment (RD) risk persist.MethodsA systematic literature review and meta-analysis was performed in Medline and Scopus.The final search was updated on 30 March 2024.ResultsOf 2415 full-text screening reports, 40 studies met inclusion criteria, encompassing 8 592 380 eyes. This included 20 264 eyes that underwent RLE and 8 572 116 eyes that underwent cataract surgery. In the RLE surgery subgroup, the RD incidence for follow-up <12 months was 0.00016% (0.00000%; 0.00034%), for follow-up between 12 and 24 months was 0.0000% (0.0000%; 0.03102%), and for follow-up >24 months was 0.02312% (0.00984%; 0.03640%) (p<0.01). In the cataract surgery subgroup, the incidence for follow-up >24 months was 0.01244% (0.00655%; 0.01832%), and for missing follow-up was 0.00429% (0.00221%; 0.00637%).ConclusionsWe found that the incidence of RD after RLE was approximately double that observed after cataract surgery with at least 24 months (median 4 years) follow-up. Thus, RD may be classified as rare complication after cataract surgery (1/1000) and an uncommon complication after RLE (1/500). It must be noted that the heterogeneity of the subgroups after RLE was low. While some limitations, such as the lack of long-term follow-up in certain studies and incomplete reporting of factors like axial length or PVD status, may slightly influence the interpretation, these findings provide valuable insights. Acknowledging the inherent uncertainty in interpreting these results, additional studies are recommended.PROSPERO registration numberCRD42023431420.

Filling clinical questionnaires to perform retrospective studies is a time-consuming task that requires strong expertise in specific domains. We exploit prompt engineering techniques to optimize the completion of clinical questionnaires through Large Language Models (LLMs), aiming to compare their performance with respect to human experts. Despite challenges related to limited access to input data, our preliminary experimental results demonstrate the potential of LLMs to streamline clinical data collection, greatly reducing the manual workload for healthcare professionals. However, human validation remains essential to ensure accuracy and reliability in real-world applications.

BACKGROUND:Nirsevimab, a long-acting monoclonal antibody against respiratory syncytial virus (RSV), was recently introduced to prevent infant RSV-related hospitalizations. Although efficacy has been demonstrated in clinical trials, real-world data on targeted immunization strategies remain limited. We aimed to evaluate the effectiveness of nirsevimab in preventing RSV-associated hospitalizations in infants under 12 months, within a seasonal program prioritizing infants born from April onwards. METHODS:We conducted a prospective, multicenter, matched case-control study across seven Italian hospitals during the 2024-2025 RSV season. Infants hospitalized with PCR-confirmed RSV bronchiolitis were matched 1:2 by age and date of admission to controls hospitalized for non-respiratory causes. Data were collected via electronic medical records. Immunization effectiveness (IE) was estimated using conditional logistic regression adjusted for sex assigned at birth, gestational age, birth weight, and clinical risk factors. Two pre-specified stratified analyses and a sensitivity analysis using inverse probability of treatment weighting (IPTW) were performed. RESULTS:A total of 138 infants were included (46 cases, 92 controls). Adjusted IE was 89.5% (95% CI: 60.3-97.2%). Stratified analyses yielded similar results among infants born after April 1 (IE: 88.4%, 95% CI: 56.5-96.9%) and those without risk factors (IE: 88.1%, 95% CI: 45.7-97.4%). IPTW analysis confirmed protection (IE: 79.6%, 95% CI: 53.5-91.0%). CONCLUSIONS:This study provides real-world evidence supporting the effectiveness of nirsevimab in a targeted seasonal immunization framework. These findings may inform phased implementation strategies and RSV prophylaxis policies in varied healthcare settings.

