33 results on '"Okpara C"'
Search Results
2. Characterization and Management of Adverse Reactions in Patients With Advanced Endometrial Cancer Receiving Lenvatinib Plus Pembrolizumab
- Author
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Colombo, N, Lorusso, D, Monk, B, Slomovitz, B, Hasegawa, K, Nogueira-Rodrigues, A, Zale, M, Okpara, C, Barresi, G, Mckenzie, J, Makker, V, Colombo, Nicoletta, Lorusso, Domenica, Monk, Bradley J, Slomovitz, Brian, Hasegawa, Kosei, Nogueira-Rodrigues, Angélica, Zale, Melissa, Okpara, Chinyere E, Barresi, Gianmaria, McKenzie, Jodi, Makker, Vicky, Colombo, N, Lorusso, D, Monk, B, Slomovitz, B, Hasegawa, K, Nogueira-Rodrigues, A, Zale, M, Okpara, C, Barresi, G, Mckenzie, J, Makker, V, Colombo, Nicoletta, Lorusso, Domenica, Monk, Bradley J, Slomovitz, Brian, Hasegawa, Kosei, Nogueira-Rodrigues, Angélica, Zale, Melissa, Okpara, Chinyere E, Barresi, Gianmaria, McKenzie, Jodi, and Makker, Vicky
- Abstract
Background: Lenvatinib plus pembrolizumab significantly improved efficacy compared with chemotherapy in patients with advanced endometrial cancer (aEC) regardless of microsatellite instability status or histologic subtype, who had disease progression following prior platinum-based therapy, in Study-309/KEYNOTE-775. The safety profile of the combination was generally consistent with that of each monotherapy drug and of the combination in patients with endometrial cancer and other solid tumors. Given the medical complexity of patients with aEC, this paper aims to characterize key adverse reactions (ARs) of the combination treatment and review management strategies, providing a guide for AR management to maximize anticancer benefits and minimize treatment discontinuation. Materials and Methods: In Study-309/KEYNOTE-775, patients received lenvatinib (20 mg orally once daily) plus pembrolizumab (200 mg intravenously every 3 weeks) or chemotherapy (doxorubicin or paclitaxel). The incidence and median time to the first onset of ARs, dose modifications, and concomitant medications are described. Key ARs characterized include hypothyroidism, hypertension, fatigue, diarrhea, musculoskeletal disorders, nausea, decreased appetite, vomiting, stomatitis, weight decreased, proteinuria, and palmar-plantar erythrodysesthesia syndrome. Results: As expected, the most common any-grade key ARs included: hypothyroidism, hypertension, fatigue, diarrhea, and musculoskeletal disorders. Grades 3-4 key ARs with incidence ≥10% included: hypertension, fatigue, and weight decreased. Key ARs first occurred within approximately 3 months of treatment initiation. AR management strategies consistent with the prescribing information and the study protocol are discussed. Conclusion: Successful AR management strategies for lenvatinib plus pembrolizumab include education of the patient and entire treatment team, preventative measures and close monitoring, and judicious use of dose modifications and conco
- Published
- 2024
3. Rapid programmatic adoption of robotic pancreaticoduodenectomy can be done safely and efficiently
- Author
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Krell, M., primary, Maglione, M., additional, Okpara, C., additional, Abdelfatah, E., additional, Allendorf, J., additional, Hewitt, B., additional, Cohen, S., additional, Wolfgang, C., additional, and Winner, M., additional
- Published
- 2024
- Full Text
- View/download PDF
4. Characterization and Management of Adverse Reactions in Patients With Advanced Endometrial Cancer Receiving Lenvatinib Plus Pembrolizumab (Interpretation In Rus.)
- Author
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Colombo, N, Lorusso, D, Monk, B, Slomovitz, B, Hasegawa, K, Nogueira-Rodrigues, A, Zale, M, Okpara, C, Barresi, G, Mckenzie, J, Makker, V, Colombo N., Lorusso D., Monk B. J., Slomovitz B., Hasegawa K., Nogueira-Rodrigues A., Zale M., Okpara C. E., Barresi G., McKenzie J., Makker V., Colombo, N, Lorusso, D, Monk, B, Slomovitz, B, Hasegawa, K, Nogueira-Rodrigues, A, Zale, M, Okpara, C, Barresi, G, Mckenzie, J, Makker, V, Colombo N., Lorusso D., Monk B. J., Slomovitz B., Hasegawa K., Nogueira-Rodrigues A., Zale M., Okpara C. E., Barresi G., McKenzie J., and Makker V.
- Abstract
Background. Lenvatinib plus pembrolizumab significantly improved efficacy compared with chemotherapy in patients with advanced endome-trial cancer (aEC) regardless of microsatellite instability status or histologic subtype, who had disease progression following prior platinum-based therapy, in Study-309/KEYNOTE-775. The safety profile of the combination was generally consistent with that of each monotherapy drug and of the combination in patients with endometrial cancer and other solid tumors. Given the medical complexity of patients with aEC, this paper aims to characterize key adverse reactions (ARs) of the combination treatment and review management strategies, providing a guide for AR management to maximize anticancer benefits and minimize treatment discontinuation. Materials and methods. In Study-309/KEYNOTE-775, patients received lenvatinib (20 mg orally once daily) plus pembrolizumab (200 mg intravenously every 3 weeks) or chemotherapy (doxorubicin or paclitaxel). The incidence and median time to the first onset of ARs, dose modifications, and concomitant medications are described. Key ARs characterized include hypothyroidism, hypertension, fatigue, diarrhea, musculoskeletal disorders, nausea, decreased appetite, vomiting, stomatitis, weight decreased, proteinuria, and palmar-plantar erythrodysesthesia syndrome. Results. As expected, the most common any-grade key ARs included: hypothyroidism, hypertension, fatigue, diarrhea, and musculoskeletal disorders. Grades 3-4 key ARs with incidence ≥10% included: hypertension, fatigue, and weight decreased. Key ARs first occurred within approximately 3 months of treatment initiation. AR management strategies consistent with the prescribing information and the study protocol are discussed. Conclusion. Successful AR management strategies for lenvatinib plus pembrolizumab include education of the patient and entire treatment team, preventative measures and close monitoring, and judicious use of dose modifications and conc
- Published
- 2023
5. Tumor Response by Baseline Metastases in Patients (Pts) With Renal Cell Carcinoma (RCC) Treated with Lenvatinib (L) Plus Pembrolizumab (P) vs Sunitinib (S): Post Hoc Analysis of the CLEAR Trial
