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Objectives: Analytical frameworks are graphical representation of the key questions answered by a systematic review and can support the development of guideline recommendations. Our objectives were to a) conduct a systematic review to identify, describe and compare all analytical frameworks published as part of a systematic and guideline development process related to colorectal cancer (CRC), and b) to use this case study to develop guidance on how to conduct systematic reviews of analytical frameworks. Methods: We developed a search strategy to identify eligible studies in Medline and Embase from 1996 until December 2020. We also manually searched guideline databases and websites to identify all guidelines and systematic reviews in CRC that used an analytical framework. We assessed the quality of the guidelines using the Appraisal of Guidelines for Research and Evaluation II tool. The systematic review was registered in International Prospective Register of Systematic Reviews, registration CRD42020172117. Results: We screened 34,505 records and identified 1,166 guidelines and 3,127 systematic reviews on CRC of which five met our inclusion criteria. These five publications included four analytical frameworks in colorectal cancer (one update). We also describe our methodological approach to systematic reviews for analytical frameworks and underlying concepts for developing analytical framework using a bottom-up or top-down approach. Conclusion: Few guidelines and systematic reviews are utilizing analytical frameworks in the development of recommendations. Development of analytical frameworks should begin with a systematic search for existing analytical frameworks and follow a structured conceptual approach for their development to support guideline recommendations. Our methods may be helpful in achieving these objectives.

Objective Having up-to-date health policy recommendations accessible in one location is in high demand by guideline users. We developed an easy to navigate interactive approach to organize recommendations and applied it to tuberculosis (TB) guidelines of the World Health Organization (WHO). Study Design We used a mixed-methods study design to develop a framework for recommendation mapping with seven key methodological considerations. We define a recommendation map as an online repository of recommendations from several guidelines on a condition, providing links to the underlying evidence and expert judgments that inform them, allowing users to filter and cross-tabulate the search results. We engaged guideline developers, users, and health software engineers in an iterative process to elaborate the WHO eTB recommendation map. Results Applying the seven-step framework, we included 228 recommendations, linked to 103 guideline questions and organized the recommendation map according to key components of the health question, including the original recommendations and rationale (https://who.tuberculosis.recmap.org/). Conclusion The recommendation mapping framework provides the entire continuum of evidence mapping by framing recommendations within a guideline questions’ population, interventions, and comparators domains. Recommendation maps should allow guideline developers to organize their work meaningfully, standardize the automated publication of guidelines through links to the GRADEpro guideline development tool, and increase their accessibility and usability., Highlights • What this adds to what is known: This work transfers evidence mapping methods to guidelines in a process we call “recommendation mapping.” • What is the implication, what should change now: Recommendation mapping provides a digital curation of guidelines for a particular condition or disease. In this article we describe how we created an online map of WHO guidance on tuberculosis prevention and care to enhance accessibility of recommendation data and other key guideline components, facilitate their prompt update as needed, allow cross-tabulation of recommendations to help visualize any priority gaps and clustering and facilitate the adaptation of recommendations by users. • Recommendation maps are accessory to the notion of “living guidelines” that are promptly updated to reflect the state of the science, providing a digital solution to improve upon the organization, accessibility, and ultimately, uptake of guideline recommendations to benefit individual wellbeing or public health. It is directly linked to the GRADEpro guideline development tool., Graphical abstract Image, graphical abstract

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.

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.

There may be many predictors of venous thromboembolism (VTE) and bleeding in hospitalized medical patients, but until now, systematic reviews and assessments of the certainty of the evidence have not been published. We conducted a systematic review to identify prognostic factors for VTE and bleeding in hospitalized medical patients and searched Medline and EMBASE from inception through May 2018. We considered studies that identified potential prognostic factors for VTE and bleeding in hospitalized adult medical patients. Reviewers extracted data in duplicate and independently and assessed the certainty of the evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach. Of 69 410 citations, we included 17 studies in our analysis: 14 that reported on VTE, and 3 that reported on bleeding. For VTE, moderate-certainty evidence showed a probable association with older age; elevated C-reactive protein (CRP), D-dimer, and fibrinogen levels; tachycardia; thrombocytosis; leukocytosis; fever; leg edema; lower Barthel Index (BI) score; immobility; paresis; previous history of VTE; thrombophilia; malignancy; critical illness; and infections. For bleeding, moderate-certainty evidence showed a probable association with older age, sex, anemia, obesity, low hemoglobin, gastroduodenal ulcers, rehospitalization, critical illness, thrombocytopenia, blood dyscrasias, hepatic disease, renal failure, antithrombotic medication, and presence of a central venous catheter. Elevated CRP, a lower BI, a history of malignancy, and elevated heart rate are not included in most VTE risk assessment models. This study informs risk prediction in the management of hospitalized medical patients for VTE and bleeding; it also informs guidelines for VTE prevention and future research.

