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Background Underreporting of harms in randomized controlled trials (RCTs) may lead to incomplete or erroneous assessments of the perceived benefit-to-harm profile of an intervention. To compare benefit with harm in clinical practice and future clinical studies, adverse event (AE) profiles including severity need to be understood. Even though patients report harm symptoms earlier and more frequently than clinicians, rheumatology RCTs currently do not provide a reporting framework from the patient's perspective regarding harms. Our objective for this meta-research project was to identify AEs in order to determine harm clusters and whether these could be self-reported by patients. Our other objective was to examine reported severity grading of the reported harms. Methods We considered primary publications of RCTs eligible if they were published between 2008 and 2018 evaluating pharmacological interventions in patients with a rheumatic or musculoskeletal condition and if they were included in Cochrane reviews. We extracted data on harms such as reported AE terms together with severity (if described), and categorized AE- and severity-terms into overall groups. We deemed all AEs with felt components appropriate for patient self-reporting. Results The literature search identified 187 possible Cochrane reviews, of which 94 were eligible for evaluation, comprising 1,297 articles on individual RCTs. Of these RCTs, 93 pharmacological trials met our inclusion criteria (including 31,023 patients; representing 20,844 accumulated patient years), which reported a total of 21,498 AEs, corresponding to 693 unique reported terms for AEs. We further sub-categorized these terms into 280 harm clusters (i.e., themes). AEs appropriate for patient self-reporting accounted for 58% of the AEs reported. Among the reported AEs, we identified medical terms for all of the 117 harm clusters appropriate for patient reporting and lay language terms for 86%. We intended to include severity grades of the reported AEs, but there was no evidence for systematic reporting of clinician- or patient-reported severity in the primary articles of the 93 trials. However, we identified 33 terms suggesting severity, but severity grading was discernible in only 9%, precluding a breakdown by severity in this systematic review. Conclusions Our results support the need for a standardized framework for patients’ reporting of harms in rheumatology trials. Reporting of AEs with severity should be included in future reporting of harms, both from the patients’ and investigators’ perspectives. Registration PROSPERO: CRD42018108393

BACKGROUND AND OBJECTIVES: There is considerable actual and potential waste in research. The aim of this article is to describe how using an evidence-based research approach before conducting a study helps to ensure that the new study truly adds value.STUDY DESIGN AND SETTING: Evidence-based research is the use of prior research in a systematic and transparent way to inform a new study so that it is answering questions that matter in a valid, efficient, and accessible manner. In this second article of the evidence-based research series, we describe how to apply an evidence-based research approach before starting a new study.RESULTS: Before a new study is performed, researchers need to provide a solid justification for it using the available scientific knowledge as well as the perspectives of end users. The key method for both is to conduct a systematic review of earlier relevant studies.CONCLUSION: Describing the ideal process illuminates the challenges and opportunities offered through the suggested evidence-based research approach. A systematic and transparent approach is needed to provide justification for and to optimally design a relevant and necessary new study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a global pandemic. Governments have implemented combinations of "lockdown" measures of various stringencies, including school and workplace closures, cancellations of public events, and restrictions on internal and external movements. These policy interventions are an attempt to shield high-risk individuals and to prevent overwhelming countries' healthcare systems, or, colloquially, "flatten the curve." However, these policy interventions may come with physical and psychological health harms, group and social harms, and opportunity costs. These policies may particularly affect vulnerable populations and not only exacerbate pre-existing inequities but also generate new ones. METHODS: We developed a conceptual framework to identify and categorize adverse effects of COVID-19 lockdown measures. We based our framework on Lorenc and Oliver's framework for the adverse effects of public health interventions and the PROGRESS-Plus equity framework. To test its application, we purposively sampled COVID-19 policy examples from around the world and evaluated them for the potential physical, psychological, and social harms, as well as opportunity costs, in each of the PROGRESS-Plus equity domains: Place of residence, Race/ethnicity, Occupation, Gender/sex, Religion, Education, Socioeconomic status, Social capital, Plus (age, and disability). RESULTS: We found examples of inequitably distributed adverse effects for each COVID-19 lockdown policy example, stratified by a low- or middle-income country and high-income country, in every PROGRESS-Plus equity domain. We identified the known policy interventions intended to mitigate some of these adverse effects. The same harms (anxiety, depression, food insecurity, loneliness, stigma, violence) appear to be repeated across many groups and are exacerbated by several COVID-19 policy interventions. CONCLUSION: Our conceptual framework highlights the fact that COVID-19 policy interventions can generate or exacerbate interactive and multiplicative equity harms. Applying this framework can help in three ways: (1) identifying the areas where a policy intervention may generate inequitable adverse effects; (2) mitigating the policy and practice interventions by facilitating the systematic examination of relevant evidence; and (3) planning for lifting COVID-19 lockdowns and policy interventions around the world.

Background Social media are an increasingly commonly used platform for delivering health promotion interventions. Although recent research has focused on the effectiveness of social media interventions for health promotion, very little is known about the optimal content within such interventions, and the active ingredients to promote health behavior change using social media are not clear. Identifying which behavior change techniques (BCTs) are reported may help to clarify the content of interventions using a generalizable terminology that may facilitate future intervention development. Objective This study aimed to identify which BCTs are reported in social media interventions for promoting health behavior change in adults. Methods We included 71 studies conducted with adult participants (aged ≥18 years) and for which social media intervention was considered interactive in a Cochrane review of the effectiveness of such interventions. We developed a coding manual informed by the Behavior Change Technique Taxonomy version 1 (BCTTv1) to identify BCTs in the included studies. We identified BCTs in all study arms (including control) and described BCTs in the group and self-directed components of studies. We characterized the dose of delivery for each BCT by low and high intensity. We used descriptive analyses to characterize the reported BCTs. Results Our data consisted of 71 studies published from 2001 to 2017, mainly conducted in high-income countries (n=65). Most studies (n=31) used tailored, interactive websites to deliver the intervention; Facebook was the most used mainstream platform. In developing our coding manual, we adapted some BCTTv1 instructions to better capture unique nuances of how BCTs were operationalized in social media with respect to likes, retweets, smiles, congratulations, and badges. Social support (unspecified), instruction on how to perform the behavior, and credible source were most frequently identified BCTs in intervention arms of studies and group-delivery settings, whereas instruction on how to perform the behavior was most commonly applied in self-directed components of studies, control arms, and individual participant settings. Instruction on how to perform the behavior was also the most frequently reported BCT in both intervention and control arms simultaneously. Instruction on how to perform the behavior, social support (unspecified), self-monitoring of behavior, information about health consequences, and credible source were identified in the top 5 BCTs delivered with the highest intensity. Conclusions This study within a review provides a detailed description of the BCTs and their dose to promote behavior change in web-based, interactive social media interventions. Clarifying active ingredients in social media interventions and the intensity of their delivery may help to develop future interventions that can more clearly build upon the existing evidence.

