56 research outputs found
Multiplicity of tests, and sample size determination of clinical trials
Ce travail a eu pour objectif de rĂ©pondre aux problĂ©matiques inhĂ©rentes aux tests multiples dans le contexte des essais cliniques. A lâheure actuelle un nombre croissant dâessais cliniques ont pour objectif dâobserver lâeffet multifactoriel dâun produit, et nĂ©cessite donc lâutilisation de co-critĂšres de jugement principaux. La significativitĂ© de lâĂ©tude est alors conclue si et seulement si nous observons le rejet dâau moins r hypothĂšses nulles parmi les m hypothĂšses nulles testĂ©es. Dans ce contexte, les statisticiens doivent prendre en compte la multiplicitĂ© induite par cette pratique. Nous nous sommes consacrĂ©s dans un premier temps Ă la recherche dâune correction exacte pour lâanalyse des donnĂ©es et le calcul de taille dâĂ©chantillon pour r = 1. Puis nous avons travaillĂ© sur le calcul de taille dâÂŽechantillon pour toutes valeurs de r, quand les procĂ©dures en une Ă©tape, ou les procĂ©dures sĂ©quentielles sont utilisĂ©es. Finalement nous nous sommes intĂ©ressĂ©s Ă la correction du degrĂ© de signification engendrĂ© par la recherche dâun codage optimal dâune variable explicative continue dans un modĂšle linĂ©aire gĂ©nĂ©ralisĂ©This work aimed to meet multiple testing problems in clinical trials context. Nowadays, in clinical research it is increasingly common to define multiple co-primary endpoints in order to capture a multi-factorial effect of the product. The significance of the study is concluded if and only if at least r null hypotheses are rejected among the m null hypotheses. In this context, statisticians need to take into account multiplicity problems. We initially devoted our work on exact correction of the multiple testing for data analysis and sample size computation, when r = 1. Then we worked on sample size computation for any values of r, when stepwise and single step procedures are used. Finally we are interested in the correction of significance level generated by the search for an optimal coding of a continuous explanatory variable in generalized linear model
Multiplicity of tests, and sample size determination of clinical trials
Ce travail a eu pour objectif de rĂ©pondre aux problĂ©matiques inhĂ©rentes aux tests multiples dans le contexte des essais cliniques. A lâheure actuelle un nombre croissant dâessais cliniques ont pour objectif dâobserver lâeffet multifactoriel dâun produit, et nĂ©cessite donc lâutilisation de co-critĂšres de jugement principaux. La significativitĂ© de lâĂ©tude est alors conclue si et seulement si nous observons le rejet dâau moins r hypothĂšses nulles parmi les m hypothĂšses nulles testĂ©es. Dans ce contexte, les statisticiens doivent prendre en compte la multiplicitĂ© induite par cette pratique. Nous nous sommes consacrĂ©s dans un premier temps Ă la recherche dâune correction exacte pour lâanalyse des donnĂ©es et le calcul de taille dâĂ©chantillon pour r = 1. Puis nous avons travaillĂ© sur le calcul de taille dâÂŽechantillon pour toutes valeurs de r, quand les procĂ©dures en une Ă©tape, ou les procĂ©dures sĂ©quentielles sont utilisĂ©es. Finalement nous nous sommes intĂ©ressĂ©s Ă la correction du degrĂ© de signification engendrĂ© par la recherche dâun codage optimal dâune variable explicative continue dans un modĂšle linĂ©aire gĂ©nĂ©ralisĂ©This work aimed to meet multiple testing problems in clinical trials context. Nowadays, in clinical research it is increasingly common to define multiple co-primary endpoints in order to capture a multi-factorial effect of the product. The significance of the study is concluded if and only if at least r null hypotheses are rejected among the m null hypotheses. In this context, statisticians need to take into account multiplicity problems. We initially devoted our work on exact correction of the multiple testing for data analysis and sample size computation, when r = 1. Then we worked on sample size computation for any values of r, when stepwise and single step procedures are used. Finally we are interested in the correction of significance level generated by the search for an optimal coding of a continuous explanatory variable in generalized linear model
MĂ©tastases digestives des carcinomes bronchiques non Ă petites cellules (Ă propos de cinq cas)
