60 results on '"Dupuis LL"'
Search Results
2. Prevention of cisplatin-induced ototoxicity in children and adolescents with cancer: a clinical practice guideline
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Freyer, DR, Brock, PR, Chang, KW, Dupuis, LL, Epelman, S, Knight, K, Mills, D, Phillips, R, Potter, E, Risby, D, Simpkin, P, Sullivan, M, Cabral, S, Robinson, PD, Sung, L, Freyer, DR, Brock, PR, Chang, KW, Dupuis, LL, Epelman, S, Knight, K, Mills, D, Phillips, R, Potter, E, Risby, D, Simpkin, P, Sullivan, M, Cabral, S, Robinson, PD, and Sung, L
- Abstract
Despite ototoxicity being a prevalent consequence of cisplatin chemotherapy, little guidance exists on interventions to prevent this permanent and progressive adverse event. To develop a clinical practice guideline for the prevention of cisplatin-induced ototoxicity in children and adolescents with cancer, we convened an international, multidisciplinary panel of experts and patient advocates to update a systematic review of randomised trials for the prevention of cisplatin-induced ototoxicity. The systematic review identified 27 eligible adult and paediatric trials that evaluated amifostine, sodium diethyldithiocarbamate or disulfiram, systemic sodium thiosulfate, intratympanic therapies, and cisplatin infusion duration. Regarding systemic sodium thiosulfate, the panel made a strong recommendation for administration in non-metastatic hepatoblastoma, a weak recommendation for administration in other non-metastatic cancers, and a weak recommendation against its routine use in metastatic cancers. Amifostine, sodium diethyldithiocarbamate, and intratympanic therapy should not be routinely used. Cisplatin infusion duration should not be altered as a means to reduce ototoxicity. Further research to determine the safety of sodium thiosulfate in patients with metastatic cancer is encouraged.
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- 2020
3. Clinical Practice Guideline for Systemic Antifungal Prophylaxis in Pediatric Patients With Cancer and Hematopoietic Stem-Cell Transplantation Recipients
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Lehrnbecher, T, Fisher, BT, Phillips, B, Beauchemin, M, Carlesse, F, Castagnola, E, Duong, N, Dupuis, LL, Fioravantti, V, Groll, AH, Haeusler, GM, Roilides, E, Science, M, Steinbach, WJ, Tissing, W, Warris, A, Patel, P, Robinson, PD, Sung, L, Lehrnbecher, T, Fisher, BT, Phillips, B, Beauchemin, M, Carlesse, F, Castagnola, E, Duong, N, Dupuis, LL, Fioravantti, V, Groll, AH, Haeusler, GM, Roilides, E, Science, M, Steinbach, WJ, Tissing, W, Warris, A, Patel, P, Robinson, PD, and Sung, L
- Abstract
PURPOSE: To develop a clinical practice guideline for systemic antifungal prophylaxis in pediatric patients with cancer and hematopoietic stem-cell transplantation (HSCT) recipients. METHODS: Recommendations were developed by an international multidisciplinary panel that included a patient advocate. We conducted a systematic review of systemic antifungal prophylaxis in children and adults with cancer and HSCT recipients. The Grading of Recommendations Assessment, Development, and Evaluation approach was used to make strong or weak recommendations and to classify level of evidence as high, moderate, low, or very low. The panel considered directness of the data to pediatric patients. RESULTS: There were 68 randomized trials included in the systematic review, of which 6 (9%) were conducted in a solely pediatric population. Strong recommendations were made to administer systemic antifungal prophylaxis to children and adolescents receiving treatment of acute myeloid leukemia, to those undergoing allogeneic HSCT pre-engraftment, and to those receiving systemic immunosuppression for graft-versus-host disease treatment. A strong recommendation was made to administer a mold-active agent with an echinocandin or a mold-active azole when systemic antifungal prophylaxis is warranted. For children younger than 13 years of age, an echinocandin, voriconazole, or itraconazole is suggested. Posaconazole may also be used in those age 13 years or older. A strong recommendation against routine administration of amphotericin as systemic antifungal prophylaxis was made. CONCLUSION: We developed a clinical practice guideline for systemic antifungal prophylaxis administration in pediatric patients with cancer and HSCT recipients. Implementation and assessment of guideline-concordant rates and impacts are important future steps.
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- 2020
4. Guideline for Antibacterial Prophylaxis Administration in Pediatric Cancer and Hematopoietic Stem Cell Transplantation
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Lehrnbecher, T, Fisher, BT, Phillips, B, Alexander, S, Ammann, RA, Beauchemin, M, Carlesse, F, Castagnola, E, Davis, BL, Dupuis, LL, Egan, G, Groll, AH, Haeusler, GM, Santolaya, M, Steinbach, WJ, van de Wetering, M, Wolf, J, Cabral, S, Robinson, PD, Sung, L, Lehrnbecher, T, Fisher, BT, Phillips, B, Alexander, S, Ammann, RA, Beauchemin, M, Carlesse, F, Castagnola, E, Davis, BL, Dupuis, LL, Egan, G, Groll, AH, Haeusler, GM, Santolaya, M, Steinbach, WJ, van de Wetering, M, Wolf, J, Cabral, S, Robinson, PD, and Sung, L
- Abstract
BACKGROUND: Bacteremia and other invasive bacterial infections are common among children with cancer receiving intensive chemotherapy and in pediatric recipients of hematopoietic stem cell transplantation (HSCT). Systemic antibacterial prophylaxis is one approach that can be used to reduce the risk of these infections. Our purpose was to develop a clinical practice guideline (CPG) for systemic antibacterial prophylaxis administration in pediatric patients with cancer and those undergoing HSCT. METHODS: An international and multidisciplinary panel was convened with representation from pediatric hematology/oncology and HSCT, pediatric infectious diseases (including antibiotic stewardship), nursing, pharmacy, a patient advocate, and a CPG methodologist. The panel used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to generate recommendations based on the results of a systematic review of the literature. RESULTS: The systematic review identified 114 eligible randomized trials of antibiotic prophylaxis. The panel made a weak recommendation for systemic antibacterial prophylaxis for children receiving intensive chemotherapy for acute myeloid leukemia and relapsed acute lymphoblastic leukemia (ALL). Weak recommendations against the routine use of systemic antibacterial prophylaxis were made for children undergoing induction chemotherapy for ALL, autologous HSCT and allogeneic HSCT. A strong recommendation against its routine use was made for children whose therapy is not expected to result in prolonged severe neutropenia. If used, prophylaxis with levofloxacin was recommended during severe neutropenia. CONCLUSIONS: We present a CPG for systemic antibacterial prophylaxis administration in pediatric cancer and HSCT patients. Future research should evaluate the long-term effectiveness and adverse effects of prophylaxis.
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- 2020
5. Reducing pain in children with cancer: Methodology for the development of a clinical practice guideline
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Loeffen, EAH, Kremer, LCM (Leontien), Wetering, MD, Mulder, RL, Font-Gonzalez, A, Dupuis, LL, Campbell, F, Tissing, WJE, Anghelescu, DL, Birnie, K, Bont, JM, Bredlau, AL, Cullen, P, Daniels, S, Dick, B, van Dijk, Monique, Dingeman, RS, Evan, E, Gegg, J, Gibson, F, Grotel, M, Jibb, L, Kao, R, Knops, R, Kulkarni, K, Leroy, P, Liossi, C, Ljungman, G, McLean, J, Mensink, M, Michiels, E, Muckaden, MA, Newman, B, Positano, K, Rijsdijk, M, Rowe, E, Sangha, G, Stinson, J, Taddio, A, Taylor, H, Tutelman, P, Twycross, A, Wijnen, Mark, Zeltzer, L, Loeffen, EAH, Kremer, LCM (Leontien), Wetering, MD, Mulder, RL, Font-Gonzalez, A, Dupuis, LL, Campbell, F, Tissing, WJE, Anghelescu, DL, Birnie, K, Bont, JM, Bredlau, AL, Cullen, P, Daniels, S, Dick, B, van Dijk, Monique, Dingeman, RS, Evan, E, Gegg, J, Gibson, F, Grotel, M, Jibb, L, Kao, R, Knops, R, Kulkarni, K, Leroy, P, Liossi, C, Ljungman, G, McLean, J, Mensink, M, Michiels, E, Muckaden, MA, Newman, B, Positano, K, Rijsdijk, M, Rowe, E, Sangha, G, Stinson, J, Taddio, A, Taylor, H, Tutelman, P, Twycross, A, Wijnen, Mark, and Zeltzer, L
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- 2019
6. Measurement properties of instruments to assess pain in children and adolescents with cancer: a systematic review protocol
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Loeffen, EAH, Stinson, JN, Birnie, KA, van Dijk, Monique, Kulkarni, K, Rijsdijk, M, Font-Gonzalez, A, Dupuis, LL, van Dalen, EC, Mulder, RL, Campbell, F, Tissing, WJE, Wetering, MD, Gibson, F, Loeffen, EAH, Stinson, JN, Birnie, KA, van Dijk, Monique, Kulkarni, K, Rijsdijk, M, Font-Gonzalez, A, Dupuis, LL, van Dalen, EC, Mulder, RL, Campbell, F, Tissing, WJE, Wetering, MD, and Gibson, F
- Published
- 2019
7. Guideline for the Management of Clostridium Difficile Infection in Children and Adolescents With Cancer and Pediatric Hematopoietic Stem-Cell Transplantation Recipients
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Diorio, C, Robinson, PD, Ammann, RA, Castagnola, E, Erickson, K, Esbenshade, A, Fisher, BT, Haeusler, GM, Kuczynski, S, Lehrnbecher, T, Phillips, R, Cabral, S, Dupuis, LL, Sung, L, Diorio, C, Robinson, PD, Ammann, RA, Castagnola, E, Erickson, K, Esbenshade, A, Fisher, BT, Haeusler, GM, Kuczynski, S, Lehrnbecher, T, Phillips, R, Cabral, S, Dupuis, LL, and Sung, L
- Abstract
PURPOSE: The aim of this work was to develop a clinical practice guideline for the prevention and treatment of Clostridium difficile infection (CDI) in children and adolescents with cancer and pediatric hematopoietic stem-cell transplantation (HSCT) patients. METHODS: An international multidisciplinary panel of experts in pediatric oncology and infectious diseases with patient advocate representation was convened. We performed systematic reviews of randomized controlled trials for the prevention or treatment of CDI in any population and considered the directness of the evidence to children with cancer and pediatric HSCT patients. We used the Grading of Recommendations Assessment, Development, and Evaluation approach to generate recommendations. RESULTS: The panel made strong recommendations to administer either oral metronidazole or oral vancomycin for the initial treatment of nonsevere CDI and oral vancomycin for the initial treatment of severe CDI. Fidaxomicin may be considered in the setting of recurrent CDI. The panel suggested that probiotics not be routinely used for the prevention of CDI, and that monoclonal antibodies and probiotics not be routinely used for the treatment of CDI. A strong recommendation to not use fecal microbiota transplantation was made in this population. We identified key knowledge gaps and suggested directions for future research. CONCLUSION: We present a guideline for the prevention and treatment of CDI in children and adolescents with cancer and pediatric HSCT patients. Future research should include randomized controlled trials that involve children with cancer and pediatric HSCT patients to improve the management of CDI in this population.
