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Purpose: We assessed the efficacy of cediranib, olaparib, and cediranib/olaparib compared with standard-of-care chemotherapy (SOC) in platinum-resistant or platinum-refractory epithelial ovarian cancer (PROC)., Patients and Methods: NRG-GY005 is an open-label, four-arm, phase II/III superiority trial enrolling patients with high-grade serous/endometrioid PROC and one to three previous therapies. Key exclusion criteria included previous receipt of poly(ADP-ribose) polymerase inhibitor or receipt of antiangiogenic therapy in the recurrent setting. Treatment arms (SOC [once weekly paclitaxel, topotecan, or pegylated liposomal doxorubicin], cediranib, olaparib, or cediranib/olaparib) were equally randomized. A preplanned interim futility analysis on the basis of progression-free survival (PFS) selected treatment arms to advance to phase III. PFS and overall survival (OS) were phase III coprimary end points, with hierarchical testing of PFS followed by OS to preserve type 1 error control, designed to have 90% power for a 0.625 PFS hazard ratio (HR). OS was tested after PFS in the multiple hierarchical testing procedure. Secondary end points included objective response rate (ORR) and patient-reported outcomes., Results: Five hundred sixty-two eligible patients were enrolled for phase II/III. Three arms met PFS criteria to carry forward to phase III (SOC, cediranib/olaparib, and cediranib). Median PFS was 3.4, 5.2, and 4 months with SOC, cediranib/olaparib, and cediranib, respectively, with a median follow-up duration of 42.2 months. PFS HR estimates for cediranib/olaparib and cediranib ( v SOC) were 0.796 (98.3% CI, 0.597 to 1.060) and 0.972 (98.3% CI, 0.726 to 1.300), respectively. Median OS was 13.6, 12.8, and 10.5 months, and of 443 patients with measurable disease, ORR was 8.6%, 24.7%, and 13.1% for SOC, cediranib/olaparib, and cediranib, respectively. No new safety signals were identified. In patients receiving cediranib/olaparib, no statistically significant difference was observed on the NFOSI-DRS-P subscale compared with SOC (98.3% CI, -1.3 to 1.5, P = .8725)., Conclusion: The cediranib-containing arms demonstrated clinical activity on the basis of PFS but were not superior compared with SOC.

Background: The bag-valve-mask (BVM) or manual resuscitator bag is used as a first-line technique to ventilate patients with respiratory failure. Volume-restricted manual resuscitator bags (eg, pediatric bags) have been suggested to minimize overventilation and associated complications. There are studies that both support and caution against the use of a pediatric resuscitator bag to ventilate an adult patient. In this study, we evaluated the ability of pre-hospital clinicians to adequately ventilate an adult manikin with both an adult- and pediatric-size manual resuscitator bag without the assistance of an advanced airway or airway adjunct device., Methods: This study was conducted at an international conference in 2022. Conference attendees with pre-hospital health care experience were recruited to ventilate an adult manikin using a BVM for 1 min with both an adult and pediatric resuscitator bag, without the use of adjunct airway devices, while 6 ventilatory variables were collected or calculated: tidal volume (V T ), breathing frequency, adequate breaths (V T > 150 mL), proportion of adequate breaths, peak inspiratory pressure (PIP), and estimated alveolar ventilation (EAV)., Results: A total of 208 participants completed the study. Ventilation with the adult-sized BVM delivered an average V T of 290.4 mL compared to 197.1 mL ( P < .001) when using the pediatric BVM. PIP with the adult BVM was higher than with the pediatric BVM (10.6 cm H 2 O vs 8.6 cm H 2 O, P < .001). The median EAV with the adult bag (1,138.1 [interquartile range [IQR] 194.0-2,869.9] mL/min) was markedly greater than with the pediatric BVM (67.7 [IQR 0-467.3] mL/min, P < .001)., Conclusions: Both pediatric- and adult-sized BVM provided lower ventilation volumes than those recommended by professional guidelines for an adult. Ventilation with the pediatric BVM was significantly worse than with the adult bag when ventilating a simulated adult subject., Competing Interests: Dr Slutsky discloses a relationship with SafeBVM Corporation. The remaining authors have disclosed no conflicts of interest., (Copyright © 2024 by Daedalus Enterprises.)