Diretrizes clínicas para tratamento da depressão: análise de fatores associados à qualidade e comparação de recomendações para pacientes não respondedores e com depressão resistente / Clinical guidelines for the treatment of depression: analysis of factors associated with quality and comparison of recommendations for nonresponding patients and for patients with resistant depression

Diretrizes clínicas (DCs) de alta qualidade são importantes para a assistência efetiva de pacientes com doenças crônicas, incluindo a depressão. A depressão é um dos principais problemas de saúde mundial, sendo um dos transtornos psiquiátricos mais comumente encontrados na prática médica, afetando cerca de 300 milhões de pessoas. Além de sua natureza debilitante e onerosa, muitas vezes pode levar a desfechos graves, tal como o suicídio, principalmente em pacientes que não respondem aos tratamentos. Assim, o objetivo geral desta tese foi identificar fatores das DCs associados à qualidade metodológica desses documentos e de suas recomendações, e comparar as recomendações para duas situações de falhas da farmacoterapia: pacientes não respondedores e pacientes com depressão resistente ao tratamento (DRT). Operacionalmente, foram feitas revisões sistemáticas da literatura em bases científicas e específicas de DCs, e incluídas DCs publicadas nos últimos onze anos que contivessem recomendações para o tratamento farmacológico de adultos com depressão. Para avaliação geral das DCs, foi aplicado o instrumento AGREE II, e para avaliação específica das recomendações, o instrumento AGREE-REX. As DCs foram consideradas de alta qualidade quando pontuaram com escores maiores ou iguais a 60% (no estudo descrito no capítulo 2) e maiores ou iguais a 80% (no estudo descrito no capítulo 3) no domínio 3 (Rigor de desenvolvimento) do AGREE II. As DCs com recomendações de alta qualidade foram as que pontuaram com mais de 60% no domínio 1 (Aplicabilidade Clínica) do AGREE-REX. Das 63 DCs selecionadas, 17 (27%) apresentaram alta qualidade, e 7 (11%) apresentaram recomendações de alta qualidade. Os fatores associados à maior qualidade foram gerenciamento de conflitos de interesses, equipe multiprofissional e tipo de instituição. A inclusão de representante do paciente na equipe também foi associada a recomendações de maior qualidade. Verificou-se que a maioria das DCs concorda com a necessidade de: reavaliar o diagnóstico, a presença de comorbidades, a adesão ao tratamento, ajustar a dosagem do antidepressivo e adicionar psicoterapia como os primeiros passos para aqueles que não respondem ao tratamento antidepressivo de primeira linha. Em relação às recomendações, há falhas importantes, incluindo a não apresentação de definição padronizada de resposta adequada/inadequada/parcial, e o não estabelecimento de tempo de tratamento necessário para declarar DRT. Todas as DCs incluíram a possibilidade de substituição do antidepressivo, potencialização com outros medicamentos e combinação de antidepressivos. Todavia, três DCs não recomendaram uma sequência entre eles. Por fim, verificou-se que das 17 DCs de alta qualidade e das 7 DCs com recomendações de alta qualidade, apenas duas incluíram definição e recomendações para DRT. Não existe consenso entre as DCs de alta qualidade quanto à definição e uso do termo DRT. Não foi possível extrair uma estratégia terapêutica convergente para DRT em adultos. Os resultados obtidos reforçam a necessidade de maior foco no aprimoramento da qualidade das DCs e de suas recomendações, especialmente nos subgrupos relativos à resposta inadequada ao tratamento e a DRT, nas quais as definições não são claras

