Clinical Decision Support and Palivizumab: A Means to Protect from Respiratory Syncytial Virus

Background and Objectives

Palivizumab can reduce hospitalizations due to respiratory syncytial virus (RSV), but many eligible infants fail to receive the full 5-dose series. The efficacy of clinical decision support (CDS) in fostering palivizumab receipt has not been studied. We sought a comprehensive solution for identifying eligible patients and addressing barriers to palivizumab administration.

Methods

We developed workflow and CDS tools targeting patient identification and palivizumab administration. We randomized 10 practices to receive palivizumab-focused CDS and 10 to receive comprehensive CDS for premature infants in a 3-year longitudinal cluster-randomized trial with 2 baseline and 1 intervention RSV seasons.

Results

There were 356 children eligible to receive palivizumab, with 194 in the palivizumab-focused group and 162 in the comprehensive CDS group. The proportion of doses administered to children in the palivizumab-focused intervention group increased from 68.4% and 65.5% in the two baseline seasons to 84.7% in the intervention season. In the comprehensive intervention group, proportions of doses administered declined during the baseline seasons (from 71.9% to 62.4%) with partial recovery to 67.9% during the intervention season. The palivizumab-focused group improved by 19.2 percentage points in the intervention season compared to the prior baseline season (p < 0.001), while the comprehensive intervention group only improved 5.5 percentage points (p = 0.288). The difference in change between study groups was significant (p = 0.05).

Conclusions

Workflow and CDS tools integrated in an EHR may increase the administration of palivizumab. The support focused on palivizumab, rather than comprehensive intervention, was more effective at improving palivizumab administration.     

Platelet-derived growth factor enhances platelet recovery in a murine model of radiation-induced thrombocytopenia and reduces apoptosis in megakaryocytes via its receptors and the PI3-k/Akt pathway

Background

Platelet-derived growth factor is involved in the regulation of hematopoiesis. Imatinib mesylate, a platelet-derived growth factor receptor inhibitor, induces thrombocytopenia in a significant proportion of patients with chronic myeloid leukemia. Although our previous studies showed that platelet-derived growth factor enhances megakaryocytopoiesis in vitro, the in vivo effect of platelet-derived growth factor in a model of radiation-induced thrombocytopenia has not been reported.

Design and Methods

In this study, we investigated the effect of platelet-derived growth factor on hematopoietic stem/progenitor cells and platelet production using an irradiated-mouse model. We also explored the potential molecular mechanisms of platelet-derived growth factor on thrombopoiesis in M-07e cells.

Results

Platelet-derived growth factor, like thrombopoietin, significantly promoted the recovery of platelets and the formation of bone marrow colony-forming unit-megakaryocyte in irradiated mice. Histology confirmed the protective effect of platelet-derived growth factor, as shown by an increased number of hematopoietic stem/progenitor cells and a reduction of apoptosis. In a megakaryocytic apoptotic model, platelet-derived growth factor had a similar anti-apoptotic effect as thrombopoietin on megakaryocytes. We also demonstrated that platelet-derived growth factor activated the PI3-k/Akt signaling pathway, while addition of imatinib mesylate reduced p-Akt expression.

Conclusions

Our findings show that platelet-derived growth factor enhances platelet recovery in mice with radiation-induced thrombocytopenia. This radioprotective effect is likely to be mediated via platelet-derived growth factor receptors with subsequent activation of the PI3-k/Akt pathway. We also provide a possible explanation that blockage of platelet-derived growth factor receptors may reduce thrombopoiesis and play a role in imatinib mesylate-induced thrombocytopenia.     

c-Jun knockdown sensitizes osteosarcoma to doxorubicin

The oncogene c-Jun has been found to be up-regulated in a variety of cancers, including osteosarcoma. Doxorubicin is a frontline chemotherapeutic against osteosarcoma, but is limited by toxicity. DNAzymes are oligonucleotides capable of specific catalysis of target mRNA. A biocompatible c-Jun DNAzyme nanoparticle formulated from chitosan regressed the growth and metastasis of pre-established tumors, especially in combination with doxorubicin. In vitro data confirmed that c-Jun knockdown chemosensitized these cells to doxorubicin treatment. c-Jun down-regulation-mediated tumor inhibition also led to concomitant decreased osteolysis. Clinically, knockdown of c-Jun with chitosan nanobiotechnology may proffer an improved treatment outcome for osteosarcoma.     

Evaluation of posterior tibial pathology: comparison of sonography and MR imaging

Objective To compare the results of sonographic (US) and magnetic resonance (MR) imaging in detecting pathology of the posterior tibial tendon (PTT) in patients with PTT dysfunction.Design Twenty-two ankles that were clinically suspected by the orthopedic surgeon to have PTT dysfunction were evaluated with US (10 MHz linear-array transducer) and 1.5 T MR examinations within the same day. The US and MR studies were conducted and interpreted by two sonologists and two musculoskeletal radiologists who were masked to the results of the other study. Four patients had bilateral studies. Classic clinical findings were utilized as a standard reference in staging PTT dysfunction.Patients Eighteen women (mean age 61 years, age range 3986 years).Results Based on a commonly accepted staging system for PTT dysfunction, 6 ankles were classified as stage I, 11 ankles as stage II, and 5 ankles as stage III. All stage I ankles were interpreted as having an intact PTT by both MR imaging and US. In the stage II and III tendons, MR imaging demonstrated PTT tears in 12 of 22 examinations, including 11 partial tears and 1 complete tear. US demonstrated PTT tears in 8 of 22 examinations, including 8 partial tears and no complete tears. The findings of US and MR imaging were consistent in 17 of 22 cases (77%). The five inconsistencies were as follows: in 4 cases, US reported tendinosis when MR imaging interpreted partial tears (no change in management); in one case, US diagnosed a partial tear when MR reported a complete tear of the PTT (no change in management because the clinical findings were more consistent with a partial tear).Conclusions In this study, US and MR imaging of the PTT were concordant in the majority of cases. US was slightly less sensitive than MR imaging for PTT pathology, but these discrepancies did not affect clinical management.