Development, validity and reliability testing of the East Midlands Evaluation Tool (EMET) for measuring impacts on trainees' confidence and competence following end of life care training.

OBJECTIVES: To develop, test and validate a versatile questionnaire, the East Midlands Evaluation Tool (EMET), for measuring effects of end of life care training events on trainees' self-reported confidence and competence. METHODS: A paper-based questionnaire was designed on the basis of the English Department of Health's core competences for end of life care, with sections for completion pretraining, immediately post-training and also for longer term follow-up. Preliminary versions were field tested at 55 training events delivered by 13 organisations to 1793 trainees working in diverse health and social care backgrounds. Iterative rounds of development aimed to maximise relevance to events and trainees. Internal consistency was assessed by calculating interitem correlations on questionnaire responses during field testing. Content validity was assessed via qualitative content analysis of (1) responses to questionnaires completed by field tester trainers and (2) field notes from a workshop with a separate cohort of experienced trainers. Test-retest reliability was assessed via repeat administration to a cohort of student nurses. RESULTS: The EMET comprises 27 items with Likert-scaled responses supplemented with questions seeking free-text responses. It measures changes in self-assessed confidence and competence on 5 subscales: communication skills; assessment and care planning; symptom management; advance care planning; overarching values and knowledge. Test-retest reliability was found to be good, as was internal consistency: the questions successfully assess different aspects of the same underlying concept. CONCLUSIONS: The EMET provides a time-efficient, reliable and flexible means of evaluating effects of training on self-reported confidence and competence in the key elements of end of life care.

A single center's experience using four different front line mobilization strategies in lymphoma patients planned to undergo autologous hematopoietic cell transplantation.

In an otherwise eligible patient with relapsed lymphoma, inadequate mobilization of hematopoietic stem cells (HSCs) is a limiting factor to proceeding with an autologous hematopoietic cell transplantation (auto-HCT). Multiple strategies have been used to mobilize an adequate number of HSCs with no obvious front-line strategy. We report a single institutional experience mobilizing HSCs using four different approaches in lymphoma patients. We prospectively collected mobilization outcomes on patients planned to undergo auto-HCT at Ohio State University. We report results of first mobilization attempts for all relapsed or refractory lymphoma patients between 2008 and 2014. We identified 255 lymphoma patients who underwent mobilization for planned auto-HCT. The 255 lymphoma patients underwent the following front line mobilization strategies: 95 (37%) G-CSF alone, 38 (15%) chemomobilization (G-CSF+chemotherapy), 97 (38%) preemptive day 4 plerixafor, and 25 (10%) rescue day 5 plerixafor. As expected, there were significant differences between cohorts including age, comorbidity indices, histology, and amount of prior chemotherapy. After controlling for differences between groups, the odds of collecting 2 × 106/kg HSCs on the first day of collection and 5 × 106/kg HSCs in total was the highest in the cohort undergoing chemomobilization. In conclusion, our experience highlights the effectiveness of chemomobilization.

An effective mobilization strategy for lymphoma patients after failed upfront mobilization with plerixafor.

In an otherwise eligible patient, inadequate mobilization of PBSCs is a limiting factor to proceeding with an auto-ASCT. In such situations, plerixafor is commonly added to improve PBSC collection yields along with cytokine (G-CSF alone) or chemomobilization (chemotherapy+G-CSF). Individually, both strategies are proven to be safe and effective. Here we report six patients who underwent successful mobilization with combination chemomobilization plus plerixafor after upfront failure of cytokine mobilization plus plerixafor. The median CD34(+) cell yield after chemomobilization was 2.48 × 10(6)/kg (range 0.99-8.49) after receiving one to two doses of plerixafor. All patients subsequently underwent ASCT without major unforeseen toxicities and engrafted successfully. No significant delays in time to neutrophil recovery were observed. Our experience highlights the safety and effectiveness of chemomobilization with plerixafor after G-CSF plus plerixafor (G+P) failure and suggests this is a viable salvage strategy after initial failed G+P mobilization.

Recombinant human antithrombin III improves survival and attenuates inflammatory responses in baboons lethally challenged with Escherichia coli.

