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ObjectiveTo systematically compare the effect of direct oral anticoagulants and low molecular weight heparin for thromboprophylaxis on the benefits and harms to patients undergoing non-cardiac surgery.DesignSystematic review and network meta-analysis of randomised controlled trials.Data sourcesMedline, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL), up to August 2021.Review methodsRandomised controlled trials in adults undergoing non-cardiac surgery were selected, comparing low molecular weight heparin (prophylactic (low) or higher dose) with direct oral anticoagulants or with no active treatment. Main outcomes were symptomatic venous thromboembolism, symptomatic pulmonary embolism, and major bleeding. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used for network meta-analyses. Abstracts and full texts were screened independently in duplicate. Data were abstracted on study participants, interventions, and outcomes, and risk of bias was assessed independently in duplicate. Frequentist network meta-analysis with multivariate random effects models provided odds ratios with 95% confidence intervals, and GRADE (grading of recommendations, assessment, development, and evaluation) assessments indicated the certainty of the evidence.Results68 randomised controlled trials were included (51 orthopaedic, 10 general, four gynaecological, two thoracic, and one urological surgery), involving 45 445 patients. Low dose (odds ratio 0.33, 95% confidence interval 0.16 to 0.67) and high dose (0.19, 0.07 to 0.54) low molecular weight heparin, and direct oral anticoagulants (0.17, 0.07 to 0.41) reduced symptomatic venous thromboembolism compared with no active treatment, with absolute risk differences of 1-100 per 1000 patients, depending on baseline risks (certainty of evidence, moderate to high). None of the active agents reduced symptomatic pulmonary embolism (certainty of evidence, low to moderate). Direct oral anticoagulants and low molecular weight heparin were associated with a 2-3-fold increase in the odds of major bleeding compared with no active treatment (certainty of evidence, moderate to high), with absolute risk differences as high as 50 per 1000 in patients at high risk. Compared with low dose low molecular weight heparin, high dose low molecular weight heparin did not reduce symptomatic venous thromboembolism (0.57, 0.26 to 1.27) but increased major bleeding (1.87, 1.06 to 3.31); direct oral anticoagulants reduced symptomatic venous thromboembolism (0.53, 0.32 to 0.89) and did not increase major bleeding (1.23, 0.89 to 1.69).ConclusionsDirect oral anticoagulants and low molecular weight heparin reduced venous thromboembolism compared with no active treatment but probably increased major bleeding to a similar extent. Direct oral anticoagulants probably prevent symptomatic venous thromboembolism to a greater extent than prophylactic low molecular weight heparin.Systematic review registrationPROSPERO CRD42018106181.

Objective To develop an instrument to evaluate the credibility of anchor based minimal important differences (MIDs) for outcome measures reported by patients, and to assess the reliability of the instrument. Design Instrument development and reliability study. Data sources Initial criteria were developed for evaluating the credibility of anchor based MIDs based on a literature review (Medline, Embase, CINAHL, and PsycInfo databases) and the experience of the authors in the methodology for estimation of MIDs. Iterative discussions by the team and pilot testing with experts and potential users facilitated the development of the final instrument. Participants With the newly developed instrument, pairs of masters, doctoral, or postdoctoral students with a background in health research methodology independently evaluated the credibility of a sample of MID estimates. Main outcome measures Core credibility criteria applicable to all anchor types, additional criteria for transition rating anchors, and inter-rater reliability coefficients were determined. Results The credibility instrument has five core criteria: the anchor is rated by the patient; the anchor is interpretable and relevant to the patient; the MID estimate is precise; the correlation between the anchor and the outcome measure reported by the patient is satisfactory; and the authors select a threshold on the anchor that reflects a small but important difference. The additional criteria for transition rating anchors are: the time elapsed between baseline and follow-up measurement for estimation of the MID is optimal; and the correlations of the transition rating with the baseline, follow-up, and change score in the patient reported outcome measures are satisfactory. Inter-rater reliability coefficients (ĸ) for the core criteria and for one item from the additional criteria ranged from 0.70 to 0.94. Reporting issues prevented the evaluation of the reliability of the three other additional criteria for the transition rating anchors. Conclusions Researchers, clinicians, and healthcare policy decision makers can consider using this instrument to evaluate the design, conduct, and analysis of studies estimating anchor based minimal important differences.

