Pulmonary tularaemia: a differential diagnosis to lung cancer.

BACKGROUND: Pulmonary manifestations of tularaemia are reported to be infrequent in previous publications. During 2016, we noticed an increase in the number of hospitalised patients with pulmonary tularaemia in Eastern Norway. We aimed to investigate primary pulmonary tularaemia in Eastern Norway in terms of symptoms, radiological and microbiological findings, incidence and risk exposure. METHODS: A retrospective analysis of consecutive primary pulmonary tularaemia cases from 2016 until 2018 was conducted. RESULTS: From 1 September, 2016 until 31 December, 2018, 22 patients were diagnosed with primary pulmonary tularaemia at Innlandet Hospital Trust, representing 48% of all reported tularaemia cases in the region. A peak annual incidence of 3.4 in 100 000 was found in 2017.All 22 patients lived in, or had recently visited, rural areas. Eighteen patients reported risk exposure for tularaemia, such as wood chopping, outdoor activities and farming prior to symptom onset. All patients experienced fever, and 19 patients had respiratory symptoms. Ten patients were in spontaneous recovery at diagnosis.All patients had a chest computed tomography scan. Overall, 19 patients had pulmonary lesions and 18 had enlarged intrathoracic lymph nodes. The computed tomography images were described as suspicious of malignancy in 17 patients. CONCLUSION: Pulmonary manifestations in tularaemia occurred more frequently in our region than expected from previous reports. Although all patients had symptoms consistent with infection, the majority were primarily investigated considering lung cancer due to the radiology report. In endemic areas, pulmonary tularaemia may be an important differential diagnosis to lung cancer.

Do clinicians want recommendations? A multicenter study comparing evidence summaries with and without GRADE recommendations.

OBJECTIVES: Evidence-based clinical practice guidelines provide recommendations to assist clinicians in decision-making and to reduce the gap between best current research evidence and clinical practice. However, some argue that providing preappraised evidence summaries alone, rather than recommendations, is more appropriate. The objective of the study is to evaluate clinicians' preferences, and understanding of the evidence and intended course of action in response to evidence summaries with and without recommendations. STUDY DESIGN SETTING: We included practicing clinicians attending educational sessions across 10 countries. Clinicians were randomized to receive relevant clinical scenarios supported by research evidence of low or very low certainty and accompanied by either strong or weak recommendations developed with the GRADE system. Within each group, participants were further randomized to receive the recommendation plus the corresponding evidence summary or the evidence summary alone. We evaluated participants' preferences and understanding for the presentation strategy, as well as their intended course of action. RESULTS: One hundred eighty-nine of 219 (86%) and 201 of 248 (81%) participants preferred having recommendations accompanying evidence summaries for both strong and weak recommendations, respectively. Across all scenarios, less than half of participants correctly interpreted information provided in the evidences summaries (e.g., estimates of effect, certainty in the research evidence). The presence of a recommendation resulted in a more appropriate intended course of action for two scenarios involving strong recommendations. CONCLUSION: Evidence summaries alone are not enough to impact clinicians' course of action. Clinicians clearly prefer having recommendations accompanying evidence summaries in the context of low or very low certainty of evidence (Trial registration NCT02006017).

UpToDate adherence to GRADE criteria for strong recommendations: an analytical survey.

