Automatic lung segmentation in COVID-19 patients: Impact on quantitative computed tomography analysis.

PURPOSE: To assess the impact of lung segmentation accuracy in an automatic pipeline for quantitative analysis of CT images. METHODS: Four different platforms for automatic lung segmentation based on convolutional neural network (CNN), region-growing technique and atlas-based algorithm were considered. The platforms were tested using CT images of 55 COVID-19 patients with severe lung impairment. Four radiologists assessed the segmentations using a 5-point qualitative score (QS). For each CT series, a manually revised reference segmentation (RS) was obtained. Histogram-based quantitative metrics (QM) were calculated from CT histogram using lung segmentationsfrom all platforms and RS. Dice index (DI) and differences of QMs (ΔQMs) were calculated between RS and other segmentations. RESULTS: Highest QS and lower ΔQMs values were associated to the CNN algorithm. However, only 45% CNN segmentations were judged to need no or only minimal corrections, and in only 17 cases (31%), automatic segmentations provided RS without manual corrections. Median values of the DI for the four algorithms ranged from 0.993 to 0.904. Significant differences for all QMs calculated between automatic segmentations and RS were found both when data were pooled together and stratified according to QS, indicating a relationship between qualitative and quantitative measurements. The most unstable QM was the histogram 90th percentile, with median ΔQMs values ranging from 10HU and 158HU between different algorithms. CONCLUSIONS: None of tested algorithms provided fully reliable segmentation. Segmentation accuracy impacts differently on different quantitative metrics, and each of them should be individually evaluated according to the purpose of subsequent analyses.

On skin dose estimation software in interventional radiology.

In recent years, a growing interest has been shown in the implementation of software dedicated to the skin dose calculation, since the Fluoroscopically Guided Interventions are expanding in various medical areas. In this regard, a review article recently published by Malchair et al. (2020) is of great importance as it provides the reader with useful references to the software currently available to estimate the patient's skin dose. Despite the usefulness of collecting and summarizing in one paper the different software solutions, a few critical issues have emerged related to some parameters and configurations used in the estimation; additional details concerning patient's size and position can be added to the information cited by the authors, giving greater robustness to the software calculation. Furthermore, software results cited in the benchmarking without reference cause a lack of solid information. Our suggestion is to adopt the given criteria to evaluate every available software solutions thus helping the eventual user to analyse the tool before adopting it.

Study of suitability of Fricke-gel-layer dosimeters for in-air measurements to characterise epithermal/thermal neutron beams for NCT.

The reliability of Fricke gel dosimeters in form of layers for measurements aimed at the characterization of epithermal neutron beams has been studied. By means of dosimeters of different isotopic composition (standard, containing (10)B or prepared with heavy water) placed against the collimator exit, the spatial distribution of gamma and fast neutron doses and of thermal neutron fluence are attained. In order to investigate the accuracy of the results obtained with in-air measurements, suitable MC simulations have been developed and experimental measurements have been performed utilizing Fricke gel dosimeters, thermoluminescence detectors and activation foils. The studies were related to the epithermal beam designed for BNCT irradiations at the research reactor LVR-15 (Rez). The results of calculation and measurements have revealed good consistency of gamma dose and fast neutron 2D distributions obtained with gel dosimeters in form of layers. In contrast, noticeable modification of thermal neutron fluence is caused by the neutron moderation produced by the dosimeter material. Fricke gel dosimeters in thin cylinders, with diameter not greater than 3mm, have proved to give good results for thermal neutron profiling. For greater accuracy of all results, a better knowledge of the dependence of gel dosimeter sensitivity on radiation LET is needed.

Successful private-public funding of paediatric medicines research: lessons from the EU programme to fund research into off-patent medicines.

UNLABELLED: The European Paediatric Regulation mandated the European Commission to fund research on off-patent medicines with demonstrated therapeutic interest for children. Responding to this mandate, five FP7 project calls were launched and 20 projects were granted. This paper aims to detail the funded projects and their preliminary results. Publicly available sources have been consulted and a descriptive analysis has been performed. Twenty Research Consortia including 246 partners in 29 European and non-European countries were created (involving 129 universities or public-funded research organisations, 51 private companies with 40 SMEs, 7 patient associations). The funded projects investigate 24 medicines, covering 10 therapeutic areas in all paediatric age groups. In response to the Paediatric Regulation and to apply for a Paediatric Use Marketing Authorisation, 15 Paediatric Investigation Plans have been granted by the EMA-Paediatric Committee, including 71 studies of whom 29 paediatric clinical trials, leading to a total of 7,300 children to be recruited in more than 380 investigational centres. CONCLUSION: Notwithstanding the EU contribution for each study is lower than similar publicly funded projects, and also considering the complexity of paediatric research, these projects are performing high-quality research and are progressing towards the increase of new paediatric medicines on the market. Private-public partnerships have been effectively implemented, providing a good example for future collaborative actions. Since these projects cover a limited number of off-patent drugs and many unmet therapeutic needs in paediatrics remain, it is crucial foreseeing new similar initiatives in forthcoming European funding programmes.