IntroductionProper strategies to minimise the risk of infection in individuals handling the bodies of deceased persons infected with 2019 novel coronavirus (2019-nCoV) are urgently needed. The objective of this study was to systematically review the literature to scope and assess the effects of specific strategies for the management of the bodies.MethodsWe searched five general, three Chinese and four coronavirus disease (COVID-19)–specific electronic databases. We searched registries of clinical trials, websites of governmental and other relevant organisations, reference lists of the included papers and relevant systematic reviews, and Epistemonikos for relevant systematic reviews. We included guidance documents providing practical advice on the handling of bodies of deceased persons with suspected or confirmed COVID-19. Then, we sought primary evidence of any study design reporting on the efficacy and safety of the identified strategies in coronaviruses. We included evidence relevant to contextual factors (ie, acceptability). A single reviewer extracted data using a pilot-tested form and graded the certainty of the evidence using the GRADE approach. A second reviewer verified the data and assessments.ResultsWe identified one study proposing an uncommon strategy for autopsies for patients with severe acute respiratory syndrome. The study provided very low-certainty evidence that it reduced the risk of transmission. We identified 23 guidance documents providing practical advice on the steps of handling the bodies: preparation, packing, and others and advice related to both the handling of the dead bodies and the use of personal protective equipment by individuals handling them. We did not identify COVID-19 evidence relevant to any of these steps.ConclusionWhile a substantive number of guidance documents propose specific strategies, we identified no study providing direct evidence for the effects of any of those strategies. While this review highlights major research gaps, it allows interested entities to build their own guidance.

This article describes how the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to grading the quality of evidence and strength of recommendations considers the Bradford Hill criteria for causation and how GRADE may relate to questions in public health. A primary concern in public health is that evidence from non-randomised studies may provide a more adequate or best available measure of a public health strategy's impact, but that such evidence might be graded as lower quality in the GRADE framework. GRADE, however, presents a framework that describes both criteria for assessing the quality of research evidence and the strength of recommendations that includes considerations arising from the Bradford Hill criteria. GRADE places emphasis on recommendations and in assessing quality of evidence; GRADE notes that randomisation is only one of many relevant factors. This article describes how causation may relate to developing recommendations and how the Bradford Hill criteria are considered in GRADE, using examples from the public health literature with a focus on immunisation.

Objective Summary of findings (SoF) tables present results of systematic reviews in a concise and explicit format. Adopted by many review groups including the Cochrane Collaboration and the Agency for Healthcare Research and Quality (AHRQ), optimal understanding of SoF table may be influenced by the type of information being conveyed and objectives or preferences of the end user. This study aims to compare three SoF table formats in terms of understanding, accessibility, satisfaction and preference with systematic review users. Methods The primary objective of this three-arm randomised controlled non-inferiority trial is to investigate whether an alternative Grading of Recommendations Assessment, Development and Evaluation (GRADE) SoF table or Evidence-based Practice Center SoF table is non-inferior to the current GRADE SoF table in the understanding of the information presented to systematic review users, particularly for descriptive findings. Researchers, clinical practice guideline developers, policy-makers or knowledge transfer professionals will be recruited. Data will be collected electronically at baseline and after randomisation. Non-inferiority would be declared if the difference in the proportion of participants who understand the information displayed in the alternative SoF table is 10% or less. Ethics and dissemination The Hamilton Integrated Research Ethics Board reviewed this protocol. The findings from this study will be disseminated through a publication in a peer-reviewed journal. Trial registration number NCT02813941.

Updating of systematic reviews is generally more efficient than starting all over again when new evidence emerges, but to date there has been no clear guidance on how to do this. This guidance helps authors of systematic reviews, commissioners, and editors decide when to update a systematic review, and then how to go about updating the review.