High-quality clinical practice guidelines (CPGs) are important for treating patients with chronic diseases such as depression. Depression is a major health concern worldwide, affecting approximately 300 million people. It is one of the most prevalent psychiatric disorders in medical practice. It is not only debilitating and costly but can also lead to tragic consequences such as suicide, particularly in patients who do not respond to treatment. The objective of this thesis was to identify CPGs factors associated with the methodological quality of these documents and their recommendations. Furthermore, this thesis aimed to compare the recommendations in two pharmacotherapy failure situations: inadequate response to treatment and treatment-resistant depression (TRD). Systematic literature reviews were conducted on scientific and CPG-specific databases. Reviews were also conducted on CPGs published in the last eleven years that included recommendations for pharmacological treatment of adults with depression. The AGREE II instrument was used for the CPGs general assessment, while the AGREE-REX instrument was used specifically to assess their recommendations. CPGs were considered high quality if they achieved a score of at least 60% in the study mentioned in Chapter 2 and a score of at least 80% in the study mentioned in Chapter 3 in the AGREE II, rigour of development domain. The CPGs with high-quality recommendations were those that scored greater than 60% in Domain 1 (Clinical Applicability) of the AGREE-REX. Of the 63 selected CPGs, 17 (27%) were high quality, and 7 (11.1%) had recommendations of high quality. Factors associated with higher quality were conflict of interest management, multi-professional team, and type of institution. Inclusion of a patients representative on the team was associated with higher quality recommendations. Most CPGs agreed with the need to reassess diagnoses, comorbidities, and treatment adherence. They also agreed on adjusting antidepressant dosage and providing psychotherapy as a first step for patients who do not respond to first-line antidepressant treatment. There are significant shortcomings in the recommendations. In particular, the lack of a standardized definition of adequate, inadequate, or partial response to treatment and the lack of clarity surrounding the duration of treatment required to establish TRD. All CPGs included the possibility of antidepressant substitution, potentiation with other drugs, and a combination of antidepressants. However, three CPGs did not recommend a preferred sequence for these interventions. Finally, of the 17 high-quality CPGs and the 7 CPGs with high-quality recommendations, only two included definition and recommendations for TRD. There is no consensus among the high-quality CPGs regarding the definition and use of the term TRD. Ultimately, finding a convergent therapeutic strategy for TRD in adults was not possible. These results highlighted the need to focus more on improving the quality of CPGs and their recommendations, especially in the subgroups related to inadequate response to treatment and TRD, where definitions are unclear

Extração de recomendações farmacológicas para subsidiar o processo de adaptação de guias de prática clínica utilizados no tratamento da fibrilação atrial não valvar - uma revisão sistemática de guias de prática clínica / Extraction of pharmacological recommendations to support the process of adaptation of clinical practice guides used in the treatment of non-valvular atrial fibrillation a systematic review of clinical practice guidelines

A fibrilação atrial (FA) não valvar é a arritmia cardíaca mais comum em adultos, principalmente na população idosa. Para o tratamento da FA, recomenda-se a utilização de guias de prática clínica (GPCs), que são documentos que apresentam as melhores e mais atualizadas evidências para o tratamento dos pacientes acometidos por essa arritmia. Todavia, o processo de desenvolvimento dos GPCs requer recursos humanos, financeiros e tempo. Assim, a adaptação dos referidos documentos é uma opção para reduzir a duplicação de esforços e possibilitar sua adequação para uso local. O objetivo deste trabalho foi elaborar uma matriz de recomendações farmacológicas para subsidiar o processo de adaptação de GPCs utilizados no tratamento da fibrilação atrial não valvar. Para tanto, aplicou-se o método ADAPTE: revisão sistematizada de GPCs, avaliação e seleção dos GPCs de qualidade e elaboração da matriz. Foram considerados elegíveis 26 GPCs com recomendações farmacológicas para assistência primária da fibrilação atrial não valvar em adultos, publicados em inglês, espanhol ou português no período de abril de 2014 a abril de 2019 e indexados às bases de referência: MEDLINE, Embase, Cochrane Library e em 12 bases de dados específicas. A qualidade dos GPCs, foi avaliada pela aplicação do instrumento Appraisal of Guidelines for Research & Evaluarion II (AGREE II), sendo considerados de alta qualidade aqueles que apresentaram nota igual ou superior a 60 % no domínio Rigor de desenvolvimento. Todas as etapas foram realizadas por, pelo menos, 2 avaliadores e em caso de discrepância, um terceiro avaliador participou do processo. Dos 26 GPCs avaliados apenas 7 (26,9%) foram considerados de alta qualidade. A maioria dos GPCs utiliza o escore CHA2DS2-VASc, que indica a profilaxia tromboembólica em pacientes com FA não valvar a partir da pontuação 1 (fator de risco não sexual) e sugere a anticoagulação com anticoagulantes de ação direta. Houve pouca ênfase à complexidade da profilaxia de eventos tromboembólicos em idosos. Esta matriz visa contribuir para que sejam realizadas discussões e adaptações de GPCs destinado ao tratamento da FA não valvar com ênfase nas demandas e necessidades locais

