Canadian Institutes of Health Research

AGREE II (Appraisal of Guidelines, Research and Evaluation), which comprises 23 items and a user's manual, offers refinements of a new way to develop, report and evaluate practice guidelines.

BACKGROUND: The increased use of meta-analysis in systematic reviews of healthcare interventions has highlighted several types of bias that can arise during the completion of a randomised controlled trial. Study publication bias has been recognised as a potential threat to the validity of meta-analysis and can make the readily available evidence unreliable for decision making. Until recently, outcome reporting bias has received less attention. METHODOLOGY/PRINCIPAL FINDINGS: We review and summarise the evidence from a series of cohort studies that have assessed study publication bias and outcome reporting bias in randomised controlled trials. Sixteen studies were eligible of which only two followed the cohort all the way through from protocol approval to information regarding publication of outcomes. Eleven of the studies investigated study publication bias and five investigated outcome reporting bias. Three studies have found that statistically significant outcomes had a higher odds of being fully reported compared to non-significant outcomes (range of odds ratios: 2.2 to 4.7). In comparing trial publications to protocols, we found that 40-62% of studies had at least one primary outcome that was changed, introduced, or omitted. We decided not to undertake meta-analysis due to the differences between studies. CONCLUSIONS: Recent work provides direct empirical evidence for the existence of study publication bias and outcome reporting bias. There is strong evidence of an association between significant results and publication; studies that report positive or significant results are more likely to be published and outcomes that are statistically significant have higher odds of being fully reported. Publications have been found to be inconsistent with their protocols. Researchers need to be aware of the problems of both types of bias and efforts should be concentrated on improving the reporting of trials.

Endothelial dysfunction is characterized by a shift of the actions of the endothelium toward reduced vasodilation, a proinflammatory state, and prothrombic properties. It is associated with most forms of cardiovascular disease, such as hypertension, coronary artery disease, chronic heart failure, peripheral artery disease, diabetes, and chronic renal failure. Mechanisms that participate in the reduced vasodilatory responses in endothelial dysfunction include reduced nitric oxide generation, oxidative excess, and reduced production of hyperpolarizing factor. Upregulation of adhesion molecules, generation of chemokines such as macrophage chemoattractant peptide-1, and production of plasminogen activator inhibitor-1 participate in the inflammatory response and contribute to a prothrombic state. Vasoactive peptides such as angiotensin II and endothelin-1; the accumulation of asymmetric dimethylarginine, an endogenous nitric oxide inhibitor; hypercholesterolemia; hyperhomocysteinemia; altered insulin signaling; and hyperglycemia can contribute to these different mechanisms. Detachment and apoptosis of endothelial cells (anoikis) are associated phenomena. Endothelial dysfunction is an important early event in the pathogenesis of atherosclerosis, contributing to plaque initiation and progression. Reductions in circulating endothelial progenitor cells that participate in regeneration of the endothelium participate in endothelial pathophysiology. The severity of endothelial dysfunction has been shown to have prognostic value for cardiovascular events. Correction of endothelial dysfunction may be associated with reduced cardiovascular risk. Circulating endothelial progenitor cells may represent a potential therapeutic approach for endothelial dysfunction.

