Showing papers by "University of Ottawa published in 2006"

Lost in knowledge translation: time for a map?

Abstract: There is confusion and misunderstanding about the concepts of knowledge translation, knowledge transfer, knowledge exchange, research utilization, implementation, diffusion, and dissemination. We review the terms and definitions used to describe the concept of moving knowledge into action. We also offer a conceptual framework for thinking about the process and integrate the roles of knowledge creation and knowledge application. The implications of knowledge translation for continuing education in the health professions include the need to base continuing education on the best available knowledge, the use of educational and other transfer strategies that are known to be effective, and the value of learning about plannedaction theories to be better able to understand and influence change in practice settings.

The epithelial–mesenchymal transition: new insights in signaling, development, and disease

Abstract: The conversion of an epithelial cell to a mesenchymal cell is critical to metazoan embryogenesis and a defining structural feature of organ development. Current interest in this process, which is described as an epithelial-mesenchymal transition (EMT), stems from its developmental importance and its involvement in several adult pathologies. Interest and research in EMT are currently at a high level, as seen by the attendance at the recent EMT meeting in Vancouver, Canada (October 1-3, 2005). The meeting, which was hosted by The EMT International Association, was the second international EMT meeting, the first being held in Port Douglas, Queensland, Australia in October 2003. The EMT International Association was formed in 2002 to provide an international body for those interested in EMT and the reverse process, mesenchymal-epithelial transition, and, most importantly, to bring together those working on EMT in development, cancer, fibrosis, and pathology. These themes continued during the recent meeting in Vancouver. Discussion at the Vancouver meeting spanned several areas of research, including signaling pathway activation of EMT and the transcription factors and gene targets involved. Also covered in detail was the basic cell biology of EMT and its role in cancer and fibrosis, as well as the identification of new markers to facilitate the observation of EMT in vivo. This is particularly important because the potential contribution of EMT during neoplasia is the subject of vigorous scientific debate (Tarin, D., E.W. Thompson, and D.F. Newgreen. 2005. Cancer Res. 65:5996-6000; Thompson, E.W., D.F. Newgreen, and D. Tarin. 2005. Cancer Res. 65:5991-5995).

Measuring health: A guide to rating scales and questionnaires, 3rd ed.

Abstract: This is a convenient guide to the health measurement methods used in health and social surveys, epidemiological studies, and clinical trials. It describes the theory and the leading methods of measurement, all of which rely on subjective judgments in questionnaires and rating scales. The authors discuss the validity and reliability of each method, showing readers how to select the most suitable one, apply it, and score the results. Epidemiologists and health care researchers; social scientists; health care planners and analysts.

Developing a quality criteria framework for patient decision aids: online international Delphi consensus process

Abstract: Objective To develop a set of quality criteria for patient decision support technologies (decision aids). Design and setting Two stage web based Delphi process using online rating process to enable international collaboration. Participants Individuals from four stakeholder groups (researchers, practitioners, patients, policy makers) representing 14 countries reviewed evidence summaries and rated the importance of 80 criteria in 12 quality domains ona1to9 scale. Second round participants received feedback from the first round and repeated their assessment of the 80 criteria plus three new ones. Main outcome measure Aggregate ratings for each criterion calculated using medians weighted to compensate for different numbers in stakeholder groups; criteria rated between 7 and 9 were retained. Results 212 nominated people were invited to participate. Of those invited, 122 participated in the first round (77 researchers, 21 patients, 10 practitioners, 14 policy makers); 104/122 (85%) participated in the second round. 74 of 83 criteria were retained in the following domains: systematic development process (9/9 criteria); providing information about options (13/13); presenting probabilities (11/13); clarifying and expressing values (3/3); using patient stories (2/5); guiding/coaching (3/5); disclosing conflicts of interest (5/5); providing internet access (6/6); balanced presentation of options (3/3); using plain language (4/6); basing information on up to date evidence (7/7); and establishing effectiveness (8/8). Conclusions Criteria were given the highest ratings where evidence existed, and these were retained. Gaps in research were highlighted. Developers, users, and purchasers of patient decision aids now have a checklist for appraising quality. An instrument for measuring quality of decision aids is being developed.

Beyond accuracy, f-score and ROC: a family of discriminant measures for performance evaluation

Abstract: Different evaluation measures assess different characteristics of machine learning algorithms. The empirical evaluation of algorithms and classifiers is a matter of on-going debate among researchers. Most measures in use today focus on a classifier's ability to identify classes correctly. We note other useful properties, such as failure avoidance or class discrimination, and we suggest measures to evaluate such properties. These measures – Youden's index, likelihood, Discriminant power – are used in medical diagnosis. We show that they are interrelated, and we apply them to a case study from the field of electronic negotiations. We also list other learning problems which may benefit from the application of these measures.