Non-valvular atrial fibrillation (AF) is the most common cardiac arrhythmia in adults, especially in the elderly population. For the treatment of AF, the use of clinical practice guidelines (CPGs) is recommended, which are documents that present the best and most up-to-date evidence for the treatment of patients who are affected by this arrhythmia. However, the CPGs development process requires human, financial and time resources. However, the adaptation of documents is an option to reduce the duplication of efforts and make it possible to adapt them for any local use. The objective of this work was to elaborate a matrix of pharmacological treatment to support the process of adaptation of CPGs used in the treatment of non-valvular atrial fibrillation. Therefore, the ADAPTE method was applied: systematic review of CPGs, evaluation and selection of quality CPGs and matrix definition. Twenty-six CPGs were considered eligible with pharmacological recommendations for primary care of non-valvular atrial fibrillation valid in adults, published in English, Spanish or Portuguese from April 2014 to April 2019 and indexed to the following reference databases: MEDLINE, Embase, Cochrane Library and in 12 specific databases. The quality of the CPGs was assessed by applying the Assessment of Guidelines for Research and Assessment II (AGREE II) instrument, being considered of high those who had a grade equal to or greater than 60% in the domain Rigour of development. All steps were performed by a least 2 evaluators and in case of discrepancy, a third evaluator participated in the process. Of the 26 CPGs evaluated, only 7 (26.9%) were considered to be of high quality. Most CPGs use the CHA2DS2-VASc score, which indicates thromboembolic prophylaxis in patients with non-valvular AF from score 1 (non-sexual risk factor), and suggest anticoagulation with direct-acting anticoagulants. There was little emphasis on the complexity of prophylaxis for thromboembolic events in the elderly. This matrix aims to contribute to discussion and adaptations of CPGs for the treatment of non-valvar AF with the emphasis on local demands and needs

Declining use of neurological eponyms in cases where a non-eponymous alternative exists.

Eponyms are common in neurology, but their use is controversial. Recent studies have demonstrated increasing eponym use over time in the scientific literature, but it is unclear whether this is a result of authors choosing to use eponyms more frequently, or is merely a product of increasing rates of scientific publication. Our goal was to explore trends in decision-making pertaining to eponym usage. We identified cases where an eponym and a corresponding non-eponymous term existed, and assessed temporal trends in the relative usage of these terms using Google's n-gram viewer for each decade from 1900-2019. Relative to corresponding non-eponymous terms, the use of eponyms increased across the 20th century, peaking in the decade from 1980 to 1989, before sharply declining after the turn of the 21st century. This indicates that when faced with a choice between using an eponym and non-eponymous term, contemporary authors increasingly chose the non-eponymous term. This recent trend may reflect increased awareness of the limitations of eponyms, greater attention to the personal and political lives of namesakes, and a cultural shift toward viewing scientific advances as the result of collective and collaborative efforts rather than the solitary achievements of eminent individuals.

Evidence-based medicine self-assessment, knowledge, and integration into daily practice: a survey among Romanian physicians and comparison between trainees and specialists.

BACKGROUND: A gap between the attitude towards evidence-based medicine (EBM), knowledge and awareness has been reported among physicians from different parts of the world. However, no investigation on Romanian physicians is available in the scientific literature. Our study aimed, firstly, to assess EBM awareness and the knowledge used by Romanian physicians, and, secondly, to compare resident trainees with specialists. METHODS: Romanian trainee and specialist physicians were invited to participate in this cross-sectional study. The study tool was an online questionnaire designed to explore their awareness, knowledge, usefulness, the attitude in medical documentation, and the use of professional EBM resources. Data were collected by Google Form from January 1st to April 30th, 2017, respecting the responders' anonymity. Two groups of physicians were investigated as trainees and specialists, respectively. Descriptive statistics (number, percentage, median and interquartile range) was used to describe the survey-related variables. Statistical significance on qualitative data was calculated with the Chi-square test, Fisher's exact test, or the Z-test for proportions. RESULTS: Two hundred and 50 physicians participated in this study (68% trainees vs. 32% specialists). In both groups, a significantly high percentage was represented by women as compared to men (trainees 72.4%, specialists 70%). The correct definition of EBM was identified by most respondents (75.6%). Affirmatively, both trainees and specialists always looked at levels of evidence when reading scientific literature, but a small percentage (6.5% trainees and 3% specialists) adequately identified the uppermost types of evidence in the hierarchy. Almost a quarter of the respondents shared the name of mobile EBM resources that they used to support the daily practice. Only six out of the 49 listed mobile resources met the EBM criteria. CONCLUSIONS: The participants proved to have limited knowledge of EBM and a positive attitude towards the concept. They made use of mobile medical resources without understanding which of these were evidence-based.

Definition of a systematic review used in overviews of systematic reviews, meta-epidemiological studies and textbooks.

