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The edTPA, a recent example of a teacher candidate assessment, has influenced how teacher education classes are taught and how teacher candidates are learning. We describe three tensions present in...

Objectives To investigate whether interim changes in hetereogeneity (measured using entropy features) on MRI were associated with pathological residual cancer burden (RCB) at final surgery in patients receiving neoadjuvant chemotherapy (NAC) for primary breast cancer. Methods This was a retrospective study of 88 consenting women (age: 30–79 years). Scanning was performed on a 3.0 T MRI scanner prior to NAC (baseline) and after 2–3 cycles of treatment (interim). Entropy was derived from the grey-level co-occurrence matrix, on slice-matched baseline/interim T2-weighted images. Response, assessed using RCB score on surgically resected specimens, was compared statistically with entropy/heterogeneity changes and ROC analysis performed. Association of pCR within each tumour immunophenotype was evaluated. Results Mean entropy percent differences between examinations, by response category, were: pCR: 32.8%, RCB-I: 10.5%, RCB-II: 9.7% and RCB-III: 3.0%. Association of ultimate pCR with coarse entropy changes between baseline/interim MRI across all lesions yielded 85.2% accuracy (area under ROC curve: 0.845). Excellent sensitivity/specificity was obtained for pCR prediction within each immunophenotype: ER+: 100%/100%; HER2+: 83.3%/95.7%, TNBC: 87.5%/80.0%. Conclusions Lesion T2 heterogeneity changes are associated with response to NAC using RCB scores, particularly for pCR, and can be useful across all immunophenotypes with good diagnostic accuracy. Key Points • Texture analysis provides a means of measuring lesion heterogeneity on MRI images. • Heterogeneity changes between baseline/interim MRI can be linked with ultimate pathological response. • Heterogeneity changes give good diagnostic accuracy of pCR response across all immunophenotypes. • Percentage reduction in heterogeneity is associated with pCR with good accuracy and NPV.

Objective: Despite having a detailed MRI-safety questionnaire check at the point of referral, we have encountered a significant number of near-misses with patients being identified with MRI-Unsafe devices at the time of appointments, making this an important safety hazard. Methods and materials: A two-part survey was performed to assess referrer compliance of asking MRI-questionnaires. 120 outpatients across 3 MRI sites were interviewed at the time of appointment to confirm whether their referrers completed the MRI questionnaires with them at the time of referral. Location: Department of Radiology, Ninewells Hospital, Perth Royal Infirmary and Stracathro Hospital in Scotland. Results: Only 50–55 % of patients confirmed that they were asked about presence of a pacemaker at the point of referral. Less than 50 % of patients reported being asked about other potential hazards. Suggested strategies for change: (1) Risk Alert—Sent to all MRI referrers in the organization. ( 2) Changes to MRI Safety Questionnaire. (3) Feedback mechanism to referrers—NHS trust website publications on number of recorded near-misses and wasted appointments due to MRI-safety issues. (4) Compulsory education/training of future referrers (junior doctors/allied health professionals). (5) Education of patients/public on MRI safety—Displaying patient information leaflets/posters in waiting areas of the hospital. Key measures for improvement: (1) Reduction in number of recorded near-misses. (2) System improvements, referrer and patient education, reduction of wasted MRI appointments and improvement of waiting-times for MRI appointments Effects of survey and conclusions: The survey highlights the possibility of inadequate referrer attention, and poor patient communication about MRI safety questionnaire with regards to potential hazards of MRI examination in presence of undeclared implants. It initiated several interventions resulting in improved patient safety, with no events in next 12 months, whilst promoting public and referrer’s understanding of potential MRI safety issues. Such actions are recommended for all NHS centres across UK since there are significant similarities in functioning across UK.

article i nfo Introduction: Variability in platelet response to aspirin has been reported in patients undergoing cardiac sur- gery but has rarely been described in other operative settings and its mechanism remains uncertain. We per- formed a prospective cohort study to investigate the variability in platelet response to aspirin and to explore its mechanism in patients undergoing major orthopedic surgery. Materials and Methods: Twelve aspirin-treated patients undergoing elective hip or knee replacement were recruited. Once-daily aspirin was continued throughout the perioperative period. We measured platelet function using light transmission aggregation (LTA) in response to arachidonic acid (PLAA) and serum throm- boxane B2 (TXB2) at baseline (before surgery) as well as on days 1, 2, 3, 4, 5, 6, and 8 after surgery. We defined aspirin low response as a PLAA>20%. Results: Six patients exhibited aspirin low response, which typically started on post-operative days 3 or 4; the remaining 6 patients had normal response to aspirin. Compared to aspirin responders, patients with aspirin low response showed significantly higher serum TXB2 levels, a more pronounced early decrease in platelet count, and a significantly more rapid recovery of the platelet count after surgery. Conclusion: Aspirin response variability occurred in patients after major orthopedic surgery, with one-half of the patients in our study exhibiting post-operative aspirin low response. Increased platelet turnover might be a contributor to aspirin response variability after orthopedic surgery.