Physical Activity/Exercise and Type 2 Diabetes A consensus statement from the American Diabetes Association

Abstract: For decades, exercise has been considered a cornerstone of diabetes management, along with diet and medication. However, high-quality evidence on the importance of exercise and fitness in diabetes was lacking until recent years. The present document summarizes the most clinically relevant recent advances related to people with type 2 diabetes and the recommendations that follow from these. Our recently published technical review on physical activity/exercise and type 2 diabetes (1) includes greater detail on individual studies, on prevention of diabetes, and on the physiology of exercise. The present statement focuses on type 2 diabetes. Issues primarily germane to type 1 diabetes will be covered in a subsequent technical review and ADA Statement. The levels of evidence used are defined by the ADA in ref. 2. Two randomized trials each found that lifestyle interventions including ∼150 min/week of physical activity and diet-induced weight loss of 5–7% reduced the risk of progression from impaired glucose tolerance (IGT) to type 2 diabetes by 58% (3,4). A cluster-randomized trial found that diet alone, exercise alone, and combined diet and exercise were equally effective in reducting the progression from IGT to diabetes (5). Therefore, there is firm and consistent evidence that programs of increased physical activity and modest weight loss reduce the incidence of type 2 diabetes in individuals with IGT. Boule et al. (6) undertook a systematic review and meta-analysis on the effects of structured exercise interventions in clinical trials of ≥8 weeks duration on HbA1c (A1C) and body mass in people with type 2 diabetes. Postintervention A1C was significantly lower in exercise than control groups (7.65 vs. 8.31%, weighted mean difference −0.66%; P < 0.001). In contrast, postintervention body weight did not differ between the exercise and control groups. Meta-regression confirmed that the beneficial effect of exercise on A1C …

Adherence to antiretroviral therapy in sub-Saharan Africa and North America: a meta-analysis.

Abstract: ContextAdherence to antiretroviral therapy is a powerful predictor of survival for individuals living with human immunodeficiency virus (HIV) and AIDS. Concerns about incomplete adherence among patients living in poverty have been an important consideration in expanding the access to antiretroviral therapy in sub-Saharan Africa.ObjectiveTo evaluate estimates of antiretroviral therapy adherence in sub-Saharan Africa and North America.Data SourcesEleven electronic databases were searched along with major conference abstract databases (inclusion dates: inception of database up until April 18, 2006) for all English-language articles and abstracts; and researchers and treatment advocacy groups were contacted.Study Selection and Data AbstractionTo best reflect the general population, studies of mixed populations in both North America and Africa were selected. Studies evaluating specific populations such as men only, homeless individuals, or drug users, were excluded. The data were abstracted in duplicate on study adherence outcomes, thresholds used to determine adherence, and characteristics of the populations. A random-effects meta-analysis was performed in which heterogeneity was examined using multivariable random-effects logistic regression. A sensitivity analysis was performed using Bayesian methods.Data SynthesisThirty-one studies from North America (28 full-text articles and 3 abstracts) and 27 studies (9 full-text articles and 18 abstracts) from sub-Saharan Africa were included. African studies represented 12 sub-Saharan countries. Of the North American studies, 71% used patient self-report to assess adherence; this was true of 66% of the African assessments. Studies reported similar thresholds for adherence monitoring (eg, 100%, >95%, >90%, >80%). A pooled analysis of the North American studies (17 573 patients total) indicated a pooled estimate of 55% (95% confidence interval, 49%-62%; I2, 98.6%) of the populations achieving adequate levels of adherence. Our pooled analysis of African studies (12 116 patients total) indicated a pooled estimate of 77% (95% confidence interval, 68%-85%; I2, 98.4%). Study continent, adherence thresholds, and study quality were significant predictors of heterogeneity. Bayesian analysis was used as an alternative statistical method for combining adherence rates and provided similar findings.ConclusionOur findings indicate that favorable levels of adherence, much of which was assessed via patient self-report, can be achieved in sub-Saharan African settings and that adherence remains a concern in North America.

Palladium-catalyzed benzene arylation: incorporation of catalytic pivalic acid as a proton shuttle and a key element in catalyst design.

