Mutua disponibilità, prezzi e rimborsabilità di farmaci autorizzati con procedura centralizzata europea

The european pharmaceutical market doesn’t seem to be a common integrated european market as far as prices and reimbursements within different countries are concerned. Moreover, to better define such differences, little information is available because of the lack of homogeneous and updated european databases. The aim of this study is to assess mutual availability, prices and reimbursements of innovative drugs authorised by EMEA under European Centralised Procedure between 1995-2000 and marketed in five european countries (Italy, Spain, United Kingdom, France and Denmark). Our results demonstrate that the adoption of different drug-price definition models, within different Member States, is the main cause of the heterogeneity. Currently, in countries adopting a controlled drug-price system, prices are lower than prices set in countries that adopt an uncontrolled drug-price system. In this regard, Italy ranks in a middle position as products marketed in Italy generally have prices lower than in the United Kingdom and Denmark, and higher than in France and Spain. Product availability and level of drug breakthrough in the national markets seem to greatly affect the variations we noted among prices and reimbursements in different countries. Differences we observed emphasize the need of finding a common methodology at european level, in order to define the proven “therapeutic benefit” and the “therapeutic advantage” of innovative drugs, allowing a “right price” and reimbursement to the entitled

Impiego degli Inibitori della Pompa protonica (IPP) in Piemonte: indagine sulle abitudini prescrittive dei Medici di Medicina Generale

Proton Pump Inhibitors (PPIs) (Omeprazole, Lansoprazole, Pantoprazole, Rabeprazole and Esomeprazole), one of the most commonly prescribed classes of medications in the primary care setting, are considered a major advance in the treatment of acid-peptic diseases. In Italy PPIs are reimbursed by National Health Service on the basis of CUF (Commissione Unica del Farmaco) 1 and 48 Notes. In 2002 and 2003 a significant increase in PPIs consumption and expenditure have been documented, showing differences between regions. The aim of this study is to investigate and monitor, at regional level, type and entity of PPIs use through a drug utilization study, evaluating prescribing behaviour and compliance of PPIs treatments with CUF Notes indications. The study has been carried out on a sample of 436 General Practitioners belonging to 22 Piemonte's ASL (Aziende Sanitarie Locali). The data analysis shows that acid-related pathologies are significantly more common in patients with at least 50 years of age and the most frequent condition is represented by gastroesophageal reflux disease. Despite the general conditions of PPIs use by General Practitioners in terms of duration and dosage of therapy result in most cases (from 49% to 80% for duration and from 54% to 97% for dosage) compliant with what proposed by CUF Notes, in some cases the same CUF Notes indications seem to be not observed. Consequently the Piemonte Region has decided to plan a guideline on PPIs rational use. Such guideline, expected to be introduced in the regional area, may also be considered as an instrument able to lead to a more appropriate expenditure for this drug class. Moreover, in order to control PPIs expenditure, pharmacoeconomic methodologies can be applied allowing to identify the most cost - effective active substance and therapeutic scheme, overcoming CUF Notes which consider all PPIs use under the same reimbursement conditions

Diagnosis and Treatment of Chronic Neuropathic and Mixed Pain in Children and Adolescents: Results of a Survey Study amongst Practitioners