BACKGROUND: Understanding the risk factors for ventilator-associated pneumonia can help to assess prognosis and devise and test preventive strategies. OBJECTIVE: To examine the baseline and time-dependent risk factors for ventilator-associated pneumonia and to determine the conditional probability and cumulative risk over the duration of stay in the intensive care unit. DESIGN: Prospective cohort study. SETTING: 16 intensive care units in Canada. PATIENTS: 1014 mechanically ventilated patients. MEASUREMENTS: Demographic and time-dependent variables reflecting illness severity, ventilation, nutrition, and drug exposure. Pneumonia was classified by using five methods: adjudication committee, bedside clinician's diagnosis, Centers for Disease Control and Prevention definition, Clinical Pulmonary Infection score, and positive culture from bronchoalveolar lavage or protected specimen brush. RESULTS: 177 of 1014 patients (17.5%) developed ventilator-associated pneumonia 9.0 +/- 5.9 days (median, 7 days [interquartile range, 5 to 10 days]) after admission to the intensive care unit. Although the cumulative risk increased over time, the daily hazard rate decreased after day 5 (3.3% at day 5, 2.3% at day 10, and 1.3% at day 15). Independent predictors of ventilator-associated pneumonia in multivariable analysis were a primary admitting diagnosis of burns (risk ratio, 5.09 [95% CI, 1.52 to 17.03]), trauma (risk ratio, 5.00 [CI, 1.91 to 13.11]), central nervous system disease (risk ratio, 3.40 [CI, 1.31 to 8.81]), respiratory disease (risk ratio, 2.79 [CI, 1.04 to 7.51]), cardiac disease (risk ratio, 2.72 [CI, 1.05 to 7.01]), mechanical ventilation in the previous 24 hours (risk ratio, 2.28 [CI, 1.11 to 4.68]), witnessed aspiration (risk ratio, 3.25 [CI, 1.62 to 6.50]), and paralytic agents (risk ratio, 1.57 [CI, 1.03 to 2.39]). Exposure to antibiotics conferred protection (risk ratio, 0.37 [CI, 0.27 to 0.51]). Independent risk factors were the same regardless of the pneumonia definition used. CONCLUSIONS: The daily risk for pneumonia decreases with increasing duration of stay in the intensive care unit. Witnessed aspiration and exposure to paralytic agents are potentially modifiable independent risk factors. Exposure to antibiotics was associated with low rates of early ventilator-associated pneumonia, but this effect attenuates over time.

BACKGROUND: The efficacy of prophylaxis against stress ulcers in preventing gastrointestinal bleeding in critically ill patients has led to its widespread use. The side effects and cost of prophylaxis, however, necessitate targeting preventive therapy to those patients most likely to benefit. METHODS: We conducted a prospective multicenter cohort study in which we evaluated potential risk factors for stress ulceration in patients admitted to intensive care units and documented the occurrence of clinically important gastrointestinal bleeding (defined as overt bleeding in association with hemodynamic compromise or the need for blood transfusion). RESULTS: Of 2252 patients, 33 (1.5 percent; 95 percent confidence interval, 1.0 to 2.1 percent) had clinically important bleeding. Two strong independent risk factors for bleeding were identified: respiratory failure (odds ratio, 15.6) and coagulopathy (odds ratio, 4.3). Of 847 patients who had one or both of these risk factors, 31 (3.7 percent; 95 percent confidence interval, 2.5 to 5.2 percent) had clinically important bleeding. Of 1405 patients without these risk factors, 2 (0.1 percent; 95 percent confidence interval, 0.02 to 0.5 percent) had clinically important bleeding. The mortality rate was 48.5 percent in the group with bleeding and 9.1 percent in the group without bleeding (P < 0.001). CONCLUSIONS: Few critically ill patients have clinically important gastrointestinal bleeding, and therefore prophylaxis against stress ulcers can be safely withheld from critically ill patients unless they have coagulopathy or require mechanical ventilation.

We cannot pick up a magazine or surf the Internet without facing reminders of the challenges to health care and the “sorry state” of health systems. [1][1] All health care systems are faced with the challenges of improving quality of care and reducing the risk of adverse events. [2][2] Globally

Mosaic tablet, dynamic document, or dinosaur?

