Search

Le informazioni disponibili sul profilo rischio-beneficio dei farmaci nel periodo prenatale e neonatale sono molto limitate, principalmente per la difficoltà nel condurre sperimentazioni cliniche. La ricerca farmaco-epidemiologica può svolgere un importante ruolo nell’aumento delle conoscenze sulla sicurezza d’uso dei farmaci in questa popolazione. Le tematiche di ricerca del presente progetto di Dottorato sono state: (i) impatto dell’esposizione pre-natale a psicofarmaci sullo sviluppo neuro-comportamentale nel bambino, (ii) pattern di utilizzo dei farmaci in neonati prematuri, e (iii) valutazione della funzionalità renale in neonati prematuri e ruolo dei farmaci nell’insorgenza di danno renale. Con il primo studio si è analizzato il database della Société Marcé Francophone presso l’Unità INSERM 1219 (Università di Bordeaux), che include dati collezionati in 10 anni presso le Unità Madre-Figlio del Network Francofono. Le analisi hanno mostrato come, indipendentemente dalla patologia psichiatrica materna, l’esposizione prenatale ad alcune classi di psicofarmaci è stata associata ad alterazioni dello sviluppo neuro-comportamentale nei bambini. Con lo studio di farmaco-utilizzazione in neonati prematuri si è voluto descrivere il reale impiego dei farmaci in questa popolazione, in particolare le associazioni di farmaci nefrotossici. I risultati di questo studio retrospettivo indicano che i neonati prematuri con inferiore peso alla nascita sono stati più frequentemente esposti a combinazioni di farmaci nefrotossici rispetto ad altri neonati; inoltre, sono state identificate le associazioni di principi attivi nefrotossici più utilizzate. Il terzo studio, di natura prospettica, ha coinvolto una coorte di neonati prematuri ricoverati presso la Terapia Intensiva Neonatale, con l’obiettivo di identificare i fattori di rischio correlati ad alterazione della funzione renale. I risultati delle analisi preliminari hanno mostrato come i neonati con alterata funzione renale hanno inferiori peso alla nascita ed età gestazionale e superiore incidenza di sepsi; questi risultati mettono in luce la necessità di nuovi biomarcatori per la diagnosi di danno renale in questa popolazione., The benefit-risk profile of drugs in the prenatal and neonatal period is still largely unexplored, because of the difficulties in performing clinical trials. The pharmaco-epidemiological approach could play and important role in increasing knowledge on the benefit-risk profile of drugs used in this special population. The present thesis addressed three specific aspects: (i) impact of prenatal exposure to psychotropic drugs on developmental skills in babies up to 6 months, (ii) pattern of drug use in neonates born prematurely, and (iii) identification of risk factors, including drugs, for renal damage in preterm neonates. In the first study, the analysis of the database of the Société Marcé Francophone at INSERM Unit 1219 (University of Bordeaux), which included data collected over 10 years in the Mother-Baby Units of the Francophone Network, showed that the prenatal exposure to some classes of psychotropic drugs were associated to alterations of developmental skills in babies, independently from maternal psychiatric diagnosis. With the second study, we aimed at assessing the actual use of drugs in preterm neonates, especially the combination of those drugs with known nephrotoxicity in adults. Results of this retrospective study showed that preterm neonates with lower birth weight were more likely to receive combinations of nephrotoxic agents compared to other neonates; moreover, we identified most commonly reported combination of drugs with known nephrotoxicity. The third study was conducted prospectively in a cohort of preterm neonates admitted to a tertiary-level Neonatal Intensive Care Unit (NICU), aiming at identifying risk factors, especially drugs, for renal function alteration. Preliminary data show that neonates with altered renal function had lower gestational age and lower weight at birth as well as higher frequency of diagnosis of sepsis; these results highlight the need for novel biomarkers to diagnose renal damage in neonates.