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Grünwald, V., primary, McKay, R.R., additional, Buchler, T., additional, Masatoshi, E., additional, Park, S.H., additional, Takagi, T., additional, Zanetta, S., additional, Keizman, D., additional, Suárez, C., additional, Négrier, S., additional, Lee, J.L., additional, Santini, D., additional, Bedke, J., additional, Staehler, M., additional, Kollmannsberger, C., additional, Choueiri, T., additional, Motzer, R., additional, Burgents, J., additional, Okpara, C., additional, and Powles, T., additional
- Published
- 2023
- Full Text
- View/download PDF
6. Lenvatinib Plus Pembrolizumab in Previously Treated Advanced Endometrial Cancer: Updated Efficacy and Safety From the Randomized Phase III Study 309/KEYNOTE-775
- Author
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Makker, V, Colombo, N, Herráez, A, Monk, B, Mackay, H, Santin, A, Miller, D, Moore, R, Baron-Hay, S, Ray-Coquard, I, Ushijima, K, Yonemori, K, Kim, Y, Guerra Alia, E, Sanli, U, Bird, S, Orlowski, R, Mckenzie, J, Okpara, C, Barresi, G, Lorusso, D, Makker, Vicky, Colombo, Nicoletta, Herráez, Antonio Casado, Monk, Bradley J, Mackay, Helen, Santin, Alessandro D, Miller, David S, Moore, Richard G, Baron-Hay, Sally, Ray-Coquard, Isabelle, Ushijima, Kimio, Yonemori, Kan, Kim, Yong Man, Guerra Alia, Eva M, Sanli, Ulus A, Bird, Steven, Orlowski, Robert, McKenzie, Jodi, Okpara, Chinyere, Barresi, Gianmaria, Lorusso, Domenica, Makker, V, Colombo, N, Herráez, A, Monk, B, Mackay, H, Santin, A, Miller, D, Moore, R, Baron-Hay, S, Ray-Coquard, I, Ushijima, K, Yonemori, K, Kim, Y, Guerra Alia, E, Sanli, U, Bird, S, Orlowski, R, Mckenzie, J, Okpara, C, Barresi, G, Lorusso, D, Makker, Vicky, Colombo, Nicoletta, Herráez, Antonio Casado, Monk, Bradley J, Mackay, Helen, Santin, Alessandro D, Miller, David S, Moore, Richard G, Baron-Hay, Sally, Ray-Coquard, Isabelle, Ushijima, Kimio, Yonemori, Kan, Kim, Yong Man, Guerra Alia, Eva M, Sanli, Ulus A, Bird, Steven, Orlowski, Robert, McKenzie, Jodi, Okpara, Chinyere, Barresi, Gianmaria, and Lorusso, Domenica
- Abstract
Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.We report the final prespecified analysis for overall survival (OS), along with updated progression-free survival (PFS) and objective response rate (ORR), and safety from the open-label, randomized, phase III Study 309/KEYNOTE-775. In total, 827 patients with advanced, recurrent, or metastatic endometrial cancer (EC) were randomly assigned to receive lenvatinib 20 mg orally once daily plus pembrolizumab 200 mg intravenously once every 3 weeks (n = 411) or chemotherapy of the treating physician's choice (doxorubicin 60 mg/m2 intravenously once every 3 weeks or paclitaxel 80 mg/m2 intravenously once weekly [3 weeks on; 1 week off] [n = 416]). Efficacy was reported for patients with mismatch repair proficient (pMMR) tumors and all-comers, and by subgroups (histology, prior therapy, MMR status). Updated safety was also reported.Lenvatinib plus pembrolizumab showed benefits in OS (pMMR HR, 0.70; 95% CI, 0.58 to 0.83; all-comer HR, 0.65; 95% CI, 0.55 to 0.77), PFS (pMMR HR, 0.60; 95% CI, 0.50 to 0.72; all-comer HR, 0.56; 95% CI, 0.48 to 0.66), and ORR (pMMR patients, 32.4% v 15.1%; all-comers, 33.8% v 14.7%) versus chemotherapy. OS, PFS, and ORR favored lenvatinib plus pembrolizumab in all subgroups of interest. No new safety signals were observed. Lenvatinib plus pembrolizumab continued to show improved efficacy versus chemotherapy and manageable safety in patients with previously treated advanced EC.
- Published
- 2023
7. Quality Characteristics of Bread Made from Flour Blends of Wheat, Cooking Banana and Mungbean
- Author
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Okakpu, K. G., primary, Offia-Olua, B. I., primary, Okakpu, C. J., primary, and Okpara, C. M., primary
- Published
- 2023
- Full Text
- View/download PDF
8. Effect of using instructional Materials in enhancing teaching and learning of Mathematics in Junior Schools in Obio-Akpor LGA of Rivers state
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Ugorji, O. Clifford, King-Agboto, Felicia., and Okpara, C. Catherine
- Subjects
Effect , Mathematics, Instructional material, Junior secondary school, teaching and learning - Abstract
This study was designed to examine the effect of using instructional materials in enhancing teaching and learning of Mathematics in junior secondary schools four research questions and two hypotheses were formulated to guide the study. The study adopted quasi experimental pretest, posttest control group design was used for the study .Eighty (80) students (40 males and 40 females)randomly selected from two Junior public secondary schools were used for the study. The stratified sampling technique was used for the study. The participants in the experimental group were taught using numbers and numeration using flipped classroom method while the control groups were taught using traditional lecture and assignment method. The students were randomly assigned to the experimental group and control groups respectively. Effect of instructional material on Mathematics assessment scale (EIMMAS). This was a 20 – item assessment scale structured in four points Likert scale of strongly agree (4 points), Agree (3points), disagree (2 points), strongly agree (1 point). Test re-test method was used to determine the reliability of the instrument which yielded a coefficient of 0.84.The data collected were analyzed using mean, standard deviation and t-test statistics. Data collected was analyzed using descriptive statistical method including mean, standard deviation and t-test. The analysis indicated that instructional material enhanced learning; it also revealed no gender effect on treatment. Based on these findings, it was recommended that government should provide enough instructional materials for the schools to enable teachers teach with ease. Teachers and administrators should attend seminar and workshops in order to know and be able to utilize available resources.
- Published
- 2023
9. W189 Remnant cholesterol, fasting plasma glucose and other lipid fractions in some obese and non-obese individuals in Nnewi, south east Nigeria
- Author
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Nnamdi, C., primary, Amah, U., additional, Onuegbu, A., additional, Okpara, C., additional, and Okwara, J., additional
- Published
- 2022
- Full Text
- View/download PDF
10. ROLE OF ACADEMIC LIBRARIES IN RESEARCH DATA MANAGEMENT IN TERTIARY INSTITUTIONS.
- Author
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Ekeh, D. O., Ojemuyide, C. C., Eze, C. N., Ani, M. I., Igu, O. F., Okpara, C. M., and Duru, C. K.