Summary. Background: Guidelines recommend stopping aspirin and clopidogrel 7 to 10 days before surgery to allow time for replacement of permanently inhibited platelets by newly released uninhibited platelets.Objectives: The purpose of the present study was to determine the rate of offset of the anti-platelet effects of aspirin and clopidogrel after stopping treatment and the proportion of untreated donor platelets that are required to reverse their anti-platelet effects.Methods: Cohort 1 consisted of 15 healthy subjects who received aspirin 81 mg day−1 or clopidogrel 75 mg day−1 for 7 days and underwent serial blood sampling until platelet function testing results normalized. Cohort 2 consisted of 36 healthy subjects who received aspirin 325 mg day−1, clopidogrel 75 mg day−1, aspirin 81 mg day−1 plus clopidogrel 75 mg day−1 or no treatment for 7 days and underwent a single blood sampling.Results: In cohort 1, arachidonic acid (AA)-induced light transmission aggregation (LTA) returned to baseline levels in all subjects within 4 days of stopping aspirin, coinciding with the partial recovery of plasma thromboxane B2 concentrations. ADP-induced LTA did not return to baseline levels until 10 days after stopping clopidogrel. In cohort 2, AA-induced LTA in patient treated with aspirin reached control levels after mixing with 30% untreated donor platelets whereas ADP-induced LTA in patients treated with clopidogrel reached control levels only after the addition of 90% or more donor platelets.Conclusions: Platelet aggregation recovers within 4 days of stopping aspirin but clopidogrel must be stopped for 10 days to achieve a normal aggregatory response.

Summary. Background: The role of D-dimer in excluding deep vein thrombosis (DVT) in pregnancy is currently uncertain. We hypothesized that the specificity of sensitive D-dimer assays could be improved without compromising sensitivity by using higher D-dimer cut-off values. Objective: To determine the test characteristics of two rapid enzyme-linked immunosorbent assays and three latex agglutination assays in pregnancy. Method: We recruited consecutive pregnant women who presented to participating centers with suspected DVT for the study. Symptomatic women were investigated with compression ultrasonography, and received 3 months of clinical follow-up to assess for the presence of venous thrombosis. Plasma samples for D-dimer were collected and frozen at the time of presentation. The median and mean D-dimer values for respective trimesters of pregnancy in patients with and without DVT were calculated. Receiver operating curves (ROCs) were plotted for respective assays to establish the best cut-points. The test characteristics corresponding to standard cut-points and these ‘pregnancy’ cut-points are presented. Results: The prevalence of DVT in our cohort was 6.6% (95% confidence interval 4.0–10.6%). The mean and median D-dimer values were significantly increased throughout pregnancy. Overall, women with confirmed DVT had higher D-dimer levels than women without DVT (P

BACKGROUND: Plasma transfusion is standard therapy for urgent warfarin reversal in the United States. “Four-factor” prothrombin complex concentrate (PCC), available in Europe, has advantages over plasma therapy for warfarin reversal; however, only “three-factor” PCCs (containing relatively low Factor [F]VII) are available in the United States. STUDY DESIGN AND METHODS: The efficacy of a three-factor PCC for urgent warfarin reversal was evaluated in 40 patients presenting with supratherapeutic international normalized ratio (ST-INR > 5.0) with bleeding (n = 29) or at high risk for bleeding (n = 11). In 13 patients, pre- and posttherapy vitamin K-dependent factors were assayed. Historical controls (n = 42) treated with plasma alone were used for rate of ST-INR correction comparison. RESULTS: Treatment with plasma alone (mean, 3.6 units) lowered the INR to less than 3.0 in 63 percent of historical controls. Low-dose (25 U/kg) and high-dose (50 U/kg) PCC alone lowered INR to less than 3.0 in 50 and 43 percent of patients, respectively. Additional transfusion of a small amount of plasma (mean, 2.1 units) increased the rate of achieving an INR of less than 3.0 to 89 and 88 percent for low- and high-dose PCC therapy, respectively. FII, F IX, and FX increments were similar for PCC-treated patients with or without supplemental plasma; FVII was significantly higher in the PCC plus plasma group compared to the PCC-only group (p = 0.001). CONCLUSION: Three-factor PCC does not satisfactorily lower ST-INR due to low FVII content. Infusion of a small amount of plasma increases the likelihood of satisfactory INR lowering.

This paper documents our learning over a 3-year period from students of colour in our M.Ed. certification programme. Students of colour are always a minority (8% to 20%) in our programmes. Despite a variety of efforts, these students continued to complain that we were not meeting their needs or dealing adequately with diversity issues. The students of colour became our cultural consultants as we talked about their perceptions of our teaching and the programme. As two white middle-class professors and one Asian doctoral student, we learned different things from this self-study. Our major recommendation is that students of colour be given a separate space to talk with each other and with those who are teaching them.

The major focus of the paper is devoted to describing a five‐year study of the initial implementation of a nationally adopted integrated curriculum course as it was implemented in one university teacher education programme in Indonesia and, subsequently, the challenges faced in developing a field‐based course that built on the university course. The primary author (Udin Saud) describes his research in Indonesia on the implementation of an innovative professional education course for an integrated curriculum for pre‐service elementary teachers conducted in a teacher education programme and analyses this implementation from his Indonesian perspective. The secondary author (Marilyn Johnston) contributes another perspective, qua his dissertation advisor, as she questions the imposition of ‘western’ ideas into eastern contexts. In this comparative manner issues related to the teacher educators' beliefs and the ‘transportation of ideas’ are both considered.