Peer Reviewed

Failure to attain handwriting competency during the school-age years often has far-reaching negative effects on both academic success and self-esteem. This complex occupational task has many underlying component skills that may interfere with handwriting performance. Fine motor control, bilateral and visual-motor integration, motor planning, in-hand manipulation, proprioception, visual perception, sustained attention, and sensory awareness of the fingers are some of the component skills identified. Poor handwriting may be related to intrinsic factors, which refer to the child's actual handwriting capabilities, or extrinsic factors which are related to environmental or biomechanical components, or both. It is important that handwriting performance be evaluated using a valid, reliable, standardized tool combined with informal classroom observation and teacher consultation. Studies of handwriting remediation suggest that intervention is effective. There is evidence to indicate that handwriting difficulties do not resolve without intervention and affect between 10 and 30% of school-aged children. Despite the widespread use of computers, legible handwriting remains an important life skill that deserves greater attention from educators and health practitioners.

BACKGROUND: Shared decision making (SDM) is a process by which a healthcare choice is made jointly by the practitioner and the patient and is said to be the crux of patient-centred care. Policy makers perceive SDM as desirable because of its potential to a) reduce overuse of options not clearly associated with benefits for all (e.g., prostate cancer screening); b) enhance the use of options clearly associated with benefits for the vast majority (e.g., cardiovascular risk factor management); c) reduce unwarranted healthcare practice variations; d) foster the sustainability of the healthcare system; and e) promote the right of patients to be involved in decisions concerning their health. Despite this potential, SDM has not yet been widely adopted in clinical practice. OBJECTIVES: To determine the effectiveness of interventions to improve healthcare professionals' adoption of SDM. SEARCH STRATEGY: We searched the following electronic databases up to 18 March 2009: Cochrane Library (1970-), MEDLINE (1966-), EMBASE (1976-), CINAHL (1982-) and PsycINFO (1965-). We found additional studies by reviewing a) the bibliographies of studies and reviews found in the electronic databases; b) the clinicaltrials.gov registry; and c) proceedings of the International Shared Decision Making Conference and the conferences of the Society for Medical Decision Making. We included all languages of publication. SELECTION CRITERIA: We included randomised controlled trials (RCTs) or well-designed quasi-experimental studies (controlled clinical trials, controlled before and after studies, and interrupted time series analyses) that evaluated any type of intervention that aimed to improve healthcare professionals' adoption of shared decision making. We defined adoption as the extent to which healthcare professionals intended to or actually engaged in SDM in clinical practice or/and used interventions known to facilitate SDM. We deemed studies eligible if the primary outcomes were evaluated with an objective measure of the adoption of SDM by healthcare professionals (e.g., a third-observer instrument). DATA COLLECTION AND ANALYSIS: At least two reviewers independently screened each abstract for inclusion and abstracted data independently using a modified version of the EPOC data collection checklist. We resolved disagreements by discussion. Statistical analysis considered categorical and continuous primary outcomes. We computed the standard effect size for each outcome separately with a 95% confidence interval. We evaluated global effects by calculating the median effect size and the range of effect sizes across studies. MAIN RESULTS: The reviewers identified 6764 potentially relevant documents, of which we excluded 6582 by reviewing titles and abstracts. Of the remainder, we retrieved 182 full publications for more detailed screening. From these, we excluded 176 publications based on our inclusion criteria. This left in five studies, all RCTs. All five were conducted in ambulatory care: three in primary clinical care and two in specialised care. Four of the studies targeted physicians only and one targeted nurses only. In only two of the five RCTs was a statistically significant effect size associated with the intervention to have healthcare professionals adopt SDM. The first of these two studies compared a single intervention (a patient-mediated intervention: the Statin Choice decision aid) to another single intervention (also patient-mediated: a standard Mayo patient education pamphlet). In this study, the Statin Choice decision aid group performed better than the standard Mayo patient education pamphlet group (standard effect size = 1.06; 95% CI = 0.62 to 1.50). The other study compared a multifaceted intervention (distribution of educational material, educational meeting and audit and feedback) to usual care (control group) (standard effect size = 2.11; 95% CI = 1.30 to 2.90). This study was the only one to report an assessment of barriers prior to the elaboration of its multifaceted intervention. AUTHORS' CONCLUSIONS: The results of this Cochrane review do not allow us to draw firm conclusions about the most effective types of intervention for increasing healthcare professionals' adoption of SDM. Healthcare professional training may be important, as may the implementation of patient-mediated interventions such as decision aids. Given the paucity of evidence, however, those motivated by the ethical impetus to increase SDM in clinical practice will need to weigh the costs and potential benefits of interventions. Subsequent research should involve well-designed studies with adequate power and procedures to minimise bias so that they may improve estimates of the effects of interventions on healthcare professionals' adoption of SDM. From a measurement perspective, consensus on how to assess professionals' adoption of SDM is desirable to facilitate cross-study comparisons.