This is a protocol for a co‐registered Cochrane and Campbell Review (Methodology). The objectives are as follows: To identify, describe and assess methods for: when to replicate a systematic review; how to replicate a systematic review.

Objective: To evaluate how and to what extent health equity considerations are assessed in World Health Organization (WHO) guidelines. Study Design and Setting: We evaluated WHO guidelines published between January 2014 and May 2019. Health equity consider-ations were assessed in relation to differences in baseline risk, importance of outcomes for socially disadvantaged populations, inclusion of health inequity as an outcome, equity-related subgroup analysis, and indirectness in each recommendation. Results: We identified 111 WHO guidelines, and 54% (60 of 111) of these used the Evidence to Decision (EtD) framework. For the 60 guidelines using an EtD framework, the likely impact on health equity was supported by research evidence in 28% of the recommendations (94 of 332). Research evidence was mostly provided as differences in baseline risk (23%, 78/332). Research evidence less frequently addressed the importance of outcomes for socially disadvantaged populations (11%, 36/332), considered indirectness of the evidence for socially disadvantaged populations (2%, 5/332), considered health inequities as an outcome (2%, 5/332) and considered differences in the magnitude of effect in relative terms between disadvantaged and more advantaged populations (1%, 3/332). Conclusion: The provision of research evidence to support equity judgements in WHO guidelines is still suboptimal, suggesting the need for better guidance and more training. (c) 2020 Elsevier Inc. All rights reserved.

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: The primary objective is to compare the benefits and harms of different disease‐modifying anti‐rheumatic drugs (DMARDs) as initial therapy and after failure of conventional synthetic DMARDs or biologic or targeted synthetic DMARDs in adults with rheumatoid arthritis through a network meta‐analysis (NMA). A secondary objective is to rank the interventions for both benefits and harms. This protocol describes the approach for separate NMAs for the three populations of interest (described below), which we intend to publish as three separate Cochrane Reviews. 1) Disease‐modifying anti‐rheumatic drugs for rheumatoid arthritis as initial therapy: a systematic review and network meta‐analysis 2) Disease‐modifying anti‐rheumatic drugs for rheumatoid arthritis after failure of conventional synthetic disease‐modifying anti‐rheumatic drugs: a systematic review and network meta‐analysis 3) Disease‐modifying anti‐rheumatic drugs for rheumatoid arthritis after failure of biologic or targeted synthetic therapy: a systematic review and network meta‐analysis

Background Stakeholder engagement has become widely accepted as a necessary component of guideline development and implementation. While frameworks for developing guidelines express the need for those potentially affected by guideline recommendations to be involved in their development, there is a lack of consensus on how this should be done in practice. Further, there is a lack of guidance on how to equitably and meaningfully engage multiple stakeholders. We aim to develop guidance for the meaningful and equitable engagement of multiple stakeholders in guideline development and implementation. Methods This will be a multi-stage project. The first stage is to conduct a series of four systematic reviews. These will (1) describe existing guidance and methods for stakeholder engagement in guideline development and implementation, (2) characterize barriers and facilitators to stakeholder engagement in guideline development and implementation, (3) explore the impact of stakeholder engagement on guideline development and implementation, and (4) identify issues related to conflicts of interest when engaging multiple stakeholders in guideline development and implementation. Discussion We will collaborate with our multiple and diverse stakeholders to develop guidance for multi-stakeholder engagement in guideline development and implementation. We will use the results of the systematic reviews to develop a candidate list of draft guidance recommendations and will seek broad feedback on the draft guidance via an online survey of guideline developers and external stakeholders. An invited group of representatives from all stakeholder groups will discuss the results of the survey at a consensus meeting which will inform the development of the final guidance papers. Our overall goal is to improve the development of guidelines through meaningful and equitable multi-stakeholder engagement, and subsequently to improve health outcomes and reduce inequities in health.

Background Given the complex nature of opioid addiction treatment and the rising number of available opioid substitution and antagonist therapies (OSAT), there is no ‘gold standard’ measure of treatment effectiveness, and each successive trial measures a different set of outcomes which reflect success in arbitrary or opportune terms. We sought to describe the variation in current outcomes employed across clinical trials for opioid addiction, as well as determine whether a discrepancy exists between the treatment targets that patients consider important and how treatment effectiveness is measured in the literature. Methods We searched nine commonly used databases (e.g., EMBASE, MEDLINE) from inception to August 1, 2015. Outcomes used across trials were extracted and categorized according to previously established domains. To evaluate patient-reported goals of treatment, semi-structured interviews were conducted with 18 adults undergoing methadone treatment. Results We identified 60 trials eligible for inclusion. Once outcomes were categorized into eight broad domains (e.g., abstinence/substance abuse), we identified 21 specific outcomes with furthermore 53 subdomains and 118 measurements. Continued opioid use and treatment retention were the most commonly reported measures (46%, n = 28). The majority of patients agreed that abstinence from opioids was a primary goal in their treatment, although they also stressed goals under-reported in clinical trials. Conclusions There is inconsistency in the measures used to evaluate the effectiveness of OSATs. Individual and population level decision making is being guided by a standard of effect considered useful to researchers yet in direct conflict with what patients deem important. Trial registration PROSPERO, CRD42013006507.

