Indirect treatment comparison of oral versus injectable azacitidine as maintenance therapy for acute myeloid leukemia.

Aim: Evaluate the relative efficacy of oral versus injectable azacitidine (AZA) maintenance therapy in acute myeloid leukemia (AML) after complete remission. Materials & methods: Systematic literature review identified QUAZAR AML-001, HOVON 97 AML, UK NCRI AML16 and QoLESS-AZA-AMLE (sensitivity analysis) trials. Network meta-analysis and matching-adjusted indirect comparisons assessed survival outcomes. Results: In the network meta-analysis, combining the HOVON 97 and UK NCRI trials, oral AZA (QUAZAR) was associated with significantly improved overall survival (OS) versus injectable AZA (hazard ratio: 0.744; 95% credible interval: 0.557-0.998). After matching-adjusted indirect comparisons, to address differences in patient characteristics across trials, OS improvements were maintained with oral versus injectable AZA (hazard ratio: 0.753; credible interval: 0.563-0.998). Conclusion: In AML, maintenance therapy with oral AZA was associated with improved OS versus injectable AZA.

Older people with acute myeloid leukemia (AML) may have remission with or without blood count recovery, after first-line chemotherapy; however, remission is short lived and overall survival is limited (7­12 months). Ongoing treatment (maintenance therapy) after response to initial chemotherapy may prolong remission. Maintenance therapy with azacitidine (AZA) given by injection beneath the skin (subcutaneous) or into a vein (intravenous) can extend disease-free survival compared with no further treatment and best supportive care. However, treatment with intravenous AZA may only extend overall survival in certain patients. ONUREG^® is a novel formulation of AZA that can be taken by mouth (orally), remains in the body for longer periods and has the potential for significant clinical benefits compared with intravenous AZA. Presently, there are no studies directly comparing outcomes of maintenance therapy with oral and injectable AZA in older people with AML. In this analysis, we used an indirect treatment comparison method including four clinical trials to explore the survival benefit associated with ONUREG and injectable AZA when used as maintenance therapies after response to initial chemotherapy in older people with AML. Findings showed ONUREG significantly improved overall survival compared with injectable AZA, with an almost 26% reduction in the risk of death. These results suggest that maintenance therapy with ONUREG significantly improves overall survival compared with injectable AZA in older people with AML who may have remission with or without blood count recovery, after first-line chemotherapy.

Antineoplastic Therapy Administration Safety Standards for Adult and Pediatric Oncology: ASCO-ONS Standards.

PURPOSE: To update the ASCO-Oncology Nursing Society (ONS) standards for antineoplastic therapy administration safety in adult and pediatric oncology and highlight current standards for antineoplastic therapy for adult and pediatric populations with various routes of administration and location. METHODS: ASCO and ONS convened a multidisciplinary Expert Panel with representation of multiple organizations to conduct literature reviews and add to the standards as needed. The evidence base was combined with the opinion of the ASCO-ONS Expert Panel to develop antineoplastic safety standards and guidance. Public comments were solicited and considered in preparation of the final manuscript. RESULTS: The standards presented here include clarification and expansion of existing standards to include home administration and other changes in processes of ordering, preparing, and administering antineoplastic therapy; the advent of immune effector cellular therapy; the importance of social determinants of health; fertility preservation; and pregnancy avoidance. In addition, the standards have added a fourth verification. STANDARDS: Standards are provided for which health care organizations and those involved in all aspects of patient care can safely deliver antineoplastic therapy, increase the quality of care, and reduce medical errors.Additional information is available at www.asco.org/standards and www.ons.org/onf.

Antineoplastic Therapy Administration Safety Standards for Adult and Pediatric Oncology: ASCO-ONS Standards.

