RESUMO
OBJECTIVES: This study developed and validated the children's voice questionnaire (CVQ), a new self-administered instrument for children, and evaluated its internal consistency and reliability. STUDY DESIGN: Observational, prospective, cross-sectional study. METHODS: The initial preparation of the CVQ was conducted in four steps. First, individual interviews were conducted with dysphonic and non-dysphonic children and their parents, teachers, and speech pathologists. Second, the responses collected from the interviews were arranged into a comprehensive list of 175 items. Third, this list was reduced to a preliminary 21-item version of the questionnaire, which was tested as a pilot with 254 children. Fourth, a further reduction to 18 items was performed to construct the final version of the CVQ. The questionnaire was then administered to 342 children (73 dysphonic, 269 non-dysphonic) aged 6-18. Simultaneously, the parents of these children completed the pediatric voice handicap index (pVHI). Finally, after 2 weeks, 30 randomly selected children (nine dysphonic, 21 non-dysphonic) completed the CVQ again to evaluate test-retest reliability. RESULTS: High reliability was found for the CVQ (Cronbach's α = 0.94). Test-retest revealed strong and statistically significant reliability (r = 0.79, P < 0.001). A highly significant group difference was found between the CVQ scores obtained for the dysphonic and non-dysphonic groups (t[78.25] = 6.22, P < 0.001). In addition, significant medium-to-strong positive correlations were found between the children's evaluations using the CVQ and their parents' evaluations using the pVHI (0.59 < r < 0.66, P < 0.01). CONCLUSIONS: The newly developed CVQ is a valid and reliable instrument. Findings reveal general agreement between children and their parents, but also show that children's perspective on their dysphonia is not equivalent to the parent's perspective. This demonstrates that combining both perspectives provides a more holistic and complete overview of dysphonic children's voice-related quality of life. The self-administered CVQ reliably differentiates dysphonic from non-dysphonic children and may serve as a valuable tool for the initial or ongoing evaluation of children with voice disorders in clinical and research settings.
RESUMO
PURPOSE: A benefit:risk assessment for a less-frequent nivolumab 480 mg every 4 weeks + cabozantinib 40 mg every day dosing regimen was predicted using modeling and simulation of clinical trial data from nivolumab monotherapy studies and from the nivolumab 240 mg every 2 weeks + cabozantinib 40 mg every day dosing regimen, which demonstrated clinical benefit versus sunitinib in previously untreated advanced renal cell carcinoma (aRCC) in the phase III CheckMate 9ER trial (NCT03141177). PATIENTS AND METHODS: Multivariable Cox proportional hazards analyses were conducted using nivolumab monotherapy data in previously treated aRCC and data from CheckMate 9ER to evaluate progression-free survival (PFS), overall survival (OS), and grade ≥2 immune-mediated adverse events (IMAE). RESULTS: Nivolumab 240 mg every 2 weeks + cabozantinib versus nivolumab monotherapy showed improvement in PFS (HR, 0.38; 95% CI, 0.31-0.47), OS (HR, 0.63; 95% CI, 0.46-0.85), and increased risk of grade ≥2 IMAEs (HR, 2.19; 95% CI, 1.79-2.67). Nivolumab exposure was not a predictor of PFS/OS or grade ≥2 IMAEs. Lower nivolumab clearance, male sex, higher baseline bodyweight, and Karnofsky performance (100) were each associated with PFS/OS improvements. Region and International Metastatic Renal Cell Carcinoma Database Consortium poor score were negative OS predictors. Age, baseline albumin, and programmed death ligand 1 status were not significant PFS/OS predictors. Cabozantinib was a significant grade ≥2 IMAE predictor, driven by diarrhea and hepatic events. Model-predicted PFS/OS and grade ≥2 IMAE rates were similar (<2.5% difference) for nivolumab 240 mg every 2 weeks + cabozantinib and 480 mg every 4 weeks + cabozantinib. CONCLUSIONS: Comparable benefit:risk was predicted for nivolumab 480 mg every 4 weeks + cabozantinib and nivolumab 240 mg every 2 weeks + cabozantinib.