LYON1-BU Santé (693882101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF
Molybdenum Occupational Study in a French Cohort of Workers
International audienceAbstract Objectives Occupational exposure to molybdenum has been poorly documented to date. Here, we present a retrospective study evaluating urinary molybdenum concentration before and after shift over a period of 2 years in exposed workers. Methods This retrospective study was conducted across eight industrial sites in France and included all workers undergoing medical follow-up for occupational molybdenum exposure. A mean of six sequential samples (before and after shift) was performed for each worker. The urinary molybdenum concentration was determined using a validated method of inductively coupled plasma-mass spectrometry. A mixed linear model was built and linear regression was used to verify the extent to which the urinary molybdenum concentration depends on the age of the workers and the sampling period. Additionally, an analysis based on individual trajectory was also performed. Results Seventy-seven workers were included in the present study. Post-shift urinary molybdenum concentrations were significantly higher than pre-shift values [median (95th percentile) 37.9 (91.1), versus 60.6 (190.0) ”g gâ1 creatinine, respectively, P < 0.009]. No accumulation of molybdenum over time was observed. The urinary molybdenum concentrations were not influenced by age. Four workers presented high post-shift values as a result of not adhering to protection measures (maxima of 529.8, 359.7, 386.3, and 1459.7 ”g gâ1 creatinine, respectively). Conclusions To our knowledge, this is the first study of occupational molybdenum exposure in France to include an individual trajectory analysis. No accumulation of molybdenum was seen but high post-shift molybdenum urinary concentrations were observed for some workers. The study emphasizes the importance of molybdenum monitoring in exposed workers
Power and sample size determination in clinical trials with multiple primary continuous correlated end points
The use of two or more primary correlated endpoints is becoming increasingly common. A mandatory approach when analyzing data from such clinical trials is to control the family-wise error rate (FWER). In this context, we provide formulas for computation of sample size and for data analysis. Two approaches are discussed: an individual method based on a unionâintersection procedure and a global procedure, based on a multivariate model that can take into account adjustment variables. These methods are illustrated with simulation studies and applications. An R package known as rPowerSampleSize is also available
Assessment of the Compliance of Cystitis Management According to French Recommendations through the Analysis of Prescriptions Collected in Community Pharmacies
Urinary tract infections, especially cystitis, are common infections; they are the second most prevalent cause of antibiotic prescriptions in community pharmacies. To reduce antimicrobial resistance, guidelines are revised regularly. This study aims to assess compliance between prescriptions collected in community pharmacies and French cystitis guidelines. A treatment is considered compliant if the nature, dosage, and duration of the antibiotics are correct. Only women aged 18–65 years with a diagnosis of cystitis were eligible. The participation of 16 pharmacies resulted in 303 prescriptions. Most infections were classified as uncomplicated cystitis (79.2%), general practitioners were the prescribers in more than 9 out of 10 cases, and fosfomycin trometamol was the antibiotic dispensed for 1 in 2 women. An average compliance of 66% was observed, but with disparities according to the type of cystitis. Two-thirds of cases of uncomplicated cystitis and recurrent cystitis followed the recommendations, whereas only 15% of cystitis cases that were at risk of complication did so. The inclusion of a urine examination in uncomplicated cystitis decreased the overall compliance rate to 5.8%. These results show the essential role played by pharmacists; they are the last line of defence before dispensing antibiotics. They must know the recommendations in order to apply them
Validation of risk assessment models predicting venous thromboembolism in acutely ill medical inpatients: a cohort study.