BACKGROUND: A standard or consensus definition of a systematic review does not exist. Therefore, if there is no definition about a systematic review in secondary studies that analyse them or the definition is too broad, inappropriate studies might be included in such evidence synthesis. The aim of this study was to analyse the definition of a systematic review (SR) in health care literature, elements of the definitions that are used and to propose a starting point for an explicit and non-ambiguous SR definition. METHODS: We included overviews of systematic reviews (OSRs), meta-epidemiological studies and epidemiology textbooks. We extracted the definitions of SRs, as well as the inclusion and exclusion criteria that could indicate which definition of a SR the authors used. We extracted individual elements of SR definitions, categorised and quantified them. RESULTS: Among the 535 analysed sources of information, 188 (35%) provided a definition of a SR. The most commonly used reference points for the definitions of SRs were Cochrane and the PRISMA statement. We found 188 different elements of SR definitions and divided them into 14 categories. The highest number of SR definition elements was found in categories related to searching (N = 51), analysis/synthesis (N = 23), overall methods (N = 22), quality/bias/appraisal/validity (N = 22) and aim/question (N = 13). The same five categories were also the most commonly used combination of categories in the SR definitions. CONCLUSION: Currently used definitions of SRs are vague and ambiguous, often using terms such as clear, explicit and systematic, without further elaboration. In this manuscript we propose a more specific definition of a systematic review, with the ultimate aim of motivating the research community to establish a clear and unambiguous definition of this type of research.

Hierarchies of evidence applied to lifestyle Medicine (HEALM): introduction of a strength-of-evidence approach based on a methodological systematic review.

BACKGROUND: Current methods for assessing strength of evidence prioritize the contributions of randomized controlled trials (RCTs). The objective of this study was to characterize strength of evidence (SOE) tools in recent use, identify their application to lifestyle interventions for improved longevity, vitality, or successful aging, and to assess implications of the findings. METHODS: The search strategy was created in PubMed and modified as needed for four additional databases: Embase, AnthropologyPlus, PsycINFO, and Ageline, supplemented by manual searching. Systematic reviews and meta-analyses of intervention trials or observational studies relevant to lifestyle intervention were included if they used a specified SOE tool. Data was collected for each SOE tool. Conditions necessary for assigning the highest SOE grading and treatment of prospective cohort studies within each SOE rating framework were summarized. The expert panel convened to discuss the implications of findings for assessing evidence in the domain of lifestyle medicine. RESULTS AND CONCLUSIONS: A total of 15 unique tools were identified. Ten were tools developed and used by governmental agencies or other equivalent professional bodies and were applicable in a variety of settings. Of these 10, four require consistent results from RCTs of high quality to award the highest rating of evidence. Most SOE tools include prospective cohort studies only to note their secondary contribution to overall SOE as compared to RCTs. We developed a new construct, Hierarchies of Evidence Applied to Lifestyle Medicine (HEALM), to illustrate the feasibility of a tool based on the specific contributions of diverse research methods to understanding lifetime effects of health behaviors. Assessment of evidence relevant to lifestyle medicine requires a potential adaptation of SOE approaches when outcomes and/or exposures obviate exclusive or preferential reliance on RCTs. This systematic review was registered with the International Prospective Register of Systematic Reviews, PROSPERO [CRD42018082148].

Size and Shape of the Human Anterior Cruciate Ligament and the Impact of Sex and Skeletal Growth: A Systematic Review.

BACKGROUND: High rates of anterior cruciate ligament (ACL) injury and surgical reconstruction in both skeletally immature and mature populations have led to many studies investigating the size and shape of the healthy ligament. The purposes of the present study were to compile existing quantitative measurements of the geometry of the ACL, its bundles, and its insertion sites and to describe effects of common covariates such as sex and age. METHODS: A search of the Web of Science was conducted for studies published from January 1, 1900, to April 11, 2018, describing length, cross-sectional area, volume, orientation, and insertion sites of the ACL. Two reviewers independently screened and reviewed the articles to collect quantitative data for each parameter. RESULTS: Quantitative data were collected from 92 articles in this systematic review. In studies of adults, reports of average ACL length, cross-sectional area, and volume ranged from 26 to 38 mm, 30 to 53 mm, and 854 to 1,858 mm, respectively. Reported values were commonly found to vary according to sex and skeletal maturity as well as measurement technique. CONCLUSIONS: Although the geometry of the ACL has been described widely in the literature, quantitative measurements can depend on sex, age, and measurement modality, contributing to variability between studies. As such, care must be taken to account for these factors. The present study condenses measurements describing the geometry of the ACL, its individual bundles, and its insertion sites, accounting for common covariates when possible, to provide a resource to the clinical and scientific communities. CLINICAL RELEVANCE: Quantitative measures of ACL geometry are informative for developing clinical treatments such as ACL reconstruction. Age and sex can impact these parameters.

