Contract Governance and the Canadian Public Sector

This essay examines the changing character of public sector work in the Canadian federal public service context. It is based on an empirical examination of various forms of contractual relations currently operative within the Canadian state and on a comparative approach of other western liberal state reform initiatives. We argue that contract governance is an ongoing process involving distinct interrelations between the public and private sectors. In this context, we identify various forms of contract governance and flexibility schemes that have been enfolded and refolded into the conventional structures of governance, and unfolded into a liminal space between the state and civil society through the establishment of nonstandard work and the creation of alternative service delivery programmes

Heart Rate or Beta-Blocker Dose? Association With Outcomes in Ambulatory Heart Failure Patients With Systolic Dysfunction Results From the HF-ACTION Trial

AbstractObjectivesThis study aimed to compare whether reduced heart rate (HR) or higher beta-blocker (BB) dose affected outcomes to a greater extent in the HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training) trial population.BackgroundRecent data have shown that HR is an important modifiable factor in reducing mortality in heart failure (HF) patients. It has also been shown that titration of doses of BBs improves outcomes of morbidity and mortality in chronic HF patients with reduced ejection fraction. We aimed to compare whether reduced HR or higher BB dose affected outcomes to a greater extent in the HF-ACTION trial population.MethodsHF-ACTION was a randomized, multicenter trial enrolling 2,331 ambulatory HF patients with systolic dysfunction (New York Heart Association functional class II to IV, left ventricular ejection fraction <0.35) randomized to exercise training versus usual care, with median follow-up of 2.5 years. BB dose at baseline was standardized by use of carvedilol equivalents. BB dose and HR were analyzed by discrete groups (higher/lower dose; higher/lower HR). The relationship of BB dose, HR, and the primary endpoint of all-cause mortality or all-cause hospitalization and other cardiovascular secondary endpoints were determined before and after adjustment for variables found to be significantly associated with outcome in the HF-ACTION cohort.ResultsThere was a significant inverse relationship between either BB dose (higher was better) or HR (lower was better) and all-cause death or hospitalization in unadjusted analysis; however, only BB dose was significant for improved mortality outcomes. After adjustment for other predictors of outcome, only BB dose remained significant for improving all-cause death or hospitalization. BB dose, but not HR, was associated with improved outcomes of other cardiovascular endpoints in unadjusted analysis but did not remain significant when adjusted for other predictors of outcome in this cohort.ConclusionsThere were more associated improvements in outcomes with higher BB dose than with reduced HR in this well-treated HF cohort with systolic dysfunction, which suggests that titration of BB doses may confer a greater benefit than reduction of HR in such patients. (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training [HF-ACTION]; NCT00047437

A combined clinical and biomarker approach to predict diuretic response in acute heart failure

Background: Poor diuretic response in acute heart failure is related to poor clinical outcome. The underlying mechanisms and pathophysiology behind diuretic resistance are incompletely understood. We evaluated a combined approach using clinical characteristics and biomarkers to predict diuretic response in acute heart failure (AHF). Methods and results: We investigated explanatory and predictive models for diuretic response—weight loss at day 4 per 40 mg of furosemide—in 974 patients with AHF included in the PROTECT trial. Biomarkers, addressing multiple pathophysiological pathways, were determined at baseline and after 24 h. An explanatory baseline biomarker model of a poor diuretic response included low potassium, chloride, hemoglobin, myeloperoxidase, and high blood urea nitrogen, albumin, triglycerides, ST2 and neutrophil gelatinase-associated lipocalin (r2 = 0.086). Diuretic response after 24 h (early diuretic response) was a strong predictor of diuretic response (β = 0.467, P &lt; 0.001; r2 = 0.523). Addition of diuretic response after 24 h to biomarkers and clinical characteristics significantly improved the predictive model (r2 = 0.586, P &lt; 0.001). Conclusions: Biomarkers indicate that diuretic unresponsiveness is associated with an atherosclerotic profile with abnormal renal function and electrolytes. However, predicting diuretic response is difficult and biomarkers have limited additive value. Patients at risk of poor diuretic response can be identified by measuring early diuretic response after 24 h

Serum potassium levels and outcome in acute heart failure (data from the PROTECT and COACH trials)