Objective:To evaluate and update the evidence for the measurement properties of the Psoriatic Arthritis Impact of Disease (PsAID12) questionnaire to measure health-related quality of life (HRQoL) in psoriatic arthritis (PsA).Methods:The PsAID12 psychometric evidence was gathered in a systematic literature review in PsA (registration number: CRD42016032546). The study quality was appraised using the Consensus-based Standards for the selection of health Measurement Instruments–Outcome Measures in Rheumatology (COSMIN-OMERACT) good methods check-list. Content validity, test–retest reliability, construct validity, longitudinal construct validity, discrimination, and thresholds of meaning were appraised. Additional analyses for construct validity, responsiveness, and sensitivity to change were conducted in available observational data sets after prespecified hypotheses were formulated.Results:Eight publications (129-474 patients) were analyzed. The PsAID12 fulfilled OMERACT criteria for content validity (patients and physicians endorsed content match with PsA HRQoL domain), feasibility (endorsed by patients and physicians), and test–retest reliability (intraclass correlation coefficient: 0.91-0.95). A priori construct validity hypotheses were mostly met: Psoriatic Arthritis Impact of Disease had high correlation with generic ( r = 0.76-0.87) and PsA-specific HRQol measures (0.8), and with measures of physical function (0.66-0.72), work productivity (0.69-0.75), pain (0.83), and fatigue (0.84). Psoriatic Arthritis Impact of Disease had moderate-high correlation with measures of patient global (0.49-0.84) and dermatologic HRQoL (0.36-0.53). Correlations were higher with generic HRQoL measured by short form-36 physical component score (0.47-0.73) versus short form-36 mental component score (0.22-0.60). Three studies confirmed known group validity of PsAID12 according to PsA disease activity. Psoriatic Arthritis Impact of Disease discriminated between change groups in 2 longitudinal studies (standardized response mean: 0.74-0.91, 53 and 105 patients). The minimal clinically important improvement was 3 and 1.4 points.Conclusion:Psoriatic Arthritis Impact of Disease had evidence for good content and construct validity, reliability, and longitudinal construct validity and is ready to evaluate in clinical trials.

Background Health systems are recommended to capture routine patient sociodemographic data as a key step in providing equitable person-centred care. However, collection of this information has the potential to cause harm, especially for vulnerable or potentially disadvantaged patients. Objective To identify harms perceived or experienced by patients, their families, or health-care providers from collection of sociodemographic information during routine health-care visits and to identify best practices for when, by whom and how to collect this information. Search strategy We searched OVID MEDLINE, PubMed "related articles" via NLM and healthevidence.org to the end of January 2018 and assessed reference lists and related citations of included studies. Inclusion criteria We included studies reporting on harms of collecting patient sociodemographic information in health-care settings. Data extraction and synthesis Data on study characteristics and types of harms were extracted and summarized narratively. Main results Eighteen studies were included; 13 provided patient perceptions or experiences with the collection of these data and seven studies reported on provider perceptions. Five reported on patient recommendations for collecting sociodemographic information. Patients and providers reported similar potential harms which were grouped into the following themes: altered behaviour which may affect care-seeking, data misuse or privacy concerns, discomfort, discrimination, offence or negative reactions, and quality of care. Patients suggested that sociodemographic information be collected face to face by a physician. Discussion and conclusions Overall, patients support the collection of sociodemographic information. However, harms are possible, especially for some population subgroups. Harms may be mitigated by providing a rationale for the collection of this information.

Background The randomized controlled trial (RCT) is considered the gold standard study design to inform decisions about the effectiveness of interventions. However, a common limitation is inadequate reporting of the applicability of the intervention and trial results for people who are “socially disadvantaged” and this can affect policy-makers’ decisions. We previously developed a framework for identifying health-equity-relevant trials, along with a reporting guideline for transparent reporting. In this study, we provide a descriptive assessment of health-equity considerations in 200 randomly sampled equity-relevant trials. Methods We developed a search strategy to identify health-equity-relevant trials published between 2013 and 2015. We randomly sorted the 4316 records identified by the search and screened studies until 100 individually randomized (RCTs) and 100 cluster randomized controlled trials (CRTs) were identified. We developed and pilot-tested a data extraction form based on our initial work, to inform the development of our reporting guideline for equity-relevant randomized trials. Results In total, 39 trials (20%) were conducted in a low- and middle-income country and 157 trials (79%) in a high-income country focused on socially disadvantaged populations (78% CRTs, 79% RCTs). Seventy-four trials (37%) reported a subgroup analysis across a population characteristic associated with disadvantage (25% CRT, 49% RCTs), with 19% of included studies reporting subgroup analyses across sex, 9% across race/ethnicity/culture, and 4% across socioeconomic status. No subgroup analyses were reported for place of residence, occupation, religion, education, or social capital. One hundred and forty-one trials (71%) discussed the applicability of their results to one or more socially disadvantaged populations (68% of CRT, 73% of RCT). Discussion In this set of trials, selected for their relevance to health equity, data that were disaggregated for socially disadvantaged populations were rarely reported. We found that even when the data are available, opportunities to analyze health-equity considerations are frequently missed. The recently published equity extension of the Consolidated Reporting Standards for Randomized Trials (CONSORT-Equity) may help improve delineation of hypotheses related to socially disadvantaged populations, and transparency and completeness of reporting of health-equity considerations in RCTs. This study can serve as a baseline assessment of the reporting of equity considerations.

IntroductionAs vaccine-preventable disease outbreaks increase, there is growing international interest in monitoring public attitudes towards vaccination and implementing and evaluating vaccine promotion interventions. Outcome selection and measurement are central to intervention evaluation. Measuring uptake rates alone cannot determine which elements in a multicomponent vaccine-promotion intervention are most effective, why specific populations are undervaccinated or when confidence in vaccines is wavering. To develop targeted and cost-effective interventions and policies, it is necessary to measure vaccination-related psychosocial factors such as knowledge, attitudes and aspects of decision-making. This scoping review aims to identify, compare and summarise the properties and validation of instruments for measuring vaccination-related psychosocial factors and identify gaps where no instruments exist.Methods and analysisWe will search Medline OVID, Embase OVID, CINAHL and PsycINFO with no date restriction, using a pilot-tested search strategy of terms related to vaccination: knowledge, attitudes, trust, acceptance and decision-making and measurement, psychometric testing or validation. This search will be supplemented with manual search and expert consultation. We will include studies that describe instrument development, adaptation or testing and include evaluation of at least two measurement properties (eg, content, criterion, or construct validity; test–retest reliability; internal consistency; sensitivity; responsiveness). Instruments measuring a vaccination-related psychosocial factor in any population will be included. All studies will be screened by one reviewer, with a sample double-screened to confirm accuracy. Disagreements will be resolved with a third reviewer. Data will be synthesised narratively and through summary tables to chart and compare instrument characteristics such as factors measured, date and/or location of development or validation, measurement properties evaluated and population.Ethics and disseminationThis scoping review aims to provide an overview of existing instruments and ascertain measurement gaps where no measurement instruments currently exist. The identified instruments will form the basis of an open-access online repository of instruments.