- Abstract
An institution cannot exist and function properly without the presence of a library because the services provided by an academic library reflect the quality of the institution. This paper attempts to present a brief overview of the concept of library, research data, Research Data Management (RDM) and its constraints as well as the roles of academic libraries. These roles has experienced new paradigm shift, unprecedented reshaping and alterations as a result of emerging waves of information communication technology (ICT) and its accompanying sustainable and disruptive technologies. Scholars are now producing, storing and disseminating digital data in much larger volumes than the text. The continued existence and access of this data is an issue, since the data is not stored in libraries. It is therefore crucial to preserve data for future generations. This paper tries to delineate the emerging role of academic libraries in Research Data Management (RDM) in tertiary institutions. [ABSTRACT FROM AUTHOR]
- Published
- 2023
11. Phase I/II study of single-agent lenvatinib in children and adolescents with refractory or relapsed solid malignancies and young adults with osteosarcoma (ITCC-050)☆
- Author
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Gaspar, N., Campbell-Hewson, Q., Gallego Melcon, S., Locatelli, Franco, Venkatramani, R., Hecker-Nolting, S., Gambart, M., Bautista, F., Thebaud, E., Aerts, I., Morland, B., Rossig, C., Canete Nieto, A., Longhi, A., Lervat, C., Entz-Werle, N., Strauss, S. J., Marec-Berard, P., Okpara, C. E., He, C., Dutta, L., Casanova, M., Locatelli F. (ORCID:0000-0002-7976-3654), Gaspar, N., Campbell-Hewson, Q., Gallego Melcon, S., Locatelli, Franco, Venkatramani, R., Hecker-Nolting, S., Gambart, M., Bautista, F., Thebaud, E., Aerts, I., Morland, B., Rossig, C., Canete Nieto, A., Longhi, A., Lervat, C., Entz-Werle, N., Strauss, S. J., Marec-Berard, P., Okpara, C. E., He, C., Dutta, L., Casanova, M., and Locatelli F. (ORCID:0000-0002-7976-3654)
- Abstract
Background: We report results from the phase I dose-finding and phase II expansion part of a multicenter, open-label study of single-agent lenvatinib in pediatric and young adult patients with relapsed/refractory solid tumors, including osteosarcoma and radioiodine-refractory differentiated thyroid cancer (RR-DTC) (NCT02432274). Patients and methods: The primary endpoint of phase I was to determine the recommended phase II dose (RP2D) of lenvatinib in children with relapsed/refractory solid malignant tumors. Phase II primary endpoints were progression-free survival rate at 4 months (PFS-4) for patients with relapsed/refractory osteosarcoma; and objective response rate/best overall response for patients with RR-DTC at the RP2D. Results: In phase I, 23 patients (median age, 12 years) were enrolled. With lenvatinib 14 mg/m2, three dose-limiting toxicities (hypertension, n = 2; increased alanine aminotransferase, n = 1) were reported, establishing 14 mg/m2 as the RP2D. In phase II, 31 patients with osteosarcoma (median age, 15 years) and 1 patient with RR-DTC (age 17 years) were enrolled. For the osteosarcoma cohort, PFS-4 (binomial estimate) was 29.0% [95% confidence interval (CI) 14.2% to 48.0%; full analysis set: n = 31], PFS-4 by Kaplan–Meier estimate was 37.8% (95% CI 20.0% to 55.4%; full analysis set) and median PFS was 3.0 months (95% CI 1.8-5.4 months). The objective response rate was 6.7% (95% CI 0.8% to 22.1%). The patient with RR-DTC had a best overall response of partial response. Some 60.8% of patients in phase I and 22.6% of patients in phase II (with osteosarcoma) had treatment-related treatment-emergent adverse events of grade ≥3. Conclusions: The lenvatinib RP2D was 14 mg/m2. Single-agent lenvatinib showed activity in osteosarcoma; however, the null hypothesis could not be rejected. The safety profile was consistent with previous tyrosine kinase inhibitor studies. Lenvatinib is currently being investigated in osteosarcoma in combination with chemotherap
- Published
- 2021
12. Lenvatinib with etoposide plus ifosfamide in patients with refractory or relapsed osteosarcoma (ITCC-050): a multicentre, open-label, multicohort, phase 1/2 study
- Author
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Gaspar, N., Venkatramani, R., Hecker-Nolting, S., Melcon, S. G., Locatelli, Franco, Bautista, F., Longhi, A., Lervat, C., Entz-Werle, N., Casanova, M., Aerts, I., Strauss, S. J., Thebaud, E., Morland, B., Nieto, A. C., Marec-Berard, P., Gambart, M., Rossig, C., Okpara, C. E., He, C., Dutta, L., Campbell-Hewson, Q., Locatelli F. (ORCID:0000-0002-7976-3654), Gaspar, N., Venkatramani, R., Hecker-Nolting, S., Melcon, S. G., Locatelli, Franco, Bautista, F., Longhi, A., Lervat, C., Entz-Werle, N., Casanova, M., Aerts, I., Strauss, S. J., Thebaud, E., Morland, B., Nieto, A. C., Marec-Berard, P., Gambart, M., Rossig, C., Okpara, C. E., He, C., Dutta, L., Campbell-Hewson, Q., and Locatelli F. (ORCID:0000-0002-7976-3654)
- Abstract
Background: Tyrosine kinase inhibitors have shown activity in osteosarcoma and might enhance the efficacy of chemotherapy. We aimed to determine the recommended phase 2 dose and antitumour activity of lenvatinib with etoposide plus ifosfamide in patients with refractory or relapsed osteosarcoma. Methods: This multicentre, open-label, multicohort, phase 1/2 trial was done at 17 hospitals in six countries. Eligible patients were aged 2–25 years, had relapsed or refractory osteosarcoma, measurable or evaluable disease per Response Evaluation Criteria in Solid Tumors version 1.1, Lansky play–performance score or Karnofsky performance score of 50% or higher, up to one previous VEGF or VEGF receptor-targeted therapy, and a life expectancy of at least 3 months. This study includes a combination dose-finding phase 1 part (cohort 3A) and a phase 2 combination expansion in patients with osteosarcoma (cohort 3B). Lenvatinib was administered orally at a starting dose of 11 mg/m2 per day, capped at 24 mg per day, and etoposide (100 mg/m2 per day) plus ifosfamide (3000 mg/m2 per day) were administered intravenously on days 1–3 of each 21-day cycle for a maximum of five cycles. Lenvatinib monotherapy continued after these five cycles until disease progression, toxic effects, or patient choice to discontinue. The phase 1 primary endpoint was to determine the recommended phase 2 dose by evaluating dose-limiting toxicity and the phase 2 primary endpoint was progression-free survival at 4 months. Progression-free survival was measured in the full analysis set, which included all patients enrolled for efficacy outcomes; safety was assessed in all patients who received any study drug. This study is registered with ClinicalTrials.gov, NCT02432274. Findings: 30 patients were screened for enrolment into cohort 3A between May 9, 2016, and June 3, 2019, and 22 patients for enrolment into cohort 3B between Sept 13, 2018, and July 18, 2019. Eight patients from cohort 3A and two from cohort 3B
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- 2021
13. O12 - Tumor Response by Baseline Metastases in Patients (Pts) With Renal Cell Carcinoma (RCC) Treated with Lenvatinib (L) Plus Pembrolizumab (P) vs Sunitinib (S): Post Hoc Analysis of the CLEAR Trial
- Author
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Grünwald, V., McKay, R.R., Buchler, T., Masatoshi, E., Park, S.H., Takagi, T., Zanetta, S., Keizman, D., Suárez, C., Négrier, S., Lee, J.L., Santini, D., Bedke, J., Staehler, M., Kollmannsberger, C., Choueiri, T., Motzer, R., Burgents, J., Okpara, C., and Powles, T.
- Published
- 2023
- Full Text
- View/download PDF
14. Strategies for Improving Agricultural Extension Service Delivery in Afikpo North Local Government Area, Ebonyi State
- Author
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Ndem, J. U., primary, Okafor, B. N., primary, Ochijenu, M. A., primary, Azuuku, F., primary, Eni, L. I., primary, Nwovu, C., primary, Edu, C. N., primary, and Okpara, C. M., primary
- Published
- 2020
- Full Text
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15. Effects of Solid Waste Disposal on the Physicochemical Properties of Borehole Water along FUTO Road, Eziobodo, Owerri-West, Nigeria
- Author
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Ejiogu, C, primary, Okpara, C, additional, Opara, K, additional, Onyeocha, I, additional, Azubuike, C, additional, and Emeh, A, additional
- Published
- 2018
- Full Text
- View/download PDF
16. Effects of NIOMR smoking kiln and oven on the crude protein, minerals and vitamins of catfish Clarias gariepinus
- Author
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Okereke, A.N., Okpara, J.Y., Cliffe, P.C., and Okpara, C.
