Caregiver availability and patient access to hematopoietic cell transplantation: social worker perspectives inform practice.

PURPOSE: Hematopoietic cell transplantation (HCT) often involves a long hospitalization and recovery period, with patients generally required to have a caregiver. This study aimed to identify transplant center (TC) requirements for a caregiver, describe challenges that impact caregiver availability, and identify potential solutions. METHODS: An exploratory sequential mixed-methods approach was used. Qualitative data was obtained from focus groups of TC social workers in the United States (US) (three focus groups; n = 15 total participants). Results informed the development of a national, web-based survey that was administered to the primary social worker contact at TCs in the National Marrow Donor Program (NMDP)/Be The Match Network (n = 133). RESULTS: Respondents included social workers from adult (n = 47) and pediatric (n = 19) TCs (response rate = 49%). The majority (89%) of both adult and pediatric TCs required a caregiver for a patient to proceed to transplant, but requirements varied in length of time, formality, transplant type, and HCT setting. Regardless of transplant type or patient population, social workers identified loss of caregiver income as the greatest challenge to caregiver availability, with the most common solution being allowing patients to have multiple caregivers throughout the transplant course. DISCUSSION: Caregiver availability is an important concern for patients considering and receiving HCT, and may be a barrier proceeding to HCT when a caregiver is unavailable. Results from this study highlight caregiver availability barriers and solutions of TCs across the US. These results can inform TCs about other center experiences with caregiver availability and identify potential practice changes for individual TCs.

Patient housing barriers to hematopoietic cell transplantation: results from a mixed-methods study of transplant center social workers.

PURPOSE: Hematopoietic cell transplantation (HCT) is performed in select centers in the United States (U.S.), and patients are often required to temporarily relocate to receive care. The purpose of this study was to identify housing barriers impacting access to HCT and potential solutions. METHODS: A mixed-methods primary study of HCT social workers was conducted to learn about patient housing challenges and solutions in place that help address those barriers. Three telephone focus groups were conducted with adult and pediatric transplant social workers (n = 15). Focus group results informed the design of a national survey. The online survey was e-mailed to a primary social worker contact at 133 adult and pediatric transplant centers in the U.S. Transplant centers were classified based on the patient population cared for by the social worker. RESULTS: The survey response rate was 49%. Among adult programs (n = 45), 93% of centers had patients that had to relocate closer to the transplant center to proceed with HCT. The most common type of housing option offered was discounted hotel rates. Among pediatric programs (n = 20), 90% of centers had patients that had to relocate closer to the transplant center to proceed with HCT. Ronald McDonald House was the most common option available. CONCLUSIONS: This study is the first to explore housing challenges faced by patients undergoing HCT in the U.S. from the perspective of social workers and to highlight solutions that centers use. Transplant centers will benefit from this knowledge by learning about options for addressing housing barriers for their patients.

Pharmacoeconomics of hematopoietic stem cell mobilization: an overview of current evidence and gaps in the literature.

Adequate hematopoietic stem cell (HSC) mobilization and collection is required prior to proceeding with high dose chemotherapy and autologous hematopoietic stem cell transplant. Cytokines such as G-CSF, GM-CSF, and peg-filgrastim, alone or in combination with plerixafor, and after chemotherapy have been used to mobilize HSCs. Studies have shown that the efficiency of HSC mobilization and collection may vary when different methods of mobilization are used. No studies have shown that survival is significantly affected by the method of mobilization, but some studies have suggested that cost and resource utilization may be different between different mobilization techniques. After the FDA approval of plerixafor with G-CSF to mobilize HSCs many transplant centers became concerned about the cost of HSC mobilization. A panel of experts was convened ant this paper reviews the current literature on the pharmacoeconomics of HSC mobilization.

Methamphetamine causes anorexia in Drosophila melanogaster, exhausting metabolic reserves and contributing to mortality.