Abstract: A palladium−pivalic acid cocatalyst system has been developed that exhibits unprecedented reactivity in direct arylation This reactivity is illustrated with the first examples of high yielding direct metalation−arylation reactions of a completely unactivated arene, benzene Experimental and computational evidence indicates that the pivalate anion is a key component in the palladation/C−H bond breaking event, that it lowers the energy of C−H bond cleavage and acts as a catalytic proton shuttle from benzene to the stoichiometric carbonate base Eight examples of substituted aryl bromides are included which undergo direct arylation with benzene in 55−85% yield

Adherence to HAART: A Systematic Review of Developed and Developing Nation Patient-Reported Barriers and Facilitators

Abstract: Ontario HIV Treatment Network; Canadian Institutes for Health Research; National Institues of Health (AI005535901, K23A106858201, AA015287, MH54907, AI27763); British Columbia Michael Smith Foundation; The Doris Duke Charitable Foundation

Does the CONSORT checklist improve the quality of reports of randomised controlled trials? A systematic review.

Abstract: Objective To determine whether the adoption of the CONSORT checklist is associated with improvement in the quality of reporting of randomised controlled trials (RCTs). Data sources MEDLINE, EMBASE, Cochrane CENTRAL, and reference lists of included studies and of experts were searched to identify eligible studies published between 1996 and 2005. Study selection Studies were eligible if they (a) compared CONSORT-adopting and non-adopting journals after the publication of CONSORT, (b) compared CONSORT adopters before and after publication of CONSORT, or (c) a combination of (a) and (b). Outcomes examined included reports for any of the 22 items on the CONSORT checklist or overall trial quality. Data synthesis 1128 studies were retrieved, of which 248 were considered possibly relevant. Eight studies were included in the review. CONSORT adopters had significantly better reporting of the method of sequence generation (risk ratio [RR], 1.67; 95% CI, 1.19-2.33), allocation concealment (RR, 1.66; 95% CI, 1.37-2.00) and overall number of CONSORT items than non-adopters (standardised mean difference, 0.83; 95% CI, 0.46-1.19). CONSORT adoption had less effect on reporting of participant flow (RR, 1.14; 95% CI, 0.89-1.46) and blinding of participants (RR, 1.09; 95% CI, 0.84-1.43) or data analysts (RR, 5.44; 95% CI, 0.73-36.87). In studies examining CONSORT-adopting journals before and after the publication of CONSORT, description of the method of sequence generation (RR, 2.78; 95% CI, 1.78-4.33), participant flow (RR, 8.06; 95% CI, 4.10-15.83), and total CONSORT items (standardised mean difference, 3.67 items; 95% CI, 2.09-5.25) were improved after adoption of CONSORT by the journal. Conclusions Journal adoption of CONSORT is associated with improved reporting of RCTs.

Viscosupplementation for the treatment of osteoarthritis of the knee

Abstract: Background Osteoarthritis (OA) is the most prevalent chronic joint disorder worldwide and is associated with significant pain and disability. Objectives To assess the effects of viscosupplementation in the treatment of OA of the knee. The products were hyaluronan and hylan derivatives (Adant, Arthrum H, Artz (Artzal, Supartz), BioHy (Arthrease, Euflexxa, Nuflexxa), Durolane, Fermathron, Go-On, Hyalgan, Hylan G-F 20 (Synvisc Hylan G-F 20), Hyruan, NRD-101 (Suvenyl), Orthovisc, Ostenil, Replasyn, SLM-10, Suplasyn, Synject and Zeel compositum). Search strategy MEDLINE (up to January (week 1) 2006 for update), EMBASE, PREMEDLINE, Current Contents up to July 2003, and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched. Specialised journals and reference lists of identified randomised controlled trials (RCTs) and pertinent review articles up to December 2005 were handsearched. Selection criteria RCTs of viscosupplementation for the treatment of people with a diagnosis of OA of the knee were eligible. Single and double-blinded studies, placebo-based and comparative studies were eligible. At least one of the four OMERACT III core set outcome measures had to be reported (Bellamy 1997). Data collection and analysis Each trial was assessed independently by two reviewers for its methodological quality using a validated tool. All data were extracted by one reviewer and verified by a second reviewer. Continuous outcome measures were analysed as weighted mean differences (WMD) with 95% confidence intervals (CI). However, where different scales were used to measure the same outcome, standardized mean differences (SMD) were used. Dichotomous outcomes were analyzed by relative risk (RR). Main results Seventy-six trials with a median quality score of 3 (range 1 to 5) were identified. Follow-up periods varied between day of last injection and eighteen months. Forty trials included comparisons of hyaluronan/hylan and placebo (saline or arthrocentesis), ten trials included comparisons of intra-articular (IA) corticosteroids, six trials included comparisons of nonsteroidal anti-inflammatory drugs (NSAIDs), three trials included comparisons of physical therapy, two trials included comparisons of exercise, two trials included comparisons of arthroscopy, two trials included comparisons of conventional treatment, and fifteen trials included comparisons of other hyaluronans/hylan. The pooled analyses of the effects of viscosupplements against 'placebo' controls generally supported the efficacy of this class of intervention. In these same analyses, differential efficacy effects were observed for different products on different variables and at different timepoints. Of note is the 5 to 13 week post injection period which showed a percent improvement from baseline of 28 to 54% for pain and 9 to 32% for function. In general, comparable efficacy was noted against NSAIDs and longer-term benefits were noted in comparisons against IA corticosteroids. In general, few adverse events were reported in the hyaluronan/hylan trials included in these analyses. Authors' conclusions Based on the aforementioned analyses, viscosupplementation is an effective treatment for OA of the knee with beneficial effects: on pain, function and patient global assessment; and at different post injection periods but especially at the 5 to 13 week post injection period. It is of note that the magnitude of the clinical effect, as expressed by the WMD and standardised mean difference (SMD) from the RevMan 4.2 output, is different for different products, comparisons, timepoints, variables and trial designs. However, there are few randomised head-to-head comparisons of different viscosupplements and readers should be cautious, therefore, in drawing conclusions regarding the relative value of different products. The clinical effect for some products, against placebo, on some variables at some timepoints is in the moderate to large effect-size range. Readers should refer to relevant tables to review specific detail given the heterogeneity in effects across the product class and some discrepancies observed between the RevMan 4.2 analyses and the original publications. Overall, the analyses performed are positive for the HA class and particularly positive for some products with respect to certain variables and timepoints, such as pain on weight bearing at 5 to 13 weeks postinjection. In general, sample-size restrictions preclude any definitive comment on the safety of the HA class of products; however, within the constraints of the trial designs employed no major safety issues were detected. In some analyses viscosupplements were comparable in efficacy to systemic forms of active intervention, with more local reactions but fewer systemic adverse events. In other analyses HA products had more prolonged effects than IA corticosteroids. Overall, the aforementioned analyses support the use of the HA class of products in the treatment of knee OA.

