Delayed engraftment is a significant limitation of umbilical cord blood (UCB) transplantation due to low stem cell numbers. Inhibition of dipeptidyl peptidase (DPP)-4 enhanced engraftment in murine transplants. We evaluated the feasibility of systemic DPP-4 inhibition using sitagliptin to enhance engraftment of single-unit UCB grafts in adults with hematological malignancies. Twenty-four patients (21-58 years) received myeloablative conditioning, followed by sitagliptin 600 mg orally days -1 to + 2, and single UCB grafts day 0. Seventeen receiving red cell-depleted (RCD) grafts, matched at 4 (n = 10) or 5 (n = 7) of 6 human leucocyte antigen (HLA) loci with median nucleated cell dose 3.6 (2.5-5.2) · 10 7 /kg, engrafted at median of 21 (range, 13-50) days with cumulative incidence of 94% (95% confidence interval, 84%-100%) at 50 days. Plasma DDP-4 activity was reduced to 23% -7% within 2 h. Area under DPP-4 activity-time curve (AUC A ) correlated with engraftment; 9 of 11 with AUC A < 6,000 activity$h engrafted within £ 21 days, while all 6 with higher AUC A engrafted later (P = 0.002). Seven patients receiving red cell replete grafts had 10-fold lower colony forming units after thawing compared with RCD grafts, with poor engraftment. Systemic DPP-4 inhibition was well tolerated and may enhance engraftment. Optimizing sitagliptin dosing to achieve more sustained DPP-4 inhibition may further improve outcome.
This study examined the course of adaptation as indicated by the level of emotional distress for family caregivers of adult BM recipients across the acute phase of the transplant trajectory. Factors influencing caregivers' adaptation that could be potential markers of vulnerability to psychological and social morbidity were identified. The sample included 192 caregivers of either an autologous or allogeneic BMT recipient. Data were collected by self-report questionnaires at three time points in the trajectory: pre-transplant/pre-hospitalization (T1); during hospitalization, post-infusion (T2); 1 month postdischarge (T3). There was a decline in emotional distress from T1 to T3, and bivariate correlations indicated significant association of distress with variables hypothesized to be theoretically relevant. Specifically, greater personal control, a greater sense of spiritual connectedness, less disruption in the life of the caregiver and less use of avoidance coping were the strongest factors associated with lower emotional distress. In conclusion (1) levels of personal control and spirituality remained stable across time and were negatively associated with emotional distress. Therefore, they may provide an indication of caregiver resilience pre-transplant; (2) level of recipient symptomatology rather than BMT type appears to influence caregiver distress; (3) there are indications of the need for post-hospitalization follow-up with caregivers by the BMT team.
In this paper, we discuss the use of cost-benefit analysis (CBA) for evaluating new healthcare interventions, present the theoretical basis for the use of willingness to pay as a method for valuing benefits in a CBA and describe how to obtain willingness-to-pay (WTP) measures of health benefits and how to use these values in a CBA. We review selected economic studies on consumer demand and consumer surplus and studies presenting WTP estimates for healthcare interventions. The theoretical foundations of willingness to pay as a measure of commodity value are rooted in consumer demand theory. The area under the fixed income consumer demand curve represents the consumer's maximum willingness to pay for the commodity. We identify 3 types of potential benefits from a new healthcare intervention, namely patient benefits, option value and altruistic value, and suggest WTP questions for valuing different combinations of these benefits. We demonstrate how responses to these questions can be adjusted for income effects and incorporated into economic evaluations. We suggest that the lack of popularity of CBAs in the health area is related to the perceived difficulty in valuing health benefits as well as concern over how CBA incorporates the distribution of income. We show that health benefits can be valued using simple survey techniques and that these values can be adjusted to any desired income distribution.
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