- Subjects
Fisheries - Abstract
The effects of two different preservative methods, NIOMR Smoking Kiln and Oven drying on Crude Protein minerals and Vitamin of clarias gariepinus were studied. Clarias gariepinus were obtained from the fish farm of African Regional Aquaculture Centre, Aluu, Port Harcourt. The crude protein, minerals and vitamins of the fresh fish were determined immediately while two other batches were separately dried using oven at 50~'C for 30minutes and NIOMR Smoking Kiln at 70~'C for 3 hours. Result of the crude protien of fresh fish was 21.84 ~c 1.10 which increased to 59.53 ~c 1.88 and 35.41 ~c 1.00 in both NIOMR smoking and oven, respectively. This means that, there was a significant different in both dryers on the crude protein. This will improve the knowledge and capacity of rural women and agricultural communities on the appropriate processing method for fish. The mineral and vitamins of oven dried and NIOMR Smoking kiln were analyzed. The vitamin content of both the fish, dried and smoking kiln shows no significant different except in vitamin A which was significant (p
- Published
- 2012
17. Lenvatinib Plus Pembrolizumab in Previously Treated Advanced Endometrial Cancer: Updated Efficacy and Safety From the Randomized Phase III Study 309/KEYNOTE-775
- Author
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Vicky Makker, Nicoletta Colombo, Antonio Casado Herráez, Bradley J. Monk, Helen Mackay, Alessandro D. Santin, David S. Miller, Richard G. Moore, Sally Baron-Hay, Isabelle Ray-Coquard, Kimio Ushijima, Kan Yonemori, Yong Man Kim, Eva M. Guerra Alia, Ulus A. Sanli, Steven Bird, Robert Orlowski, Jodi McKenzie, Chinyere Okpara, Gianmaria Barresi, Domenica Lorusso, Makker, V, Colombo, N, Herráez, A, Monk, B, Mackay, H, Santin, A, Miller, D, Moore, R, Baron-Hay, S, Ray-Coquard, I, Ushijima, K, Yonemori, K, Kim, Y, Guerra Alia, E, Sanli, U, Bird, S, Orlowski, R, Mckenzie, J, Okpara, C, Barresi, G, and Lorusso, D
- Subjects
Cancer Research ,Oncology ,Endometrial Cancer - Abstract
Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. We report the final prespecified analysis for overall survival (OS), along with updated progression-free survival (PFS) and objective response rate (ORR), and safety from the open-label, randomized, phase III Study 309/KEYNOTE-775. In total, 827 patients with advanced, recurrent, or metastatic endometrial cancer (EC) were randomly assigned to receive lenvatinib 20 mg orally once daily plus pembrolizumab 200 mg intravenously once every 3 weeks (n = 411) or chemotherapy of the treating physician's choice (doxorubicin 60 mg/m2 intravenously once every 3 weeks or paclitaxel 80 mg/m2 intravenously once weekly [3 weeks on; 1 week off] [n = 416]). Efficacy was reported for patients with mismatch repair proficient (pMMR) tumors and all-comers, and by subgroups (histology, prior therapy, MMR status). Updated safety was also reported. Lenvatinib plus pembrolizumab showed benefits in OS (pMMR HR, 0.70; 95% CI, 0.58 to 0.83; all-comer HR, 0.65; 95% CI, 0.55 to 0.77), PFS (pMMR HR, 0.60; 95% CI, 0.50 to 0.72; all-comer HR, 0.56; 95% CI, 0.48 to 0.66), and ORR (pMMR patients, 32.4% v 15.1%; all-comers, 33.8% v 14.7%) versus chemotherapy. OS, PFS, and ORR favored lenvatinib plus pembrolizumab in all subgroups of interest. No new safety signals were observed. Lenvatinib plus pembrolizumab continued to show improved efficacy versus chemotherapy and manageable safety in patients with previously treated advanced EC.
- Published
- 2023
18. Independent contribution of gonads and sex chromosomes to sex differences in bone mass and strength in the four-core genotypes mouse model.
- Author
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Ramirez G, Okpara C, Arnett M, Segvich DM, Deosthale P, González PO, Kritikos AE, Melo JB, Sanz N, Pin F, Wallace JM, and Plotkin LI
- Subjects
- Animals, Female, Male, Mice, Bone and Bones metabolism, Gonads metabolism, Bone Density genetics, Organ Size, Mice, Inbred C57BL, Y Chromosome genetics, Models, Animal, Sex Characteristics, Sex Chromosomes genetics, Genotype
- Abstract
Vertebrate sexual dimorphism is ascribed to the presence of testes or ovaries, and, hence, to the secretion of gonad-specific hormones. However, mounting evidence indicates that sex differences in tissues and organs also stem from the presence of sex chromosomes (XX or XY). To tease out the contribution of gonads from sex chromosomes to the musculoskeletal system, we used the Four-Core Genotypes (FCG) mouse model, in which the Sry gene, which dictates testis formation, was either deleted from the Y chromosome, resulting in XY mice with ovaries (XY-SryO), or overexpressed in XX mice, resulting in XX mice with testes (XXT), together with gonadal males with XY-SryT (Sry deletion and overexpression of the Sry transgene in chromosome 3) and females with XXO. The FCG mice are generated by crossing XXO with XY-SryT mice, all of C57BL/6 J background. We now show that the musculoskeletal phenotype of 2- to 4-mo-old FCG mice varies based on both gonads and sex chromosomes, depending on the age and the organ/tissue/cell analyzed. The effect of sex chromosomes on body weight, fat and lean/skeletal muscle mass, and bone mass and structure is minor in 2-/3-mo-old mice, soon after sexual maturation. The contribution of sex chromosomes (XX vs XY-Sry in mice with the same gonads and sex hormones) to several of our measurements becomes apparent in adult 4-mo-old mice. The contribution of 1X and 1Y-Sry vs 2X chromosomes varies among different measurements in gonadal males or females, and mice with XY-Sry chromosomes might have higher or lower values that XX mice. Our study shows XX vs XY-Sry chromosome contribution to the musculoskeletal phenotype, which becomes more evident as the animals reach peak bone mass, suggesting that although gonadal sex has a major role, sex chromosomes are also an unrecognized contributor to musculoskeletal mass and bone strength., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2024
- Full Text
- View/download PDF
19. Cholera outbreak trends in Nigeria: policy recommendations and innovative approaches to prevention and treatment.
- Author
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Eneh S, Onukansi F, Anokwuru C, Ikhuoria O, Edeh G, Obiekwe S, Dauda Z, Praise-God A, and Okpara C
- Subjects
- Nigeria epidemiology, Humans, Health Policy, Sanitation, Public Health, Cholera epidemiology, Cholera prevention & control, Cholera mortality, Disease Outbreaks prevention & control
- Abstract
Cholera, an acute diarrheal infection from ingesting contaminated food or water, remains a significant public health threat in Nigeria, especially in areas lacking safe water and sanitation. Characterized by severe watery diarrhea, cholera can cause dehydration and death if untreated. Historical data shows cholera's endemic nature in Nigeria, with notable outbreaks since 1970, including major ones in 1991, 1999, 2010, 2018, and 2024. According to a descriptive study in Nigeria, the 1991 outbreak reported 59,478 cases and 7,654 deaths, with a Case Fatality Ratio (CFR) of 12.9%. In 2010, there were 41,787 cases and 1,716 deaths, with a CFR of 4.1% across 18 states, mainly affecting impoverished communities and children. The 2018 outbreak had 43,996 cases and 836 deaths, with a CFR of 2% in 20 states, a 240% increase from 2017. By mid-2024, there were 1,579 suspected cases and 54 deaths (CFR 3.4%) in 32 states. This paper evaluates cholera trends in Nigeria and proposes effective preventive and treatment strategies. Policy recommendations highlight the need for improved WASH infrastructure, enhanced surveillance, and rapid response mechanisms. Innovative approaches like case-area targeted interventions (CATI) and increased public health education are crucial for mitigating future outbreaks and achieving the goal of reducing cholera deaths by 90% by 2030., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Eneh, Onukansi, Anokwuru, Ikhuoria, Edeh, Obiekwe, Dauda, Praise-God and Okpara.)