SENTIMENT CLASSIFICATION of MOVIE REVIEWS USING CONTEXTUAL VALENCE SHIFTERS

Abstract: We present two methods for determining the sentiment expressed by a movie review. The semantic orientation of a review can be positive, negative, or neutral. We examine the effect of valence shifters on classifying the reviews. We examine three types of valence shifters: negations, intensifiers, and diminishers. Negations are used to reverse the semantic polarity of a particular term, while intensifiers and diminishers are used to increase and decrease, respectively, the degree to which a term is positive or negative. The first method classifies reviews based on the number of positive and negative terms they contain. We use the General Inquirer to identify positive and negative terms, as well as negation terms, intensifiers, and diminishers. We also use positive and negative terms from other sources, including a dictionary of synonym differences and a very large Web corpus. To compute corpus-based semantic orientation values of terms, we use their association scores with a small group of positive and negative terms. We show that extending the term-counting method with contextual valence shifters improves the accuracy of the classification. The second method uses a Machine Learning algorithm, Support Vector Machines. We start with unigram features and then add bigrams that consist of a valence shifter and another word. The accuracy of classification is very high, and the valence shifter bigrams slightly improve it. The features that contribute to the high accuracy are the words in the lists of positive and negative terms. Previous work focused on either the term-counting method or the Machine Learning method. We show that combining the two methods achieves better results than either method alone.

Effects of quality improvement strategies for type 2 diabetes on glycemic control: a meta-regression analysis.

Abstract: ContextThere have been numerous reports of interventions designed to improve the care of patients with diabetes, but the effectiveness of such interventions is unclearObjectiveTo assess the impact on glycemic control of 11 distinct strategies for quality improvement (QI) in adults with type 2 diabetesData Sources and Study SelectionMEDLINE (1966-April 2006) and the Cochrane Collaboration's Effective Practice and Organisation of Care Group database, which covers multiple bibliographic databases Eligible studies included randomized or quasi-randomized controlled trials and controlled before-after studies that evaluated a QI intervention targeting some aspect of clinician behavior or organizational change and reported changes in glycosylated hemoglobin (HbA1c) valuesData ExtractionPostintervention difference in HbA1c values were estimated using a meta-regression model that included baseline glycemic control and other key intervention and study features as predictorsData SynthesisFifty randomized controlled trials, 3 quasi-randomized trials, and 13 controlled before-after trials met all inclusion criteria Across these 66 trials, interventions reduced HbA1c values by a mean of 042% (95% confidence interval [CI], 029%-054%) over a median of 13 months of follow-up Trials with fewer patients than the median for all included trials reported significantly greater effects than did larger trials (061% vs 027%, P = 004), strongly suggesting publication bias Trials with mean baseline HbA1c values of 80% or greater also reported significantly larger effects (054% vs 020%, P = 005) Adjusting for these effects, 2 of the 11 categories of QI strategies were associated with reductions in HbA1c values of at least 050%: team changes (067%; 95% CI, 043%-091%; n = 26 trials) and case management (052%; 95% CI, 031%-073%; n = 26 trials); these also represented the only 2 strategies conferring significant incremental reductions in HbA1c values Interventions involving team changes reduced values by 033% more (95% CI, 012%-054%; P = 004) than those without this strategy, and those involving case management reduced values by 022% more (95% CI, 000%-044%; P = 04) than those without case management Interventions in which nurse or pharmacist case managers could make medication adjustments without awaiting physician authorization reduced values by 080% (95% CI, 051%-110%), vs only 032% (95% CI, 014%-049%) for all other interventions (P = 002)ConclusionsMost QI strategies produced small to modest improvements in glycemic control Team changes and case management showed more robust improvements, especially for interventions in which case managers could adjust medications without awaiting physician approval Estimates of the effectiveness of other specific QI strategies may have been limited by difficulty in classifying complex interventions, insufficient numbers of studies, and publication bias