BackgroundCOVID-19–related acute illness is associated with an increased risk of venous thromboembolism (VTE).ObjectiveThese 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 in patients with COVID-19 who do not have confirmed or suspected VTE.MethodsASH formed a multidisciplinary guideline panel, including 3 patient representatives, and applied strategies to minimize potential bias from conflicts of interest. The McMaster University GRADE Centre supported the guideline development process, including performing systematic evidence reviews (up to March 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.ResultsThe panel agreed on 1 additional recommendation. The panel issued a conditional recommendation against the use of outpatient anticoagulant prophylaxis in patients with COVID-19 who are discharged from the hospital and who do not have suspected or confirmed VTE or another indication for anticoagulation.ConclusionsThis recommendation was based on very low certainty in the evidence, underscoring the need for high-quality randomized controlled trials assessing the role of postdischarge thromboprophylaxis. Other key research priorities include better evidence on assessing risk of thrombosis and bleeding outcomes in patients with COVID-19 after hospital discharge.

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.

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., Visual Abstract

Risk assessment models (RAMs) for venous thromboembolism (VTE) and bleeding in hospitalized medical patients inform appropriate use of thromboprophylaxis. Our aim was to use a novel approach for selecting risk factors for VTE and bleeding to be included in RAMs. First, we used the results of a systematic review of all candidate factors. Second, we used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to assess the certainty of the evidence for the identified factors. Third, we using a structured approach to select factors to develop the RAMs, by building on clinical and methodological expertise. The expert panel made judgments on whether to include, potentially include, or exclude risk factors, according to domains of the GRADE approach and the Delphi method. The VTE RAM included age >60 years, previous VTE, acute infections, immobility, acute paresis, active malignancy, critical illness, and known thrombophilia. The bleeding RAM included age ≥65 years, renal failure, thrombocytopenia, active gastroduodenal ulcers, hepatic disease, recent bleeding, and critical illness. We identified acute infection as a factor that was not considered in widely used RAMs. Also, we identified factors that require further research to confirm or refute their importance in a VTE RAM (eg, D-dimer). We excluded autoimmune disease which is included in the IMPROVE (International Medical Prevention Registry on Venous Thromboembolism) bleeding RAM. Our results also suggest that sex, malignancy, and use of central venous catheters (factors in the IMPROVE bleeding RAM) require further research. In conclusion, our study presents a novel approach to systematically identifying and assessing risk factors to be included or further explored during RAM development.

Multiple risk-assessment models (RAMs) for venous thromboembolism (VTE) in hospitalized medical patients have been developed. To inform the 2018 American Society of Hematology (ASH) guidelines on VTE, we conducted an overview of systematic reviews to identify and summarize evidence related to RAMs for VTE and bleeding in medical inpatients. We searched Epistemonikos, the Cochrane Database, Medline, and Embase from 2005 through June 2017 and then updated the search in January 2020 to identify systematic reviews that included RAMs for VTE and bleeding in medical inpatients. We conducted study selection, data abstraction and quality assessment (using the Risk of Bias in Systematic Reviews [ROBIS] tool) independently and in duplicate. We described the characteristics of the reviews and their included studies, and compared the identified RAMs using narrative synthesis. Of 15 348 citations, we included 2 systematic reviews, of which 1 had low risk of bias. The reviews included 19 unique studies reporting on 15 RAMs. Seven of the RAMs were derived using individual patient data in which risk factors were included based on their predictive ability in a regression analysis. The other 8 RAMs were empirically developed using consensus approaches, risk factors identified from a literature review, and clinical expertise. The RAMs that have been externally validated include the Caprini, Geneva, IMPROVE, Kucher, and Padua RAMs. The Padua, Geneva, and Kucher RAMs have been evaluated in impact studies that reported an increase in appropriate VTE prophylaxis rates. Our findings informed the ASH guidelines. They also aim to guide health care practitioners in their decision-making processes regarding appropriate individual prophylactic management.

Norovirus (NoV) is considered the second leading cause of viral acute gastroenteritis (AGE). To our knowledge, there are no systematic reviews assessing the role of NoV in AGE in the Middle East and North Africa (MENA) region. Consequently, we conducted an extensive systematic literature review on articles studying NoV in the 24 countries of the MENA region during the past 15 years (2000-2015). The methods and reporting were set according to the 2015 PRISMA-P and based on the elements from the international prospective register of systematic reviews (PROSPERO). We retrieved 38 studies meeting our predefined inclusion criteria and were used to extract full data. Studies reporting on NoV were conducted in 15 out of the 24 countries of the region. The reported NoV infection rates in MENA countries ranged between 0.82% and 36.84%. The majority of studies were clinical observational studies assessing NoV rates mainly among children. Participants were recruited from in- and outpatient clinics. NoV infection was reported all year round with with peaks observed mainly during cold months. GII.4 was the predominant genotype detected in stool of participants as reported by 16 out of 25 studies (64%). Overall, there is an increasing recognition of NoV as an important causative agent of AGE across all age groups in the MENA region. Further studies are needed to assess the national and the regional burden of NoV among different age groups, its molecular diversity and seasonal variability.