- Published
- 2024
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20. Solvent-cast 3D printing with molecular weight polymer blends to decouple effects of scaffold architecture and mechanical properties on mesenchymal stromal cell fate.
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Tolbert JW, French T, Kitson A, Okpara C, Hammerstone DE, Lazarte S, Babuska TF, Gonzalez-Fernandez T, Krick BA, and Chow LW
- Subjects
- Humans, Molecular Weight, Solvents chemistry, Osteogenesis drug effects, Mesenchymal Stem Cells cytology, Mesenchymal Stem Cells drug effects, Mesenchymal Stem Cells metabolism, Printing, Three-Dimensional, Tissue Scaffolds chemistry, Polyesters chemistry, Cell Differentiation drug effects, Chondrogenesis drug effects
- Abstract
The biochemical and physical properties of a scaffold can be tailored to elicit specific cellular responses. However, it is challenging to decouple their individual effects on cell-material interactions. Here, we solvent-cast 3D printed different ratios of high and low molecular weight (MW) poly(caprolactone) (PCL) to fabricate scaffolds with significantly different stiffnesses without affecting other properties. Ink viscosity was used to match processing conditions between inks and generate scaffolds with the same surface chemistry, crystallinity, filament diameter, and architecture. Increasing the ratio of low MW PCL resulted in a significant decrease in modulus. Scaffold modulus did not affect human mesenchymal stromal cell (hMSC) differentiation under osteogenic conditions. However, hMSC response was significantly affected by scaffold stiffness in chondrogenic media. Low stiffness promoted more stable chondrogenesis whereas high stiffness drove hMSC progression toward hypertrophy. These data illustrate how this versatile platform can be used to independently modify biochemical and physical cues in a single scaffold to synergistically enhance desired cellular response., (© 2024 The Authors. Journal of Biomedical Materials Research Part A published by Wiley Periodicals LLC.)
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- 2024
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21. Immunomodulatory Strategies for Cartilage Regeneration in Osteoarthritis.
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Kennedy O, Kitson A, Okpara C, Chow LW, and Gonzalez-Fernandez T
- Subjects
- Humans, Tissue Engineering, Anti-Inflammatory Agents, Cartilage, Articular, Mesenchymal Stem Cell Transplantation, Osteoarthritis therapy
- Abstract
Osteoarthritis (OA) is the most prevalent musculoskeletal disorder and a leading cause of disability globally. Although many efforts have been made to treat this condition, current tissue engineering (TE) and regenerative medicine strategies fail to address the inflammatory tissue environment that leads to the rapid progression of the disease and prevents cartilage tissue formation. First, this review addresses in detail the current anti-inflammatory therapies for OA with a special emphasis on pharmacological approaches, gene therapy, and mesenchymal stromal cell (MSC) intra-articular administration, and discusses the reasons behind the limited clinical success of these approaches at enabling cartilage regeneration. Then, we analyze the state-of-the-art TE strategies and how they can be improved by incorporating immunomodulatory capabilities such as the optimization of biomaterial composition, porosity and geometry, and the loading of anti-inflammatory molecules within an engineered structure. Finally, the review discusses the future directions for the new generation of TE strategies for OA treatment, specifically focusing on the spatiotemporal modulation of anti-inflammatory agent presentation to allow for tailored patient-specific therapies. Impact statement Osteoarthritis (OA) is a prevalent and debilitating musculoskeletal disorder affecting millions worldwide. Despite significant advancements in regenerative medicine and tissue engineering (TE), mitigating inflammation while simultaneously promoting cartilage tissue regeneration in OA remains elusive. In this review article, we discuss current anti-inflammatory therapies and explore their potential synergy with cutting-edge cartilage TE strategies, with a special focus on novel spatiotemporal and patient-specific anti-inflammatory strategies.
- Published
- 2024
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22. Exploring participant attrition in a longitudinal follow-up of older adults: the Global Longitudinal Study of Osteoporosis in Women (GLOW) Hamilton cohort.
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Okpara C, Adachi J, Papaioannou A, Ioannidis G, and Thabane L
- Subjects
- Humans, Female, Aged, Longitudinal Studies, Follow-Up Studies, Prospective Studies, Quality of Life, Osteoporosis epidemiology
- Abstract
Objective: We explored the magnitude of attrition, its pattern and risk factors for different forms of attrition in the cohort from the Global Longitudinal Study of Osteoporosis in Women., Design: Prospective cohort study., Setting: Participants were recruited from physician practices in Hamilton, Ontario., Participants: Postmenopausal women aged ≥55 years who had consulted their primary care physician within the last 2 years., Outcome Measures: Time to all-cause, non-death, death, preventable and non-preventable attrition., Results: All 3985 women enrolled in the study were included in the analyses. The mean age of the cohort was 69.4 (SD: 8.9) years. At the end of the follow-up, 30.2% (1206/3985) of the study participants had either died or were lost to follow-up. The pattern of attrition was monotone with most participants failing to return after a missed survey. The different types of attrition examined shared common risk factors including age, smoking and being frail but differed on factors such as educational level, race, hospitalisation, quality of life and being prefrail., Conclusion: Attrition in this ageing cohort was selective to some participant characteristics. Minimising potential bias associated with such non-random attrition would require targeted measures to achieve maximum possible follow-rates among the high-risk groups identified and dealing with specific reasons for attrition in the study design and analysis., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2023
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23. The Geras virtual frailty rehabilitation program to build resilience in older adults with frailty during COVID-19: a randomized feasibility trial.
