Background: Health-related quality of life (HRQoL) has become a major endpoint to assess the clinical benefit of new therapeutic strategies in oncology clinical trials. Typically, HRQoL outcomes are analyzed using linear mixed models (LMMs). However, longitudinal analysis of HRQoL in the presence of missing data remains complex and unstandardized. Our objective was to compare the modeling alternatives that account for informative dropout.Methods: We investigated three alternative methods—the selection model (SM), pattern-mixture model (PMM), and shared-parameters model (SPM)—in relation to the LMM. We first compared them on the basis of methodological arguments highlighting their advantages and drawbacks. Then, we applied them to data from a randomized clinical trial that included 267 patients with advanced esophageal cancer for the analysis of four HRQoL dimensions evaluated using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire.Results: We highlighted differences in terms of outputs, interpretation, and underlying modeling assumptions; this methodological comparison could guide the choice of method according to the context. In the application, none of the four models detected a significant difference between the two treatment arms. The estimated effect of time on HRQoL varied according to the method: for all analyzed dimensions, the PMM estimated an effect that contrasted with those estimated by the SM and SPM; the LMM estimated effects were confirmed by the SM (on two of four HRQoL dimensions) and SPM (on three of four HRQoL dimensions).Conclusions: The PMM, SM, or SPM should be used to confirm or invalidate the results of LMM analysis when informative dropout is suspected. Of these three alternative methods, the SPM appears to be the most interesting from both theoretical and practical viewpoints.Trial registration: This study is registered withClinicalTrials.gov, numberNCT00861094.
Background: The 2018–2020 Ebola outbreak in the Democratic Republic of the Congo marked the first major cohort of Ebola survivors treated with advanced therapeutics, including monoclonal antibodies (REGN-EB3, ansuvimab, ZMapp) and remdesivir. This study explored factors influencing long-term sequelae in survivors who received these specific therapies. Methods: A prospective multicenter study enrolled 750 Ebola survivors from the 10th outbreak in the Democratic Republic of the Congo between April and October 2020. Participants were followed for 12 months to assess the recurrence of clinical sequelae according to Weibull and shared frailty models. Results: Of 750 of Ebola survivors, 650 (86.7%) experienced post-Ebola sequalae. The median age of survivors was 32 years and 56.7% were female. Among them, 463 (61.7%) experienced neurologic sequelae, 373 (49.7%) musculoskeletal sequelae, and 288 (38.4%) general sequelae. Globally, these persisted for at least 38 months postdischarge, with slight decreases over time. At enrollment (median time to baseline visit, 330 days after discharge), neurologic sequelae were more frequent in the REGN-EB3 group (hazard ratio, 2.14; 95% CI, 1.28–3.57) as compared with the remdesivir group. Musculoskeletal sequelae were associated with age (1.02; 1.00–1.03), ZMapp treatment (3.17; 1.81–5.56), and acute-phase hemorrhagic symptoms (1.64; 1.14–2.36). Ocular sequelae were associated with age (1.04; 1.02–1.06). Female sex, older age, metabolic comorbidities, and REGN-EB3 therapy were associated with recurrent neurologic and musculoskeletal sequelae. Recurrent ocular sequelae were more frequent in adults (1.02; 1.01–1.03). Conclusions: Despite improved survival with monoclonal antibody therapy, our findings highlight a high incidence of neurologic sequelae in the REGN-EB3 group and musculoskeletal sequelae in the ZMapp group as compared with the remdesivir group, as well as among older survivors, women, and those with comorbidities. These results underscore the need for targeting long-term care to effectively manage post-Ebola sequelae.
Individuals with high Loa loa microfilarial densities (MFD) risk serious adverse events (SAEs) following ivermectin treatment. A single dose of levamisole (LEV) induces a temporary, progressive MFD decrease. This double-blind, randomized, placebo-controlled trial evaluated the safety and efficacy of 3-day and 5-day LEV regimens for the treatment of loiasis in the Republic of the Congo. Participants were randomly assigned to receive placebo (PLA), LEV-3, or LEV-5. Safety was assessed by the occurrence of SAEs and the frequency and severity of AEs. Efficacy was measured by changes in Loa loa MFD. No SAEs were reported, and AE severity was comparable across treatment arms. On day 5, MFD reductions were greater in the LEV-3 and LEV-5 groups compared to PLA ( −1.6%, 29.3%, and 51.4%, respectively; P < 0.001). By day 7, a higher proportion of participants achieved ≥40% MFD reduction in the LEV-5 group (44.4%) compared to LEV-3 (34.6%) and PLA (8.3%) (P = 0.051). Post hoc contrasts confirmed significantly greater MFD reduction with LEV-5 versus LEV-3. These findings suggest that a 5-day LEV regimen is safe and moderately effective for reducing L. loa MFD and may represent a promising alternative for individualised management in loiasis-endemic areas, particularly where onchocerciasis is hypoendemic and coendemic with loiasis. Trial registration: NCT06252961.
Objectives: Although oral pre-exposure prophylaxis (PrEP) for HIV is being rolled out in West Africa, data on sexually transmitted infections (STIs) in PrEP users are scarce. We assessed the prevalence, incidence and determinants of bacterial STIs in men who have sex with men (MSM) taking PrEP in Burkina Faso, Côte d’Ivoire, Mali and Togo. Methods: A prospective cohort study among MSM initiating PrEP as part of a comprehensive HIV prevention package was conducted between 2017 and 2021 in community-based clinics in the four study countries. Molecular screening for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) was performed at months 0, 6 and 12. Serological testing for syphilis was performed every 3 months over the first year of follow-up. Determinants of CT and/or NG incidence were identified using Poisson generalised linear mixed models. Results: A total of 598 participants with a median age of 24.7 years were included. Prevalence of CT and/or NG was 24.4% (95% CI 21.0 to 28.1), 22.4% (95% CI 18.4 to 26.8) and 29.0% (95% CI 24.2 to 34.1) at months 0, 6 and 12, respectively. The prevalence of syphilis ranged from 0.2% (95% CI 0.0 to 0.9) at month 0 to 0.8% (95% CI 0.2 to 2.4) at month 12. Ninety incident CT and/or NG infections occurred during a total follow-up time of 280.6 person-years (incidence rate 32.1 per 100 person-years, 95% CI 25.8 to 39.4). Three incident syphilis infections were detected during a total follow-up time of 459.7 person-years (incidence rate 0.7 per 100 person-years, 95% CI 0.1 to 1.9). CT and/or NG incidence was associated with condomless insertive anal sex (adjusted incidence rate ratio 1.96, 95% CI 1.04 to 3.71, p=0.038). Conclusions: CT and NG were frequent but syphilis was very infrequent in MSM using HIV PrEP in West Africa. HIV programme managers should integrate STI services into PrEP programmes.