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Background: Case investigations and contact tracing are essential disease control measures used by health departments. Early in the pandemic, they were seen as a key strategy to stop COVID-19 spread. The CDC urged rapid action to scale up and train a large workforce and collaborate across public and private agencies to halt COVID-19 transmission., Methods: We developed a program for case investigation and contact tracing that followed CDC and local health guidelines, compliant with the Occupational Safety and Health Administration (OSHA) regulations and tailored to the needs and resources of our institution. Program staff were trained and assessed for competency before joining the program., Results: From March 2020 to May 2021, we performed 838 COVID-19 case investigations, which led to 136 contacts. Most employees reported a known SARS-CoV-2 exposure from the community ( n  = 435) or household ( n  = 343). Only seven (5.1%) employees were determined as more likely than not to have SARS-CoV-2 infection related to workplace exposure, and when so, lapses in following the masking recommendations were identified. Between June 2021-February 2022, our program adjusted to the demand of the different waves, particularly omicron, by significantly reducing the amount of data collected. No transmission from employees to patients or caregivers was observed during this period., Conclusion: Prompt implementation of case investigation and contact tracing is possible, and it effectively reduces workplace exposures. This approach can be adapted to suit the specific needs and requirements of various healthcare settings, particularly those serving the most vulnerable patient populations., Competing Interests: RH has served on advisory boards for Abbott Diagnostics and T2 Diagnostics. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Hijano, Dennis, Hoffman, Tang, Hayden, St. Jude COVID-19 Case Investigation and Contact Tracing Team, Gaur and Hakim.)

Objectives: Develop and deploy a disease cohort-based machine learning algorithm for timely identification of hospitalized pediatric patients at risk for clinical deterioration that outperforms our existing situational awareness program., Design: Retrospective cohort study., Setting: Nationwide Children's Hospital, a freestanding, quaternary-care, academic children's hospital in Columbus, OH., Patients: All patients admitted to inpatient units participating in the preexisting situational awareness program from October 20, 2015, to December 31, 2019, excluding patients over 18 years old at admission and those with a neonatal ICU stay during their hospitalization., Interventions: We developed separate algorithms for cardiac, malignancy, and general cohorts via lasso-regularized logistic regression. Candidate model predictors included vital signs, supplemental oxygen, nursing assessments, early warning scores, diagnoses, lab results, and situational awareness criteria. Model performance was characterized in clinical terms and compared with our previous situational awareness program based on a novel retrospective validation approach. Simulations with frontline staff, prior to clinical implementation, informed user experience and refined interdisciplinary workflows. Model implementation was piloted on cardiology and hospital medicine units in early 2021., Measurements and Main Results: The Deterioration Risk Index (DRI) was 2.4 times as sensitive as our existing situational awareness program (sensitivities of 53% and 22%, respectively; p < 0.001) and required 2.3 times fewer alarms per detected event (121 DRI alarms per detected event vs 276 for existing program). Notable improvements were a four-fold sensitivity gain for the cardiac diagnostic cohort (73% vs 18%; p < 0.001) and a three-fold gain (81% vs 27%; p < 0.001) for the malignancy diagnostic cohort. Postimplementation pilot results over 18 months revealed a 77% reduction in deterioration events (three events observed vs 13.1 expected, p = 0.001)., Conclusions: The etiology of pediatric inpatient deterioration requires acknowledgement of the unique pathophysiology among cardiology and oncology patients. Selection and weighting of diverse candidate risk factors via machine learning can produce a more sensitive early warning system for clinical deterioration. Leveraging preexisting situational awareness platforms and accounting for operational impacts of model implementation are key aspects to successful bedside translation., Competing Interests: Dr. Gorham received funding from LDA Research. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Purpose: Burnout is a syndrome of emotional exhaustion, depersonalization, and reduced personal accomplishment because of chronic occupational stress. Approximately one third of pediatric hematology-oncology physicians experience burnout. The goal of this mixed methods study was to determine the prevalence and drivers of burnout among physicians caring for pediatric hematology-oncology patients at our institution., Materials and Methods: This mixed methods, cross-sectional study was conducted at a large academic cancer center. Validated survey instruments were used to measure burnout, job demands, experience with patient safety events, and workplace culture. Quantitative data informed development of a semistructured interview guide, and physicians were randomly selected to participate in individual interviews. Interviews were transcribed and analyzed via content analysis based on a priori codes., Results: The survey was distributed to 132 physicians, and 53 complete responses were received (response rate 40%). Of the 53 respondents, 15 (28%) met criteria for burnout. Experiencing burnout was associated with increased temporal demand. Twenty-six interviews were conducted. Qualitative themes revealed that frequent meetings, insufficient support staff, and workflow interruptions were key drivers of temporal demand and that temporal demand contributed to burnout through emotional exhaustion and reduced personal accomplishment., Conclusion: Nearly one-third of participating physicians met criteria for burnout, and burnout was associated with increased temporal demand. Qualitative interviews identified specific drivers of temporal demand and burnout, which can be targeted for intervention. This methodology can be easily adapted for broad use and may represent an effective strategy for identifying and mitigating institution-specific drivers of burnout.