Methamphetamine (MA) appears to produce neurotoxic effects, in part, through disruptions of energy metabolism. A recent study of the whole-body proteome of Drosophila melanogaster showed many changes in energy metabolism-related proteins, leading us to hypothesize that MA toxicity may cause whole-body disruptions of energy metabolism. To test this, we monitored the response of energy reserves and other metabolites to MA-exposure with and without the addition of dietary glucose. We also monitored changes in feeding behavior, locomotor activity and respiration rates associated with MA-exposure to investigate how MA affects energy balance. We observed that glycogen and triglyceride levels decreased dramatically within 48 hr of MA-exposure, indicating a strongly negative caloric balance. Behavioral assays revealed that MA-treated flies decreased food consumption by 60-80% and exhibited a 2-fold increase in locomotion. Caloric expenditure decreased with MA-exposure, apparently due to a compensatory decrease in resting metabolism, showing that anorexia was the primary driver of the negative caloric balance. Additionally, we observed that glucose supplementation of MA-containing diet increased glycogen reserves by 44% at 48 hr, leading to a commensurate increase in survivorship. We conclude that dietary sugar supplementation enhances survivorship by partially compensating for decreased caloric intake resulting from MA-induced anorexia. The observation that MA produces similar behavioral changes in Drosophila and humans, i.e. increased locomotor activity and anorexia, further supports the use of Drosophila as a model organism for the study of the effects of MA.

Systems-scale analysis reveals pathways involved in cellular response to methamphetamine.

BACKGROUND: Methamphetamine (METH), an abused illicit drug, disrupts many cellular processes, including energy metabolism, spermatogenesis, and maintenance of oxidative status. However, many components of the molecular underpinnings of METH toxicity have yet to be established. Network analyses of integrated proteomic, transcriptomic and metabolomic data are particularly well suited for identifying cellular responses to toxins, such as METH, which might otherwise be obscured by the numerous and dynamic changes that are induced. METHODOLOGY/RESULTS: We used network analyses of proteomic and transcriptomic data to evaluate pathways in Drosophila melanogaster that are affected by acute METH toxicity. METH exposure caused changes in the expression of genes involved with energy metabolism, suggesting a Warburg-like effect (aerobic glycolysis), which is normally associated with cancerous cells. Therefore, we tested the hypothesis that carbohydrate metabolism plays an important role in METH toxicity. In agreement with our hypothesis, we observed that increased dietary sugars partially alleviated the toxic effects of METH. Our systems analysis also showed that METH impacted genes and proteins known to be associated with muscular homeostasis/contraction, maintenance of oxidative status, oxidative phosphorylation, spermatogenesis, iron and calcium homeostasis. Our results also provide numerous candidate genes for the METH-induced dysfunction of spermatogenesis, which have not been previously characterized at the molecular level. CONCLUSION: Our results support our overall hypothesis that METH causes a toxic syndrome that is characterized by the altered carbohydrate metabolism, dysregulation of calcium and iron homeostasis, increased oxidative stress, and disruption of mitochondrial functions.

Assessing the charges associated with hematopoietic stem cell mobilization and remobilization in patients with lymphoma and multiple myeloma undergoing autologous hematopoietic peripheral blood stem cell transplantation.

BACKGROUND: The purpose of this study was to perform a detailed analysis of the charges associated with chemomobilization and remobilization of autologous hematopoietic stem cells (HSCs) and to quantify medical costs and resource utilization associated with these procedures. STUDY DESIGN AND METHODS: Patients with lymphoma underwent chemomobilization with ifosfamide and etoposide with or without rituximab (IE ± R). Patients with multiple myeloma (MM) received a modified hyperfractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone (hyper-CVAD) regimen after failing to mobilize with growth factors only. RESULTS: Between January 2004 and October 2006, 98 patients with lymphoma underwent HSC mobilization with IE ± R. Mobilization with IE ± R was effective, with 90.8% of patients collecting at least 2 × 10(6) CD34+ cells/kg. The total charges for treatment were $27,996 and $37,667 for patients mobilized with IE and IE + R, respectively. Hospital readmission for complications occurred in 26.5% of patients, resulting in additional charges of $10,356. The preapheresis procedure charge was estimated to be $2522, the charge for a 2-day apheresis session was $5160, and the postapheresis phase resulted in charges of $8040. Our analysis determined that reducing apheresis by 1 day has the potential to save $6600. We also performed a retrospective analysis of 16 patients with MM remobilized with a modified hyper-CVAD regimen. Remobilization was successful, with 87.5% of patients. Our analysis determined that mobilization, preapheresis, apheresis, and postapheresis phase charges were $24,968, $2522, $6158, and $12,060, respectively. CONCLUSIONS: Optimization of HSC mobilization regimens to reduce failure rates would not only benefit patients but also reduce the overall medical costs.