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- 2018
8. Genetic Determinants of Busulfan Clearance and Outcomes in Pediatric Patients Undergoing Hematopoietic Stem Cell Transplantation- Result of a Multicentric Prospective Study on Behalf of the Pediatric Disease Working Party of the European Blood and Marrow Transplantation Group
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Ansari, Marc, primary, Rezgui, M A, additional, Uppugunduri, Chakradhara Rao S, additional, Théoret, Yves, additional, Chalandon, Yves, additional, Dupuis, LL, additional, Schechter, Tal, additional, Bartelink, IH, additional, Boelens, Jaap Jan, additional, Dalle, Jean-Hugues, additional, Azarnoush, Saba, additional, Sedlacek, Petr, additional, Lewis, Victor A., additional, Mezziani, S, additional, Vachon, M-F, additional, Duval, Michel, additional, Champagne, Martin A., additional, Peters, Christina, additional, Bittencourt, Henrique, additional, and Krajinovic, Maja, additional
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- 2014
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9. Guideline for the management of Clostridioides difficile infection in pediatric patients with cancer and hematopoietic cell transplantation recipients: 2024 update.
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Patel P, Robinson PD, Fisher BT, Phillips R, Morgan JE, Lehrnbecher T, Kuczynski S, Koenig C, Haeusler GM, Esbenshade A, Elgarten C, Duong N, Diorio C, Castagnola E, Beauchemin MP, Ammann RA, Dupuis LL, and Sung L
- Abstract
Our objective was to update a clinical practice guideline for the prevention and treatment of Clostridioides difficile infection (CDI) in pediatric patients with cancer and hematopoietic cell transplantation recipients. We reconvened an international multi-disciplinary panel. A systematic review of randomized controlled trials (RCTs) for the prevention or treatment of CDI in any population was updated and identified 31 new RCTs. Strong recommendations were made to use either oral metronidazole or oral vancomycin for non-severe CDI treatment, and to use either oral vancomycin or oral fidaxomicin for severe CDI. A strong recommendation that fecal microbiota transplantation should not be routinely used to treat CDI was also made. The panel made two new good practice statements to follow infection control practices including isolation in patients experiencing CDI, and to minimize systemic antibacterial administration where feasible, especially in patients who have experienced CDI., Competing Interests: BTF has served on a data safety monitoring board for Astellas and BTF's institution has received grant support from Allovir and Pfizer as well as CDC, FDA and NIH for research performed. CD has received support from Abramson Cancer Center K12 and a CIHR Fellowship Award. TL's institution has received an unrestricted research grant by Gilead Sciences and TL has received payments or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from: Astra Zeneca, EUSA Pharma, Gilead Sciences, MSD/Merck and Pfizer. TL has received support for attending meetings and/or travel from EUSA Pharma and has served on a data safety monitoring board or advisory board for: EUSA Pharma, Gilead Sciences, Merck/MSD, Mundipharma, Pfizer and Pharming. TL has had a leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid at: Working Party Infection German Society of Pediatric Oncology and Hematology and Working Party Infection German Society of Pediatric Infectious Diseases. LS is supported by the Canada Research Chair in Pediatric Oncology Supportive Care. No other authors declared a conflict of interest., (© 2024 The Author(s).)
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- 2024
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10. Supportive Care in Pediatric Oncology: Opportunities and Future Directions.
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Freedman JL, Beeler DM, Bowers A, Bradford N, Cheung YT, Davies M, Dupuis LL, Elgarten CW, Jones TM, Jubelirer T, Miller TP, Patel P, Phillips CA, Wardill HR, and Orsey AD
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The optimization of outcomes for pediatric cancer patients relies on the successful advancement of supportive care to ease the treatment burden and mitigate the long-term impacts of cancer therapy. Advancing pediatric supportive care requires research prioritization as well as the development and implementation of innovations. Like the prevailing theme throughout pediatric oncology, there is a clear need for personalized or precision approaches that are consistent, evidence-based, and guided by clinical practice guidelines. By incorporating technology and datasets, we can address questions which may not be feasible to explore in clinical trials. Now is the time to listen to patients' voices by using patient-reported outcomes (PROs) to ensure that their contributions and experiences inform clinical care plans. Furthermore, while the extrapolation of knowledge and approaches from adult populations may suffice in the absence of pediatric-specific evidence, there is a critical need to specifically understand and implement elements of general and developmental pediatrics like growth, nutrition, development, and physical activity into care. Increased research funding for pediatric supportive care is critical to address resource availability, equity, and disparities across the globe. Our patients deserve to enjoy healthy, productive lives with optimized and enriched supportive care that spans the spectrum from diagnosis to survivorship.
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- 2023
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11. Guideline for the management of fatigue in children and adolescents with cancer or pediatric hematopoietic cell transplant recipients: 2023 update.
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Patel P, Robinson PD, van der Torre P, Tomlinson D, Seelisch J, Oberoi S, Morgan JE, Hinds PS, Götte M, Gibson F, Duong N, Davis H, Culos-Reed SN, Cataudella D, Miranda V, Dupuis LL, and Sung L
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Objective was to update a clinical practice guideline (CPG) for the management of fatigue in children and adolescents with cancer or pediatric hematopoietic cell transplant recipients. We reconvened a multi-disciplinary and multi-national panel. While the previous 2018 CPG evaluated adult and pediatric randomized controlled trials (RCTs) to manage fatigue, this 2023 update revised previous recommendations based only on pediatric RCTs. Twenty RCTs were included in the updated systematic review. Physical activity significantly reduced fatigue (standardized mean difference -0.44, 95% confidence interval -0.64 to -0.24; n = 8 RCTs). Using the 2018 recommendations as a basis, the panel continued to make strong recommendations to use physical activity, and to offer relaxation, mindfulness or both, to manage fatigue in pediatric patients. Cognitive or cognitive behavioral therapies may be offered. Pharmacological approaches should not be routinely used. The panel made a new good practice statement to routinely assess for fatigue, ideally using a validated scale., Competing Interests: PSH received grants or research support from NIH; royalties or licenses from Lippincott; consulting fees from MSKCC and participated on the REACH Board at Nemours, Delaware. SNCR received grants from CIHR, CCS and Kids Cancer Care-IMPACT. LS is supported by the Canada Research Chair in Pediatric Oncology Supportive Care. No other authors declared a conflict of interest., (© 2023 The Author(s).)
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- 2023
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12. Symptom management care pathway adaptation process and specific adaptation decisions.
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Vettese E, Sherani F, King AA, Yu L, Aftandilian C, Baggott C, Agarwal V, Nagasubramanian R, Kelly KM, Freyer DR, Orgel E, Bradfield SM, Kyono W, Roth M, Klesges LM, Beauchemin M, Grimes A, Tomlinson G, Dupuis LL, and Sung L
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- Child, Humans, Palliative Care, Critical Pathways, Neoplasms
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Background: There is substantial heterogeneity in symptom management provided to pediatric patients with cancer. The primary objective was to describe the adaptation process and specific adaptation decisions related to symptom management care pathways based on clinical practice guidelines. The secondary objective evaluated if institutional factors were associated with adaptation decisions., Methods: Fourteen previously developed symptom management care pathway templates were reviewed by an institutional adaptation team composed of two clinicians at each of 10 institutions. They worked through each statement for all care pathway templates sequentially. The institutional adaptation team made the decision to adopt, adapt or reject each statement, resulting in institution-specific symptom management care pathway drafts. Institutional adaption teams distributed the 14 care pathway drafts to their respective teams; their feedback led to care pathway modifications., Results: Initial care pathway adaptation decision making was completed over a median of 4.2 (interquartile range 2.0-5.3) weeks per institution. Across all institutions and among 1350 statements, 551 (40.8%) were adopted, 657 (48.7%) were adapted, 86 (6.4%) were rejected and 56 (4.1%) were no longer applicable because of a previous decision. Most commonly, the reason for rejection was not agreeing with the statement (70/86, 81.4%). Institutional-level factors were not significantly associated with statement rejection., Conclusions: Acceptability of the 14 care pathways was evident by most statements being adopted or adapted. The adaptation process was accomplished over a relatively short timeframe. Future work should focus on evaluation of care pathway compliance and determination of the impact of care pathway-consistent care on patient outcomes., Trial Registration: clinicaltrials.gov, NCT04614662. Registered 04/11/2020, https://clinicaltrials.gov/ct2/show/NCT04614662?term=NCT04614662&draw=2&rank=1 ., (© 2023. The Author(s).)
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- 2023
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13. Clinical practice guideline recommendation summaries for pediatric oncology health care professionals: A qualitative study.
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Santesso N, Beauchemin M, Robinson PD, Walsh AM, Sugalski AJ, Lo T, Dang H, Fisher BT, Grimes AC, Wrightson AR, Yu LC, Sung L, and Dupuis LL
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- Child, Humans, Qualitative Research, Medical Oncology, Health Personnel, Neoplasms
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Objective: To develop a summary format of clinical practice guideline (CPG) recommendations to improve understandability among health care professionals., Methods: We developed a summary format based on current research and used the "Think Aloud" technique in one-on-one cognitive interviews to iteratively improve it. Interviews of health care professionals from Children's Oncology Group-member, National Cancer Institute Community Oncology Research Program sites were conducted. After every five interviews (a round), responses were reviewed, and changes made to the format until it was well understood and no new, substantive suggestions for revision were raised. We took a directed (deductive) approach to content analysis of the interview notes to identify concerns related to recommendation summary usability, understandability, validity, applicability and visual appeal., Results: During seven rounds of interviews with 33 health care professionals, we identified important factors that influenced understandability. Participants found understanding weak recommendations more challenging than strong recommendations. Understanding was improved when the term 'conditional' recommendation was used instead of 'weak' recommendation. Participants found a Rationale section to be very helpful but desired more information when a recommendation entailed a practice change. In the final format, the recommendation strength is clearly indicated in the title, highlighted, and defined within a text box. The rationale for the recommendation is in a column on the left, with supporting evidence on the right. In a bulleted list, the Rationale section describes the benefits and harms and additional factors, such as implementation, that were considered by the CPG developers. Each bullet under the supporting evidence section indicates the level of evidence with an explanation and the supporting studies with hyperlinks when applicable., Conclusions: A summary format to present strong and conditional recommendations was created through an iterative interview process. The format is straightforward, making it easy for organizations and CPG developers to use it to communicate recommendations clearly to intended users., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Santesso et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
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- 2023
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14. Feasibility of three times weekly symptom screening in pediatric cancer patients.