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Okpara C, Ioannidis G, Thabane L, Adachi JD, Rabinovich A, Hewston P, Lee J, McArthur C, Kennedy C, Woo T, Boulos P, Bobba R, Wang M, Thrall S, Mangin D, Marr S, Armstrong D, Patterson C, Bray S, de Wit K, Maharaj S, Misiaszek B, Sookhoo JB, Thompson K, and Papaioannou A
- Abstract
Background: The Coronavirus (COVID-19) pandemic has exacerbated the risk for poor physical and mental health outcomes among vulnerable older adults. Multicomponent interventions could potentially prevent or reduce the risk of becoming frail; however, there is limited evidence about utilizing alternative modes of delivery where access to in-person care may be challenging. This randomized feasibility trial aimed to understand how a multicomponent rehabilitation program can be delivered remotely to vulnerable older adults with frailty during the pandemic., Methods: Participants were randomized to either a multimodal or socialization arm. Over a 12-week intervention period, the multimodal group received virtual care at home, which included twice-weekly exercise in small group physiotherapy-led live-streamed sessions, nutrition counselling and protein supplementation, medication consultation via a videoconference app, and once-weekly phone calls from student volunteers, while the socialization group received only once-weekly phone calls from the volunteers. The RE-AIM (Reach, Effectiveness, Adoption, Implementation and Maintenance) framework was used to evaluate the feasibility of the program. The main clinical outcomes were change in the 5-times sit-to-stand test (5 × STS) and Depression, Anxiety and Stress Scale (DASS-21) scores. The feasibility outcomes were analyzed using descriptive statistics and expressed as frequencies and mean percent with corresponding confidence intervals (CI). Analysis of covariance (ANCOVA) was used for the effectiveness component., Results: The program enrolled 33% (n = 72) of referrals to the study (n = 220), of whom 70 were randomized. Adoption rates from different referral sources were community self-referrals (60%), community organizations (33%), and healthcare providers (25%). At the provider level, implementation rates varied from 75 to 100% for different aspects of program delivery. Participant's adherence levels included virtual exercise sessions 81% (95% CI: 75-88%), home-based exercise 50% (95% CI: 38-62%), protein supplements consumption 68% (95% CI: 55-80%), and medication optimization 38% (95% CI: 21-59%). Most participants (85%) were satisfied with the program. There were no significant changes in clinical outcomes between the two arms., Conclusion: The GERAS virtual frailty rehabilitation study for community-dwelling older adults living with frailty was feasible in terms of reach of participants, adoption across referral settings, adherence to implementation, and participant's intention to maintain the program. This program could be feasibly delivered to improve access to socially isolated older adults where barriers to in-person participation exist. However, trials with larger samples and longer follow-up are required to demonstrate effectiveness and sustained behavior change., Trial Registration: ClinicalTrials.gov NCT04500366. Registered August 5, 2020, https://clinicaltrials.gov/ct2/show/NCT04500366., (© 2023. The Author(s).)
- Published
- 2023
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24. Coronavirus disease 2019 vaccine skin testing and graded challenges in vaccine-hesitant patients.
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Heffes-Doon A, Horne N, Okpara C, Akerman M, and Fonacier L
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- Humans, Parents, Vaccination adverse effects, Vaccination Hesitancy, COVID-19 Vaccines adverse effects, COVID-19 prevention & control
- Published
- 2023
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25. Lenvatinib Plus Pembrolizumab in Previously Treated Advanced Endometrial Cancer: Updated Efficacy and Safety From the Randomized Phase III Study 309/KEYNOTE-775.
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Makker V, Colombo N, Casado Herráez A, Monk BJ, Mackay H, Santin AD, Miller DS, Moore RG, Baron-Hay S, Ray-Coquard I, Ushijima K, Yonemori K, Kim YM, Guerra Alia EM, Sanli UA, Bird S, Orlowski R, McKenzie J, Okpara C, Barresi G, and Lorusso D
- Subjects
- Female, Humans, Phenylurea Compounds adverse effects, Antineoplastic Combined Chemotherapy Protocols adverse effects, Antibodies, Monoclonal, Humanized therapeutic use, Endometrial Neoplasms drug therapy
- Abstract
Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. We report the final prespecified analysis for overall survival (OS), along with updated progression-free survival (PFS) and objective response rate (ORR), and safety from the open-label, randomized, phase III Study 309/KEYNOTE-775. In total, 827 patients with advanced, recurrent, or metastatic endometrial cancer (EC) were randomly assigned to receive lenvatinib 20 mg orally once daily plus pembrolizumab 200 mg intravenously once every 3 weeks (n = 411) or chemotherapy of the treating physician's choice (doxorubicin 60 mg/m
2 intravenously once every 3 weeks or paclitaxel 80 mg/m2 intravenously once weekly [3 weeks on; 1 week off] [n = 416]). Efficacy was reported for patients with mismatch repair proficient (pMMR) tumors and all-comers, and by subgroups (histology, prior therapy, MMR status). Updated safety was also reported.Lenvatinib plus pembrolizumab showed benefits in OS (pMMR HR, 0.70; 95% CI, 0.58 to 0.83; all-comer HR, 0.65; 95% CI, 0.55 to 0.77), PFS (pMMR HR, 0.60; 95% CI, 0.50 to 0.72; all-comer HR, 0.56; 95% CI, 0.48 to 0.66), and ORR (pMMR patients, 32.4% v 15.1%; all-comers, 33.8% v 14.7%) versus chemotherapy. OS, PFS, and ORR favored lenvatinib plus pembrolizumab in all subgroups of interest. No new safety signals were observed. Lenvatinib plus pembrolizumab continued to show improved efficacy versus chemotherapy and manageable safety in patients with previously treated advanced EC.- Published
- 2023
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26. Fragile X Messenger Ribonucleoprotein 1 (FMR1), a novel inhibitor of osteoblast/osteocyte differentiation, regulates bone formation, mass, and strength in young and aged male and female mice.
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Deosthale P, Balanta-Melo J, Creecy A, Liu C, Marcial A, Morales L, Cridlin J, Robertson S, Okpara C, Sanchez DJ, Ayoubi M, Lugo JN, Hernandez CJ, Wallace JM, and Plotkin LI
- Abstract
Fragile X Messenger Ribonucleoprotein 1 (FMR1) gene mutations lead to fragile X syndrome, cognitive disorders, and, in some individuals, scoliosis and craniofacial abnormalities. Four-month-old (mo) male mice with deletion of the FMR1 gene exhibit a mild increase in cortical and cancellous femoral bone mass. However, consequences of absence of FMR1 in bone of young/aged male/female mice and the cellular basis of the skeletal phenotype remain unknown. We found that absence of FMR1 results in improved bone properties with higher bone mineral density in both sexes and in 2- and 9-mo mice. The cancellous bone mass is higher only in females, whereas, cortical bone mass is higher in 2- and 9-mo males, but higher in 2- and lower in 9-mo female FMR1-knockout mice. Furthermore, male bones show higher biomechanical properties at 2mo, and females at both ages. Absence of FMR1 increases osteoblast/mineralization/bone formation and osteocyte dendricity/gene expression in vivo/ex vivo/in vitro, without affecting osteoclasts in vivo/ex vivo. Thus, FMR1 is a novel osteoblast/osteocyte differentiation inhibitor, and its absence leads to age-, site- and sex-dependent higher bone mass/strength., (© 2023. The Author(s).)
- Published
- 2023
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27. Comparative results of focal-cryoablation and stereotactic body radiotherapy in the treatment of unilateral, low-to-intermediate-risk prostate cancer.
- Author
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Monaco A, Sommer J, Okpara C, Lischalk JW, Haas J, Corcoran A, and Katz A
- Subjects
- Aged, Aged, 80 and over, Humans, Male, Middle Aged, Prostate-Specific Antigen, Treatment Outcome, Cryosurgery adverse effects, Prostatic Neoplasms pathology, Prostatic Neoplasms radiotherapy, Prostatic Neoplasms surgery, Radiosurgery adverse effects, Radiosurgery methods
- Abstract
Objective: The purpose of this study is to compare oncologic and functional outcomes of men with unilateral, localized PCa treated with stereotactic body radiotherapy (SBRT) versus focal cryoablation (FC)., Methods: Patients from our IRB-approved PCa database who underwent FC or SBRT and were eligible for both treatments were included. Patients with less than 1 year of follow-up or prior PCa treatment were excluded. The primary outcome was treatment failure, defined as salvage treatment or a Gleason group (GG) of ≥ 2 on post-treatment biopsy. Biochemical recurrence (BCR) was evaluated with Phoenix. Functional outcomes were based on EPIC surveys. Complications were categorized with the CTCAE 5.0. Outcomes were compared using descriptive statistics, univariate analyses, and Kaplan-Meier curve for failure-free survival (FFS) and BCR-free survival. P < 0.05 was significant., Results: 68 FC and 51 SBRT patients with a median age of 68 years (48-86) and a median follow-up time of 84 (70-101) months were included in this analysis. There was no difference in tumor risk (p = 0.47), GG (p = 0.20), or PSA (p = 0.70) among the two cohorts at baseline. At 7-year follow-up, no difference in FFS was found between the two cohorts (p = 0.70); however, significantly more FC patients had BCR (p < 0.001). At 48 months, no differences existed in urinary or bowel function; however, SBRT patients had significantly worse sexual function (p = 0.032)., Conclusion: FC and SBRT are associated with similar oncologic and functional outcomes 7-year post-treatment. These results underscore the utility of FC and SBRT for the management of unilateral low-to-intermediate-risk PCa., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)
- Published
- 2022
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28. The reporting and handling of missing data in longitudinal studies of older adults is suboptimal: a methodological survey of geriatric journals.