Clinicians do not have the time or resources to consider the underlying evidence for the myriad decisions they must make each day and, as a consequence, rely on recommendations from clinical practice guidelines. Guideline panels should consider all the relevant factors (criteria) that influence a decision or recommendation in a structured, explicit, and transparent way and provide clinicians with clear and actionable recommendations. In this article, we will describe the Evidence to Decision (EtD) frameworks for clinical practice recommendations. The general structure of the EtD framework for clinical recommendations is similar to EtD frameworks for other types of recommendations and decisions, and includes formulation of the question, an assessment of the different criteria, and conclusions. Clinical recommendations require considering criteria differently, depending on whether an individual patient or a population perspective is taken. For example, from an individual patient's perspective, out-of-pocket costs are an important consideration, whereas, from a population perspective, resource use (not only out-of-pocket costs) and cost effectiveness are important. From a population perspective, equity, acceptability, and feasibility are also important considerations, whereas the importance of these criteria is often limited from an individual patient perspective. Specific subgroups for which different recommendations may be required should be clearly identified and considered in relation to each criterion because judgments might vary across subgroups. This article is a translation of the original article published in the British Medical Journal. The EtD frameworks are currently used in the Clinical Practice Guideline Programme of the Spanish National Health System, co-ordinated by GuíaSalud.

Background Conducting systematic evidence reviews on a set of focused clinical questions has become one of the “gold standards” for development of “trustworthy” clinical guidance. Time, resource constraints, and other issues, however, may require the application of more pragmatic means for reviewing the evidence to support rapid guidance development. Target Group, Suggested Audience Developers of guidance for health systems and health policy settings. Objectives/Goals To actively engage panellists and session participants in a discussion of the role of rapid systematic reviews in the development of rapid guidance, the strengths and limitations of rapid vs. full/complete systematic review methods, and lessons learned from recent national and international rapid review and guidance efforts within health care and health policy settings. Description of Session and Speaker Topics Chantelle Garritty will discuss OHRI’s rapid review work with the Ottawa Hospital Technology Assessment Programme, and the Cochrane Collaboration’s new “Cochrane Response” rapid review methodology; Catherine Gallagher will present results of a pilot Cochrane Response rapid review within the GMU Health System, and organisation of an international group to develop rapid review standards; Holger Schunemann will present examples of rapid systematic reviews and their value in rapid guidance development; and Susan Norris will present on the WHO’s development of rapid guidance in the setting of urgent public health needs. Marguerite Koster will moderate the discussion.

Background Guidelines often take two or more years to be developed. This timeframe is not practical for providing guidance in situations when rapid advice is needed. Objectives To describe current practices about the development of rapid guidelines and to provide advice about adequate methodology. Methods We performed a systematic review, including grey literature, to identify (1) rapid guidelines, defined as guidelines produced in a shortened time frame, and (2) methodological manuals addressing its development. Results We only documents by WHO and NICE that described methods and actual guidelines. The WHO handbook describes “rapid advice guidelines”; guidelines produced in response to a public health emergency in which WHO is required to provide rapid global leadership and guidance. This advice should be produced within 1 to 3 months and be evidence-informed, however, it may not be supported by full reviews of the evidence. We identified six WHO rapid guidelines and one methodological guidance paper based on a WHO guideline. NICE produces “short clinical guidelines”; guidelines that address only part of a care pathway, allowing rapid (11–13-month) development of guidance on aspects of care for which the NHS requires urgent advice. We identified 18 NICE short clinical guidelines. Discussion Literature is lacking about rapid guidelines and the intended role appears to differ. Despite its relevance, there are few rapid guidelines published and clarity about the terminology is needed. Implications for Guideline Developers We will provide a framework for those developing rapid guidelines, including practical advice and clarification about the terminology used.

Background Moving from evidence to recommendations (EtR) in guideline development requires balancing evidence quality with the benefits and harms of interventions, patient preferences, and resource and cost considerations. Developing recommendation about diagnostic tests and strategies is particularly challenging and requires tackling complex challenges, different than those needed for therapeutic interventions. The GRADE Working Group, has developed an approach to integrate these factors into development of clinical practice recommendations that is currently further defined in the DECIDE (Developing and Evaluating Communication Strategies to Support Informed Decisions and Practice Based on Evidence) project. This workshop will introduce this approach and evaluate the EtR framework based on examples and hands-on exercises. Objectives To learn how to use and evaluate the EtR framework for diagnostic questions. Target Group, Suggested Audience Guideline developers, systematic reviewers, clinicians. Description of the Workshop and of the Methods used to Facilitate Interactions This workshop provides a brief didactic overview of GRADE for diagnostic questions. Each group will use a systematic review and a partially pre-filled EtR framework. During the small group work, participants will discuss challenges and advantages of the approach. Participants will then apply these concepts in small groups to develop a recommendation based on the workshop material; there will be a plenary to provide feedback that will help to enhance the work and provide opportunities for collaboration.