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Calligan M, Chakkalackal L, Dadzie G, Tardif-Theriault C, Cook S, Vettese E, Soman D, Kuczynski S, Schechter T, Dupuis LL, and Sung L
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- Humans, Child, Feasibility Studies, Symptom Assessment, Psychometrics, Early Detection of Cancer, Neoplasms complications, Neoplasms diagnosis
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Objective: Primary objective was to determine the feasibility of three times weekly symptom reporting by pediatric cancer patients for eight weeks., Methods: We included English-speaking patients 8-18 years of age with cancer. Patients were sent reminders by text or email to complete Symptom Screening in Pediatrics Tool (SSPedi) three times weekly for eight weeks. When patients reported at least one severely bothersome symptom, the symptom report was emailed to the primary healthcare team. Patient-reported outcomes were obtained at baseline, week 4 ± 1 and week 8 ± 1. Symptom documentation, intervention provision for symptoms and unplanned healthcare encounters were determined by chart review at weeks 4 and 8. The primary endpoint was feasibility, defined as at least 75% patients achieving adherence with at least 60% of SSPedi evaluations. We planned to enroll successive cohorts until this threshold was met., Results: Two cohorts consisting of 30 patients (cohort 1 (n = 20) and cohort 2 (n = 10)) were required to meet the feasibility threshold. In cohort 1, 11/20 (55%) met the SSPedi completion threshold. Interventions applied after cohort 1 included engaging parents to facilitate pediatric patient self-report, offering mechanisms to remember username and password and highlighting potential benefits of symptom feedback to clinicians. In cohort 2, 9/10 (90%) met the SSPedi completion threshold and thus feasibility was met. Patient-reported outcomes and chart review outcomes were obtained for all participants in cohort 2., Conclusions: Three times weekly symptom reporting by pediatric patients with cancer for eight weeks was feasible. Mechanisms to enhance three times weekly symptom reporting were identified and implemented. Future studies of longitudinal symptom screening can now be planned., (© 2023. The Author(s).)
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- 2023
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15. Reliability and validity of proxy-SSPedi and mini-SSPedi in pediatric patients 2-7 years receiving cancer treatments.
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Tomlinson D, Dupuis LL, Johnston DL, Kuczynski S, Patel S, Schechter T, Vettese E, Mairs M, Tomlinson GA, and Sung L
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- Advance Directives, Ambulatory Care Facilities, Child, Child, Preschool, Humans, Quality of Life, Reproducibility of Results, Neoplasms drug therapy, Pediatrics
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Background: Symptom Screening in Pediatrics Tool (SSPedi) was developed for symptom screening by children 8-18 years. Objectives were to evaluate the reliability and validity of proxy-SSPedi and self-report mini-SSPedi for younger children., Methods: This multi-center study enrolled guardians of children 2-7 years receiving cancer treatments (proxy-SSPedi) and their children 4-7 years (mini-SSPedi). The two populations were: (1) More symptomatic group where children were receiving active cancer treatment and were in hospital or clinic for four consecutive days; and (2) Less symptomatic group where children were receiving maintenance therapy for acute lymphoblastic leukemia or had completed cancer therapy. Proxy-SSPedi or mini-SSPedi were completed with measures of mucositis, nausea, pain, quality of life and overall symptoms. Respondents in the more symptomatic group repeated proxy-SSPedi/mini-SSPedi and a global symptom change scale 3 days later., Results: There were 402 guardians and 326 children included in the analysis. Test re-test reliability of proxy-SSPedi showed intraclass correlation coefficient (ICC) 0.83 (95% confidence interval (CI) 0.72-0.90). Mean difference in proxy-SSPedi between more and less symptomatic groups was 9.7 (95% CI 8.3-11.1). Proxy-SSPedi was responsive to change and hypothesized relationships between measures were observed. With a priori threshold ≥0.6, inter-rater ICC among all dyads and those 6-7 years were 0.54 (95% CI 0.45-0.62) and 0.62 (95% CI 0.50-0.71) respectively. Among participating children, other hypothesized reliability and validity thresholds were generally met., Conclusions: Proxy-SSPedi is reliable, valid and responsive in children 2-7 years old receiving cancer treatments. Mini-SSPedi can be used for children 6-7 years of age., (© 2022. The Author(s).)
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- 2022
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16. Barriers to symptom management care pathway implementation in pediatric Cancer.
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Dupuis LL, Grimes A, Vettese E, Klesges LM, and Sung L
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- Child, Humans, Palliative Care, Pandemics, SARS-CoV-2, United States epidemiology, COVID-19, Neoplasms epidemiology, Neoplasms therapy
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Background: Objectives were to describe barriers to pediatric cancer symptom management care pathway implementation and the impact of the COVID-19 pandemic on clinical research evaluating their implementation., Methods: We included 25 pediatric oncology hospitals in the United States that supported a grant submission to perform a cluster randomized trial in which the intervention encompassed care pathways for symptom management. A survey was distributed to site principal investigators prior to randomization to measure contextual elements related to care pathway implementation. Questions included the inner setting measures of the Consolidated Framework for Implementation Research (CFIR), study-specific potential barriers and the impact of the COVID-19 pandemic on clinical research. The Wilcoxon rank sum test was used to compare characteristics of institutions that agreed that their department supported the implementation of symptom management care pathways vs. institutions that did not agree., Results: Of the 25 sites, one withdrew because of resource constraints and one did not respond, leaving 23 institutions. Among the seven CFIR constructs, the least supported was implementation climate; 57% agreed there was support, 39% agreed there was recognition and 39% agreed there was prioritization for symptom management care pathway implementation at their institution. Most common barriers were lack of person-time to create care pathways and champion their use (35%), lack of interest from physicians (30%) and lack of information technology resources (26%). Most sites reported no negative impact of the COVID-19 pandemic across research activities. Sites with fewer pediatric cancer patients were more likely to agree that staff are supported to implement symptom management care pathways (P = 0.003)., Conclusions: The most commonly reported barriers to implementation were lack of support, recognition and prioritization. The COVID-19 pandemic may not be a major barrier to clinical research activities in pediatric oncology., (© 2021. The Author(s).)
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- 2021
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17. Facilitators and barriers to clinical practice guideline-consistent supportive care at pediatric oncology institutions: a Children's Oncology Group study.
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Sugalski AJ, Lo T, Beauchemin M, Grimes AC, Robinson PD, Walsh AM, Santesso N, Dang H, Fisher BT, Wrightson AR, Yu LC, Sung L, and Dupuis LL
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Background: Clinical practice guideline (CPG)-consistent care improves patient outcomes, but CPG implementation is poor. Little is known about CPG implementation in pediatric oncology. This study aimed to understand supportive care CPG implementation facilitators and barriers at pediatric oncology National Cancer Institute (NCI) Community Oncology Research Program (NCORP) institutions., Methods: Healthcare professionals at 26 pediatric, Children's Oncology Group-member, NCORP institutions were invited to participate in face-to-face focus groups. Serial focus groups were held until saturation of ideas was reached. Supportive care CPG implementation facilitators and barriers were solicited using nominal group technique (NGT), and implementation of specific supportive care CPG recommendations was discussed. Notes from each focus group were analyzed using a directed content analysis. The top five themes arising from an analysis of NGT items were identified, first from each focus group and then across all focus groups., Results: Saturation of ideas was reached after seven focus groups involving 35 participants from 18 institutions. The top five facilitators of CPG implementation identified across all focus groups were organizational factors including charging teams with CPG implementation, individual factors including willingness to standardize care, user needs and values including mentorship, system factors including implementation structure, and implementation strategies including a basis in science. The top five barriers of CPG implementation identified were organizational factors including tolerance for inconsistencies, individual factors including lack of trust, system factors including administrative hurdles, user needs and values including lack of inclusivity, and professional including knowledge gaps., Conclusions: Healthcare professionals at pediatric NCORP institutions believe that organizational factors are the most important determinants of supportive care CPG implementation. They believe that CPG-consistent supportive care is most likely to be delivered in organizations that prioritize evidence-based care, provide structure and resources to implement CPGs, and eliminate implementation barriers., Trial Registration: ClinicalTrials.gov Identifier: NCT02847130. Date of registration: July 28, 2016., (© 2021. The Author(s).)
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- 2021
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18. The Pediatric Nausea Assessment Tool: French translation and face validity in Francophone-Canadian pediatric oncology patients.
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Choquette A, Sivananthan A, Guillemette A, O'Shaughnessy E, Pinheiro-Maltez M, MacKeigan L, Langevin AM, and Dupuis LL
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Competing Interests: CONFLICT OF INTEREST The authors have no conflicts of interest to disclose.
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- 2021
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19. Instrument de mesure de la nausée chez l’enfant : traduction française et validité des visages pour les patients canadiens francophones en oncopédiatrie.
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Choquette A, Sivananthan A, Guillemette A, O'Shaubhnessy E, Pinheiro-Maltez M, MacKeigan L, Langevin AM, and Dupuis LL
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Competing Interests: CONFLIT D’INTÉRÊTS Les auteurs n’ont aucun conflit d’intérêts à divulguer.
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- 2021
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20. Development of the SPARK family member web pages to improve symptom management for pediatric patients receiving cancer treatments.
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Watling CZ, McCarthy C, Theodorakidis A, Cook S, Vettese E, Schechter T, Abubeker H, Dupuis LL, and Sung L
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- Adolescent, Adult, Child, Child, Preschool, Female, Humans, Infant, Infant, Newborn, Internet, Male, Middle Aged, Young Adult, Neoplasms therapy
- Abstract
Background: Supportive care Prioritization, Assessment and Recommendations for Kids (SPARK) is a web-based application that facilitates symptom screening and access to supportive care clinical practice guidelines (CPGs) for children and adolescents receiving cancer treatments. Objective was to develop SPARK family member web pages for pediatric patient family members accessing: (1) proxy symptom screening and symptom reports, and (2) care recommendations for symptom management based on CPGs., Methods: SPARK family member web pages were developed and included access to symptom screening and care recommendations sections. Care recommendations for fatigue and mucositis were created. These were iteratively refined based upon cognitive interviews with English-speaking family members ≥16 years of age until less than two participants incorrectly understood sections as adjudicated by two independent raters., Results: A total of 100 family members were enrolled who evaluated the SPARK family member web pages (n = 40), fatigue care recommendation (n = 30) and mucositis prevention care recommendation (n = 30). Among the last 10 participants, none said that the SPARK family member web pages were hard or very hard to use, one incorrectly understood one web page, none said either care recommendation was hard to understand and none were incorrect in their understanding of the care recommendations., Conclusions: We successfully developed SPARK web pages for use by family members of pediatric patients receiving cancer treatments. We also developed a process for translating CPG recommendations designed for healthcare professionals to lay language. The utility of SPARK family member web pages after clinical implementation could be a focus for future research.