Catalytic intermolecular direct arylation of perfluorobenzenes.

Abstract: Penta-, tetra-, tri-, and difluorobenzenes undergo direct arylation with a wide range of arylhalides in high yield. Inverse reactivity is observed compared to the common electrophilic aromatic substitution pathway since electron-deficient, C−H acidic arenes react preferentially. Computational studies indicate that C−H bond cleavage occurs via a concerted carbon−palladium and carbon−hydrogen bond cleaving event involving a carbonate or a bromide ligand. The reactions are rapid, require only a slight excess of the perfluoroarene reagent, and utilize commercially available, air-stable catalyst precursors.

Uses and abuses of EIDORS: an extensible software base for EIT

Abstract: EIDORS is an open source software suite for image reconstruction in electrical impedance tomography and diffuse optical tomography, designed to facilitate collaboration, testing and new research in these fields. This paper describes recent work to redesign the software structure in order to simplify its use and provide a uniform interface, permitting easier modification and customization. We describe the key features of this software, followed by examples of its use. One general issue with inverse problem software is the difficulty of correctly implementing algorithms and the consequent ease with which subtle numerical bugs can be inadvertently introduced. EIDORS helps with this issue, by allowing sharing and reuse of well-documented and debugged software. On the other hand, since EIDORS is designed to facilitate use by non-specialists, its use may inadvertently result in such numerical errors. In order to address this issue, we develop a list of ways in which such errors with inverse problems (which we refer to as 'cheats') may occur. Our hope is that such an overview may assist authors of software to avoid such implementation issues.

Barriers and facilitators to implementing shared decision-making in clinical practice: a systematic review of health professionals' perceptions

Abstract: Shared decision-making is advocated because of its potential to improve the quality of the decision-making process for patients and ultimately, patient outcomes. However, current evidence suggests that shared decision-making has not yet been widely adopted by health professionals. Therefore, a systematic review was performed on the barriers and facilitators to implementing shared decision-making in clinical practice as perceived by health professionals. Covering the period from 1990 to March 2006, PubMed, Embase, CINHAL, PsycINFO, and Dissertation Abstracts were searched for studies in English or French. The references from included studies also were consulted. Studies were included if they reported on health professionals' perceived barriers and facilitators to implementing shared decision-making in their practices. Shared decision-making was defined as a joint process of decision making between health professionals and patients, or as decision support interventions including decision aids, or as the active participation of patients in decision making. No study design was excluded. Quality of the studies included was assessed independently by two of the authors. Using a pre-established taxonomy of barriers and facilitators to implementing clinical practice guidelines in practice, content analysis was performed. Thirty-one publications covering 28 unique studies were included. Eleven studies were from the UK, eight from the USA, four from Canada, two from the Netherlands, and one from each of the following countries: France, Mexico, and Australia. Most of the studies used qualitative methods exclusively (18/28). Overall, the vast majority of participants (n = 2784) were physicians (89%). The three most often reported barriers were: time constraints (18/28), lack of applicability due to patient characteristics (12/28), and lack of applicability due to the clinical situation (12/28). The three most often reported facilitators were: provider motivation (15/28), positive impact on the clinical process (11/28), and positive impact on patient outcomes (10/28). This systematic review reveals that interventions to foster implementation of shared decision-making in clinical practice will need to address a broad range of factors. It also reveals that on this subject there is very little known about any health professionals others than physicians. Future studies about implementation of shared decision-making should target a more diverse group of health professionals.

