American Society of Hematology, ABHH, ACHO, Grupo CAHT, Grupo CLAHT, SAH, SBHH, SHU, SOCHIHEM, SOMETH, Sociedad Panamena de Hematología, Sociedad Peruana de Hematología, and SVH 2023 guidelines for diagnosis of venous thromboembolism and for its management in special populations in Latin America.

Implementation of international guidelines in Latin American settings requires additional considerations (ie, values and preferences, resources, accessibility, feasibility, and impact on health equity). The purpose of this guideline is to provide evidence-based recommendations about the diagnosis of venous thromboembolism (VTE) and its management in children and during pregnancy. We used the GRADE ADOLOPMENT method to adapt recommendations from 3 American Society of Hematology (ASH) VTE guidelines (diagnosis of VTE, VTE in pregnancy, and VTE in the pediatric population). ASH and 12 local hematology societies formed a guideline panel comprising medical professionals from 10 countries in Latin America. Panelists prioritized 10 questions about the diagnosis of VTE and 18 questions about its management in special populations that were relevant for the Latin American context. A knowledge synthesis team updated evidence reviews of health effects conducted for the original ASH guidelines and summarized information about factors specific to the Latin American context. In comparison with the original guideline, there were significant changes in 2 of 10 diagnostic recommendations (changes in the diagnostic algorithms) and in 9 of 18 management recommendations (4 changed direction and 5 changed strength). This guideline ADOLOPMENT project highlighted the importance of contextualizing recommendations in other settings based on differences in values, resources, feasibility, and health equity impact.

The impact of climate change on health needs structured evidence assessment and an evidence to action framework to make decisions: a proposal to adopt the GRADE approach.

OBJECTIVES: To highlight how using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach to understand the certainty in the evidence about the impact of climate change in health outcomes increases transparency. Also, how GRADE can enhance communication and decisions about adaptation and mitigation strategies. STUDY DESIGN AND SETTING: We developed a narrative review based on an assessment of exiting systematic reviews addressing the effect of climate change on health outcomes and the impact of mitigation and adaptation strategies. RESULTS: Adopting structured approaches such as GRADE to tackle the impact of climate change on health may help to (1) define the specific question to be addressed; (2) summarize the evidence in a structured way and assess uncertainty; (3) provide a systematic framework to move from evidence to action and to offer recommendations of different strength; (4) provide a systematic way to adapt recommendations to specific settings; and (5) provide a framework to assess the certainty of modeled evidence. CONCLUSION: In this article, we describe epidemiologic principles that could be used to move decision-making in climate change forward.

American Society of Hematology living guidelines on the use of anticoagulation for thromboprophylaxis for patients with COVID-19: March 2022 update on the use of anticoagulation in critically ill patients.

BACKGROUND: COVID-19-related critical illness is associated with an increased risk of venous thromboembolism (VTE). OBJECTIVE: These evidence-based guidelines of the American Society of Hematology (ASH) are intended to support patients, clinicians, and other health care professionals in decisions about the use of anticoagulation for patients with COVID-19. METHODS: ASH formed a multidisciplinary guideline panel, including 3 patient representatives, and applied strategies to minimize potential bias from conflicts of interest. The McMaster University Grading of Recommendations Assessment, Development and Evaluation (GRADE) Centre supported the guideline development process, including performing systematic evidence reviews (up to January 2022). The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The panel used the GRADE approach to assess evidence and make recommendations, which were subject to public comment. This is an update to guidelines published in February 2021 and May 2021 as part of the living phase of these guidelines. RESULTS: The panel made 1 additional recommendation: a conditional recommendation for the use of prophylactic-intensity over therapeutic-intensity anticoagulation for patients with COVID-19-related critical illness who do not have suspected or confirmed VTE. The panel emphasized the need for an individualized assessment of thrombotic and bleeding risk. CONCLUSIONS: This conditional recommendation was based on very low certainty in the evidence, underscoring the need for additional, high-quality, randomized controlled trials comparing different intensities of anticoagulation for patients with COVID-19-related critical illness.