PurposeThis paper aims to describe a qualitative study of a four‐year, state‐wide portfolio evaluation system for new principals. The State of Ohio (USA) was one of five states that participated in a field test of the Portfolio Assessment for School Leaders designed by the Interstate School Leaders Licensure Consortium (ISLLC) and the Educational Testing Service (ETS).Design/methodology/approachThe central research question was: Does the Portfolio Assessment for School Leaders process benefit or burden the practice of school leaders? The participants were a subset of the 70 principals who completed the portfolio in Ohio between September 1999 and January 2002. The data included focus group interviews, phone interviews, surveys, and the principals' completed portfolios.FindingsFrom analysis of the data three levels of benefits from level 1 are desribed, where the portfolio was seen primarily as extra work and had little benefit for the leadership in the principals' schools, to level 3, where there was a reciprocal benefit between the portfolio process and the principals' growth and developed as leaders.Research limitations/implicationsThis study was limited to one state in the USA, a particular portfolio system, and data were collected from only a subset of principals who completed their portfolios (26 out of 70).Practical implicationsThe results of this research indicated that the portfolio work was seen as professional development by principals only if it was contextualized in a larger supportive social network of professional practice. It was the use of the portfolio to promote professional development that allowed the portfolio to be a learning tool, and not just a tool of policy compliance.Originality/valueThis research adds to the literature on professional development for principals by providing evidence that portfolios can be used with novice principals to support their development as leaders in their schools. It also indicates the kinds of social and professional support necessary to make this work.

Although the incidence and prognostic significance of elevated cardiac troponins are known in patients with massive pulmonary embolism (PE), few studies have addressed this issue in patients with hemodynamically stable, submassive PE, who comprise the majority of patients presenting with PE. This prospective cohort study was, therefore, designed to determine the incidence and prognostic significance of elevated cardiac troponins in patients with submassive PE. Consecutive patients with acute, symptomatic, submassive PE that was confirmed by objective diagnostic testing were studied. All patients received treatment with either unfractionated heparin or fondaparinux followed by a coumarin derivative and underwent clinical follow-up for 3 months. Cardiac troponin I (cTnI) levels were measured within 24 h of clinical presentation. An elevated cTnI was defined as > 0.5 microg L(-1) and indicated myocardial injury. Major myocardial injury, that is associated with myocardial infarction, was defined by a cTnI > 2.3 microg L(-1). The clinical outcomes were recurrent venous thromboembolism and all-cause death. In 458 patients with submassive PE, the incidence of cTnI > 0.5 microg L(-1) was 13.5%[95% confidence interval (CI): 10.4-16.7], and the incidence of cTnI > 2.3 microg L(-1) was 3.5% (95% CI: 2.0-5.6). An elevated cTnI > 0.5 microg L(-1) was associated with an increased risk of all-cause death [odds ratio (OR) = 3.5; 95% CI: 1.0-11.9], but did not appear to confer an increased risk of recurrent venous thromboembolism (OR = 1.1; 95% CI: 0.2-4.9). In patients who present with submassive PE, an elevated cTnI occurs in about one in seven patients and is associated with a 3.5-fold increased risk of all-cause death.

SummaryAbnormalities of the Protein C (PC) pathway are found in the majority of patients with thrombophilia. ProC Global is a coagulation assay that reflects the net effect of the PC pathway by measuring the activated partial thromboplastin time (APTT) of patient and control plasma, before and after activation of endogenous PC by Protac, a snake venom. Previous studies have suggested that abnormalities in this test are associated with an increased risk of venous thromboembolism (VTE). A retrospective analysis was performed using frozen plasma samples from 140 patients with confirmed VTE to determine whether an abnormal ProC Global result (in the presence and in the absence of known abnormalities in the PC pathway) is a predictor of initial and recurrent VTE. Patients were tested for the presence of activated protein C resistance, Factor V Leiden, PC and protein S (PS) deficiency, and non-specific inhibitor positivity. Mean ProC Global results were significantly lower in patients with recurrent VTE than in patients without recurrent VTE. The association between abnormal ProC Global result and recurrent VTE showed a strong trend, before (odds ratio, OR 3.6) and after (OR 3.1) exclusion of known thrombophilic abnormalities. Patients with a first episode of idiopathic VTE also expressed significant lower ProC Global results than those with secondary VTE. After exclusion of known PC pathway abnormalities, there was a statistically significant association between abnormal ProC Global and initial idiopathic VTE (p=0.04). These results suggest that ProC Global may serve as a predictor of recurrent VTE and potentially for first episode of idiopathic VTE. ProC Global may help identify patients at increased risk of initial and recurrent VTE.

Summary. Background: The risk of recurrence is lower after treatment of an episode of venous thromboembolism associated with a transient risk factor, such as recent surgery, than after an episode associated with a permanent, or no, risk factor. Retrospective analyses suggest that 1 month of anticoagulation is adequate for patients whose venous thromboembolic event was provoked by a transient risk factor. Methods: In this double-blind study, patients who had completed 1 month of anticoagulant therapy for a first episode of venous thromboembolism provoked by a transient risk factor were randomly assigned to continue warfarin or to placebo for an additional 2 months. Our goal was to determine if the duration of treatment could be reduced without increasing the rate of recurrent venous thromboembolism during 11 months of follow-up. Results: Of 84 patients assigned to placebo, five (6.0%) had recurrent venous thromboembolism, compared with three of 81 (3.7%) assigned to warfarin, resulting in an absolute risk difference of 2.3%[95% confidence interval (CI) − 5.2, 10.0]. The incidence of recurrent venous thromboembolism after discontinuation of warfarin was 6.8% per patient-year in those who received warfarin for 1 month and 3.2% per patient-year in those who received warfarin for 3 months (rate difference of 3.6% per patient-year; 95% CI − 3.8, 11.0). There were no major bleeds in either group. Conclusion: Duration of anticoagulant therapy for venous thromboembolism provoked by a transient risk factor should not be reduced from 3 months to 1 month as this is likely to increase recurrent venous thromboembolism without achieving a clinically important decrease in bleeding.

