Mortality Associated with Neurofibromatosis 1: A Cohort Study of 1895 Patients in 1980-2006 in France

<p>Abstract</p> <p>Background</p> <p>Neurofibromatosis 1 (NF1), a common autosomal dominant disorder, was shown in one study to be associated with a 15-year decrease in life expectancy. However, data on mortality in NF1 are limited. Our aim was to evaluate mortality in a large retrospective cohort of NF1 patients seen in France between 1980 and 2006.</p> <p>Methods</p> <p>Consecutive NF1 patients referred to the National French Referral Center for Neurofibromatoses were included. The standardized mortality ratio (SMR) with its 95% confidence interval (CI) was calculated as the ratio of observed over expected numbers of deaths. We studied factors associated with death and causes of death.</p> <p>Results</p> <p>Between 1980 and 2006, 1895 NF1 patients were seen. Median follow-up was 6.8 years (range, 0.4-20.6). Vital status was available for 1226 (65%) patients, of whom 1159 (94.5%) survived and 67 (5.5%) died. Overall mortality was significantly increased in the NF1 cohort (SMR, 2.02; CI, 1.6-2.6; <it>P </it>< 10^-4). The excess mortality occurred among patients aged 10 to 20 years (SMR, 5.2; CI, 2.6-9.3; <it>P </it>< 10^-4) and 20 to 40 years (SMR, 4.1; 2.8-5.8; <it>P </it>< 10^-4). Significant excess mortality was found in both males and females. In the 10-20 year age group, females had a significant increase in mortality compared to males (SMR, 12.6; CI, 5.7-23.9; and SMR, 1.8; CI, 0.2-6.4; respectively). The cause of death was available for 58 (86.6%) patients; malignant nerve sheath tumor was the main cause of death (60%).</p> <p>Conclusions</p> <p>We found significantly increased SMRs indicating excess mortality in NF1 patients compared to the general population. The definitive diagnosis of NF1 in all patients is a strength of our study, and the high rate of death related to malignant transformation is consistent with previous work. The retrospective design and hospital-based recruitment are limitations of our study. Mortality was significantly increased in NF1 patients aged 10 to 40 years and tended to be higher in females than in males.</p

Impact of STROBE Statement Publication on Quality of Observational Study Reporting: Interrupted Time Series versus Before-After Analysis

Background:In uncontrolled before-after studies, CONSORT was shown to improve the reporting of randomised trials. Before-after studies ignore underlying secular trends and may overestimate the impact of interventions. Our aim was to assess the impact of the 2007 STROBE statement publication on the quality of observational study reporting, using both uncontrolled before-after analyses and interrupted time series.Methods:For this quasi-experimental study, original articles reporting cohort, case-control, and cross-sectional studies published between 2004 and 2010 in the four dermatological journals having the highest 5-year impact factors (≥4) were selected. We compared the proportions of STROBE items (STROBE score) adequately reported in each article during three periods, two pre STROBE period (2004-2005 and 2006-2007) and one post STROBE period (2008-2010). Segmented regression analysis of interrupted time series was also performed.Results:Of the 456 included articles, 187 (41%) reported cohort studies, 166 (36.4%) cross-sectional studies, and 103 (22.6%) case-control studies. The median STROBE score was 57% (range, 18%-98%). Before-after analysis evidenced significant STROBE score increases between the two pre-STROBE periods and between the earliest pre-STROBE period and the post-STROBE period (median score2004-0548% versus median score2008-1058%, p<0.001) but not between the immediate pre-STROBE period and the post-STROBE period (median score2006-0758% versus median score2008-1058%, p = 0.42). In the pre STROBE period, the six-monthly mean STROBE score increased significantly, by 1.19% per six-month period (absolute increase 95%CI, 0.26% to 2.11%, p = 0.016). By segmented analysis, no significant changes in STROBE score trends occurred (-0.40%; 95%CI, -2.20 to 1.41; p = 0.64) in the post STROBE statement publication.Interpretation:The quality of reports increased over time but was not affected by STROBE. Our findings raise concerns about the relevance of uncontrolled before-after analysis for estimating the impact of guidelines

Nfs1core, un score prédictif de la masse tumorale interne au cours de la neurofibromatose 1

