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Sources of error in measurement of minimal residual disease in childhood acute lymphoblastic leukemia
Get PDFThis is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Introduction
The level of minimal residual disease (MRD) in marrow predicts outcome and guides treatment in childhood acute lymphoblastic leukemia (ALL) but accurate prediction depends on accurate measurement.
Methods
Forty-one children with ALL were studied at the end of induction. Two samples were obtained from each iliac spine and each sample was assayed twice. Assay, sample and side-to-side variation were quantified by analysis of variance and presumptively incorrect decisions related to high-risk disease were determined using the result from each MRD assay, the mean MRD in the patient as the measure of the true value, and each of 3 different MRD cut-off levels which have been used for making decisions on treatment.
Results
Variation between assays, samples and sides each differed significantly from zero and the overall standard deviation for a single MRD estimation was 0.60 logs. Multifocal residual disease seemed to be at least partly responsible for the variation between samples. Decision errors occurred at a frequency of 13–14% when the mean patient MRD was between 10−2 and 10−5. Decision errors were observed only for an MRD result within 1 log of the cut-off value used for assessing high risk. Depending on the cut-off used, 31–40% of MRD results were within 1 log of the cut-off value and 21–16% of such results would have resulted in a decision error.
Conclusion
When the result obtained for the level of MRD is within 1 log of the cut-off value used for making decisions, variation in the assay and/or sampling may result in a misleading assessment of the true level of marrow MRD. This may lead to an incorrect decision on treatment
Opposing effects of rheumatoid arthritis and low dose prednisolone on arginine metabolomics
Get PDFThis manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
This author accepted manuscript is made available following 12 month embargo from date of publication (Oct 2017) in accordance with the publisher’s archiving policyBackground and aims
The effects of low dose prednisolone on circulating markers of endothelial function, the arginine metabolites asymmetric dimethyl arginine (ADMA), mono methyl arginine (MMA), and homoarginine, are uncertain. We assessed whether patients with rheumatoid arthritis have perturbations in arginine metabolite concentrations that are reversed by low dose prednisolone.
Methods
Eighteen rheumatoid arthritis patients who had not taken prednisolone for >6 months (non-glucocorticoid (GC) users), 18 rheumatoid arthritis patients taking continuous oral prednisolone (6.5 ± 1.8 mg/day) for >6 months (GC users) and 20 healthy controls were studied. Fasting plasma concentrations of ADMA, MMA, and homoarginine were measured by ultra-performance liquid-chromatography. Baseline data from non-GC users were compared with healthy controls to assess the effect of rheumatoid arthritis. The change in arginine metabolites in non-GC users after 7 days of prednisolone (6 mg/day) was used to assess the acute effects of prednisolone. Baseline data from non-GC users were compared with GC users to assess the chronic effects of prednisolone.
Results
Non-GC users had higher ADMA (0.59 ± 0.03 vs. 0.47 ± 0.01 μM, p = 0.004) and MMA concentrations (0.10 ± 0.01 vs. 0.05 ± 0.00 μM, p < 0.001) than controls. The only change with acute prednisolone was a reduction in homoarginine (1.23 ± 0.06 vs. 1.08 ± 0.06 μM, p = 0.04) versus baseline. GC users had lower concentrations of ADMA (0.51 ± 0.02 vs. 0.59 ± 0.03 μM, p = 0.03) than non-GC users.
Conclusions
Rheumatoid arthritis patients have higher concentrations of ADMA and MMA, inhibitors of endothelial function. Chronic, but not acute, prednisolone therapy is associated with a lower ADMA concentration, suggesting a salutary effect of long-term glucocorticoid treatment on endothelial function
Comparison of formula and number-right scoring in undergraduate medical training: a Rasch model analysis
Get PDFThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Background
Progress testing is an assessment tool used to periodically assess all students at the end-of-curriculum level. Because students cannot know everything, it is important that they recognize their lack of knowledge. For that reason, the formula-scoring method has usually been used. However, where partial knowledge needs to be taken into account, the number-right scoring method is used. Research comparing both methods has yielded conflicting results. As far as we know, in all these studies, Classical Test Theory or Generalizability Theory was used to analyze the data. In contrast to these studies, we will explore the use of the Rasch model to compare both methods.
Methods
A 2 × 2 crossover design was used in a study where 298 students from four medical schools participated. A sample of 200 previously used questions from the progress tests was selected. The data were analyzed using the Rasch model, which provides fit parameters, reliability coefficients, and response option analysis.
Results
The fit parameters were in the optimal interval ranging from 0.50 to 1.50, and the means were around 1.00. The person and item reliability coefficients were higher in the number-right condition than in the formula-scoring condition. The response option analysis showed that the majority of dysfunctional items emerged in the formula-scoring condition.
