Toxicity Associated with Stavudine Dose Reduction from 40 to 30 mg in First-Line Antiretroviral Therapy

To compare the incidence and timing of toxicity associated with the use of a reduced dose of stavudine from 40 to 30 mg in first-line antiretroviral therapy (ART) for HIV treatment and to investigate associated risk factors

Optimism Bias Correction in Omics Studies with Big Data: Assessment of Penalized Methods on Simulated Data

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Mortalité liée à la SEP et aux autres causes de décès chez les patients SEP [P29.32]

Special issue : Journées de Neurologie de Langue Française 2023International audienceIntroductionPour une maladie chronique à évolution longue, telle que la sclérose en plaques (SEP), il est difficile de déterminer si la maladie est à la cause du décès.ObjectifsProposer une approche pour estimer la probabilité de décès par la SEP ainsi que la probabilité de décès par les autres causes sans recourir aux causes de décès.MéthodesL’approche proposée repose sur le concept de « mortalité en excès », qui est obtenue en confrontant la mortalité « toutes causes » des patients SEP à la mortalité attendue en population générale. Les données proviennent de 18 centres experts participant à l’OFSEP. Les probabilités ont été estimées selon le phénotype initial de la SEP (rémittent : R-MS, progressif : PPMS) pour les hommes et les femmes après 30 ans de maladie.RésultatsL’analyse portait sur 33 005 patients R-MS et 4519 PPMS (71 % de femmes au total, décès après 30 ans de maladie R-MS : 1522 (4,6 %), PPMS : 635 (14,0 %)). La probabilité de décéder de la SEP variait de 7,5 à 24,0 % chez les R-MS selon le sexe et l’âge de début, et de 25,4 à 36,8 % chez les PPMS. La probabilité de décéder d’autres causes variait de 2,8 à 42,8 % chez les deux phénotypes, soulignant que les autres causes contribuent, elles aussi, de façon importante au risque de décès.DiscussionL’approche proposée présente un double avantage : d’une part, elle évite de recourir aux causes de décès contenus dans les certificats de décès, dont la qualité n’est pas toujours optimale ; d’autre part, elle est plus pertinente au plan conceptuel, car elle aide à définir ce que décéder de la SEP signifie et évite d’avoir à déterminer pour chaque sujet si le décès est (directement ou indirectement) causé par la maladie.ConclusionJusqu’à près d’un quart des patients R-MS et un tiers des patients PPMS décèdent de leur SEP dans les 30 ans après son début. La part des autres causes de décès rappelle l’importance du management des autres pathologies non liées à la SEP, et le renforcement de la prévention

Improving survival in end-stage renal disease: A case study

International audienceBackground: With the increase of life expectancy, *On behalf of the REIN registry. end-stage renal disease (ESRD) is affecting a growing number of people. Simultaneously, renal replacement therapies (RRTs) have considerably improved patient survival. We investigated the way current RRT practices would affect patients' survival. Methods: We used a multi-state model to represent the transitions between RRTs and the transition to death. The concept of “crude probability of death” combined with this model allowed estimating the proportions of ESRD-related and ESRD-unrelated deaths. Estimating the ESRD-related death rate requires comparing the mortality rate between ESRD patients and the general population. Predicting patients' courses through RRTs and Death states could be obtained by solving a system of Kolmogorov differential equations. The impact of practice on patient survival was quantified using the restricted mean survival time (RMST) which was compared with that of healthy subjects with same characteristics. Results: The crude probability of ESRD-unrelated death was nearly zero in the youngest patients (18–45 years) but was a sizeable part of deaths in the oldest (≥70 years). Moreover, in the oldest patients, the proportion of expected death was higher in patient without vs. with diabetes because the former live older. In men aged 75 years at first RRT, the predicted RMSTs in patients with and without diabetes were, respectively, 61% and 69% those of comparable healthy men. Conclusion: Using the concept of “crude probability of death” with multi-state models is feasible and useful to assess the relative benefits of various treatments in ESRD and help patient long-term management

Trends in probabilities of death owing to cancer and owing to other causes in patients with colon cancer

