Health utility scores of family caregivers for leukemia patients measured by EQ-5D-3L: a cross-sectional survey in China.

BACKGROUND: This study assessed the health related quality of life of family caregivers (FCs) of leukemia patients by using the health utility scores derived from the EuroQol five-dimensional (EQ-5D) questionnaire. METHODS: A cross-sectional survey was undertaken on 306 family caregivers of leukemia patients to assess their health utility using the EQ-5D-3L. Participants were recruited from three hospitals in China's Heilongjiang province. The health utility scores of the participants were estimated based on the Chinese EQ-5D-3L value set and compared with those of the local general population. Factors predicting the health utility scores were identified through the Kruskal-Wallis analysis of variance and median regression analyses. RESULTS: FCs had lower health utility scores than the general population (p < 0.001). The participants with a lower socioeconomic status had lower utility scores and reported more problems than those with a higher socio-economic status. Better family function and higher social support were associated with higher health utility scores. The type of leukemia, household income, and social support are significant predictors of health utility scores of the FCs. Chronic lymphocytic leukemia, low socio-economic status, and low social support are associated with lower health utility scores of the FCs. CONCLUSIONS: FCs for leukemia patients have lower health utility scores than the local general population, as measured by the EQ-5D-3L. There is an immediate need to address the health concerns of FCs, who play an important role in the Chinese health care system.

Procoagulant activity and phosphatidylserine of amniotic fluid cells.

Amniotic fluid (AF) may induce disseminated intravascular coagulation (DIC) when it enters maternal circulation by breaching the placental-maternal circulation barrier. The precise mechanism of the procoagulant activity of AF is unclear, but tissue factor (TF) has been proposed to be the main cause. As one constituent of AF, AF cells accumulate and undergo apoptosis continuously. Therefore, we speculate that AF cells have procoagulant activity due to the externalisation of phosphatidylserine (PS). The present study aims to demonstrate that, in addition to TF, the PS that is externalised on AF cells is important for the procoagulant activity of AF. Ten AF samples from parturient women were analysed using lactadherin as the probe for PS. Anti-TF antibody also was used to identify TF and its associated coagulation functions in AF cells. Normal platelets, neutrophils, and lymphocytes were harvested as controls. Confocal microscopy and flow cytometry was used to assess PS expression on AF cells. The procoagulant activity of AF cells was demonstrated by a plasma coagulation assay and further confirmed by factor Xase/prothrombinase assays. PS and TF were present on most AF cells, providing substantial procoagulant activity. Furthermore, factor Xase and prothrombinase assays showed that AF cells substantially enforced the activation of factor X and prothrombin. PS on AF cells is an important procoagulant source for AF. Lactadherin is an ideal anticoagulant for inhibiting the procoagulant activity of AF cells.

Identification of high-risk habitats of Oncomelania hupensis, the intermediate host of schistosoma japonium in the Poyang Lake region, China: A spatial and ecological analysis.

BACKGROUND: Identifying and eliminating snail habitats is the key measure for schistosomiasis control, critical for the nationwide strategy of eliminating schistosomiasis in China. Here, our aim was to construct a new analytical framework to predict high-risk snail habitats based on a large sample field survey for Oncomelania hupensis, providing guidance for schistosomiasis control and prevention. METHODOLOGY/PRINCIPAL FINDINGS: Ten ecological models were constructed based on the occurrence data of Oncomelania hupensis and a range of variables in the Poyang Lake region of China, including four presence-only models (Maximum Entropy Models, Genetic Algorithm for rule-set Production, Bioclim and Domain) and six presence-absence models (Generalized Linear Models, Multivariate Adaptive Regression Splines, Flexible Discriminant Analysis, as well as machine algorithmic models-Random Forest, Classification Tree Analysis, Generalized Boosted Model), to predict high-risk snail habitats. Based on overall predictive performance, we found Presence-absence models outperformed the presence-only models and the models based on machine learning algorithms of classification trees showed the highest accuracy. The highest risk was located in the watershed of the River Fu in Yugan County, as well as the watershed of the River Gan and the River Xiu in Xingzi County, covering an area of 52.3 km2. The other high-risk areas for both snail habitats and schistosomiasis were mainly concentrated at the confluence of Poyang Lake and its five main tributaries. CONCLUSIONS/SIGNIFICANCE: This study developed a new distribution map of snail habitats in the Poyang Lake region, and demonstrated the critical role of ecological models in risk assessment to directing local field investigation of Oncomelania hupensis. Moreover, this study could also contribute to the development of effective strategies to prevent further spread of schistosomiasis from endemic areas to non-endemic areas.