A scoping study of frameworks for adapting public health evidence-based interventions.

Evidence-based public health translation of research to practice is essential to improve the public's health. Dissemination and implementation researchers have explored what happens once practitioners adopt evidence-based interventions (EBIs) and have developed models and frameworks to describe the adaptation process. This scoping study identified and summarized adaptation frameworks in published reports and grey literature. We followed the recommended steps of a scoping study: (a) identifying the research question; (b) identifying relevant studies; (c) selecting studies; (d) charting the data; (e) collating, summarizing, and reporting the results; and (f) consulting with experts. We searched PubMed, PsycINFO, PsycNET, and CINAHL databases for articles referencing adaptation frameworks for public health interventions in the published and gray literature, and from reference lists of framework articles. Two reviewers independently coded the frameworks and their steps and identified common steps. We found 13 adaptation frameworks with 11 program adaptation steps: (a) assess community, (b) understand the EBI(s), (c) select the EBI, (d) consult with experts, (e) consult with stakeholders, (f) decide on needed adaptations, (g) adapt the original EBI, (h) train staff, (i) test the adapted materials, (j) implement the adapted EBI, and (k) evaluate. Eight of these steps were recommended by more than five frameworks: #1-3, 6-7, and 9-11. This study is the first to systematically identify, review, describe, and summarize frameworks for adapting EBIs. It contributes to the literature by consolidating key steps in program adaptation of EBIs and describing the associated tasks in each step.

The evolution of GRADE (part 3): A framework built on science or faith?

RATIONALE, AIMS, AND OBJECTIVES: The Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) framework has undergone several modifications since it was first presented as a method for developing clinical practice recommendations. In the previous two articles of this series, we showed that absent, in the first three versions of GRADE, is a justification (theoretical and/or empirical) for why the presented criteria for determining the quality of evidence and the components for determining the strength of a recommendation were included (and others not included) in the framework. Furthermore, it was often not clear how to operationalize and integrate the criteria/components when using the framework. In part 3 of this series, we examine the literature since version 3 to see if the GRADE working group has provided an overall justification scheme for GRADE or clear instruction on how to operationalize and integrate the criteria/components in the framework. METHODS: Narrative review. RESULTS: GRADE has undergone further modification since the last version was presented. In the recent literature, we see additional shifts in terminology (eg, "quality of evidence" is now "certainty of evidence"), clarification on the construct of certainty of evidence, continued emphasis on "transparency" and new emphasis on "trustworthiness," the addition of health equity as a component for determining strength of a recommendation, and the development of the Evidence to Decision frameworks. However, these modifications have done little to improve the justification scheme that sustains GRADE or clarify how to operationalize the criteria/components. CONCLUSIONS: If we desire that our clinical recommendations be based on scientific teaching rather than faith-based preaching, then the GRADE framework should be justified theoretically and/or empirically. Until such time that the working group provides a theoretical justification that the use of the GRADE framework should produce valid recommendations, and/or empirical evidence to support that it does, enthusiasm for the framework should be tempered.

From MARS to MAGIC: The remarkable journey through time and space of the Grading of Recommendations Assessment, Development and Evaluation initiative.

For over 30 years, "evidence-based" clinical guidelines remained entrenched in an oversimplified, design-based, framework for rating the strength of evidence supporting clinical recommendations. The approach frequently equated the rating of evidence with that of the recommendations themselves. "Grading Recommendations Assessment, Development and Evaluation (GRADE)" has emerged as a proposed antidote to obsolete guideline methodology. GRADE sponsors and collaborators are in the process of attempting to amplify and extend the framework to encompass implementation and adaptation of guidelines, above and beyond the evaluation and rating of clinical research. Alternative schemes and models for such extensions are beginning to appear. This commentary reviews the strengths and weaknesses of GRADE with reference to other recent critiques. It considers the GRADE Working Group's "evidence-to-decision" extension of the evidence rating framework, together with proposed alternatives. It identifies pitfalls of the GRADE system's cooptation of relational processes necessary to the interpretation and uptake of recommendations that properly belong to end-users. It also identifies dangers inherent in blurring important boundaries between clinical and policy applications of guidelines. Finally, it addresses criticisms regarding the lack of a theoretical framework supporting the different facets of the GRADE approach and proposes a social constructivist orientation to clinical guideline development and use. Recommendations are offered to potential guideline developers and users regarding how to draw upon the strengths of the GRADE framework without succumbing to its pitfalls.