Catalytic direct arylation with aryl chlorides, bromides, and iodides: intramolecular studies leading to new intermolecular reactions.

Abstract: A catalyst for the intramolecular direct arylation of a broad range of simple and heterocyclic arenes with aryl iodides, bromides, and chlorides has been developed. These reactions occur in excellent yield and are highly selective. Studies with aryl iodides substrates revealed that catalyst poisoning occurs due to the accumulation of iodide in the reaction media. This can be overcome by the addition of silver salts which also permits these reactions to occur at lower temperature. The utility of the methodology is illustrated by a rapid synthesis of a carbazole natural product and by the synthesis of sterically encumbered tetra-ortho-substituted biaryls via ring-opening reactions of the direct arylation products. Mechanistic investigations have provided insight into the catalyst's mode of action and show the presence of a kinetically significant C-H bond cleavage in palladium-catalyzed direct arylation of simple arenes. Knowledge garnered from these studies has led to the development of new intermolecular arylation reactions with previously inaccessible arenes, opening the door for the development of other new direct arylation processes.

Intraarticular corticosteroid for treatment of osteoarthritis of the knee

Abstract: BACKGROUND: Osteoarthritis (OA) is a common joint disorder. In the knee, injections of corticosteroids into the joint (intra-articular (IA)) may relieve inflammation, and reduce pain and disability. OBJECTIVES: To evaluate the efficacy and safety of IA corticosteroids in treatment of OA of the knee. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 2, 2003), MEDLINE, EMBASE, PREMEDLINE (all to July 2003), and Current Contents (Sept 2000). Specialised journals, trial reference lists and review articles were handsearched. SELECTION CRITERIA: Randomised controlled trials of IA corticosteroids for patients with OA of the knee: single/double blind, placebo-based/comparative studies, reporting at least one core OMERACT III outcome measure. DATA COLLECTION AND ANALYSIS: Methodological quality of trials was assessed, and data were extracted in duplicate. Fixed effect and random effects models, giving weighted mean differences (WMD), were used for continuous variables. Dichotomous outcomes were analysed by relative risk AUTHORS CONCLUSIONS : The short-term benefit of IA corticosteroids in treatment of knee OA is well established, and few side effects have been reported. Longer term benefits have not been confirmed based on the RevMan analysis. The response to HA products appears more durable. In this review, some discrepancies were observed between the RevMan 4.2 analysis and the original publication. These are likely the result of using secondary rather than primary data and the statistical methods available in RevMan 4.2. Future trials should have standardised outcome measures and assessment times, run longer, investigate different patient subgroups, and clinical predictors of response (those associated with inflammation and structural damage)

Toward Evidence-Based Quality Improvement: Evidence (and its Limitations) of the Effectiveness of Guideline Dissemination and Implementation Strategies 1966–1998

Abstract: Health systems internationally are investing substantial resources in quality improvement (QI) initiatives to promote effective and cost-effective health care. Such initiatives have the potential to improve the care received by patients by promoting interventions of proven benefit and discouraging ineffective interventions. However, individual health care organizations have relatively few resources for QI initiatives and decision makers need to consider how best to use these to maximize benefits. In some circumstances, the costs of QI initiatives are likely to outweigh their potential benefits while in others it may be more efficient to adopt less costly but less effective QI initiatives. In order to make informed judgments, decision makers need to consider a range of factors.1 First, what are the potential clinical areas for QI initiatives? These may reflect national or local priorities. Decision makers should consider the prevalence of the condition, whether there are effective and efficient health care interventions available to improve patient outcome, and whether there is evidence that current practice is suboptimal. Second, what are the likely benefits and costs required for specific QI strategies? Decision makers need to consider the likely effectiveness of different dissemination and implementation strategies for the targeted condition in their settings as well as the resources required to deliver the different strategies. Third, what are the likely benefits and costs as a result of any changes in provider behavior? In order to answer these questions, decision makers need evidence about the effects of specific QI strategies, the resources needed to deliver them, and how the effects of QI strategies vary depending on factors such as the context, targeted professionals, and targeted behaviors. Despite the current interest in QI, uncertainty remains as to the likely effectiveness of different QI strategies and the resources required to deliver them. In 1998, we conducted an overview of 41 published systematic reviews of professional behavior change strategies.2 The findings of these reviews suggest that passive dissemination of educational materials (e.g., mailing guidelines to professionals) is largely ineffective, whereas reminders and educational outreach are largely effective and multifaceted interventions are more likely to be effective than single interventions. However, these reviews commonly used vote counting methods that add up the number of positive and negative comparisons to conclude whether or not interventions are effective.3 The vote counting method fails to provide an estimate of the effect size of an intervention (giving equal weight to comparisons that show a 1% change or a 50% change) and ignores the precision of the estimate from the primary comparisons (giving equal weight to comparisons with 100 or 1,000 participants).3,4 Further comparisons with potential unit of analysis errors need to be excluded because of the uncertainty of their statistical significance. Underpowered comparisons observing clinically significant but statistically insignificant effects would be counted as “no effect comparisons.”3,4 Previous reviews have also tended to describe interventions based on the author's main description of the intervention, which often ignores co-interventions. In this paper, we describe the available evidence published between 1966 and 1998 (and highlight its limitations) concerning the effectiveness of clinical practice guideline dissemination and implementation strategies (a common component of QI initiatives) based upon the findings of a systematic review that attempted to address the methodologic weaknesses of previous reviews by adopting a more explicit analytical approach.1,5