Валідовані діагностичні засоби для діагностики хронічного невропатичного та змішаного болю у дітей відсутні. Терапевтичні варіанти часто походять від терапевтичних засобів для дорослих. Щоб дослідити міжнародну практику серед практикуючих лікарів з діагностики та лікування хронічного невропатичного болю у дітей та підлітків, ми провели опитування серед членів наукових товариств або груп, члени яких залучені до лікування дитячого болю. Опитування включало питання стосовно практиків та характеристик практики, оцінки та діагностики, лікування та прийому ліків. Ми проаналізували 117 повернутих анкет, з яких 41 (35%) була повністю заповнена, а 76 (65%) заповнені частково. Більшість респондентів базували діагноз невропатичного болю на фізичному обстеженні (68 (58,1%)), анамнезі пацієнтів (67 (57,3%)) та основному захворюванні (59 (50,4%)). Габапентин, амітриптилін та прегабалін були першим вибором засобів для лікування помірного невропатичного болю. Трамадол, ібупрофен, амітриптилін і парацетамол були першочерговими методами лікування помірного змішаного болю. Консенсусу щодо діагностичного процесу невропатичного болю у дітей та підлітків бракує. Медикаментозне лікування широко варіюється у разі помірного, сильного невропатичного та змішаного болю. Отже, діагностичні засоби та терапію необхідно узгодити та перевірити для використання у дітей.Утвержденные диагностические инструменты для диагностики хронической невропатической и смешанной боли у детей отсутствуют. Варианты лечения часто основываются на терапии для взрослых. Чтобы изучить международную практику среди практикующих врачей по диагностике и лечению хронической нейропатической боли у детей и подростков, мы провели исследование среди членов научных обществ или групп, члены которых принимают участие в лечении педиатрической боли. Опрос включал вопросы, касающиеся практикующих врачей и характеристик практики, оценки и диагноза, лечения и приема медикаментов. Мы проанализировали 117 возвращенных анкет, из которых 41 (35%) были заполнены полностью, а 76 (65%) - частично. Большинство респондентов ставили диагноз невропатической боли на основании медицинского осмотра (68 (58,1%)), истории болезни (67 (57,3%)) и основного заболевания (59 (50,4%)). Габапентин, амитриптилин и прегабалин были препаратами первого выбора при умеренной невропатической боли. Трамадол, ибупрофен, амитриптилин и парацетамол были препаратами первого выбора при умеренной смешанной боли. Единого мнения о диагностическом процессе невропатической боли у детей и подростков нет. Медикаментозное лечение умеренной, тяжелой невропатической и смешанной боли широко варьируется. Следовательно, диагностические инструменты и терапия должны быть согласованы и утверждены для использования у детей.Validated diagnostic tools to diagnose chronic neuropathic and mixed pain in children are missing. Therapeutic options are often derived from therapeutics for adults. To investigate the international practice amongst practitioners for the diagnosis and treatment of chronic, neuropathic pain in children and adolescents, we performed a survey study among members of learned societies or groups whose members are known to treat pediatric pain. The survey included questions concerning practitioners and practice characteristics, assessment and diagnosis, treatment and medication. We analyzed 117 returned questionnaires, of which 41 (35%) were fully completed and 76 (65%) were partially completed. Most respondents based the diagnosis of neuropathic pain on physical examination (68 (58.1%)), patient history (67 (57.3%)), and underlying disease (59 (50.4%)) combined. Gabapentin, amitriptyline, and pregabalin were the first-choice treatments for moderate neuropathic pain. Tramadol, ibuprofen, amitriptyline, and paracetamol were the first-choice treatments for moderate mixed pain. Consensus on the diagnostic process of neuropathic pain in children and adolescents is lacking. Drug treatment varies widely for moderate, severe neuropathic, and mixed pain. Hence, diagnostic tools and therapy need to be harmonized and validated for use in children

Diagnosis and Treatment of Chronic Neuropathic and Mixed Pain in Children and Adolescents: Results of a Survey Study amongst Practitioners

Validated diagnostic tools to diagnose chronic neuropathic and mixed pain in children are missing. Therapeutic options are often derived from therapeutics for adults. To investigate the international practice amongst practitioners for the diagnosis and treatment of chronic, neuropathic pain in children and adolescents, we performed a survey study among members of learned societies or groups whose members are known to treat pediatric pain. The survey included questions concerning practitioners and practice characteristics, assessment and diagnosis, treatment and medication. We analyzed 117 returned questionnaires, of which 41 (35%) were fully completed and 76 (65%) were partially completed. Most respondents based the diagnosis of neuropathic pain on physical examination (68 (58.1%)), patient history (67 (57.3%)), and underlying disease (59 (50.4%)) combined. Gabapentin, amitriptyline, and pregabalin were the first-choice treatments for moderate neuropathic pain. Tramadol, ibuprofen, amitriptyline, and paracetamol were the first-choice treatments for moderate mixed pain. Consensus on the diagnostic process of neuropathic pain in children and adolescents is lacking. Drug treatment varies widely for moderate, severe neuropathic, and mixed pain. Hence, diagnostic tools and therapy need to be harmonized and validated for use in children