In this article we describe a self-study research project. As one professor and six doctoral students, we co-taught a course on action research while doing a self-study of our teaching. We studied ourselves, and our students, as we taught this course. We report on what we learned from this co-teaching and co-researching. We analyze how we worked together, how we conducted the research, and the process used to integrate our individual and collective reflections into a collaborative text. There were common themes in our learning but at times we speak in individual voices because our experiences were not all the same. The co-teaching, the collaborative analysis of our data, and writing about our research were separate aspects of our self-study yet each of these fed our relationships, our thinking about teacher education and action research within it, and our future, and present, lives as university professors in teacher education.

Aims The Clopidogrel in Unstable angina to prevent Recurrent Events (CURE) Study demonstrated that clopidogrel plus aspirin was superior to aspirin alone for prevention of recurrent vascular events in patients with acute coronary syndromes. The aim of this study was to compare the effect of these two regimens on biochemical markers of platelet and coagulation activation. Methods and Results We studied 485 patients with non-ST-elevation acute coronary syndrome who were randomized to clopidogrel (300 mg loading dose followed by 75 mg daily) or placebo for a period of 3-12 months. All patients also received aspirin (recommended dose 75-325 mg daily). Blood levels of P-selectin, prothrombin fragment F1.2, D-dimer, and von Willebrand factor were measured at baseline, day 7 (or hospital discharge), and at day 30 after randomization. Patients receiving clopidogrel plus aspirin compared with aspirin alone had similar baseline geometric mean plasma levels of P-selectin (50.2 vs 51.7 ng. ml - 1 , P=0.45), prothrombin fragment F1.2 (1.13 vs 1.12 nmol.l - 1 , P=0.94), D-dimer (467 vs 460 ng.ml - 1 , P=0.85), and von Willebrand factor levels (1.89 vs 1.85 U.ml - 1 , P=0.59) and there also were no significant differences at day 7, or day 30. However, compared with baseline, there was a significant rise in prothrombin fragment F1.2 at day 7 (from 1.12 to 1.39nmol.l - 1 , P

Background — We studied whether aspirin resistance, defined as failure of suppression of thromboxane generation, increases the risk of cardiovascular events in a high-risk population. Methods and Results — Baseline urine samples were obtained from 5529 Canadian patients enrolled in the Heart Outcomes Prevention Evaluation (HOPE) Study. Using a nested case-control design, we measured urinary 11-dehydro thromboxane B 2 levels, a marker of in vivo thromboxane generation, in 488 cases treated with aspirin who had myocardial infarction, stroke, or cardiovascular death during 5 years of follow-up and in 488 sex- and age-matched control subjects also receiving aspirin who did not have an event. After adjustment for baseline differences, the odds for the composite outcome of myocardial infarction, stroke, or cardiovascular death increased with each increasing quartile of 11-dehydro thromboxane B 2 , with patients in the upper quartile having a 1.8-times-higher risk than those in the lower quartile (OR, 1.8; 95% CI, 1.2 to 2.7; P =0.009). Those in the upper quartile had a 2-times-higher risk of myocardial infarction (OR, 2.0; 95% CI, 1.2 to 3.4; P =0.006) and a 3.5-times-higher risk of cardiovascular death (OR, 3.5; 95% CI, 1.7 to 7.4; P Conclusions — In aspirin-treated patients, urinary concentrations of 11-dehydro thromboxane B 2 predict the future risk of myocardial infarction or cardiovascular death. These findings raise the possibility that elevated urinary 11-dehydro thromboxane B 2 levels identify patients who are relatively resistant to aspirin and who may benefit from additional antiplatelet therapies or treatments that more effectively block in vivo thromboxane production or activity.

This paper describes an action research project conducted in the course of teaching about action research. Eight doctoral students and a professor co-taught the course. We organized it to demonstrate aspects of action research and conducted our research as an example of action research methodology. We shared our proposal, data collection strategies, and beginning data analyses with our students. Our action research project thus served two purposes: (1) it helped us to study our own teaching and the emerging understandings of our students, and (2) it demonstrated action research for our students while they designed their own research proposals.

SummaryLocal ISI calibration has been proposed to improve INR accuracy and inter-laboratory precision. We evaluated the affect of local PT calibration on INR precision and accuracy using six levels of frozen plasma calibrants prepared and pooled from normal donors and patients stabilized on sodium warfarin (coumarin) based oral anticoagulant therapy (OAT). Reference prothrombin time (PT) and INR values were assigned to these calibrants in accordance with World Health Organization (WHO) procedure using rTF 95 international reference preparation (IRP) of thromboplastin (human recombinant). These calibrants, along with five similarly characterized individual OAT patient plasmas, were distributed to 127 laboratories in a multi-center study. Calibrant plasmas were evaluated and INR’s subsequently determined on the 5 OAT test samples using: 1) the ISI and MNPT in place before the study (the local system), 2) the locally calibrated ISI value (local system with ISI calibration) and 3) a PT-INR calibration curve. Precision of INR results improved across the study group using the local system with ISI calibration and the PT-INR calibration curve methods, while accuracy of INR results improved using the PT-INR calibration curve approach only and not the local ISI calibration. The authors conclude that frozen plasma calibrants can be used locally to enhance precision and accuracy of PT results as reported in INR. These calibrants are effective over a range of reagents and instrument combinations. Furthermore, the PT-INR calibration curve appears to be the superior method for local calibration.