Several novel UDP glycosyltransferase (UGT) genes, mainly UDP glucuronosyltransferases, have been identified in the human, mouse and rat genomes and in other mammalian species. This review provides an update of the UGT nomenclature to include these new genes and prevent the confusion that arises when the same gene is given different names. The new genes are named following previously established recommendations, taking into consideration evolutionary relatedness and the names already in general usage in the literature. The mammalian UGT gene superfamily currently has 117 members that can be divided into four families, UGT1, UGT2, UGT3 and UGT8. The 5-exon genes of the UGT1 family each contain a unique first exon, plus four exons that are shared between the genes; the exons 1 appear to have evolved by a process of duplication, leading to the synthesis of proteins with identical carboxyl-terminal and variable amino-terminal domains. Exon-sharing is also seen with the 6-exon UGT2A1 and UGT2A2 genes. However, UGT2A3 and those of the UGT2B (six exons), UGT3 (seven exons) and UGT8 gene families (five or six exons) do not share exons and most likely were derived by a process of duplication of all exons in the gene. Most UGT1 and UGT8 enzymes have been characterized in detail; however, the catalytic functions of the UGT3A enzymes and several UGT2 enzymes remain to be characterized.

BACKGROUND: Competency-based education (CBE) has emerged in the health professions to address criticisms of contemporary approaches to training. However, the literature has no clear, widely accepted definition of CBE that furthers innovation, debate, and scholarship in this area. AIM: To systematically review CBE-related literature in order to identify key terms and constructs to inform the development of a useful working definition of CBE for medical education. METHODS: We searched electronic databases and supplemented searches by using authors' files, checking reference lists, contacting relevant organizations and conducting Internet searches. Screening was carried out by duplicate assessment, and disagreements were resolved by consensus. We included any English- or French-language sources that defined competency-based education. Data were analyzed qualitatively and summarized descriptively. RESULTS: We identified 15,956 records for initial relevancy screening by title and abstract. The full text of 1,826 records was then retrieved and assessed further for relevance. A total of 173 records were analyzed. We identified 4 major themes (organizing framework, rationale, contrast with time, and implementing CBE) and 6 sub-themes (outcomes defined, curriculum of competencies, demonstrable, assessment, learner-centred and societal needs). From these themes, a new definition of CBE was synthesized. CONCLUSION: This is the first comprehensive systematic review of the medical education literature related to CBE definitions. The themes and definition identified should be considered by educators to advance the field.

The conclusions of thousands of peer-reviewed publications rely on data obtained using fluorescence-based quantitative real-time PCR technology. However, the inadequate reporting of experimental detail, combined with the frequent use of flawed protocols is leading to the publication of papers that may not be technically appropriate. We take the view that this problem requires the delineation of a more transparent and comprehensive reporting policy from scientific journals. This editorial aims to provide practical guidance for the incorporation of absolute minimum standards encompassing the key assay parameters for accurate design, documentation and reporting of qPCR experiments (MIQE précis) and guidance on the publication of pure 'reference gene' articles.

Histamine has an important role as a chemical messenger in physiologic responses, neurotransmission, allergic inflammation, and immunomodulation by way of the H1-receptor. Most H1-antihistamines, which are useful in treating these effects, possess similar efficacy in allergic rhinoconjunctivitis and chronic urticaria. However, there are clinically relevant differences among them in their pharmacology and safety profiles.