BACKGROUND
As hospital-acquired venous thromboembolism (VTE) represents a frequent cause of preventable deaths in medical inpatients, identifying at risk patients requiring thromboprophylaxis is critical. We aimed to externally assess the Caprini, IMPROVE and Padua VTE risk scores and to compare their performance to advanced age as a stand-alone predictor.
METHODS
We performed a retrospective analysis of patients prospectively enrolled in the PREVENU trial. Patients aged 40-years and older, hospitalised for at least 2-days on a medical ward were consecutively enrolled and followed for three months. Critical ill patients were not recruited. Patients diagnosed with VTE within 48-hours from admission, or receiving full dose anticoagulant treatment or who underwent surgery were excluded. All suspected VTE and deaths occurring during the three-month follow-up were adjudicated by an independent committee. The three scores were retrospectively assessed. Body mass index, needed for the Padua and Caprini scores were missing in 44% of patients.
RESULTS
Among 14,910 eligible patients, 14,660 were evaluable, of which 1.8% experienced symptomatic VTE or sudden unexplained death during the three-month follow-up. The area under the receiver operating characteristic curves (AUC) were 0.60 (95%CI 0.57-0.63), 0.63 (95%CI 0.60-0.66) and 0.64 (95%CI 0.61-0.67) for Caprini, IMPROVE and Padua scores, respectively. None of these scores performed significantly better than advanced age as a single predictor (AUC 0.61, 95%CI 0.58-0.64).
CONCLUSION
In our study, Caprini, IMPROVE and Padua VTE risk scores have poor discriminative ability to identify not-critically ill medical inpatients at risk of VTE, and do not perform better than a risk evaluation based on patient's age alone
Bilan de la conciliation médicamenteuse dans un service de médecine interne
IntroductionLâinitiative medication reconciliation (MedâRec) a Ă©tĂ© crĂ©Ă©e par lâorganisation mondiale de la santĂ© en 2006 pour sĂ©curiser la prescription aux points de transition du parcours de soin. Dans notre service de mĂ©decine interne, la conciliation mĂ©dicamenteuse a dĂ©marrĂ© en 2014. OĂč en est-on en 2016 ?MatĂ©riels et mĂ©thodesUne Ă©tude rĂ©trospective a Ă©tĂ© rĂ©alisĂ©e dans le service durant 4 mois (05/09/16 au 31/12/16). Les patients inclus avaient plus de 75 ans et au moins 5 mĂ©dicaments. La conciliation Ă©tait rĂ©alisĂ©e par une Ă©tudiante en pharmacie affectĂ©e au service. Les donnĂ©es de conciliation (Ăąge, sexe, nombre de mĂ©dicaments Ă lâadmission, durĂ©e de la conciliation dâentrĂ©e et de sortie, divergences non intentionnelles (DNI), sources dâinformation des mĂ©dicaments) sont ont Ă©tĂ© recueillies sur fichier ExcelÂź puis analysĂ©es. A partir de ces donnĂ©es, nous avons calculĂ© les indicateurs de suivi MedâRec.RĂ©sultatsSur 60 patients Ă©ligibles, 53 ont Ă©tĂ© conciliĂ©s (entrĂ©e et sortie). La moyenne dâĂąge des patients Ă©tait de 84,4 ans, le sex-ratio Ă©tait de 0,66 et le nombre moyen de mĂ©dicament Ă lâentrĂ©e Ă©tait de 9,6. La durĂ©e de conciliation Ă lâentrĂ©e (50 minutes) Ă©tait plus longue quâĂ la sortie (30 minutes). On a observĂ© davantage de DNI Ă la sortie (18 Ă lâentrĂ©e contre 30 Ă la sortie). En moyenne, 3,4 sources ont Ă©tĂ© utilisĂ©es. DâaprĂšs les indicateurs