American Society of Hematology living guidelines on the use of anticoagulation for thromboprophylaxis in patients with COVID-19: January 2022 update on the use of therapeutic-intensity anticoagulation in acutely ill patients.

BACKGROUND: COVID-19-related acute illness is associated with an increased risk of venous thromboembolism (VTE). OBJECTIVE: These evidence-based guidelines from the American Society of Hematology (ASH) are intended to support patients, clinicians, and other health care professionals in making decisions about the use of anticoagulation in patients with COVID-19. METHODS: ASH formed a multidisciplinary guideline panel that included patient representatives and applied strategies to minimize potential bias from conflicts of interest. The McMaster University GRADE Centre supported the guideline development process and performed systematic evidence reviews (through November 2021). The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to assess evidence and make recommendations, which were subject to public comment. This is an update to guidelines published in February 2021 as part of the living phase of these guidelines. RESULTS: The panel made one additional recommendation. The panel issued a conditional recommendation in favor of therapeutic-intensity over prophylactic-intensity anticoagulation in patients with COVID-19-related acute illness who do not have suspected or confirmed VTE. The panel emphasized the need for an individualized assessment of risk of thrombosis and bleeding. The panel also noted that heparin (unfractionated or low molecular weight) may be preferred because of a preponderance of evidence with this class of anticoagulants. CONCLUSION: This conditional recommendation was based on very low certainty in the evidence, underscoring the need for additional, high-quality, randomized controlled trials comparing different intensities of anticoagulation in patients with COVID-19-related acute illness.

Using Explicit Thresholds were valuable for judging Benefits and Harms in partially contextualized GRADE Guidelines.

OBJECTIVES: Guideline panels must assess the magnitude of health benefits and harms to develop sensible recommendations. However, they rarely use explicit thresholds. In this paper we report on the piloting and the use thresholds for benefits and harms. STUDY DESIGN AND SETTING: We piloted the use of thresholds in a Chilean COVID-19 living guideline. For each of the critical outcomes, we asked panelists to suggest values of the thresholds for large, moderate, small, or trivial or no effect. We collected this information through a survey and an on-line discussion. RESULTS: Twelve panelists decided on thresholds for three critical outcomes (mortality, need for mechanical ventilation and serious adverse events). For all outcomes, an absolute risk reduction was considered larger with more than 50 events, moderate with less than 50 events, small with less than 25 events, and trivial with less than 10 events. Having these a priori thresholds in place significantly impacted on the development of recommendations. CONCLUSION: Explicit thresholds were a valuable addition to the judgment of the certainty in the evidence, to decide the direction and strength of the recommendation and to evaluate the need for update. We believe this is a line of research worth perusing.

Formulations of desensitizing toothpastes for dentin hypersensitivity: a scoping review.

OBJECTIVE: This study aimed to review evidence from randomized controlled trials (RCTs) to describe: 1) the active ingredients and desensitizing toothpaste brands; 2) the evaluation of these active ingredients over time, and 3) the fluoride and abrasive content in the formulations designed to treat dentin hypersensitivity (DH). METHODOLOGY: In total, 138 RCTs and their tested toothpastes were included. Searches were updated up to August 19, 2021. Formulations, reported brands, active ingredients over time, and type of fluoride (ionizable or ionic fluoride) and abrasive (calcium or silica-based) were analyzed (PROSPERO #CRD42018086815). RESULTS: Our trials assessed 368 toothpaste formulations, including 34 placebo (9%), 98 control toothpastes with fluoride (27%), and 236 (64%) with active ingredients to treat DH. We tested the following active ingredients: potassium compounds (n=68, 19%), calcium sodium phosphosilicate (CSP) (n=37, 10%), strontium compounds (n=28, 8%), arginine (n=29, 8%), stannous fluoride (SnF2) (n=21, 6%), hydroxyapatite (n=9, 2%), potassium combined with another active ingredient (n=19, 5%), inorganic salt compounds (n=11, 3%), citrate (n=5, 1%), formaldehyde (n=3, 1%), herbal (n=4, 1%), copolymer (n=1, 0.5%), and trichlorophosphate (TCP) (n=1, 0.5%). The number of toothpaste formulations increased since 1968, with the greatest increment after 2010. Most toothpastes described their type of fluoride as sodium monofluorphosphate (MFP) (n=105, 29%) and NaF (n=82, 22%), with silica-based (n=84, 23%) and calcium-based (n=64, 17%) abrasives. CONCLUSION: Patients and dentists enjoy an increasing number of brands and active ingredients to decide what desensitizing toothpaste to use. The most common types of fluoride are MFP and NaF.

