High-Dose Methotrexate: Nursing Considerations for Administration and Supportive Care.

BACKGROUND: High-dose methotrexate (HDMTX) is the backbone of many pediatric and adult oncology treatment protocols. It requires appropriate monitoring and supportive care because delayed elimination of MTX can lead to serious toxicities. No reviews specifically addressing nursing management regarding standard treatment protocols and delayed MTX elimination exist. OBJECTIVES: This article provides an overview of HDMTX treatment and nursing considerations, including toxicities, components of supportive care management, and strategies to manage administration and delayed elimination of MTX. METHODS: A review of published literature and guidelines was performed to evaluate nursing considerations for patients receiving HDMTX. FINDINGS: Using existing and novel tools, nurses can closely monitor patients and provide supportive care to mitigate HDMTX toxicity. Early identification of delayed MTX elimination and subsequent treatment with glucarpidase, if appropriate, has been associated with shorter length of hospital stay and decreased incidence of grade 4 toxicities and mortality.

Increased Utilization of Low-Dose CT for Lung Cancer Screening at an Arkansas Community Oncology Clinic.

BACKGROUND: Low-dose CT (LDCT) is underused in Arkansas for lung cancer screening, a rural state with a high incidence of lung cancer. The objective was to determine whether offering free LDCT increased the number of high-risk individuals screened in a rural catchment area. METHODS: There were 5,402 patients enrolled in screening at Highlands Oncology, a community oncology clinic in Northwest Arkansas, from 2013 to 2020. Screenings were separated into time periods: period 1 (10 months for-fee), period 2 (10 months free with targeted advertisements and primary care outreach), and period 3 (62 months free with only primary care outreach). In all, 5,035 high-risk participants were eligible for analysis based on National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology. Enrollment rates, incidence densities (IDs), Cox proportional hazard models, and Kaplan-Meier curves were performed to investigate differences between enrollment periods and high-risk groups. RESULTS: Patient volume increased drastically once screenings were offered free of charge (period 1 = 4.6 versus period 2 = 66.0 and period 3 = 69.8 average patients per month). Incidence density per 1,000 person-years increased through each period (IDPeriod 1 = 17.2; IDPeriod 2 = 20.8; IDPeriod 3 = 25.5 cases). Cox models revealed significant differences in lung cancer risk between high-risk groups (P = .012) but not enrollment periods (P = .19). Kaplan-Meier lung cancer-free probabilities differed significantly between high-risk groups (log-rank P = .00068) but not enrollment periods (log-rank P = .18). CONCLUSIONS: This study suggests that eligible patients are more receptive to free LDCT screening, despite most insurances not having a required copay for eligible patients.

Frustrative nonreward and cannabinoid receptors: Chronic (but not acute) WIN 55,212-2 treatment increased resistance to change in two reward downshift tasks.

Assessing the role of cannabinoid (CB) receptors in behavior is relevant given the trend toward the legalization of medicinal and recreational marijuana. The present research aims at bridging a gap in our understanding of CB-receptor function in animal models of frustrative nonreward. These experiments were designed to (1) determine the effects of chronic administration of the nonselective CB1-receptor agonist WIN 55,212-2 (WIN) on reward downshift in rats and (2) determine whether the effects of chronic WIN were reducible to acute effects. In Experiment 1, chronic WIN (7 daily injections, 10 mg/kg, ip) accelerated the recovery of consummatory behavior after a 32-to-4% sucrose downshift relative to vehicle controls. In addition, chronic WIN eliminated the preference for an unshifted lever when the other lever was subject to a 12-to-2 pellet downshift in free-choice trials, but only in animals with previous experience with a sucrose downshift. In Experiment 2, acute WIN (1 mg/kg, ip) reduced consummatory behavior, but did not affect recovery from a 32-to-4% sucrose downshift. The antagonist SR 141716A (3 mg/kg, ip) also failed to interfere with recovery after the sucrose downshift. In Experiment 3, acute WIN administration (1 mg/kg, ip) did not affect free-choice behavior after a pellet downshift, although it reduced lever pressing and increased magazine entries relative to vehicle controls. The effects of chronic WIN on frustrative nonreward were not reducible to acute effects of the drug. Chronic WIN treatment in rats, like chronic marijuana use in humans, seems to increase resistance to the effects of frustrative nonreward.

