Effects of Age and Disease Duration on Excess Mortality in Patients With Multiple Sclerosis From a French Nationwide Cohort

International audienceObjective - To determine the effects of current age and disease duration on excess mortality in multiple sclerosis (MS), we describe the dynamics of excess death rates over these 2 time scales and study the effect of age at MS clinical onset on these dynamics, separately in each initial phenotype. Methods - We used data from 18 French MS expert centers participating in the Observatoire Français de la Sclérose en Plaques. Patients with MS living in metropolitan France and having a clinical onset between 1960 and 2014 were included. Vital status was updated on January 1, 2016. For each MS phenotype separately (relapsing onset [RMS] or primary progressive [PPMS]), we used an innovative statistical method to model the logarithm of excess death rates by a multidimensional penalized spline of age and disease duration. Results - Among 37,524 patients (71% women, mean age at MS onset ± SD 33.0 ± 10.6 years), 2,883 (7.7%) deaths were observed and 7.8% of patients were lost to follow-up. For patients with RMS, there was no excess mortality during the first 10 years after disease onset; afterwards, whatever the age at onset, excess death rates increased with current age. From current age 70, the excess death rate values converged and became identical whatever the age at disease onset, which means that disease duration had no more effect. Excess death rates were higher in men, with an excess hazard ratio of 1.46 (95% confidence interval 1.25-1.70). In contrast, in patients with PPMS, excess death rates rapidly increased from disease onset, and were associated with age at onset, but not with sex. Conclusions - In RMS, current age has a stronger effect on MS mortality than disease duration, while their respective effects are not clear in PPMS

Estimating infra-national and national thyroid cancer incidence in France from cancer registries data and national hospital discharge database.

International audienceOBJECTIVE: As in many countries, cancer registries cover only part of the population in France. Incidence/mortality ratio observed in registries is usually extrapolated to produce national estimates of cancer incidence. District-level estimates are not currently available. For cancer sites such as thyroid, the incidence/mortality ratio widely varies between districts, and alternative indicators must be explored. This study aims to produce national and district-level estimations of thyroid cancer incidence in France, using the ratio between incidence and hospital-based incidence. METHODS: Analyses concerned population living in France and aged over 20, for the period 1998-2000. For each sex, number of incident cases were analysed according to number of surgery admissions for thyroid cancer (Poisson model) in the districts covered by a registry. Age was included in the model as fixed effect and district as random effect. The model's ability to predict incidence was tested through cross-validation. The model was then extrapolated to produce national incidence estimations, and for women, district-level estimations. RESULTS: The national estimations of incidence rate age-standardised on the world population were 3.1 [95% prediction interval: 2.8-3.4] for men and 10.6 [9.8-11.4] for women, corresponding respectively to 1,148 [1,042-1,264] and 4,104 [3,817-4,413] annual new cases. For women, district-level incidence rates presented wide geographical variations, ranging broadly from 5 to 20 per 100,000. These estimations were quite imprecise, but their imprecision was smaller than the extent of geographical disparities. CONCLUSION: National incidence estimations obtained are relatively precise. District-level estimations in women are imprecise and should be treated carefully. They are informative though regarding the extent of geographical disparities. The approach can be useful to improve national incidence estimates and to produce district-level estimates for cancer sites presenting a high variability of the incidence/mortality ratio

Int J Epidemiol

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

Comparison of Two Methods for Estimating MS-Related Mortality: The Excess Mortality vs. the Cause-Specific Frameworks

Background and objective: Determining whether multiple sclerosis (MS) causes death is challenging. Our objective was to contrast two frameworks to estimate probabilities of death attributed to MS (PMS) and to other causes (POther): the cause-specific framework (CSF) which requires the causes of death and the excess mortality framework (EMF) which does not.Methods: We used data from the Observatoire Français de la Sclérose en Plaques (OFSEP, n=37,524) and from a comparative subset where causes of death was available (4,004 women with relapsing onset (R-MS)). In CSF, the probabilities were estimated using Aalen-Johansen method. In EMF, they were estimated from the excess mortality hazard, which is the additional mortality among MS patients as compared to the expected mortality in the matched general population. PMS were estimated at 30 years of follow-up, i) with both frameworks in the comparative subset, by age group at onset, and ii) with EMF only in the OFSEP population, by initial phenotype, sex and age at onset.Results: In the comparative subset, the estimated 30-year PMS were greater using EMF than CSF: respectively 10.9% [95%CI 8.3-13.6] vs 8.7% [6.4-11.8] among the youngest, and 20.4% [11.3-29.5] vs 16.2% [8.7-30.2] for the oldest groups. In the CSF, probabilities of death from unknown causes ranged from 1.5% [0.7-3.0] to 6.4% [2.5-16.4], and even after their reallocation, PMS remained lower with CSF than with EMF. The estimated probabilities of being alive were close using the two frameworks and the estimated POther (EMF vs CSF) were 2.6% [2.5-2.6] vs 2.1% [1.2-3.9] and 18.1% [16.9-19.3] vs 26.4% [16.5-42.2] respectively for the youngest and oldest groups. In the OFSEP population, the estimated 30-year PMS ranged from 7.5 [6.4-8.7] to 24.0% [19.1-28.9] in R-MS patients and from 25.4 [21.1-29.7] to 36.8% [28.3-45.3] in primary progressive patients, depending on sex and age.Discussion: EMF has the strong advantage of not requiring death certificates, which quality is sub-optimal. Conceptually, it also appears more relevant as it avoids having to state, for each individual, if death was directly or indirectly caused by MS or if it would have occurred anyway, which is especially difficult in such chronic diseases