American Society of Hematology, ABHH, ACHO, Grupo CAHT, Grupo CLAHT, SAH, SBHH, SHU, SOCHIHEM, SOMETH, Sociedad Panameña de Hematología, Sociedad Peruana de Hematología, and SVH 2022 guidelines for prevention of venous thromboembolism in surgical and medical patients and long-distance travelers in Latin America.

BACKGROUND: Venous thromboembolism (VTE) is a common disease in Latin American settings. Implementation of international guidelines in Latin American settings requires additional considerations. OBJECTIVE: To provide evidence-based guidelines about VTE prevention for Latin American patients, clinicians, and decision makers. METHODS: We used the GRADE ADOLOPMENT method to adapt recommendations from 2 American Society of Hematology (ASH) VTE guidelines (Prevention of VTE in Surgical Patients and Prophylaxis for Medical Patients). ASH and 12 local hematology societies formed a guideline panel composed of medical professionals from 10 countries in Latin America. Panelists prioritized 20 questions relevant to the Latin American context. A knowledge synthesis team updated evidence reviews of health effects conducted for the original ASH guidelines and summarized information about factors specific to the Latin American context, that is, values and preferences, resources, accessibility, feasibility, and impact on health equity. RESULTS: The panel agreed on 21 recommendations. In comparison with the original guideline, 6 recommendations changed direction and 4 recommendations changed strength. CONCLUSIONS: This guideline ADOLOPMENT project highlighted the importance of contextualization of recommendations in other settings, based on differences in values, resources, feasibility, and health equity impact.

Formulations of desensitizing toothpastes for dentin hypersensitivity: a scoping review

Abstract Objective: This study aimed to review evidence from randomized controlled trials (RCTs) to describe: 1) the active ingredients and desensitizing toothpaste brands; 2) the evaluation of these active ingredients over time, and 3) the fluoride and abrasive content in the formulations designed to treat dentin hypersensitivity (DH). Methodology: In total, 138 RCTs and their tested toothpastes were included. Searches were updated up to August 19, 2021. Formulations, reported brands, active ingredients over time, and type of fluoride (ionizable or ionic fluoride) and abrasive (calcium or silica-based) were analyzed (PROSPERO #CRD42018086815). Results: Our trials assessed 368 toothpaste formulations, including 34 placebo (9%), 98 control toothpastes with fluoride (27%), and 236 (64%) with active ingredients to treat DH. We tested the following active ingredients: potassium compounds (n=68, 19%), calcium sodium phosphosilicate (CSP) (n=37, 10%), strontium compounds (n=28, 8%), arginine (n=29, 8%), stannous fluoride (SnF2) (n=21, 6%), hydroxyapatite (n=9, 2%), potassium combined with another active ingredient (n=19, 5%), inorganic salt compounds (n=11, 3%), citrate (n=5, 1%), formaldehyde (n=3, 1%), herbal (n=4, 1%), copolymer (n=1, 0.5%), and trichlorophosphate (TCP) (n=1, 0.5%). The number of toothpaste formulations increased since 1968, with the greatest increment after 2010. Most toothpastes described their type of fluoride as sodium monofluorphosphate (MFP) (n=105, 29%) and NaF (n=82, 22%), with silica-based (n=84, 23%) and calcium-based (n=64, 17%) abrasives. Conclusion: Patients and dentists enjoy an increasing number of brands and active ingredients to decide what desensitizing toothpaste to use. The most common types of fluoride are MFP and NaF.

