Outcomes following intolerance to calcineurin inhibitor-based graft-versus-host disease prophylaxis in children after allogeneic hematopoietic cell transplantation.

Calcineurin inhibitors (CNI), cyclosporine and tacrolimus, are commonly used for pharmacologic prophylaxis of graft-versus-host disease after allogeneic hematopoietic cell transplantation (HCT). Unfortunately, their use is associated with significant toxicities. While intolerance to CNI is well defined, there is very little information on how they impact outcomes after HCT in children. Our retrospective study in a cohort of 82 children shows a high intolerance rate of 39% in this population associated with lower event-free survival and a higher transplant-related mortality.

Effect of Mobile Device-Assisted N-of-1 Trial Participation on Analgesic Prescribing for Chronic Pain: Randomized Controlled Trial.

OBJECTIVES: Opioids and non-steroidal anti-inflammatory drugs (NSAIDs) are frequently prescribed for chronic musculoskeletal pain, despite limited evidence of effectiveness and well-documented adverse effects. We assessed the effects of participating in a structured, personalized self-experiment ("N-of-1 trial") on analgesic prescribing in patients with chronic musculoskeletal pain. METHODS: We randomized 215 patients with chronic pain to participate in an N-of-1 trial facilitated by a mobile health app or to receive usual care. Medical records of participating patients were reviewed at enrollment and 6 months later to assess analgesic prescribing. We established thresholds of ≥ 50, ≥ 20, and > 0 morphine milligram equivalents (MMEs) per day to capture patients taking relatively high doses only, patients taking low-moderate as well as relatively high doses, and patients taking any dose of opioids, respectively. RESULTS: There was no significant difference between the N-of-1 and control groups in the percentage of patients prescribed any opioids (relative odds ratio (ROR) = 1.05; 95% confidence interval [CI] = 0.61 to 1.80, p = 0.87). There was a clinically substantial but statistically not significant reduction of the percentage of patients receiving ≥ 20 MME (ROR = 0.58; 95% CI = 0.33 to 1.04, p = 0.07) and also in the percentage receiving ≥ 50 MME (ROR = 0.50; 95% CI = 0.19 to 1.34, p = 0.17). There was a significant reduction in the proportion of patients in the N-of-1 group prescribed NSAIDs compared with control (relative odds ratio = 0.53; 95% CI = 0.29 to 0.96, p = 0.04), with no concomitant increase in average pain intensity. There was no significant change in use of adjunctive medications (acetaminophen, gabapentenoids, or topicals). DISCUSSION: These exploratory results suggest that participation in N-of-1 trials may reduce long-term use of NSAIDs; there is also a weak signal for an effect on use of opioids. Additional research is needed to confirm these results and elucidate possible mechanisms. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02116621.

Pharmacokinetic basis for dosing high-dose methotrexate in infants and young children with malignant brain tumours.

AIMS: No population pharmacokinetic studies of high-dose methotrexate (HDMTX) have been conducted in infants with brain tumours, which are a vulnerable population. The aim of this study was to evaluate HDMTX disposition in these children to provide a rational basis for MTX dosing. METHODS: Patients received 4 monthly courses of HDMTX (5 g/m2 or 2.5 g/m2 for infants aged ≤31 days) as a 24-h infusion. Serial samples were analysed for MTX by an enzyme immunoassay method. Pharmacokinetic parameters were estimated using nonlinear mixed effects population modelling. Demographics, concomitant medications and genetic polymorphisms were considered as pharmacokinetic covariates while MTX exposure and patient age were considered as covariates for Grade 3 and 4 toxicities. RESULTS: The population pharmacokinetics of HDMTX were estimated in 178 patients (age range 0.02-4.7 years) in 648 courses. The population clearance and volume were 90 mL/min/m2 and 14.4 L/m2 , respectively. Significant covariates on body surface area adjusted MTX clearance included estimated glomerular filtration rate and co-treatment with dexamethasone or vancomycin. No significant association was observed between MTX toxicity and MTX exposure, patient age, leucovorin dosage or duration. MTX clearance in infants ≤31 days at enrolment was 44% lower than in older infants, but their incidence of toxicity was not higher since they also received a lower MTX dosage. CONCLUSIONS: By aggressively following institutional clinical guidelines, HDMTX-related toxicities were low, and using covariates from the population pharmacokinetic model enabled the calculation of a rational dosage for this patient population for future clinical trials.

