Recording Risk Factors of Physical Abuse in Children Younger Than 36 Months With Bone Fractures: A 12-Years Retrospective Study in an Italian General Hospital Emergency Room

Skeletal fractures (SFs) are very common in pediatrics. In some cases, they are secondary to child abuse. Differentiation of accidental from non-accidental fractures (NAFs) is essential as in abused children risk of further injuries leading to severe clinical problems and death is significant. Main objectives of this study were to evaluate the characteristics of SFs of children ≤3 years of age presenting to the Emergency Room (ER) of a Children's Teaching Hospital over a 12-year period and the attention paid by ER physicians to the identification of the indicators that increase suspicion of NAF and that suggest referring of the patient to the child protection agencies. This is a descriptive, retrospective study of the medical records of all the pediatric patients ≤ 36 months of age admitted to the ER of the Azienda Ospedaliera Santa Maria della Misericordia, University of Perugia, Perugia, Italy, for radiological documented SFs between January 1, 2004, and March 31, 2016. Available information was used to evaluate whether indicators of possible child abuse were documented by the ER staff and whether diagnosis of potential abuse was followed by further screening or referral to child protection agencies. During the study period, 11,136 accesses of the ER by children younger than 36 months were documented, among whom 417 presented long bone or skull fractures. Skull fractures were significantly more common among children <12 months of age (p = 0.001), whereas radius/ulna and humerus fractures were diagnosed significantly more frequently in children 12–36 months of age (p = 0.036 and p = 0.022, respectively). Recorded medical history was considered inadequate in 255 (61.2%) cases with no difference related to patient's age. Our study showed that the majority of charts in case of SFs were found to contain inadequate documentation to explain causes at the heart of the fractures and, therefore, to rule out any inflicted trauma. The development of specific referral guidelines, along with the continuous education and training of health professionals, as well as the preparation of structured medical forms, are essential measures to activate in order to improve the referral of children from the ER to child protection agencies

Comparing comparators: A look at control arms in kidney cancer studies over the years

In the past decade, an increasing number of frequently positive randomised clinical trials have been completed, allowing new consideration of the present therapeutic armamentarium for advanced renal cell carcinoma. These studies were predominantly designed to compare the experimental drugs with 1 of 2 active control arms: interferon alpha-2a or sorafenib. Different from expectations, the final results of some of these studies were not in line with the predictions, and the reasons have not been fully investigated. Consequently, there is a great need for careful analysis of the studies carried out so far, chiefly the role and validity of the control arms. In this regard, the examination of patient baseline characteristics and other factors of potential interest seems fundamental for a correct analysis of the results of these trials and consequent optimal use of the available targeted agents

Diffusion of biosimilar hemopoietic growth factors use in oncology practice: an Italian experience

Background: Biosimilars of hemopoietic growth factors present an important saving opportunity in oncology. However, while pharmacologists are aware of their potential benefits, biosimilars are still under-used in Italy. Improved information and guided clinical experience may help to increase the clinical acceptance of these drugs. To this aim, a collaborative educational project was set between an Hospital Oncology Unit and the Local Health Care Authority in Pavia, Italy. Methods: The project lasted 12 months. The strategy included an education-information seminar at startup, a reporting meeting at +6$+6$ months, electronic prescription monitoring and implementation of pharmacovigilance. The target was set to reach 90% of all naïve patients treated with biosimilars. Results: At the end of the study (2013), a dramatic relative increase in the prescription of biosimilar drugs was noted, with virtually 100% of new patients receiving biosimilar drugs during the last 4 months, with a positive impact on average per capita drug expenses. Active pharmacovigilance did not report any serious adverse drug reactions. An anonymous questionnaire showed that oncologists judged the experience quite positively, acquired a positive attitude toward these drugs and considered biosimilars a relevant saving opportunity, while adherence to prescription guidelines was maintained. Analysis of the year following the end of the project, 2014, showed a persistent prescription change. Conclusions: Results from this local experience suggests that specifically designed pragmatic interventions focused on information-education and monitoring may help in promoting the use and acceptance of biosimilar drugs in the real clinical setting

Exposure to NO2, CO, and PM2.5 is linked to regional DNA methylation differences in asthma.