American Society of Hematology living guidelines on the use of anticoagulation for thromboprophylaxis in patients with COVID-19: May 2021 update on the use of intermediate-intensity anticoagulation in critically ill patients.

BACKGROUND: COVID-19-related critical illness is associated with an increased risk of venous thromboembolism (VTE). OBJECTIVE: These evidence-based guidelines of the American Society of Hematology (ASH) are intended to support patients, clinicians, and other health care professionals in making decisions about the use of anticoagulation for thromboprophylaxis in patients with COVID-19-related critical illness who do not have confirmed or suspected VTE. METHODS: ASH formed a multidisciplinary guideline panel that included 3 patient representatives and applied strategies to minimize potential bias from conflicts of interest. The McMaster University Grading of Recommendations Assessment, Development and Evaluation (GRADE) Centre supported the guideline development process by performing systematic evidence reviews (up to 5 March 2021). The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The panel used the GRADE approach to assess evidence and make recommendations, which were subject to public comment. This is an update on guidelines published in February 2021. RESULTS: The panel agreed on 1 additional recommendation. The panel issued a conditional recommendation in favor of prophylactic-intensity over intermediate-intensity anticoagulation in patients with COVID-19-related critical illness who do not have confirmed or suspected VTE. CONCLUSIONS: This recommendation was based on low certainty in the evidence, which underscores the need for additional high-quality, randomized, controlled trials comparing different intensities of anticoagulation in critically ill patients. Other key research priorities include better evidence regarding predictors of thrombosis and bleeding risk in critically ill patients with COVID-19 and the impact of nonanticoagulant therapies (eg, antiviral agents, corticosteroids) on thrombotic risk.

Global access to affordable direct oral anticoagulants.

Poor control of cardiovascular disease accounts for a substantial proportion of the disease burden in developing countries, but often essential anticoagulant medicines for preventing strokes and embolisms are not widely available. In 2019, direct oral anticoagulants were added to the World Health Organization's WHO Model list of essential medicines. The aims of this paper are to summarize the benefits of direct oral anticoagulants for patients with cardiovascular disease and to discuss ways of increasing their usage internationally. Although the cost of direct oral anticoagulants has provoked debate, the affordability of introducing these drugs into clinical practice could be increased by: price negotiation; pooled procurement; competitive tendering; the use of patent pools; and expanded use of generics. In 2017, only 14 of 137 countries that had adopted national essential medicines lists included a direct oral anticoagulant on their lists. This number could increase rapidly if problems with availability and affordability can be tackled. Once the types of patient likely to benefit from direct oral anticoagulants have been clearly defined in clinical practice guidelines, coverage can be more accurately determined and associated costs can be better managed. Government action is required to ensure that direct oral anticoagulants are covered by national budgets because the absence of reimbursement remains an impediment to achieving universal coverage. Tackling cardiovascular disease with the aid of direct oral anticoagulants is an essential component of efforts to achieve the World Health Organization's target of reducing premature deaths due to noncommunicable disease by 25% by 2025.