Conclusions
The findings of this study support the use of number-right scoring over formula scoring. Rasch model analyses showed that tests with number-right scoring have better psychometric properties than formula scoring. However, choosing the appropriate scoring method should depend not only on psychometric properties but also on self-directed test-taking strategies and metacognitive skills
Depression - A Major Contributor to Poor Quality of Life in Patients With Advanced Cancer
Get PDFThis manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/Context
Quality of life (QoL) and depression are important patient-reported outcomes in cancer care. However, the relative importance of depression severity in predicting QoL remains unclear because of few methodologically sound studies.
Objectives
To examine whether depression contributes to impairment of QoL irrespective of prognostic factors and symptom burden.
Methods
A total of 563 patients were included from the European Palliative Care Research Collaborative–Computerized Symptom Assessment Study, an international, multi-center, cross-sectional study. The relative importance of prognostic factors (systemic inflammation [modified Glasgow Prognostic Score—mGPS]), co-morbidities and physical performance (Karnofsky Performance Status), symptom burden (loss of appetite, breathlessness, nausea [Edmonton Symptom Assessment Scale], and pain [Brief Pain Inventory]), and depression severity (Patient Health Questionnaire 9) in predicting Global Health/QoL (European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire [EORTC-QLQ-C30]) were assessed using hierarchical multiple regression models.
Results
Fifty-five percent were women, median age was 64 years, 87% had metastatic disease, median Karnofsky Performance Status was 70, and mean global QoL was 50.5 (SD = 23.3). Worse QoL was associated with increased systemic inflammation (mGPS = 1 β = −0.12, P = 0.003; mGPS = 2 β = −0.09, P = 0.023), lower physical performance (β = 0.17, P < 0.001), reduced appetite (β = −0.15, P < 0.001), breathlessness (β = −0.11, P = 0.004), pain (β = −0.14, P = 0.002), and higher depression severity (β = −0.27, P < 0.001). The full model accounted for 29% of the observed variance in QoL scores. The strongest predictor was depression severity, accounting for 5.8% of the variance.
Conclusion
Depression severity was the strongest single predictor of poorer QoL in this sample of patients with advanced cancer, after accounting for a wide range of clinically relevant variables. Future studies should investigate the contribution of psychosocial variables on QoL. Our findings emphasize the importance of managing depression to achieve the best possible QoL for these patients
A systematic review and meta-analysis of written self-administered psychosocial interventions among adults with a physical illness
Get PDFThis manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
This author accepted manuscript is made available following 12 month embargo from date of publication (July 2017) in accordance with the publisher’s archiving policyObjective
The cost of implementing professionally-led psychosocial interventions has limited their integration into routine care. To enhance the translation of effective psychosocial interventions in routine care, a self-administered format is sometimes used. The meta-analysis examined the efficacy of written self-administered, psychosocial interventions to improve outcomes among individuals with a physical illness.
Methods
Studies comparing a written self-administered intervention to a control group were identified through electronic databases searching. Pooled effect sizes were calculated across follow-up time points using random-effects models. Studies were also categorised according to three levels of guidance (self-administered, minimal contact, or guided) to examine the effect of this variable on outcomes.
Results
Forty manuscripts were retained for the descriptive review and 28 for the meta-analysis. Findings were significant for anxiety, depression, distress, and self-efficacy. Results were not significant for quality of life and related domains as well as coping. Purely self-administered interventions were efficacious for depression, distress, and self-efficacy; only guided interventions had an impact on anxiety.
Conclusions
Findings showed that written self-administered interventions show promise across a number of outcomes.
Practice implications
Self-administered interventions are a potentially efficacious and cost-effective approach to address some of the most common needs of patients with a physical illness
“Do-it-yourself”: Vaccine rejection and complementary and alternative medicine (CAM)
Get PDF© 2017 Elsevier. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
This author accepted manuscript is made available following 24 month embargo from date of publication (Nov 2017) in accordance with the publisher’s archiving policyIn this article, we elucidate a symbiotic relationship between complementary and alternative medicine (CAM) and rejection of, or hesitancy towards, vaccination. In Fremantle, Western Australia, and Adelaide, South Australia, we conducted in-depth interviews from September 2013–December 2015 with 29 parents who had refused or delayed some or all of their children's vaccines. Our qualitative analysis found that for many, their do-it-yourself ethic and personal agency was enhanced by self-directed CAM use, alongside (sometimes informal) CAM practitioner instruction. Reifying ‘the natural,’ these parents eschewed vaccines as toxic and adulterating, and embraced CAM as a protective strategy for immune systems before, during and after illness. Users saw CAM as harm-free, and when it came to experiences that non-users might interpret as demonstrating CAM's ineffectiveness, they rationalised to the contrary. They also generally glossed over its profit motive. CAM emerged as part of an expert system countering Western medicine. CAM's faces were trusted and familiar, and its cottage capitalism appeared largely free from the taint of “Big Pharma.” A few parents employed a scientific critique of CAM modalities – and a minority were dubious of its profit motive – but others rejected the epistemology underpinning biomedicine, framing CAM as a knowledge not poisoned by avarice; a wisdom whose very evidence-base (anecdote and history) was demeaned by an arrogant scientific process only permitting belief in that which could be quantified. However, all parents engaged with Western medicine for broken bones and, sometimes, medical diagnoses. Our analysis suggests that pro-vaccination health professionals, policymakers and information-providers seeking to address the role of CAM in vaccine rejection face significant challenges due to the epistemic basis of some parents' decisions. However, we make some suggestions for professional practice and policy to enhance trust in vaccination