Increased procoagulant activity of red blood cells in the presence of cisplatin.

BACKGROUND: Cisplatin based chemotherapy is a well recognized risk factor for coagulation disorders and thrombosis. The pathophysiological mechanisms by which cisplatin promote thrombosis are not well understood. METHODS: Red blood cells (RBCs) were separated from peripheral blood of patients with breast cancer (n = 10) and healthy adults (n = 6) and treated with cisplatin. Coagulation time of RBCs was assessed by one step recalcification time and the productions of thrombin, intrinsic and extrinsic factor Xa were measured in the presence or absence of various concentrations of lactadherin. Exposed phosphatidylserine was stained with lactadherin and observed by confocal microscopy and flow cytometry. RESULTS: Neither fresh RBCs nor RBCs treated without cisplatin had potent procoagulant activity. Cisplatin treatment increased procoagulant activity of RBCs in a cell number- and concentration-dependent manner. Exposed phosphatidylserine was stained with lactadherin and after cisplatin treatment, strong fluorescence was revealed by confocal microscopy. Lactadherin bound RBCs from patients with breast cancer increased from (1.9 +/- 0.5)% on control RBCs to (68.0 +/- 3.5)% on RBCs treated with 10 micromol/L cisplatin for 24 hours. CONCLUSIONS: Cisplatin treatment increases procoagulant activity of RBCs, which have a strong association with exposure of phosphatidylserine. The increased procoagulant activity may contribute to the pathogenesis of thrombophilia during cisplatin based chemotherapy in breast cancer patients.

The effect of arsenic trioxide on QT interval prolongation during APL therapy.

OBJECTIVE: To investigate the cardiac effect of QT interval prolongation in the treatment of acute promyelocytic leukemia (APL) with arsenic trioxide (As(2)O(3)), and the relationship between QT and serum arsenic concentration. METHODS: Blood serum arsenic concentrations of thirty APL patients were determined at 2 hours, 4 hours, 8 hours, and 24 hours after As(2)O(3) injection using atomic fluorophotometry. Cardiac functions were measured simultaneously using a 12-lead body-surface electrocardiogram (ECG). Q-T intervals were manually measured, and then corrected using Bazett's formula (QTc). QT dispersion (QTd) was also calculated. In order to assess the effects of arsenic on the symptoms of anemia, twenty-four anemia patients were divided into two groups on the basis hemoglobin concentration: Group 1 (Hb > or = 90 g/L), and Group 2 (60 g/L < or = Hb < 90 g/L). QTc and QTd of these patients were also manually measured. RESULTS: All QT intervals of APL patients treated with As(2)O(3) injection were prolonged [32.2 ms (27, 41 ms); P < 0.05], but the changes of QTd were not prominent [3 ms (-8, 7 ms), P > 0.05]. There was a delay of 2 hours in maximum QTc following peaks in serum arsenic concentration. Changes in QTc and QTd of the two anemic groups were not prominent. CONCLUSIONS: As(2)O(3) can prolong QTc intervals in APL patients, but the effects are delayed compared to peak serum arsenic concentrations. As(2)O(3) has no prolongation effect on QTd. Mild and moderate anemia do not effect QTc and QTd.

[Study on cardiac toxicity in acute promyelocyte leukemia treatment of arsenic trioxide intravenous infusion in general dose].

OBJECTIVE: To study the cardiac toxicity of arsenic trioxide (As(2)O(3)). METHODS: To investigate and analyze the probable mechanisms of cardiac toxicity of As(2)O(3) by dynamic monitoring of clinical manifestations, basal cardiac rate and electrocardiographic data of acute promyelocyte leukemia (APL) patients during As(2)O(3) therapy. The instant change of the action potential, the I(Ca-L) and I(k) of single cardiac myocyte of guinea pig was also observed with patch clamp dynamically. RESULTS: Approximately 71.4% of the 28 cases of APL showed cardiac toxic reaction in different degree in the first week after As(2)O(3) intravenous infusion in general dose, mainly expressing rapid heart rate or prolonged QT interval. As(2)O(3) could prolong the action potential duration from (563.0 +/- 55.8) ms to (737.7 +/- 131.7) ms (P < 0.05) and increased the I(Ca-L) and I(k) of single cardiac myocyte of guinea pig in vitro. CONCLUSION: As(2)O(3) intravenous infusion in general therapeutic dose can cause tachycardia and prolong QT interval in some of the APL patients. The probable mechanism of these side-effects may be due to instant involvement of ionic channel of cardiac myocyte.