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- 2020
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21. Response to Kawedia et al Letter to Editor in Response to the Article by McCune Et Al "Harmonization of Busulfan Plasma Exposure Unit (BPEU): A Community-Initiated Consensus Statement".
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Dupuis LL, Quinones CM, Ritchie J, Carpenter PA, Bauters T, Yeh RF, Anasetti C, Boelens JJ, Hamerschlak N, Hassan M, Kang HJ, Kanda Y, Paci A, Perales MA, Shaw PJ, Seewaldt VL, Savani BN, Militano O, Pulsipher MA, and McCune JS
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- Consensus, Humans, Busulfan, Plasma
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- 2020
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22. Discordance between pediatric self-report and parent proxy-report symptom scores and creation of a dyad symptom screening tool (co-SSPedi).
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Tomlinson D, Plenert E, Dadzie G, Loves R, Cook S, Schechter T, Furtado J, Dupuis LL, and Sung L
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- Adolescent, Child, Child, Preschool, Female, Humans, Male, Mass Screening, Self Report, Psychometrics methods
- Abstract
Symptom Screening in Pediatrics Tool (SSPedi) (age 8-18 years) and mini-SSPedi (age 4-7 years) can be used to self-report and proxy-report bothersome symptoms in pediatric patients receiving cancer treatments. There are limitations of sole child self-report or proxy-report. An approach in which children and parents complete symptom reports together may be useful. The aim of our study was to describe discordance between child self-report and parent proxy-report symptom scores, and to determine how these scores compare to an approach in which reporting is performed together (co-SSPedi). Children and parents completed SSPedi or mini-SSPedi separately. Discordant symptoms were shared with respondents and discussed. Next, the dyad completed co-SSPedi together and were asked which approach they preferred. Discordance was evaluated for each symptom and was defined as a difference of at least 2 points on an ordinal scale ranging from 0 (not at all bothered) to 4 (extremely bothered). Of the 48 enrolled dyads (children, median age, 10.8 years; 54.2% male), 41 (85.4%) had discordance in at least one symptom. There was no clear pattern in discordance by age group. When a dyad approach was used, more co-SSPedi scores agreed with the original child self-report scores (59 dyads, 56.2%) compared to original parent proxy-report scores (15 dyads, 14.3%) for discordant symptoms. Forty-three (89.6%) dyads preferred to complete SSPedi together. Future work should evaluate the psychometric properties of co-SSPedi., (© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)
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- 2020
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23. Optimizing symptom control in children and adolescents with cancer.
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Dupuis LL, Cook S, Robinson PD, Tomlinson D, Vettese E, and Sung L
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- Adolescent, Child, Humans, Narration, Neoplasms physiopathology
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There is growing recognition of the degree to which symptoms negatively impact on children receiving cancer treatments. A recent study described that almost all inpatient pediatric oncology patients are experiencing at least one bothersome symptom and almost 60% are experiencing at least one severely bothersome symptom. Poor symptom control occurs because of challenges with communication of bothersome symptoms to clinicians, lack of clinical practice guidelines (CPGs) for most of these symptoms, and failure to administer preventative and therapeutic interventions known to be effective for symptom control. This article reviews approaches used to improve symptom control for children receiving cancer treatments. Areas addressed include systematic symptom screening and creation of CPGs for symptom management. Challenges with electronic health integration are also addressed. Several multi-symptom assessment scales have been developed but none have yet been used to directly influence patient management. The number of CPGs applicable to symptom control in pediatric oncology is increasing but remains small. Improving the creation of and adherence to CPGs for symptom management is an important priority. Finally, identifying ways that symptom management systems can be integrated into clinical work flows is essential; these will likely need to focus on electronic health records.
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- 2019
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24. Harmonization of Busulfan Plasma Exposure Unit (BPEU): A Community-Initiated Consensus Statement.
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McCune JS, Quinones CM, Ritchie J, Carpenter PA, van Maarseveen E, Yeh RF, Anasetti C, Boelens JJ, Hamerschlak N, Hassan M, Kang HJ, Kanda Y, Paci A, Perales MA, Shaw PJ, Seewaldt VL, Savani BN, Hsieh A, Poon B, Mohty M, Pulsipher MA, Pasquini M, and Dupuis LL
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- Allografts, Female, Humans, Male, Busulfan administration & dosage, Busulfan pharmacokinetics, Consensus, Databases, Factual, Drug Monitoring, Hematopoietic Stem Cell Transplantation, Registries
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Busulfan therapeutic drug monitoring (TDM) is often used to achieve target plasma exposures. Variability in busulfan plasma exposure units (BPEU) is a potential source for misinterpretation of publications and protocols and is a barrier to data capture by hematopoietic cell transplantation (HCT) registry databases. We sought to harmonize to a single BPEU for international use. Using Delphi consensus methodology, iterative surveys were sent to an increasing number of relevant clinical stakeholders. In survey 1, 14 stakeholders were asked to identify ideal properties of a BPEU. In survey 2, 52 stakeholders were asked (1) to evaluate BPEU candidates according to ideal BPEU properties established by survey 1 and local position statements for TDM and (2) to identify potential facilitators and barriers to adoption of the harmonized BPEU. The most frequently used BPEU identified, in descending order, were area under the curve (AUC) in μM × min, AUC in mg × h/L, concentration at steady state (Css) in ng/mL, AUC in μM × h, and AUC in μg × h/L. All respondents conceptually agreed on the ideal properties of a BPEU and to adopt a harmonized BPEU. Respondents were equally divided between selecting AUC in μM × min versus mg × h/L for harmonization. AUC in mg × h/L was finally selected as the harmonized BPEU, because it satisfied most of the survey-determined ideal properties for the harmonized BPEU and is read easily understood in the clinical practice environment. Furthermore, 10 major professional societies have endorsed AUC in mg × h/L as the harmonized unit for reporting to HCT registry databases and for use in future protocols and publications., (Copyright © 2019 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)
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- 2019
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25. Improving paediatric medications: A prescription for Canadian children and youth.
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Hepburn CM, Gilpin A, Autmizguine J, Denburg A, Dupuis LL, Finkelstein Y, Gruenwoldt E, Ito S, Jong G', Lacaze-Masmonteil T, Levy D, Macleod S, P Miller S, Offringa M, Pinsk M, Power B, Rieder M, and Litalien C
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- 2019
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26. Efficacy of antibiotic prophylaxis in patients with cancer and hematopoietic stem cell transplantation recipients: A systematic review of randomized trials.
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Egan G, Robinson PD, Martinez JPD, Alexander S, Ammann RA, Dupuis LL, Fisher BT, Lehrnbecher T, Phillips B, Cabral S, Tomlinson G, and Sung L
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- Adult, Anti-Bacterial Agents therapeutic use, Bacteremia prevention & control, Child, Humans, Randomized Controlled Trials as Topic, Treatment Outcome, Antibiotic Prophylaxis methods, Antineoplastic Agents adverse effects, Bacteremia epidemiology, Hematopoietic Stem Cell Transplantation adverse effects, Neoplasms therapy
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Purpose: To determine the efficacy and safety of different prophylactic systemic antibiotics in adult and pediatric patients receiving chemotherapy or undergoing hematopoietic stem cell transplantation (HSCT)., Methods: We conducted a systematic review and performed searches of Ovid MEDLINE, MEDLINE in-process and Embase; and Cochrane Central Register of Controlled Trials. Studies were included if patients had cancer or were HSCT recipients with anticipated neutropenia, and the intervention was systemic antibacterial prophylaxis. Strategies synthesized included fluoroquinolone vs no antibiotic/nonabsorbable antibiotic; fluoroquinolone vs trimethoprim-sulfamethoxazole; trimethoprim-sulfamethoxazole vs no antibiotic; and cephalosporin vs. no antibiotic. Fluoroquinolone vs cephalosporin and levofloxacin vs ciprofloxacin were compared by network meta-analysis. Primary outcome was bacteremia., Results: Of 20 984 citations screened, 113 studies comparing prophylactic antibiotic to control were included. The following were effective in reducing bacteremia: fluoroquinolone vs no antibiotic/nonabsorbable antibiotic (risk ratio (RR) 0.56, 95% confidence interval (CI) 0.41-0.76), trimethoprim-sulfamethoxazole vs no antibiotic (RR 0.59, 95% CI 0.41-0.85) and cephalosporin vs no antibiotic (RR 0.30, 95% CI 0.16-0.58). Fluoroquinolone was not significantly associated with increased Clostridium difficile infection (RR 0.62, 95% CI 0.31-1.24) or invasive fungal disease (RR 1.28, 95% CI 0.79-2.08) but did increase resistance to fluoroquinolone among bacteremia isolates (RR 3.35, 95% CI 1.12 to 10.03). Heterogeneity in fluoroquinolone effect on bacteremia was not explained by evaluated study, population, or methodological factors. Network meta-analysis revealed no direct comparisons for pre-specified analyses; superior regimens were not identified., Conclusions: Fluoroquinolone, trimethoprim-sulfamethoxazole, and cephalosporin prophylaxis reduced bacteremia. A clinical practice guideline to facilitate prophylactic antibiotic decision-making is required., (© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)
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- 2019
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27. Association of Antiepileptic Medications with Outcomes after Allogeneic Hematopoietic Cell Transplantation with Busulfan/Cyclophosphamide Conditioning.
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McCune JS, Wang T, Bo-Subait K, Aljurf M, Beitinjaneh A, Bubalo J, Cahn JY, Cerny J, Chhabra S, Cumpston A, Dupuis LL, Lazarus HM, Marks DI, Maziarz RT, Norkin M, Prestidge T, Mineishi S, Krem MM, Pasquini M, and Martin PJ
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- Adolescent, Adult, Aged, Allografts, Anticonvulsants adverse effects, Busulfan adverse effects, Child, Child, Preschool, Cyclophosphamide adverse effects, Disease-Free Survival, Female, Humans, Infant, Male, Middle Aged, Phenytoin adverse effects, Survival Rate, Anticonvulsants administration & dosage, Busulfan administration & dosage, Cyclophosphamide administration & dosage, Hematologic Neoplasms mortality, Hematologic Neoplasms therapy, Hematopoietic Stem Cell Transplantation, Phenytoin administration & dosage, Seizures drug therapy, Seizures etiology, Seizures mortality, Transplantation Conditioning
- Abstract
High-dose busulfan (BU) followed by high-dose cyclophosphamide (CY) before allogeneic hematopoietic cell transplantation (HCT) has long been used as treatment for hematologic malignancies. Administration of phenytoin or newer alternative antiepileptic medications (AEMs) prevents seizures caused by BU. Phenytoin induces enzymes that increase exposure to active CY metabolites in vivo, whereas alternative AEMs do not have this effect. Lower exposure to active CY metabolites with the use of alternative AEMs could decrease the risk of toxicity but might increase the risk of recurrent malignancy after HCT. Previous studies have not determined whether outcomes with alternative AEMs differ from those with phenytoin in patients treated with BU/CY before allogeneic HCT. We studied a cohort of 2155 patients, including 1460 treated with phenytoin and 695 treated with alternative AEMs, who received BU/CY before allogeneic HCT between 2004 and 2014. We found no differences suggesting decreased overall survival or relapse-free survival or increased risks of relapse, nonrelapse mortality, acute or chronic graft-versus-host disease, or regimen-related toxicity associated with the use of alternative AEMs compared with phenytoin. The risk of dialysis was lower in the alternative AEM group than in the phenytoin group. Alternative AEMs are safe for prevention of seizures after BU administration and can avoid the undesirable toxicities and drug interactions caused by phenytoin., (Copyright © 2019 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
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- 2019
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28. Longitudinal evaluation of Supportive care Prioritization, Assessment and Recommendations for Kids (SPARK), a symptom screening and management application.
