Vibration of effects resulting from treatment selection in mixed-treatment comparisons: a multiverse analysis on network meta-analyses of antidepressants in major depressive disorder

International audienceObjective It is frequent to find overlapping network meta-analyses (NMAs) on the same topic with differences in terms of both treatments included and effect estimates. We aimed to evaluate the impact on effect estimates of selecting different treatment combinations (ie, network geometries) for inclusion in NMAs. Design Multiverse analysis, covering all possible NMAs on different combinations of treatments. Setting Data from a previously published NMA exploring the comparative effectiveness of 22 treatments (21 antidepressants and a placebo) for the treatment of acute major depressive disorder. Participants Cipriani et al explored a dataset of 116 477 patients included in 522 randomised controlled trials. Main outcome measures For each possible treatment selection, we performed an NMA to estimate comparative effectiveness on treatment response and treatment discontinuation for the treatments included (231 between-treatment comparisons). The distribution of effect estimates of between-treatment comparisons across NMAs was computed, and the direction, magnitude and statistical significance of the 1st and 99th percentiles were compared. Results 4 116 254 different NMAs concerned treatment response. Among possible network geometries, 172/231 (74%) pairwise comparisons exhibited opposite effects between the 1st and 99th percentiles, 57/231 (25%) comparisons exhibited statistically significant results in opposite directions, 118 of 231 (51%) comparisons derived results that were both significant and non-significant at 5% risk and 56/231 (24%) treatment pairs obtained consistent results with only significant differences (or only non-significant differences) at 5% risk. Comparisons based on indirect evidence only were associated with greater variability in effect estimates. Comparisons with small absolute values observed in the complete NMA more frequently obtained statistically significant results in opposite directions. Similar results were observed for treatment discontinuation. Conclusion In this multiverse analysis, we observed that the selection of treatments to be included in an NMA could have considerable consequences on treatment effect estimations. Trial registration https://osf.io/mb5dy

Efficacy of local budesonide therapy in the management of persistent hyposmia in COVID-19 patients without signs of severity: A structured summary of a study protocol for a randomised controlled trial

To assess the efficacy of local intranasal treatment with budesonide (nasal irrigation), in addition to olfactory rehabilitation, in the management of loss of smell in COVID-19 patients without signs of severity and with persistent hyposmia 30 days after the onset of symptoms. To search for an association between the presence of an obstruction on MRI and the severity of olfactory loss, at inclusion and after 30 days of treatment

Amantadine use in the French prospective NS-Park cohort

International audienceObjective: To assess amantadine use and associated factors in the patients with Parkinson's disease (PD).Background: Immediate-release amantadine is approved for the treatment of PD and is largely used in clinical practice to treat "levodopa-induced dyskinesia (LIDs). Its use varies according to countries and PD stages. The prospective NS-Park cohort collects features of PD patients followed by 26 French PD Expert Centres.Methods: Variables used for the analyses included demographics, motor and non-motor PD symptoms and motor complications [motor fluctuations (MFs), LIDs)], antiparkinsonian pharmacological classes and levodopa equivalent daily dose (LEDD). We evaluated: (i) prevalence of amantadine use and compared clinical features of amantadine users vs. non-users (cross-sectional analysis); (ii) factors associated with amantadine initiation (longitudinal analysis); (iii) amantadine effect on LIDs, MFs, apathy, impulse control disorders and freezing of gait (Fog) (longitudinal analysis).Results: Amantadine use prevalence was 12.6% (1,585/12,542, median dose = 200 mg). Amantadine users were significantly younger, with longer and more severe PD symptoms, greater LEDD and more frequent use of device-aided/surgical treatment. Factors independently associated with amantadine initiation were younger age, longer PD duration, more frequent LIDs, MFs and FoG, higher LEDD and better cognitive function. 9 of the 658 patients on amantadine had stopped it at the following visit, after 12-18 months (1.3%). New users of amantadine presented a higher improvement in LIDs and MF compared to amantadine never users.Conclusions: About 12% of PD patients within the French NS-Park cohort used amantadine, mostly those with younger age and more severe PD. Amantadine initiation was associated with a subsequent reduction in LIDs and MFs