Plasma-derived antithrombin III (ATIII) prevents the lethal effects of Escherichia coli infusion in baboons, but the mechanisms behind this effect are not clear. In the present study, we evaluated the effects of recombinant human ATIII (rhATIII) on the clinical course and the inflammatory cytokine and coagulation responses in baboons challenged with lethal dose of E coli. Animals in the treatment group (n = 5) received high doses of rhATIII starting 1 hour before an E coli challenge. Those in the control group were administered saline. Survival was significantly improved in the treatment group (P =.002). Both groups had similar hemodynamic responses to E coli challenge but different coagulation and inflammatory responses. The rhATIII group had an accelerated increase of thrombin-ATIII complexes and significantly less fibrinogen consumption compared to controls. In addition, the rhATIII group had much less severe thrombotic pathology on autopsy and virtually no fibrinolytic response to E coli challenge. Furthermore, the rhATIII group had a significantly attenuated inflammatory response as evidenced by marked reduction of the release of various cytokines. We conclude that the early administration of high doses of rhATIII improves the outcome in baboons lethally challenged with E coli, probably due to the combined anticoagulation and anti-inflammatory effects of this therapy. (Blood. 2000;95:1117-1123)

Effects of mixed-function oxidase and aflatoxin B1 on lysogenic and indicator strains of Bacillus subtilis.

The present study was conducted to determine the effects of metabolized aflatoxin B1 (via a mammalian liver mixed-function oxidase system) and native aflatoxin B1 upon induction of bacteriophage in Bacillus subtilis and growth of B. subtilis. A lysogenic strain of B. subtilis (BDS-1, phi 105) and an indicator strain of this species (DBS-1) were utilized in the present experiment. Lysogenic cultures were incubated for various lengths of time in the presence of either native or metabolized toxin, and plaque-forming units were determined. Identical experiments were conducted with the indicator strain and colony-forming units were determined. At a native toxin concentration of 25 micrograms/ml of medium, the maximum number of plaque-forming units was induced in lysogenic cells. However, when cells were incubated in the presence of aflatoxin B1 and mixed-function oxidase, neither plaque-forming units nor colony-forming units could be detected from lysogenic or indicator cells, respectively. This organism is apparently much more susceptible to inhibition of cellular replication than to lysis via bacteriophage induction. Thus, from the present study and from previously reported research, differences in susceptibility to native and metabolized aflatoxin B1 exist among species of Bacillus.

Interaction of aflatoxin B1 with bacterial DNA: possible relationship to bacteriophage induction in lysogenic Bacillus megaterium.

Studies were conducted to determine possible interactions between aflatoxin B1 and deoxyribonucleic acid (DNA) and induction of bacteriophage formation in lysogenic Bacillus megaterium NRRL-B-3695. At pH 7.4, the spectrophotometric characteristics of B1 with various concentrations of calf thymus DNA were altered with both a hypochromic shift and a shift of the wavelength for maximum absorbance of the toxin. Aflatoxin B1 apparently interacted with DNA as indicated by spectrophotometric analysis and ultrafiltration studies. Under alkaline conditions (pH 10.0), spectrophotometric characteristics of this interaction were altered from those observed at pH 7.4. Toxin incubated at pH 7.4 could induce bacteriophage formation but failed to do so at pH 10. Preincubation of toxin with calf thymus DNA did not block subsequent induction. It is proposed that a bacterial DNA-toxin interaction, involving an alkaline-labile bond of aflatoxin B1, is necessary to cause induction of bacteriophage formation in lysogenic B. megaterium.

Enthalpies of ligand binding to bovine neurophysins.

Flow microcalorimetry and batch microcalorimetry have been used to survey the energetics of ligand binding by bovine neurophysins I and II. Calorimetry studies were supplemented by van't Hoff analyses of binding constants determined by circular dichroism. Free energies of binding of a series of di- and tripeptides that bind to the strong hormone binding site of neurophysin were partitioned into their enthalpic and entropic components. The results indicate that, at 25 degrees C, the binding of most peptides is an enthalpy-driven reaction associated with negative entropy and heat capacity changes. Studies elsewhere, supported by evidence here, indicate that the principal component of the negative enthalpy change does not arise from the increase in neurophysin dimerization associated with peptide binding. Accordingly, the negative enthalpy change is attributed to direct bonding interactions with peptide and possibly also to peptide-induced changes in tertiary or quaternary organization. Comparison of the binding enthalpies of different peptides indicated two types of bonding interactions that contribute to the negative enthalpy change of peptide ligation. Substitution of an aromatic- or sulfur-containing side chain for an aliphatic side chain in position 1 of bound peptides led to increases in negative enthalpy of from 1 to 6 kcal/mol, demonstrating that interactions typically classified as hydrophobic can have a significant exothermic component at 25 degrees C. Similarly, loss of hydrogen bonding potential in the peptide decreased the enthalpy change upon binding, in keeping with the expected enthalpic contribution of hydrogen bonds. In particular, the data suggested that the peptide backbone between residues 2 and 3 and the phenolic hydroxyl group in position 2 participate in hydrogen bonding.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of self-association of bovine neurophysins by gel chromatography.