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Vettese E, Cook S, Soman D, Kuczynski S, Spiegler B, Davis H, Duong N, Schechter T, Dupuis LL, and Sung L
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- Adolescent, Child, Delivery of Health Care, Feasibility Studies, Female, Humans, Internet, Longitudinal Studies, Male, Neoplasms therapy, Hematopoietic Stem Cell Transplantation, Neoplasms diagnosis, Software, Symptom Assessment
- Abstract
Background: Supportive care Prioritization, Assessment and Recommendations for Kids (SPARK) is a web application focused on improving symptom control. It enables pediatric cancer and hematopoietic stem cell transplant (HSCT) patients to self-report and track symptoms, and allows healthcare professionals to access guidelines for symptom management. Objective was to determine the feasibility of longitudinal collection of symptom data., Methods: In this longitudinal, single-armed feasibility study, respondents were children 8-18 years of age with cancer or pediatric HSCT recipients. Participants completed symptom reporting daily for 5 days. Cognitive interviews were conducted on day 5. Quantitative evaluation included SPARK ease of use and understandability of SPARK reports. Qualitative feedback on facilitators and barriers to daily symptom screening was solicited. Feasibility was defined as ≥75% of participants completing symptom screening on at least 60% of on-study days during the five-day study., Results: Among the 30 children enrolled, the median number of days SSPedi was completed at least once was 5 (range 3 to 5). Overall, 28/29 (96.6%) thought completing symptom screening using SPARK was easy or very easy. All participants understood SPARK symptom reports. Severe symptoms was the most common barrier to daily reporting while an alarm reminder system was the most commonly identified facilitator., Conclusions: Daily completion of symptom screening using SPARK over 5 days was feasible in children aged 8 to 18 years with cancer and pediatric HSCT recipients. SPARK is now appropriate for use in randomized trials to evaluate the effect of symptom screening and symptom feedback.
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- 2019
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29. Measurement properties of instruments to assess pain in children and adolescents with cancer: a systematic review protocol.
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Loeffen EAH, Stinson JN, Birnie KA, van Dijk M, Kulkarni K, Rijsdijk M, Font-Gonzalez A, Dupuis LL, van Dalen EC, Mulder RL, Campbell F, Tissing WJE, van de Wetering MD, and Gibson F
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- Adolescent, Child, Child, Preschool, Humans, Infant, Infant, Newborn, Pain Measurement methods, Research Design, Cancer Pain diagnosis, Neoplasms physiopathology, Systematic Reviews as Topic
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Background: Pain in children and adolescents with cancer has been identified as an area where many healthcare professionals seek guidance. This protocol details a systematic review whose aim is to explore current knowledge regarding measurement instruments to assess pain (and pain-related distress) in children and adolescents with cancer. After completion of the review, the information will be used in the development of a clinical practice guideline., Methods: We will search four electronic databases (MEDLINE via PubMed, CINAHL, PsycINFO and HaPI). Additional relevant studies will be identified by reference checking and expert consultation. All citations will be screened independently by two reviewers in a three-step approach: first selection based on title, second selection based on abstract, third selection based on full-text. Studies in children and adolescents with cancer that aimed to evaluate the clinimetric properties of an existing pain measurement instrument or to develop a new pain measurement instrument and that include at least one relevant outcome (reliability, validity, responsiveness, interpretability, clinical utility) are eligible for inclusion. For all steps of evidence selection, a detailed list with eligibility criteria will be determined a priori. Data extraction and quality assessment of included studies (according to the COnsensus-based Standards for the selection of health Measurement INstruments, COSMIN criteria) will be conducted independently by two authors., Discussion: This systematic review will provide an overview of the current literature regarding measurement instruments to assess pain in children and adolescents with cancer. This knowledge synthesis will be used to formulate recommendations for clinical practice. Also, by synthesizing existing evidence, knowledge gaps will be identified., Systematic Review Registration: PROSPERO CRD42017072879.
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- 2019
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30. Development of mini-SSPedi for children 4-7 years of age receiving cancer treatments.
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Tomlinson D, Hyslop S, Stein E, Spiegler B, Vettese E, Kuczynski S, Schechter T, Dupuis LL, and Sung L
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- Child, Child, Preschool, Female, Humans, Male, Neoplasms epidemiology, Neoplasms pathology, Psychometrics methods, Self Report, Surveys and Questionnaires, Symptom Assessment methods, Early Detection of Cancer methods, Neoplasms diagnosis, Pediatrics methods
- Abstract
Background: The Symptom Screening in Pediatrics Tool (SSPedi) is valid for assessing symptoms in children aged 8-18 years receiving cancer treatments. The objective was to develop a new self-report symptom screening tool for children receiving cancer treatments who are 4-7 years of age (mini-SSPedi), based on SSPedi., Methods: Respondents were children with cancer or pediatric hematopoietic stem cell transplantation (HSCT) recipients who were 4-7 years of age. We included the same 15 symptoms contained in SSPedi. Using cognitive interviewing, we developed mini-SSPedi in three phases and made decisions based upon respondent understanding. First, we developed questionnaire structure regarding recall period, concept of bother and response option format. Second, we determined wording of each symptom. Third, we evaluated the entire mini-SSPedi instrument for understanding and ease of completion., Results: We enrolled 100 participants in total and included 30, 40 and 30 in each of the three phases. Questionnaire structure was satisfactory with a recall period of "today" and a faces-based 3-point Likert scale. Bother was well-understood. Five symptoms required modification to achieve satisfactory understanding while the remaining 10 SSPedi symptoms did not require modification. Among the last 10 children enrolled, all understood each mini-SSPedi item and none thought mini-SSPedi was hard to complete., Conclusion: We developed a symptom screening tool for children with cancer and pediatric HSCT recipients between 4 and 7 years of age that is understandable and easy to complete. Future work will evaluate the psychometric properties of mini-SSPedi and develop an electronic version of the instrument.
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- 2019
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31. Validation of the Proxy Version of Symptom Screening in Pediatrics Tool in Children Receiving Cancer Treatments.
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Hyslop S, Dupuis LL, Baggott C, Dix D, Gibson P, Kuczynski S, Johnston DL, Orsey A, Portwine C, Price V, Spiegler B, Tomlinson D, Vanan M, Tomlinson GA, and Sung L
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- Adolescent, Child, Cohort Studies, Female, Hematopoietic Stem Cell Transplantation, Humans, Male, Observer Variation, Parents, Psychometrics, Neoplasms diagnosis, Neoplasms therapy, Proxy, Symptom Assessment methods
- Abstract
Objectives: Primary objectives were to evaluate the interrater reliability and validity of proxy-report Symptom Screening in Pediatrics Tool (SSPedi) in children with cancer and pediatric hematopoietic stem cell transplant (HSCT) recipients. Secondary objective was to describe the interrater reliability of each SSPedi item., Methods: Respondents were children aged eight to 18 years with cancer or HSCT recipients, and their parents or guardians. We enrolled two pediatric respondent groups. The more symptomatic group was receiving active treatment for cancer, admitted to hospital, and expected to be in a hospital three days later. The less symptomatic group either was in maintenance therapy for acute lymphoblastic leukemia or had completed cancer treatments. Convergent validity was evaluated by comparing proxy-reported mucositis, nausea and vomiting, pain, and total SSPedi scores, with child self-reported validated scales, and we hypothesized fair correlations. Discriminant validity was evaluated by comparing proxy-reported total SSPedi scores between groups. Interrater reliability of each SSPedi item was evaluated., Results: Four hundred thirty-nine child and parent or guardian pairs were recruited. Mean difference in proxy-reported SSPedi scores between the more and less symptomatic groups was 8.2, 95% CI 6.6-9.8. All hypothesized relationships among measures were observed. Intraclass correlation coefficients for SSPedi items ranged from 0.34 (problems with thinking) to 0.80 (diarrhea)., Conclusion: Proxy-report SSPedi is reliable and valid in children aged 8 years to 18 years with cancer and HSCT recipients. Future work should support proxy-reported symptom assessment in clinical settings where children are not able to self-report or communicate bothersome symptoms., (Copyright © 2018 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)
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- 2018
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32. Validation of the Symptom Screening in Pediatrics Tool in Children Receiving Cancer Treatments.
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Dupuis LL, Johnston DL, Baggott C, Hyslop S, Tomlinson D, Gibson P, Orsey A, Dix D, Price V, Vanan M, Portwine C, Kuczynski S, Spiegler B, Tomlinson GA, and Sung L
- Subjects
- Adolescent, Age of Onset, Child, Female, Hematopoietic Stem Cell Transplantation adverse effects, Hematopoietic Stem Cell Transplantation psychology, Humans, Male, Mass Screening methods, Mass Screening standards, Neoplasms epidemiology, Neoplasms psychology, Psychometrics, Reproducibility of Results, Transplant Recipients psychology, Diagnostic Self Evaluation, Neoplasms therapy, Pediatrics methods, Pediatrics standards, Self Report standards, Symptom Assessment methods, Symptom Assessment standards
- Abstract
Background: The objective was to evaluate the reliability and validity of the self-report Symptom Screening in Pediatrics Tool (SSPedi) from the perspective of children with cancer and pediatric hematopoietic stem cell transplant (HSCT) recipients., Methods: In this multicenter study, respondents were children age eight to 18 years who had cancer or had received HSCT, and their parents. Two different child respondent populations were targeted. More symptomatic respondents were receiving active treatment for cancer, admitted to the hospital, and expected to be in the hospital three days later. Less symptomatic respondents were in maintenance therapy for acute lymphoblastic leukemia or had completed cancer therapy. Children completed SSPedi and then responded to validated self-report measures of mucositis, nausea, pain, and global quality of life. Children in the more symptomatic group repeated SSPedi and a global symptom change scale three days later. Parent proxy-report was optional. Reliability was evaluated using intraclass correlations while convergent validity was evaluated using Spearman correlations., Results: Of 502 children enrolled, 302 were in the more symptomatic group and 200 were in the less symptomatic group. Intraclass correlation coefficients were 0.88 (95% confidence interval [CI] = 0.82 to 0.92) for test-retest reliability and 0.76 (95% CI = 0.71 to 0.80) for inter-rater reliability. The mean difference in SSPedi scores between more and less symptomatic groups was 7.8 (95% CI = 6.4 to 9.2). SSPedi was responsive to change in global symptoms. All hypothesized relationships among measures were observed., Conclusions: SSPedi is a self-report symptom bother tool for children with cancer and HSCT recipients that is reliable, valid, and responsive to change. SSPedi can be used for clinical and research purposes. Future work should focus on integration into care delivery.
