Use of induction therapy post-heart transplantation: Clinical practice recommendations based on systematic review and network meta-analysis of evidence.

BACKGROUND: The use of induction therapy (IT) agents in the early post-heart transplant period remains controversial. The following recommendations aim to provide guidance on the use of IT agents, including Basiliximab and Thymoglobulin, as part of routine care in heart transplantation (HTx). METHODS: We recruited an international, multidisciplinary panel of 15 stakeholders, including patient partners, transplant cardiologists and surgeons, nurse practitioners, pharmacists, and methodologists. We commissioned a systematic review on benefits and harms of IT on patient-important outcomes, and another on patients' values and preferences to inform our recommendations. We used the GRADE framework to summarize our findings, rate certainty in the evidence, and develop recommendations. The panel considered the balance between benefits and harms, certainty in the evidence, and patient's values and preferences, to make recommendations for or against the routine post-operative use of Thymoglobulin or Basiliximab. RESULTS: The panel made recommendations on three major clinical problems in HTx: (1) We suggest against the routine post-operative use of Basiliximab compared to no IT, (2) we suggest against the routine use of Thymoglobulin compared to no IT, and (3) for those patients for whom IT is deemed desirable, we suggest for the use of Thymoglobulin as compared to Basiliximab. CONCLUSION: This report highlights gaps in current knowledge and provides directions for clinical research in the future to better understand the clinical utility of IT agents in the early post heart transplant period, leading to improved management and care.

Case studies to explore the optimal use of randomized and nonrandomized studies in evidence syntheses that use GRADE.

OBJECTIVES: Randomized controlled trials (RCTs) are the preferred source of evidence for the relative effect of healthcare interventions summarized in knowledge syntheses. Nonrandomized studies of interventions (NRSI) may provide replacement, sequential, or complementary evidence to RCTs. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach can provide different options for properly using RCTs and NRSI integrated in health syntheses. In this article, we discuss different implications on the certainty of evidence when authors consider the use of NRSI and RCTs in systematic reviews using GRADE. Although this is a GRADE-related article, it is not an official GRADE guidance or concept article. STUDY DESIGN AND SETTING: We present case studies used during GRADE working group meetings for discussion of the effects of using NRSI and RCTs on GRADE domains and on the certainty of evidence. Several concepts were discussed through iterative feedback with experts in GRADE methods and Cochrane authors. We compared suggested solutions for possible scenarios that can be met in evidence syntheses informing decisions and future guidance. RESULTS: Different scenarios for the use of RCTs and NRSI in evidence syntheses are presented, focusing on how different GRADE ratings between RCTs and NRSI affect the overall assessment of the evidence and possible health recommendations. CONCLUSIONS: Considering differences and similarities grounded in the GRADE approach between NRSI and RCTs may help complement one another and maximize the value of knowledge syntheses and health recommendations.

The ecosystem of health decision making: from fragmentation to synergy.

Clinicians, patients, policy makers, funders, programme managers, regulators, and science communities invest considerable amounts of time and energy in influencing or making decisions at various levels, using systematic reviews, health technology assessments, guideline recommendations, coverage decisions, selection of essential medicines and diagnostics, quality assurance and improvement schemes, and policy and evidence briefs. The criteria and methods that these actors use in their work differ (eg, the role economic analysis has in decision making), but these methods frequently overlap and exist together. Under the aegis of WHO, we have brought together representatives of different areas to reconcile how the evidence that influences decisions is used across multiple health system decision levels. We describe the overlap and differences in decision-making criteria between different actors in the health sector to provide bridging opportunities through a unifying broad framework that we call theory of everything. Although decision-making activities respond to system needs, processes are often poorly coordinated, both globally and on a country level. A decision made in isolation from other decisions on the same topic could cause misleading, unnecessary, or conflicted inputs to the health system and, therefore, confusion and resource waste.

2021 American College of Rheumatology Guideline for the Treatment of Juvenile Idiopathic Arthritis: Recommendations for Nonpharmacologic Therapies, Medication Monitoring, Immunizations, and Imaging.

OBJECTIVE: To provide recommendations for the management of juvenile idiopathic arthritis (JIA) with a focus on nonpharmacologic therapies, medication monitoring, immunizations, and imaging, irrespective of JIA phenotype. METHODS: We developed clinically relevant Patient/Population, Intervention, Comparison, and Outcomes questions. After conducting a systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation approach was used to rate the quality of evidence (high, moderate, low, or very low). A Voting Panel including clinicians and patients/caregivers achieved consensus on the direction (for or against) and strength (strong or conditional) of recommendations. RESULTS: Recommendations in this guideline include the use of physical therapy and occupational therapy interventions; a healthy, well-balanced, age-appropriate diet; specific laboratory monitoring for medications; widespread use of immunizations; and shared decision-making with patients/caregivers. Disease management for all patients with JIA is addressed with respect to nonpharmacologic therapies, medication monitoring, immunizations, and imaging. Evidence for all recommendations was graded as low or very low in quality. For that reason, more than half of the recommendations are conditional. CONCLUSION: This clinical practice guideline complements the 2019 American College of Rheumatology JIA and uveitis guidelines, which addressed polyarthritis, sacroiliitis, enthesitis, and uveitis, and a concurrent 2021 guideline on oligoarthritis, temporomandibular arthritis, and systemic JIA. It serves as a tool to support clinicians, patients, and caregivers in decision-making. The recommendations take into consideration the severity of both articular and nonarticular manifestations as well as patient quality of life. Although evidence is generally low quality and many recommendations are conditional, the inclusion of caregivers and patients in the decision-making process strengthens the relevance and applicability of the guideline. It is important to remember that these are recommendations. Clinical decisions, as always, should be made by the treating clinician and patient/caregiver.