INTRODUCTION: UpToDate is widely used by clinicians worldwide and includes more than 9400 recommendations that apply the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. GRADE guidance warns against strong recommendations when certainty of the evidence is low or very low (discordant recommendations) but has identified five paradigmatic situations in which discordant recommendations may be justified. OBJECTIVES: Our objective was to document the strength of recommendations in UpToDate and assess the frequency and appropriateness of discordant recommendations. DESIGN: Analytical survey of all recommendations in UpToDate. METHODS: We identified all GRADE recommendations in UpToDate and examined their strength (strong or weak) and certainty of the evidence (high, moderate or low certainty). We identified all discordant recommendations as of January 2015, and pairs of reviewers independently classified them either into one of the five appropriate paradigms or into one of three categories inconsistent with GRADE guidance, based on the evidence presented in UpToDate. RESULTS: UpToDate included 9451 GRADE recommendations, of which 6501 (68.8%) were formulated as weak recommendations and 2950 (31.2%) as strong. Among the strong, 844 (28.6%) were based on high certainty in effect estimates, 1740 (59.0%) on moderate certainty and 366 (12.4%) on low certainty. Of the 349 discordant recommendations 204 (58.5%) were judged appropriately (consistent with one of the five paradigms); we classified 47 (13.5%) as good practice statements; 38 (10.9%) misclassified the evidence as low certainty when it was at least moderate and 60 (17.2%) warranted a weak rather than a strong recommendation. CONCLUSION: The proportion of discordant recommendations in UpToDate is small (3.7% of all recommendations) and the proportion that is truly problematic (strong recommendations that would best have been weak) is very small (0.6%). Clinicians should nevertheless be cautious and look for clear explanations-in UpToDate and elsewhere-when guidelines offer strong recommendations based on low certainty evidence.

Multilayered and digitally structured presentation formats of trustworthy recommendations: a combined survey and randomised trial.

OBJECTIVES: To investigate practicing physicians' preferences, perceived usefulness and understanding of a new multilayered guideline presentation format-compared to a standard format-as well as conceptual understanding of trustworthy guideline concepts. DESIGN: Participants attended a standardised lecture in which they were presented with a clinical scenario and randomised to view a guideline recommendation in a multilayered format or standard format after which they answered multiple-choice questions using clickers. Both groups were also presented and asked about guideline concepts. SETTING: Mandatory educational lectures in 7 non-academic and academic hospitals, and 2 settings involving primary care in Lebanon, Norway, Spain and the UK. PARTICIPANTS: 181 practicing physicians in internal medicine (156) and general practice (25). INTERVENTIONS: A new digitally structured, multilayered guideline presentation format and a standard narrative presentation format currently in widespread use. PRIMARY AND SECONDARY OUTCOME MEASURES: Our primary outcome was preference for presentation format. Understanding, perceived usefulness and perception of absolute effects were secondary outcomes. RESULTS: 72% (95% CI 65 to 79) of participants preferred the multilayered format and 16% (95% CI 10 to 22) preferred the standard format. A majority agreed that recommendations (multilayered 86% vs standard 91%, p value=0.31) and evidence summaries (79% vs 77%, p value=0.76) were useful in the context of the clinical scenario. 72% of participants randomised to the multilayered format vs 58% for standard formats reported correct understanding of the recommendations (p value=0.06). Most participants elected an appropriate clinical action after viewing the recommendations (98% vs 92%, p value=0.10). 82% of the participants considered absolute effect estimates in evidence summaries helpful or crucial. CONCLUSIONS: Clinicians clearly preferred a novel multilayered presentation format to the standard format. Whether the preferred format improves decision-making and has an impact on patient important outcomes merits further investigation.

Compression Stockings for Preventing the Postthrombotic Syndrome in Patients with Deep Vein Thrombosis.