The evolution of GRADE (part 1): Is there a theoretical and/or empirical basis for the GRADE framework?

RATIONALE, AIMS, AND OBJECTIVES: The Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) framework has been presented as the best method available for developing clinical recommendations. GRADE has undergone a series of modifications. Here, we present the first part of a three article series examining the evolution of GRADE. Our purpose is to explore if (and if so, how) GRADE provides: (1) a justification (ie, theoretical and/or empirical) for why the criteria/components under consideration in the system are included (and other factors excluded), as well as why some criteria/components where added/modified in the evolution process, (2) clear and functional (ie, how to operationalize them) definitions of the included criteria/components, and (3) instruction and justification for how all the criteria/components are to be integrated when determining a recommendation. In part 1 of the series, we examine the first two versions of GRADE. METHODS: Narrative review. RESULTS: The justification scheme that sustains GRADE is not articulated in the first two versions of the framework. Why some criteria/components were included, and others excluded, is not justified theoretically nor is empirical support provided to suggest that the framework as presented includes that which is needed to produce valid recommendations. The first two versions of GRADE show a lack of clear instruction on how to operationalize the criteria for assessing the quality of evidence and the components for making a recommendation (including how to integrate the criteria/components at each step), which leaves substantial room for judgement on the part of the user of GRADE for guideline development. CONCLUSIONS: This article revealed an absence of a justification (theoretical and/or empirical) to support important aspects of the GRADE framework, as well as a lack of clear instruction on how to operationalize the criteria and components in the framework. These issues limit one's ability to scientifically assess the appropriateness of GRADE for determining clinical recommendations.

The evolution of GRADE (part 2): Still searching for a theoretical and/or empirical basis for the GRADE framework.

RATIONALE, AIMS, AND OBJECTIVES: The GRADE framework has been widely adopted as the preferred method for developing clinical practice recommendations. In the first article of our three part series examining the evolution of GRADE, we showed an absence (in the first two versions of GRADE) of a theoretical basis and/or empirical data to support why the presented criteria for determining the quality of evidence regarding the effect estimate and the components under consideration for determining the strength of the recommendation were included and other criteria/components excluded. Furthermore, often, it was not clear how to operationalize the included criteria/components (and integrate them) when using the framework. In part 2 of this series, we examine if version 3 of GRADE offered improvements on previous versions with respect to a justification scheme and how to operationalize the framework's criteria/components. METHODS: Narrative review. RESULTS: Our examination suggests that version 3 has done little to improve on the justification scheme that sustains GRADE. Still absent is a justification (theoretical and/or empirical) for why the criteria/components were chosen. Likewise, version 3 is still lacking clarity regarding how to implement and integrate the criteria/considerations in the framework (ie, operationalize the framework) when determining the quality of evidence or strength of recommendation. Transparency is now emphasized as the merit of GRADE. However, we are offered no theoretical justification for how the use of GRADE should achieve transparency or empirical evidence to support that transparency is achieved. CONCLUSIONS: While version 3 reveals acknowledgement by the authors of GRADE that the framework is a work in progress, it still lacks a justification scheme (theoretical and/or empirical) to sustain it and clarity in its criteria/components to operationalize it. As was suggested in part 1, such issues limit one's ability to scientifically assess the appropriateness of GRADE for its stated purpose.

Determinants Used to Justify the Strength of Recommendations among Korean Clinical Practice Guidelines.

BACKGROUND: A standardized systematic approach to grade evidence and the strength of recommendations is important for guideline users to minimize bias and help interpret the most suitable decisions at the point of care. The study aims to identify and classify determinants used to make judgement for the strength of recommendations among 56 Korean clinical practice guidelines (CPGs), and explore strong recommendations based on low quality of evidence. METHODS: Determinants used in the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach among 34 CPGs which have reported both strength of recommendations and level of evidence were reviewed. RESULTS: Five of 34 CPGs (14.7%) considered quality of evidence, benefits and harms, patients' values and preferences, and costs. And 24 of 34 CPGs (70.6%) considered both magnitude of effect and feasibility as additional determinants. Judgement table was not widely provided for use to translate evidence into recommendations. Eighty-two of 121 recommendations (67.8%, ranged 20.0% to 100.0%) among 11 CPGs using the same judgement scheme showed 'strong' strength of recommendations based on low or very low quality of evidence. Among 5 paradigmatic situations that justify strong recommendations based on low or very low evidence, situation classified as 'potential equivalence, one option clearly less risky or costly' was 87.8% for 82 strong recommendations. Situation classified as 'uncertain benefit, certain harm' was 4.9%. CONCLUSION: There is a need to introduce and systematize an evidence-based grading system. Using judgement table to justify the strength of recommendations and applying the 5 paradigmatic situations mentioned above is also recommended in the near future.