OBJECTIVE:To characterize multinational trends and patterns of opioid analgesic prescribing by sex and age. DESIGN, SETTING, AND PARTICIPANTS:We studied opioid analgesic prescribing from 2001 to 2019 with common protocol using population-based databases from eighteen countries and one special administrative region. MAIN OUTCOME MEASURES:We measured opioid prescribing by geographical region, sex and age, estimating annual prevalent, incident, and nonincident opioid prescribing per 100 population with a 95% confidence interval (CI) and meta-analyzed the multinational and regional opioid prescribing with a random-effects model. Time trends were reported through average annual absolute changes, estimated using linear mixed models. We further explored the effect of sex and age on prevalent opioid prescribing in the multivariable analysis. RESULTS:Over 248 million individuals were included. Pooled multinational opioid prescribing prevalence was 9.0% amongst included countries/regions. Opioid prescribing prevalence in 2015 ranged from 2.7% in Japan to 19.7% in Iceland. Average annual absolute changes in opioid prescribing prevalence per year ranged from - 1.53% (95% CI - 2.06, - 1.00; United States Medicaid) to + 1.24% (95% CI 1.02, 1.46; South Korea). Pooled multinational incident opioid prescribing (4.9%; 95% CI 4.1, 5.9) was higher than pooled multinational nonincident opioid prescribing (3.7%; 95% CI 2.9, 4.8). The female sex and older age were associated with higher opioid prescribing. Main limitations of this study include the absence of data from study duration or individuals not covered by the data sources and the lack of information on medication adherence and indication. CONCLUSIONS:Opioid prescribing remains unbalanced across geographical regions; however, results suggest a tendency to convergence across countries/regions. Differences in opioid prescribing by sex and age were identified.

This study aimed to identify and describe trajectories of adherence to biologics in patients with IBDs and to identify adherence determinants in the Italian real-world setting. We conducted a retrospective cohort study across 12 Italian regions, including new users of biologics with inflammatory bowel diseases (IBDs), between 2010 and 2019 and followed them for 3 years. We assessed adherence longitudinally, and we identified trajectories using nonparametric methods. To identify determinants of adherence, we used multinomial multivariate regression models. We included 20 150 subjects in the final cohort, mostly male (56%), < 65 years old (92%), and with Crohn's disease (58%). We identified three trajectories of adherence to biologics for IBDs: one group (19% of the cohort) maintained high adherence throughout the observation period, while the largest group (46%) initially reduced adherence, stabilizing around 70%. The remaining group (35%) gradually decreased adherence over the entire follow-up, reaching 20%. Being female (odds ratio (OR) 1.52, 95% confidence interval (CI) 1.40-1.65), older (OR 1.44, 95% CI 1.21-1.70), and having adalimumab as index drug were each positively associated with low adherence compared to high adherence. In contrast, starting treatment with a biosimilar (OR 0.47, 95% CI 0.42-0.52) was negatively associated with low adherence. Our findings highlight that one in three patients with IBDs gradually reduced adherence to biologics within the first 3 years of treatment. Differences were observed according to the initial biologic dispensed and patient characteristics such as sex and age, with females and older patients positively associated with low adherence.

Background and objective. The potential benefits of dietary supplements for human health have been known since ancient times, but high-quality evidence on their efficacy is lacking. Furthermore, the overwhelming amount of available studies contributes to the vagueness of this topic. The aim of this systematic review was to summarize the evidence on the health benefits of dietary supplements. Methods. A Medline search (via PubMed) was performed. Results. 62 umbrella reviews (also known as reviews of reviews) were retrieved. Most of the results/findings (41.3%) suggested potential beneficial effects of dietary supplements on human health, but with low to very low certainty of evidence. Twenty results/ findings (26.7%) supported the efficacy of dietary supplements in improving biochemical parameters and preserving human health, with moderate to high certainty of evidence. All other studies showed uncertain/conflicting results or inefficacy. Conclusions. The demonstration of the beneficial properties of dietary supplements is far from conclusive and high-quality studies are needed.

