Costs and Outcomes with Once-Daily versus Every-6-Hour Intravenous Busulfan in Allogeneic Hematopoietic Cell Transplantation.

The high cost of healthcare in the United States has not been consistently associated with improved health outcomes or quality of care, necessitating a focus on value-based care. We identified busulfan dosing frequency during allogeneic hematopoietic cell transplantation (HCT) conditioning as a potential target for optimization. To improve patient convenience and to decrease the cost of busulfan-based conditioning regimens, our institution changed busulfan dose frequency from every 6 hours (q6h) to once-daily (q24h). We compared costs and patient outcomes between these 2 dosing schedules. In June 2017, our institution transitioned from q6h to q24h busulfan dosing. We compared patients who received busulfan/cyclophosphamide conditioning regimens (BU/CY) for allogeneic HCT in the year before the dosing change (q6h cohort) and those who did so in the year after the dosing change (q24h cohort). The primary outcomes were differences in cost, day +90 mortality, and day +90 relapse. Between June 1, 2016, and June 1, 2018, 104 patients (median age 49 years; range, 20 to 63 years) received BU/CY before allogeneic HCT. Fifty-nine patients (57%) received q6h busulfan and 45 (43%) received q24h busulfan. There were fewer men in the q24h busulfan cohort compared with the q6h busulfan cohort (42% versus 64%; P = .024), but there were no other significant differences between the groups. There was an average annual cost savings of $19,990 per patient with q24h busulfan compared with q6h busulfan, and an annual busulfan cost savings of $899,550. There was a significantly lower day +90 mortality in the q24h busulfan cohort compared to the q6h busulfan cohort (0% versus 10%; P = .028). There were no significant differences in relapse at day +90 or in hospital length of stay. Our data indicate that i.v. busulfan dosing for allogeneic HCT conditioning is a target for improved value-based care. At our institution, patients who received q24h busulfan dosing had similar or superior outcomes compared with those receiving q6h dosing, with an average annual cost reduction of $19,990 per patient and an overall annual reduction in busulfan cost of approximately $900,000. These data support the adoption of q24h i.v. busulfan dosing as a standard of care to improve value-based care in allogeneic HCT.

Accuracy, precision, and error in age estimation of Florida manatees using growth layer groups in earbones.

Ages of Florida manatees (Trichechus manatus latirostris) can be estimated by counting annual growth layer groups (GLGs) in the periotic dome portion of the tympanoperiotic complex of their earbones. The Florida Fish and Wildlife Conservation Commission manages an archive of more than 8,700 Florida manatee earbones collected from salvaged carcasses from 1989 to 2017. Our goal was to comprehensively evaluate techniques used to estimate age, given this large sample size and changes to processing protocols and earbone readers over time. We developed new standards for estimating ages from earbones, involving two independent readers to obtain measurements of within- and between-reader precision. To quantify accuracy, precision, and error, 111 earbones from manatees with approximately known ages (first known as calves: "KAC") and 69 earbones from manatees with minimum known ages ("MKA," based on photo-identification sighting histories) were processed, and their ages were estimated. There was greater precision within readers (coefficient of variation, CV: 2.4-8.5%) than between readers (CV: 13.1-13.3%). The median of age estimates fell within the true age range for 63.1% of KAC cases and was at least the sighting duration for 75.0% of MKA cases. Age estimates were generally unbiased, as indicated by an average raw error ± SD of -0.05 ± 3.05 years for the KAC group. The absolute error (i.e., absolute value of raw error) of the KAC data set averaged 1.75 ± 2.50 years. Accuracy decreased and error increased with increasing known age, especially for animals over 15 years old, whose ages were mostly underestimated due to increasing levels of resorption (the process of bone turnover that obscures GLGs). Understanding the degree of uncertainty in age estimates will help us assess the utility of age data in manatee population models. We emphasize the importance of standardizing and routinely reviewing age estimation and processing protocols to ensure that age data remain consistent and reliable.

H2S exposure elicits differential expression of candidate genes in fish adapted to sulfidic and non-sulfidic environments.

Disentangling the effects of plasticity, genetic variation, and their interactions on organismal responses to environmental stressors is a key objective in ecological physiology. We quantified the expression of five candidate genes in response to hydrogen sulfide (H2S) exposure in fish (Poecilia mexicana, Poeciliidae) from a naturally sulfide-rich environment as well as an ancestral, non-sulfidic population to test for constitutive and environmentally dependent population differences in gene expression patterns. Common garden raised individuals that had never encountered environmental H2S during their lifetime were subjected to short or long term H2S exposure treatments or respective non-sulfidic controls. The expression of genes involved in responses to H2S toxicity (cytochrome c oxidase, vascular endothelial growth factor, and cytochrome P450-2J6), H2S detoxification (sulfide:quinone oxidoreductase), and endogenous H2S production (cystathionine γ lyase) was determined in both gill and liver tissues by real time PCR. The results indicated complex changes in expression patterns that--depending on the gene--not only differed between organs and populations, but also on the type of H2S exposure. Populations differences, both constitutive and H2S exposure dependent (i.e., plastic), in gene expression were particularly evident for sulfide:quinone oxidoreductase, vascular endothelial growth factor, and to a lesser degree for cytochrome P450-2J6. Our study uncovered putatively adaptive modifications in gene regulation that parallel previously documented adaptive changes in phenotypic traits.

Identification of early disease progression in an ALS rat model.

Transgenic rat models of amyotrophic lateral sclerosis (ALS) have recently been developed. Most assays of ALS-symptoms in these models monitor disease onset accurately, but do not identify individuals that will develop these symptoms before the motor deficits become apparent. Peak bodyweight has recently been shown to indicate affected individuals before motor deficits become apparent. However, it must be determined retrospectively due to weight fluctuation. Here, we report that exploratory activities detected by a photobeam activity system (PAS) and wire mesh ascending test can be used to detect slight motor deficits in the early phase of ALS. Thus, these tests may be used in addition to peak bodyweight to monitor early disease progression and to assay efficacy of new therapeutic interventions.