Background Guideline developers and other health care decision makers benefit from following a structured process of specifying the health care questions they intend to answer and the outcomes of interest, assessing the confidence in the available evidence, gathering information about the values and preferences of the target population, and presentation of their results and decisions to the target users. Many guideline developers use the GRADE Profiler (GRADEpro) software used to conduct this work. Context GRADE’s approach is currently being further defined in the DECIDE (Developing and Evaluating Communication Strategies to Support Informed Decisions and Practice Based on Evidence) project. Description of Best Practice The Guideline Development Tool (GDT) is the extension of the GRADE Profiler (GRADEpro) software. The GDT provides an integrated platform-independent web-based solution for health care decision makers offering support for the whole process of making decisions and developing recommendations including question formulation, generation and prioritisation of outcomes, support for teamwork, management of potential conflicts of interest, presentation of results (including the functionality of GRADEpro) and decision support. We tested the software with individual users and in workshops as well as in guideline development processes. Lessons for Guideline Developers, Adaptors, Implementers, and/or Users Following a structured and systematic process, transparency and clarity of presentation facilitates the use of results of systematic reviews and facilitates development, updating and adaptation of evidence-based recommendations and decisions. Storing all information in a uniform, structured, transparent and annotated way also greatly facilitates updating and adaptation of systematic reviews and guidelines.

Background The GRADE Working Group developed Summary tables adapted to summarise and present evidence from diagnostic test accuracy (DTA) systematic reviews. Objective To develop guidance on what information to include in these summary tables and to determine the best method(s) for presentation for different end users, including healthcare providers, systematic reviewers and guideline developers. Methods We presented a number of alternative summary tables to participants. We conducted questionnaires and one-on-one user testing interviews with target end users. We presented printed copies of summary tables and asked open-ended and 7-point Likert-scale questions to obtain information about users’ understanding and preferences. Results All participants (n = 60) agreed that using summary tables to present results of DTA reviews is helpful. Presentation of several disease prevalence values was identified as a source of confusion. There was an overall preference for placement of sensitivity and specificity values inside summary tables to allow making a link to individual test results (TP, FN, TN, FP). A third of the participants read explanatory content in table footnotes. Two thirds of the participants noted that additional data, including adverse effects, costs, and treatment consequences, would be helpful for making appropriate conclusions and decisions about diagnostic tests. Discussion As results of DTA reviews are conceptually complicated, presenting the data in a clear, comprehensive, comprehensible way that is tailored to different end users is critical. Implications for Guideline Developers/Users We are developing a 3-layer approach, with varied content in summary tables of each layer tailored to the needs of different end users.

Background To maximise uptake, CPG recommendations must avoid of bias and be responsive to the needs of clinicians and patients from different populations and settings. Objectives/Goal To discuss three key challenges to CPG use: 1) building consensus and minimising conflicts of interest in formulating recommendations for specific patient populations; 2) taking account of patient multi-morbidity; 3) incorporating patient values and preferences for specific outcomes. Target group Suggested audience Guideline developers and writing groups, clinical researchers, users of guidelines (clinicians, patients). Moderator Prof Ian A Scott, Director of Internal Medicine and Clinical Epidemiology, Princess Alexandra Hospital, Brisbane, Australia. Invited Speakers Dr Susan L Norris, Department of Medical Informatics and Clinical Epidemiology, Oregon Health and Science University, Portland, USA. SLN is Technical Officer for the secretariat of the Guideline Review Committee at the World Health Association in Geneva, Switzerland and has conducted research on conflicts of interest. Professor Holger J Schunemann, Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada. HJS is co-chair of the GRADE working group, member of the GIN board of trustees and has co-authored reports on guideline methodology, including multimorbidity. Professor Gordon H Guyatt, Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada. GHG is co-chair of the GRADE working group and chaired the executive of 9th iteration of the American College of Chest Physicians Antithrombotic Guidelines. Description of session and speaker topics Session will comprise 3 presentations (15 mins), one for each challenge, with 5 mins for questions of clarification then 30 mins of panel discussion.

