Eltrombopag for Treating Thrombocytopenia after Allogeneic Stem Cell Transplantation.

Thrombocytopenia after allogeneic hematopoietic stem cell transplantation (allo-SCT) can pose significant problems in management of patients. Eltrombopag is a small-molecule thrombopoietin receptor agonist that has been approved for use in immune thrombocytopenic purpura and aplastic anemia; but its use after allo-SCT is limited. Between 2014 and 2017, we treated 13 patients with eltrombopag for poor platelet engraftment without evidence of relapse at the time of initiation, including 6 patients with primary platelet engraftment failure and 7 with secondary platelet engraftment failure. Eltrombopag was started at an initial dose of 25 or 50 mg per day, and dose adjustments were made in accordance with the manufacturer's recommendation. The cumulative incidence of platelet recovery to ≥50,000/µL without the need for transfusion for at least 7 days was defined as response. The overall response rate was 62% (n = 8). Of the 6 patients with primary isolated platelet failure, 3 (50%) responded, and of the 7 patients with secondary platelet failure, 5 (71%) responded. The median time to response was 33 days (range, 11 to 68 days). In addition, no significant differences in platelet recovery were noted in patients with adequate and decreased bone marrow megakaryocytic reserve (60% and 67%, respectively). Although eltrombopag was well tolerated, and no patient discontinued treatment because of adverse events, only 3 patients were alive at the end of the observation period, with relapse and graft-versus-host disease accounting for majority of the deaths. This suggested that despite the relatively good overall response rate to eltrombopag, inadequate platelet engraftment is a harbinger of poor outcome in allo-SCT.

Maternal antibodies to pneumolysin but not to pneumococcal surface protein A delay early pneumococcal carriage in high-risk Papua New Guinean infants.

Immunization of pregnant women can be an efficient strategy to induce early protection in infants in developing countries. Pneumococcal protein-based vaccines may have the capacity to induce pneumococcal serotype-independent protection. To understand the potential of maternal pneumococcal protein-specific antibodies in infants in high-risk areas, we studied the placental transfer of naturally acquired antibodies to pneumolysin (Ply) and pneumococcal surface protein A family 1 and 2 (PspA1 and PspA2) in relation to onset of pneumococcal nasopharyngeal carriage in infants in Papua New Guinea (PNG). In this study, 76% of the infants carried Streptococcus pneumoniae in the upper respiratory tract within the first month of life, at a median age of 19 days. Maternal and cord blood antibody titers to Ply (rho = 0.824, P < 0.001), PspA1 (rho = 0.746, P < 0.001), and PspA2 (rho = 0.631, P < 0.001) were strongly correlated. Maternal pneumococcal carriage (hazard ratio [HR], 2.60; 95% confidence interval [CI], 1.25 to 5.39) and younger maternal age (HR, 0.74; 95% CI, 0.54 to 1.00) were independent risk factors for early carriage, while higher cord Ply-specific antibody titers predicted a significantly delayed onset (HR, 0.71; 95% CI, 0.52 to 1.00) and cord PspA1-specific antibodies a significantly younger onset of carriage in PNG infants (HR, 1.57; 95% CI, 1.03 to 2.40). Maternal vaccination with a pneumococcal protein-based vaccine should be considered as a strategy to protect high-risk infants against pneumococcal disease by reducing carriage risks in both mothers and infants.

Cluster-randomized controlled trial of oscillometric vs. manual sphygmomanometer for blood pressure management in primary care (CRAB).

BACKGROUND: Although mercury sphygmomanometers are seen as the gold standard instrument for blood pressure (BP) measurement, they are being withdrawn due to safety concerns. CRAB was a cluster-randomized controlled trial in 24 family practices in Tasmania, Australia, which aimed to determine the effect of an oscillometric device on BP management. METHODS: Cluster-randomized controlled trial. Intervention practices were supplied with automated monitors and control (usual care) practices used mercury or aneroid sphygmomanometers. They were subsequently audited by a research nurse. Usual care practice audit periods were matched to intervention practices. All analyses were intention-to-treat and adjusted for potential clustering. Differences in BP were analyzed using generalized estimating equations. All other outcomes were analyzed using multilevel mixed-effects Poisson regression. Post hoc analyses were performed to determine the mediators of changes in prescribing behavior. RESULTS: A total of 3,355 records were reviewed (828 visits had BP recordings). The percentage of BP recordings ending in "0" was significantly lower in intervention vs. usual care practices (systolic BP (SBP) 18% (107/587) vs. 71% (233/329), diastolic BP (DBP) 20% (119/584) vs. 70% (229/328), P < 0.001). The mean of SBP recordings in the intervention group was 7.5 mm Hg (95% confidence interval (CI) 5.2, 9.9 mm Hg, P < 0.001) higher than in the usual care group. Patients taking BP lowering drugs were more likely (incidence rate ratio (IRR) 1.3, 95% CI 1.1, 1.7, P = 0.01) to have a BP lowering drug prescribed if they were in the intervention compared to the usual care. CONCLUSIONS: Although digit preference was largely eliminated by oscillometric measurement, prescribing behavior was mediated by SBP.