In-label and off-label use of respiratory drugs in the Italian paediatric population.

AIM: To evaluate the prescription rate of respiratory drugs (ATC code R03) in an Italian community setting and to estimate the extent of off-label use by both age and indication. METHODS: A cohort study aimed at evaluating prescriptions of drugs with ATC code R03 was conducted for the period 2002-2006. Data source was the PEDIANET Database. RESULTS: Ninety percent of R03 prescriptions are covered by 11 active substances or combinations, corresponding to 67 medicinal products. Inhaled corticosteroids are the most prescribed anti-asthmatic agents, followed by short-acting beta2 mimetics. The mean off-label rate is 19 and 56%, by age and indication respectively. The majority of off-label uses is among children under the age of 2. Five active substances are used at dosages not supported by adequate dose-finding studies. CONCLUSION: In Italy, many respiratory drugs are approved for the treatment of paediatric respiratory diseases, but a remarkable percentage of their prescriptions is off-label. This pharmaco-utilization study demonstrates that there is a need to perform clinical studies aimed at increasing the current knowledge on marketed paediatric drugs, and to revise and re-label the existing regulatory documents to reduce their off-label uses.

Medicines for children licensed by the European Medicines Agency (EMEA): the balance after 10 years.

OBJECTIVE: The 1995-2005 balance of EMEA activities in the field of paediatric medicines was evaluated, taking into account the number both of drugs authorised for children and paediatric studies supporting the Marketing Authorisation (MA). METHODS: Data on drugs authorised by EMEA were extracted from EPARs (European Public Assessment Reports). Active substance, year of approval, anatomical, therapeutic and chemical (ATC) code, indication, orphan status, ages, and registrative clinical studies characteristics were assessed. RESULTS: The percentage of authorised substances for paediatrics is 33.3%. This percentage decreased or increased when different subsets of medicines were considered [medicines for children under 2 years (23.4%), N-ATC code drugs (6%) and orphan drugs (46.4%)]. A total of 165 trials were included in the MA dossiers of 51 drugs at the time of approval, and additional 22 studies were added to the dossiers of 12 active substances submitted for paediatric variations. PK and Efficacy/Safety studies were performed for 32 (52%) active substances, while either one PK or one Efficacy/Safety study was carried out for 43 (69%) and 45 (73%) substances, respectively. CONCLUSIONS: This report demonstrates that the total number of paediatric medicines approved by EMEA is stable over the 10-year period, while an increase in drugs to treat serious or orphan diseases has been observed. In addition, under the Centralised Procedure, a valuable number of paediatric trials have been submitted to support drug approval.

Medicines for children licensed by the European Agency for the Evaluation of Medicinal Products.

OBJECTIVE: . The aim of this study was to evaluate the number and the characteristics of medicines approved for children in Europe by the European Agency for the Evaluation of Medicinal Products (EMEA) and whether the paediatric studies supporting the authorisation were in accordance with the Note for Guidance on the Clinical Investigation of Medicinal Products in children (CPMP/ICH/2711/99). We also considered any possible difference between the EMEA and the Food and Drug Administration (FDA) paediatric medicines evaluations. METHODS: . We examined the drugs authorised by the EMEA through the centralised procedure from January 1995 to September 2001 deriving information from the "European Medicines - Database" (EMD) set up in 1998 by the Italian Group for Pharmacoeconomic Studies (GISF) and sponsored by the Italian Ministry of Health. The analysis of paediatric data has been managed by experts belonging to the Clinical Pharmacology Working Group of the Italian Paediatric Society. The following parameters were assessed: active substance, year of approval, anatomical therapeutic and chemical (ATC) code, therapeutic indications, age for which the drug is authorised, interest to children and paediatric studies supporting a paediatric authorisation. European Public Assessment Reports (EPARs) were considered as reference sources. RESULTS: . The median percentage of drugs authorised for children from 1995 to 2001 (September) is 35% of the total of commercially available drugs; only 16 medicines have been approved for children under 2 years of age (11%), ten of these being vaccines. Medicines for children shared out 9 ATC classes, 24 belonging to the J- (anti-infective agents) -ATC class. Thirty-nine medicines were authorised on the basis of at least one clinical trial (27 phase III, 6 phase II, 6 phase I) while eight active substances have been licensed without any paediatric investigation. CONCLUSIONS: . Under the EMEA centralised procedure, several active substances have been licensed for children. Consequently serious and life-threatening diseases as AIDS and diabetes are now treatable, in a legal framework overcoming the orphan status of the past years. Despite the reported encouraging results, the number of drugs devoted to children remain low and important ATC classes, as L-(oncology) or N-(neurology), are still 'orphans' of innovative medicines. At the same time few medicinal products are specifically studied in children. Consequently, more efforts have to be made to increase the number of drugs assessed and licensed for the paediatric population, and manufacturers should be required to supply data on the effects of new drugs in children when the products are expected to offer a benefit over existing therapies.