Objective: Several studies have suggested that cancer is associated with a reduced risk of the development of Alzheimer's disease (AD). This study seeks to improve our understanding of the association between cancer and the development of AD by showing how mortality selection alters this relationship., Method: A retrospective cohort study was carried out examining 92,425 individuals (47,873 women and 44,552 men) from the Utah Population Database with and without a history of any primary cancer identified by the Utah Cancer Registry. All individuals were aged 65-79 years and free of dementia in 1992 and followed for upwards of 18 years (1992-2009) for AD ascertainment, which was identified using diagnostic information from Medicare claims data., Results: We replicate previous results suggesting that cancer is associated with reduced risk of subsequent AD under specific statistical model specifications. However, these results should not be interpreted as evidence of an etiological association. We conclude that higher rates of overall mortality among individuals with cancer relative to those without cancer induce the widely reported putative protective association with cancer., Conclusion: Careful consideration of model specification and the profound effects of mortality selection in the older adult population is essential when investigating the relationship between aging-related diseases such as cancer and AD. We show that cancer does not provide protection from AD as previously described in the literature. Social scientists seeking to understand social disparities in disease outcomes among older adults may therefore want to strongly consider the role of mortality selection which, if uncorrected, may generate biased associations., (© The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The Uniform Protocols for Imaging in Clinical Trials (UPICT) (18)F-FDG PET/CT protocol is intended to guide the performance of whole-body FDG PET/CT studies within the context of single- and multiple-center clinical trials of oncologic therapies by providing acceptable (minimum), target, and ideal standards for all phases of imaging. The aim is to minimize variability in intra- and intersubject, intra- and interplatform, interexamination, and interinstitutional primary or derived data. The goal of this condensed version of the much larger document is to make readers aware of the general content and subject area. The document has several main subjects: context of the imaging protocol within the clinical trial; site selection, qualification, and training; subject scheduling; subject preparation; imaging-related substance preparation and administration; imaging procedure; image postprocessing; image analysis; image interpretation; archiving and distribution of data; quality control; and imaging-associated risks and risk management., (© 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

Objective: To investigate the use of a trigger tool for the detection of adverse drug events (ADE) in a pediatric hospital specializing in oncology, hematology, and other catastrophic diseases., Study Design: A medication-based trigger tool package analyzed electronic health records from February 2009 to February 2013. Chart review determined whether an ADE precipitated the trigger. Severity was assigned to ADEs, and preventability was assessed. Preventable ADEs were compared with the hospital's electronic voluntary event reporting system to identify whether these ADEs had been previously identified. The positive predictive values (PPVs) of the entire trigger tool and individual triggers were calculated to assess their accuracy to detect ADEs., Results: Trigger occurrences (n = 706) were detected in 390 patients from 6 medication triggers, 33 of which were ADEs (overall PPV = 16%). Hyaluronidase had the greatest PPV (60%). Most ADEs were category E harm (temporary harm) per the National Coordinating Council for Medication Error Reporting and Prevention index. One event was category H harm (intervention to sustain life). Naloxone was associated with the most grade 4 ADEs per the Common Terminology Criteria for Adverse Events v4.03. Twenty-one (64%) ADEs were preventable, 3 of which were submitted via the voluntary reporting system., Conclusion: Most of the medication-based triggers yielded low PPVs. Refining the triggers based on patients' characteristics and medication usage patterns could increase the PPVs and make them more useful for quality improvement. To efficiently detect ADEs, triggers must be revised to reflect specialized pediatric patient populations such as hematology and oncology patients., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Positron emission tomography (PET) can image a wide variety of functional and physiological parameters in vivo using different radiotracers. As more is learned about the molecular basis for disease and treatment, the potential value of molecular imaging for characterizing and monitoring disease status has increased. Characterizing multiple aspects of tumor physiology by imaging multiple PET tracers in a single patient provides additional complementary information, and there is a significant body of literature supporting the potential value of multi-tracer PET imaging in oncology. However, imaging multiple PET tracers in a single patient presents a number of challenges. A number of techniques are under development for rapidly imaging multiple PET tracers in a single scan, where signal-recovery processing algorithms are employed to recover various imaging endpoints for each tracer. Dynamic imaging is generally used with tracer injections staggered in time, and kinetic constraints are utilized to estimate each tracers' contribution to the multi-tracer imaging signal. This article summarizes past and ongoing work in multi-tracer PET tumor imaging, and then organizes and describes the main algorithmic approaches for achieving multi-tracer PET signal-recovery. While significant advances have been made, the complexity of the approach necessitates protocol design, optimization, and testing for each particular tracer combination and application. Rapid multi-tracer PET techniques have great potential for both research and clinical cancer imaging applications, and continued research in this area is warranted.