BACKGROUND: In the experience of health professionals, it appears that interacting with peers in the workplace fosters learning and information sharing. Informal groups and networks present good opportunities for information exchange. Communities of practice (CoPs), which have been described by Wenger and others as a type of informal learning organization, have received increasing attention in the health care sector; however, the lack of uniform operating definitions of CoPs has resulted in considerable variation in the structure and function of these groups, making it difficult to evaluate their effectiveness. OBJECTIVE: To critique the evolution of the CoP concept as based on the germinal work by Wenger and colleagues published between 1991 and 2002. DISCUSSION: CoP was originally developed to provide a template for examining the learning that happens among practitioners in a social environment, but over the years there have been important divergences in the focus of the concept. Lave and Wenger's earliest publication (1991) centred on the interactions between novices and experts, and the process by which newcomers create a professional identity. In the 1998 book, the focus had shifted to personal growth and the trajectory of individuals' participation within a group (i.e., peripheral versus core participation). The focus then changed again in 2002 when CoP was applied as a managerial tool for improving an organization's competitiveness. SUMMARY: The different interpretations of CoP make it challenging to apply the concept or to take full advantage of the benefits that CoP groups may offer. The tension between satisfying individuals' needs for personal growth and empowerment versus an organization's bottom line is perhaps the most contentious of the issues that make CoPs difficult to cultivate. Since CoP is still an evolving concept, we recommend focusing on optimizing specific characteristics of the concept, such as support for members interacting with each other, sharing knowledge, and building a sense of belonging within networks/teams/groups. Interventions that facilitate relationship building among members and that promote knowledge exchange may be useful for optimizing the function of these groups.

Although there is ample evidence that motor imagery activates similar cerebral regions to those solicited during actual movements, it is still unknown whether visual (VI) and kinesthetic imagery (KI) recruit comparable or distinct neural networks. The present study was thus designed to identify, through functional magnetic resonance imaging at 3.0 Tesla in 13 skilled imagers, the cerebral structures implicated in VI and KI. Participants were scanned in a perceptual control condition and while physically executing or focusing during motor imagery on either the visual or kinesthetic components of an explicitly known sequence of finger movements. Subjects' imagery abilities were assessed using well-established psychological, chronometric, and new physiological measures from the autonomic nervous system. Compared with the perceptual condition, physical executing, VI, and KI resulted in overlapping (albeit non-identical) brain activations, including motor-related regions and the inferior and superior parietal lobules. By contrast, a divergent pattern of increased activity was observed when VI and KI were compared directly: VI activated predominantly the occipital regions and the superior parietal lobules, whereas KI yielded more activity in motor-associated structures and the inferior parietal lobule. These results suggest that VI and KI are mediated through separate neural systems, which contribute differently during processes of motor learning and neurological rehabilitation.

CONTEXT: In humans, the prevalence, mass, and glucose-uptake activity of (18)F-fluorodeoxyglucose ((18)F-FDG)-detected brown adipose tissue (BAT), which are expectedly enhanced by a cold stimulus, also appear modulated by other factors that still have to be disentangled. OBJECTIVE: The objective of the study was to investigate the factors determining the prevalence, mass, and glucose-uptake activity of (18)F-FDG-detected BAT in humans. RESEARCH DESIGN AND METHODS: We retrospectively analyzed all (18)F-FDG positron emission tomography/computed tomography examinations performed between January 2007 and December 2008 at our institution for (18)F-FDG uptake within the cervical/supraclavicular, mediastinal, paravertebral, and perirenal fat areas. The influence of outdoor temperature, sex, age, body mass index (BMI), plasma glucose level, diabetes diagnosis, day length, and cancer status on the prevalence, mass, and glucose-uptake activity of (18)F-FDG-detected BAT depots was investigated. RESULTS: Three hundred twenty-eight of the 4842 patients (6.8%) had (18)F-FDG-detected BAT. The prevalence of (18)F-FDG BAT was negatively associated with outdoor temperature (P < 0.0001), age (P < 0.0001), BMI (P < 0.0001), and diabetes status (P = 0.0003). Moreover, there was a significant age × sex interaction for the prevalence of (18)F-FDG BAT (the younger the subjects, the greater the sex difference). The mass and glucose-uptake activity of (18)F-FDG-detected BAT also decreased with increasing outdoor temperature (P < 0.0001), age (P < 0.0001), and BMI (P < 0.0001). They were lower in men than in women (P < 0.001) and lower in diabetic than in nondiabetic patients (P = 0.0002). CONCLUSIONS: The present study identifies outdoor temperature, age, sex, BMI, and diabetes status as determinants of the prevalence, mass, and glucose-uptake activity of (18)F-FDG-detected BAT.

