Résumé
The Covid-19 pandemic outbreak was followed by a huge amount of modelling studies in order to rapidly gain insights to implement the best public health policies. Most of these compartmental models involved ordinary differential equations (ODEs) systems. Such a formalism implicitly assumes that the time spent in each compartment does not depend on the time already spent in it, which is at odds with the clinical data. To overcome this "memoryless" issue, a widely used solution is to increase and chain the number of compartments of a unique reality (e.g. have infected individual move between several compartments). This allows for greater heterogeneity and thus be closer to the observed situation, but also tends to make the whole model more difficult to apprehend and parameterize. We develop a non-Markovian alternative formalism based on partial differential equations (PDEs) instead of ODEs, which, by construction, provides a memory structure for each compartment thereby allowing us to limit the number of compartments. We apply our model to the French 2021 SARS-CoV-2 epidemic and, while accounting for vaccine-induced and natural immunity, we analyse and determine the major components that contributed to the Covid-19 hospital admissions. The results indicate that the observed vaccination rate alone is not enough to control the epidemic, and a global sensitivity analysis highlights a huge uncertainty attributable to the age-structured contact matrix. Our study shows the flexibility and robustness of PDE formalism to capture national COVID-19 dynamics and opens perspectives to study medium or long-term scenarios involving immune waning or virus evolution.
Résumé
Background: Recent trials support the clinical efficacy and safety of subcutaneous (sc) biologic treatment for IBD maintenance therapy. Administration of sc injections could reduce the financial burden and time required to attend for infusions and allow IBD service providers to manage increasing clinical demand. We evaluated the uptake and rationale for choosing to switch from intravenous (iv) infusions to sc injections, including the impact of the Covid-19 pandemic on IBD service provision. Methods: All adult patients receiving standard dosing maintenance iv Infliximab or Vedolizumab therapy at a tertiary IBD centre were offered a switch to the respective sc formulations. We investigated the uptake of the switch from iv infusions to sc injections and utilised a standardised patient questionnaire to determine the rationale for switching to sc injections or not, and to identify areas for improvement in IBD service provision for the switching process. Results: In a cohort of, 232 eligible patients (258 total patients, 190 infliximab, 68 vedolizumab, 26 no longer eligible), 58% of patients receiving Infliximab and, 59% of patients chose to switch to sc treatment. Of the, 26 ineligible patients, 6 were switched to an intensified treatment schedule, 12 switched to a different biologic, 2 moved out of area, 5 had treatment stopped for clinical reasons and, 1 required operative treatment. There were no significant predictors for willingness to switch relating to patient age, sex, diagnosis, drug, line of treatment or duration of treatment (p>0.05). Early results from patient questionnaires (n=23) demonstrate that a decision to switch was not influenced by the impact on their mental health, Covid-19 risk, the impact on wider IBD service provision or financial savings, but, 70% of switchers did report that time savings influenced their decision. A minority of patients reported feeling pressured to switch (10% switchers and, 15% non-switchers) or had concerns about the safety (20% switchers, 0% non-switchers) and efficacy (40% switchers, 31% non-switchers) of sc injections. The majority of patients feel they were provided with sufficient Conclusion: Switch uptake rates were, 58% with, 90% of patients eligible to switch. We found no evidence that a decision to switch was influenced by age, sex, diagnosis, drug, line of treatment or duration of treatment. Non-switchers value face-to-face support at the IBD unit highly, and switchers value the time saved by administering injections at home. Switching to sc formulation not only provided patients with a choice of saving time usually required for iv administration but also reduced pressure in an overstretched IBD service.