Background The terms applicability, generalizability, external validity, transferability generally describe one overarching theme: can available research evidence be utilised to answer the health care questions at hand, ideally supported by a judgement about the degree of confidence in this utilisation. This concept has been called directness. Objectives To offer conceptual and practical guidance to those judging directness and using research evidence from non-randomised studies (NRS). Methods We used a literature review and feedback from participants of a workshop funded by the Agency for Healthcare Quality and Research and the Cochrane Collaboration. Results Guideline developers can use NRS as a source of complementary, sequential or replacement evidence for randomised controlled trials (RCTs) by focusing on judgements about the population, intervention, comparison and outcomes. They use NRS to complement judgements about inconsistency, the rationale and credibility of subgroup analysis, baseline risk estimates for the determination of absolute benefits and downsides, and the directness of surrogate outcomes. Authors use NRS as sequential evidence to provide evidence when the evidence from RCTs is insufficient (e.g. long-term harms). Use of evidence from NRS may also replace RCT evidence when RCTs provide indirect evidence but NRS provide overall higher quality, direct evidence. We developed a simple tool and algorithm to make judgements about indirectness more transparent. Discussions These judgements need to be made in the context of other quality of evidence domains. Implications for Guideline Developers/Users The transparency of the framework will support interaction with those making health care decision and policy.

Systematic reviews have become a sine non qua in guideline development. The reasons for this are obvious: recommendations must be based on the best available evidence and systematic reviews allow for transparent methods and processes for evaluating the evidence. However, best practice of collaborating and implementing the laudable goal of basing recommendations in guidelines on systematic reviews has not been defined. For example, better coordination between guideline developers and systematic review authors is required to efficiently use resources (e.g. avoid unnecessary duplication of efforts, delays and non-credible evidence reviews). The Cochrane Collaboration and the Guideline International Network are looking for ways to collaborate. Attractive models include the development of a database of health care questions for which systematic reviews exist, are planned or missing. A database will allow guideline developers and systematic reviewers to work in synergy and ensure that evidence is synthesised when needed and used when recommendations are formulated. An interactive database of questions, linked to summaries of evidence and systematic reviews would support guideline developers and systematic reviewers to work together. This collaboration is not simple; it requires involvement of both review authors and guideline developers early on in the process of systematic reviews. In this presentation we will review challenges and proposed solutions based on existing models, examples and ideas to advance the field. It will report on work from the GIN Partnership Taskforce, the Cochrane Applicability and Recommendations Methods Group, other Cochrane entities and the GRADE working group to support these solutions.

Background The challenges facing guideline developers when making recommendations about diagnostic tests and strategies (DTS) are considerably different when compared to treatment recommendations. Objectives To identify, describe and compare all available instruments, checklists, critical appraisal tools, and indices designed for assessing the quality of evidence (QoE) or strength of recommendations (SoR) dealing with diagnostic tests and strategies. Methods We conducted a comprehensive systematic search of the literature including state of the art diagnostic guidelines, methods papers and diagnostic systematic reviews. Results We identified 45 tools and modifications of existing tools to assess the QoE and SoR of DTS. Most tools acknowledge the importance of assessing the QoE and SoR separately. Most tools include individual quality criteria and study design but no tool rates all quality criteria suggested by the GRADE working group. Only two tools explicitly consider factors that increase the confidence in the evidence. When moving from evidence to recommendations, patient values and preferences and resources were rarely considered. Discussion There is confusion about the terminology that describes the various factors that influence the QoE and SoR. The criteria for evaluating the QoE and moving from evidence to recommendations are incomplete for most guideline development frameworks that we evaluated. Implications for Guideline Developers/Users The GRADE approach is the most complete approach encompassing all factors but users will benefit from a better description of the evidence to recommendation framework in GRADE and clarification of issues that relate to laboratory validity parameters.