The Art of Analgesia: A Pilot Study of Art Museum Tours to Decrease Pain and Social Disconnection Among Individuals with Chronic Pain.

OBJECTIVE: This mixed-methods study examines the feasibility of art museum tours (Art Rx) as an intervention for individuals with chronic pain. METHODS: Art Rx provided 1-hour docent-led tours in an art museum to individuals with chronic pain. Survey data were collected pre-tour, immediately post-tour, and at three weeks post-tour. Pain intensity and unpleasantness were measured with a 0-10 numerical rating scale. Social disconnection was measured with a 12-item social disconnection scale. Participants also reported percent pain relief during the tour and program satisfaction in the post-tour survey. Change in pain and social disconnection was analyzed with paired t tests, bias-corrected and accelerated bootstrap confidence intervals (BCa CIs), and Cohen's d. Thematic analysis of semistructured interviews with participants explored the feasibility and perceived impact of the program. RESULTS: Fifty-four individuals participated in this study (mean age [SD] = 59 [14.5] years, 64.8% female), and 14 were interviewed. Fifty-seven percent of participants reported pain relief during the tour, with an average pain relief (SD) of 47% (34.61%). Participants reported decreased social disconnection and pain unpleasantness pre- to post-tour (3.65, BCa 95% CI = 1.70-5.73, P < 0.001, d = 0.37; and 0.49, BCa 95% CI = 0.06-0.90, P = 0.016, d = 0.20, respectively). Participants indicated high satisfaction with the program. Interviewees remarked on the isolating impact of chronic pain and how negative experiences with the health care system often compounded this sense of isolation. Participants experienced Art Rx as a positive and inclusive experience, with potential lasting benefit. CONCLUSIONS: Art museum tours for individuals with chronic pain are feasible, and participants reported positive effects on perceived social disconnection and pain.

A phase II trial evaluating the feasibility of adding bevacizumab to standard osteosarcoma therapy.

Increased vascular endothelial growth factor (VEGF) expression in osteosarcoma correlates with a poor outcome. We conducted a phase II trial to evaluate the feasibility and efficacy of combining bevacizumab, a monoclonal antibody against VEGF, with methotrexate, doxorubicin and cisplatin (MAP) in patients with localized osteosarcoma. Eligible patients received two courses of MAP chemotherapy before definitive surgery at week 10. Bevacizumab (15 mg/kg) was administered 3 days before starting chemotherapy then on day 1 of weeks 3 and 5 of chemotherapy. After surgery, patients received MAP for a total of 29 weeks; bevacizumab was added every 2 or 3 weeks on day 1 of chemotherapy at least 5 weeks after surgery. Group sequential monitoring rules were used to monitor for unacceptable bevacizumab-related targeted toxicity (grade 4 hypertension, proteinuria or bleeding, grade 3 or 4 thrombosis/embolism, and grade 2-4 major wound complications). Thirty-one patients (median age 12.8 years) with localized osteosarcoma were enrolled. No unacceptable targeted toxicities were observed except for wound complications (9 minor and 6 major), which occurred in 15 patients; none required removal of prosthetic hardware or amputation. The estimated 4-year event-free survival (EFS) rate and overall survival rate were 57.5 ± 10.0% and 83.4 ± 7.8%, respectively. Eight (28%) of 29 evaluable patients had good histologic response (<5% viable tumor) to preoperative chemotherapy. The addition of bevacizumab to MAP for localized osteosarcoma is feasible but frequent wound complications are encountered. The observed histologic response and EFS do not support further evaluation of bevacizumab in osteosarcoma.