A thermal hysteresis-producing xylomannan glycolipid antifreeze associated with cold tolerance is found in diverse taxa.

The presence of large-molecular-mass, thermal hysteresis (TH)-producing antifreezes (e.g., antifreeze proteins) has been reported in numerous and diverse taxa, including representative species of fish, arthropods, plants, fungi, and bacteria. However, relatively few of these antifreeze molecules have been chemically characterized. We screened diverse species by subjecting their homogenates to ice-affinity purification and discovered the presence of a newly identified class of antifreeze, a xylomannan-based TH-producing glycolipid that was previously reported in one species of freeze-tolerant Alaskan beetle. We isolated xylomannan-based antifreeze glycolipids from one plant species, six insect species, and the first frog species to be shown to produce a large-molecular-mass antifreeze. (1)H NMR spectra of the ice-purified molecules isolated from these diverse freeze-tolerant and freeze-avoiding organisms were nearly identical, indicating that the chemical structures of the glycolipids were highly similar. Although the exact functions remain uncertain, it appears that antifreeze glycolipids play a role in cold tolerance.

A nonprotein thermal hysteresis-producing xylomannan antifreeze in the freeze-tolerant Alaskan beetle Upis ceramboides.

Thermal hysteresis (TH), a difference between the melting and freezing points of a solution that is indicative of the presence of large-molecular-mass antifreezes (e.g., antifreeze proteins), has been described in animals, plants, bacteria, and fungi. Although all previously described TH-producing biomolecules are proteins, most thermal hysteresis factors (THFs) have not yet been structurally characterized, and none have been characterized from a freeze-tolerant animal. We isolated a highly active THF from the freeze-tolerant beetle, Upis ceramboides, by means of ice affinity. Amino acid chromatographic analysis, polyacrylamide gel electrophoresis, UV-Vis spectrophotometry, and NMR spectroscopy indicated that the THF contained little or no protein, yet it produced 3.7 +/- 0.3 degrees C of TH at 5 mg/ml, comparable to that of the most active insect antifreeze proteins. Compositional and structural analyses indicated that this antifreeze contains a beta-mannopyranosyl-(1-->4) beta-xylopyranose backbone and a fatty acid component, although the lipid may not be covalently linked to the saccharide. Consistent with the proposed structure, treatment with endo-beta-(1-->4)xylanase ablated TH activity. This xylomannan is the first TH-producing antifreeze isolated from a freeze-tolerant animal and the first in a new class of highly active THFs that contain little or no protein.

Cryoprotectant biosynthesis and the selective accumulation of threitol in the freeze-tolerant Alaskan beetle, Upis ceramboides.

Adult Upis ceramboides do not survive freezing in the summer but tolerate freezing to -60 degrees C in midwinter. The accumulation of two cryoprotective polyols, sorbitol and threitol, is integral to the extraordinary cold-hardiness of this beetle. U. ceramboides are the only animals known to accumulate high concentrations of threitol; however, the biosynthetic pathway has not been studied. A series of (13)C-labeled compounds was employed to investigate this biosynthetic pathway using (13)C{(1)H} NMR spectroscopy. In vivo metabolism of (13)C-labeled glucose isotopomers demonstrates that C-3-C-6 of glucose become C-1-C-4 of threitol. This labeling pattern is expected for 4-carbon saccharides arising from the pentose phosphate pathway. In vitro experiments show that threitol is synthesized from erythrose 4-phosphate, a C(4) intermediate in the PPP. Erythrose 4-phosphate is epimerized and/or isomerized to threose 4-phosphate, which is subsequently reduced by a NADPH-dependent polyol dehydrogenase and dephosphorylated by a sugar phosphatase to form threitol. Threitol 4-phosphate appears to be the preferred substrate of the sugar phosphatase(s), promoting threitol synthesis over that of erythritol. In contrast, the NADPH-dependent polyol dehydrogenase exhibits broad substrate specificity. Efficient erythritol catabolism under conditions that promote threitol synthesis, coupled with preferential threitol biosynthesis, appear to be responsible for the accumulation of high concentrations of threitol (250 mm) without concomitant accumulation of erythritol.