SummaryPregnancy is associated with a physiological increase in coagulation factors and heparin binding proteins; both can affect the activated partial thromboplastin time (APTT) in response to unfractionated heparin (UFH) invalidating the use of a non-pregnant APTT therapeutic range. We compared the anticoagulant response of UFH added in vitro to the plasma of 13 pregnant (third trimester) and 15 nonpregnant women to determine whether the measured APTT and antifactor Xa activities are lower in pregnancy. Increasing concentrations of UFH were added to platelet-poor plasma from each subject and the APTT and anti-factor Xa activity were measured. The amount of UFH which was reversibly bound and neutralised by plasma heparin binding proteins was assessed by comparing the anti-factor Xa activity before and after addition of low affinity heparin (LAH). Fibrinogen, von Willebrand factor antigen (vWF Ag) and factor VIII levels, were also measured. The APTT response, assessed by the slope of the regression line of log APTT versus added heparin concentration, was attenuated in pregnant plasma (0.76 s/U/mL versus 1.2 s/U/mL, p = 0.005) and was highly correlated to increased non-specific plasma protein binding (47% versus 35% p

In this chapter we describe a process of using dialogue to construct and re-construct interpretations in narrative inquiry. We used narrative and dialogue as partners in the pursuit of learning, what Bakhtin called ‘consciousness.’ Our approach to inquiry was collaborative and well suited to research that is multivocal and socially critical. We define dialogue as more than comfortable talk or questions/answers in an interview; it requires a willingness to ask hard questions, learn from differences, and maybe change one’s mind. It is nurtured by trust and openness. Dialogue carries ethical considerations and is burdened by the acknowledgement that learning involves taking risks and will likely call one’s assumptions and meanings into question. To develop our chapter, we used narrative in the initial telling of research stories. As authors (a professor and five U.S. and international doctoral student advisees) we narrated our individual research plans and experiences using dialogue to interrogate what we were writing and learning. We considered our work together as both a theoretical and methodological project that involved a particular approach to dialogue in narrative inquiry that was necessarily highly interpretation throughout. This process led us to new ways of thinking about dialogue in narrative inquiry as well as new methods to make our research more thoroughly narrative.

Background: Clinical situations occur where expedient assessment of the anticoagulant activity of the direct factor Xa (FXa) inhibitors is required. Although quantitative anti-FXa (FXa) assays can be used to measure plasma levels of apixaban or rivaroxaban, turnaround is often slow and many laboratories do not perform these assays. Objective: We compared the in vitro effects of apixaban and rivaroxaban on two readily available laboratory tests, the prothrombin time (PT) and activated partial thromboplastin time (APTT), performed with different reagents. We aimed to identify the most sensitive reagents. Methods: Rivaroxaban or apixaban was added to human plasma at a range of concentrations covering expected peak and trough levels, and concentrations were confirmed using calibrated anti-FXa assays. Samples were assayed with six PT and seven APTT reagents using different coagulometers. Results and Conclusions: TriniCLOT PT Excel S was the only reagent to demonstrate sensitivity to apixaban. All of the PT reagents were sensitive to rivaroxaban with TriniCLOT PT Excel S and HemosIL HS PLUS being the most sensitive. Sensitivity to rivaroxaban varied among APTT reagents; four reagents exhibited the greatest responsiveness, and of these, Actin FSL was the most responsive. Commonly used coagulation tests may be useful for assessing the anticoagulant effect of rivaroxaban but not of apixaban. The reason for the different effects of apixaban and rivaroxaban on the PT and APTT is unknown. Refereed/Peer-reviewed

SummaryTo determine whether fibrinolytic testing predicts recurrent venous thrombosis, we have performed a prospective cohort study in which 303 patients with a first episode of venous thromboembolism underwent comprehensive fibrinolytic testing while receiving oral anticoagulants, and after anticoagulants had been discontinued. They were then followed for up to 3 years for recurrent venous thrombosis. No systematic differences in the levels or activity of type 1 plasminogen activator inhibitor (PAI-1), tissue plasminogen activator (tPA) or euglobulin clot lysis times were detected between patients who did, or did not, suffer recurrent thrombosis. There were also no differences in these variables when patients whose initial thrombosis was idiopathic were compared to patients whose thrombosis occurred in the setting of a known thrombotic risk factor. Based on these results, neither measuring fibrinolytic parameters in patients with venous thromboembolism, nor modification of treatment based on the results of such testing, are justified. Our study also confirms that patients with idiopathic venous thromboembolism have a high risk of recurrence.

Recent studies have found that hormone replacement therapy (HRT) is associated with a two- to fourfold increased risk of venous thromboembolism, but the thrombogenic mechanism of HRT remains unclear. To investigate whether HRT use induces a procoagulant state, we undertook a prospective cohort study in postmenopausal women to investigate the effects of 3 months of treatment with oral HRT (conjugated equine estrogen 0.625 mg daily and medroxyprogesterone 2.5 mg daily) on markers of thrombin generation (prothrombin fragment 1+2, thrombin–antithrombin complexes), fibrinolytic potential (plasminogen activator inhibitor-1 (PAI-1) activity), and activated protein C (APC) resistance. In addition, we reviewed the literature for studies investigating the effects of HRT on markers of thrombin generation and fibrinolytic potential. In 12 patients who received HRT for a mean of 3.8 months, there was no significant effect of HRT on levels of F1+2, thrombin–antithrombin complexes, or the APC ratio. HRT use had the greatest effect on PAI-1 activity (mean difference=−3.76 IU/mL; 95% confidence interval: −8.9, 1.1) compared to other coagulation parameters, but this did not attain statistical significance p=0.12 . In the literature review, the effects of HRT on markers of thrombin generation were inconsistent across studies. There was a consistent pattern of increased fibrinolytic potential with HRT use associated with one marker (PAI-1), but not with another marker (tissue plasminogen activator antigen). We conclude that there is a lack of consistence evidence that the increased risk of venous thromboembolism associated with HRT use is due to a procoagulant state related to increased thrombin generation, decreased fibrinolytic potential, or acquired APC resistance.