The Athena X-ray Integral Field Unit: a consolidated design for the system requirement review of the preliminary definition phase

The Athena X-ray Integral Unit (X-IFU) is the high resolution X-ray spectrometer, studied since 2015 for flying in the mid-30s on the Athena space X-ray Observatory, a versatile observatory designed to address the Hot and Energetic Universe science theme, selected in November 2013 by the Survey Science Committee. Based on a large format array of Transition Edge Sensors (TES), it aims to provide spatially resolved X-ray spectroscopy, with a spectral resolution of 2.5 eV (up to 7 keV) over an hexagonal field of view of 5 arc minutes (equivalent diameter). The X-IFU entered its System Requirement Review (SRR) in June 2022, at about the same time when ESA called for an overall X-IFU redesign (including the X-IFU cryostat and the cooling chain), due to an unanticipated cost overrun of Athena. In this paper, after illustrating the breakthrough capabilities of the X-IFU, we describe the instrument as presented at its SRR, browsing through all the subsystems and associated requirements. We then show the instrument budgets, with a particular emphasis on the anticipated budgets of some of its key performance parameters. Finally we briefly discuss on the ongoing key technology demonstration activities, the calibration and the activities foreseen in the X-IFU Instrument Science Center, and touch on communication and outreach activities, the consortium organisation, and finally on the life cycle assessment of X-IFU aiming at minimising the environmental footprint, associated with the development of the instrument. Thanks to the studies conducted so far on X-IFU, it is expected that along the design-to-cost exercise requested by ESA, the X-IFU will maintain flagship capabilities in spatially resolved high resolution X-ray spectroscopy, enabling most of the original X-IFU related scientific objectives of the Athena mission to be retained. (abridged).Comment: 48 pages, 29 figures, Accepted for publication in Experimental Astronomy with minor editin

The Athena X-ray Integral Field Unit: a consolidated design for the system requirement review of the preliminary definition phase

The Athena X-ray Integral Unit (X-IFU) is the high resolution X-ray spectrometer studied since 2015 for flying in the mid-30s on the Athena space X-ray Observatory. Athena is a versatile observatory designed to address the Hot and Energetic Universe science theme, as selected in November 2013 by the Survey Science Committee. Based on a large format array of Transition Edge Sensors (TES), X-IFU aims to provide spatially resolved X-ray spectroscopy, with a spectral resolution of 2.5 eV (up to 7 keV) over a hexagonal field of view of 5 arc minutes (equivalent diameter). The X-IFU entered its System Requirement Review (SRR) in June 2022, at about the same time when ESA called for an overall X-IFU redesign (including the X-IFU cryostat and the cooling chain), due to an unanticipated cost overrun of Athena. In this paper, after illustrating the breakthrough capabilities of the X-IFU, we describe the instrument as presented at its SRR (i.e. in the course of its preliminary definition phase, so-called B1), browsing through all the subsystems and associated requirements. We then show the instrument budgets, with a particular emphasis on the anticipated budgets of some of its key performance parameters, such as the instrument efficiency, spectral resolution, energy scale knowledge, count rate capability, non X-ray background and target of opportunity efficiency. Finally, we briefly discuss the ongoing key technology demonstration activities, the calibration and the activities foreseen in the X-IFU Instrument Science Center, touch on communication and outreach activities, the consortium organisation and the life cycle assessment of X-IFU aiming at minimising the environmental footprint, associated with the development of the instrument. Thanks to the studies conducted so far on X-IFU, it is expected that along the design-to-cost exercise requested by ESA, the X-IFU will maintain flagship capabilities in spatially resolved high resolution X-ray spectroscopy, enabling most of the original X-IFU related scientific objectives of the Athena mission to be retained. The X-IFU will be provided by an international consortium led by France, The Netherlands and Italy, with ESA member state contributions from Belgium, Czech Republic, Finland, Germany, Poland, Spain, Switzerland, with additional contributions from the United States and Japan.The French contribution to X-IFU is funded by CNES, CNRS and CEA. This work has been also supported by ASI (Italian Space Agency) through the Contract 2019-27-HH.0, and by the ESA (European Space Agency) Core Technology Program (CTP) Contract No. 4000114932/15/NL/BW and the AREMBES - ESA CTP No.4000116655/16/NL/BW. This publication is part of grant RTI2018-096686-B-C21 funded by MCIN/AEI/10.13039/501100011033 and by “ERDF A way of making Europe”. This publication is part of grant RTI2018-096686-B-C21 and PID2020-115325GB-C31 funded by MCIN/AEI/10.13039/501100011033