L'absence de lutte efficace contre les maladies cardiovasculaires contribue grandement à la charge de morbidité pesant sur les pays en développement. Pourtant, les anticoagulants essentiels permettant d'éviter les accidents vasculaires cérébraux et les embolies sont souvent difficiles à obtenir. En 2019, les anticoagulants oraux directs ont été ajoutés à la Liste modèle des médicaments essentiels publiée par l'Organisation mondiale de la Santé. Le présent document vise à résumer les avantages des anticoagulants oraux directs pour les patients souffrant d'une maladie cardiovasculaire, et à évoquer les moyens d'encourager leur utilisation au niveau international. Bien que le coût des anticoagulants oraux directs ait fait débat, intégrer ces médicaments dans la pratique clinique les rendrait plus abordables grâce à diverses méthodes: négociation des prix; achats groupés; appels d'offres concurrentiels; communautés de brevets; et recours accru aux alternatives génériques. En 2017, seulement 14 des 137 pays ayant adopté des listes nationales de médicaments essentiels y avaient inclus des anticoagulants oraux directs. Ce chiffre pourrait augmenter rapidement si les problèmes de disponibilité et d'accessibilité peuvent être résolus. Dès que les profils des patients susceptibles d'être traités par des anticoagulants oraux directs sont clairement établis dans les directives de pratique clinique, la couverture peut être définie avec plus de précision et les dépenses correspondantes, mieux gérées. Les gouvernements doivent s'assurer que ces médicaments sont bien pris en compte dans les budgets nationaux, car l'absence de remboursement demeure un obstacle à la couverture maladie universelle. La lutte contre les maladies cardiovasculaires à l'aide des anticoagulants oraux directs est un élément essentiel des efforts destinés à atteindre l'objectif de l'OMS: faire baisser de 25% d'ici 2025 les décès prématurés dus aux maladies non transmissibles de 25% d'ici 2025.

El mal control de las enfermedades cardiovasculares representa una proporción importante de la carga de enfermedades en los países en desarrollo, y a menudo los medicamentos anticoagulantes esenciales para prevenir los accidentes cerebrovasculares y las embolias no son fácilmente accesibles. En 2019, los anticoagulantes orales directos se añadieron a la lista modelo de medicamentos esenciales de la Organización Mundial de la Salud. Los objetivos del presente artículo son resumir los beneficios de los anticoagulantes orales directos para los pacientes con enfermedades cardiovasculares y discutir las formas de aumentar su uso a nivel internacional. Aunque el coste de los anticoagulantes orales directos ha suscitado debate, la asequibilidad de introducir estos medicamentos en la práctica clínica podría aumentarse al: negociar precios; hacer adquisiciones conjuntas; hacer licitaciones competitivas; utilizar consorcios de patentes; y ampliar el uso de genéricos. En 2017, solo 14 de los 137 países que habían adoptado listas nacionales de medicamentos esenciales incluían un anticoagulante oral directo en sus listas. Este número podría aumentar rápidamente si se pueden abordar los problemas de disponibilidad y asequibilidad. Cuando los tipos de pacientes que pueden beneficiarse de los anticoagulantes orales directos se hayan definido claramente en las directrices de la práctica clínica, la cobertura podrá determinarse con mayor precisión y los costes asociados podrán gestionarse mejor. Es necesario que los gobiernos actúen para garantizar que los anticoagulantes orales directos estén cubiertos por los presupuestos nacionales, ya que la ausencia de reembolso sigue siendo un impedimento para lograr la cobertura universal. La lucha contra las enfermedades cardiovasculares con la ayuda de los anticoagulantes orales directos es un componente esencial de los esfuerzos por alcanzar el objetivo de la OMS de reducir las muertes prematuras debidas a enfermedades no transmisibles en un 25 % para 2025.

Methodology for adaptation of the ASH Guidelines for Management of Venous Thromboembolism for the Latin American context.