Background\ud Health care workers (HCWs) are essential for the delivery of health care services in conflict areas and in rebuilding health systems post-conflict.\ud Objective\ud The aim of this study was to systematically identify and map the published evidence on HCWs in conflict and post-conflict settings. Our ultimate aim is to inform researchers and funders on research gap on this subject and support relevant stakeholders by providing them with a comprehensive resource of evidence about HCWs in conflict and post-conflict settings on a global scale.\ud Methods\ud We conducted a systematic mapping of the literature. We included a wide range of study designs, addressing any type of personnel providing health services in either conflict or post-conflict settings. We conducted a descriptive analysis of the general characteristics of the included papers and built two interactive systematic maps organized by country, study design and theme.\ud Results\ud Out of 13,863 identified citations, we included a total of 474 studies: 304 on conflict settings, 149 on post-conflict settings, and 21 on both conflict and post-conflict settings. For conflict settings, the most studied counties were Iraq (15%), Syria (15%), Israel (10%), and the State of Palestine (9%). The most common types of publication were opinion pieces in conflict settings (39%), and primary studies (33%) in post-conflict settings. In addition, most of the first and corresponding authors were affiliated with countries different from the country focus of the paper. Violence against health workers was the most tackled theme of papers reporting on conflict settings, while workforce performance was the most addressed theme by papers reporting on post-conflict settings. The majority of papers in both conflict and post-conflict settings did not report funding sources (81% and 53%) or conflicts of interest of authors (73% and 62%), and around half of primary studies did not report on ethical approvals (45% and 41%).\ud Conclusions\ud This systematic mapping provides a comprehensive database of evidence about HCWs in conflict and post-conflict settings on a global scale that is often needed to inform policies and strategies on effective workforce planning and management and in reducing emigration. It can also be used to identify evidence for policy-relevant questions, knowledge gaps to direct future primary research, and knowledge clusters.

Introduction: Waterpipe tobacco smoking is harmful to health however its prevalence estimates remain uncertain. We aimed to systematically review the medical literature on waterpipe tobacco prevalence and trends. Methods: We searched Medline, Embase and ISI Web of Science for 'waterpipe' and its synonyms, without using language or date restrictions. We included any measure of waterpipe tobacco smoking prevalence in jurisdictionally representative populations. We stratified findings by prevalence measure (past 30 day, ever, regular or occasional, daily, other or unspecified) and age (adults or youth). Results: We included 129 studies reporting 355 estimates for 68 countries. In general, prevalence estimates among adults were highest in the Eastern Mediterranean, and among youth were about equal between Eastern Mediterranean and European regions. Past 30 day use was highest among Lebanese youth (37.2% in 2008), ever use was highest among Lebanese youth in 2002 and Lebanese university students in 2005 (both 65.3%), regular or occasional use was highest in among Iranian university students (16.3% in 2005), and daily use was highest among Egyptian youth (10.4% in 2005). Trend data were limited but most studies reported increased use over time, ranging from 0.3-1.0% per year among youth in the US to 2.9% per year among youth in Jordan (both for past 30 day use). Results were similar for ever use trends. Turkey (2.3% in 2008 to 0.8% in 2010) and Iraq (6.3% in 2008 and 4.8% in 2012) both witnessed decreased waterpipe use. Conclusion: Waterpipe tobacco smoking is most prevalent in Eastern Mediterranean and European countries, and appears higher among youth than adults. Continued surveillance will be important to assess and inform policy measures to control waterpipe tobacco use.

Rotavirus (RV) is the leading cause of severe acute gastroenteritis (AGE) worldwide. Consequently, we conducted a systematic literature review on articles studying RV in the 25 countries of the MENA region during the past 15 years (2000–2015). The methods and reporting were set according to the 2015 preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) and based on the elements from the international prospective register of systematic reviews (PROSPERO). Our literature search identified 169 studies meeting our predefined inclusion criteria. Studies reporting on RV were conducted in 19 out of the 24 countries of the MENA region. The largest number of studies was reported in Turkey (n = 32), Iran (n = 31), Saudi Arabia (n = 19) and Egypt (n = 17). The majority of studies reporting on RV gastroenteritis rates were clinical observational studies. In 115 studies out of 169, RV was reported among in-patients whereas 35 studies reported RV among outpatients. The predominantly reported RV genotype in the region was G1[P8] followed by G2[P4] and G9[P8]. The majority of studies (n = 108) were conducted among children less than 5 years of age whereas the remaining studies reported on AGE among other age groups and rarely adults. In MENA countries, RV infection was reported all year round with peaks described in cold as well as hot months. This systematic review provides a current update on the epidemiology of RV-associated gastroenteritis in countries of the MENA region and draws attention to the major gaps existing in the continuous monitoring of RV.