Redox signaling in hypertension.

Abstract: Diseases such as hypertension, atherosclerosis and diabetes are associated with vascular functional and structural changes including endothelial dysfunction, altered contractility and vascular remodeling. Cellular events underlying these processes involve changes in vascular smooth muscle cell (VSMC) growth, apoptosis/anoikis, cell migration, inflammation, and fibrosis. Many stimuli influence cellular changes, including mechanical forces, such as shear stress, and vasoactive agents, of which angiotensin II (Ang II) appears to be amongst the most important. Ang II mediates many of its pleiotropic vascular effects through NAD(P)H oxidase-derived reactive oxygen species (ROS). Mechanical forces, comprising both unidirectional laminar and oscillatory shear, are increasingly being recognized as important inducers of vascular NO and ROS generation. In general, laminar flow is associated with upregulation of eNOS and NO production and increased expression of antioxidants glutathione peroxidase and superoxide dismutase, thereby promoting a healthy vascular wall and protecting against oxidative vascular injury. On the other hand, oscillatory shear is linked to increased ROS production with consequent oxidative damage, as occurs in hypertension. ROS function as important intracellular and intercellular second messengers to modulate many downstream signaling molecules, such as protein tyrosine phosphatases, protein tyrosine kinases, transcription factors, mitogen-activated protein kinases, and ion channels. Induction of these signaling cascades leads to VSMC growth and migration, expression of pro-inflammatory mediators, and modification of extracellular matrix. In addition, ROS increase intracellular free Ca(2+) concentration, a major determinant of vascular reactivity. ROS influence signaling molecules by altering the intracellular redox state and by oxidative modification of proteins. In physiological conditions, low concentrations of intracellular ROS play an important role in normal redox signaling involved in maintaining vascular function and integrity. Under pathological conditions ROS contribute to vascular dysfunction and remodeling through oxidative damage. The present review describes some of the redox-sensitive signaling pathways that are involved in the functional and structural vascular changes associated with hypertension.

Do Poor Children Become Poor Adults? Lessons from a Cross-Country Comparison of Generational Earnings Mobility

Abstract: A cross-country comparison of generational earnings mobility is offered, and the reasons for the degree to which the long-run labour market success of children is related to that of their parents is examined. The rich countries differ significantly in the extent to which parental economic status is related to the labour market success of children in adulthood. The strength of these associations should not be interpreted as offering a target or menu for the conduct of policy. A framework for understanding the underlying causal process as well as the conception of equality of opportunity is reviewed as a guide for public policy.

Quantifying axonal loss after optic neuritis with optical coherence tomography.

Abstract: Objective To determine to what degree changes in retinal nerve fiber layer (RNFL) thickness after optic neuritis (ON) correlate with either visual recovery or impairment. Methods ON can cause visible defects within the RNFL, which can be quantified using optical coherence tomography (OCT). It may be possible to predict visual recovery by measuring RNFL loss after ON. Fifty-four patients underwent repeated evaluations with optical coherence tomography and standardized ophthalmic testing after ON. Regression analyses were used to determine the relationship between RNFL thickness and visual function. Results Thinning of the RNFL was seen in the majority of patients (74%), and it tended to occur within 3 to 6 months of ON. The average RNFL value was thinner (p < 0.0001) in the affected (78μm) compared with the unaffected eye (100μm). Patients with incomplete visual recovery demonstrated greater RNFL loss after ON. Regression analyses demonstrated a threshold of RNFL thickness (75μm), below which RNFL measurements predicted persistent visual dysfunction. Interpretation Determination of RNFL thickness may predict visual recovery after ON, and lower RNFL values correlate with impaired visual function. Optical coherence tomography may have a potential role as a surrogate marker for axonal integrity within the optic nerve among patients with ON. Ann Neurol 2006;59:963–969

