Effectiveness of an intervention for improving drug prescription in primary care patients with multimorbidity and polypharmacy:Study protocol of a cluster randomized clinical trial (Multi-PAP project)

This study was funded by the Fondo de Investigaciones Sanitarias ISCIII (Grant Numbers PI15/00276, PI15/00572, PI15/00996), REDISSEC (Project Numbers RD12/0001/0012, RD16/0001/0005), and the European Regional Development Fund ("A way to build Europe").Background: Multimorbidity is associated with negative effects both on people's health and on healthcare systems. A key problem linked to multimorbidity is polypharmacy, which in turn is associated with increased risk of partly preventable adverse effects, including mortality. The Ariadne principles describe a model of care based on a thorough assessment of diseases, treatments (and potential interactions), clinical status, context and preferences of patients with multimorbidity, with the aim of prioritizing and sharing realistic treatment goals that guide an individualized management. The aim of this study is to evaluate the effectiveness of a complex intervention that implements the Ariadne principles in a population of young-old patients with multimorbidity and polypharmacy. The intervention seeks to improve the appropriateness of prescribing in primary care (PC), as measured by the medication appropriateness index (MAI) score at 6 and 12months, as compared with usual care. Methods/Design: Design:pragmatic cluster randomized clinical trial. Unit of randomization: family physician (FP). Unit of analysis: patient. Scope: PC health centres in three autonomous communities: Aragon, Madrid, and Andalusia (Spain). Population: patients aged 65-74years with multimorbidity (≥3 chronic diseases) and polypharmacy (≥5 drugs prescribed in ≥3months). Sample size: n=400 (200 per study arm). Intervention: complex intervention based on the implementation of the Ariadne principles with two components: (1) FP training and (2) FP-patient interview. Outcomes: MAI score, health services use, quality of life (Euroqol 5D-5L), pharmacotherapy and adherence to treatment (Morisky-Green, Haynes-Sackett), and clinical and socio-demographic variables. Statistical analysis: primary outcome is the difference in MAI score between T0 and T1 and corresponding 95% confidence interval. Adjustment for confounding factors will be performed by multilevel analysis. All analyses will be carried out in accordance with the intention-to-treat principle. Discussion: It is essential to provide evidence concerning interventions on PC patients with polypharmacy and multimorbidity, conducted in the context of routine clinical practice, and involving young-old patients with significant potential for preventing negative health outcomes. Trial registration: Clinicaltrials.gov, NCT02866799Publisher PDFPeer reviewe

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Évaluation de l impact de Fiches d Information Patient (FIP) sur le comportement des patients face à des pathologies courantes en médecine générale (étude randomisée et contrôlée)

1/ Contexte scientifique : Dans la relation médecin-malade, la communication joue un rôle majeur. L information écrite est un complément utile à l information orale puisqu elle permet aux patients une meilleure gestion de leur pathologie. Dans ce contexte, 125 FIP ont été crées en 2007. En 2008, l étude EDIMAP a validé les FIP en termes de satisfaction et de compréhension. L'objectif principal de notre étude était d évaluer l'impact des FIP sur le comportement des patients avec comme critère de jugement principal un score de modification du comportement. 2/ Matériel et Méthode : Etude randomisée, comparative, multicentrique et prospective réalisée en cluster de novembre 2009 à janvier 2011. 4 FIP ont été choisies : la gastroentérite aiguë chez l enfant et l adulte ; l angine virale chez l enfant et l adulte. 30 médecins généralistes français ont été réunis par coaptation pour participer à l'étude. Déroulement de l étude : - Inclusion au cours d une consultation pour une des 4 pathologies : envoi du fax d inclusion au CIC de Grenoble, remise de la lettre d information au patient, remise ou non d une FIP.- Questionnaire téléphonique entre J10 et J15 après la consultation : recueil des données avec calcul des scores compréhension et de modification du comportement. 4/ Résultats : 24 médecins ont participé et inclus 400 patients dont 12 perdus de vue (3%). Les patients ayant reçu les FIP avaient un comportement plus adapté (scores de modification du comportement de 1,1 vs 1,8, p<0,01). Les FIP avaient donc un impact sur le comportement des patients et sur celui de leurs proches permettant, une moindre consultation de ceux-ci pour les mêmes symptômes. 5/ Conclusion : Cette étude valide l intérêt de l utilisation des FIP en médecine générale et suggère l intérêt de leur mise à disposition à plus grande échelle.1/ Background : Communication is an important part of the relation between the patient and the practitioner. Written information can be a usefull tool as it leads patients to deal better with their illness. 125 Patient Information Leaflets (PIL) have been created in 2007. In 2008, the EDIMAP study valided these PIL regarding patients satisfaction and comprehension. The main outcome of this study was to evaluate their utility in primary care by testing their impact on patient s behavior. The assessment endpoint was a modification of behavior score. 2/ Material & Method : A randomised, multicentric, prospective and comparative trial was realized in cluster between november 2009 and january 2011 in France. 4 PIL were chosen : the adults and children s gatroenteritis ones and the adults and children s pharyngitis ones. 30 general practitioners were found by coaptation and asked to participate. Intervention : Inclusions were made during a consultation for one of the 4 pathologies : an inclusion fax was sent to the Centre d Investigation Clinique of Grenoble ; an information letter was given to the patient and then the patient was given either a PIF with the oral information or the oral information only. Questions were asked by phone 10 to 15 days after the consultation ; data collection and calculation of two scores : a comprehension score and a modification of behavior s one. 3/ Results: 24 general practitioners included 400 patients out of wich 12 were lost during the study (3%). The behavior was more adapted in the groupe with the PIL (modification of behavior s score of 1,1 on average versus 1,8 in the control group, p<0,01). These results show that the PIL had a significative impact on patient s behavior and also on their closes. There were less consultations of these closes for the same symptoms. 4/ Conclusion : This study illustrates the interest of the utilisation of PIL in primary care. They could be a tool for general practitioners as they are supporting by an oral information at the point of delivery.GRENOBLE1-BU Médecine pharm. (385162101) / SudocSudocFranceF

Notch Activation Is an Early and Critical Event during T-Cell Leukemogenesis in Ikaros-Deficient Mice

The Ikaros transcription factor is both a key regulator of lymphocyte differentiation and a tumor suppressor in T lymphocytes. Mice carrying a hypomorphic mutation (Ik(L/L)) in the Ikaros gene all develop thymic lymphomas. Ik(L/L) tumors always exhibit strong activation of the Notch pathway, which is required for tumor cell proliferation in vitro. Notch activation occurs early in tumorigenesis and may precede transformation, as ectopic expression of the Notch targets Hes-1 and Deltex-1 is detected in thymocytes from young Ik(L/L) mice with no overt signs of transformation. Notch activation is further amplified by secondary mutations that lead to C-terminal truncations of Notch 1. Strikingly, restoration of Ikaros activity in tumor cells leads to a rapid and specific downregulation of Notch target gene expression and proliferation arrest. Furthermore, Ikaros binds to the Notch-responsive element in the Hes-1 promoter and represses Notch-dependent transcription from this promoter. Thus, Ikaros-mediated repression of Notch target gene expression may play a critical role in defining the tumor suppressor function of this factor