Anticoagulant therapy during pregnancy is problematic. Patients are frequently treated with long-term low-molecular weight heparin despite a lack of evidence for its effectiveness, and in the absence of validated dosing recommendations. The objectives of this investigation were to characterize the safety and pharmacokinetic behavior of a low-molecular weight heparin (reviparin) administered throughout pregnancy. Forty-two patients followed in a tertiary-care rheumatology clinic who received prophylactic doses of reviparin (4900 anti-Xa units subcutaneously once daily) were enrolled in this investigation. Anti-Xa heparin levels, weights, and gestational ages of the patients were obtained on up to four occasions distributed throughout their pregnancy. The achieved anti-Xa heparin levels were highly correlated with the patient's weight, irrespective of the gestational age. No toxicity other than injection site hematomas was observed. The achieved intensity of anticoagulation with reviparin varies during pregnancy in direct proportion to the patient's weight. This variability may mandate dose adjustment in response to changes in a patient's weight during pregnancy, particularly if low-molecular weight heparin is administered at therapeutic doses.

SummaryOur study compared point-of-care (POC) device monitoring with traditional clinical laboratory methods device of patients on oral anticoagulant therapy. The POC devices used in the study were Coumatrak, CoaguChek, CoaguChek Plus, Thrombolytic Assessment System (TAS) PT-One, TAS PTNC, TAS PT, Hemachron Jr. Signature, Protime Microcoagulation System, and Medtronics ACT II. The clinical laboratory method used thromboplastins with different ISI values: Innovin and Thromboplastin C Plus (TPC). All POC INRs showed strong correlation with both laboratory methods, with correlation coefficients of >0.900. All POC methods demonstrated a significant (p 0.93), but there were still significant (p

Background Patients who have a first episode of venous thromboembolism in the absence of known risk factors for thrombosis (idiopathic thrombosis) are often treated with anticoagulant therapy for three months. Such patients may benefit from longer treatment, however, because they appear to have an increased risk of recurrence after anticoagulant therapy is stopped. Methods In this double-blind study, we randomly assigned patients who had completed 3 months of anticoagulant therapy for a first episode of idiopathic venous thromboembolism to continue receiving warfarin, with the dose adjusted to achieve an international normalized ratio of 2.0 to 3.0, or to receive placebo for a further 24 months. Our goal was to determine the effects of extended anticoagulant therapy on rates of recurrent symptomatic venous thromboembolism and bleeding. Results A prespecified interim analysis of efficacy led to the early termination of the trial after 162 patients had been enrolled and followed for an average of 10 months....

The physiology of the hemostatic system in children is different from that in adults. Reference ranges for components of the hemostatic system are age dependent. During early childhood, physiologic values may overlap with values observed in congenital deficiencies of acquired pathological conditions. Physiologically decreased plasma concentrations of hemostatic components also influence the response to antithrombotic therapy. The relevance of developmental hemostasis for the laboratory diagnosis and management of hemorrhagic and thrombotic disorders during childhood is discussed.

In this article, we describe our initial apprehensions, difficulties of working across our differences, and changes in our understandings and teaching practice as we collaboratively taught a social studies methods course. We began with stereotypes of each other implied by our university/school and professor/graduate student/classroom teacher roles. After 4 years of working together, we have come to understand our positions, knowledge, and expertise in different ways and as a result have changed our teaching. We began our co-teaching experience as members of a Professional Development School (PDS) project. In this PDS, university faculty, graduate associates, school principals, and class, room teachers work closely to construct and evaluate the redesign of the university's elementary teacher education programs. One important aspect of this collaboration is co-teaching the methods courses for the M aster of Education certification students in the program. Classroom teachers, doctoral students, and university professors make shared decisions about course syllabi, assignments, and evaluation to bring theory and practice into a productive dialogue. Despite initial support for co-teaching the methods courses, both university faculty and classroom teachers were reluctant. Classroom teachers were uncertain about working with university faculty, about the time necessary for planning, and especially about leaving their classrooms for half a day each week. University faculty were hesitant to relinquish their autonomy and worried about the time required to team teach. These hesitancies resulted in less concern about teachers' expertise in the subject area and more on their willingness to participate. Rather than participating in a formal selection process, faculty and teachers were asked to volunteer; decisions about which teachers would teach with which faculty were left to informal negotiations. This article focuses on the co-teaching of a social studies methods course. We do not include practical descriptions of how we organized the social studies course, the students' evaluations of the course, or assessment of student learning. This is not to deny the importance of student outcomes that we discuss in other work in progress, but to situate this study within the literature on collaborative work and professional development. Studies of teachers' professional development supported our interest in looking at our own learning and development. Traditionally evaluation of change initiatives have considered classroom instruction and student performance more than the teachers who managed the learning environments. Attention to teachers' growth and development has been slow in coming, particularly studies that include self-study and reflection. Recently, researchers have been using case studies, collaborative methodologies, narrative forms, and feminist theories to look at the complexities and perspectives of teachers (Miller, 1990; Witherell & Noddings, 1991). Action research is enjoying a resurgence, and teachers are increasingly studying and publishing reports on their own teaching and beliefs (Bricher, Hawk, & Tingley, 1993; Nalle, 1993; Paley, 1989). Journals are increasingly including collaborative studies by teachers or between teachers and researchers (Gitlin, 1992; Hunsaker & Johnston, 1992). Greene (1988) argues that stories--and myths, and diaries, and histories--give shape and expression to what would otherwise be untold about `our lives' (p. x). Multiple forms of expression help to reveal the complexities of personal lives as they are reflected in professional lives and development. These studies point to the value of teachers considering their own thinking and teaching as sites for reflection, inquiry, and change. The authors (Lisa Westhoven, a classroom teacher; JoAnn Hohenbrink, a graduate teaching associate; and Marilyn Johnston, a professor) co-taught a two-quarter course for 2 years (1991-1993). …