Objective.Nonadherence to medications is common in rheumatic conditions and associated with increased morbidity. Heterogeneous outcome reporting by researchers compromises the synthesis of evidence of interventions targeting adherence. We aimed to assess the scope of outcomes in interventional studies of medication adherence.Methods.We searched electronic databases to February 2019 for published randomized controlled trials and observational studies of interventions with the primary outcome of medication adherence including adults with any rheumatic condition, written in English. We extracted and analyzed all outcome domains and adherence measures with prespecified extraction and analysis protocols.Results.Overall, 53 studies reported 71 outcome domains classified into adherence (1 domain), health outcomes (38 domains), and adherence-related factors (e.g., medication knowledge; 32 domains). We subdivided adherence into 3 phases: initiation (n = 13 studies, 25%), implementation (n = 32, 60%), persistence (n = 27, 51%), and phase unclear (n = 20, 38%). Thirty-seven different instruments reported adherence in 115 unique ways (this includes different adherence definitions and calculations, metric, and method of aggregation). Forty-one studies (77%) reported health outcomes. The most frequently reported were medication adverse events (n = 24, 45%), disease activity (n = 11, 21%), bone turnover markers/physical function/quality of life (each n = 10, 19%). Thirty-three studies (62%) reported adherence-related factors. The most frequently reported were medication beliefs (n = 8, 15%), illness perception/medication satisfaction/satisfaction with medication information (each n = 5, 9%), condition knowledge/medication knowledge/trust in doctor (each n = 3, 6%).Conclusion.The outcome domains and adherence measures in interventional studies targeting adherence are heterogeneous. Consensus on relevant outcomes will improve the comparison of different strategies to support medication adherence in rheumatology.

Summary Canada's history of nation building, combined with its status as a so-called middle power in international affairs, has been translated into an approach to global health that is focused on equity and global citizenship. Canada has often aspired to be a socially progressive force abroad, using alliance building and collective action to exert influence beyond that expected from a country with moderate financial and military resources. Conversely, when Canada has primarily used economic self-interest to define its global role, the country's perceived leadership in global health has diminished. Current Prime Minister Justin Trudeau's Liberal federal government has signalled a return to progressive values, driven by appreciation for diversity, equality, and Canada's responsibility to be a good global citizen. However, poor coordination of efforts, limited funding, and the unaddressed legacy of Canada's colonisation of Indigenous peoples weaken the potential for Canadians to make meaningful contributions to improvement of global health equity. Amid increased nationalism and uncertainty towards multilateral commitments by some major powers in the world, the Canadian federal government has a clear opportunity to convert its commitments to equity and global citizenship into stronger leadership on the global stage. Such leadership will require the translation of aspirational messages about health equity and inclusion into concrete action at home and internationally.

Background Fatigue is a prevalent and debilitating symptom in patients receiving hemodialysis. We aimed to identify and evaluate the characteristics and psychometric properties of patient-reported outcome measures for fatigue in patients receiving hemodialysis, to inform the selection of a robust and feasible measure for use in randomized trials in hemodialysis. Study Design Systematic review of outcome measures for fatigue. Setting & Population Patients receiving hemodialysis. Search Strategy & Sources MEDLINE, Embase, PsycINFO, and CINAHL from inception to April 2017 were searched for all studies that reported fatigue in patients receiving hemodialysis. Analytical Approach With a focus on addressing methods, items (individual questions) from all measures were categorized into content and measurement dimensions of fatigue. We assessed the general characteristics (eg, number of items and cost) and psychometric properties of all measures. Results From 123 studies, we identified 43 different measures: 24 (55%) were developed specifically for the hemodialysis population (of which 18 were nonvalidated author-developed measures for use in their study only), 17 (40%) for other populations, and 2 (5%) for chronic kidney disease (all stages). The measures assessed 11 content dimensions of fatigue, the 3 most frequent being level of energy (19 [44%]), tiredness (15 [35%]), and life participation (14 [33%]); and 4 measurement dimensions: severity (34 [79%]), frequency (10 [23%]), duration (4 [9%]), and change (1 [2%]). The vitality subscale of the 36-Item Short Form Health Survey (SF-36) was the most frequently used (19 [15%] studies), but has only been tested for reliability in hemodialysis. Of the fatigue-specific measures, the Chalder Fatigue Scale was the only one evaluated in hemodialysis, but the full psychometric robustness remains uncertain. Limitations For feasibility, we searched for validation studies in the hemodialysis population using the names of measures identified in the primary search strategy. Conclusions A very wide range of measures have been used to assess fatigue in patients receiving hemodialysis, each varying in content and length. Many have limited validation data available in this population. A standardized and psychometrically robust measure that captures dimensions of fatigue that are important to patients is needed to estimate and improve this disabling complication of hemodialysis.

Decision aids help patients make total joint arthroplasty decisions, but presurgical evaluation might influence the effects of a decision aid. We compared the effects of a decision aid among patients considering total knee arthroplasty at 2 surgical screening clinics with different evaluation processes.We performed a subgroup analysis of a randomized controlled trial. Patients were recruited from 2 surgical screening clinics: an academic clinic providing 20-minute physician consultations and a community clinic providing 45-minute physiotherapist/nurse consultations with education. We compared the effects of decision quality, decisional conflict and surgery rate using Cochran-Mantel-Haenszel χWe evaluated 242 patients: 123 from the academic clinic (61 who used the decision aid and 62 controls) and 119 from the community clinic (59 who used the decision aid and 60 controls). Results suggested a between-site difference in the effect of the decision aid on the patients' decision quality (The decision aid had a greater effect at the academic site than at the community site, which provided longer consultations with more verbal education. Hence, decision aids might be of greater value when more extensive total knee arthroplasty presurgical assessment and counselling are either impractical or unavailable.Les aides à la décision guident les patients dans leurs choix quant à l'arthroplastie par prothèse totale, mais l'évaluation préopératoire pourrait modifier leur influence. Nous avons comparé cette influence chez les patients qui envisagent une arthroplastie totale du genou dans 2 cliniques de dépistage chirurgical ayant des processus d'évaluation différents.Nous avons effectué une analyse par sous-groupes d'un essai clinique randomisé. Les patients ont été recrutés dans 2 cliniques de dépistage chirurgical : une clinique universitaire offrant des consultations de 20 minutes avec un médecin et une clinique communautaire offrant des consultations de 45 minutes avec un physiothérapeute ou une infirmière et de l'enseignement. Nous avons comparé l'influence sur la qualité des décisions, les conflits décisionnels et le taux d'intervention chirurgicale à l'aide des tests de Cochran-Mantel-Haenszel (χ2) et du test de Breslow-Day.Nous avons évalué 242 patients : 123 de la clinique universitaire (61 qui ont utilisé l'outil et 62 témoins) et 119 de la clinique communautaire (59 qui ont utilisé l'outil et 60 témoins). Les résultats semblaient indiquer une différence entre les sites quant à l'influence de l'aide sur la qualité des décisions des patients (L'aide à la décision a eu un plus grand effet au site universitaire qu'au site communautaire, qui offrait de plus longues consultations et plus d'enseignement verbal. Ce type d'outil aurait donc plus de valeur dans les cas où il est difficile ou impossible d'offrir une évaluation préopératoire détaillée et des conseils approfondis pour l'arthroplastie totale du genou.

