Alessandra Atzei

Off-label and unlicensed prescribing for newborns and children in different settings: a review of the literature and a consideration about drug safety

This review aims to give an updated overview of the worldwide situation of off-label and unlicensed drug use in the paediatric field, also taking into account the safety of this kind of treatment. A Medline and Embase search was performed between 1990 and 2006 and a total of 52 studies were identified and included in the systematic review. From the authors’ analysis of the literature, the extent of paediatric unlicensed/off label use is higher in neonatal and paediatric intensive care units and oncology wards, compared with primary care. Moreover, among the nine studies reporting the contribution of an off-label/unlicensed drug use to the occurrence of adverse events, the percentage of unlicensed and/or off-label prescriptions involved in an adverse drug reaction ranged between 23 and 60%. To ensure that children are not exposed to unnecessary risks, controlled clinical trials are required. In addition, future research should be directed towards the identification of individual drugs that cause serious adverse drug reactions and lack product information.

Metabolomics in newborns with intrauterine growth retardation (IUGR): urine reveals markers of metabolic syndrome

To date, we have little knowledge on the overall metabolic status of neonates with intrauterine growth retardation (IUGR). In the last few years, the analysis of metabolomics has assumed an important clinical role in identifying “disorders” in the metabolic profile of patients. The aim of this work has been to analyze the urine metabolic profiles of neonates with IUGR and compare them with controls to define the metabolic patterns associated with this pathology. To our knowledge, this is the first study of metabolomics performed on neonates with IUGR. Recruited for the study were 26 neonates with IUGR diagnosed in the neonatal period and with weight at birth below the 10th percentile and 30 neonates of proper gestational weight at birth (controls). In the first 24 hours (prior to feeding) (T1) and about 4 days after birth (T2), a urine sample was taken non-invasively from each neonate. The samples were then frozen at −80°C up to the time of the analysis by proton nuclear magnetic resonance spectroscopy (1H-NMR). The data contained in the NMR spectra obtained from the single samples were statistically analyzed using the Principal Components Analysis and the Partial Least Squares-Discriminate Analysis. By means of a multivariate analysis of the NMR spectra obtained, it was possible to highlight the differences between the two groups (IUGRs and controls) owing to the presence of different metabolic patterns. The discriminants in the urine metabolic profiles derived essentially from significant differences in certain metabolites such as: myo-inositol, sarcosine, creatine and creatinine. The metabolomic analysis showed different urine metabolic profiles between neonates with IUGR and controls and made it possible to identify the molecules responsible for such differences.

Antibiotics and Antifungals in Neonatal Intensive Care Units: A Review

Abstract The incidence of infections is higher in the neonatal period than at any time of life. The basic treatment of infants with infection has not changed substantially over the last years. Antibiotics (with or without supportive care) are one of the most valuable resources in managing sick newborn babies. Early-onset (ascending or transplacental) or late-onset (hospital acquired) infections present different chronology, epidemiology, physiology and outcome. Some classes of antibiotics are frequently used in the neonatal period: penicillins, cephalosporins, aminoglycosides, glycopeptides, monobactams, carbapenems. Other classes of antibiotics (chloramphenicol, cotrimoxazole, macrolides, clindamycin, rifampicin and metronidazole) are rarely used. Due to emergence of resistant bacterial strains in Neonatal Intensive Care Units (NICU), other classes of antibiotics such as quinolones and linezolid will probably increase their therapeutic role in the future. Although new formulations have been developed for treatment of fungal infections in infants, amphotericin B remains first-line treatment for systemic Candida infection. Prophylactic antibiotic therapy is almost always undesirable. Challenges from pathogens and antibiotic resistance in the NICU may warrant modification of traditional antibiotic regimens. Knowledge of local flora and practical application of different antibiotic characteristics are key to an effective and safe utilization of antibiotics and antifungals in critical newborns admitted to the NICU, and especially in very low birth weight infants.

Metabolomics in paediatric respiratory diseases and bronchiolitis

The metabolic study of an organism may make it possible to monitor, through the metabolites,the physiology and/or pathology of the organism itself. Metabolomics, in the strictest sense, “the set of metabolites, the final products of the genetic expression”. Most clinical chemistry tests available today rely on old technologies that measure only a single chemical in blood, urine or other biofluids, and these tests are neither sensitive nor specific for any particular disease. Metabolomics offers a holistic approach to systems medicine, with the promise to enhance clinical chemistry diagnostics in several pathologic conditions. The present review covers the application of clinical metabolomics in three different areas of respiratory diseases in pediatrics: asthma, pneumonia and bronchiolitis. Comparison between two 1H-NMR urine spectra by two bronchiolitis patients are also presented.