Reinforcing properties of alcohol in rats: Progressive ratio licking performance reinforced with 66% alcohol.

Rodents are generally reluctant to consume high concentrations of alcohol. However, few experiments have reported the behavior of rats when they are given access to high alcohol concentrations. Four experiments with food-deprived Wistar rats were designed to determine whether 66% alcohol could be used as a positive reinforcer for operant responses. In Experiment 1, animals learned to lick an empty sipper to gain access to 66% alcohol in a second tube; licking extinguished after it if provided a only access to water (operant licking task, OL). Experiment 2 used the OL task combined with a progressive ratio (PR) schedule in a within-subject design with the order of alcohol concentrations counterbalanced across subjects. The breakpoint (the last completed ratio in the PR schedule) was higher for 10% and 66% alcohol concentrations than for water. In Experiment 3, animals trained in the same PR task gained access to water, 10%, or 66% alcohol in a between-subject design. Breakpoints were higher for 66% alcohol than for water, but not for 10% alcohol relative to water. Experiment 4 tested the effects of the orexin-1 receptor antagonist SB-334,867 on licking reinforced with access to 66% alcohol in the PR task. The antagonist reduced the breakpoint at 1- and 5-mg/kg doses, but not at 10 mg/kg. These results suggest that 66% alcohol can be used to reinforce operant behavior. Although the effects were modest, they were reliable. The estimated amount of alcohol consumed in the OL task suggests that these reinforcing effects were not dependent on the pharmacological effects of 66% alcohol, but could perhaps reflect a sensation-seeking effect.

Recovery profiles from reward downshift are correlated with operant licking maintained by alcohol, but not with genetic variation in the mu opioid receptor.

After ten 5-min sessions of access to 32% sucrose, a reward downshift (RD) to 2% sucrose induces a transient rejection of the reward. Animals were segregated according to the speed of recovery from RD into Fast-recovery and Slow-recovery subgroups. Animals were subsequently trained in an operant licking (OL) task in which licking at an empty tube provided 10 s of access to a second tube containing 66% alcohol. Licking on the first tube was subjected to a progressive ratio (PR) schedule with a step of 4 licks. Fast-recovery animals (both males and females) licked to a higher ratio than Slow-recovery animals. Animals were also exposed to a well-lit open field (OF) for 20 min. Fast- and Slow-recovery males and females exhibited equal levels of activity in the OF. Tissue samples from tails were assessed for two well-known allelic variations of the human opioid receptor gene, OPRM1, known to affect mu opioid sensitivity: The C17T and A118G single nucleotide polymorphisms. There was no evidence of a relationship between genotype and behavior, suggesting that these genetic mechanisms in humans do not account for the individual differences in recovery from RD and OL for alcohol in rats.

Augmented voluntary consumption of ethanol induced by reward downshift increases locomotor activity of male Wistar rats in the elevated plus maze.

Rats exposed to unexpected reward loss increase voluntary oral consumption of ethanol. Such consumption has been assumed to attenuate loss-induced negative affect (called emotional self-medication). To test this assumption, food-deprived male Wistar rats were exposed to 10 sessions of access to 32% sucrose followed by 5 sessions of access to 4% sucrose (reward downshift). A two-bottle preference test was initiated immediately after each consummatory session to assess ethanol intake. The experimental group received access to 2% ethanol and water, whereas the control group received access to two water bottles. On sessions 11, 12, and 15, immediately after the preference test, animals were tested in the elevated plus maze (EPM) for signs of anxiety. Sucrose consumption was reduced after the 32-to-4% sucrose downshift on sessions 11 and 12, but behavior recovered by session 15. Consummatory suppression was followed by increased ethanol intake in the preference test after sessions 11 and 12, but intake was reduced to preshift levels by session 15; no changes were observed in water controls. Finally, general activity (closed-arm entries and total arm entries) in the EPM increased in the ethanol group on session 12, but not on session 15, relative to water controls. The increase in ethanol consumption induced by reward downshift had measurable effects on activity as assessed in the EPM. These results show that voluntary oral 2% ethanol consumption after reward downshift can affect subsequent behavior, but fall short of providing unambiguous evidence that such ethanol consumption reduces negative affect.

5-Fluorouracil and Capecitabine: Assessment and Treatment of Uncommon Early-Onset Severe Toxicities Associated With Administration.