This review summarizes the evidence from six randomized controlled trials that judged the effectiveness of systematic review summaries on policymakers' decision making, or the most effective ways to present evidence summaries to increase policymakers' use of the evidence. This review included six randomized controlled studies. A randomized controlled study is one in which the participants are divided randomly (by chance) into separate groups to compare different treatments or other interventions. This method of dividing people into groups means that the groups will be similar and that the effects of the treatments they receive will be compared more fairly. At the time the study is done, it is not known which treatment is the better one. The researchers who did these studies invited people from Europe, North America, South America, Africa, and Asia to take part in them. Two studies looked at “policy briefs,” one study looked at an “evidence summary,” two looked at a “summary of findings table,” and one compared a “summary of findings table” to an evidence summary. None of these studies looked at how policymakers directly used evidence from systematic reviews in their decision making, but two studies found that there was little to no difference in how they used the summaries. The studies relied on reports from decision makers. These studies included questions such as, “Is this summary easy to understand?” Some of the studies looked at users' knowledge, understanding, beliefs, or how credible (trustworthy) they believed the summaries to be. There was little to no difference in the studies that looked at these outcomes. Study participants rated the graded entry format higher for usability than the full systematic review. The graded entry format allows the reader to select how much information they want to read. The study participants felt that all evidence summary formats were easier to understand than full systematic reviews. Plain language summary Policy briefs make systematic reviews easier to understand but little evidence of impact on use of study findings It is likely that evidence summaries are easier to understand than complete systematic reviews. Whether these summaries increase the use of evidence from systematic reviews in policymaking is not clear. What is this review about? Systematic reviews are long and technical documents that may be hard for policymakers to use when making decisions. Evidence summaries are short documents that describe research findings in systematic reviews. These summaries may simplify the use of systematic reviews. Other names for evidence reviews are policy briefs, evidence briefs, summaries of findings, or plain language summaries. The goal of this review was to learn whether evidence summaries help policymakers use evidence from systematic reviews. This review also aimed to identify the best ways to present the evidence summary to increase the use of evidence. What is the aim of this review? This review summarizes the evidence from six randomized controlled trials that judged the effectiveness of systematic review summaries on policymakers' decision making, or the most effective ways to present evidence summaries to increase policymakers' use of the evidence. What are the main findings of this review? This review included six randomized controlled studies. A randomized controlled study is one in which the participants are divided randomly (by chance) into separate groups to compare different treatments or other interventions. This method of dividing people into groups means that the groups will be similar and that the effects of the treatments they receive will be compared more fairly. At the time the study is done, it is not known which treatment is the better one. The researchers who did these studies invited people from Europe, North America, South America, Africa, and Asia to take part in them. Two studies looked at “policy briefs,” one study looked at an “evidence summary,” two looked at a “summary of findings table,” and one compared a “summary of findings table” to an evidence summary. None of these studies looked at how policymakers directly used evidence from systematic reviews in their decision making, but two studies found that there was little to no difference in how they used the summaries. The studies relied on reports from decision makers. These studies included questions such as, “Is this summary easy to understand?” Some of the studies looked at users' knowledge, understanding, beliefs, or how credible (trustworthy) they believed the summaries to be. There was little to no difference in the studies that looked at these outcomes. Study participants rated the graded entry format higher for usability than the full systematic review. The graded entry format allows the reader to select how much information they want to read.. The study participants felt that all evidence summary formats were easier to understand than full systematic reviews. What do the findings of this review mean? Our review suggests that evidence summaries help policymakers to better understand the findings presented in systematic reviews. In short, evidence summaries should be developed to make it easier for policymakers to understand the evidence presented in systematic reviews. However, right now there is very little evidence on the best way to present systematic review evidence to policymakers. How up to date is this review? The authors of this review searched for studies through June 2016. Executive summary/Abstract Background Systematic reviews are important for decision makers. They offer many potential benefits but are often written in technical language, are too long, and do not contain contextual details which makes them hard to use for decision‐making. Strategies to promote the use of evidence to decision makers are required, and evidence summaries have been suggested as a facilitator. Evidence summaries include policy briefs, briefing papers, briefing notes, evidence briefs, abstracts, summary of findings tables, and plain language summaries. There are many organizations developing and disseminating systematic review evidence summaries for different populations or subsets of decision makers. However, evidence on the usefulness and effectiveness of systematic review summaries is lacking. We present an overview of the available evidence on systematic review evidence summaries. Objectives This systematic review aimed to 1) assess the effectiveness of evidence summaries on policy‐makers' use of the evidence and 2) identify the most effective summary components for increasing policy‐makers' use of the evidence. Search methods We searched several online databases (Medline, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials, Global Health Library, Popline, Africa‐wide, Public Affairs Information Services, Worldwide Political Science Abstracts, Web of Science, and DfiD), websites of research groups and organizations which produce evidence summaries, and reference lists of included summaries and related systematic reviews. These databases were searched in March‐April, 2016. Selection criteria Eligible studies included randomised controlled trials (RCTs), non‐randomised controlled trials (NRCTs), controlled before‐after (CBA) studies, and interrupted time series (ITS) studies. We included studies of policymakers at all levels as well as health system managers. We included studies examining any type of “evidence summary”, “policy brief”, or other product derived from systematic reviews that presented evidence in a summarized form. These interventions could be compared to active comparators (e.g. other summary formats) or no intervention. The primary outcomes were: 1) use of systematic review summaries decision‐making (e.g. self‐reported use of the evidence in policy‐making, decision‐making) and 2) policymaker understanding, knowledge, and/or beliefs (e.g. changes in knowledge scores about the topic included in the summary). We also assessed perceived relevance, credibility, usefulness, understandability, and desirability (e.g. format) of the summaries. Results Our database search combined with our grey literature search yielded 10,113 references after removal of duplicates. From these, 54 were reviewed in full text and we included 6 studies (reported in 7 papers, 1661 participants) as well as protocols from 2 ongoing studies. Two studies assessed the use of evidence summaries in decision‐making and found little to no difference in effect. There was also little to no difference in effect for knowledge, understanding or beliefs (4 studies) and perceived usefulness or usability (3 studies). Summary of Findings tables and graded entry summaries were perceived as slightly easier to understand compared to complete systematic reviews. Two studies assessed formatting changes and found that for Summary of Findings tables, certain elements, such as reporting study event rates and absolute differences were preferred as well as avoiding the use of footnotes. No studies assessed adverse effects. The risks of bias in these studies were mainly assessed as unclear or low however, two studies were assessed as high risk of bias for incomplete outcome data due to very high rates of attrition. Authors' conclusions Evidence summaries may be easier to understand than complete systematic reviews. However, their ability to increase the use of systematic review evidence in policymaking is unclear.