ABSTRACTBackgroundItaly presently does not have a pediatric organ donation program after cardiocirculatory determination of death (pDCDD). Before implementing a pDCDD program, many centers globally have conducted studies on the attitudes of pediatric intensive care unit (PICU) staff. This research aims to minimize potential adverse reactions and evaluate the acceptance of the novel donation practice.MethodsWe conducted an electronic and anonymous survey on attitudes toward pDCDD among healthcare professionals (HCPs) working at eight Italian PICUs. The survey had three parts: (I) questions about general demographic data; (II) 18 statements about personal wishes to donate, experience of discussing donation, and knowledge about donation; (III) attitudinal statements regarding two pediatric Maastricht III scenarios of organ donation.ResultsThe response rate was 54.4%, and the majority of respondents were nurses. Of those who responded, 45.3% worked in the Center, 40.8% in the North, and 12.8% in the South of Italy. In total, 93.9% supported pediatric organ and tissue donation, 90.3% supported donation after neurological determination of death (DNDD), 78.2% supported pDCDD, and 69.7% felt comfortable about the idea of participating in pDCDD on Type III patients, with a higher percentage of supportive responses in the Center (77.2%) than in the North (65.1%) and South (54.5%) of Italy (p‐value < 0.004). Concerning scenarios, 79.3% of participants believed that organ retrieval took place in a patient who was already deceased. Overall, 27.3% considered their knowledge about DCDD to be adequate.ConclusionsOur study provides insight into the attitudes and knowledge of PICU staff members regarding pDCDD in Italy. Despite a general lack of knowledge on the subject, respondents showed positive attitudes toward pDCDD and a strong consensus that the Italian legislation protocol for determining death based on cardiocirculatory criteria respects the “dead donor rule.” There were several distinctions among the northern, central, and southern regions of Italy, and in our view, these disparities can be attributed to the varying practices of commemorating the deceased. In order to assess how practice and training influence the attitude of PICU staff members, it would be interesting to repeat the survey after the implementation of a program.

BACKGROUND:Monitoring biologic drug therapy during pregnancy in women with immune-mediated inflammatory diseases (IMIDs) is crucial to ensure treatments align with evidence-based practices. RESEARCH DESIGN AND METHODS:A retrospective cohort study based on healthcare claims data from eight Italian regions was conducted, analyzing deliveries between 2009 and 2021. The study included women receiving biologic drugs within nine months before their last menstruation. Exposures to biologics, conventional disease-modifying anti-rheumatic drugs (DMARDs) and symptom-relieving medications were assessed in the trimesters (T) before, during and after pregnancy. Factors influencing biologic treatment persistence during pregnancy were analyzed. RESULTS:A cohort of 1,763 deliveries was considered. Biologic drugs were prescribed for rheumatic (33.6%), dermatological (32.6%), and gastrointestinal diseases (28.4%). Biologic use declined during pregnancy (TI = 37.3%; TII = 17.6%; TIII = 11.3%), increasing again postpartum. During pregnancy, there was increased use of symptom-relieving medications for rheumatic diseases and DMARDs for gastrointestinal diseases. Factors associated with continued biologic treatment included being older than 35 years and the region of delivery. CONCLUSIONS:This study found a decrease in biologics drug use during pregnancy and highlights the necessity for personalized therapeutic approaches. Geographic variations in biologic drug use emphasize the need for educational initiatives about the risk-benefit profiles of these therapies during pregnancy.

Maintenance immunosuppressive therapy used in kidney transplantation typically involves calcineurin inhibitors, such as tacrolimus or cyclosporine, in combination with mycophenolate or mechanistic target of rapamycin (mTORi) with or without corticosteroids. An Italian retrospective multicentre observational study was conducted to investigate the risk-benefit profile of different immunosuppressive regimens. We identified all subjects who underwent kidney transplant between 2009 and 2019, using healthcare claims data. Patients on cyclosporine and tacrolimus-based therapies were matched 1:1 based on propensity score, and effectiveness and safety outcomes were compared using Cox models (HR; 95%CI). Analyses were also conducted comparing mTORi versus mycophenolate among tacrolimus-treated patients. Patients treated with cyclosporine had a higher risk of rejection or graft loss (HR:1.69; 95%CI:1.16-2.46) and a higher incidence of severe infections (1.25;1.00-1.55), but a lower risk of diabetes (0.66;0.47-0.91) compared to those treated with tacrolimus. Among tacrolimus users, mTORi showed non-inferiority to MMF in terms of mortality (1.01;0.68-1.62), reject/graft loss (0.61;0.36-1.04) and severe infections (0.76;0.56-1.03). In a real-life setting, tacrolimus-based immunosuppressive therapy appeared to be superior to cyclosporine in reducing rejection and severe infections, albeit with an associated increased risk of diabetes. The combination of tacrolimus and mTORi may represent a valid alternative to the combination with mycophenolate, although further studies are needed to confirm this finding.