Background: Limited information exists regarding the use of posaconazole for treating systemic fungal infections in children, adolescents, and young adults with cancer. At St. Jude Children's Research Hospital, the recommended posaconazole dose in patients weighing less than 34 kg is 18-24 mg/kg daily, given in 4 divided doses. For patients aged 13 years or older or those weighing 34 kg or more, the recommended dose is 800 mg daily, given orally in 4 divided doses., Objective: To determine whether the current posaconazole dosing guidelines achieve target posaconazole plasma concentrations of 0.7 μg/mL or greater., Methods: This retrospective clinical study examined data from patients who received treatment-dose posaconazole and had at least 1 posaconazole plasma concentration measurement., Results: Data from 33 patients who received posaconazole for the treatment of fungal infections were analyzed. The median age of patients was 11.5 years (range 0.5-23.2). Twenty-one of 33 patients (63.6%) had posaconazole concentrations of 0.7 μg/mL or greater (median 1.4; range 0.7-2.98) at the first measurement. The median posaconazole dosage referenced to total body weight in these patients was 20 mg/kg/day. Patients with concentrations less than 0.7 μg/mL (median 0.4; range 0.025-0.69) received lower posaconazole dosages when referenced to body weight (median 12.9 mg/kg/day; p = 0.02). Of the 12 patients with concentrations less than 0.7 μg/mL, 7 (58.3%) were aged 13 years or older., Conclusions: The current dosing approach for posaconazole yielded therapeutic plasma concentrations more frequently in patients younger than 13 years than in those 13 years or older. This difference may be related to the practice of capping adolescent and young adult doses at the suggested maximum adult daily dose. Therefore, we recommend weight-based dosing in all pediatric, adolescent, and young adult patients with cancer, with routine therapeutic drug monitoring to ensure adequate concentrations.

Background: Concern has been raised about possible increased mortality associated with the use of cefepime. There are limited data available on the pragmatic use of beta-lactam antibiotics, especially in children., Procedure: This retrospective study included 532 pediatric oncology patients. The outcomes of patients treated with cefepime for suspected serious bacterial infections were compared to those of patients treated with ceftazidime. Primary outcomes included 30- and 90-day all-cause mortality., Results: The demographic and clinical characteristics of 337 patients treated with ceftazidime were similar to those of 195 patients receiving cefepime. Thirty-day and 90-day all cause mortality rates were comparable (30-day OR for cefepime: 3.48, 95% CI 0.31-38.84, P = 0.3; 90-day OR: 0.99, 95% CI 0.29-3.42, P = 1.0). There were also no differences in infection-related mortality rates, secondary infections, or adverse drug events. Deaths occurring within 30 days of hospitalization were judged to be attributable to infection, but not the result of treatment failure or adverse drug events. Deaths occurring between 30 and 90 days were associated with progressive or new malignancy. Secondary infection was significantly associated with mortality., Conclusions: The use of cefepime in pediatric oncology patients is not associated with increased mortality when compared to ceftazidime, however the small number of deaths in this study limits the strength of this conclusion. Previous associations between antimicrobial therapy and increased all-cause mortality may have been confounded by patients' demographic characteristics and co-morbid conditions. All-cause mortality may be an insensitive outcome for studies examining the efficacy and safety of these agents., (Copyright © 2013 Wiley Periodicals, Inc.)