Background A focus on equity in health can be seen in many global development goals and reports, research and international declarations. With the development of a relevant framework and methods, the Campbell and Cochrane Equity Methods Group has encouraged the application of an ‘equity lens’ to systematic reviews, and many organizations publish reviews intended to address health equity. The purpose of the Evidence for Equity (E4E) project was to conduct a priority-setting exercise and apply an equity lens by developing a knowledge translation product comprising summaries of systematic reviews from the Cochrane Library. E4E translates evidence from systematic reviews into ‘friendly front end’ summaries for policy makers. Methods The following topic areas with high burdens of disease globally, were selected for the pilot: diabetes/obesity, HIV/AIDS, malaria, nutrition, and mental health/depression. For each topic area, a “stakeholder panel” was assembled that included policymakers and researchers. A systematic search of Cochrane reviews was conducted for each area to identify equity-relevant interventions with a meaningful impact. Panel chairs developed a rating sheet which was used by all panels to rank the importance of these interventions by: 1) Ease of Implementation; 2) Health System Requirements; 3)Universality/Generalizability/Share of Burden; and 4) Impact on Inequities/Effect on equity. The ratings of panel members were averaged for each intervention and criterion, and interventions were ordered according to the average overall ratings. Results Stakeholder panels identified the top 10 interventions from their respective topic areas. The evidence on these interventions is being summarized with an equity focus and the results posted online, at http://methods.cochrane.org/equity/e4e-series. Conclusions This method provides an explicit approach to setting priorities by systematic review groups and funders for providing decision makers with evidence for the most important equity-relevant interventions. Electronic supplementary material The online version of this article (10.1186/s12939-017-0697-5) contains supplementary material, which is available to authorized users.

New approaches to evidence synthesis, which use human effort and machine automation in mutually reinforcing ways, can enhance the feasibility and sustainability of living systematic reviews. Human effort is a scarce and valuable resource, required when automation is impossible or undesirable, and includes contributions from online communities (“crowds”) as well as more conventional contributions from review authors and information specialists. Automation can assist with some systematic review tasks, including searching, eligibility assessment, identification and retrieval of full-text reports, extraction of data, and risk of bias assessment. Workflows can be developed in which human effort and machine automation can each enable the other to operate in more effective and efficient ways, offering substantial enhancement to the productivity of systematic reviews. This paper describes and discusses the potential—and limitations—of new ways of undertaking specific tasks in living systematic reviews, identifying areas where these human/machine “technologies” are already in use, and where further research and development is needed. While the context is living systematic reviews, many of these enabling technologies apply equally to standard approaches to systematic reviewing.

Objective.Despite advances integrating patient-centered outcomes into rheumatologic studies, concerns remain regarding their representativeness across diverse patient groups and how this affects equity. The Outcome Measures in Rheumatology (OMERACT) Equity Working Group aims to determine whether and how to address equity issues within the core outcome sets of domains and instruments.Methods.We surveyed current and previous OMERACT meeting attendees and members of the Campbell and Cochrane Equity Group regarding whether to address equity issues within the OMERACT Filter 2.0 Core Outcome Sets and how to assess the appropriateness of domains, instruments, and measurement properties among diverse patients. At OMERACT 2016, results of the survey and a narrative review of differential psychosocial effects of rheumatoid arthritis (i.e., on men) were presented to stimulate discussion and develop a research agenda.Results.We proposed 6 moments for which an equity lens could be added to the development, selection, or testing of patient-reported outcome measures (PROM): (1) recruitment, (2) domain selection, (3) feasibility in diverse settings, (4) instrument validity, (5) thresholds of meaning, and (6) consideration of statistical power of subgroup analyses for outcome reporting.Conclusion.There is a need to (1) conduct a systematic review to assess how equity and population characteristics have been considered in PROM development and whether these differences influence the ranking of importance of outcome domains or a patient’s response to questionnaire items, and (2) conduct the same survey described above with patients representing groups experiencing health inequities.

The availability of evidence-based guidelines does not ensure their implementation and use in clinical practice or policy making. Inequities in health have been defined as those inequalities within or between populations that are avoidable, unnecessary and also unjust and unfair. Evidence-based clinical practice and public health guidelines (‘guidelines’) can be used to target health inequities experienced by disadvantaged populations, although guidelines may unintentionally increase health inequities. For this reason, there is a need for evidence-based clinical practice and public health guidelines to intentionally target health inequities experienced by disadvantaged VC The Author 2017. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine. 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 reuse, distribution, and reproduction in any medium, provided the original work is properly cited. 1484 Health Policy and Planning, 32, 2017, 1484–1490 doi: 10.1093/heapol/czx126 Advance Access Publication Date: 3 October 2017 Methodological Musings Downloaded from https://academic.oup.com/heapol/article/32/10/1484/4318813 by BLS - The Librarian user on 12 February 2023 populations. Current guideline development processes do not include steps for planned implementation of equity-focused guidelines. This article describes nine steps that provide guidance for consideration of equity during guideline implementation. A critical appraisal of the literature followed by a process to build expert consensus was undertaken to define how to include consideration of equity issues during the specific GRADE guideline development process. Using a case study from Colombia we describe nine steps that were used to implement equity-focused GRADE recommendations: (1) identification of disadvantaged groups, (2) quantification of current health inequities, (3) development of equity-sensitive recommendations, (4) identification of key actors for implementation of equity-focused recommendations, (5) identification of barriers and facilitators to the implementation of equity-focused recommendations, (6) development of an equity strategy to be included in the implementation plan, (7) assessment of resources and incentives, (8) development of a communication strategy to support an equity focus and (9) development of monitoring and evaluation strategies. This case study can be used as model for implementing clinical practice guidelines, taking into account equity issues during guideline development and implementation.