FTER 5 YEARS of collaborative involvement in a professional development school (PDS) project,' those of us who write this article have learned that collaboration is not what we thought it was. It involves much more than just talking and working together, and it is more complicated than simply "bridging the differences" that separate schools and universities. We now believe that collaboration is about altering relationships, not just among ourselves but with everyone with whom we come into contact. Collaboration, in short, is a powerful means of significant and lasting personal growth that may, through our other relationships, lead to substantial organizational change. In this article we write from the perspectives of five people who have taken on new roles and responsibilities. Four of us-Mike, Francee, Kathy and Mary-write as clinical educators, teachers who are released from normal duties for some percentage of time to do PDS work. One of us, Marilyn, writes from the perspective of a collaborating college faculty member. By assuming these new and ambiguous roles without abandoning our prior institutional roles, we have come to see ourselves and our work

SummaryIn order to determine the clinical utility of an enzyme immunoassay (EIA) for soluble fibrin in patients with suspected pulmonary embolism (PE), 195 unselected patients with suspected PE underwent blood sampling for measurement of plasma levels of soluble fibrin, and objective testing for PE. A soluble fibrin result of ≤ 0.75 Μg/ml showed a sensitivity of 100% for PE and a specificity of 12.8%, whereas a soluble fibrin result of ≤ 1.35 Μg/ml showed a sensitivity of 90.3% and a specificity of 49.4% for PE. The soluble fibrin assay has potential clinical utility in excluding PE.

The clinical relevance of antiphospholipid antibodies (APLA) in patients without systemic lupus erythematosus who have venous thromboembolism (VTE) in unknown. Limited evidence suggests that there is an association between the presence of APLA and both initial and recurrent episodes of VTE and that patients with APLA and VTE are resistant to warfarin therapy. Unselected patients with a first episode of clinically suspected deep vein thrombosis or pulmonary embolism were evaluated with objective tests for VTE and with laboratory tests for APLA; the latter included tests for the lupus anticoagulant (LA) and anticardiolipin antibodies (ACLA). Patients with VTE were treated with anticoagulant therapy and observed during and after discontinuation of anticoagulants for symptomatic recurrence of VTE. There was a strong association between LA and VTE (odds ratio, 9.4; 95% confidence interval [CI], 2.1 to 46.2) and 9 to 65 (14%; 95% CI, 7% to 25%) patients with VTE had LA. There was no association between the presence of ACLA and VTE (odds ratio, 0.7; 95%CI, 0.3 to 1.7) because of the high frequency of positive ACLA assays in patients without VTE. None of the 16 patients with VTE and APLA developed recurrent VTE while receiving warfarin therapy. There was no difference in rates of recurrent VTE in patients with or without APLA after anticoagulant therapy was discontinued. The strong association between LA and VTE suggests that testing for LA in patients with VTE is useful. The measurement of ACLA in patients with VTE has no clinical usefulness because the results are abnormal in a high proportion of patients without VTE. Although the presence of APLA in patients with VTE was not associated with resistance to a conventional intensity of warfarin or an increased risk of recurrent VTE after discontinuation of warfarin, a larger study should address these issues in a subgroup of patients with VTE and LA.

SummaryBackground. The objective of this study was to determine the clinical utility of an enzyme immunoassay (HIA) for soluble fibrin in patients with clinically suspected deep vein thrombosis (DVT).Methods and Results. 101 unselected patients with clinically suspected DVT underwent blood sampling for measurement of plasma levels of soluble fibrin, and objective testing for DVT. According to results of the objective tests, patients were classified as DVT-positive (n = 34) or DVT-negative (n = 67). Using different cut-points of soluble fibrin results, the sensitivities, specificities, positive and negative predictive values of the soluble fibrin assay were calculated. A soluble fibrin result of ≤0.75 mg/ml showed a sensitivity and negative predictive value of 100%, and a specificity of 17.9% for DVT, a soluble fibrin result of ≤ 1.40 mg/ml showed a sensitivity of 91.2% and a negative predictive value of 93.6%, and a specificity of 65.7% for DVT, whereas a soluble fibrin result of ≤ 8.0 mg/ml showed a specificity and positive predicive value of 100% for DVT.Conclusions. This study demonstrates that the soluble fibrin assay used in the study has potential clinical utility as a diagnostic test in patients with clinically suspected DVT and supports further evaluation of this assay.

