Italian Medicines Agency

Gravitropism, the patterning of postembryonic growth in relation to the gravity vector, allows plants to optimize the use of limited and nonhomogenous resources in their immediate environment. Since the current model of root gravitropism has not been able to integrate all aspects of the response (perception, response, and behavior), research on gravitropism has been dominated by different theories attempting to conceptualize each aspect individually. In this work, we sought to reevaluate all the main components of the root graviresponse through the lens of angle dependence. We show angle dependence in Cholodny-Went-based auxin asymmetry and growth response, which we tracked back to angle-dependent variation in PIN asymmetry and statolith sedimentation in the columella. Thanks to this approach, we were able to suggest distinct roles for PINs and columella cell tiers, and a potential function for auxin vertical flux through the columella. Our findings provide a unifying framework to further explore the mechanisms that regulate angle-dependent gravitropic response, with major implications of time-dependent features of root graviresponse.

AimThis study builds on the environmental risk analysis presented in the 2022 National Report on Medicines Use in Italy by the Italian Medicines Agency and aims to assess the environmental risk posed by medicines in Italy and its regions.MethodsThe analysis selected 90 medicines based on three criteria: high utilization, low predicted no effect concentration (PNEC), and inclusion or candidacy for the European Watch List. For each medicine, the environmental risk was computed as the ratio between the predicted environmental concentration (PEC) and the PNEC. The PEC was derived following the approach of the Swedish Association of Pharmaceutical Industries and Italian drug utilization data. The risk was classified high if the ratio was greater than 10 and moderate if greater than 1.ResultsOverall, 13 medicines were identified as posing a high risk, including cardiovascular agents, antibiotics, analgesics, antidepressants and antiparasitic agents. The high risk was driven by either a very low PNEC (eg, estradiol and lacidipine) or high utilization (eg, amoxicillin, ibuprofen and diclofenac). Regional analysis showed higher risk due to high consumption for azithromycin and ofloxacin in central and southern Italy, and for levonorgestrel in northern Italy.ConclusionThis study points to the need for prioritizing targeted sampling in surface waters for medicines estimated at high risk. To prevent and mitigate the risk, a more conscious clinical practice coupled with appropriate waste management are required.

The Global Health Security Agenda (GHSA) provides a foundation in global health law to support legal preparedness across nations. This column examines the legal authorities necessary to meet the objectives of the GHSA Legal Preparedness Action Package and advance national law reforms to prevent, detect, and respond to public health emergencies.

The aim of this study was to perform a descriptive analysis of oropharyngeal adverse events (AEs) related to drugs and/or vaccines in order to provide useful information for clinicians. Data related to three regions of Italy were analyzed from 2019 to 2021 by using the National Pharmacovigilance database. Among overall 67,384 cases, 2773 (4.1%) reported at least one oropharyngeal AE. Most cases referred to females (71.0%) and adults (70.8%). The majority of cases were reported as not serious (68.4%) and the outcome was mainly positive (73.5%). The cases related to drugs (52.2%) were slightly more than those related to vaccines (47.8%), the latter nearly completely represented by COVID-19 vaccines. Among 3324 oropharyngeal AEs, the most commonly reported were oropharyngeal conditions (65.9%). The most reported AEs related to vaccines were paresthesia oral and oropharyngeal pain, whereas the most reported AEs related to drugs were throat tightness and angioedema. A marked under-reporting of osteonecrosis of the jaw (2.9%) was observed, despite this risk was well documented in the same country. This analysis suggested an under-reporting of oropharyngeal AEs and the need to better train dentists, dental hygienists, and also general practitioners.

We performed a cohort study that included all patients with relapsed/refractory chronic lymphocytic leukemia (R/R CLL) who received ibrutinib in the Italian National Health Service. With a median follow-up of 42.2 months (IQR 30.8-54.6 months), the study involved 3306 patients with a median age of 72.1 years, of whom 42.6% had received ≥2 previous lines of treatment. The estimated 24-month probabilities of being on treatment and alive were 57.9% (95% confidence interval [CI]: 59.6-56.2) and 76.6% (95% CI: 75.2-78.1), respectively. The median time to treatment discontinuation (TTD) was 31.3 months (95% CI: 29.5-33.5). Out of 3306 patients, 2015 (60.9%) discontinued treatment, with 993 cases attributed to death or disease progression (30.0% of all cases). Among the 1022 patients who discontinued treatment for reasons other than progression or death, 564 (17.1%) patients did so due to toxicity or medical decision, while 458 patients (13.8%) were lost to follow-up. Multivariable analysis revealed that age, Eastern Cooperative Oncology Group Performance Status, the number of previous lines of therapy, refractoriness to the last treatment, and reduced renal function were associated with shorter TTD and overall survival (OS). The coexistence of 17p- and TP53 mutations had an independent unfavorable impact on TTD and OS. Nonstandard doses were associated with shorter TTD and advanced stage with shorter OS. The median OS postprogression and postdiscontinuation for other reasons were estimated at 12.9 (95% CI: 11.3-16.2) and 22.7 months (95% CI: 20.2-28.3), respectively. This large real-world study shows that ibrutinib is an effective treatment for R/R CLL. Baseline patient characteristics and double-hit TP53 aberrations were associated with inferior prognosis, and discontinuation due to CLL progression portended a poor outcome.