Derivation of new equations to estimate glomerular filtration rate in pediatric oncology patients.

BACKGROUND AND OBJECTIVE: Monitoring renal function is critical in treating pediatric patients, especially when dosing nephrotoxic agents. We evaluated the validity of the bedside Schwartz and Brandt equations in pediatric oncology patients and developed new equations for estimated glomerular filtration rate (eGFR) in these patients. METHODS: A retrospective analysis was conducted comparing eGFR using the bedside Schwartz and Brandt equations to measured GFR (mGFR) from technetium-99m diethylenetriamine pentaacetic acid (99mTc-DTPA) between January 2007 and August 2013. An improved equation to estimate GFR was developed, simplified, and externally validated in a cohort of patients studied from September 2013 to June 2015. Carboplatin doses calculated from 99mTc-DTPA were compared with doses calculated by GFR-estimating equations. RESULTS: Overall, the bedside Schwartz and Brandt equations did not precisely or accurately predict measured GFR (mGFR). Using a data subset, we developed a five-covariate equation, which included height, serum creatinine, age, blood urea nitrogen (BUN), and gender, and a simplified version (two-covariates), which contained height and serum creatinine. These equations were used to estimate GFR in 2036 studies, resulting in precise and accurate predictors of mGFR values. Equations were validated in an external cohort of 570 studies; both new equations were more accurate in calculating carboplatin doses than either the bedside Schwartz or Brandt equation. CONCLUSIONS: Two new equations were developed to estimate GFR in pediatric oncology patients, both of which did a better job at estimating mGFR than published equations.

Comparable efficacy with varying dosages of glucarpidase in pediatric oncology patients.

BACKGROUND: Glucarpidase rapidly reduces methotrexate plasma concentrations in patients experiencing methotrexate-induced renal dysfunction. Debate exists regarding the role of glucarpidase in therapy given its high cost. The use of reduced-dose glucarpidase has been reported, and may allow more institutions to supply this drug to their patients. This report explores the relationship between glucarpidase dosage and patient outcomes in pediatric oncology patients. METHODS: The authors evaluated data from 26 patients who received glucarpidase after high-dose methotrexate. Decrease in plasma methotrexate concentrations and time to renal recovery were evaluated for an association with glucarpidase dosage, which ranged from 13 to 90 units/kg. RESULTS: No significant relationship was found between glucarpidase dosage (units/kg) and percent decrease in methotrexate plasma concentrations measured by TDx (P > 0.1) or HPLC (P > 0.5). Patients who received glucarpidase dosages <50 units/kg had a median percent reduction in methotrexate plasma concentration of 99.4% (range, 98-100) measured by HPLC compared to a median percent reduction of 99.4% (range, 77.2-100) in patients who received ≥50 units/kg. Time to SCr recovery was not related to glucarpidase dosage (P > 0.8). CONCLUSIONS: The efficacy of glucarpidase in the treatment of HDMTX-induced kidney injury was not dosage-dependent in this retrospective analysis of pediatric oncology patients.

The eHealth Enhanced Chronic Care Model: a theory derivation approach.