OBJECTIVE: We conducted a systematic review and meta-analysis to address benefits and harms of using elastic compression stockings after lower-extremity deep vein thrombosis. METHODS: We searched 7 electronic databases through January 15, 2015, including randomized controlled trials (RCTs)/quasi-randomized trials reporting on elastic compression stocking efficacy on postthrombotic syndrome incidence, recurrent venous thromboembolism, mortality, and acute pain after deep vein thrombosis. Two reviewers independently screened records, extracted data, assessed risk of bias, and assessed confidence in effect estimates using Grading of Recommendations Assessment, Development, and Evaluation methodology. We applied random-effects meta-analysis models. RESULTS: We included 5 RCTs (n = 1418) reporting on postthrombotic syndrome. The hazard ratio (HR) for postthrombotic syndrome with elastic compression stockings was 0.69 (95% confidence interval [CI], 0.47-1.02). We have very low confidence in this estimate due to heterogeneity and inclusion of unblinded studies at high risk of bias. Excluding high risk of bias studies, a single large RCT at low risk of bias provided moderate-quality evidence of no effect on postthrombotic syndrome (HR 1.00; 95% CI, 0.81-1.24). Moderate-quality evidence including all 5 studies suggests no effect of elastic compression stockings on recurrent venous thromboembolism (relative risk [RR] 0.88; 95% CI, 0.63-1.24) or mortality (RR 1.00; 95% CI, 0.73-1.37, 5 studies). Moderate-quality evidence from one large RCT does not suggest effect on acute pain after deep vein thrombosis. CONCLUSIONS: The highest-quality evidence available suggests no effect of elastic compression stockings on postthrombotic syndrome or pain relief, from a single large RCT. However, results for preventing postthrombotic syndrome differ substantially across studies, and future guideline updates should reflect uncertainty about treatment effects. Elastic compression stockings are unlikely to prevent death or recurrent venous thromboembolism.

Development of a novel, multilayered presentation format for clinical practice guidelines.

BACKGROUND: Bridging the gap between clinical research and everyday health-care practice requires effective communication strategies. To address current shortcomings in conveying practice recommendations and supporting evidence, we are creating and testing presentation formats for clinical practice guidelines (CPGs). METHODS: We carried out multiple cycles of brainstorming and sketching, developing a prototype. Physicians participating in the user testing viewed CPG formats linked to clinical scenarios and engaged in semistructured interviews applying a think-aloud method for exploring important aspects of user experience. RESULTS: We developed a multilayered presentation format that allows clinicians to successively view more in-depth information. Starting with the recommendations, clinicians can, on demand, access a rationale and a key information section containing statements on quality of the evidence, balance between desirable and undesirable consequences, values and preferences, and resource considerations. We collected feedback from 27 stakeholders and performed user testing with 47 practicing physicians from six countries. Advisory group feedback and user testing of the first version revealed problems with conceptual understanding of underlying CPG methodology, as well as difficulties with the complexity of the layout and content. Extensive revisions made before the second round of user testing resulted in most participants expressing overall satisfaction with the final presentation format. CONCLUSIONS: We have developed an electronic, multilayered, CPG format that enhances the usability of CPGs for frontline clinicians. We have implemented the format in electronic guideline tools that guideline organizations can now use when authoring and publishing their guidelines.

Adaptation of trustworthy guidelines developed using the GRADE methodology: a novel five-step process.

BACKGROUND: Adaptation of guidelines for use at the national or local level can facilitate their implementation. We developed and evaluated an adaptation process in adherence with standards for trustworthy guidelines and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology, aiming for efficiency and transparency. This article is the first in a series describing our adaptation of Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines for a Norwegian setting. METHODS: Informed by the ADAPTE framework, we developed a five-step adaptation process customized to guidelines developed using GRADE: (1) planning, (2) initial assessment of the recommendations, (3) modification, (4) publication, and (5) evaluation. We developed a taxonomy for describing how and why recommendations from the parent guideline were modified and applied a mixed-methods case study design for evaluation of the process. RESULTS: We published the adapted guideline in November 2013 in a novel multilayered format. The taxonomy for adaptation facilitated transparency of the modification process for both the guideline developers and the end users. We excluded 30 and modified 131 of the 333 original recommendations according to the taxonomy and developed eight new recommendations. Unforeseen obstacles related to acquiring a licensing agreement and procuring a publisher resulted in a 9-month delay. We propose modifications of the adaptation process to overcome these obstacles in the future. CONCLUSIONS: This case study demonstrates the feasibility of a novel guideline adaptation process. Replication is needed to further validate the usefulness of the process in increasing the organizational and methodologic efficiency of guideline adaptation.

Applying new strategies for the national adaptation, updating, and dissemination of trustworthy guidelines: results from the Norwegian adaptation of the Antithrombotic Therapy and the Prevention of Thrombosis, 9th Ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines.

