Nice Systems (Israel)

Health technology assessment (HTA) is widely used throughout Europe to make decisions about the reimbursement and/or pricing of healthcare technologies including new medicines. Several countries require evidence on cost effectiveness and budget impact. Important inputs for these analyses are estimates of healthcare use and costs. Companies and HTA agencies face multiple challenges in obtaining and generating such evidence in support of their products. Real-world evidence (RWE) could answer some of the challenges faced by companies and HTA agencies, however progress on the adoption of RWE in HTA is slow compared to the progress made in the regulatory space. EHDEN work package 2, in collaboration with GetReal Institute, organised a half-day workshop to provide an update on recent developments and discuss progress towards greater use of RWE and the federated data network approach in regulatory decision making by the European Medicines Agency (EMA) and consider the implications and opportunities for European HTA agencies and their stakeholders to use the same approach. This involved presentations on the progress of the establishment of the coordination Centre for the Data Analysis and Real World Interrogation Network (DARWIN EU®) by EMA, followed by reflections on this progress and possible implications on the use of EHDEN and the federated data network approach from an HTA perspective. A range of stakeholders also expressed their view on how to further advance the adoption of RWE for HTA. Finally, we discussed how EHDEN and not-for-profit entities emanating from IMI projects such as GetReal Institute can support the adoption of RWE in HTA. A key area of need identified was for the provision of training and upskilling, not only of HTA agencies’ staff, but also of committee members, evidence review groups, and researchers. There was also a need for key ‘driver projects’ to demonstrate the utility of RWE and the federated data network approach in HTA. Assessing the generalisability of trial data is a top priority area for the use of RWE in HTA and, hence, can be a major focus for such driver projects.

We have previously hypothesized that well-differentiated papillary mesothelial tumor (WDPMT) consists of 2 morphologically identical lesions, one of which is true WDPMT, while the other is a form of mesothelioma in situ. Here, we report 8 examples of the latter phenomenon, 3 with pleural disease (2 men/1 woman, ages 66 to 78y); and 5 with peritoneal disease (all women, ages 31 to 81y). At presentation the pleural cases all had effusions but no evidence of pleural tumor on imaging. Four of the 5 peritoneal cases had ascites as the initial finding and all 4 had nodular lesions that by imaging and/or direct inspection were thought to represent a diffuse peritoneal malignancy. The fifth peritoneal case presented with an umbilical mass. Microscopically, the pleural and peritoneal lesions looked like diffuse WDPMT, but all had lost BAP1. Occasional microscopic foci of superficial invasion were present in 3/3 pleural cases, while single nodules of invasive mesothelioma and/or occasional foci of superficial microscopic invasion were found in all of the peritoneal cases. The pleural tumor patients developed what clinically appeared to be invasive mesothelioma at 45, 69, and 94 months. Four/five peritoneal tumor patients underwent cytoreductive surgery and heated intraperitoneal chemotherapy. Three with follow-up data are alive without recurrence at 6, 24, and 36 months; 1 patient refused treatment but is alive at 24 months. We conclude that mesothelioma in situ morphologically mimicking WDPMT is strongly associated with the synchronous or metachronous development of invasive mesothelioma, but that these lesions appear to progress very slowly.

En 1922, Freud lance un concourssur les rapports entre technique et théorie psychanalytiques, auquel personne ne répondra directement. Rank et Ferenczi publient après la date limite Objectifs de développement de la psychanalyse. Du rapport mutuel entre théorie et pratique, à l’origine d’une vive polémique qui aura des retentissements majeurs sur l’histoire du mouvement analytique. Dans Thérapie contre théorie ? Les enjeux d’un concours (Puf, 2002), Mady Jeannet-Hasler ouvre une enquête approfondie sur cet épisode peu connu des pionniers de la psychanalyse, qui mêle enjeux scientifiques, politiques et passionnels. Elle dénonce vivement, à l’instar de Rank et Ferenczi, combien l’investigation scientifique avait pris le pas sur l’engagement thérapeutique, et montre que, selon elle, certaines de leurs idées (le « revécu » et la remémoration affective, le transfert et la situation analytique) qui furent rejetées à l’époque annonçaient l’évolution de la psychanalyse contemporaine.

Healthcare data, generated through the delivery of normal clinical care is increasingly being used to investigate the use of drugs in real life. As part of previous research with EHDEN, we had investigated treatment patterns of patients with asthma, COPD or asthma-COPD overlap. For this research, data from the IPCI database, a Dutch primary care database, was used. IPCI data was mapped to the OMOP CDM which allows the generation of one software script to explore treatment patterns which can then be run on other data sources. As a follow-up to our research on the treatment patterns of asthma & COPD, we wanted to explore whether the study population, as selected using IPCI data mapped to the OMOP CDM was similar to IPCI source data (thus not mapped to the OMOP CDM). To do so, we defined criteria for our study period, study population and exposure cohorts and extracted the data (IPCI source & IPCI CDM). Some differences in number of patients were identified but these could be attributed to the fact that IPCI CDM applies quality standards which result in some patients being excluded. For example, diagnoses with missing dates and multiple prescriptions of the same drug on the same day are disregarded. The remaining differences between IPCI source and IPCI CDM were related to discrepancies in mapping drugs from ATC code to RxNorm, which is challenging for inhalation therapy.