Introduction: Food supplements containing red yeast rice (RYR) are proposed as an alternative in statin-intolerant patients, although they actually contain natural statin(s) and their safety in clinical practice is still incompletely characterized. We described and compared adverse events (AEs) associated with RYR products submitted to reporting systems maintained by the Food and Drug Administration (FDA), with a focus on liver and muscular events. Methods: We extracted RYR-related AEs from the FDA Adverse Event Reporting System (FAERS) [first quarter (Q1)-2004 to Q2-2016], a drug-based archive, and the Center for Food Safety and Applied Nutrition Adverse Event Reporting System (CAERS) (Q1-2004 to Q1-2017). Disproportionality via reporting odds ratio (ROR) with 95% confidence interval (CI) calculation and case-by-case inspection were performed, with a focus on muscular and hepatic AEs. Results: One thousand three hundred AEs were extracted from FAERS (RYR mainly reported as a concomitant agent), whereas only 159 AEs were found in CAERS (RYR recorded mainly as a suspect agent). In FAERS, a large number of reports emerged for “general disorders and administration site conditions,” whereas CAERS received also a high number of reports for “investigations” and “musculoskeletal and connective tissue disorders”. Disproportionality analyses confirmed higher reporting of serious muscular and liver injuries: in FAERS, five cases of hepatic disorders (ROR = 13.71; 95% CI 5.44–34.57); in CAERS, 27 cases of rhabdomyolysis/myopathy (8.44; 5.44–13.10). Conclusions: Notwithstanding recognized limitations, these findings strengthen the importance of exploring multiple databases in safety assessment of RYR products, which should be monitored by clinicians for muscular and hepatic safety, and call for urgent review by policymakers to harmonize their regulatory status.

Acute kidney injury (AKI) is frequently diagnosed in the neonatal population, especially in those admitted to intensive care units, and poses several challenges for clinicians mainly because of difficulties in timely identification of renal impairment and the need to administer drugs with potential nephrotoxicity. In this context, research on biomarkers is growing for their implication in the early detection of renal damage and their higher sensitivity in monitoring renal activity, but also as an important tool for drug development. Areas covered: We described the tools currently used to detect renal damage in neonatal settings, their limits and applicability, as well as the role of drugs on renal toxicity occurrence. Subsequently, we discuss current knowledge on new biomarkers for the detection of kidney injury and drug-induced kidney injury in neonates, and the qualification programs developed by regulatory agencies for biomarkers intended as tools in drug development. Expert opinion: Some molecules are emerging as potential biomarkers for early detection of AKI: promising data has demonstrated higher sensitivity and accuracy compared with tools currently used in the clinical setting. In addition, novel techniques (e.g. high power magnetic resonance imaging) to assess long-term consequences of AKI in neonates are in early steps of development.

Background Use of food supplements-containing phytoestrogens among postmenopausal women is rapidly increasing. Although phytoestrogens are often perceived as safe, evidence for overall positive risk-benefit profile is still inconclusive. The chance to buy them by user’s initiative does not facilitate surveys on their prevalence and pattern of use. The aim of this study was to describe the pattern of use and self-reported positive and negative perceptions of phytoestrogens in post-menopausa. Methods A questionnaire was administered to women who were buying food supplements containing phytoestrogens in 22 pharmacies located in the Bologna area (400,000 inhabitants). Questionnaire was structured into 3 sections: (a) socio-demographic information, (b) pattern of use, (c) positive and negative perceptions. Results Data on 190 peri- and post-menopausal women (aged 38–77) were collected. Women stated to use phytoestrogens to reduce hot flushes (79%), insomnia (15%), mood disturbances (14%) and prevent osteoporosis (15%). The majority (59%) took phytoestrogens routinely, whereas 28% in 3-month cycles. Among positive perceptions between short- and long-term users, a not negligible difference was reported for relief of hot-flushes (68% in short-term vs. 81% in long-term users; p = 0.04). Negative perceptions were reported more frequently in the long-term group, and this difference was statistically significant for edema (6% in short-term vs. 17% in long-term users; p = 0.04), but not for other effects: e.g., swelling sensation (10% vs. 21%; p = 0.09), somnolence (7% vs. 10% p = 0.62), fatigue (4% vs.11% p = 0.15). Conclusions In the Bologna area, the pattern of use of phytoestrogens for menopausal symptoms is heterogeneous, and women overall find these substances to be beneficial, especially for relief of hot-flushes. Other positive perceptions decreased with long-term use. Negative perceptions, especially estrogen-like effects, seem to be infrequent and increase with long-term therapy. Physicians should pay attention to effects perceived by post-menopausal women and routinely monitor the use of phytoestrogens, in order to recognize possible adverse effects and actual benefits. Electronic supplementary material The online version of this article (doi:10.1186/1472-6882-14-262) contains supplementary material, which is available to authorized users.