MedâRec, 88,3 % patients Ă©ligibles ont Ă©tĂ© conciliĂ©s (I1), 45,3 % prĂ©sentaient au moins une DNI (I2) et 18,9 % ont Ă©tĂ© conciliĂ©s dans les 24 heures de lâadmission (MR1).DiscussionLes rĂ©sultats sont comparables Ă ceux dâautres Ă©tudes (projet MedâRec, centre hospitalier de Libourne). La durĂ©e de la conciliation Ă©tait de 50 minutes Ă lâentrĂ©e contre 30 minutes Ă la sortie, cette diffĂ©rence sâexplique par la rĂ©alisation dâentretiens Ă lâentrĂ©e. Lors du projet MedâRec, le temps nĂ©cessaire pour la conciliation Ă lâadmission Ă©tait compris entre 26 et 66 minutes. Lâoubli de prescription est la DNI la plus frĂ©quente. Le nombre de sources dâinformation utilisĂ©es est conforme aux recommandations de MedâRec (minimum 3 sources). En comparant les rĂ©sultats Ă ceux de lâĂ©tude menĂ©e dans le service de mĂ©decine interne du centre hospitalier de Libourne (I1 = 21,8 % ; I2 = 45,2 % ; MR1 = 20,6 %) : davantage de patients Ă©ligibles ont Ă©tĂ© conciliĂ©s Ă Angers (I1), autant de patients conciliĂ©s ont au moins une DNI (I2) et moins de patients ont Ă©tĂ© conciliĂ©s dans les 24 heures de lâadmission (MR1) (p = 4,8 Ă 10â6). Dans le projet MedâRec la valeur du score MR1 dans les 9 Ă©tablissements varie de 2,6 % Ă 64,9 % en 2014. Des difficultĂ©s ont Ă©tĂ© rencontrĂ©es, notamment avec le logiciel (lent, peu pratique, bugs) mais aussi dans lâinteraction avec les autres membres de lâĂ©quipe, liĂ©es notamment au manque de disponibilitĂ© des internes en mĂ©decine, Ă lâabsence dâinterne en pharmacie ou de pharmacien dans le service.ConclusionLes rĂ©sultats correspondent Ă ceux de la littĂ©rature. Cependant, le nombre de patients conciliĂ©s dans les 24 heures de lâadmission (MR1) est faible, cet indicateur est Ă amĂ©liorer notamment en augmentant les moyens humains. On notera que des amĂ©liorations sont en cours telles que la modification du formulaire de saisie, lâaffectation dâun interne en pharmacie dans le service, la sensibilisation des internes en mĂ©decine au travail de conciliation et la mise en place dâun courrier de sortie adressĂ© aux mĂ©decins gĂ©nĂ©ralistes et aux pharmaciens dâofficine.</p
Les modÚles de risque de maladie thromboembolique veineuse acquise chez les patients hospitalisés en secteur médical
IntroductionLa maladie thromboembolique veineuse (MTEV) acquise Ă lâhĂŽpital reprĂ©sente une part importante de morbi-mortalitĂ© Ă©vitable chez les patients hospitalisĂ©s en secteur mĂ©dical. Dâun autre cĂŽtĂ©, la thromboprophylaxie anticoagulante expose les patients Ă un risque hĂ©morragique et majore les dĂ©penses de santĂ©. Lâidentification des patients hospitalisĂ©s Ă risque de MTEV est en cela cruciale. Lâobjectif de cette Ă©tude est dâĂ©valuer de maniĂšre externe, les performances de 3 modĂšles de risque (score de Padua, Carpini et Improve) et de les comparer aux performances de lâĂąge pris isolĂ©ment.Patients et mĂ©thodesIl sâagit dâune Ă©tude rĂ©trospective sur une base de patients inclus prospectivement dans une Ă©tude randomisĂ©e en cluster sans intervention directe sur le patient. Les patients de plus de 40 ans, hospitalisĂ© depuis les urgences en secteur mĂ©dical plus de 48 h ont consĂ©cutivement Ă©tĂ© inclus et suivi Ă 3 mois. Les patients chez qui un diagnostic de MTEV avait Ă©tĂ© portĂ© dans les 48 premiĂšres