Using Complexity and Network Concepts to Inform Healthcare Knowledge Translation
Get PDFPublished by Kerman University of Medical Sciences. This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly citedMany representations of the movement of healthcare knowledge through society exist, and multiple models for the translation of evidence into policy and practice have been articulated. Most are linear or cyclical and very few come close to reflecting the dense and intricate relationships, systems and politics of organizations and the processes required to enact sustainable improvements. We illustrate how using complexity and network concepts can better inform knowledge translation (KT) and argue that changing the way we think and talk about KT could enhance the creation and movement of knowledge throughout those systems needing to develop and utilise it. From our theoretical refinement, we propose that KT is a complex network composed of five interdependent sub-networks, or clusters, of key processes (problem identification [PI], knowledge creation [KC], knowledge synthesis [KS], implementation [I], and evaluation [E]) that interact dynamically in different ways at different times across one or more sectors (community; health; government; education; research for example). We call this the KT Complexity Network, defined as a network that optimises the effective, appropriate and timely creation and movement of knowledge to those who need it in order to improve what they do. Activation within and throughout any one of these processes and systems depends upon the agents promoting the change, successfully working across and between multiple systems and clusters. The case is presented for moving to a way of thinking about KT using complexity and network concepts. This extends the thinking that is developing around integrated KT approaches. There are a number of policy and practice implications that need to be considered in light of this shift in thinking
Protocol for a randomised crossover trial to evaluate patient and nurse satisfaction with electronic and elastomeric portable infusion pumps for the continuous administration of antibiotic therapy in the home: the Comparing Home Infusion Devices (CHID) study
Get PDFThis is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/Introduction Previous studies comparing satisfaction with electronic and elastomeric infusion pumps are limited, and improvements in size and usability of electronic pumps have since occurred. The Comparing Home Infusion Devices (CHID) study plans to assess patient and nurse satisfaction with an elastomeric and electronic pump for delivering intravenous antibiotic treatment in the home. Secondary objectives are to determine pump-related complications and actual antibiotic dose administered, evaluate temperature variation and compare pump operating costs.
Methods and analysis The CHID study will be a randomised, crossover trial. A trained research nurse will recruit patients with infectious disease aged ≥18 years and prescribed ≥8 days of continuous intravenous antibiotic therapy from the Royal Adelaide Hospital (RAH) (Adelaide, Australia). Patients will be randomised to receive treatment at home via an elastomeric (Baxter Infusor) or an electronic (ambIT Continuous) infusion pump for 4–7 days, followed by the other for a further 4–7 days. Patient satisfaction will be assessed by a 10-item survey to be completed at the end of each arm. Nurse satisfaction will be assessed by a single 24-item survey. Patient logbooks and case notes from clinic visits will be screened to identify complications. Pumps/infusion bags will be weighed to estimate the volume of solution delivered. Temperature sensors will record skin and ambient temperatures during storage and use of the pumps throughout the infusion period. Costs relating to pumps, consumables, antibiotics and servicing will be determined. Descriptive statistics will summarise study data
Does cardiac resynchronization therapy restore peripheral circulatory homeostasis?
Get PDFESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.Aims
To evaluate whether peripheral circulatory ‘remodelling’ as measured by changes in vascular compliance and in markers of nitric oxide signalling contributes to patient response to cardiac resynchronization therapy (CRT).
Methods and results
Effects of CRT were evaluated in 33 patients pre‐procedure and 6 months post‐procedure. Peak oxygen consumption, 6 min walk distance, New York Heart Association class, and quality of life score were evaluated. Augmentation index and its interactions with nitric oxide (NO) were evaluated by applanation tonometry. Platelet NO responsiveness and content of thioredoxin‐interacting protein were assessed. Plasma concentrations of N‐terminal proBNP, asymmetric and symmetric dimethylarginine (SDMA), high sensitivity C‐reactive protein, catecholamines, and matrix metalloproteinases‐2 and ‐9 were assessed. Despite significant improvement in 6 min walk distance (P = 0.005), New York Heart Association class (P < 0.001), quality of life (P = 0.001), and all echocardiographic parameters post‐CRT, there were no significant changes in augmentation index measurements, thioredoxin‐interacting protein content, and platelet NO response. Significant falls in N‐terminal proBNP (P = 0.008) and SDMA (P = 0.013; independent of renal function) occurred. Falls in SDMA predicted reduction in high‐sensitivity C‐reactive protein (P = 0.04) and increases in peak oxygen consumption (P = 0.04). There were no correlations between changes in echocardiographic parameters and those in vascular function.
Conclusions
These data suggest that the beneficial effects of CRT over 6 months are independent of any change in peripheral NO‐related signalling. However, there is evidence that suppression of inflammation occurs, and its magnitude predicts extent of clinical improvement