BACKGROUND: Uncommon early-onset severe toxicities from 5-fluorouracil (5-FU) and capecitabine can be fatal if early warning signs are not recognized and treated promptly. OBJECTIVES: This article delineates the differences between expected side effects and uncommon early-onset severe toxicities from 5-FU and capecitabine. It also provides background for understanding the reasons patients may develop these toxicities and reviews the efficacy of standard supportive care against a novel therapy (uridine triacetate). METHODS: A panel of nurses convened to review the literature about toxicities associated with 5-FU and capecitabine administration and determined methods to educate nurses about toxicities and treatment. FINDINGS: Standard supportive care for 5-FU and capecitabine toxicities is associated with high fatality rates. Uridine triacetate treatment within 96 hours of administration is associated with survival.

Meta-analysis provides evidence-based effect sizes for a cancer-specific quality-of-life questionnaire, the FACT-G.

OBJECTIVE: To compare Cohen's guidelines for small (0.2), medium (0.5), and large (0.8) effect sizes with empirical estimates for a cancer-specific health-related quality-of-life questionnaire (HRQOL), the Functional Assessment of Cancer Therapy - General (FACT-G). METHODS: Seventy-one papers satisfied inclusion criteria for meta-analysis. Blinded to the HRQOL results, three "experts" (with expertise in interpreting the FACT-G questionnaire and managing cancer patients), predicted the relative magnitude of HRQOL mean differences. Size classes (small, medium, large) were defined in terms of relevance to clinical decision making. The experts worked independently and based their predictions on patient characteristics and clinical circumstances. Their judgments were linked with FACT-G results and inverse-variance-weighted mean effect sizes calculated for each size class. RESULTS: At least two experts were perfectly concordant and up to one was discordant by at most one size category for 833 of the mean differences; for these, weighted kappas were generally in the "substantial" range (0.60-0.79). Of these mean differences, 617 were cross-sectional; small, medium, and large mean effect sizes were physical well-being 0.42, 0.87, 1.6; functional well-being 0.37, 0.71, 1.6; emotional well-being 0.32, 0.40, no large differences; and social well-being 0.14, 0.23, no large differences. Two hundred and sixteen longitudinal mean differences yielded small and medium effect sizes: physical well-being 0.26, 0.34; functional well-being 0.14, 0.28; emotional well-being 0.27, 0.23; and social well-being 0.08, 0.01. There was virtually no evidence for large longitudinal effects. CONCLUSION: These results provide specific, evidence-based alternatives to Cohen's generic guidelines, for use in sample-size calculations for the FACT-G and interpretation of the clinical significance of effects measured with FACT-G.

Meta-analysis provides evidence-based interpretation guidelines for the clinical significance of mean differences for the FACT-G, a cancer-specific quality of life questionnaire.

Our aim was to develop evidence-based interpretation guidelines for the Functional Assessment of Cancer Therapy-General (FACT-G), a cancer-specific health-related quality of life (HRQOL) instrument, from a range of clinically relevant anchors, incorporating expert judgment about clinical significance. Three clinicians with many years' experience managing cancer patients and using HRQOL outcomes in clinical research reviewed 71 papers. Blinded to the FACT-G results, they considered the clinical anchors associated with each FACT-G mean difference, predicted which dimensions of HRQOL would be affected, and whether the effects would be trivial, small, moderate, or large. These size classes were defined in terms of clinical relevance. The experts' judgments were then linked with FACT-G mean differences, and inverse-variance weighted mean differences were calculated for each size class. Small, medium, and large differences (95% confidence interval) from 1,118 cross-sectional comparisons were as follows: physical well-being 1.9 (0.6-3.2), 4.1 (2.7-5.5), 8.7 (5.2-12); functional well-being 2.0 (0.5-3.5), 3.8 (2.0-5.5), 8.8 (4.3-13); emotional well-being 1.0 (0.1-2.6), 1.9 (0.3-3.5), no large differences; social well-being 0.7 (-0.7 to 2.1), 0.8 (-2.9 to 4.5), no large differences. Results from 436 longitudinal comparisons tended to be smaller than the corresponding cross-sectional results. These results augment other interpretation guidelines for FACT-G with information on sample size, power calculations, and interpretation of cancer clinical trials that use FACT-G.