Measurement of the top quark forward-backward production asymmetry and the anomalous chromoelectric and chromomagnetic moments in pp collisions at √s = 13 TeV

Abstract The parton-level top quark (t) forward-backward asymmetry and the anomalous chromoelectric (d̂ t) and chromomagnetic (μ̂ t) moments have been measured using LHC pp collisions at a center-of-mass energy of 13 TeV, collected in the CMS detector in a data sample corresponding to an integrated luminosity of 35.9 fb−1. The linearized variable AFB(1) is used to approximate the asymmetry. Candidate t t ¯ events decaying to a muon or electron and jets in final states with low and high Lorentz boosts are selected and reconstructed using a fit of the kinematic distributions of the decay products to those expected for t t ¯ final states. The values found for the parameters are AFB(1)=0.048−0.087+0.095(stat)−0.029+0.020(syst),μ̂t=−0.024−0.009+0.013(stat)−0.011+0.016(syst), and a limit is placed on the magnitude of | d̂ t| < 0.03 at 95% confidence level. [Figure not available: see fulltext.

Measurement of t(t)over-bar normalised multi-differential cross sections in pp collisions at root s=13 TeV, and simultaneous determination of the strong coupling strength, top quark pole mass, and parton distribution functions

Peer reviewe

An embedding technique to determine ττ backgrounds in proton-proton collision data

An embedding technique is presented to estimate standard model tau tau backgrounds from data with minimal simulation input. In the data, the muons are removed from reconstructed mu mu events and replaced with simulated tau leptons with the same kinematic properties. In this way, a set of hybrid events is obtained that does not rely on simulation except for the decay of the tau leptons. The challenges in describing the underlying event or the production of associated jets in the simulation are avoided. The technique described in this paper was developed for CMS. Its validation and the inherent uncertainties are also discussed. The demonstration of the performance of the technique is based on a sample of proton-proton collisions collected by CMS in 2017 at root s = 13 TeV corresponding to an integrated luminosity of 41.5 fb(-1).Peer reviewe

MUSiC : a model-unspecific search for new physics in proton-proton collisions at root s=13TeV

Results of the Model Unspecific Search in CMS (MUSiC), using proton-proton collision data recorded at the LHC at a centre-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 35.9 fb(-1), are presented. The MUSiC analysis searches for anomalies that could be signatures of physics beyond the standard model. The analysis is based on the comparison of observed data with the standard model prediction, as determined from simulation, in several hundred final states and multiple kinematic distributions. Events containing at least one electron or muon are classified based on their final state topology, and an automated search algorithm surveys the observed data for deviations from the prediction. The sensitivity of the search is validated using multiple methods. No significant deviations from the predictions have been observed. For a wide range of final state topologies, agreement is found between the data and the standard model simulation. This analysis complements dedicated search analyses by significantly expanding the range of final states covered using a model independent approach with the largest data set to date to probe phase space regions beyond the reach of previous general searches.Peer reviewe