BACKGROUND: Chronic illnesses are significant to individuals and costly to society. When systematically implemented, the well-established and tested Chronic Care Model (CCM) is shown to improve health outcomes for people with chronic conditions. Since the development of the original CCM, tremendous information management, communication, and technology advancements have been established. An opportunity exists to improve the time-honored CCM with clinically efficacious eHealth tools. OBJECTIVE: The first goal of this paper was to review research on eHealth tools that support self-management of chronic disease using the CCM. The second goal was to present a revised model, the eHealth Enhanced Chronic Care Model (eCCM), to show how eHealth tools can be used to increase efficiency of how patients manage their own chronic illnesses. METHODS: Using Theory Derivation processes, we identified a "parent theory", the Chronic Care Model, and conducted a thorough review of the literature using CINAHL, Medline, OVID, EMBASE PsychINFO, Science Direct, as well as government reports, industry reports, legislation using search terms "CCM or Chronic Care Model" AND "eHealth" or the specific identified components of eHealth. Additionally, "Chronic Illness Self-management support" AND "Technology" AND several identified eHealth tools were also used as search terms. We then used a review of the literature and specific components of the CCM to create the eCCM. RESULTS: We identified 260 papers at the intersection of technology, chronic disease self-management support, the CCM, and eHealth and organized a high-quality subset (n=95) using the components of CCM, self-management support, delivery system design, clinical decision support, and clinical information systems. In general, results showed that eHealth tools make important contributions to chronic care and the CCM but that the model requires modification in several key areas. Specifically, (1) eHealth education is critical for self-care, (2) eHealth support needs to be placed within the context of community and enhanced with the benefits of the eCommunity or virtual communities, and (3) a complete feedback loop is needed to assure productive technology-based interactions between the patient and provider. CONCLUSIONS: The revised model, eCCM, offers insight into the role of eHealth tools in self-management support for people with chronic conditions. Additional research and testing of the eCCM are the logical next steps.

e-Patients Perceptions of Using Personal Health Records for Self-management Support of Chronic Illness.

Chronic illness self-management is largely moving from healthcare professionals and into the hands of the patient. One tool that has been promoted to facilitate self-management support of chronic illness by policymakers, health advocates, providers, and consumers is the personal health record. Little is known about how consumers effectively use personal health records for self-management support and for productive patient-provider interactions. The purpose of this study was to learn from chronically ill engaged, experienced, and educated (e-patient) adults how and why they use personal health records for self-management support and productive patient-provider interactions. Eighteen purposively selected consumers were interviewed in two communities. Qualitative description methods were used, and we used a grounded theory approach to analyzing interview data, which was digitally recorded and transcribed verbatim. We identified four major thematic categories that capture the perceptions of the chronically ill using personal health records: (1) patient engagement and health self-management, (2) access to and control over personal health data, (3) promotion of productive communication, and (4) opportunities for training and education. Knowledge gained from the e-patient personal health record users suggest that making improvements to the portal system and providing education to consumers and providers will increase the utility among the experienced users and encourage new users to embrace adoption and use.

Hypersensitivity reaction to high-dose methotrexate and successful rechallenge in a pediatric patient with osteosarcoma.

Hypersensitivity reactions to methotrexate are rare, but have been reported. Methotrexate has shown activity against many malignancies, and omission of methotrexate therapy may increase the risk of cancer-related death in some patients. Therefore, rechallenging patients with methotrexate following hypersensitivity may be beneficial. We report a case of a child with metastatic osteosarcoma who experienced a hypersensitivity reaction to high-dose methotrexate and was successfully rechallenged with methotrexate using a 6-hour infusion. Using this regimen, adequate peak methotrexate plasma concentrations were achieved and no further hypersensitivity reactions were noted.

Sustained effects of a nurse coaching intervention via telehealth to improve health behavior change in diabetes.

BACKGROUND: Diabetes educators and self-management programs are scarce in rural communities, where diabetes is the third highest-ranking health concern. The goal of this study was to evaluate the benefits of nurse telehealth coaching for persons with diabetes living in rural communities through a person-centered approach using motivational interviewing (MI) techniques. MATERIALS AND METHODS: A randomized experimental study design was used to assign participants to receive either nurse telehealth coaching for five sessions (intervention group) or usual care (control group). Outcomes were measured in both groups using the Diabetes Empowerment Scale (DES), SF-12, and satisfaction surveys. Mean scores for each outcome were compared at baseline and at the 9-month follow-up for both groups using a Student's t test. We also evaluated the change from baseline by estimating the difference in differences (pre- and postintervention) using regression methods. RESULTS: Among the 101 participants included in the analysis, 51 received nurse telehealth coaching, and 50 received usual care. We found significantly higher self-efficacy scores in the intervention group compared with the control group based on the DES at 9 months (4.03 versus 3.64, respectively; p<0.05) and the difference in difference estimation (0.42; p<0.05). CONCLUSIONS: The nurse MI/telehealth coaching model used in this study shows promise as an effective intervention for diabetes self-management in rural communities. The sustained effect on outcomes observed in the intervention group suggests that this model could be a feasible intervention for long-term behavioral change among persons living with chronic disease in rural communities.