Objectives: The aim of this paper is to provide detailed guidance on how to incorporate health equity within the GRADE (Grading Recommendations Assessment and Development Evidence) evidence to decision process. Study Design and Setting: We developed this guidance based on the GRADE evidence to decision framework, iteratively reviewing and modifying draft documents, in person discussion of project group members and input from other GRADE members. Results: Considering the impact on health equity may be required, both in general guidelines and guidelines that focus on disadvantaged populations. We suggest two approaches to incorporate equity considerations: (1) assessing the potential impact of interventions on equity and (2) incorporating equity considerations when judging or weighing each of the evidence to decision criteria. We provide guidance and include illustrative examples. Conclusion: Guideline panels should consider the impact of recommendations on health equity with attention to remote and underserviced settings and disadvantaged populations. Guideline panels may wish to incorporate equity judgments across the evidence to decision framework. This is the fourth and final paper in a series about considering equity in the GRADE guideline development process. This series is coming from the GRADE equity subgroup. (C) 2017 Elsevier Inc. All rights reserved.

International audience; BACKGROUND: Survival and quality of life for patients on hemodialysis therapy remain poor despite substantial research efforts. Existing trials often report surrogate outcomes that may not be relevant to patients and clinicians. The aim of this project was to generate a consensus-based prioritized list of core outcomes for trials in hemodialysis. STUDY DESIGN: In a Delphi survey, participants rated the importance of outcomes using a 9-point Likert scale in round 1 and then re-rated outcomes in rounds 2 and 3 after reviewing other respondents' scores. For each outcome, the median, mean, and proportion rating as 7 to 9 (critically important) were calculated. SETTING & PARTICIPANTS: 1,181 participants (202 [17%] patients/caregivers, 979 health professionals) from 73 countries completed round 1, with 838 (71%) completing round~3. OUTCOMES & MEASUREMENTS: Outcomes included in the potential core outcome set met the following criteria for both patients/caregivers and health professionals: median score~≥q 8, mean score~≥q 7.5, proportion rating the outcome as critically important~≥q 75%, and median score in the forced ranking question~

Quasi-experimental studies are increasingly used to establish causal relationships in epidemiology and health systems research. Quasi-experimental studies offer important opportunities to increase and improve evidence on causal effects: (i) they can generate causal evidence when randomized controlled trials are impossible; (ii) they typically generate causal evidence with a high degree of external validity; (iii) they avoid the threats to internal validity that arise when participants in non-blinded experiments change their behavior in response to the experimental assignment to either intervention or control arm (such as compensatory rivalry or resentful demoralization); (iv) they are often well-suited to generate causal evidence on long-term health outcomes of an intervention, as well as non-health outcomes such as economic and social consequences; and (v) they can often generate evidence faster and at lower cost than experiments and other intervention studies.

Rigorous and transparent critical appraisal is a core component of high quality systematic reviews. Well-conducted quasi-experiments have been empirically shown to estimate credible, unbiased treatment quantities. Conversely, when inappropriately designed or executed, these estimates are likely to be biased. This paper draws on recent advances in risk of bias assessment. It presents an approach to evaluating the internal validity of credible quasi-experiments. These are non-randomised studies using design-based approaches to control for unobservable sources of confounding such as difference studies, instrumental variables, interrupted time series, natural experiments and regression discontinuity designs. Our review suggests that existing risk of bias tools provide, to different degrees, incomplete transparent criteria to assess the validity of credible quasi-experiments. We argue that a tool is needed to assess risk of bias consistently across credible quasi-experiments. Drawing on existing tools, in particular Cochrane’s new tool for non-randomized studies of interventions (Sterne et al., 2014), we discuss domains of bias and suggest directions for evaluation questions.

Although the number of quasi-experiments conducted by health researchers has increased in recent years, there clearly remains unrealized potential for using these methods for causal evaluation of health policies and programs globally. This article proposes five prescriptions for capturing the full value of quasi-experiments for health research. First, new funding opportunities targeting proposals that use quasi-experimental methods should be made available to a broad pool of health researchers. Second, administrative data from health programs, often amenable to quasi-experimental analysis, should be made more accessible to researchers. Third, training in quasi-experimental methods should be integrated into existing health science graduate programs to increase global capacity to use these methods. Fourth, clear guidelines for primary research and synthesis of evidence from quasi-experiments should be developed. Fifth, strategic investments should be made to continue to develop new innovations in quasi-experimental methodologies. Tremendous opportunities exist to expand the use of quasi-experimental methods to increase our understanding of which health programs and policies work and which do not. Health researchers should continue to expand their commitment to rigorous causal evaluation with quasi-experimental methods, and international institutions should increase their support for these efforts.

Objectives The objective of this study was to contrast the historical development of experiments and quasi-experiments and provide the motivation for a journal series on quasi-experimental designs in health research. Study Design and Setting A short historical narrative, with concrete examples, and arguments based on an understanding of the practice of health research and evidence synthesis. Results Health research has played a key role in developing today's gold standard for causal inference—the randomized controlled multiply blinded trial. Historically, allocation approaches developed from convenience and purposive allocation to alternate and, finally, to random allocation. This development was motivated both by concerns for manipulation in allocation as well as statistical and theoretical developments demonstrating the power of randomization in creating counterfactuals for causal inference. In contrast to the sequential development of experiments, quasi-experiments originated at very different points in time, from very different scientific perspectives, and with frequent and long interruptions in their methodological development. Health researchers have only recently started to recognize the value of quasi-experiments for generating novel insights on causal relationships. Conclusion While quasi-experiments are unlikely to replace experiments in generating the efficacy and safety evidence required for clinical guidelines and regulatory approval of medical technologies, quasi-experiments can play an important role in establishing the effectiveness of health care practice, programs, and policies. The papers in this series describe and discuss a range of important issues in utilizing quasi-experimental designs for primary research and quasi-experimental results for evidence synthesis.