Purpose: The results of a survey to characterize oncology drug shortages across the United States and the impact of shortages on clinical practice, patient safety, clinical trials, and health care costs are presented., Methods: A 34-item online survey was distributed to 1672 members of the Hematology/Oncology Pharmacy Association and other organizations to gather information on shortages of oncology drugs (i.e., all drugs essential in the care of cancer patients, including supportive care agents)., Results: Two hundred forty-three completed responses, almost all from pharmacists (97%), were analyzed. Delays in chemotherapy administration or changes in treatment regimens due to drug shortages were reported by 93% of survey participants; 85% of respondents reported increased costs, and 10% reported reimbursement challenges related to drug shortages. At 34% of represented institutions, at least 1000 hours of additional labor annually was needed to manage shortages. Changes in therapy leading to near-miss errors were reported by 16% of participants, with 6% reporting one or more actual medication errors attributable to a drug shortage. The oncology medications most frequently reported to be in short supply during the preceding 12 months were fluorouracil, leucovorin, liposomal doxorubicin, and paclitaxel. The conduct of clinical trials was affected by drug shortages at 44% of represented institutions., Conclusion: A survey of U.S. oncology pharmacists indicated that oncology drug shortages occurred frequently in the first half of 2011. Shortages led to delays in chemotherapy and changes in therapy, complicated the conduct of clinical research, increased the risks of medication errors and adverse outcomes, and increased medication costs.

Background: Approximately 7-10% of patients with unprovoked VTE will be diagnosed with cancer within 12 months. Although cancer screening has been proposed in these patients, the optimal strategy remains unclear. In a pilot study, we prospectively investigated the use of FDG-PET/CT to screen for occult malignancy in 40 patients with unprovoked VTE., Materials/methods: Patients were initially screened for occult malignancy with a focused history, physical, and laboratory evaluation. Patients underwent whole body FDG-PET/CT and were followed for up to two years for a new diagnosis of cancer. The total costs of using FDG-PET/CT as a comprehensive screening strategy were determined using 2010 Medicare reimbursement rates., Results: Completion of FDG-PET/CT imaging was feasible and identified abnormal findings requiring additional evaluations in 62.5% of patients. Occult malignancy was evident in only one patient (cancer incidence 2.5%) and FDG-PET/CT imaging excluded malignancy in the remainder of patients. No patients with a negative FDG-PET/CT were diagnosed with malignancy during an average (±SD) follow-up of 449 (±311) days. The use of FDG-PET/CT to screen for occult malignancy added $59,151 in total costs ($1,479 per patient). The majority of these costs were due to the cost of the FDG-PET/CT ($1,162 per patient or 78.5% of total per-patient costs)., Conclusions: FDG-PET/CT may have utility for excluding occult malignancy in patients with unprovoked VTE. The costs of this comprehensive screening strategy were comparable to other screening approaches. Larger studies are needed to further evaluate the utility and cost-effectiveness of FDG-PET/CT as a cancer screening strategy in patients with unprovoked VTE., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Computerized prescriber order entry (CPOE) for medications has been implemented in only approximately 1 in 6 United States hospitals, with CPOE for chemotherapy lagging behind that for nonchemotherapy medications. The high risks associated with chemotherapy combined with other aspects of cancer care present unique challenges for the safe and appropriate use of CPOE. This article describes the process for safe and successful implementation of CPOE for chemotherapy at a children's cancer center. A core principle throughout the development and implementation of this system was that it must be as safe (and eventually safer) as existing paper systems and processes. The history of requiring standardized, regimen-specific, preprinted paper order forms served as the foundation for safe implementation of CPOE for chemotherapy. Extensive use of electronic order sets with advanced functionality; formal process redesign and system analysis; automated clinical decision support; and a phased implementation approach were essential strategies for safe implementation of CPOE. With careful planning and adequate resources, CPOE for chemotherapy can be safely implemented.

