METHODS: A prospective pre- and post-intervention study was conducted among medical inpatients in a Malaysian secondary care hospital. DVT and bleeding risks were stratified using validated Padua Risk Assessment Model (RAM) and International Medical Prevention Registry on Venous Thromboembolism (IMPROVE) Bleeding Risk Assessment Model. Pharmacist-driven DRAT was developed and implemented post-interventional phase. DVT prophylaxis use was determined and its appropriateness was compared between pre and post study using multivariate logistic regression with IBM SPSS software version 21.0.
RESULTS: Overall, 286 patients (n=142 pre-intervention versus n=144 post-intervention) were conveniently recruited. The prevalence of DVT prophylaxis use was 10.8%. Appropriate thromboprophylaxis prescribing increased from 64.8% to 68.1% post-DRAT implementation. Of note, among high DVT risk patients, DRAT intervention was observed to be a significant predictor of appropriate thromboprophylaxis use (14.3% versus 31.3%; adjusted odds ratio=2.80; 95% CI 1.01 to 7.80; p<0.05).
CONCLUSION: The appropriateness of DVT prophylaxis use was suboptimal but doubled after implementation of DRAT intervention. Thus, an integrated risk stratification checklist is an effective approach for the improvement of rational DVT prophylaxis use.
METHODS AND RESULTS: In this study, recombinant TYMVcHis6 expressed in Escherichia coli self-assembled into VLPs of approximately 30-32 nm. SDS-PAGE and Western blot analysis of protein fractions from the immobilized metal affinity chromatography (IMAC) showed that TYMVcHis6 VLPs interacted strongly with nickel ligands in IMAC column, suggesting that the fusion peptide is protruding out from the surface of VLPs. These VLPs are highly stable over a wide pH range from 3·0 to 11·0 at different temperatures. At pH 11·0, specifically, the VLPs remained intact up to 75°C. Additionally, the disassembly and reassembly of TYMVcHis6 VLPs were studied in vitro. Dynamic light scattering and transmission electron microscopy analysis revealed that TYMVcHis6 VLPs were dissociated by 7 mol l-1 urea and 2 mol l-1 guanidine hydrochloride (GdnHCl) without impairing their reassembly property.
CONCLUSIONS: A 10-residue peptide was successfully displayed on the surface of TYMVcHis6 VLPs. This chimera demonstrated high stability under extreme thermal conditions with varying pH and was able to dissociate and reassociate into VLPs by chemical denaturants.
SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first C-terminally modified TYMVc produced in E. coli. The C-terminal tail which is exposed on the surface can be exploited as a useful site to display multiple copies of functional ligands. The ability of the chimeric VLPs to self-assemble after undergo chemical denaturation indicates its potential role to serve as a nanocarrier for use in targeted drug delivery.
CASE REPORT: A 59-year-old man was diagnosed with acute promyelocytic leukaemia. Following this, he underwent all-trans retinoic acid (ATRA) based chemotherapy and achieved remission. Four years later, the disease relapsed and he was given idarubicin, mitoxantrone and ATRA followed by maintenance chemotherapy (ATRA, mercaptopurine and methotrexate). He achieved a second remission for the next 11 years. During a follow-up later, his full blood picture showed leucocytosis, anaemia and leucoerythroblastic picture. Bone marrow examination showed hypercellular marrow with trilineage dysplasia, 3% blasts but no abnormal promyelocyte. Fluorescence in-situ hybridisation (FISH) study of the PML/RARA gene was negative. Karyotyping result revealed complex abnormalities and monosomal karyotype (MK). A diagnosis of therapy-related myelodysplastic syndrome/myeloproliferative neoplasm with unfavourable karyotypes and MK was made. The disease progressed rapidly and transformed into therapy-related acute myeloid leukaemia in less than four months, complicated with severe pneumonia. Despite aggressive treatment with antibiotics and chemotherapy, the patient succumbed to the illness two weeks after the diagnosis.
DISCUSSION AND CONCLUSION: Diagnosis of t-MN should be suspected in patients with a history of receiving cytotoxic agents. Karyotyping analysis is crucial for risk stratification as MK in addition to complex aberrant karyotypes predicts unfavourable outcome. Further studies are required to address the optimal management for patients with t-MN.