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Item Combined hydration and antibiotics with lisinopril to mitigate acute and delayed high-dose radiation injuries to multiple organs(Lippincott, Williams & Wilkins, 2016-11) Fish, Brian L.; Gao, Feng; Narayanan, Jayashree; Bergom, Carmen; Jacobs, Elizabeth R.; Cohen, Eric P.; Moulder, John E.; Orschell, Christie M.; Medhora, Meetha; Medicine, School of MedicineThe NIAID Radiation and Nuclear Countermeasures Program is developing medical agents to mitigate the acute and delayed effects of radiation that may occur from a radionuclear attack or accident. To date, most such medical countermeasures have been developed for single organ injuries. Angiotensin converting enzyme (ACE) inhibitors have been used to mitigate radiation-induced lung, skin, brain and renal injuries in rats. ACE inhibitors have also been reported to decrease normal tissue complication in radiation oncology patients. In the current study we have developed a rat partial-body irradiation (leg-out PBI) model with minimal bone marrow sparing (one leg shielded) that results in acute and late injuries to multiple organs. In this model, the ACE inhibitor lisinopril (at ∼24 mg m-2 day-1 started orally in the drinking water at 7 days after irradiation and continued to ≥150 days) mitigated late effects in the lungs and kidneys after 12.5 Gy leg-out PBI. Also in this model, a short course of saline hydration and antibiotics mitigated acute radiation syndrome following doses as high as 13 Gy. Combining this supportive care with the lisinopril regimen mitigated overall morbidity for up to 150 days after 13 Gy leg-out PBI. Furthermore lisinopril was an effective mitigator in the presence of the growth factor G-CSF (100 μg kg-1 day-1 from days 1-14) which is FDA-approved for use in a radionuclear event. In summary, by combining lisinopril (FDA-approved for other indications) with hydration and antibiotics, we mitigated acute and delayed radiation injuries in multiple organs.Item Constipation and GI diagnoses in children with solid tumours: prevalence and management(BMJ, 2022-08-30) Belsky, Jennifer; Stanek, Joseph; Yeager, Nicholas; Runco, Daniel; Pediatrics, School of MedicineObjectives Despite continued development of targeted therapies for children with cancer, patients continue to experience an array of unwanted side effects. Children with solid tumours may experience constipation as a result of vinca alkaloid therapy, psychological stressors, periods of inactivity and opioid use. Our objective was to investigate the prevalence and treatment of constipation in hospitalised children with solid tumours treated with chemotherapy. Methods We retrospectively analysed data from 48 children’s hospitals in the Pediatric Health Information System, extracting patients 0–21 years of age with a solid tumour diagnosis hospitalised from October 2015 through December 2019. Results We identified 13 375 unique patients with a solid tumour diagnosis receiving chemotherapy. Constipation was the most common gastrointestinal complaint with 8658 (64.7%; 95% Cl: 63.9% to 65.5%) having a constipation diagnosis or having received at least two laxatives during admission. Bone cancers had the highest percentage (69.9%) of patients with constipation, while Hodgkin’s lymphoma had the lowest, although 52.1% of patients were affected. A total of 44% (n=35 301) of encounters received an opioid at some point during admission. Of patients receiving constipation medications, the most commonly prescribed was polyethyl glycol (n=25 175, 31.7%), followed by docusate (n=11 297, 14.2%), senna (n=10 325, 13.0%) and lactulose (n=5501, 6.9%). Conclusions Constipation is the most common gastrointestinal issue that children with solid tumours experience while receiving chemotherapy in the inpatient setting. Increased attention should be given to constipation prophylaxis and treatment in children with solid tumours undergoing chemotherapy, particularly those identified as high risk.Item Fever and neutropenia hospital discharges in children with cancer: A 2012 update(Taylor & Francis, 2016) Mueller, Emily L.; Croop, James; Carroll, Aaron E.; Department of Pediatrics, IU School of MedicineFever and neutropenia (FN) is a common precipitant for hospitalization among children with cancer, but hospital utilization trends are not well described. This study describes national trends for hospital discharges for FN among children with cancer for the year 2012, compared with the authors’ previous analysis from 2009. Data were analyzed from the Kids’ Inpatient Database (KID), an all-payer US hospital database, for 2012. Pediatric patients with cancer who had a discharge for FN were identified using age ≤19 years, urgent or emergent admit type, nontransferred, and a combination of International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes for fever and neutropenia. The authors evaluated factors associated with a “short length of stay” (SLOS). Sampling weights were used to permit national inferences. In 2012, children with cancer accounted for 1.8% of pediatric hospital discharges (n = 120,675), with 12.2% (n = 13,456) of cancer-related discharges meeting FN criteria. Two fifths of FN discharges had a SLOS, which accounted for $91 million (2015 US$) in hospital charges. The majority had no serious infections; most common infections were viral infection (9.6%) or upper respiratory infection (9.6%). Factors significantly associated with SLOS included having a diagnosis of ear infection (odds ratio [OR] = 1.54, 95% confidence interval [CI]: 1.16–2.03), soft tissue sarcoma (OR = 1.47, CI: 1.10–1.95), and Hodgkin lymphoma (OR = 1.51, CI: 1.09–2.10), as compared with not having those diagnoses. SLOS admissions continue to be rarely associated with serious infections, but contribute substantially to the burden of hospitalization for pediatric FN. Implementation of risk stratification schemas to identify patients who meet low-risk criteria may decrease financial burden.Item Investigating the safety and feasibility of osteopathic medicine in the pediatric oncology outpatient setting(Walter de Gruyter, 2022) Belsky, Jennifer A.; Stanek, Joseph R.; Rose , Melissa J.; Pediatrics, School of MedicineContext: Pediatric patients receiving chemotherapy experience unwanted therapy-induced side effects, commonly constipation and pain that diminish quality of life. To date, few studies have investigated the safety and feasibility of osteopathic manipulative treatment (OMT) in pediatric oncology. Objectives: The primary objective of this study is to investigate the safety and feasibility of OMT in pediatric oncology outpatient clinics. Methods: This is a single institutional pilot study evaluating children aged ≥2–21 years receiving chemotherapy for an oncological diagnosis at Nationwide Children’s Hospital (NCH). Permission was obtained from the NCH Institutional Review Board. Participants were enrolled for 8 weeks and received weekly OMT. OMT was deemed feasible by participating in six out of eight weekly treatments, and safety was assessed through adverse event grading per Common Terminology Criteria for Adverse Events (CTCAE). During the clinic visit, patients answered validated surveys on constipation (Bristol Stool Scale) and pain (FACES Scale) pre/post-OMT. Feasibility was analyzed utilizing a one-sided exact binomial test while validated tools and adverse events were summarized descriptively. Results: A total of 23 patients were enrolled, with 21 included in feasibility analyses. The majority of the patients were female (n=13, 61.9%), with a median age of 12 years at enrollment (range, 2.7–20.8 years). There were no serious adverse events attributed to OMT intervention, and among the patients assessed for feasibility, 100% of them participated in at least two-thirds of their weekly OMT treatments, meeting our defined feasibility criteria. The intervention lasted an average of 14.2 min (range, 7.2–19.2 min). There were no FACES or Bristol Stool Scale scores that correlated with worsening pain on constipation post-OMT intervention. Conclusions: Pediatric oncology patients were feasibly and safely able to receive OMT during a regularly scheduled chemotherapy visit. The limitations include the small sample size. These findings support the need to further investigate the safety and feasibility, as well as efficacy, of OMT in the pediatric oncology clinical setting.