Background:DNA methylation of CpG sites on genetic loci has been linked to increased risk of asthma in children exposed to elevated ambient air pollutants (AAPs). Further identification of specific CpG sites and the pollutants that are associated with methylation of these CpG sites in immune cells could impact our understanding of asthma pathophysiology. In this study, we sought to identify some CpG sites in specific genes that could be associated with asthma regulation (Foxp3 and IL10) and to identify the different AAPs for which exposure prior to the blood draw is linked to methylation levels at these sites. We recruited subjects from Fresno, California, an area known for high levels of AAPs. Blood samples and responses to questionnaires were obtained (n = 188), and in a subset of subjects (n = 33), repeat samples were collected 2 years later. Average measures of AAPs were obtained for 1, 15, 30, 90, 180, and 365 days prior to each blood draw to estimate the short-term vs. long-term effects of the AAP exposures. Results:Asthma was significantly associated with higher differentially methylated regions (DMRs) of the Foxp3 promoter region (p = 0.030) and the IL10 intronic region (p = 0.026). Additionally, at the 90-day time period (90 days prior to the blood draw), Foxp3 methylation was positively associated with NO2, CO, and PM2.5 exposures (p = 0.001, p = 0.001, and p = 0.012, respectively). In the subset of subjects retested 2 years later (n = 33), a positive association between AAP exposure and methylation was sustained. There was also a negative correlation between the average Foxp3 methylation of the promoter region and activated Treg levels (p = 0.039) and a positive correlation between the average IL10 methylation of region 3 of intron 4 and IL10 cytokine expression (p = 0.030). Conclusions:Short-term and long-term exposures to high levels of CO, NO2, and PM2.5 were associated with alterations in differentially methylated regions of Foxp3. IL10 methylation showed a similar trend. For any given individual, these changes tend to be sustained over time. In addition, asthma was associated with higher differentially methylated regions of Foxp3 and IL10

Electrocardiographic findings in patients with arrhythmogenic cardiomyopathy and right bundle branch block ventricular tachycardia.

AIMS: Little is known about patients with right bundle branch block (RBBB)-ventricular tachycardia (VT) and arrhythmogenic cardiomyopathy (ACM). Our aims were: (i) to describe electrocardiogram (ECG) characteristics of sinus rhythm (SR) and VT; (ii) to correlate SR with RBBB-VT ECGs; and (iii) to compare VT ECGs with electro-anatomic mapping (EAM) data. METHODS AND RESULTS: From the European Survey on ACM, 70 patients with spontaneous RBBB-VT were included. Putative left ventricular (LV) sites of origin (SOOs) were estimated with a VT-axis-derived methodology and confirmed by EAM data when available. Overall, 49 (70%) patients met definite Task Force Criteria. Low QRS voltage predominated in lateral leads (n = 37, 55%), but QRS fragmentation was more frequent in inferior leads (n = 15, 23%). T-wave inversion (TWI) was equally frequent in inferior (n = 28, 42%) and lateral (n = 27, 40%) leads. TWI in inferior leads was associated with reduced LV ejection fraction (LVEF; 46 ± 10 vs. 53 ± 8, P = 0.02). Regarding SOOs, the inferior wall harboured 31 (46%) SOOs, followed by the lateral wall (n = 17, 25%), the anterior wall (n = 15, 22%), and the septum (n = 4, 6%). EAM data were available for 16 patients and showed good concordance with the putative SOOs. In all patients with superior-axis RBBB-VT who underwent endo-epicardial VT activation mapping, VT originated from the LV. CONCLUSIONS: In patients with ACM and RBBB-VT, RBBB-VTs originated mainly from the inferior and lateral LV walls. SR depolarization and repolarization abnormalities were frequent and associated with underlying variants