Objective.Managing juvenile-onset systemic lupus erythematosus (SLE) is particularly challenging. The disease may be severe, adolescent patients have complex medical and psychosocial needs, and patients must navigate the transition to adult services. To inform patient-centered care, we aimed to identify the healthcare and research priorities of young patients with SLE and describe the reasons underpinning their priorities.Methods.Face-to-face, semistructured interviews and focus groups were conducted with patients with SLE, aged from 14 to 26 years, from 5 centers in Australia. For each of the 5 allocation exercises, participants allocated 10 votes to (1) research topics; research questions on (2) medical management, (3) prevention and diagnosis, (4) lifestyle and psychosocial; and (5) healthcare specialties, and discussed the reasons for their choices. Descriptive statistics were calculated for votes and qualitative data were analyzed thematically.Results.The 26 participants prioritized research that alleviated the psychological burden of SLE. They allocated their votes toward medical and mental health specialties in the management of SLE, while fewer votes were given to physiotherapy/occupational therapy and dietetics. The following 7 themes underpinned the participants’ priorities: improving service shortfalls, strengthening well-being, ensuring cost efficiency, minimizing family/community burden, severity of comorbidity or complications, reducing lifestyle disruption, and fulfilling future goals.Conclusion.Young patients with SLE value comprehensive care with greater coordination among specialties. They prioritized research focused on alleviating poor psychological outcomes. The healthcare and research agenda for patients with SLE should include everyone involved, to ensure that the agenda aligns with patient priorities, needs, and values.

Background and objectives Patient centeredness is widely advocated as a cornerstone of health care, but it is yet to be fully realized, including in nephrology. Our study aims to describe nephrologists’ perspectives on defining and implementing patient-centered outcomes in hemodialysis. Design, setting, participants, & measurements Face-to-face, semistructured interviews were conducted with 58 nephrologists from 27 dialysis units across nine countries, including the United States, the United Kingdom, Australia, Austria, Belgium, Canada, Germany, Singapore, and New Zealand. Transcripts were thematically analyzed. Results We identified five themes on defining and implementing patient-centered outcomes in hemodialysis: explicitly prioritized by patients (articulated preferences and goals, ascertaining treatment burden, defining hemodialysis success, distinguishing a physician-patient dichotomy, and supporting shared decision making), optimizing wellbeing (respecting patient choice, focusing on symptomology, perceptible and tangible, and judging relevance and consequence), comprehending extensive heterogeneity of clinical and quality of life outcomes (distilling diverse priorities, highly individualized, attempting to specify outcomes, and broadening context), clinically hamstrung (professional deficiency, uncertainty and complexity in measurement, beyond medical purview, specificity of care, mechanistic mindset [focused on biochemical targets and comorbidities], avoiding alarm, and paradoxical dilemma), and undermined by system pressures (adhering to overarching policies, misalignment with mandates, and resource constraints). Conclusions Improving patient-centered outcomes is regarded by nephrologists to encompass strategies that address patient goals and improve wellbeing and treatment burden in patients on hemodialysis. However, efforts are hampered by ambiguities about how to prioritize, measure, and manage the plethora of critical comorbidities and broader quality of life outcomes in a care setting that is technically demanding and driven by biochemical targets. Identifying critical patient–important outcomes and mechanisms for integrating them into practice may help to deliver patient-centered care in hemodialysis and other chronic disease settings. Podcast This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2017_02_28_Tong.mp3

BACKGROUND Each year, half a million patients with a potential neck (c-spine) injury are transported to Ontario emergency departments (EDs). Less than 1.0% (1/100) of these patients have a neck bone fracture. Even less (1/200, 0.5%) have a spinal cord injury or nerve damage. Currently, paramedics transport all trauma victims (with or without an injury) by ambulance using a backboard, cervical collar, and head immobilizers. Importantly, prolonged immobilization is often unnecessary; it causes patient discomfort and pain, decreases community access to paramedics, contributes to ED crowding, and is very costly. We therefore developed the Canadian C-Spine Rule (CCR) for alert and stable trauma patients. This decision rule helps ED physicians and triage nurses to safely and selectively remove immobilization, without x-rays and missed injury. We successfully taught Ottawa paramedics to use the CCR in the field in a single-center study. OBJECTIVE This study aimed to improve patient care and health system efficiency and outcomes by allowing paramedics to assess eligible low-risk trauma patients with the CCR and selectively transport them without immobilization to the ED. METHODS We propose a pragmatic stepped-wedge cluster randomized design with health economic evaluation, designed collaboratively with knowledge users. Our 36-month study will consist of a 12-month setup and training period (year 1), followed by the stepped-wedge trial (year 2) and a 12-month period for study completion, analyses, and knowledge translation. A total of 12 Ontario paramedic services of various sizes distributed across the province will be randomly allocated to one of three sequences. Paramedic services in each sequence will cross from the control condition (usual care) to the intervention condition (CCR implementation) at intervals of 3 months until all communities have crossed to the intervention. Data will be collected on all eligible patients in each paramedic service for a total duration of 12 months. A major strength of our design is that each community will have implemented the CCR by the end of the study. RESULTS Interim results are expected in December 2019 and final results in 2020. If this multicenter trial is successful, we expect the Ontario Ministry of Health will recommend that paramedics evaluate all eligible patients with the CCR in the Province of Ontario. CONCLUSIONS We conservatively estimate that in Ontario, more than 60% of all eligible trauma patients (300,000 annually) could be transported safely and comfortably, without c-spine immobilization devices. This will significantly reduce patient pain and discomfort, paramedic intervention times, and ED length of stay, thereby improving access to paramedics and ED care. This could be achieved rapidly and with lower health care costs compared with current practices (possible cost saving of Can $36 [US $25] per immobilization or Can $10,656,000 [US $7,335,231] per year). CLINICALTRIAL ClinicalTrials.gov NCT02786966; https://clinicaltrials.gov/ct2/show/NCT02786966. INTERNATIONAL REGISTERED REPORT DERR1-10.2196/16966