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- 2018
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33. Describing symptoms using the Symptom Screening in Pediatrics Tool in hospitalized children with cancer and hematopoietic stem cell transplant recipients.
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Johnston DL, Hyslop S, Tomlinson D, Baggott C, Gibson P, Orsey A, Dix D, Price V, Vanan M, Portwine C, Kuczynski S, Spiegler B, Tomlinson GA, Dupuis LL, and Sung L
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- Adolescent, Adolescent, Hospitalized, Canada, Child, Child, Hospitalized, Early Detection of Cancer, Female, Humans, Logistic Models, Male, Psychometrics, Self Report, United States, Hematopoietic Stem Cell Transplantation adverse effects, Neoplasms diagnosis, Symptom Assessment methods
- Abstract
Objectives were to describe any bothersome symptom and severely bothersome symptoms in inpatient children with cancer and hematopoietic stem cell transplant (HSCT) recipients. We included children 8-18 years of age with cancer or HSCT recipients who were receiving active treatment for cancer, admitted to hospital, and expected to be in hospital 3 days later. We administered the self-report Symptom Screening in Pediatrics Tool (SSPedi). We described those who identified any degree of symptom bother (at least "a little") and those who rated the degree of bother as severe ("a lot" or "extremely"). Factors associated with severe symptoms and total SSPedi scores were examined using multiple logistic and linear regression. Among the 302 patients, 298 (98.7%) reported having any bothersome symptom and 181 (59.9%) had at least one severely bothersome symptom. In multiple regression, older children were significantly more likely to have at least one severely bothersome symptom (15-18 and 11-14 years vs. 8-10 years; P = 0.008) and to have higher total SSPedi scores (P = 0.0003). Those with relapsed disease were more likely to have at least one severely bothersome symptom (odds ratio 2.1, 95% confidence interval 1.1-4.3; P = 0.037) and HSCT recipients were more likely to have higher symptom scores (β = 3.48, standard error = 1.6; P = 0.030). Almost all children receiving cancer therapies experience bothersome symptoms and 60% have at least one severely bothersome symptom. Older children experienced more severely bothersome symptoms and higher symptom scores. Future studies should follow children longitudinally to better understand the symptom trajectory and should institute interventions to manage symptoms., (© 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)
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- 2018
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34. Pharmacologic interventions for fatigue in cancer and transplantation: a meta-analysis.
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Tomlinson D, Robinson PD, Oberoi S, Cataudella D, Culos-Reed N, Davis H, Duong N, Gibson F, Götte M, Hinds P, Nijhof SL, van der Torre P, Cabral S, Dupuis LL, and Sung L
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- Central Nervous System Stimulants therapeutic use, Erythropoietin therapeutic use, Fatigue etiology, Humans, Methylphenidate therapeutic use, Severity of Illness Index, Fatigue drug therapy, Hematopoietic Stem Cell Transplantation adverse effects, Neoplasms complications
- Abstract
Background: Our objective was to determine whether, compared with control interventions, pharmacologic interventions reduce the severity of fatigue in patients with cancer or recipients of hematopoietic stem-cell transplantation (hsct)., Methods: For a systematic review, we searched medline, embase, the Cochrane Central Register of Controlled Trials, cinahl, and Psychinfo for randomized trials of systemic pharmacologic interventions for the management of fatigue in patients with cancer or recipients of hsct. Two authors independently identified studies and abstracted data. Methodologic quality was assessed using the Cochrane Risk of Bias tool. The primary outcome was fatigue severity measured using various fatigue scales. Data were synthesized using random-effects models., Results: In the 117 included trials (19,819 patients), the pharmacologic agents used were erythropoietins ( n = 31), stimulants ( n = 19), l-carnitine ( n = 6), corticosteroids ( n = 5), antidepressants ( n = 5), appetite stimulants ( n = 3), and other agents ( n = 48). Fatigue was significantly reduced with erythropoietin [standardized mean difference (smd): -0.52; 95% confidence interval (ci): -0.89 to -0.14] and with methylphenidate (smd: -0.36; 95% ci: -0.56 to -0.15); modafinil (or armodafinil) and corticosteroids were not effective., Conclusions: Erythropoietin and methylphenidate significantly reduced fatigue severity in patients with cancer and in recipients of hsct. Concerns about the safety of those agents might limit their usefulness. Future research should identify effective interventions for fatigue that have minimal adverse effects.
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- 2018
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35. Response to 'Aprepitant and fosaprepitant decrease the effectiveness of hormonal contraceptives'.
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Patel P, Leeder JS, Piquette-Miller M, and Dupuis LL
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- Humans, Morpholines, Nausea, Aprepitant, Contraceptive Agents
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- 2018
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36. Chemotherapy-Colchicine Interaction in a Child with Familial Mediterranean Fever and Hodgkin Lymphoma.
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Langenberg-Ververgaert KPS, Laxer RM, Punnett AS, Dupuis LL, Finkelstein Y, and Abla O
- Abstract
Familial Mediterranean fever (FMF) has been associated with hematological malignancies but has not been reported in association with Hodgkin lymphoma (HL). We hereby describe the first pediatric patient with FMF and stage IIA nodular sclerosis HL. She was treated with prednisone, doxorubicin, vincristine and etoposide (OEPA) being on therapy with colchicine. However, she suffered more than expected treatment-related toxicity attributed either to chemotherapy (severe neutropenia) or colchicine (Abdominal pains and diarrhoea). Colchicine had to be discontinued. In the absence of colchicine, she tolerated very well the second cycle of chemotherapy. Currently, she is in remission at 17 months after her HL diagnosis, and her FMF is under control with colchicine without any signs of toxicity., Competing Interests: Competing interests: The authors have declared that no competing interests exist.
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- 2018
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37. Physical activity reduces fatigue in patients with cancer and hematopoietic stem cell transplant recipients: A systematic review and meta-analysis of randomized trials.
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Oberoi S, Robinson PD, Cataudella D, Culos-Reed SN, Davis H, Duong N, Gibson F, Götte M, Hinds P, Nijhof SL, Tomlinson D, van der Torre P, Cabral S, Dupuis LL, and Sung L
- Subjects
- Fatigue etiology, Hematopoietic Stem Cell Transplantation adverse effects, Humans, Neoplasms physiopathology, Quality of Life, Randomized Controlled Trials as Topic, Exercise physiology, Exercise Therapy methods, Fatigue therapy, Hematopoietic Stem Cell Transplantation methods, Neoplasms therapy
- Abstract
Purpose: Objective was to determine whether physical activity reduces the severity of fatigue in patients with cancer or hematopoietic stem cell transplant (HSCT) recipients., Methods: We conducted a meta-analysis of randomized trials comparing physical activity with control interventions for the management of fatigue in patients with cancer or HSCT recipients., Results: There were 170 trials included. Physical activity reduced the severity of fatigue when compared to all control groups (standardized mean difference -0.49, 95% confidence interval -0.60 to -0.37; P < 0.00001). Aerobic, neuromotor, resistance and combination exercises were all effective in reducing fatigue although smaller effects were observed with resistance exercises (P interaction = 0.01). Other intervention and patient characteristics did not influence the effect of physical activity on the severity of fatigue., Conclusions: Physical activity was effective at reducing fatigue in patients with cancer and HSCT recipients across patient sub-groups. Determining the best approaches for safe implementation should be a priority., (Copyright © 2017 Elsevier B.V. All rights reserved.)
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- 2018
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38. Mind and body practices for fatigue reduction in patients with cancer and hematopoietic stem cell transplant recipients: A systematic review and meta-analysis.
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Duong N, Davis H, Robinson PD, Oberoi S, Cataudella D, Culos-Reed SN, Gibson F, Götte M, Hinds P, Nijhof SL, Tomlinson D, van der Torre P, Ladas E, Cabral S, Dupuis LL, and Sung L
- Subjects
- Acupuncture Therapy, Fatigue etiology, Fatigue psychology, Hematopoietic Stem Cell Transplantation adverse effects, Hematopoietic Stem Cell Transplantation psychology, Humans, Massage, Mindfulness, Neoplasms psychology, Randomized Controlled Trials as Topic, Relaxation Therapy, Yoga, Fatigue therapy, Hematopoietic Stem Cell Transplantation methods, Mind-Body Therapies methods, Neoplasms therapy
- Abstract
Purpose: To determine whether non-physical activity mind and body practices reduce the severity of fatigue in patients with cancer or hematopoietic stem cell transplant (HSCT) recipients compared to control interventions., Methods: We included randomized trials which compared non-physical activity mind and body practices compared with control interventions for the management of fatigue in cancer and HSCT patients., Results: Among 55 trials (4975 patients), interventions were acupuncture or acupressure (n=12), mindfulness (n=11), relaxation techniques (n=10), massage (n=6), energy therapy (n=5), energizing yogic breathing (n=3) and others (n=8). When combined, all interventions significantly reduced fatigue severity compared to all controls (standardized mean difference -0.51, 95% confidence interval -0.73 to -0.29). More specifically, mindfulness and relaxation significantly reduced fatigue severity., Conclusions: Mindfulness and relaxation were effective at reducing fatigue severity in patients with cancer and HSCT recipients. Future studies should evaluate how to translate these findings into clinical practice across different patient groups., (Copyright © 2017 Elsevier B.V. All rights reserved.)
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- 2017
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39. Aprepitant and fosaprepitant drug interactions: a systematic review.