Interprofessional education: an overview of six initiatives across the schools of health at a single university.

The benefits of interprofessional education (IPE) amongst health professionals are well documented, however, the implementation of interprofessional initiatives across the USA is inconsistent. This report describes the development and content of a number of IPE initiatives that are in the early stages of development and implementation at the University of California, Davis, USA. The article describes several important factors that were found to be necessary for the initial implementation of these IPE initiatives. Evaluation data from these initiatives, which is providing a range of positive outcomes, are also presented and discussed in relation to the wider IPE literature.

Positive Feedback as a Lever to Boost Students' STEM Outcomes.

Although many college students intend to major in Science, Technology, Engineering, and Mathematics (STEM), dropout from these fields is high, especially among members of historically underrepresented groups, such as women and racial-ethnic minorities. We propose a minimal, yet potentially powerful intervention to broaden participation in STEM: giving positive feedback to students in STEM. Studies 1 and 2 found that giving positive feedback is less normative in math (vs. English) courses, and instructors' feedback-giving practices and students' experiences mirror these norms. However, students who received positive (vs. only objective) feedback on introductory-level college calculus exams showed greater belonging and self-efficacy in math, which predicted better STEM outcomes (i.e., increased interest in STEM and higher final math course grades, respectively, Study 3). These findings were especially strong for racial-ethnic minority students. Giving positive (vs. only objective) feedback is thus a potentially transformative tool that boosts student outcomes, especially for underrepresented groups.

Population pharmacokinetics of methotrexate and 7-hydroxymethotrexate and delayed excretion in infants and young children with brain tumors.

PURPOSE: The objectives of this study were to develop a population pharmacokinetic model of methotrexate (MTX) and its primary metabolite 7-hydroxymethotrexate (7OHMTX) in children with brain tumors, to identify the sources of pharmacokinetic variability, and to assess whether MTX and 7OHMTX systemic exposures were related to toxicity. METHODS: Patients received 2.5 or 5 g/m2 MTX as a 24-hour infusion and serial samples were analyzed for MTX and 7OHMTX by an LC-MS/MS method. Pharmacokinetic parameters were estimated using nonlinear mixed-effects modeling. Demographics, laboratory values, and genetic polymorphisms were considered as potential covariates to explain the pharmacokinetic variability. Association between MTX and 7OHMTX systemic exposures and MTX-related toxicities were explored using random intercept logistic regression models. RESULTS: The population pharmacokinetics of MTX and 7OHMTX were adequately characterized using two-compartment models in 142 patients (median 1.91 y; age range 0.09 to 4.94 y) in 513 courses. The MTX and 7OHMTX population clearance values were 4.6 and 3.0 l/h/m2, respectively. Baseline body surface area and estimated glomerular filtration rate were significant covariates on both MTX and 7OHMTX plasma disposition. Pharmacogenetic genotypes were associated with MTX pharmacokinetic parameters but had only modest influence. No significant association was observed between MTX or 7OHMTX exposure and MTX-related toxicity. CONCLUSIONS: MTX and 7OHMTX plasma disposition were characterized for the first time in young children with brain tumors. No exposure-toxicity relationship was identified in this study, presumably due to aggressive clinical management which led to a low MTX-related toxicity rate.

Using Framework Analysis in nursing research: a worked example.