IF 2.014 (2017)International audienceBACKGROUND: It is of interest to both the clinicians and patients to estimate the probability of death owing to cancer in the presence of other causes as time elapses since diagnosis. The objective of this study was to depict for patients diagnosed with colon cancer between 1990 and 2010 in France, the probability of surviving up to 10 years after diagnosis and to disentangle the probability of death owing to cancer from that of death owing to other causes.PATIENTS AND METHODS: Individuals with cancer were described, up to 10 years after diagnosis, as belonging to one of three categories: those who died owing to a cause related to cancer, those who died owing to another cause and those who survived. Net survival, crude probabilities of death related to colon cancer, death related to another cause and survival were estimated by modeling excess mortality hazard.RESULTS: In women of all ages, 5 and 10-year net survival improved over calendar time. The 10-year probability of survival decreased when age increased in both sexes. It was higher in women than in men, and this difference increased with age. Crude probabilities of death related to colon cancer decreased between 1990 and 2010 for men and women, although this was not observed in the eldest men.CONCLUSION: Crude probability of death related to colon cancer is an important indicator for patients and health policy makers. Results of cancer screening should be faced to trends in probability of death related to colorectal cancer

Toxicity Associated with Stavudine Dose Reduction from 40 to 30 mg in First-Line Antiretroviral Therapy , for the AIDS Working Group of Mé decins Sans Frontiè res

Abstract Background: To compare the incidence and timing of toxicity associated with the use of a reduced dose of stavudine from 40 to 30 mg in first-line antiretroviral therapy (ART) for HIV treatment and to investigate associated risk factors

Diverging incidence trends of oral tongue cancer compared to other head and neck cancers in young adults in France

International audienceAbstract While head and neck cancer incidence decreased worldwide due to reduced tobacco and alcohol consumption, oral tongue cancer (OTC) incidence has been reported to be increasing in several countries. Our study examines the incidence trends of OTC in France from 1990 to 2018, globally and by age; and compares the incidence trends with the evolution of the incidence of other human papilloma virus‐unrelated head and neck squamous cell carcinoma, that is, cancers of the remaining subsites of the oral cavity (RSOCC) and laryngeal cancers for the period 1990 to 2018. World age‐standardized incidence rates of oral tongue cancers ( C02 ), cancers of the remaining subsites of the oral cavity (RSOCC, C03‐06 ) and laryngeal cancers ( C32 ) were estimated using the French National Network of Cancer Registries for the period 1990 to 2018. Trends in national incidence rates were estimated from a mixed‐effect Poisson model including age and year effects using penalized splines and a district‐random effect. In women aged 30 and 40, a significant increase in OTC incidence was observed, while ROSCC showed a nonsignificant incidence decrease. In young men aged 25, a marginally significant increase of OTC incidence years was observed, while incidence rates of RSOCC significantly declined. The results suggest a tendency towards diverging incidence trends for OTC compared to RSOCC and laryngeal cancer in young adults. The observed trends may reflect changes in underlying exposures or emerging exposures not yet identified, and stress the need to further investigate the etiology of oral tongue cancers

Restricted mean survival time over 15 years for patients starting renal replacement therapy

International audienceBackground:The restricted mean survival time (RMST) estimates life expectancy up to a given time horizon and can thus express the impact of a disease. The aim of this study was to estimate the 15-year RMST of a hypothetical cohort of incident patients starting renal replacement therapy (RRT), according to their age, gender and diabetes status, and to compare it with the expected RMST of the general population.Methods:Using data from 67 258 adult patients in the French Renal Epidemiology and Information Network (REIN) registry, we estimated the RMST of a hypothetical patient cohort (and its subgroups) for the first 15 years after starting RRT (cRMST) and used the general population mortality tables to estimate the expected RMST (pRMST). Results were expressed in three different ways: the cRMST, which calculates the years of life gained under the hypothesis of 100% death without RRT treatment, the difference between the pRMST and the cRMST (the years lost), and a ratio expressing the percentage reduction of the expected RMST: (pRMST - cRMST)/pRMST.Results:Over their first 15 years of RRT, the RMST of end-stage renal disease (ESRD) patients decreased with age, ranging from 14.3 years in patients without diabetes aged 18 years at ESRD to 1.8 years for those aged 90 years, and from 12.7 to 1.6 years, respectively, for those with diabetes; expected RMST varied from 15.0 to 4.1 years between 18 and 90 years. The number of years lost in all subgroups followed a bell curve that was highest for patients aged 70 years. After the age of 55 years in patients with and 70 years in patients without diabetes, the reduction of the expected RMST was >50%.Conclusion:While neither a clinician nor a survival curve can predict with absolute certainty how long a patient will live, providing estimates on years gained or lost, or percentage reduction of expected RMST, may improve the accuracy of the prognostic estimates that influence clinical decisions and information given to patients