AimsEarly detection and treatment of neurodegenerative Langerhans cell histiocytosis (ND-LCH) have been suggested to prevent neurodegenerative progression. The aim of the study is to validate a standardized multidisciplinary diagnostic work-up to monitor the intravenous immunoglobulins (IVIG) treatment response and the natural course of the disease in untreated patients.MethodsPatients with abnormal somatosensory evoked potentials (SEPs) received monthly 0.5 g/kg IVIG. The diagnostic protocol included structural 3T MRI, neurological examination, brainstem auditory evoked potentials (BAEPs) and SEPs.ResultsTwenty-two patients were followed for 5.2 years (median) from the first MRI evidence of ND-LCH. Eleven patients received IVIG for 1.7 years (median). At treatment start neurological examination was abnormal in 10 patients, of whom two had severe clinical impairment and four had abnormal BAEPs. At last follow-up, 1/11 remained stable and 7/11 improved, while worsening of neurological or neurophysiological findings, or both, occurred in 3/11. Risk factors for worsening were a severe clinical or MRI ND-LCH at treatment initiation and prolonged exposure to LCH. Of the 11 untreated patients, none improved and three worsened.ConclusionsUsing a standardized diagnostic protocol, we demonstrated that IVIG treatment can lead to clinical stabilization or improvement in all pauci-symptomatic patients with an MRI grading of less than 4.

Dyslipidemia is a risk factor for cardiovascular diseases. Preclinical studies have shown that organosulfur compounds from the Alliaceae and Brassicaceae plants, such as garlic (Allium sativum L.) and broccoli (Brassica oleracea L.), have potential lipid-lowering effects. However, their clinical efficacy is controversial, especially in "drug-free" patients. The aim of this work was to summarize evidence on the lipid-lowering properties of extracts containing organosulfur compounds in patients with dyslipidemia. Studies were searched in four databases (Medline, Scopus, Embase, and CENTRAL), from inception to October 11, 2023.Controlled clinical studies on patients with dyslipidemia receiving Alliaceae or Brassicaceae were included. The outcome was the change in lipid parameters from baseline. Random-effect meta-analysis of the extracted data was performed using R software. The effect size was expressed as mean difference (MD) and 95% confidence interval (CI). The certainty of evidence was assessed with the GRADE approach. Out of 28 studies that were reviewed, 22 were included in the meta-analysis (publication period: 1981-2022). Results showed that Alliaceae extracts significantly reduce total cholesterol [MD: -15.2 mg/dL; 95% CI: -21.3; -9.1] and low-density lipoprotein cholesterol levels [MD: -12.0 mg/dL; 95% CI: -18.1; -5.7], although with low certainty of evidence. Conversely, the lipid-lowering properties of Brassicaceae extracts are still unexplored. Our results support the use of Alliaceae extracts in patients with hypercholesterolemia, but future high-quality studies are needed. Our work suggests further exploration of the efficacy of Brassicaceae extracts, which may have high nutraceutical/phytotherapeutic potential, opening new perspectives in the management of dyslipidemia.

AIM:The aim of this study is to describe circumstances, management and short-term outcomes of neonatal head trauma, and adherence to the Paediatric Emergency Care Applied Research Network (PECARN) head trauma prediction rule for children under 2 years. METHODS:Multicentre retrospective cohort study of neonates (<29 days) with head trauma across 25 emergency departments (ED) from January 2017 to June 2021. RESULTS:A total of 492 neonates (median age 17 days, range 0-28 days) with non-trivial head trauma were enrolled. Falls were the most common injury mechanism (375/492, 76.2%). Imaging was performed in 150/492 (30.5%) neonates. Clinically important traumatic brain injury (ciTBI), defined as death, neurosurgery, prolonged intubation, or extended hospitalisation from injury, occurred in 7/492 (1.4%) cases. Notably, 286/492 (58.1%) neonates were managed by short-term observation (<48 h), and 126/492 (25.6%) were admitted. Among high-risk neonates per PECARN criteria, 17/21 (80.9%) did not undergo recommended head CT scans but were observed within ED short observation units or underwent alternative imaging, with no ciTBI diagnoses among those discharged without CT. CONCLUSION:Severe neonatal head injuries are rare, and most neonatal head injuries have a favourable outcome, making observation a suitable approach, while remaining vigilant for signs of non-accidental injuries.