This policy report focuses on the border dispute between France and Italy over Mont Blanc in the context of climate change, examining the causes of the disagreement between the two countries and the effects of glacier melting on borders among Alpine countries. Adopting the approach of territorial singularities and mobile borders, the work analyzes the impact of initiatives such as the ETRS89 framework, which ensures GPS-validated mapping technologies in Europe, allowing measurements of border shifts. Insight is given to practices and agreements adopted by Italy, Switzerland, and Austria, such as two bilateral treaties incorporating mobile borders. Starting with a review of the current perspectives of cross-border cooperation between France and Italy after the recent Quirinal Treaty, the report suggests some steps that could be taken to strengthen synergies and mitigate the effects of the dispute: remapping the area, monitoring border shifts, and applying a shared regulation of access and off-limits areas across the entire Mont Blanc.

The COVID-19 pandemic exposed failings in preparedness and response across the world and a shortfall in global health security. The crisis also highlighted shortcomings in global and regional legal frameworks, including the International Health Regulations (2005) and relevant European Union law, as well as in national public health legislation and emergency plans. Lessons learned from the pandemic converge around strengthening preparedness and response capacities at all levels, with special attention to be paid to legal preparedness, a critical component of public health emergency preparedness. Improving legal capacities at country level is one of the strategic priorities set by the Global Health Security Agenda (GHSA), which established a new Legal Preparedness Action Package (LP AP) in order to elevate attention to and the importance of legal preparedness worldwide. Since 2021 the LP AP has been front and centre in international efforts to bridge the legal preparedness gap at national level. In bringing together technical experts in global health law and government health policy officials from a broad range of countries and partners, the LP AP seeks to set a foundation for legal preparedness by developing technical and capacity-building tools, legal guidelines, policy briefs, information and training. This article aims to illustrate and contextualize the work of the GHSA LP AP and raise awareness about the importance of its contribution to enhanced global health security. It also intends to highlight how its work promotes and develops synergies with parallel initiatives, processes and tools, facilitates regime interaction and harmonization of technical assistance and ultimately ensures consistency of action, methodology and approaches.

BackgroundThere is a global perception that psychotropic utilization in children and adolescents is increasing, especially with the onset of COVID-19 pandemic. Available literature data on paediatric psychotropic medication prescriptions in Italy are limited to one or few regions and not updated. The aim of this study was to provide updated data on psychotropic prescriptions referred to the whole Italian paediatric population, as overall and by subgroups of medications and to evaluate if the COVID-19 pandemic during 2020 had an impact on prescription rates.MethodsA descriptive study on psychotropic drug utilization in children and adolescents (< 18 years) resident in all Italian regions during 2020 was performed. Patients registered in the Pharmaceutical Prescriptions database with at least one prescription/dispensing of a psychotropic medication (antipsychotics-N05A), (antidepressants-N06A) and (psychostimulants-N06BA) during the study period were considered. The indicators used were the prescription rate (number of prescriptions per 1000 children) and prevalence of use (proportion of the paediatric population with at least one prescription in the relevant year).ResultsDuring the 2020 the prevalence of psychotropic drug use in the paediatric population was 0.3%, increased of 7.8% if compared to 2019. The same trend was observed for the prescription rate, which recorded an average of 28.2 per 1000 children with an increase of 11.6% if compared to previous year, representing the 0.6% of the overall drug use in this age group. The data showed a growing trend prescription by age, reaching the peak in adolescents aged 12–17 years old, with a prescription rate of 65 per 1000 children and a prevalence of 0.71%. Considering the subgroups of psychotropic medications, the highest prevalence of use was found for antipsychotic drugs, received by the 0.19% of the paediatric population during 2020.ConclusionsPsychotropic drug utilization in children and adolescents has grown during 2020 in Italy and worldwide, raising alarms from health care clinicians and patient advocates about the increase of burden of mental diseases in paediatric population during the COVID-19 pandemic. A more systematic monitoring of the use of psychotropic medications should be implemented in all countries for collecting relevant information about children and adolescents taking psychotropic drugs, in order to address the present and the future of the mental health of the paediatric population.

The European Medicines Agency adopted their Geriatric Medicines Strategy more than a decade ago. The strategy aims at elucidating the evidence basis for marketing authorization of new medicines which will be used in the older population, and at ensuring the appropriate communication of findings to the patient and healthcare provider. During the past decade new tools and data sources have emerged to support the strategy goals, and their use should be considered. Possible concrete actions are presented to improve the design of clinical trials, the data collection both pre- and post-approval, the assessment of the findings, and the communication to assist informed prescription and safe medicine taking. Implementation and prioritization of these actions should be done from the perspective of addressing the needs of patients while maximizing efficient use of resources, with the aim of integrating geriatric aspects into routine medicines development and assessment.