Serum potassium is routinely measured at admission for acute heart failure (AHF), but information on association with clinical variables and prognosis is limited. Potassium measurements at admission were available in 1,867 patients with AHF in the original cohort of 2,033 patients included in the Patients Hospitalized with acute heart failure and Volume Overload to Assess Treatment Effect on Congestion and Renal FuncTion trial. Patients were grouped according to low potassium (&lt;3.5 mEq/l), normal potassium (3.5 to 5.0 mEq/l), and high potassium (&gt;5.0 mEq/l) levels. Results were verified in a validation cohort of 1,023 patients. Mean age of patients was 71 – 11 years, and 66% were men. Low potassium was present in 115 patients (6%), normal potassium in 1,576 (84%), and high potassium in 176 (9%). Potassium levels increased during hospitalization (0.18 – 0.69 mEq/l). Patients with high potassium more often used angiotensin-converting enzyme inhibitors and mineralocorticoid receptor antagonists before admission, had impaired baseline renal function and a better diuretic response (p [ 0.005), independent of mineralocorticoid receptor antagonist usage. During 180-day follow-up, a total of 330 patients (18%) died. Potassium levels at admission showed a univariate linear association with mortality (hazard ratio [log] 2.36, 95% confidence interval 1.07 to 5.23; p [ 0.034) but not after multivariate adjustment. Changes of potassium levels during hospitalization or potassium levels at discharge were not associated with outcome after multivariate analysis. Results in the validation cohort were similar to the index cohort. In conclusion, high potassium levels at admission are associated with an impaired renal function but a better diuretic response. Changes in potassium levels are common, and overall levels increase during hospitalization. In conclusion, potassium levels at admission or its change during hospitalization are not associated with mortality after multivariate adjustment

Reliability of Striatal [11C]Raclopride Binding in Smokers Wearing Transdermal Nicotine Patches

PURPOSE: In studies where [(11)C]raclopride (RAC) positron emission tomography (PET) is used to assess changes in striatal dopamine, it is important to control for cognitive states, such as drug craving, that could alter dopamine levels. In cigarette smokers, transdermal nicotine patches (TNP) can control nicotine craving, but the effects of nicotine patches on RAC binding are unknown. Thus, we sought to determine the test-retest reliability of RAC binding in the presence of nicotine patches. METHODS: Eleven male smokers were scanned twice with RAC on separate days while wearing TNP. RESULTS: Across the striatum, test-retest variability was 7.63 ± 5.88; percent change in binding potential was 1.11 ± 9.83; and the intraclass correlation coefficient was 0.91 (p < 0.0001). CONCLUSION: Baseline RAC binding is highly reproducible in smokers wearing nicotine patches. This suggests that TNP are an acceptable method for controlling cigarette craving during studies that utilize RAC to examine changes in dopamine

Statistical methodologies to pool across multiple intervention studies

Combining and analyzing data from heterogeneous randomized controlled trials of complex multiple-component intervention studies, or discussing them in a systematic review, is not straightforward. The present article describes certain issues to be considered when combining data across studies, based on discussions in an NIH-sponsored workshop on pooling issues across studies in consortia (see Belle et al. in Psychol Aging, 18(3):396-405, 2003). Several statistical methodologies are described and their advantages and limitations are explored. Whether weighting the different studies data differently, or via employing random effects, one must recognize that different pooling methodologies may yield different results. Pooling can be used for comprehensive exploratory analyses of data from RCTs and should not be viewed as replacing the standard analysis plan for each study. Pooling may help to identify intervention components that may be more effective especially for subsets of participants with certain behavioral characteristics. Pooling, when supported by statistical tests, can allow exploratory investigation of potential hypotheses and for the design of future interventions

Autoantibodies Produced at the Site of Tissue Damage Provide Evidence of Humoral Autoimmunity in Inclusion Body Myositis