Acetaminophen for osteoarthritis

Abstract: Background Osteoarthritis (OA) is the most common form of arthritis. Published guidelines and expert opinion are divided over the relative role of acetaminophen (also called paracetamol or Tylenol) and non-steroidal anti-inflammatory drugs (NSAIDs) as first-line pharmacologic therapy. The comparative safety of acetaminophen and NSAIDs is also important to consider. This update to the original 2003 review includes nine additional RCTs. Objectives To assess the efficacy and safety of acetaminophen versus placebo and versus NSAIDs (ibuprofen, diclofenac, arthrotec, celecoxib, naproxen, rofecoxib) for treating OA. Search methods We searched MEDLINE (up to July 2005), EMBASE (2002-July 2005), Cochrane Central Register of Controlled Trials (CENTRAL), ACP Journal Club, DARE, Cochrane Database of Systematic Reviews (all from 1994 to July 2005). Reference lists of identified RCTs and pertinent review articles were also hand searched. Selection criteria Published randomized controlled trials (RCTs) evaluating the efficacy and safety of acetaminophen alone in OA were considered for inclusion. Data collection and analysis Pain, physical function and global assessment outcomes were reported. Results for continuous outcome measures were expressed as standardized mean differences (SMD). Dichotomous outcome measures were pooled using relative risk (RR) and the number needed to treat (NNT) was calculated. Main results Fifteen RCTs involving 5986 participants were included in this review. Seven RCTs compared acetaminophen to placebo and ten RCTs compared acetaminophen to NSAIDs. In the placebo-controlled RCTs, acetaminophen was superior to placebo in five of the seven RCTs and had a similar safety profile. Compared to placebo, a pooled analysis of five trials of overall pain using multiple methods demonstrated a statistically significant reduction in pain (SMD -0.13, 95% CI -0.22 to -0.04), which is of questionable clinical significance. The relative percent improvement from baseline was 5% with an absolute change of 4 points on a 0 to 100 scale. The NNT to achieve an improvement in pain ranged from 4 to 16. In the comparator-controlled RCTs, acetaminophen was less effective overall than NSAIDs in terms of pain reduction, global assessments and in terms of improvements in functional status. No significant difference was found overall between the safety of acetaminophen and NSAIDs, although patients taking traditional NSAIDS were more likely to experience an adverse GI event (RR 1.47, (95% CI 1.08 to 2.00). 19% of patients in the traditional NSAID group versus 13% in the acetaminophen group experienced an adverse GI event. However, the median trial duration was only 6 weeks and it is difficult to assess adverse outcomes in a relatively short time period. Authors' conclusions The evidence to date suggests that NSAIDs are superior to acetaminophen for improving knee and hip pain in people with OA. The size of the treatment effect was modest, and the median trial duration was only six weeks, therefore, additional considerations need to be factored in when making the decision between using acetaminophen or NSAIDs. In OA subjects with moderate-to-severe levels of pain, NSAIDs appear to be more effective than acetaminophen.

Work-supportive family, family-supportive supervision, use of organizational benefits, and problem-focused coping: implications for work-family conflict and employee well-being.

Abstract: Employees (n = 230) from multiple organizations and industries were involved in a study assessing how work-family conflict avoidance methods stemming from the family domain (emotional sustenance and instrumental assistance from the family), the work domain (family-supportive supervision, use of telework and flextime), and the individual (use of problem-focused coping) independently relate to different dimensions of work-family conflict and to employees' affective and physical well-being. Results suggest that support from one's family and one's supervisor and the use of problem-focused coping seem most promising in terms of avoiding work-family conflict and/or decreased well-being. Benefits associated with the use of flextime, however, are relatively less evident, and using telework may potentially increase the extent to which family time demands interfere with work responsibilities.

Why do high school students lack motivation in the classroom? Toward an understanding of academic amotivation and the role of social support

Abstract: The present series of studies sought to develop and conceptually validate a taxonomy of reasons that give rise to academic amotivation and to investigate its social antecedents and academic consequences. In Study 1 (N = 351), an exploratory factor analysis offered preliminary support for an academic amotivation taxonomy comprising four dimensions: ability beliefs, effort beliefs, characteristics of the task, and value placed on the task. In Study 2 (N = 349), the proposed taxonomy was further corroborated through 1st- and 2nd-order confirmatory factor analyses, and its discriminant validity and construct validity were documented. Study 3 (N = 741) offered evidence for a model of the relationships among social support (from parents, teachers, and friends), amotivation, and academic outcomes (e.g., achievement, academic self-esteem, intention to drop out). Results are considered in terms of an increased conceptual understanding of academic amotivation, and implications for curricula and interventions are discussed.