Daunorubicin induces procoagulant response through phosphatidylserine exposure in red blood cells.

INTRODUCTION: Cytotoxic chemotherapy induces or worsens hemostatic disorders in patients with acute myeloid leukemia. Procoagulant release and tissue factor expression on tumor cells are considered to contribute to chemotherapeutic agents-associated coagulopathy. The role of red blood cells during this process has not been determined; although they lack tissue factor, they may contribute suitable membranes for the amplification phase of blood coagulation. The present study aims to evaluate the possible impact of daunorubicin on phosphatidylserine exposure and consequent procoagulant property of red blood cells. MATERIALS AND METHODS: Red blood cells from acute myeloid leukemia patients and healthy donors were treated with daunorubicin as well as all-trans-retinoic acid, arsenic trioxide or etoposide for 0-48 h. Procoagulant activity was assessed by measurement of a clotting time and by purified coagulation complex assays. Lactadherin was used as a probe for phosphatidylserine. RESULTS: Daunorubicin treatment increased procoagulant activity of red blood cells regardless of the cell origin. Moreover, coagulation complexes assays supported daunorubicin-evoked procoagulant response. The procoagulant property of red blood cells was not affected by the other three agents. The modulating effect of procoagulant activity was concomitant with and dependent on level of phosphatidylserine on the outer surface. Blockade of phosphatidylserine with lactadherin inhibited over 90% of tenase generation and prothrombinase activity and prolonged the coagulation time. CONCLUSIONS: We conclude that daunorubicin interacts with red blood cells in a manner that increases phosphatidylserine exposure and consequent procoagulant activity. Lactadherin is an efficient anticoagulant of this process.

Lactadherin and procoagulant activities of red blood cells in cyclosporine induced thrombosis.

BACKGROUND: The side effects of cyclosporine therapy include thromboembolic complications. However, the mechanisms underlying the hypercoagulable state induced by cyclosporine are not fully understood. Cyclosporine binds to red blood cells (RBCs) with a high affinity in circulation and alters the membranes of RBCs. Therefore, we propose that such alterations in RBCs membranes play a role in cyclosporine-induced coagulopathy and this disorder may be rectified by lactadherin, a phosphatidylserine binding protein. METHODS: RBCs from healthy adults were treated with various concentrations of cyclosporine. Procoagulant activity of the RBC membrane was measured by the single stage recalcification time and confirmed by detection of tenase and thrombin assembly through enzymatic assays. Inhibition assays of coagulation were carried out in the presence of lactadherin, annexin V or antitissue factor. Phosphatidylserine exposure was detected by flow cytometry and confocal microscopy through binding with fluorescein isothiocyanate (FITC)-labeled lactadherin as well as FITC annexin V. RESULTS: RBCs treated with cyclosporine demonstrated increased procoagulant activity. Cyclosporine treatment markedly shortened the clotting time of RBCs ((305 +/- 10) seconds vs (366 +/- 15) seconds) and increased the generation of intrinsic factor Xase ((7.68 +/- 0.99) nmol/L vs (2.86 +/- 0.11) nmol/L) and thrombin ((15.83 +/- 1.37) nmol/L vs (4.88 +/- 0.13) nmol/L). Flow cytometry and confocal microscopy indicated that cyclosporine treatment induced an increased expression of phosphatidylserine on the RBC membrane. Lactadherin was more sensitive in detecting phosphatidylserine exposure of the RBC membrane than annexin V. The modulating effect of procoagulant activity was concomitant with and dependent on phosphatidylserine exposure. Blocking of phosphatidylserine with lactadherin effectively inhibited over 90% of FXa generation and prothrombinase activity and prolonged coagulation time. CONCLUSIONS: Procoagulant properties of RBCs membranes resulting from phosphatidylserine exposure may play an important role in cyclosporine-induced thrombosis. Lactadherin can be used as a sensitive probe for phosphatidylserine detection. Its high affinity for phosphatidylserine may provide a new approach for the treatment of cyclosporine induced thrombogenic properties.