Background When assessing the confidence in intervention effects, i.e. the quality of evidence, guideline developers should make their judgement about this confidence transparent and provide an overall assessment (or grade) of the evidence (GIN & IOM standards 2011). The GRADE approach requires these judgments to be described in comments and footnotes. In a recent review of GRADE evidence summaries, we observed important variability in how guideline developers and authors of Cochrane systematic reviews perform these tasks. Objectives In this interactive workshop the participants will learn how to formulate understandable and informative reasons for down- and upgrading the quality of evidence by using a footnotes checklist. Target Group Systematic reviewers and guideline developers assessing the quality or strength of evidence. Description of the Workshop and of the Methods used to Facilitate Interactions We will present the development of the footnotes checklist. To get hands-on experience the participants will work in large and small groups to: 1) use the checklist on several examples of GRADE evidence profiles and 2) make a judgement about how informative these footnotes are, in particular with guideline panel meetings in mind. The examples will include challenging topics like evidence from single RCT and narrative reviews (no pooled estimates). The outcomes of these exercises will be discussed with the large group and will be used to further improve the checklist.

Background Moving from evidence to recommendations in guideline development requires balancing evidence quality with the benefits and harms of therapeutic interventions, patient preferences, and resource and cost considerations. The GRADE Working Group has developed an approach to integrate these factors into development of clinical practice recommendations that is currently further defined in the DECIDE (Developing and Evaluating Communication Strategies to Support Informed Decisions and Practice Based on Evidence) project. Objectives/Goal To train guideline developers and those working with guideline panels to facilitate the decision-making process for development of recommendations for therapeutic interventions using the GRADE “Evidence-to-Recommendations Framework.” Target Audience Guideline developers, especially those working with guideline panels to develop recommendations for clinical practice. Description of the Workshop and of the Methods used to Facilitate Interactions An overview of the GRADE “Evidence-to-Recommendations Framework” will be followed by facilitated small group work to develop guideline recommendations. Participants will work together in a simulated guideline panel, and be asked to develop guideline recommendations taking into consideration the quality of evidence from a GRADE evidence summary profile, the balance of benefits vs. harms of an intervention, patient preferences and resource implications. Facilitators will guide the small workgroups through the decision-making process using materials from recent examples of guidelines developed using the “Evidence-to-Recommendations Framework.”

In a formerly widespread approach to medical decision making, physicians made a diagnosis, considered the management alternatives, and informed patients what would be done to help them. Decision making rested exclusively in the physicians’ domain. This parental model of patient care challenged clinicians to interpret what was best for their patients. How much benefit must a treatment offer before it was worth subjecting a patient to its short term side effects, long term risks, inconveniences, and costs? With the clinician at the centre of decision making, the question was whether a treatment effect was “clinically relevant.” Even in the discipline of health related quality of life measurement, investigators sought the “minimal clinically important difference.” The parental model has its strengths, and in the past it is very likely that many patients preferred leaving the decisions to their doctors, particularly when the knowledge gap between physicians and the lay public was greater. Consider, for instance, the results of a survey of 2472 patients with chronic disease (hypertension, diabetes, heart failure, myocardial infarction, or depression) completed between 1986 and 1990. In response to the statement: “I prefer to leave decisions about my medical care up to my doctor,” 17.1% strongly agreed, 45.5% agreed, 11.1% were uncertain, 22.5% disagreed, and only 4.8% strongly disagreed.1 Cultural changes since the 1950s suggest that in the more distant past, the percentage preferring to leave decisions up to the doctor was even greater. For example, in the survey that generated these data, older patients were less inclined to prefer an active decision making role than younger respondents. Parental approaches to decision making have limitations related to physicians’ evaluation of how patients value benefits and risks. One issue is physicians’ tendency to assume that physiological outcomes will lead to improvements in mortality …

Objective To compare quality of care in for-profit and not-for-profit nursing homes. Design Systematic review and meta-analysis of observational studies and randomised controlled trials investigating quality of care in for-profit versus not-for-profit nursing homes. Results A comprehensive search yielded 8827 citations, of which 956 were judged appropriate for full text review. Study characteristics and results of 82 articles that met inclusion criteria were summarised, and results for the four most frequently reported quality measures were pooled. Included studies reported results dating from 1965 to 2003. In 40 studies, all statistically significant comparisons (P

EDITOR—The tone and scope of the rapid responses to our users' guides confirm the central assumption of our guides: that there are emotional and economic interests that affect the objectivity of science. We think that these guides will help readers form their own opinions about the evidence. Penston pointed out an inconsistency …

Source Citation Harrison TW, Oborne J, Newton S, Tattersfield AE. Doubling the dose of inhaled corticosteroid to prevent asthma exacerbations: randomised controlled trial. Lancet. 2004;363:271-5. 1...