2021 American College of Rheumatology Guideline for the Treatment of Juvenile Idiopathic Arthritis: Therapeutic Approaches for Oligoarthritis, Temporomandibular Joint Arthritis, and Systemic Juvenile Idiopathic Arthritis.

OBJECTIVE: To provide updated guidelines for pharmacologic management of juvenile idiopathic arthritis (JIA), focusing on treatment of oligoarthritis, temporomandibular joint (TMJ) arthritis, and systemic JIA with and without macrophage activation syndrome. Recommendations regarding tapering and discontinuing treatment in inactive systemic JIA are also provided. METHODS: We developed clinically relevant Patient/Population, Intervention, Comparison, and Outcomes questions. After conducting a systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation approach was used to rate the quality of evidence (high, moderate, low, or very low). A Voting Panel including clinicians and patients/caregivers achieved consensus on the direction (for or against) and strength (strong or conditional) of recommendations. RESULTS: Similar to those published in 2019, these JIA recommendations are based on clinical phenotypes of JIA, rather than a specific classification schema. This guideline provides recommendations for initial and subsequent treatment of JIA with oligoarthritis, TMJ arthritis, and systemic JIA as well as for tapering and discontinuing treatment in subjects with inactive systemic JIA. Other aspects of disease management, including factors that influence treatment choice and medication tapering, are discussed. Evidence for all recommendations was graded as low or very low in quality. For that reason, more than half of the recommendations are conditional. CONCLUSION: This clinical practice guideline complements the 2019 American College of Rheumatology JIA and uveitis guidelines, which addressed polyarthritis, sacroiliitis, enthesitis, and uveitis. It serves as a tool to support clinicians, patients, and caregivers in decision-making. The recommendations take into consideration the severity of both articular and nonarticular manifestations as well as patient quality of life. Although evidence is generally low quality and many recommendations are conditional, the inclusion of caregivers and patients in the decision-making process strengthens the relevance and applicability of the guideline. It is important to remember that these are recommendations. Clinical decisions, as always, should be made by the treating clinician and patient/caregiver.

2021 American College of Rheumatology Guideline for the Treatment of Juvenile Idiopathic Arthritis: Recommendations for Nonpharmacologic Therapies, Medication Monitoring, Immunizations, and Imaging.

OBJECTIVE: To provide recommendations for the management of juvenile idiopathic arthritis (JIA) with a focus on nonpharmacologic therapies, medication monitoring, immunizations, and imaging, irrespective of JIA phenotype. METHODS: We developed clinically relevant Patient/Population, Intervention, Comparison, and Outcomes questions. After conducting a systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation approach was used to rate the quality of evidence (high, moderate, low, or very low). A Voting Panel including clinicians and patients/caregivers achieved consensus on the direction (for or against) and strength (strong or conditional) of recommendations. RESULTS: Recommendations in this guideline include the use of physical therapy and occupational therapy interventions; a healthy, well-balanced, age-appropriate diet; specific laboratory monitoring for medications; widespread use of immunizations; and shared decision-making with patients/caregivers. Disease management for all patients with JIA is addressed with respect to nonpharmacologic therapies, medication monitoring, immunizations, and imaging. Evidence for all recommendations was graded as low or very low in quality. For that reason, more than half of the recommendations are conditional. CONCLUSION: This clinical practice guideline complements the 2019 American College of Rheumatology JIA and uveitis guidelines, which addressed polyarthritis, sacroiliitis, enthesitis, and uveitis, and a concurrent 2021 guideline on oligoarthritis, temporomandibular arthritis, and systemic JIA. It serves as a tool to support clinicians, patients, and caregivers in decision-making. The recommendations take into consideration the severity of both articular and nonarticular manifestations as well as patient quality of life. Although evidence is generally low quality and many recommendations are conditional, the inclusion of caregivers and patients in the decision-making process strengthens the relevance and applicability of the guideline. It is important to remember that these are recommendations. Clinical decisions, as always, should be made by the treating clinician and patient/caregiver.

2021 American College of Rheumatology Guideline for the Treatment of Juvenile Idiopathic Arthritis: Therapeutic Approaches for Oligoarthritis, Temporomandibular Joint Arthritis, and Systemic Juvenile Idiopathic Arthritis.