PURPOSE: To update the American Society of Clinical Oncology (ASCO)-Oncology Nursing Society (ONS) standards for antineoplastic therapy administration safety in adult and pediatric oncology and highlight current standards for antineoplastic therapy for adult and pediatric populations with various routes of administration and location. METHODS: ASCO and ONS convened a multidisciplinary Expert Panel with representation of multiple organizations to conduct literature reviews and add to the standards as needed. The evidence base was combined with the opinion of the ASCO-ONS Expert Panel to develop antineoplastic safety standards and guidance. Public comments were solicited and considered in preparation of the final manuscript. RESULTS: The standards presented here include clarification and expansion of existing standards to include home administration and other changes in processes of ordering, preparing, and administering antineoplastic therapy; the advent of immune effector cellular therapy; the importance of social determinants of health; fertility preservation; and pregnancy avoidance. In addition, the standards have added a fourth verification. STANDARDS: Standards are provided for which health care organizations and those involved in all aspects of patient care can safely deliver antineoplastic therapy, increase the quality of care, and reduce medical errors.

Muscle Assessment by Ultrasonography: Agreement with Dual-Energy X-Ray Absorptiometry (DXA) and Relationship with Physical Performance.

BACKGROUND: Different methods have been proposed to study skeletal muscle mass in sarcopenia diagnosis, although all have inherent drawbacks. The aim of this study was to evaluate the utility of muscle ultrasound in muscle assessment by studying its correlation with dual-energy x-ray absorptiometry (DXA) and calf circumference (CC), cut-off values for ultrasound-based detection of low muscle mass, and the correlation with muscle performance. METHODS: Fifty-seven participants older than 70 years, underwent a muscle ultrasound study, DXA, calf circumference (CC) and functional assessment. Ultrasound measurements were taken in the femoral quadriceps (transverse plane) and in the medial gastrocnemius (transverse and longitudinal planes). Muscle function was assessed by gait speed, Short Physical Performance Battery (SPPB) and grip strength. RESULTS: Median age was 78.9 years (IQR 74.9 - 81.9), and 33 were women (57.9%). We found good correlation between muscle thickness of gastrocnemius muscle in transverse and longitudinal plane and appendicular lean mass measured by DXA (r=0.546 and r=0.689 respectively) and good correlations between muscle thickness of gastrocnemius in transverse and longitudinal plane with CC (r=0.651 and r=0.447 respectively). The thickness of gastrocnemius medialis optimal cut-off points for low muscle mass were 18,5mm in the transverse plane (Sensitivity: 77,8%, Specificity: 77,1%), and 17.3mm in the longitudinal plane (Sensitivity: 100%,Specificity: 68.8%). Muscle thickness was also significantly correlated with gait speed, SPPB and grip strength. CONCLUSIONS: Measures of gastrocnemius medialis thickness obtained by ultrasound are reliable and correlate well with DXA and CC values and muscle performance.

Creating randomized amino acid libraries with the QuikChange Multi Site-Directed Mutagenesis Kit.

The QuikChange Multi Site-Directed Mutagenesis Kit is a simple and efficient method for introducing point mutations at up to five sites simultaneously in plasmid DNA templates. Here we used the QuikChange Multi kit with degenerate (one codon) primers to introduce all possible amino acids at selected sites in the lacZ gene. In reactions employing two or three degenerate primers, diverse libraries (10(4)-10(5) mutants/reaction) are created consisting of random combinations of mutations at two or three different sites. This method provides a one-day procedure for performing site-directed saturation mutagenesis and, when coupled with a suitable screening assay, should greatly facilitate the process of evaluating alternative amino acid chain substitutions at key residues and evolving protein function.

[Antimicrobial drug resistance in non-typhi Salmonellae in Castilla y Leon]. / Resistencia a antimicrobianos en Salmonella no typhi en Castilla y León.

We studied the antibiotic susceptibility of 309 Salmonella isolates obtained from three hospitals serving the provinces of Salamanca, Avila and Zamora in the region of Castilla y Leon (mid-west Spain). The susceptibility to 18 antibiotics was studied using the agar dilution method, according to NCCLS guidelines, and the most common multiresistance phenotypes were determined for each province. We observed clear susceptibility differences between the two main serotypes found, S. enteritidis and S. typhimurium. Seventy percent of S. typhimurium were resistant to amoxicillin. In 44% of these isolates, amoxicillin resistance was associated with resistance to streptomycin, sulfonamides, tetracyclines and chloramphenicol. S. enteritidis was susceptible to most antibiotics tested; amoxicillin resistance was observed in 23.3%, and nalidixic acid resistance in 49.6%. Resistance to nalidixic acid was higher in S. enteritidis than in any other serotypes. According to NCCLS breakpoints, no strain was resistant to fluoroquinolones. However, according to MENSURA criteria, 9% of S. typhimurium isolates were resistant to ciprofloxacin. Resistance to cotrimazole and gentamicin was less than 10% for all the serotypes tested. The results indicate that S. typhimurium showed greater resistance and a high multidrug resistance rate. Conversely, S. enteritidis showed high resistance only to amoxicillin and nalidixic acid, though in most cases there was no correlation between this resistance and reduced susceptibility to fluoroquinolones.