- Author
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Okpara C, Edokwe C, Ioannidis G, Papaioannou A, Adachi JD, and Thabane L
- Subjects
- Aged, Databases, Factual, Humans, Longitudinal Studies, Middle Aged, Research Design, Surveys and Questionnaires, Periodicals as Topic
- Abstract
Background: Missing data are common in longitudinal studies, and more so, in studies of older adults, who are susceptible to health and functional decline that limit completion of assessments. We assessed the extent, current reporting, and handling of missing data in longitudinal studies of older adults., Methods: Medline and Embase databases were searched from 2015 to 2019 for publications on longitudinal observational studies conducted among persons ≥55 years old. The search was restricted to 10 general geriatric journals published in English. Reporting and handling of missing data were assessed using questions developed from the recommended standards. Data were summarised descriptively as frequencies and proportions., Results: A total of 165 studies were included in the review from 7032 identified records. In approximately half of the studies 97 (62.5%), there was either no comment on missing data or unclear descriptions. The percentage of missing data varied from 0.1 to 55%, with a 14% average among the studies that reported having missing data. Complete case analysis was the most common method for handling missing data with nearly 75% of the studies (n = 52) excluding individual observations due to missing data, at the initial phase of study inclusion or at the analysis stage. Of the 10 studies where multiple imputation was used, only 1 (10.0%) study followed the guideline for reporting the procedure fully using online supplementary documents., Conclusion: The current reporting and handling of missing data in longitudinal observational studies of older adults are inadequate. Journal endorsement and implementation of guidelines may potentially improve the quality of missing data reporting. Further, authors should be encouraged to use online supplementary files to provide additional details on how missing data were addressed, to allow for more transparency and comprehensive appraisal of studies., (© 2022. The Author(s).)
- Published
- 2022
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29. Outcomes of Breast Cancer Patients Treated with Chemotherapy, Biologic Therapy, Endocrine Therapy, or Active Surveillance During the COVID-19 Pandemic.
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Marks DK, Budhathoki N, Kucharczyk J, Fa'ak F, D'Abreo N, Kwa M, Plasilova M, Dhage S, Soe PP, Becker D, Hindenburg A, Lee J, Winner M, Okpara C, Daly A, Shah D, Ramdhanny A, Meyers M, Oratz R, Speyer J, Novik Y, Schnabel F, Jones SA, and Adams S
- Subjects
- Biological Therapy, COVID-19 Testing, Female, Humans, Pandemics, SARS-CoV-2, Watchful Waiting, Breast Neoplasms drug therapy, COVID-19 epidemiology
- Abstract
Purpose: Provide real-world data regarding the risk for SARS-CoV-2 infection and mortality in breast cancer (BC) patients on active cancer treatment., Methods: Clinical data were abstracted from the 3778 BC patients seen at a multisite cancer center in New York between February 1, 2020 and May 1, 2020, including patient demographics, tumor histology, cancer treatment, and SARS-CoV-2 testing results. Incidence of SARS-CoV-2 infection by treatment type (chemotherapy [CT] vs endocrine and/or HER2 directed therapy [E/H]) was compared by Inverse Probability of Treatment Weighting. In those diagnosed with SARS-CoV-2 infection, Mann-Whitney test was used to a assess risk factors for severe disease and mortality., Results: Three thousand sixty-two patients met study inclusion criteria with 641 patients tested for SARS-COV-2 by RT-PCR or serology. Overall, 64 patients (2.1%) were diagnosed with SARS-CoV-2 infection by either serology, RT-PCR, or documented clinical diagnosis. Comparing matched patients who received chemotherapy (n = 379) with those who received non-cytotoxic therapies (n = 2343) the incidence of SARS-CoV-2 did not differ between treatment groups (weighted risk; 3.5% CT vs 2.7% E/H, P = .523). Twenty-seven patients (0.9%) expired over follow-up, with 10 deaths attributed to SARS-CoV-2 infection. Chemotherapy was not associated with increased risk for death following SARS-CoV-2 infection (weighted risk; 0.7% CT vs 0.1% E/H, P = .246). Advanced disease (stage IV), age, BMI, and Charlson's Comorbidity Index score were associated with increased mortality following SARS-CoV-2 infection (P ≤ .05)., Conclusion: BC treatment, including chemotherapy, can be safely administered in the context of enhanced infectious precautions, and should not be withheld particularly when given for curative intent., (© The Author(s) 2022. Published by Oxford University Press.)
- Published
- 2022
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30. Phase I/II study of single-agent lenvatinib in children and adolescents with refractory or relapsed solid malignancies and young adults with osteosarcoma (ITCC-050) ☆ .