What kind of systematic review should I conduct? A proposed typology and guidance for systematic reviewers in the medical and health sciences.

BACKGROUND: Systematic reviews have been considered as the pillar on which evidence-based healthcare rests. Systematic review methodology has evolved and been modified over the years to accommodate the range of questions that may arise in the health and medical sciences. This paper explores a concept still rarely considered by novice authors and in the literature: determining the type of systematic review to undertake based on a research question or priority. RESULTS: Within the framework of the evidence-based healthcare paradigm, defining the question and type of systematic review to conduct is a pivotal first step that will guide the rest of the process and has the potential to impact on other aspects of the evidence-based healthcare cycle (evidence generation, transfer and implementation). It is something that novice reviewers (and others not familiar with the range of review types available) need to take account of but frequently overlook. Our aim is to provide a typology of review types and describe key elements that need to be addressed during question development for each type. CONCLUSIONS: In this paper a typology is proposed of various systematic review methodologies. The review types are defined and situated with regard to establishing corresponding questions and inclusion criteria. The ultimate objective is to provide clarified guidance for both novice and experienced reviewers and a unified typology with respect to review types.

Clinical classification in low back pain: best-evidence diagnostic rules based on systematic reviews.

BACKGROUND: Clinical examination findings are used in primary care to give an initial diagnosis to patients with low back pain and related leg symptoms. The purpose of this study was to develop best evidence Clinical Diagnostic Rules (CDR] for the identification of the most common patho-anatomical disorders in the lumbar spine; i.e. intervertebral discs, sacroiliac joints, facet joints, bone, muscles, nerve roots, muscles, peripheral nerve tissue, and central nervous system sensitization. METHODS: A sensitive electronic search strategy using MEDLINE, EMBASE and CINAHL databases was combined with hand searching and citation tracking to identify eligible studies. Criteria for inclusion were: persons with low back pain with or without related leg symptoms, history or physical examination findings suitable for use in primary care, comparison with acceptable reference standards, and statistical reporting permitting calculation of diagnostic value. Quality assessments were made independently by two reviewers using the Quality Assessment of Diagnostic Accuracy Studies tool. Clinical examination findings that were investigated by at least two studies were included and results that met our predefined threshold of positive likelihood ratio ≥ 2 or negative likelihood ratio ≤ 0.5 were considered for the CDR. RESULTS: Sixty-four studies satisfied our eligible criteria. We were able to construct promising CDRs for symptomatic intervertebral disc, sacroiliac joint, spondylolisthesis, disc herniation with nerve root involvement, and spinal stenosis. Single clinical test appear not to be as useful as clusters of tests that are more closely in line with clinical decision making. CONCLUSIONS: This is the first comprehensive systematic review of diagnostic accuracy studies that evaluate clinical examination findings for their ability to identify the most common patho-anatomical disorders in the lumbar spine. In some diagnostic categories we have sufficient evidence to recommend a CDR. In others, we have only preliminary evidence that needs testing in future studies. Most findings were tested in secondary or tertiary care. Thus, the accuracy of the findings in a primary care setting has yet to be confirmed.

Level of evidence of free papers presented at the European Society of Sports Traumatology, Knee Surgery and Arthroscopy congress from 2008 to 2016.

PURPOSE: The European Society of Sports Traumatology, Knee Surgery and Arthroscopy (ESSKA) congress is an important venue, and the research presented can be a critical source of information used to impact clinical decisions and health policies. The purpose of this study was to evaluate the level of evidence of clinical free papers presented at the ESSKA congress from 2008 to 2016. Moreover, this study evaluated whether there were any changes in the distribution of level of evidence over time. METHODS: Two reviewers screened the free papers presented at the ESSKA biannual congresses 2008-2016 for clinical evidence. Clinical papers included observational studies and trials involving direct interaction between an investigator and human subjects. Biomechanical studies, technique demonstrations, cadaveric studies, and panel discussions were excluded. The reviewers independently graded their level of evidence from level I (e.g. high-quality randomized trials) to level IV (e.g. case series and reports) using the classification system published by the American Academy of Orthopaedic Surgeons. RESULTS: Of 1036 free papers that were identified, 729 met the inclusion criteria and were evaluated. Overall, 18% of studies were level I, 24% level II, 25% level III, and 33% level IV evidence. There was a significant improvement in level of evidence over time (p < 0.0001), with the proportion of level I studies increasing most dramatically (9% in 2008, 20% in 2012, 24% in 2016). Free papers studying the knee had higher levels of evidence than those evaluating other joints (p = 0.002). CONCLUSION: The level of evidence of clinical free papers presented at the ESSKA congress between 2008 and 2016 is high relative to other orthopaedic meetings. Moreover, there has been a significant improvement in the level of evidence over time. LEVEL OF EVIDENCE: Systematic review, Level IV.