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Patel P, Leeder JS, Piquette-Miller M, and Dupuis LL
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- Antiemetics therapeutic use, Antineoplastic Agents therapeutic use, Aprepitant, Cytochrome P-450 CYP2C9 Inducers pharmacology, Cytochrome P-450 CYP2C9 Inducers therapeutic use, Cytochrome P-450 CYP3A Inhibitors therapeutic use, Drug Interactions, Ethanol pharmacology, Humans, Injection Site Reaction etiology, Morpholines therapeutic use, Nausea chemically induced, Nausea prevention & control, Oxycodone pharmacology, Oxycodone therapeutic use, Quetiapine Fumarate pharmacology, Quetiapine Fumarate therapeutic use, Selective Serotonin Reuptake Inhibitors therapeutic use, Serotonin and Noradrenaline Reuptake Inhibitors pharmacology, Serotonin and Noradrenaline Reuptake Inhibitors therapeutic use, Vomiting chemically induced, Vomiting prevention & control, Antiemetics pharmacology, Antineoplastic Agents pharmacology, Cytochrome P-450 CYP3A Inhibitors pharmacology, Morpholines pharmacology
- Abstract
Aims: Aprepitant and fosaprepitant, commonly used for the prevention of chemotherapy-induced nausea and vomiting, alter cytochrome P450 activity. This systematic review evaluates clinically significant pharmacokinetic drug interactions with aprepitant and fosaprepitant and describes adverse events ascribed to drug interactions with aprepitant or fosaprepitant., Methods: We systematically reviewed the literature to September 11, 2016, to identify articles evaluating drug interactions involving aprepitant/fosaprepitant. The clinical significance of each reported pharmacokinetic drug interaction was evaluated based on the United States Food and Drug Administration guidance document on conducting drug interaction studies. The probability of an adverse event reported in case reports being due to a drug interaction with aprepitant/fosaprepitant was determined using the Drug Interaction Probability Scale., Results: A total of 4377 publications were identified. Of these, 64 met inclusion eligibility criteria: 34 described pharmacokinetic drug interactions and 30 described adverse events ascribed to a drug interaction. Clinically significant pharmacokinetic interactions between aprepitant/fosaprepitant and bosutinib PO, cabazitaxel IV, cyclophosphamide IV, dexamethasone PO, methylprednisolone IV, midazolam PO/IV, oxycodone PO and tolbutamide PO were identified, as were adverse events resulting from an interaction between aprepitant/fosaprepitant and alcohol, anthracyclines, ifosfamide, oxycodone, quetiapine, selective serotonin reuptake inhibitors/serotonin-norepinephrine reuptake inhibitors and warfarin., Conclusions: The potential for a drug interaction with aprepitant and fosaprepitant should be considered when selecting antiemetic therapy., (© 2017 The British Pharmacological Society.)
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- 2017
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40. GSTA1 diplotypes affect busulfan clearance and toxicity in children undergoing allogeneic hematopoietic stem cell transplantation: a multicenter study.
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Ansari M, Curtis PH, Uppugunduri CRS, Rezgui MA, Nava T, Mlakar V, Lesne L, Théoret Y, Chalandon Y, Dupuis LL, Schechter T, Bartelink IH, Boelens JJ, Bredius R, Dalle JH, Azarnoush S, Sedlacek P, Lewis V, Champagne M, Peters C, Bittencourt H, and Krajinovic M
- Abstract
Busulfan (BU) dose adjustment following therapeutic drug monitoring contributes to better outcome of hematopoietic stem cell transplantation (HSCT). Further improvement could be achieved through genotype-guided BU dose adjustments. To investigate this aspect, polymorphism within glutathione S transferase genes were assessed. Particularly, promoter haplotypes of the glutathione S transferase A1 ( GSTA1 ) were evaluated in vitro, with reporter gene assays and clinically, in a pediatric multi-center study (N =138) through association with BU pharmacokinetics (PK) and clinical outcomes. Promoter activity significantly differed between the GSTA1 haplotypes (p<0.001) supporting their importance in capturing PK variability. Four GSTA1 diplotype groups that significantly correlated with clearance (p=0.009) were distinguished. Diplotypes underlying fast and slow metabolizing capacity showed higher and lower BU clearance (ml/min/kg), respectively. GSTA1 diplotypes with slow metabolizing capacity were associated with higher incidence of sinusoidal obstruction syndrome, acute graft versus host disease and combined treatment-related toxicity (p<0.0005). Among other GST genes investigated, GSTP1 313GG correlated with acute graft versus host disease grade 1-4 (p=0.01) and GSTM1 non-null genotype was associated with hemorrhagic cystitis (p=0.003). This study further strengthens the hypothesis that GST diplotypes/genotypes could be incorporated into already existing population pharmacokinetic models for improving first BU dose prediction and HSCT outcomes. (N
o Clinicaltrials.gov identifier: NCT01257854. Registered 8 December 2010, retrospectively registered)., Competing Interests: CONFLICTS OF INTEREST H.B has acted as a consultant for Jazz Pharmaceuticals and obtained an education grant from them. H.B also acted as a consultant for Seattle Genetics. The authors declare that they have no other financial relationship(s) to disclose.- Published
- 2017
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41. 2016 MASCC and ESMO guideline update for the prevention of chemotherapy- and radiotherapy-induced nausea and vomiting and of nausea and vomiting in advanced cancer patients.
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Roila F, Molassiotis A, Herrstedt J, Aapro M, Gralla RJ, Bruera E, Clark-Snow RA, Dupuis LL, Einhorn LH, Feyer P, Hesketh PJ, Jordan K, Olver I, Rapoport BL, Roscoe J, Ruhlmann CH, Walsh D, Warr D, and van der Wetering M
- Published
- 2016
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42. Strategies facilitating practice change in pediatric cancer: a systematic review.
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Robinson PD, Dupuis LL, Tomlinson G, Phillips B, Greenberg M, and Sung L
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- Child, Humans, Internationality, Models, Organizational, Neoplasms, Pediatrics, Practice Patterns, Physicians'
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Purpose: By conducting a systematic review, we describe strategies to actively disseminate knowledge or facilitate practice change among healthcare providers caring for children with cancer and we evaluate the effectiveness of these strategies., Data Sources: We searched Ovid Medline, EMBASE and PsychINFO., Study Selection: Fully published primary studies were included if they evaluated one or more professional intervention strategies to actively disseminate knowledge or facilitate practice change in pediatric cancer or hematopoietic stem cell transplantation., Data Extraction: Data extracted included study characteristics and strategies evaluated. In studies with a quantitative analysis of patient outcomes, the relationship between study-level characteristics and statistically significant primary analyses was evaluated., Results of Data Synthesis: Of 20 644 titles and abstracts screened, 146 studies were retrieved in full and 60 were included. In 20 studies, quantitative evaluation of patient outcomes was examined and a primary outcome was stated. Eighteen studies were 'before and after' design; there were no randomized studies. All studies were at risk for bias. Interrupted time series was never the primary analytic approach. No specific strategy type was successful at improving patient outcomes., Conclusions: Literature describing strategies to facilitate practice change in pediatric cancer is emerging. However, major methodological limitations exist. Studies with robust designs are required to identify effective strategies to effect practice change., (© The Author 2016. Published by Oxford University Press in association with the International Society for Quality in Health Care. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2016
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43. Reply to "Pharmacokinetic and Analytical Issues in Busulfan Area Under the Curve Estimation and Simulation".
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Dupuis LL, Zao JH, and Schechter T
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- Female, Humans, Male, Antineoplastic Agents, Alkylating therapeutic use, Busulfan therapeutic use, Drug Monitoring methods, Hematopoietic Stem Cell Transplantation methods, Transplantation Conditioning methods
- Published
- 2016
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44. Cardioprotection and Second Malignant Neoplasms Associated With Dexrazoxane in Children Receiving Anthracycline Chemotherapy: A Systematic Review and Meta-Analysis.
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Shaikh F, Dupuis LL, Alexander S, Gupta A, Mertens L, and Nathan PC
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- Anthracyclines administration & dosage, Antibiotics, Antineoplastic administration & dosage, Bias, Cardiotonic Agents administration & dosage, Child, Dexrazoxane administration & dosage, Disease-Free Survival, Evidence-Based Medicine, Heart Diseases chemically induced, Humans, Incidence, Risk, Treatment Outcome, Anthracyclines adverse effects, Antibiotics, Antineoplastic adverse effects, Cardiotonic Agents adverse effects, Dexrazoxane adverse effects, Heart drug effects, Heart Diseases prevention & control, Leukemia, Myeloid, Acute chemically induced, Neoplasms, Second Primary chemically induced
- Abstract
Background: Several randomized controlled trials (RCTs) have demonstrated that dexrazoxane reduces anthracycline cardiotoxicity in adults, but use in children has been hindered by lack of direct evidence of cardioprotection and concerns regarding second malignant neoplasms (SMNs). This study aimed to systematically review the evidence regarding dexrazoxane in children., Methods: We searched Medline, Embase, the Cochrane Library, and abstracts for RCTs and nonrandomized studies (NRSs) that compared dexrazoxane to no cardioprotection among children. We combined findings using random-effects models. All statistical tests were two-sided., Results: Eleven eligible publications reported results from five RCTs (1254 patients), and 15 publications reported results from 12 NRSs (3385 patients). Dexrazoxane did not impact clinical cardiotoxicity in RCTs because of a low cardiotoxic event rate (three events among all patients) but was associated with a reduction in subclinical cardiotoxicity. Among NRSs, dexrazoxane was associated with a reduction in clinical cardiotoxicity (relative risk (RR) = 0.29, P = .001) and clinical+subclinical cardiotoxicity (RR = 0.43, P < .001). Among RCTs, 17 of 635 (2.7%) patients treated with dexrazoxane developed an SMN compared with seven of 619 (1.1%) who did not receive dexrazoxane (RR = 2.37, P = .06). Two RCTs that used concurrent etoposide reported an increased risk of acute myeloid leukemia, while one that used cranial radiation reported an increased risk of brain tumors. Event-free survival did not differ (P = .91)., Conclusion: Dexrazoxane is associated with a statistically significant risk reduction for most cardiotoxic outcomes. Dexrazoxane is associated with a statistically borderline increase in SMNs, possibly because of an interaction with concurrent cancer therapies. The decision to use dexrazoxane in children should balance the risks of cardiotoxicity and SMNs specific to each treatment protocol., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2015
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45. Performance of Busulfan Dosing Guidelines for Pediatric Hematopoietic Stem Cell Transplant Conditioning.
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Zao JH, Schechter T, Liu WJ, Gerges S, Gassas A, Egeler RM, Grunebaum E, and Dupuis LL
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- Adolescent, Antineoplastic Agents, Alkylating administration & dosage, Busulfan administration & dosage, Busulfan pharmacokinetics, Child, Child, Preschool, Female, Humans, Infant, Infant, Newborn, Male, Retrospective Studies, Antineoplastic Agents, Alkylating therapeutic use, Busulfan therapeutic use, Drug Monitoring methods, Hematopoietic Stem Cell Transplantation methods, Transplantation Conditioning methods
- Abstract
Achievement of a busulfan area-under-the-concentration versus time curve (AUC) of 900 to 1500 μM·min is associated with improved hematopoietic stem cell transplant (HSCT) outcomes. Multiple pediatric busulfan dosing guidelines aim to achieve this target. The authors' objective was to describe the AUCs achieved after simulated dosing using available pediatric i.v. busulfan dosing guidelines. The health records of children who received i.v. busulfan for HSCT conditioning at The Hospital for Sick Children were reviewed. Busulfan AUCs were calculated for each patient based on plasma busulfan concentrations using either a 1-compartment model or a validated limited-sampling strategy. Published pediatric busulfan dosing guidelines were identified. Initial busulfan doses were determined for all patients using each dosing guideline and total body weight (TBW). For overweight patients (TBW-to-ideal body weight [IBW] ≥ 1.25), initial busulfan doses were also determined using IBW and adjusted IBW (IBWadj). The resulting AUCs were simulated. The proportion of subjects (TBW/IBW < 1.25, TBW/IBW ≥ 1.25, and infants) with an AUC within target (900 to 1500 μM·min) after dosing simulation with each guideline was compared. One hundred eleven children (mean age, 6.2 years [SD, ±5.2]) who received i.v. busulfan were included. When dosing with each of the 12 i.v. busulfan dosing guidelines identified was simulated using TBW in 97 non-overweight patients, the proportion of patients with an AUC within the target range varied from 51% to 74% and from 45% to 64% in infants. Use of IBW or IBWadj to calculate initial busulfan doses in overweight children improved the performance of most guidelines. Current busulfan dosing guidelines vary in their ability to achieve AUCs within the target range. For children who are not overweight, we recommend 1 of 3 high-performing guidelines that allow individualization of the target busulfan AUC. Use of either IBW or IBWadj in overweight children improves the performance of most guidelines. Regardless of the guideline used, therapeutic drug monitoring is essential to verify achievement of the target AUC., (Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2015
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46. Refinement of the symptom screening in pediatrics tool (SSPedi).