Probiotics and the skin

A review of the relationships between probiotics and the skin is presented. After a brief historical introduction, the main pathophysiological data on intestinal microflora, the immune system and the skin are presented. Clinical studies with probiotics in atopic children are discussed in detail. Many experimental studies have found that probiotics exert specific effects in the luminal lumen and on epithelial cells and immune cells with antiallergic potential. Not all probiotics have the same immunological properties. Moreover, although rarely, complications of probiotic use can occur and must be known and taken into account. This review underlines the potential interest in probiotics for the management of skin pathology.

Perinatal nutrient restriction reduces nephron endowment increasing renal morbidity in adulthood: A review

Perinatal malnutrition has been included among the causes of renal disease in adulthood. Here, we consider the relationships between early supply of specific nutrients (such as protein, fat, vitamins and electrolytes) and renal endowment. Prenatal and postnatal nutrition mismatch is also discussed. In addition, this article presents the role of nutrition of both mothers and pre-term infants on nephron endowment, with final practical considerations.

Ultrasonography and neonatal urinary tract infections

B-mode ultrasonography and the power-Doppler are methods for studies by images in rapid technological evolution. Their applications and limits in the study of infections of the urinary tract in the neonatal period are pointed out.

OC24: The role of magnetic resonance imaging and transvaginal ultrasonography in patients with an adnexal mass and chronic pelvic pain or infertility

Objectives: Previously we showed that sonovaginography is an accurate ultrasonographic tool in the assessment of rectovaginal endometriosis. The aim of this study was to compare the diagnostic accuracy of sonovaginography and NMR in the diagnosis of rectovaginal endometriosis. Methods: This was a longitudinal prospective study in which 28 women with rectovaginal endometriosis suspected from the medical history and/or pelvic examination were enrolled. The study group underwent transvaginal ultrasonography and sonovaginography was performed in the same session as follows: an assistant inserted a Foley catheter into the vagina and an ultrasound probe covered with a specific balloon to swell the vagina. The balloon was filled with water (mean 40 mL) and soon after 60–180 mL saline solution was inserted through the Foley catheter to fill the vagina in order to create an acoustic window through the vagina to detect rectovaginal lesions. Within a mean of 30 days after the examination patients were scheduled for pelvic NMR. Once all the diagnostic tests had been performed, patients underwent laparoscopic surgery to enucleate the endometriotic lesion, which was sent for pathological examination. Results: Twenty-three (82.1%) patients had rectovaginal endometriotic lesions. The sensitivity of sonovaginography was 91.7%, specificity 75%, PPV 95.6% and NPV 60%; the area under the receiver-operating characteristic (ROC) curve was 0.87. In comparison, NMR had a sensitivity of 73.9%, specificity 60%, PPV 89.5% and NPV 33.3%, with an area under the ROC curve of 0.67. The procedure was well tolerated with a median visual analogue scale score of 2 (range, 0–8). Conclusions: Sonovaginography is a well tolerated procedure, with higher accuracy than NMR in the detection of rectovaginal endometriosis.

OC23: Magnetic resonance imaging and transvaginal tenderness-guided ultrasonography in diagnosis of the location of deep infiltrating endometriosis

Objectives: Previously we showed that sonovaginography is an accurate ultrasonographic tool in the assessment of rectovaginal endometriosis. The aim of this study was to compare the diagnostic accuracy of sonovaginography and NMR in the diagnosis of rectovaginal endometriosis. Methods: This was a longitudinal prospective study in which 28 women with rectovaginal endometriosis suspected from the medical history and/or pelvic examination were enrolled. The study group underwent transvaginal ultrasonography and sonovaginography was performed in the same session as follows: an assistant inserted a Foley catheter into the vagina and an ultrasound probe covered with a specific balloon to swell the vagina. The balloon was filled with water (mean 40 mL) and soon after 60–180 mL saline solution was inserted through the Foley catheter to fill the vagina in order to create an acoustic window through the vagina to detect rectovaginal lesions. Within a mean of 30 days after the examination patients were scheduled for pelvic NMR. Once all the diagnostic tests had been performed, patients underwent laparoscopic surgery to enucleate the endometriotic lesion, which was sent for pathological examination. Results: Twenty-three (82.1%) patients had rectovaginal endometriotic lesions. The sensitivity of sonovaginography was 91.7%, specificity 75%, PPV 95.6% and NPV 60%; the area under the receiver-operating characteristic (ROC) curve was 0.87. In comparison, NMR had a sensitivity of 73.9%, specificity 60%, PPV 89.5% and NPV 33.3%, with an area under the ROC curve of 0.67. The procedure was well tolerated with a median visual analogue scale score of 2 (range, 0–8). Conclusions: Sonovaginography is a well tolerated procedure, with higher accuracy than NMR in the detection of rectovaginal endometriosis.