Semi-rigid ureteroscopic lithotripsy versus laparoscopic ureterolithotomy for large upper ureteral stones: a meta - analysis of randomized controlled trials.

INTRODUCTION: To provide a systematic review and meta-analysis of randomized controlled trials (RCT) comparing semi-rigid ureteroscopic lithotripsy (URS) with laparoscopic ureterolithotomy (LU) for the treatment of the large proximal ureteral stone. MATERIALS AND METHODS: A systematic literature review was performed in June 2015 using the PubMed, Scopus, and Web of Science databases to identify relevant studies. Article selection proceeded according to the search strategy based on Preferred Reporting Items for Systematic Reviews and Meta-analysis criteria. RESULTS: Six RCT including 646 patients were analyzed, 325 URS cases (50.3%) and 321 LU cases (49.7%). URS provided a significantly shorter operative time (weighted mean difference [WMD] = -31.26 min; 95%CI -46.88 to -15.64; <0.0001) and length of hospital stay (WMD = -1.48 days; 95%CI -2.78 to -0.18; p=0.03) than LU. There were no significant differences in terms of overall complications (OR = 0.78; 95%CI 0.21-2.92; p=0.71) and major complications - Clavien ≥3 - (OR = 1.79; 95%CI 0.59-5.42; p=0.30). LU led to a significantly higher initial stone-free rate (OR = 8.65; 95%CI 4.18-17.91; p<0.00001) and final stone-free rate (OR = 6.41; 95%CI 2.24-18.32; p=0.0005) than URS. There was a significantly higher need for auxiliary procedures in URS cases (OR = 6.58; 95%CI 3.42-12.68; p<0.00001). CONCLUSIONS: Outcomes with LU for larger proximal ureteral calculi are favorable compared to semi-rigid URS and should be considered as a first-line alternative if flexible ureteroscopy is not available. Utilization of flexible ureteroscopy in conjunction with semi-rigid ureteroscopy may impact these outcomes, and deserves further systematic evaluation.

Semi-rigid ureteroscopic lithotripsy versus laparoscopic ureterolithotomy for large upper ureteral stones: a meta - analysis of randomized controlled trials

ABSTRACT Introduction: To provide a systematic review and meta-analysis of randomized controlled trials (RCT) comparing semi-rigid ureteroscopic lithotripsy (URS) with laparoscopic ureterolithotomy (LU) for the treatment of the large proximal ureteral stone. Materials and methods: A systematic literature review was performed in June 2015 using the PubMed, Scopus, and Web of Science databases to identify relevant studies. Article selection proceeded according to the search strategy based on Preferred Reporting Items for Systematic Reviews and Meta-analysis criteria. Results: Six RCT including 646 patients were analyzed, 325 URS cases (50.3%) and 321 LU cases (49.7%). URS provided a significantly shorter operative time (weighted mean difference [WMD] = −31.26 min; 95%CI −46.88 to −15.64; p<0.0001) and length of hospital stay (WMD = −1.48 days; 95%CI −2.78 to −0.18; p=0.03) than LU. There were no significant differences in terms of overall complications (OR = 0.78; 95%CI 0.21-2.92; p=0.71) and major complications – Clavien ≥3 – (OR = 1.79; 95%CI 0.59-5.42; p=0.30). LU led to a significantly higher initial stone-free rate (OR = 8.65; 95%CI 4.18-17.91; p<0.00001) and final stone-free rate (OR = 6.41; 95%CI 2.24-18.32; p=0.0005) than URS. There was a significantly higher need for auxiliary procedures in URS cases (OR = 6.58; 95%CI 3.42-12.68; p<0.00001). Conclusions: Outcomes with LU for larger proximal ureteral calculi are favorable compared to semi-rigid URS and should be considered as a first-line alternative if flexible ureteroscopy is not available. Utilization of flexible ureteroscopy in conjunction with semi-rigid ureteroscopy may impact these outcomes, and deserves further systematic evaluation.