BACKGROUND: From 2017 to 2020, the American Society of Hematology (ASH) collaborated with 12 hematology societies in Latin America to adapt the ASH guidelines on venous thromboembolism (VTE). OBJECTIVE: To describe the methods used to adapt the ASH guidelines on venous thromboembolism. METHODS: Each society nominated 1 individual to serve on the guideline panel. The work of the panel was facilitated by the 2 methodologists. The methods team selected 4 of the original VTE guidelines for a first round. To select the most relevant questions, a 2-step prioritization process was conducted through an on-line survey and then through in-person discussion. During an in-person meeting in Rio de Janeiro, Brazil, from 23 April through 26 April 2018, the panel developed recommendations using the ADOLOPMENT approach. Evidence about health effects from the original guidelines was reused, but important data about resource use, accessibility, feasibility, and impact in health equity were added. RESULTS: In the guideline accompanying this paper, Latin American panelists selected 17 questions from an original pool of 49. Of the 17 questions addressed, substantial changes were introduced for 5 recommendations, and remarks were added or modified for 12 recommendations. CONCLUSIONS: By using the evidence from an international guideline, a significant amount of work and time were saved; by adding regional evidence, the final recommendations were tailored to the Latin American context. This experience offers an alternative to develop guidelines relevant to local contexts through a global collaboration.

ASH, ABHH, ACHO, Grupo CAHT, Grupo  CLAHT, SAH, SBHH, SHU, SOCHIHEM, SOMETH, Sociedad Panameña de Hematología, SPH, and SVH 2021 guidelines for management of venous thromboembolism in Latin America.

BACKGROUND: Venous thromboembolism (VTE) is a common disease in Latin American settings. Implementing international guidelinn Aes in Latimerican settings requires additional considerations. OBJECTIVE: The purpose of our study was to provide evidence-based guidelines about managing VTE for Latin American patients, clinicians, and decision makers. METHODS: We used the Grading of Recommendations, Assessment, Development and Evaluation (GRADE)-ADOLOPMENT method to adapt recommendations from 2 American Society of Hematology (ASH) VTE guidelines (Treatment of VTE and Anticoagulation Therapy). ASH and local hematology societies formed a guideline panel comprised of medical professionals from 10 countries in Latin America. Panelists prioritized 18 questions relevant for the Latin American context. A knowledge synthesis team updated evidence reviews of health effects conducted for the original ASH guidelines and summarized information about factors specific to the Latin American context (ie, values and preferences, resources, accessibility, feasibility, and impact on health equity). RESULTS: The panel agreed on 17 recommendations. Compared with the original guideline, 4 recommendations changed direction and 1 changed strength. CONCLUSIONS: This guideline adolopment project highlighted the importance of contextualization of recommendations suggested by the changes to the original recommendations. The panel also identified 2 implementation priorities for the region: expanding the availability of home treatment and increasing the availability of direct oral anticoagulants (DOACs). The guideline panel made a conditional recommendation in favor of home treatment for individuals with deep venous thrombosis and a conditional recommendation for either home or hospital treatment for individuals with pulmonary embolism. In addition, a conditional recommendation was made in favor of DOACs over vitamin K antagonists for several populations.

American Society of Hematology 2021 guidelines on the use of anticoagulation for thromboprophylaxis in patients with COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19)-related critical illness and acute illness are associated with a risk of venous thromboembolism (VTE). OBJECTIVE: These evidence-based guidelines of the American Society of Hematology (ASH) are intended to support patients, clinicians, and other health care professionals in decisions about the use of anticoagulation for thromboprophylaxis for patients with COVID-19-related critical illness and acute illness who do not have confirmed or suspected VTE. METHODS: ASH formed a multidisciplinary guideline panel and applied strict management strategies to minimize potential bias from conflicts of interest. The panel included 3 patient representatives. The McMaster University GRADE Centre supported the guideline-development process, including performing systematic evidence reviews (up to 19 August 2020). The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, including GRADE Evidence-to-Decision frameworks, to assess evidence and make recommendations, which were subject to public comment. RESULTS: The panel agreed on 2 recommendations. The panel issued conditional recommendations in favor of prophylactic-intensity anticoagulation over intermediate-intensity or therapeutic-intensity anticoagulation for patients with COVID-19-related critical illness or acute illness who do not have confirmed or suspected VTE. CONCLUSIONS: These recommendations were based on very low certainty in the evidence, underscoring the need for high-quality, randomized controlled trials comparing different intensities of anticoagulation. They will be updated using a living recommendation approach as new evidence becomes available.