Inclusion body myositis (IBM) belongs to a group of muscle diseases known as the inflammatory myopathies. The presence of antibody-secreting plasma cells in IBM muscle implicates the humoral immune response in this disease. However, whether the humoral immune response actively contributes to IBM pathology has not been established. We sought to investigate whether the humoral immune response in IBM both in the periphery and at the site of tissue damage was directed towards self-antigens. Peripheral autoantibodies present in IBM serum but not control serum recognized self-antigens in both muscle tissue and human-derived cell lines. To study the humoral immune response at the site of tissue damage in IBM patients, we isolated single plasma cells directly from IBM-derived muscle tissue sections and from these cells, reconstructed a series of recombinant immunoglobulins (rIgG). These rIgG, each representing a single muscle-associated plasma cell, were examined for reactivity to self-antigens. Both, flow cytometry and immunoblotting revealed that these rIgG recognized antigens expressed by cell lines and in muscle tissue homogenates. Using a mass spectrometry-based approach, Desmin, a major intermediate filament protein, expressed abundantly in muscle tissue, was identified as the target of one IBM muscle-derived rIgG. Collectively, these data support the view that IBM includes a humoral immune response in both the periphery and at the site of tissue damage that is directed towards self-antigens

Prognostic significance of creatinine increases during an acute heart failure admission in patients with and without residual congestion

Background: The importance of a serum creatinine increase, traditionally considered worsening renal function (WRF), during admission for acute heart failure has been recently debated, with data suggesting an interaction between congestion and creatinine changes. Methods and Results: In post hoc analyses, we analyzed the association of WRF with length of hospital stay, 30-day death or cardiovascular/renal readmission and 90-day mortality in the PROTECT study (Placebo-Controlled Randomized Study of the Selective A1 Adenosine Receptor Antagonist Rolofylline for Patients Hospitalized With Acute Decompensated Heart Failure and Volume Overload to Assess Treatment Effect on Congestion and Renal Function). Daily creatinine changes from baseline were categorized as WRF (an increase of 0.3 mg/dL or more) or not. Daily congestion scores were computed by summing scores for orthopnea, edema, and jugular venous pressure. Of the 2033 total patients randomized, 1537 patients had both available at study day 14. Length of hospital stay was longer and 30-day cardiovascular/renal readmission or death more common in patients with WRF. However, these were driven by significant associations in patients with concomitant congestion at the time of assessment of renal function. The mean difference in length of hospital stay because of WRF was 3.51 (95% confidence interval, 1.29–5.73) more days (P=0.0019), and the hazard ratio for WRF on 30-day death or heart failure hospitalization was 1.49 (95% confidence interval, 1.06–2.09) times higher (P=0.0205), in significantly congested than nonsignificantly congested patients. A similar trend was observed with 90-day mortality although not statistically significant. Conclusions: In patients admitted for acute heart failure, WRF defined as a creatinine increase of ≥0.3 mg/dL was associated with longer length of hospital stay, and worse 30- and 90-day outcomes. However, effects were largely driven by patients who had residual congestion at the time of renal function assessment

Retrospective and prospective assessments of gambling-related behaviors across the female menstrual cycle

Background and aims: Despite increases in female gambling, little research investigates female-specific factors affecting gambling behavior (GB). Although research suggests that some addictive behaviors may fluctuate across menstrual cycle phase (MCP), gambling requires further investigation. In two studies, we examined associations between MCP and three risky GBs: time spent gambling, money spent gambling, and the probability of consuming alcohol while gambling. Associations between MCP and negative affect were also examined in Study 2. We predicted that, consistent with self-medication theory, increases in negative affect (Study 2) and risky GBs (Studies 1 and 2) would occur premenstrually/menstrually relative to other phases. Methods: Data were obtained from 33 female gamblers using a retrospective timeline followback procedure (Study 1) and from 20 female gamblers using a prospective 32-day, daily diary method (Study 2). In Study 2, salivary progesterone levels verified self-reported MCP validity. Results: Findings revealed significant, but somewhat inconsistent, MCP effects on GBs across studies. The self-medication hypothesis was partially supported. Increases relative to another MCP(s) were found for alcohol consumption while gambling premenstrually, time spent gambling menstrually/premenstrually, money spent gambling menstrually, and negative affect premenstrually. Unexpectedly, findings more consistently indicated that GBs increased during ovulation, suggestive of enhanced reward sensitivity. Progesterone assays validated self-reported MCP (Study 2). Discussion and conclusions: The results suggest a role of ovarian hormones on negative affect and GBs in females. This research could lead to the identification of female-specific factors affecting gambling and the development of more effective interventions for females with, or at risk for, problematic gambling