Un entrefilet dans un quotidien a attiré notre attention sur la parution récente de cet ouvrage ; or nous avions lu il y a quelques années le texte de P. Segond dans Les Temps modernes sur le destin tragique d’Eva Freud. Lecture faite, un contact fut pris avec son auteure, Isabelle Sieurin, et nous avons eu envie de comprendre sa démarche et de lui faire raconter sa route d’enquêtrice. Or celle-ci s’est effectuée par étapes associant une recherche en divers lieux (Nice, Marseille et Washington essentiellement), mais aussi avec la découverte de rares et touchantes personnes qui se souvenaient encore de l’adolescente. Enfin, comme Isabelle Sieurin est professeure de philosophie, un travail d’exploitation avec ses élèves l’a conduite à illustrer l’histoire en mettant en scène les échanges épistolaires dans un spectacle. Ainsi sa démarche illustre-t-elle ce que peut être une transmission vivante d’une histoire qui ne s’oublie pas.

Abstract Background Elderly patients with chronic kidney disease (CKD) frequently present comorbidities that put them at risk of polypharmacy and medication-related problems. This study aims to describe the overall medication profile of patients aged ≥ 75 years with advanced CKD from a multicenter French study and specifically the renally (RIMs) and potentially inappropriate-for-the-elderly medications (PIMs) that they take. Methods This is a cross-sectional analysis of medication profiles of individuals aged ≥ 75 years with eGFR < 20 ml/min/1.73m2 followed by a nephrologist, who collected their active prescriptions at the study inclusion visit. Medication profiles were first analyzed according to route of administration, therapeutic classification. Second, patients were classified according to their risk of potential medication-related problems, based on whether the prescription was a RIM or a PIM. RIMs and PIMs have been defined according to renal appropriateness guidelines and to Beer’s criteria in the elderly. RIMs were subclassified by 4 types of category : (a) contraindication; (b) dose modification is recommended based on creatinine clearance (CrCl); (c) dose modification based on CrCl is not recommended but a maximum daily dose is mentioned, (d) no specific recommendations based on CrCl : “use with caution”, “avoid in severe impairment”, “careful monitoring of dose is required” “reduce the dose”. Results We collected 5196 individual medication prescriptions for 556 patients, for a median of 9 daily medications [7-11]. Antihypertensive agents, antithrombotics, and antianemics were the classes most frequently prescribed. Moreover, 77.0% of patients had at least 1 medication classified as a RIM. They accounted 31.3% of the drugs prescribed and 9.25% was contraindicated drugs. At least 1 PIM was taken by 57.6% and 45.5% of patients had at least one medication classified as RIM and PIM. The prescriptions most frequently requiring reassessment due to potential adverse effects were for proton pump inhibitors and allopurinol. The PIMs for which deprescription is especially important in this population are rilmenidine, long-term benzodiazepines, and anticholinergic drugs such as hydroxyzine. Conclusion We showed potential drug-related problems in elderly patients with advanced CKD. Healthcare providers must reassess each medication prescribed for this population, particularly the specific medications identified here.

This paper presents a facile strategy to activate citric acid (CA) for room temperature curing.

Abstract Background Acute myeloid leukemia is the most common acute leukemia in adults with an unacceptably low cure rate. In recent years a number of new treatment strategies and compounds were developed for the treatment of acute myeloid leukemia. There were several randomized, controlled clinical trials with the objective to improve patients’ management and patients’ outcome in acute myeloid leukemia. Unfortunately, these trials are not always directly comparable, as they do not measure the same outcomes and currently there are no core outcome sets that can be utilized to guide outcome selection and harmonization in this disease area. The HARMONY Alliance is a public-private European Network established in 2017, which currently includes 53 partners and 32 associated members from 22 countries. Amongst many other goals of the HARMONY Alliance, Work Package 2 focuses on defining outcomes that are relevant to each hematological malignancy. In accordance, a pilot study will be performed to define core outcome set in acute myeloid leukemia. Methods The pilot study will use a three-round Delphi survey and a final consensus meeting to define a core outcome set. Participants will be recruited from different stakeholder groups, including patients, clinicians, regulators and members of the European Federation of Pharmaceutical Industries and Associations (EFPIA). At the pre-Delphi stage a literature research was conducted followed by several semi-structured interviews of clinical public and private key opinion leaders. Subsequently the preliminary outcome list was discussed in several multi-stakeholder face-to-face meetings. The Delphi survey will reduce the preliminary outcome list to essential core outcomes. After completing the last Delphi round a final face-to-face meeting is planned to achieve consensus about core outcome set in acute myeloid leukemia. Discussion The pilot Delphi as part of HARMONY Alliance aims to define a core outcome set in acute myeloid leukemia based on a multi-stakeholder consensus. Such a core outcome set will help to allow consistent comparison of future clinical trials and real world evidence research and ensures that appropriate outcomes valued by a range of stakeholders are measured within future trials.

Although in the section A chi legge he suggested otherwise, Beccaria owes much to Hobbes. This is evinced by three theses advanced in Dei delitti e delle pene: human beings are by nature unsociable; there is no natural law prior to the establishment of the civil society; natural rights derive from our inborn tendency to self-preservation. From these assumptions, however, Beccaria draws three conclusions that contradict Hobbes: even the most fundamental rights, being guaranteed only by the civil law, are in fact created by it; sovereignty, which is intrinsically limited, is legitimate only insofar as it acknowledges the right to live; the death penalty is illegitimate because it brings men back to the state of permanent war they meant to overcome.