Clinical practice guidelines in Brazil - developing a national programme.

In Brazil, governmental and non-governmental organisations develop practice guidelines (PGs) in order to optimise patient care. Although important improvements have been made over the past years, many of these documents still lack transparency and methodological rigour. In order to conduct a critical analysis and define future steps in PG development in Brazil, we carried out a structured assessment of strengths, weaknesses, opportunities and threats (SWOT analysis) for the development of a national guideline programme. Participants consisted of academia, methodologists, medical societies and healthcare system representatives. In summary, the PG development process has improved in Brazil and current investments in methodological research and capacity-building are ongoing. Despite the centralised processes for public PGs, standardised procedures for their development are not well established and human resources are insufficient in number and capacity to develop the amount of trustworthy documents needed. Brazil's capacity could be strengthened and initial efforts have been made such as the adoption of standards proposed by world-renowned institutions in PG development and enhancement of the involvement of key stakeholders. Further steps involve the alignment between health technology assessment and PG processes for synergy and the development of a national network to promote the interaction between groups involved in the development of PGs. The lessons learned from this paper could be used to foster debate on guideline development, especially for countries facing similar threats on this topic.

A user guide to the American Society of Hematology clinical practice guidelines.

Since November 2018, Blood Advances has published American Society of Hematology (ASH) clinical practice guidelines on venous thromboembolism, immune thrombocytopenia, and sickle cell disease. More ASH guidelines on these and other topics are forthcoming. These guidelines have been developed using consistent processes, methods, terminology, and presentation formats. In this article, we describe how patients, clinicians, policymakers, researchers, and others may use ASH guidelines and the many related derivates by describing how to interpret information and how to apply it to clinical decision-making. Also, by exploring how these documents are developed, we aim to clarify their limitations and possible inappropriate usage.

DOACs vs LMWHs in hospitalized medical patients: a systematic review and meta-analysis that informed 2018 ASH guidelines.

Venous thromboembolism (VTE) is a relatively frequent complication in hospitalized patients, especially in those with risk factors. The benefit of using direct oral anticoagulants (DOACs) for prevention is controversial. This systematic review was performed as part of the American Society of Hematology (ASH) guidelines on VTE, developed in partnership with McMaster University. MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Epistemonikos were used as data sources from date of inception to November 2019. We included randomized trials in patients hospitalized for an acute medical disease, evaluating any DOACs vs other pharmacological prophylaxis, and included 3 trials with low risk of bias. We analyzed the effects of DOACs vs low-molecular-weight heparins (LMWHs) at 2 different time points: at the end of the short-term treatment phase (both drugs given for the same period of time) and at the end of the extended prophylaxis period (extended DOACs vs a shorter course of LMWHs). We observed that the use of DOACs did not reduce the risk of pulmonary embolism or symptomatic deep venous thrombosis (DVT) in comparison with LMWHs. However, the risk of major bleeding was slightly increased. Additionally, we observed that the benefit of DOACs previously reported was largely based on the reduction of asymptomatic DVT and was not apparent when only symptomatic events were considered. The use of DOACs in hospitalized medical patients slightly increases the risk of major bleeding with no appreciable benefit over LMWHs.

Thrombolytics for venous thromboembolic events: a systematic review with meta-analysis.