Freeze tolerance in an arctic Alaska stonefly.

Most aquatic insects do not survive subzero temperatures and, for those that do, the physiology has not been well characterized. Nemoura arctica is a species of stonefly widely distributed throughout arctic and subarctic Alaska. We collected nymphs from the headwaters of the Chandalar River, where we recorded streambed temperatures as low as -12.7 degrees C in midwinter. When in contact with ice, autumn-collected N. arctica cool to -1.5+/-0.4 degrees C before freezing, but individuals survived temperatures as low as -15 degrees C, making this the first described species of freeze-tolerant stonefly. N. arctica clearly survive freezing in nature, as winter-collected nymphs encased in ice demonstrated high survivorship when thawed. In the laboratory, 87% of N. arctica nymphs frozen to -15 degrees C for 2.5 weeks survived and, within one month of thawing, 95% of the last-instar nymphs emerged. N. arctica produce both glycerol and ice-binding factors (e.g. antifreeze protein) in response to low temperature. Hemolymph glycerol concentrations increased from 3 mmol l(-1) to 930+/-114 mmol l(-1) when temperatures were decreased from 4 degrees C to -8 degrees C, and N. arctica continued to produce glycerol even while frozen. Although the hemolymph of individual cold-acclimated nymphs occasionally exhibited more than a degree of thermal hysteresis, typically the hemolymph exhibited only hexagonal crystal growth, indicating a low concentration of ice-binding factor. Hemolymph of nymphs acclimated to subzero temperatures had recrystallization inhibition. These results demonstrate that, in the face of freezing conditions, N. arctica exhibit overwintering adaptations similar to those of terrestrial insects.

Comparative overwintering physiology of Alaska and Indiana populations of the beetle Cucujus clavipes (Fabricius): roles of antifreeze proteins, polyols, dehydration and diapause.

The beetle Cucujus clavipes is found in North America over a broad latitudinal range from North Carolina (latitude approximately 35 degrees N) to near tree line in the Brooks Range in Alaska (latitude, approximately 67 degrees 30' N). The cold adaptations of populations from northern Indiana (approximately 41 degrees 45' N) and Alaska were compared and, as expected, the supercooling points (the temperatures at which they froze) of these freeze-avoiding insects were significantly lower in Alaska insects. Both populations produce glycerol, but the concentrations in Alaska larvae were much higher than in Indiana insects (approximately 2.2 and 0.5 mol l(-1), respectively). In addition, both populations produce antifreeze proteins. Interestingly, in the autumn both populations have the same approximate level of hemolymph thermal hysteresis, indicative of antifreeze protein activity, suggesting that they synthesize similar amounts of antifreeze protein. A major difference is that the Alaska larvae undergo extreme dehydration in winter wherein water content decreases from 63-65% body water (1.70-1.85 g H2O g(-1) dry mass) in summer to 28-40% body water (0.40-0.68 g H2O g(-1) dry mass) in winter. These 2.5-4.6-fold reductions in body water greatly increase the concentrations of antifreeze in the Alaska insects. Glycerol concentrations would increase to 7-10 mol l(-1) while thermal hysteresis increased to nearly 13 degrees C (the highest ever measured in any organism) in concentrated hemolymph. By contrast, Indiana larvae do not desiccate in winter. The Alaska population also undergoes a diapause while insects from Indiana do not. The result of these, and likely additional, adaptations is that while the mean winter supercooling points of Indiana larvae were approximately -23 degrees C, those of Alaska larvae were -35 to -42 degrees C, and at certain times Alaska C. clavipes did not freeze when cooled to -80 degrees C.