BACKGROUND: The Antithrombotic Therapy and the Prevention of Thrombosis, 9th Edition: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (AT9) represent trustworthy international guidelines for antithrombotic treatment and thromboprophylaxis. We describe major changes to the format and content resulting from applying new strategies for guideline adaptation and dissemination. METHODS: A Norwegian guideline panel of 46 experts completed a structured and systematic adaptation process, updated the recommendations based on new evidence, and rewrote the recommendations in an electronic multilayered presentation format. We published the adapted guideline using the web-based Making GRADE the Irresistible Choice Guideline Authoring and Publication Platform. RESULTS: We applied a novel presentation format to 333 recommendations from 11 of the 15 management chapters in AT9 and condensed and restructured them into 249 recommendations in a multilayered format. We added additional relevant information, such as 29 best-practice statements about new oral anticoagulants and practical information sections for 121 recommendations. Common reasons for modifications included feasibility of the recommendations in a national context, disagreement with applied baseline risk estimates, and reevaluation of the balance between the benefits and harms of interventions in relation to assumed typical patient preferences and values. The adapted guideline was published and disseminated online in November 2013. CONCLUSIONS: New strategies for adapting, updating, and disseminating trustworthy guidelines proved feasible and will provide Norwegian health-care professionals and patients with up-to-date guidance tailored to national circumstances.

Initiation and continuation of randomized trials after the publication of a trial stopped early for benefit asking the same study question: STOPIT-3 study design.

BACKGROUND: Randomized control trials (RCTs) stopped early for benefit (truncated RCTs) are increasingly common and, on average, overestimate the relative magnitude of benefit by approximately 30%. Investigators stop trials early when they consider it is no longer ethical to enroll patients in a control group. The goal of this systematic review is to determine how investigators of ongoing or planned RCTs respond to the publication of a truncated RCT addressing a similar question. METHODS/DESIGN: We will conduct systematic reviews to update the searches of 210 truncated RCTs to identify similar trials ongoing at the time of publication, or started subsequently, to the truncated trials ('subsequent RCTs'). Reviewers will determine in duplicate the similarity between the truncated and subsequent trials. We will analyze the epidemiology, distribution, and predictors of subsequent RCTs. We will also contact authors of subsequent trials to determine reasons for beginning, continuing, or prematurely discontinuing their own trials, and the extent to which they rely on the estimates from truncated trials. DISCUSSION: To the extent that investigators begin or continue subsequent trials they implicitly disagree with the decision to stop the truncated RCT because of an ethical mandate to administer the experimental treatment. The results of this study will help guide future decisions about when to stop RCTs early for benefit.

Creating clinical practice guidelines we can trust, use, and share: a new era is imminent.

Standards and guidance for developing trustworthy clinical practice guidelines are now available, and a number of leading guidelines adhere to the key standards. Even current trustworthy guidelines, however, generally suffer from a cumbersome development process, suboptimal presentation formats, inefficient dissemination to clinicians at the point of care, high risk of becoming quickly outdated, and suboptimal facilitation of shared decision-making with patients. To address these limitations, we have--in our innovative research program and nonprofit organization, MAGIC (Making GRADE the Irresistible Choice)--constructed a conceptual framework and tools to facilitate the creation, dissemination, and dynamic updating of trustworthy guidelines. We have developed an online application that constitutes an authoring and publication platform that allows guideline content to be written and structured in a database, published directly on our web platform or exported in a computer-interpretable language (eg, XML) enabling dissemination through a wide range of outputs that include electronic medical record systems, web portals, and applications for smartphones/tablets. Modifications in guidelines, such as recommendation updates, will lead to automatic alterations in these outputs with minimal additional labor for guideline authors and publishers, greatly facilitating dynamic updating of guidelines. Semiautomated creation of a new generation of decision aids linked to guideline recommendations should facilitate face-to-face shared decision-making in the clinical encounter. We invite guideline organizations to partner with us (www.magicproject.org) to apply and further improve the tools for their purposes. This work will result in clinical practice guidelines that we cannot only trust, but also easily share and use.