- Author
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Gaspar N, Campbell-Hewson Q, Gallego Melcon S, Locatelli F, Venkatramani R, Hecker-Nolting S, Gambart M, Bautista F, Thebaud E, Aerts I, Morland B, Rossig C, Canete Nieto A, Longhi A, Lervat C, Entz-Werle N, Strauss SJ, Marec-Berard P, Okpara CE, He C, Dutta L, and Casanova M
- Subjects
- Adolescent, Child, Humans, Iodine Radioisotopes therapeutic use, Neoplasm Recurrence, Local drug therapy, Phenylurea Compounds, Quinolines, Young Adult, Antineoplastic Agents adverse effects, Bone Neoplasms drug therapy, Osteosarcoma drug therapy
- Abstract
Background: We report results from the phase I dose-finding and phase II expansion part of a multicenter, open-label study of single-agent lenvatinib in pediatric and young adult patients with relapsed/refractory solid tumors, including osteosarcoma and radioiodine-refractory differentiated thyroid cancer (RR-DTC) (NCT02432274)., Patients and Methods: The primary endpoint of phase I was to determine the recommended phase II dose (RP2D) of lenvatinib in children with relapsed/refractory solid malignant tumors. Phase II primary endpoints were progression-free survival rate at 4 months (PFS-4) for patients with relapsed/refractory osteosarcoma; and objective response rate/best overall response for patients with RR-DTC at the RP2D., Results: In phase I, 23 patients (median age, 12 years) were enrolled. With lenvatinib 14 mg/m
2 , three dose-limiting toxicities (hypertension, n = 2; increased alanine aminotransferase, n = 1) were reported, establishing 14 mg/m2 as the RP2D. In phase II, 31 patients with osteosarcoma (median age, 15 years) and 1 patient with RR-DTC (age 17 years) were enrolled. For the osteosarcoma cohort, PFS-4 (binomial estimate) was 29.0% [95% confidence interval (CI) 14.2% to 48.0%; full analysis set: n = 31], PFS-4 by Kaplan-Meier estimate was 37.8% (95% CI 20.0% to 55.4%; full analysis set) and median PFS was 3.0 months (95% CI 1.8-5.4 months). The objective response rate was 6.7% (95% CI 0.8% to 22.1%). The patient with RR-DTC had a best overall response of partial response. Some 60.8% of patients in phase I and 22.6% of patients in phase II (with osteosarcoma) had treatment-related treatment-emergent adverse events of grade ≥3., Conclusions: The lenvatinib RP2D was 14 mg/m2 . Single-agent lenvatinib showed activity in osteosarcoma; however, the null hypothesis could not be rejected. The safety profile was consistent with previous tyrosine kinase inhibitor studies. Lenvatinib is currently being investigated in osteosarcoma in combination with chemotherapy as part of a randomized, controlled trial (NCT04154189), in pediatric solid tumors in combination with everolimus (NCT03245151), and as a single agent in a basket study with enrollment ongoing (NCT04447755)., Competing Interests: Disclosure SGM: personal fees from Loxo Oncology, Bayer, and EUSA Pharma, outside the submitted work. FL: consultant or advisory role for Novartis, Amgen, Bellicum Pharmaceuticals, and Pfizer; honoraria for speaking at symposia from Amgen, Novartis, bluebird bio, Miltenyi, Bellicum Pharmaceuticals, and Jazz Pharmaceuticals. FB: consultant or advisory role for Bayer, Amgen, Roche, Sanofi, and EUSA Pharma; honoraria for speaking at symposia from Amgen and Jazz Pharmaceuticals; support for attending symposia from Takeda, EUSA Pharma, Shire, and Jazz Pharmaceuticals. CR: consultant or advisory role for Amgen, Bristol Myers Squibb (BMS), Celgene, Genentech, Novartis, Pfizer, and Roche. ACN: personal fees from Bayer and EUSA Pharma, outside of the submitted work. AL: nonfinancial support and ‘other’ from PharmaMar; grants and nonfinancial support from Takeda, during the conduct of the study. SJS: consultant or advisory role for Lilly outside the submitted work. CO: employee of Eisai Ltd. CH: employee of Eisai Inc. LD: employee of Eisai Inc. MC: advisory roles for AstraZeneca, Bayer, BMS, Eisai, Lilly, and Roche outside the submitted work. All other authors have declared no conflicts of interest., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)- Published
- 2021
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31. Risk Factors for Chronic Kidney Disease in Newly Diagnosed Hypertensive Subjects in Southeast Nigeria.
- Author
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Obi EC, Chukwuonye II, Anyabolu EN, Okpara C, Ohagwu KA, Oladele CO, Oviasu E, Uwa O, Agaba EI, and Ojogwu LI
- Subjects
- Cross-Sectional Studies, Humans, Nigeria epidemiology, Prevalence, Risk Factors, Uric Acid, Hypertension complications, Hypertension epidemiology, Renal Insufficiency, Chronic diagnosis, Renal Insufficiency, Chronic epidemiology, Renal Insufficiency, Chronic etiology
- Abstract
Background: The aim of this study was to determine the prevalence and associated risk factors for chronic kidney disease (CKD) in newly diagnosed hypertensive patients., Materials and Methods: This was a cross-sectional analytical study involving consenting newly diagnosed hypertensive patients who presented at GOPD of Federal Medical Centre, Umuahia, within 0-3 months of diagnosis; and non-hypertensive controls. A semi-structured interviewer- administered questionnaire was used to record the socio-demographic, anthropometric, clinical and bio-chemical characteristics of the respondents. Data were analyzed and compared between the hypertensive group and the non-hypertensive control group., Results: Two hundred and sixty participants took part in the study. However, only 240 completed the study (120 hypertensive, and 120 control participants). After follow-up for 3 months, 42 (35.0%) hypertensive patients had CKD compared to 11 (9.2%) of the non-hypertensive control group. The prevalence of CKD in the hypertensive participants was significantly higher (2=23.27, p<0.001). Multivariate regression analysis of CKD with variables in the hypertensive study group showed an association between CKD and sex (p=0.020), serum triglycerides (p=0.030) as well as serum uric acid (p=0.030). In the control group there was significant association between CKD and sex (p=0.020), serum total cholesterol (p=0.030) as well as serum uric acid (p=0.030)., Conclusion: The prevalence of CKD among newly diagnosed hypertensives in southeast Nigeria was high. In this group, CKD had an association with sex, serum uric acid and serum triglyceride.
- Published
- 2020
32. The socioeconomic impact of burns in Lagos, Nigeria: a one-year prospective study.
- Author
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Ahachi CN, Fadeyibi IO, Chira MK, Abikoye FO, and Okpara CO
- Abstract
A one-year prospective study of burn patients presenting to the National Orthopaedic Hospital, Igbobi, Lagos from June 1, 2007 to May 31, 2008 was conducted to evaluate the socioeconomic impact of burn injuries sustained by the patients. A proforma reflecting the various data of interest was the main instrument of the study. The data was subjected to simple statistical analysis. A total of 52 patients with a mean age of 25 ± 17.1 years were studied. There were 27 males and 25 females giving a M:F ratio of 1.1:1. Man-hours were lost by 88.5% of the patients, 55.8% of whom were income earners. About 74% of the patients had returned to work or school at the conclusion of the study. The most common opportunity cost of treatment was a relative stopping work or school. Half of the patients were unsatisfied with their appearance and 26.9% desired cosmetic surgery. Social interactions were normal in 74.5% of the patients and none reported a poor quality of life. The study showed a significant socioeconomic burden from burns. It highlighted the importance of the informal sociocultural support system and the need for formal, well-structured social support systems.
- Published
- 2017
33. Factors Influencing Antenatal Haematinics Prescription Behaviour of Physicians in Calabar, Nigeria.
- Author
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Akpan U, Agan T, Monjok E, Okpara C, and Etuk S
- Abstract
Background: Routine iron and folic acid supplementation in pregnancy have been proved to be effective in reducing the prevalence and morbidities of anaemia. However, there is limited data regarding the prescription habits of physician obstetric care givers., Aim: This study set to investigate the attitudes and factors which influence the practice among physicians in University of Calabar Teaching Hospital (UCTH)., Material and Methods: A questionnaire based cross-sectional survey was conducted among randomly recruited physician offering antenatal services between August and September 2015. Systemic sampling was used to select 70 doctors in the departmental duty roster. Data were presented in percentages and proportion. Chi-square test was used to test the association between variables. Statistical significance was set at p < 0.05., Results: The response rate was 100%. The mean age of the respondents was 30.26 ± 6.67 years. All the respondents routinely prescribed haematinics to pregnant women but 34.3% of them did not prescribe to apparently healthy clients in their first trimester. Only 30% and 11.4% of them prescribed it in the postnatal and preconception periods respectively. Brands that contained iron, folate and vitamins as a single capsule were mostly favoured, and information about brands of drugs was mostly provided by the pharmaceutical sales representatives. Younger doctors were more likely to offer haematinics with nutritional counselling compared to older respondents. However, there was no significant relationship between haematinics prescription and sex (p = 0.3560), Age (p = 0.839), current professional status (p = 0.783), and client complaint of side effect of medication (p = 0.23). Oral medication was mostly utilised., Conclusion: Effort to effectively control anaemia in pregnancy should involve re-orientation of physician obstetric care providers especially about prenatal and postnatal medication and counselling.
- Published
- 2017
- Full Text
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