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O'Sullivan C, Dupuis LL, Gibson P, Johnston DL, Baggott C, Portwine C, Spiegler B, Kuczynski S, Tomlinson D, de Mol Van Otterloo S, Tomlinson GA, and Sung L
- Subjects
- Adolescent, Antineoplastic Agents therapeutic use, Anxiety chemically induced, Anxiety diagnosis, Child, Female, Humans, Male, Nausea chemically induced, Nausea diagnosis, Neoplasms pathology, Pain chemically induced, Pain diagnosis, Antineoplastic Agents adverse effects, Neoplasms drug therapy, Self Report
- Abstract
Background: Objective was to evaluate and refine a new instrument for paediatric cancer symptom screening named the Symptom Screening in Pediatrics Tool (SSPedi)., Methods: Respondents were children 8-18 years of age undergoing active cancer treatment and parents of eligible children. Respondents completed SSPedi once and then responded to semi-structured questions. They rated how easy or difficult SSPedi was to complete. For items containing two concepts, we asked respondents whether concepts should remain together or be separated into two questions. We also asked about each item's importance and whether items were missing. Cognitive probing was conducted in children to evaluate their understanding of items and the response scale. After each group of 10 children and 10 parents, responses were reviewed to determine whether modifications were required. Recruitment ceased with the first group of 10 children in which modifications were not required., Results: Thirty children and 20 parents were required to achieve a final version of SSPedi. Fifteen items remain in the final version; the score ranges from 0 to 60., Conclusions: Using opinions of children with cancer and parents of paediatric cancer patients, we successfully developed a symptom screening tool that is easy to complete, is understandable and demonstrates content validity.
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- 2014
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47. Comparative effectiveness research in antineoplastic-induced nausea and vomiting control in children.
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Flank J and Dupuis LL
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- Adolescent, Child, Child, Preschool, Female, Humans, Male, Nausea chemically induced, Pediatrics methods, Vomiting chemically induced, Antiemetics therapeutic use, Antineoplastic Agents adverse effects, Comparative Effectiveness Research methods, Nausea drug therapy, Vomiting drug therapy
- Abstract
Antineoplastic-induced nausea and vomiting (AINV) is one of the most distressing adverse effects experienced by adult and pediatric patients receiving antineoplastic agents. Despite this, evidence of the efficacy and safety of antiemetic interventions in children is limited, and prevention and treatment approaches vary widely between centers. The purpose of this review is: first, to describe the barriers to comparative antiemetic effectiveness research in AINV control in children; second, to highlight limitations of the currently available pediatric AINV evidence; third, to summarize and discuss comparative effectiveness research specific to AINV control in children, with a focus on agents recommended in evidence-based guidelines developed for acute phase AINV control; and finally, to offer guidance regarding future comparative effectiveness research in this field.
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- 2014
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48. Development and testing of a multidimensional iPhone pain assessment application for adolescents with cancer.
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Stinson JN, Jibb LA, Nguyen C, Nathan PC, Maloney AM, Dupuis LL, Gerstle JT, Alman B, Hopyan S, Strahlendorf C, Portwine C, Johnston DL, and Orr M
- Subjects
- Adolescent, Feasibility Studies, Female, Humans, Male, Pain physiopathology, Patient Compliance, Patient Satisfaction, Cell Phone, Microcomputers, Neoplasms complications, Pain etiology, Pain Measurement methods
- Abstract
Background: Pain is one of the most common and distressing symptoms reported by adolescents with cancer. Despite advancements in pain assessment and management research, pain due to cancer and/or its treatments continues to be poorly managed. Our research group has developed a native iPhone application (app) called Pain Squad to tackle the problem of poorly managed pain in the adolescent with cancer group. The app functions as an electronic pain diary and is unique in its ability to collect data on pain intensity, duration, location, and the impact pain has on an adolescent's life (ie, relationships, school work, sleep, mood). It also evaluates medications and other physical and psychological pain management strategies used. Users are prompted twice daily at configurable times to complete 20 questions characterizing their pain and the app transmits results to a database for aggregate reporting through a Web interface. Each diary entry represents a pain case filed by an adolescent with cancer and a reward system (ie, moving up through law-enforcement team ranks, built-in videotaped acknowledgements from fictitious officers) encourages consistent use of the diary., Objective: Our objective was to design, develop, and test the usability, feasibility, compliance, and satisfaction of a game-based smartphone pain assessment tool for adolescents with cancer., Methods: We used both low- and high-fidelity qualitative usability testing with qualitative semi-structured, audio-taped interviews and iterative cycles to design and refine the iPhone based Pain Squad app. Qualitative thematic analysis of interviews using constant comparative methodology captured emergent themes related to app usability. Content validity was assessed using question importance-rating surveys completed by participants. Compliance and satisfaction data were collected following a 2-week feasibility trial where users were alarmed to record their pain twice daily on the app., Results: Thematic analysis of usability interviews showed the app to be appealing overall to adolescents. Analyses of both low- and high-fidelity testing resulted in minor revisions to the app to refine the theme and improve its usability. Adolescents resoundingly endorsed the game-based nature of the app and its virtual reward system. The importance of app pain diary questions was established by content validity analysis. Compliance with the app, assessed during feasibility testing, was high (mean 81%, SD 22%) and adolescents from this phase of the study found the app likeable, easy to use, and not bothersome to complete., Conclusions: A multifaceted usability approach demonstrated how the Pain Squad app could be made more appealing to children and adolescents with cancer. The game-based nature and built-in reward system of the app was appealing to adolescents and may have resulted in the high compliance rates and satisfaction ratings observed during clinical feasibility testing.
- Published
- 2013
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49. Prediction of area under the cyclosporine concentration versus time curve in children undergoing hematopoietic stem cell transplantation.
- Author
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Dupuis LL, Seto W, Teuffel O, Gibson P, Schultz KR, Doyle JD, Gassas A, Egeler RM, Sung L, and Schechter T
- Subjects
- Adolescent, Area Under Curve, Child, Child, Preschool, Cyclosporine pharmacology, Drug Administration Schedule, Female, Humans, Immunosuppressive Agents pharmacology, Infant, Infusions, Intravenous, Linear Models, Male, Myeloablative Agonists pharmacology, Myeloablative Agonists therapeutic use, Prospective Studies, Transplantation, Homologous, Treatment Outcome, Cyclosporine therapeutic use, Drug Monitoring statistics & numerical data, Graft vs Host Disease prevention & control, Hematopoietic Stem Cell Transplantation, Immunosuppressive Agents therapeutic use, Transplantation Conditioning
- Abstract
This prospective study aimed to validate a previously developed first-dose limited sampling strategy (LSS) to predict the area under the cyclosporine concentration-versus-time curve (AUC) and to develop and then validate an LSS to predict cyclosporine AUC at steady state. This two-center Canadian study included children (ages .4 to 17.2 years) undergoing myeloablative allogeneic hematopoietic stem cell transplantation receiving cyclosporine for acute graft-versus-host disease prophylaxis. There were three cohorts, each incorporating 24 AUC determinations: first-dose LSS validation, steady-state LSS development, and steady-state LSS validation. Patients contributing data to either of the development cohorts were excluded from the corresponding validation group. Cyclosporine was given every 12 hours as a 2-hour infusion. Cyclosporine AUC was determined after administration of the first cyclosporine dose (8 samples) and then once weekly (9 samples) until engraftment. Steady-state LSSs were developed using stepwise multiple linear regression. An LSS was considered to provide an acceptable estimate of AUC if the lower limit of the 95% confidence limit (CL) of the intraclass coefficient was .8 or higher and both bias and precision were 15% or less. Fifty-three children age .4 to 18 years participated. Cyclosporine concentrations drawn up to 4 hours from the start of the infusion correlated most strongly with AUC. The previously developed first-dose LSSs and three steady-state LSSs met criteria for acceptability. The intraclass coefficients of the three-point first-dose LSS validation cohort, three-point steady-state LSS development cohort, and three-point steady-state LSS validation cohort were .974 (95% CL: .941 to .988), .984 (95% CL: .965 to .993), and .993 (95% CL: .984 to .997), respectively. The three-point first-dose (2, 6, and 8 hours) and steady-state (2, 2.5, and 8 hours) LSSs are valid measures of cyclosporine AUC after intravenous administration over 2 hours. Their use in a prospective evaluation of the relationship between cyclosporine AUC and hematopoietic stem cell transplantation clinical outcomes in children is suggested., (Copyright © 2013 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2013
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50. A systematic review of symptom assessment scales in children with cancer.
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Dupuis LL, Ethier MC, Tomlinson D, Hesser T, and Sung L
- Subjects
- Adolescent, Child, Female, Humans, Male, Neoplasms pathology, Neoplasms psychology, Quality of Life, Severity of Illness Index, Neoplasms therapy, Outcome Assessment, Health Care methods, Symptom Assessment methods
- Abstract
Background: The objective was to describe symptom assessment scales that have been used in children with cancer., Methods: We conducted electronic searches of OVID Medline and EMBASE in order to identify all symptom assessment scales that have been used in pediatric cancer. Two reviewers abstracted information from each identified study. Data collected included study demographics and information related to the instrument and children enrolled. We also collected information about the purpose of instrument administration and whether treatment was altered as a result of this information., Results: Fourteen studies were identified which evaluated eight different symptom assessment scales. Eight studies used child self-report and all studies included children on active treatment for cancer although 4 studies also included children following completion of treatment. The most common purpose of instrument administration was to measure the prevalence of symptom burden (n = 8). None of the 14 studies used the scale to screen for symptoms and none changed patient management on the basis of identified symptoms., Conclusions: We failed to identify any symptom assessment scales that were used as a symptom screening tool. There is a need to develop such a tool for use in children with cancer.
- Published
- 2012
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