Introduction. Une diminution de l espérance de vie d une quinzaine d années est observée chez les sujets atteints de neurofibromatose 1 (NF1). Les neurofibromes internes, notamment paravertébraux, sont associés à une morbi-mortalité accrue liée à un risque de transformation maligne ou de compression des organes voisins. Notre objectif était donc d élaborer et de valider un score prédictif de la masse tumorale interne. Malades et méthodes. L échantillon de construction comprenait 208 patients, l échantillon de validation 191. Un score de risque a été développé par des modèles de régression logistique. Les performances du score (adéquation et discrimination) ont ensuite été évaluées. Résultats. Echantillon de construction: 129 femmes et 90 hommes âgés de 41 ans (+-13) ont été analysés; 46 avaient des neurofibromes internes (22.1%). L âge <= 30 ans (OR=3.1 ; 1.4-6.8), l absence de neurofibromes cutanés (OR=2.6 ; 0.9-7.5), moins de 6 taches café-au-lait (OR=2.0 ; 0.9-4.6), au moins 2 neurofibromes sous-cutanés (OR=4.7 ; 2.1-10.5) étaient indépendamment associés à la masse tumorale interne. Le score a été obtenu à partir des coefficients pondérés et arrondis du modèle (score=11.8 +- 10,0, extrêmes de 0 à 40). Le risque de masse tumorale interne a été estimé à partir de l équation suivante : p = exp (-2.93 + 0.11xScore) / (1 + exp (-2.93 + 0,11xScore)). Les statistiques d adéquation (test C d Hosmer-Lemeshow =12.3 avec 8 ddl, p=0.20) et la capacité discriminante du score (indice C de Harrell = 0.73), évaluées sur le deuxième échantillon, étaient satisfaisantes. Discussion. Notre étude a permis d élaborer un score, le NF1Score, prédictif de la masse tumorale interne au cours de la NF1, et ainsi de cibler cliniquement les malades à risque de complications. Selon l objectif (forte sensibilité ou forte spécificité) différents seuils pourront être considérés.Neurofibromatosis-1 is associated with a 15-year decrease in life expectancy. Internal neurofibromas are associated with increased morbidity and mortality via malignant transformation and compression of neighboring organs. Our purpose was to develop and to validate a clinical score for predicting internal neurofibromas in adults. The development sample comprised 208 patients and the validation sample 191 patients. The score was developed using logistic regression. Discrimination and calibration of the model were evaluated. Four variables were independently associated with internal neurofibromas: at least two subcutaneous neurofibromas (OR=4.7, [2.1-10.5]), age <=30 years (OR=3.1, [1.4-6.8]), absence of cutaneous neurofibromas (OR=2.6, [0.9-7.5]), and fewer than six café-au-lait spots (OR=2, [0.9-4.6]). The score computed by linear combination of the rounded coefficients of these four variables ranged from 0 to 40 (mean, 12.8 10.8). The probability of internal neurofibromas was computed as exp (-2.93 + 0.11*Score)/exp (1 + (-2.93 + 0.11*Score)). Probabilities agreed well with observed frequencies indicating good calibration and discrimination was adequate (area under receiver-operating curve, 0.75) in both data sets. The presence of internal neurofibromas can be accurately predicted using a simple clinical score. Further work will establish the score threshold that identifies patients at high risk for complications.PARIS12-CRETEIL BU Médecine (940282101) / SudocSudocFranceF

A Markov chain approach for ranking treatments in network meta‐analysis

International audienceWhen interpreting the relative effects from a network meta-analysis (NMA), researchers are usually aware of the potential limitations that may render the results for some comparisons less useful or meaningless. In the presence of sufficient and appropriate data, some of these limitations (eg, risk of bias, small-study effects, publication bias) can be taken into account in the statistical analysis. Very often, though, the necessary data for applying these methods are missing and data limitations cannot be formally integrated into ranking. In addition, there are other important characteristics of the treatment comparisons that cannot be addressed within a statistical model but only through qualitative judgments; for example, the relevance of data to the research question, the plausibility of the assumptions, and so on. Here, we propose a new measure for treatment ranking called the Probability of Selecting a Treatment to Recommend (POST-R). We suggest that the order of treatments should represent the process of considering treatments for selection in clinical practice and we assign to each treatment a probability of being selected. This process can be considered as a Markov chain model that allows the end-users of NMA to select the most appropriate treatments based not only on the NMA results but also to information external to the NMA. In this way, we obtain rankings that can inform decision-making more efficiently as they represent not only the relative effects but also their potential limitations. We illustrate our approach using a NMA comparing treatments for chronic plaque psoriasis and we provide the Stata commands

TNF-alpha inhibitors biosimilar use in France: a nationwide population-based study using the French National Health Data System

International audienceAbstract TNF-alpha inhibitors have revolutionized the therapeutic care in chronic inflammatory diseases. Several biosimilar products were commercialized at their patent expiry, substantially decreasing the cost of treatment. This longitudinal descriptive study aimed at assessing infliximab, etanercept and adalimumab biosimilar penetration rates using data of the French National Health Data System. A total of 207,118 new or prevalent users from the date of first biosimilar commercialization in France (respectively January 2015, May 2016 and October 2018) were included in the study and followed until September 30, 2021. Biosimilars represented respectively 78%, 46% and 53% of the overall initiations, and 94%, 66% and 60% last year’s initiations. A total of 46%, 19% and 17% of originator product prevalent users switched for a biosimilar during the follow-up. Biosimilar penetration rate was much higher for infliximab than for its counterparts, due to its hospital delivery modality. Biosimilar initiation and originator-to-biosimilar switch tended to be observed more in rheumatology than in the other specialties. Biosimilar use was mostly consistent across patient socio-demographic characteristics. Biosimilar initiation rate increased rapidly from their market arrival and originator-to-biosimilar switch rate remained moderate, highlighting the need and usefulness of political action and biosimilar use tracking