AIMS: To demonstrate Framework Analysis using a worked example and to illustrate how criticisms of qualitative data analysis including issues of clarity and transparency can be addressed. BACKGROUND: Critics of the analysis of qualitative data sometimes cite lack of clarity and transparency about analytical procedures; this can deter nurse researchers from undertaking qualitative studies. Framework Analysis is flexible, systematic, and rigorous, offering clarity, transparency, an audit trail, an option for theme-based and case-based analysis and for readily retrievable data. This paper offers further explanation of the process undertaken which is illustrated with a worked example. DATA SOURCE AND RESEARCH DESIGN: Data were collected from 31 nursing students in 2009 using semi-structured interviews. DISCUSSION: The data collected are not reported directly here but used as a worked example for the five steps of Framework Analysis. Suggestions are provided to guide researchers through essential steps in undertaking Framework Analysis. The benefits and limitations of Framework Analysis are discussed. IMPLICATIONS FOR NURSING: Nurses increasingly use qualitative research methods and need to use an analysis approach that offers transparency and rigour which Framework Analysis can provide. Nurse researchers may find the detailed critique of Framework Analysis presented in this paper a useful resource when designing and conducting qualitative studies. CONCLUSION: Qualitative data analysis presents challenges in relation to the volume and complexity of data obtained and the need to present an 'audit trail' for those using the research findings. Framework Analysis is an appropriate, rigorous and systematic method for undertaking qualitative analysis.

Pursuing safety in social connection regulates the risk-regulation, social-safety, and behavioral-immune systems.

A new goal-systems model is proposed to help explain when individuals will protect themselves against the risks inherent to social connection. This model assumes that people satisfy the goal to feel included in safe social connections-connections where they are valued and protected rather than at risk of being harmed-by devaluing rejecting friends, trusting in expectancy-consistent relationships, and avoiding infectious strangers. In the hypothesized goal system, frustrating the fundamental goal to feel safe in social connection sensitizes regulatory systems that afford safety from the risk of being interpersonally rejected (i.e., the risk-regulation system), existentially uncertain (i.e., the social-safety system), or physically infected (i.e., the behavioral-immune system). Conversely, fulfilling the fundamental goal to feel safe in social connection desensitizes these self-protective systems. A 3-week experimental daily diary study (N = 555) tested the model hypotheses. We intervened to fulfill the goal to feel safe in social connection by repeatedly conditioning experimental participants to associate their romantic partners with highly positive, approachable words and images. We then tracked how vigilantly experimental versus control participants protected themselves when they encountered social rejection, unexpected behavior, or contagious illness in everyday life. Multilevel analyses revealed that the intervention lessoned self-protective defenses against each of these risks for participants who ordinarily felt most vulnerable to them. The findings provide the first evidence that the fundamental goal to feel safe in social connection can co-opt the risk-regulation, social-safety, and behavioral-immune systems as independent means for its pursuit. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Happiness-To enjoy now or later? Consequences of delaying happiness and living in the moment beliefs.

How do people think about happiness? Is it something best enjoyed as an investment over time, or is it something fleeting that should be savored? When people view happiness as an investment, they may endorse delaying happiness (DH)-the belief that working hard and sacrificing opportunities for happiness now will contribute to greater future happiness. When people view happiness as fleeting, they may endorse living in the moment (LM)-the belief that one should seize proximal opportunities to experience happiness now, rather than later. Using a mix of cross-sectional, meta-analytic (Studies 1, 2a, 2b, 2c), experimental (Study 3), and daily diary methods (Study 4), people who endorsed DH or LM beliefs anticipated more positive affect upon goal attainment and experienced greater well-being, but only DH was related to more negative affect when pursuing nonfocal goals and less delay discounting of future rewards. Implications for self-regulation and emotion are discussed. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

SalB inactivation modulates culture supernatant exoproteins and affects autolysis and viability in Enterococcus faecalis OG1RF.