Analytical gel chromatography has been used to examine self-association of bovine neurophysins I and II under several sets of conditions. The data provide no evidence for associated species larger than the dimer. Association constants and Stokes radii of both monomer and dimer are very similar for both proteins in both 0.1 M KOAc, 0.16 M KCl and 0.1 M KPO4, 0.16 M KCl at pH 5.6 and 25 degrees C. The average values derived for the Stokes radii of the monomer and dimer under these conditions are 14.5 +/- 0.7 and 23.0 +/- 0.4 A, respectively. These results confirm the conclusion of Rholam and Nicolas [(1981) Biochemistry 20, 5837-5843] that the monomer and, to a lesser extent, the dimer are highly assymmetric. The Stokes radius of the monomer calculated by Rholam and Nicolas (op cit.) is approximately 30% larger than the value derived here. This discrepancy is probably the result of end-on penetration of the gel by elongated molecules [Y. Nozaki, N. M. Schechter, J. A. Reynolds, and C. Tanford (1976) Biochemistry 15, 3884-3890]. In contrast to Tellam and Winzor [(1980) Arch. Biochem. Biophys. 201, 20-24], it was found that neurophysin II does not exist solely as the dimer in 0.1 M KPO4, pH 5.6, although substitution of 0.1 M KPO4 for 0.1 M KOAc does increase the association constant by a factor of seven. Addition of 1.4 M LiCl at pH 8.1 also increases the association constant sevenfold, as well as increasing the Stokes radius of the monomer approximately 20%. The effects of ionic strength are consistent with the conclusion of Nicolas et al. [(1978) J. Biol. Chem 253, 2633-2639] that formation of the dimer depends upon hydrophobic bonding.

Fluoride supplements for children. A survey of physicians' prescription practices.

We present the results of a survey to determine how physicians prescribe fluoride supplements for their child patients. A questionnaire was mailed to a representative nationwide sample of 2,604 physicians who treat children. The response rate of completed returns was 49.4%. Results showed that while most respondents prescribed fluoride appropriately, there was some inappropriate prescribing for children receiving fluoridated water. Some physicians also neglected to prescribe for children who were not receiving fluoridated water. Previous differences in recommended schedules of administration between the American Academy of Pediatrics and the American Dental Association may have led to some of these problems. However, these two organizations have now standardized their recommendations.

Conditions for induction of bacteriophage from lysogenic Bacillus megaterium with aflatoxin B1.

The present study was conducted to determine whether or not aflatoxin B1 was an effective inducing agent for lysogenic bacteria and to characterize some of the parameters involved in induction. A lysogenic strain of Bacillus megaterium (NRRL-B-3695) and an indicator strain of this species (NRRL-B-3694) were used. Cultures of the lysogenic strain were incubated for various periods of time in the presence of aflatoxin B1. Plaque-forming units as well as colony-forming units were then determined. Results of the present study indicated that bacteriophage lysogenizing B. megaterium could be induced with aflatoxin B1. The optimum concentration for induction was 25 micrograms of toxin per ml of early-log-phase culture. Evidence suggested that: (i) higher concentrations of aflatoxin B1 formed hydrophobic complexes which would not efficiently induce B. megaterium; (ii) the toxic effect of aflatoxin B1 severely limited the number of cells which could be induced prior to killing action of the toxin; and (iii) concentrations less than 25 micrograms of aflatoxin B1 per ml were not efficient inducers of bacteriophage production nor did they demonstrate the toxic effect observed at higher concentrations.

The hemostatic mechanism after open-heart surgery. II. Frequency of abnormal platelet functions during and after extracorporeal circulation.

In a prospective study of 13 patients undergoing open-heart surgery with extracorporeal circulation, marked qualitative platelet function defects were observed in addition to the usually occurring drop of the thrombocyte count. At the end of bypass, the following test results were significantly abnormal: concentration of fibrinogen and of circulating fibrin degradation products, platelet count, platelet adhesiveness to glass beads, and platelet aggregation induced by low and high doses of ADP. One to 2 hours after neutralization of heparin with protamine sulfate all abnormal test results improved, but the template bleeding time was markedly prolonged in 10 patients. There was no correlation between length of bypass and platelet fall and between concentration of circulating fibrin degradation products and extent of platelet dysfunction. An apparent correlation was found between the length of the postoperative bleeding time and the number of units of blood transfued during surgery. The results of this study suggest that dilution of the patient's own platelets by nonviable platelets contained in 3-day-old transfused ACD blood and the production of a refractory state of the patient's circulating platelets to ADP induced aggregation played a significant role in the development of platelet function abnormalities during extracorporeal circulation.