Molecular imaging of the body involves new techniques to image cellular biochemical processes, which results in studies with high sensitivity, specificity, and signal-to-background. The most prevalently used molecular imaging technique in body imaging is currently fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET). FDG PET has become the method of choice for the staging and restaging of many of the most common cancers, including lymphoma, lung cancer, breast cancer, and colorectal cancer. FDG PET has also become extremely valuable in monitoring the response to therapeutic drugs in many cancers. New PET agents, such as fluorothymidine and acetate, have also shown promise in the evaluation of response to therapy and in the staging of prostate cancer. Magnetic resonance (MR) spectroscopy has shown promise in the evaluation of prostate cancer. Breast cancer evaluation benefits from advances in spectroscopic imaging and contrast-enhanced kinetic evaluation of vascular permeability, which is altered in neoplastic processes because of release of angiogenic factors. Superparamagnetic iron oxide (SPIO) particles represent the first of an expanding line of MR contrast agents that target specific cellular processes. SPIO particles have also been used in the evaluation of the cirrhotic liver and at MR lymphangiography.

The use of positron emission tomography (PET) is increasing rapidly in the United States, with the most common use of PET scanning related to oncology. It is especially useful in the staging and management of lymphoma, lung cancer, and colorectal cancer, according to a panel of expert radiologists, surgeons, radiation oncologists, nuclear medicine physicians, medical oncologists, and general internists convened in November 2006 by the National Comprehensive Cancer Network. The Task Force was charged with reviewing existing data and developing clinical recommendations for the use of PET scans in the evaluation and management of breast cancer, colon cancer, non-small cell lung cancer, and lymphoma. This report summarizes the proceedings of this meeting, including discussions of the background of PET, possible future developments, and the role of PET in oncology.

As addressed by the recent Food and Drug Administration Critical Path Initiative, tools are urgently needed to increase the speed, efficiency, and cost-effectiveness of drug development for cancer and other diseases. Molecular imaging probes developed based on recent scientific advances have great potential as oncologic drug development tools. Basic science studies using molecular imaging probes can help to identify and characterize disease-specific targets for oncologic drug therapy. Imaging end points, based on these disease-specific biomarkers, hold great promise to better define, stratify, and enrich study groups and to provide direct biological measures of response. Imaging-based biomarkers also have promise for speeding drug evaluation by supplementing or replacing preclinical and clinical pharmacokinetic and pharmacodynamic evaluations, including target interaction and modulation. Such analyses may be particularly valuable in early comparative studies among candidates designed to interact with the same molecular target. Finally, as response biomarkers, imaging end points that characterize tumor vitality, growth, or apoptosis can also serve as early surrogates of therapy success. This article outlines the scientific basis of oncology imaging probes and presents examples of probes that could facilitate progress. The current regulatory opportunities for new and existing probe development and testing are also reviewed, with a focus on recent Food and Drug Administration guidance to facilitate early clinical development of promising probes.

2-[(18)F]Fluoro-2-deoxyglucose positron emission tomography (FDG-PET) assesses a fundamental property of neoplasia, the Warburg effect. This molecular imaging technique offers a complementary approach to anatomic imaging that is more sensitive and specific in certain cancers. FDG-PET has been widely applied in oncology primarily as a staging and restaging tool that can guide patient care. However, because it accurately detects recurrent or residual disease, FDG-PET also has significant potential for assessing therapy response. In this regard, it can improve patient management by identifying responders early, before tumor size is reduced; nonresponders could discontinue futile therapy. Moreover, a reduction in the FDG-PET signal within days or weeks of initiating therapy (e.g., in lymphoma, non-small cell lung, and esophageal cancer) significantly correlates with prolonged survival and other clinical end points now used in drug approvals. These findings suggest that FDG-PET could facilitate drug development as an early surrogate of clinical benefit. This article reviews the scientific basis of FDG-PET and its development and application as a valuable oncology imaging tool. Its potential to facilitate drug development in seven oncologic settings (lung, lymphoma, breast, prostate, sarcoma, colorectal, and ovary) is addressed. Recommendations include initial validation against approved therapies, retrospective analyses to define the magnitude of change indicative of response, further prospective validation as a surrogate of clinical benefit, and application as a phase II/III trial end point to accelerate evaluation and approval of novel regimens and therapies.

The adaptation and development of imaging technologies for use in small animals has the potential to be a refinement with profound effects on how basic cancer research using animals is conducted. The authors describe how NCI funding is helping to advance research in this area.