An ecological perspective on health emphasises both individual and contextual systems and the interdependent relations between the two. Origins of this approach have emanated from multiple disciplines over the past century or more. This article provides a glossary of perspectives, processes, and settings that pertain to an ecological approach in health research.

Protein kinase B (PKB/Akt) is a regulator of cell survival and apoptosis. To become fully activated, PKB/Akt requires phosphorylation at two sites, threonine 308 and serine 473, in a phosphatidylinositol (PI) 3-kinase-dependent manner. The kinase responsible for phosphorylation of threonine 308 is the PI 3-kinase-dependent kinase-1 (PDK-1), whereas phosphorylation of serine 473 has been suggested to be regulated by PKB/Akt autophosphorylation in a PDK-1-dependent manner. However, the integrin-linked kinase (ILK) has also been shown to regulate phosphorylation of serine 473 in a PI 3-kinase-dependent manner. Whether ILK phosphorylates this site directly or functions as an adapter molecule has been debated. We now show by in-gel kinase assay and matrix-assisted laser desorption-ionization time-of-flight mass spectrometry that biochemically purified ILK can phosphorylate PKB/Akt directly. Co-immunoprecipitation analysis of cell extracts demonstrates that ILK can complex with PKB/Akt as well as PDK-1 and that ILK can disrupt PDK-1/PKB association. The amino acid residue serine 343 of ILK within the activation loop is required for kinase activity as well as for its interaction with PKB/Akt. Mutational analysis of ILK further shows a crucial role for arginine 211 of ILK within the phosphoinositide phospholipid binding domain in the regulation of PKB- serine 473 phosphorylation. A highly selective small molecule inhibitor of ILK activity also inhibits the ability of ILK to phosphorylate PKB/Akt in vitro and in intact cells. These data demonstrate that ILK is an important upstream kinase for the regulation of PKB/Akt.

CONTEXT: In order to design interventions that increase research use in nursing, it is necessary to have an understanding of what influences research use. OBJECTIVE: To report findings on a systematic review of studies that examine individual characteristics of nurses and how they influence the utilization of research. SEARCH STRATEGY: A survey of published articles in English that examine the influence of individual factors on the research utilization behaviour of nurses, without restriction of the study design, from selected computerized databases and hand searches. INCLUSION CRITERIA: Articles had to measure one or more individual determinants of research utilization, measure the dependent variable (research utilization), and evaluate the relationship between the dependent and independent variables. The studies also had to indicate the direction of the relationship between the independent and dependent variables, report a P-value and the statistic used, and indicate the magnitude of the relationship. RESULTS: Six categories of potential individual determinants were identified: beliefs and attitudes, involvement in research activities, information seeking, professional characteristics, education and other socio-economic factors. Research design, sampling, measurement, and statistical analysis were examined to evaluate methodological quality. Methodological problems surfaced in all of the studies and, apart from attitude to research, there was little to suggest that any potential individual determinant influences research use. CONCLUSION: Important conceptual and measurement issues with regard to research utilization could be better addressed if research in the area were undertaken longitudinally by multi-disciplinary teams of researchers.