Thrombolytic therapy might reduce venous thromboembolism-related mortality and morbidity, but it could also increase the risk of major bleeding. We systematically reviewed the literature to evaluate the effectiveness and safety of thrombolytics in patients with pulmonary embolism (PE) and/or deep venous thrombosis (DVT). We searched Medline, Embase, and Cochrane databases for relevant randomized controlled trials up to February 2019. Multiple investigators independently screened and collected data. We included 45 studies (4740 participants). Pooled estimates of PE studies indicate probable reduction in mortality with thrombolysis (risk ratio [RR], 0.61; 95% confidence interval [CI], 0.40-0.94) (moderate certainty) and possible reduction in nonfatal PE recurrence (RR, 0.56; 95% CI, 0.35-0.89) (low certainty). Pooled estimates of DVT studies indicate the possible absence of effects on mortality (RR, 0.77; 95% CI, 0.26-2.28) (low certainty) and recurrent DVT (RR, 0.99; 95% CI, 0.56-1.76) (low certainty), but possible reduction in postthrombotic syndrome (PTS) with thrombolytics (RR, 0.70; 95% CI, 0.59-0.83) (low certainty). Pooled estimates of the complete body of evidence indicate increases in major bleeding (RR, 1.89; 95% CI, 1.46-2.46) (high certainty) and a probable increase in intracranial bleeding (RR, 3.17; 95% CI 1.19-8.41) (moderate certainty) with thrombolytics. Our findings indicate that thrombolytics probably reduce mortality in patients with submassive- or intermediate-risk PE and may reduce PTS in patients with proximal DVT at the expense of a significant increase in major bleeding. Because the balance between benefits and harms is profoundly influenced by the baseline risks of critical outcomes, stakeholders involved in decision making would need to weigh these effects to define which clinical scenarios merit the use of thrombolytics.

Development of the summary of findings table for network meta-analysis.

OBJECTIVES: The aim of the study was to develop a Grading of Recommendations, Assessment, Development and Evaluation (GRADE) summary of findings (SoF) table format that displays the critical information from a network meta-analysis (NMA). STUDY DESIGN AND SETTING: We applied a user experience model for data analysis based on four rounds of semistructured interviews. RESULTS: We interviewed 32 stakeholders who conduct or use MA. Four rounds of interviews produced six candidate NMA-SoF tables. Users found a final NMA-SoF table that included the following components highly acceptable: (1) details of the clinical question (PICO), (2) a plot depicting network geometry, (3) relative and absolute effect estimates, (4) certainty of evidence, (5) ranking of treatments, and (6) interpretation of findings. CONCLUSION: Using stakeholder feedback, we developed a new GRADE NMA-SoF table that includes the relevant components that facilitate understanding NMA findings and health decision-making.

A scoping review and survey provides the rationale, perceptions, and preferences for the integration of randomized and nonrandomized studies in evidence syntheses and GRADE assessments.

OBJECTIVES: To review the literature and obtain preferences and perceptions from experts regarding the role of randomized studies (RSs) and nonrandomized studies (NRSs) in systematic reviews of intervention effects. STUDY DESIGN AND SETTING: Scoping review and survey of experts. Using levels of certainty developed by the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group, experts expressed their preferences about the use of RS and NRS in health syntheses. RESULTS: Of 189 respondents, 123 had the expertise required to answer the questionnaire; 116 provided their extent of agreement with approaches to use NRS with RS. Most respondents would include NRS when RS was unfeasible (83.6%) or unethical (71.5%) and a majority to maximize the body of evidence (66.3%), compare results in NRS and RS (53.5%) and to identify subgroups (51.7%). Sizable minorities would include NRS and RS to address the effect of randomization (29.5%) or because the question being addressed was a public-health intervention (36.5%). In summary of findings tables, most respondents would include both bodies of evidence-in two rows in the same table-when RS provided moderate, low, or very-low certainty evidence; even when RS provided high certainty evidence, a sizable minority (25%) would still present results from both bodies of evidence. Very few (3.6%) would, under realistic circumstances, pool RS and NRS results. CONCLUSIONS: Most experts would include both RS and NRS in the same review under a wide variety of circumstances, but almost all would present results of two bodies of evidence separately.