heures dâhospitalisation, ou ayant reçu un traitement anticoagulant pour une raison autre que la MTEV, ou encore ayant subi une chirurgie sous anesthĂ©sie gĂ©nĂ©rale ont Ă©tĂ© exclus. Les modĂšles de risques ont Ă©tĂ© calculĂ©s Ă posteriori. La rĂ©duction de mobilitĂ© a Ă©tĂ© dĂ©duite de la durĂ©e dâhospitalisation moins un jour. Le critĂšre de jugement principal Ă©tait la survenue dâun Ă©pisode thrombotique veineux symptomatique ou le dĂ©cĂšs brutal inexpliquĂ© adjudiquĂ© Ă 3 mois.RĂ©sultatsParmi les 14 910 patient Ă©ligibles, 14 659 (98,3) Ă©taient Ă©valuables. 263 (1,8 %) ont prĂ©sentĂ© une MTEV symptomatique ou un dĂ©cĂšs brutal inexpliquĂ©. Les aires sous la courbe ROC Ă©taient respectivement 0,60 [0,57â0,63], 0,62 [0,58â0,64] et 0,62 [0,59â0,65] pour les scores Caprini, Improve et Padua. Aucun de ces modĂšles nâa montrĂ© de performances supĂ©rieures Ă lâĂąge pris isolĂ©ment (AUC 0,61 [0,58â0,64]). Ces rĂ©sultats Ă©taient similaires ne considĂ©rant que les Ă©vĂšnements symptomatiques non fatals : (0,62 [0,58â0,66], 0,62 [0,58â0,66], 0,63 [0,59â0,67] et 0,58 [0,54â0,62]) ; ou dans le sous-groupe de patients ne recevant pas de thromboprophylaxie anticoagulante : 0,62 [0,58â0,67], 0,64 [0,60â0,68], 0,64 [0,59â0,68] et 0,66 [0,62â0,70] pour le score Caprini, Improve, Padua et lâĂąge, respectivement.ConclusionLes scores de Padua, Caprini et Improve ont des capacitĂ©s de discrimination faible vis-Ă -vis de la MTEV acquise Ă lâhĂŽpital, similaire Ă une Ă©valuation se basant uniquement sur lâĂąge. Les meilleurs modĂšles de risque sont nĂ©cessaires.</p
Regular Use of VKA Prior to COVID-19 Associated with Lower 7-Day Survival in Hospitalized Frail Elderly COVID-19 Patients: The GERIA-COVID Cohort Study
International audienceBackground : Vitamin K concentrations are inversely associated with the clinical severity of COVID-19. The objective of this cohort study was to determine whether the regular use of vitamin K antagonist (VKA) prior to COVID-19 was associated with short-term mortality in frail older adults hospitalized for COVID-19. Methods : Eighty-two patients consecutively hospitalized for COVID-19 in a geriatric acute care unit were included. The association of the regular use of VKA prior to COVID-19 with survival after 7 days of COVID-19 was examined using a propensity-score-weighted Cox proportional-hazards model accounting for age, sex, severe undernutrition, diabetes mellitus, hypertension, prior myocardial infarction, congestive heart failure, prior stroke and/or transient ischemic attack, CHA2DS2-VASc score, HAS-BLED score, and eGFR. Results : Among 82 patients (mean ± SD age 88.8 ± 4.5 years; 48% women), 73 survived COVID-19 at day 7 while 9 died. There was no between-group difference at baseline, despite a trend for more frequent use of VKA in those who did not survive on day 7 (33.3% versus 8.2%, p = 0.056). While considering âusing no VKAâ as the reference (hazard ratio (HR) = 1), the HR for 7-day mortality in those regularly using VKA was 5.68 [95% CI: 1.17; 27.53]. Consistently, COVID-19 patients using VKA on a regular basis had shorter survival times than the others (p = 0.031). Conclusions : Regular use of VKA was associated with increased mortality at day 7 in hospitalized frail elderly patients with COVID-19
- âŠ