Epidemiologic study of patients with psoriatic arthritis in a real-world analysis: a cohort study of the French health insurance database

International audienceAbstract Objective PsA is a chronic inflammatory arthritis with heterogeneous disease manifestations. Data on the prevalence of PsA in adults differ widely depending on the study and the country. This study aimed to estimate the prevalence and incidence of PsA in France, characterize comorbidities associated to PsA and identify prescribed treatments. Methods This nationwide cohort study involved the administrative healthcare database (Système National des Données de Santé) of the French health insurance scheme linked to the national hospital discharge database. All adults with PsA registered in the database and identified with a specific International Classification of Diseases, 10th revision code (M07) were included between 1 January 2015 and 31 December 2018. Results A total of 63 598 patients were identified as having PsA [55.9 years (s.d. 14.4), 45.6% males]. The prevalence of PsA was estimated at 0.1% and the incidence at 8.4 per 100 000 person-years in the general population. The most common comorbidities were hypertension, diabetes, chronic obstructive pulmonary disease and dyslipidaemia. The prevalence of treatment with conventional synthetic DMARDs (csDMARDs), biological or biosimilar DMARDs (b/bsDMARDs) and apremilast for PsA was 25.9% (16 453), 30.4% (19 325) and 3.5% (2231), respectively. Overall, 8966 (14.1%) patients were new users of csDMARDs, 8311 (13.1%) were new users of b/bsDMARDs and 1529 (7.4%) were new users of apremilast. The most common first-line csDMARD was methotrexate (70.9%) and the most frequent first-line b/bsDMARD was adalimumab (30.8%). Conclusion Our results lead to a better understanding of PsA. Results were similar to those from other published studies using other data sources, which highlights the reliability of insurance databases for studies

Twenty Percent of Secondary Publications of Randomized Controlled Trials of Drugs Did Not Provide New Results Relative to the Primary Publication

International audienceOBJECTIVE: The objective of the study was to estimate the proportion of secondary publications of randomized controlled trials (RCTs) that provide new results relative to the primary publication. STUDY DESIGN AND SETTING: We searched for RCTs published in 2014 in the five medical journals with the highest impact factors. Secondary publications for each primary publication were then identified by their registration number. The main outcome measure was the proportion of secondary publications providing results already reported in the primary publication and/or nonprespecified analyses and/or a meta-analysis pooling results of studies not identified by systematic review. RESULTS: A total of 144 primary publications were identified; 94 (65%) had at least one secondary publication within 30~months after a primary publication. Of the secondary publications, 20% reported only results present in the primary publication, and 35% reported results not prespecified or pooled analyses not based on a systematic review. Factors associated with having at least one secondary publication were a large number of randomized trial participants (odds ratio [95% confidence interval]: 3.2 [1.1-9.3] for trials with >1,000 vs.~≤q500 participants), investigating a biologic product (4.8 [1.4-16.3] vs. a nonbiologic product) and cardiologic field vs. other fields (7.6 [1.46-39.8]). CONCLUSION: Most drug RCTs with results published in high-impact-factor journals had secondary publications. More than half of these secondary publications provided results already reported in the primary publication or results of nonprespecified analyses

Typology of the primary outcome construction in dermatology: a systematic review of published randomized controlled trials

International audienceThe primary outcome is a major component of a randomized clinical trial (RCT) and several types of outcome can be chosen in a given disease. We systematically reviewed RCTs on nonneoplastic dermatological diseases published in 2009 and referenced in Medline, and described how the main outcome was defined and constructed. We assessed whether those characteristics were associated with a clearly defined primary outcome and whether they were associated with a significant statistical test for the primary outcome. Outcome construction variables were the three "VIP" questions (V denoting Variable: binary vs. quantitative variable; I denoting Item: data collection based on multiple vs. single item(s); and P denoting time Points: outcome assessment based on a "final time point" vs. "final and initial time points"). Among 122 RCTs, 32% did not have a clearly defined primary outcome. In multivariable analyses, a clearly defined primary outcome was associated with a binary variable (odds ratio (OR)=6.7; 2.5-17.7) and the composite variable "both blinding/placebo-controlled arm" (OR=4.5; 1.8-11.2); a significant statistical test was associated with a "final time point"-based outcome construction (OR=2.6; 1.2-5.5). Our study points to areas of improvement related to the definition and construction of the primary outcome in RCTs in dermatology