Impact of positive psychological capital on employee well-being over time.

The recently recognized core construct of psychological capital or PsyCap (consisting of the positive psychological resources of efficacy, hope, optimism, and resilience) has been demonstrated to be related to various employee attitudinal, behavioral, and performance outcomes. However, to date, the impact of this positive core construct over time and on important employee well-being outcomes has not been tested. This study meets this need by analyzing the relationship between a broad cross-section of employees' (N = 280) level of PsyCap and two measures of psychological well-being over time. The results indicated that employees' PsyCap was related to both measures of well-being and, importantly, that PsyCap explained additional variance in these well-being measures over time. The limitations, needed future research, and practical implications conclude the article.

Contrasting roles for domain 4 of VCAM-1 in the regulation of cell adhesion and soluble VCAM-1 binding to integrin alpha4beta1.

Cell adhesion mediated by the interaction between integrin alpha4beta1 and VCAM-1 is important in normal physiologic processes and in inflammatory and autoimmune disease. Numerous studies have mapped the alpha4beta1 binding sites in VCAM-1 that mediate cell adhesion; however, little is known about the regions in VCAM-1 important for regulating soluble binding. In the present study, we demonstrate that 6D VCAM-1 (an alternatively spliced isoform of VCAM-1 lacking Ig-like domain 4) binds alpha4beta1 with a higher relative affinity than does the full-length form of VCAM-1 containing 7 Ig-like extracellular domains (7D VCAM-1). In indirect binding assays, the EC50 of soluble 6D VCAM-1 binding to alpha4beta1 on Jurkat cells (in 1 mM MnCl2) was 2 x 10(-9) M, compared with 7D VCAM-1 at 11 x 10(-9) M. When used in solution to inhibit alpha4beta1 mediated cell adhesion, the IC50 of 6D VCAM-1 was 13 x 10(-9) M, compared with 7D VCAM-1 measured at 150 x 10(-9) M. Removal of Ig-like domains 4, 5, or 6, or simply substituting Asp328 in domain 4 of 7D VCAM-1 with alanine, caused increased binding of soluble 7D VCAM-1 to alpha4beta1. In contrast, cells adhered more avidly to 7D VCAM-1 under shear force, as it induced cell spreading at lower concentrations than did 6D VCAM-1. Finally, soluble 6D VCAM-1 acts as an agonist through alpha4beta1 by augmenting cell migration and inducing cell aggregation. These results indicate that the domain 4 of VCAM-1 plays a contrasting role when VCAM-1 is presented in solution or as a cell surface-expressed adhesive substrate.

Listeria in Seafoods: A Review.

Listeria is an environmental contaminant which has been isolated from marine and fresh waters, as well as various seafoods. Furthermore, Listeria , including Listeria monocytogenes , has been isolated from processed seafood products such as smoked fish, cooked and frozen seafoods, marinated fish, surimi products, etc. The pathogen, L. monocytogenes , does have a certain degree of heat resistance. It was found to survive in internally infected shrimp after boiled for up to 5 min. However, the commercial pasteurization process for crab meat was found to be sufficient to inactivate Listeria . The current recovery methodology for L. monocytogenes from seafoods is the Food and Drug Administration Listeria protocol.

Suppression of immune parameters in animal models of morphine dependence.