The culture supernatant fraction of an Enterococcus faecalis gelE mutant of strain OG1RF contained elevated levels of the secreted antigen SalB. Using differential fluorescence gel electrophoresis (DIGE) the salB mutant was shown to possess a unique complement of exoproteins. Differentially abundant exoproteins were identified using matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry. Stress-related proteins including DnaK, Dps family protein, SOD, and NADH peroxidase were present in greater quantity in the OG1RF salB mutant culture supernatant. Moreover, several proteins involved in cell wall synthesis and cell division, including d-Ala-d-Lac ligase and EzrA, were present in reduced quantity in OG1RF salB relative to the parent strain. The salB mutant displayed reduced viability and anomalous cell division, and these phenotypes were exacerbated in a gelE salB double mutant. An epistatic relationship between gelE and salB was not identified with respect to increased autolysis and cell morphological changes observed in the salB mutant. SalB was purified as a six-histidine-tagged protein to investigate peptidoglycan hydrolytic activity; however, activity was not evident. High-pressure liquid chromatography (HPLC) analysis of reduced muropeptides from peptidoglycan digested with mutanolysin revealed that the salB mutant and OG1RF were indistinguishable.

Proteomics and in silico approaches to extend understanding of the glutathione transferase superfamily of the tropical liver fluke Fasciola gigantica.

Fasciolosis is an important foodborne, zoonotic disease of livestock and humans, with global annual health and economic losses estimated at several billion US$. Fasciola hepatica is the major species in temperate regions, while F. gigantica dominates in the tropics. In the absence of commercially available vaccines to control fasciolosis, increasing reports of resistance to current chemotherapeutic strategies and the spread of fasciolosis into new areas, new functional genomics approaches are being used to identify potential new drug targets and vaccine candidates. The glutathione transferase (GST) superfamily is both a candidate drug and vaccine target. This study reports the identification of a putatively novel Sigma class GST, present in a water-soluble cytosol extract from the tropical liver fluke F. gigantica. The GST was cloned and expressed as an enzymically active recombinant protein. This GST shares a greater identity with the human schistosomiasis GST vaccine currently at Phase II clinical trials than previously discovered F. gigantica GSTs, stimulating interest in its immuno-protective properties. In addition, in silico analysis of the GST superfamily of both F. gigantica and F. hepatica has revealed an additional Mu class GST, Omega class GSTs, and for the first time, a Zeta class member.

Resumption of high-dose methotrexate after acute kidney injury and glucarpidase use in pediatric oncology patients.

BACKGROUND: High-dose methotrexate (HDMTX)-induced acute kidney injury is a rare but life-threatening complication. The methotrexate rescue agent glucarpidase rapidly hydrolyzes methotrexate to inactive metabolites. The authors retrospectively reviewed glucarpidase use in pediatric cancer patients at their institution and evaluated whether subsequent resumption of HDMTX was tolerated. METHODS: Clinical data and outcomes of all patients who received glucarpidase after HDMTX administration were reviewed. RESULTS: Of 1141 patients who received 4909 courses of HDMTX, 20 patients (1.8% of patients, 0.4% of courses) received 22 doses of glucarpidase. The median glucarpidase dose was 51.6 U/kg (range, 13-65.6 U/kg). At the time of administration, the median plasma methotrexate concentration was 29.1 µM (range, 1.3-590.6 µM). Thirteen of the 20 patients received a total of 39 courses of HDMTX therapy after glucarpidase. The median time to complete methotrexate excretion was 355 hours (range, 244-763 hours) for the HDMTX course during which glucarpidase was administered, 90 hours (range, 66-268 hours) for the next HDMTX course, and 72 hours (range, 42-116 hours) for subsequent courses. The median peak serum creatinine level during these HDMTX courses was 2.2 mg/dL (range, 0.8-9.6 mg/dL), 0.8 mg/dL (range, 0.4-1.6 mg/dL), and 0.6 mg/dL (range, 0.4-0.9 mg/dL), respectively. One patient experienced nephrotoxicity upon rechallenge with HDMTX. Renal function eventually returned to baseline in all patients, and no patient died as a result of methotrexate toxicity. CONCLUSIONS: The current results indicated that it is possible to safely resume HDMTX therapy after glucarpidase treatment for HDMTX-induced acute kidney injury.