Clopidogrel is a prodrug that undergoes bioconversion via cytochrome P450 system to form an active metabolite (AM) that binds to the platelet ADP receptor. The antiplatelet effect of clopidogrel is commonly assessed by measuring the aggregatory response to 5 μM ADP by light transmission aggregation (LTA) or multiple electrode aggregometry (MEA) or by the vasodilator-stimulated phosphoprotein platelet reactivity index (VASP-PRI). To determine which of these three tests of platelet ADP receptor pathway inhibition most closely correlates with clopidogrel AM levels. We analyzed blood samples from 82 patients with coronary artery disease who were randomized to receive double-dose or standard dose clopidogrel for 2 weeks. We measured peak clopidogrel AM levels, platelet aggregation in response to ADP and VASP-PRI on days 1, and repeated all the measures on days 7 and 14. Linear regression analysis was used to examine the correlation between clopidogrel AM and LTA, MEA and VASP-PRI. Bland-Altman plots were used to explore the agreement between tests of the antiplatelet effects of clopidogrel. Clopidogrel AM on day 1 correlated most closely with VASP-PRI (r = -0.5767) and demonstrated weaker correlations with LTA (r = -0.4656) and MEA (r = -0.3384) (all p

(1994). Postmodern Considerations of School/University Collaboration. Teaching Education: Vol. 6, No. 2, pp. 99-106.

A 68-year-old man on chronic hemodialysis for 6 years, presented with a spontaneous psoas muscle hemorrhage. Investigations showed intermittently elevated activated partial-thromboplastin time and thrombin time. Preliminary investigations suggested a heparin-like inhibitor in the patient's plasma, but no anti-Xa activity could be detected. Investigation of the ability of patient plasma to inhibit exogenous thrombin showed that most thrombin was inhibited by heparin cofactor II, in contrast to normal plasma in which most thrombin was inhibited by antithrombin III. Treatment of plasma with glycosaminoglycan-degrading enzymes suggested the presence of dermatan sulfate (DS) in patient plasma. This was confirmed in a heparin cofactor II-dependent antithrombin assay for DS that showed anticoagulant equivalent to 2.2 +/- 0.3 micrograms/mL (mean +/- SD) of porcine mucosal DS. Of this activity, approximately 90% was sensitive to enzymes that degrade DS. The glycosaminoglycan containing fraction of plasma was isolated and subjected to gel chromatography. Anticoagulant activity eluted from Sephadex G-100 (Pharmacia, Montreal, Quebec, Canada) as two peaks with Kav of 0.10 and 0.45. After treatment with base, the Kav of the higher molecular weight species was increased to 0.55. This activity was completely sensitive to enzymes that degrade DS. Thus, the active DS was present as a proteoglycan. The lower molecular weight material was not sensitive to enzymes that degrade DS or heparan sulfate and it was active in the heparin cofactor II- dependent antithrombin assay but not in an antithrombin III-dependent antithrombin assay. This activity was not degraded by heating. Subsequently, measurement of DS activity was performed in plasmas obtained from eight other patients on hemodialysis before administration of heparin that showed that all patients had DS activity present that varied from 0.05 to 0.4 microgram/mL. No enzyme-resistant activity could be shown in these patients. In summary, a circulating anticoagulant with properties of DS is present in patients requiring hemodialysis.

This 5-year case study of teacher change documents an elementary classroom teacher's transition from a personal to a professional perspective. In this transition she moves from classroom concerns that feel individually determined to an awareness of the historical and socio-political nature of educational ideas and teaching practices. The teacher and researchers' interpretations of this transition are each included and their process of collaboration to construct them is described.

SummaryHeparin therapy for children undergoing cardiopulmonary bypass (CPB) is monitored in the operating room by automated whole blood activated clotting times (ACT). For many years our institution used Hemochron (HC) ACT machines but changed to HemoTec (HT) ACT machines because they required a smaller blood sample and provided results in duplicate. When HemoTec ACT machines were introduced at our institution, the surgical team was concerned that increased amounts of heparin were being administered to our patients during CPB. This study was conducted to investigate the potential mechanisms responsible for these clinical observations. First, we compared ACT values on ex vivo blood samples from 20 consecutive pediatric patients (6 samples each) during CPB. The HC ACT values were significantly and systematically increased over HT ACT values (HC: 750 ± 40 vs HT: 418 ± 26, Mean ± SEM, p

SummaryBackground: Disseminated intravascular coagulation (DIC) is usually diagnosed in sick infants who have prolonged clotting times, depletion of platelets and coagulation factors, and elevated levels of fibrin derivatives. However, the diagnostic accuracy of abnormal coagulation profiles in neonates at risk of DIC has been uncertain. Since DIC is characterized by activation of both the coagulation and fibrinolytic systems, the objective of this study was to determine whether coagulation screening tests correctly identify infants with biochemical evidence of increased thrombin and plasmin generation.Methods: Non-surgical patients in a tertiary care nursery who were sick enough to require an indwelling arterial catheter for monitoring purposes, were enrolled in a prospective cohort study. Blood samples for thrombin/antithrombin III (TAT) complexes and the plasmin-derived fibrinopeptide Bβ1-42 were drawn 36 to 72 h after birth from a free-flowing arterial line. Platelet counts, D-Dimer levels, plasma fibrinogen concentrations and prothrombin times, expressed as International Normalized Ratios or INR, were measured at the same time.Results: One hundred patients were studied. Fifty-seven infants had elevated levels of TAT (≥4 μg/l) and Bβ1-42 (≥4 nmol/l). The sensitivities of platelets 500 ng/ml, fibrinogen 1.5 were 39%, 30%, 12%, and 11%, respectively. Corresponding specificities were 88%, 91%, 98%, and 95%.Conclusions: Abnormal coagulation screens in sick newborn infants strongly support a diagnosis of DIC. However, normal screens do not exclude activation of the coagulation and fibrinolytic systems.