Implantation of pellets containing 75 mg of morphine induced short term (4 day) morphine dependence and markedly reduced total number of spleen cells of BALB/c mice, without affecting total body or liver weight. Polyclonal responses induced by anti-CD3 antibodies, Concanavalin A or Escherichia coli lipopolysaccharide in the remaining spleen cells of morphine-treated mice were also inhibited. Cytofluorimetric analysis indicated that the proportion of major functional lymphocyte populations (Ig+, CD3+, CD4+ and CD8+ lymphocytes) were not significantly changed in the spleen from morphine-dependent mice. Furthermore, expression levels of surface Ig, CD3, CD4, and CD8, were similar in spleen cells from control or morphine-treated mice. So, morphine dependence in BALB/c mice under these controlled conditions results in a specific defect in lymphoid cell number and function, with no incidence on body weight or particular lymphocyte subsets.

Genetic and immunochemical evidence for CD4-dependent association of p56lck with the alpha beta T-cell receptor (TCR): regulation of TCR-induced activation.

Recent observations suggest that the tyrosine kinase p56lck is involved in the transduction of transmembrane signals through the antigen specific T cell receptor (TCR) in CD4+ T cells. By means of in vitro kinase assays, we have found that p56lck coprecipitated with the TCR from lysates of a murine CD4+ T cell line in the absence of TCR-mediated stimuli. Analysis of CD4- mutants and CD4-transfected cells shows that p56lck-TCR association occurred only when CD4 was present. The functional importance of CD4:p56lck-TCR association was demonstrated by low activating potential of rare clonotypic antibodies which did not coprecipitate CD4:p56lck, as well as by total or partial loss of anti-TCR or antigen induced stimulation in CD4- cells, which could be recovered by CD4 transfection. Complementation assays using different anti-TCR antibodies suggest that cross linking of TCR-p56lck:CD4 plus structural changes in the complex are needed for efficient transduction of activating signals through the TCR in these cells.

Polyerga, a biological response modifier enhancing T-lymphocyte-dependent responses.

Cancer patients are often treated with biological response modifiers to enhance immunological functions. However, little is known about the actual mechanism of action of many of these substances. Therefore, we were interested in the effect of i.p. treatment with porcine low-molecular-weight spleen peptides, which are used during supportive cancer therapy, on lymphoid cell populations and function in mice. After treatment with 0.5 microgram peptides/kg body weight for 14 consecutive days, lymphokine secretion and the generation of cytotoxic T-cells were significantly enhanced as compared with controls. However, there was no effect on the number of cells or the percentage of cells expressing functional surface markers in secondary lymphoid organs.

A hyperreactive variant of a CD4+ T cell line is activated by syngeneic antigen presenting cells in the absence of antigen.

A variant of the murine CD4+ T helper cell clone D10.G4.1 (D10) has been isolated and cloned. This line, which we have named "syngeneic-reactive D10", or SR.D10, maintains the I-Ak-restricted specificity for Conalbumin and the allogeneic specificities characteristic of D10 cells. However, it is hyperreactive to TCR-dependent and-independent stimuli, indicating a lower activation threshold than the original D10.G4.1 clone. The hyperreactivity of SR.D10 runs in parallel with the acquisition of a reactive phenotype against syngeneic antigen presenting cells (APCs). As in antigen activation, reactivity to syngeneic APCs can be inhibited by anti-TCR, anti-CD4, or anti-class II monoclonal antibodies. The role of CD4 in this phenomenon is highlighted as "syngeneic reactivity" disappears in CD4- mutants of SR.D10 and is recovered in CD4 transfectants. The expression of several cell surface molecules involved in T cell activation show qualitative and/or quantitative differences between SR.D10 and the original D10. No significant differences in quantity and activity of p56lck and p59fyn were detected between the hyperreactive and the original clone. Our results suggest that high sensitivity to activation, concomitant with expression of CD4, might allow the acquisition of an autoreactive phenotype and confirm the important contribution of coreceptors to determine the activation threshold of the cells. The characteristics of SR.D10 and the possibility of growing them in the presence of interleukins make this cell line a experimental model of great interest for analyzing activation mechanisms in T cells.

Actuaciones de enfermeria inmediatas en situaciones de emergencia en HD / Nursing actions in haemodyalisis emergency situations

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