Protocol for a prospective quasi-experimental study on SARS-CoV-2 transmission during outdoor sports events in France: the COVID-ESO project

International audienceIntroduction The spread of SARS-CoV-2 and its variants in the community remains a major concern despite the application of control measures including the banning of mass sporting events. The circulation of SARS-CoV-2 within the general population, and potentially within the population practicing outdoor sports activities, suggests contexts conducive to the transmission of the virus. We hypothesise that outdoor sports events (OSEs) do not present a higher risk of SARS-CoV-2 contamination. The objective of the COVID-ESO project is to measure if individuals participating in OSE present a similar risk of SARS-CoV-2 transmission compared with individuals not participating in OSE, in France. Methods and analysis The COVID-ESO project is a prospective, quasi-experimental study to be conducted in volunteer individuals likely to participate in OSE. Six events are targeted across France to be included. Three sport trials will be eligible for the study: running, cycling and triathlon. Each individual participating in the OSE will choose one of his or her usual training partner to be eligible for the unexposed control group. Individuals will be matched (1:1) on age, sex and the district of residence. Individuals assigned to the exposed group will participate in the OSE, whereas individuals assigned to the unexposed group will not participate in the OSE. All individuals will be asked to perform saliva tests on the day of the event and 7 days after the event. A questionnaire including sociodemographic, clinical and exposure data to SARS-CoV-2 will be sent by email for both groups on the day before the event and 7 days after the event. Differences in SARS-CoV-2 infection rates between the exposed versus the unexposed group will be analysed by fitting a conditional logistic regression model, adjusted for potential confounders. As the sport events unfold, data will be analyzed by performing sequential meta-analyses. Ethics and dissemination This protocol has been approved by the ethical committee. Ethical approval has been obtained for the Clinical research and committee of South West of France, 10 June 2021. COMITE DE PROTECTION DES PERSONNES DU SUD-OUEST ET OUTRE-MER 4 under the reference number 21.03.23.71737/CPP2021-04-045 a COVID/2021-A00845-36. Findings generated from this study will be shared to national health and sport authorities

Multidimensional penalized splines for survival models: illustration for net survival trend analyses

International audienceAbstract Background In descriptive epidemiology, there are strong similarities between incidence and survival analyses. Because of the success of multidimensional penalized splines (MPSs) in incidence analysis, we propose in this pedagogical paper to show that MPSs are also very suitable for survival or net survival studies. Methods The use of MPSs is illustrated in cancer epidemiology in the context of survival trends studies that require specific statistical modelling. We focus on two examples (cervical and colon cancers) using survival data from the French cancer registries (cases 1990–2015). The dynamic of the excess mortality hazard according to time since diagnosis was modelled using an MPS of time since diagnosis, age at diagnosis and year of diagnosis. Multidimensional splines bring the flexibility necessary to capture any trend patterns while penalization ensures selecting only the complexities necessary to describe the data. Results For cervical cancer, the dynamic of the excess mortality hazard changed with the year of diagnosis in opposite ways according to age: this led to a net survival that improved in young women and worsened in older women. For colon cancer, regardless of age, excess mortality decreases with the year of diagnosis but this only concerns mortality at the start of follow-up. Conclusions MPSs make it possible to describe the dynamic of the mortality hazard and how this dynamic changes with the year of diagnosis, or more generally with any covariates of interest: this gives essential epidemiological insights for interpreting results. We use the R package survPen to do this type of analysis