OBJECTIVE: To provide updated guidelines for pharmacologic management of juvenile idiopathic arthritis (JIA), focusing on treatment of oligoarthritis, temporomandibular joint (TMJ) arthritis, and systemic JIA with and without macrophage activation syndrome. Recommendations regarding tapering and discontinuing treatment in inactive systemic JIA are also provided. METHODS: We developed clinically relevant Patient/Population, Intervention, Comparison, and Outcomes questions. After conducting a systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation approach was used to rate the quality of evidence (high, moderate, low, or very low). A Voting Panel including clinicians and patients/caregivers achieved consensus on the direction (for or against) and strength (strong or conditional) of recommendations. RESULTS: Similar to those published in 2019, these JIA recommendations are based on clinical phenotypes of JIA, rather than a specific classification schema. This guideline provides recommendations for initial and subsequent treatment of JIA with oligoarthritis, TMJ arthritis, and systemic JIA as well as for tapering and discontinuing treatment in subjects with inactive systemic JIA. Other aspects of disease management, including factors that influence treatment choice and medication tapering, are discussed. Evidence for all recommendations was graded as low or very low in quality. For that reason, more than half of the recommendations are conditional. CONCLUSION: This clinical practice guideline complements the 2019 American College of Rheumatology JIA and uveitis guidelines, which addressed polyarthritis, sacroiliitis, enthesitis, and uveitis. It serves as a tool to support clinicians, patients, and caregivers in decision-making. The recommendations take into consideration the severity of both articular and nonarticular manifestations as well as patient quality of life. Although evidence is generally low quality and many recommendations are conditional, the inclusion of caregivers and patients in the decision-making process strengthens the relevance and applicability of the guideline. It is important to remember that these are recommendations. Clinical decisions, as always, should be made by the treating clinician and patient/caregiver.

Patient values and preferences regarding VTE disease: a systematic review to inform American Society of Hematology guidelines.

Values and preferences relate to the importance that patients place on health outcomes (eg, bleeding, having a deep venous thrombosis) and are essential when weighing benefits and harms in guideline recommendations. To inform the American Society of Hematology guidelines for management of venous thromboembolism (VTE) disease, we conducted a systematic review of patients' values and preferences related to VTE. We searched Medline, Embase, Cochrane Central Register of Controlled Trials, PsycINFO, and the Cumulative Index to Nursing and Allied Health Literature from inception to April of 2018 (PROSPERO-CRD42018094003). We included quantitative and qualitative studies. We followed Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidance for rating the certainty and presenting findings for quantitative research about the relative importance of health outcomes and a grounded theory approach for qualitative thematic synthesis. We identified 14 quantitative studies (2465 participants) describing the relative importance of VTE-related health states in a widely diverse population of patients, showing overall small to important impact on patients' lives (certainty of the evidence from low to moderate). Additionally, evidence from 34 quantitative studies (6424 participants) and 15 qualitative studies (570 participants) revealed that patients put higher value on VTE risk reduction than on the potential harms of the treatment (certainty of evidence from low to moderate). Studies also suggested a clear preference for oral medication over subcutaneous medication (moderate certainty). The observed variability in health state values may be a result of differences in the approaches used to elicit them and the diversity of included populations rather than true variability in values. This finding highlights the necessity to explore the variability induced by different approaches to ascertain values.

2019 American College of Rheumatology/Arthritis Foundation Guideline for the Screening, Monitoring, and Treatment of Juvenile Idiopathic Arthritis-Associated Uveitis.

OBJECTIVE: To develop recommendations for the screening, monitoring, and treatment of uveitis in children with juvenile idiopathic arthritis (JIA). METHODS: Pediatric rheumatologists, ophthalmologists with expertise in uveitis, patient representatives, and methodologists generated key clinical questions to be addressed by this guideline. This was followed by a systematic literature review and rating of the available evidence according to the GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology. A group consensus process was used to compose the final recommendations and grade their strength as conditional or strong. RESULTS: Due to a lack of literature with good quality of evidence, recommendations were formulated on the basis of available evidence and a consensus expert opinion. Regular ophthalmic screening of children with JIA is recommended because of the risk of uveitis, and the frequency of screening should be based on individual risk factors. Regular ophthalmic monitoring of children with uveitis is recommended, and intervals should be based on ocular examination findings and treatment regimen. Ophthalmic monitoring recommendations were strong primarily because of concerns of vision-threatening complications of uveitis with infrequent monitoring. Topical glucocorticoids should be used as initial treatment to achieve control of inflammation. Methotrexate and the monoclonal antibody tumor necrosis factor inhibitors adalimumab and infliximab are recommended when systemic treatment is needed for the management of uveitis. The timely addition of nonbiologic and biologic drugs is recommended to maintain uveitis control in children who are at continued risk of vision loss. CONCLUSION: This guideline provides direction for clinicians and patients/parents making decisions on the screening, monitoring, and management of children with JIA and uveitis, using GRADE methodology and informed by a consensus process with input from rheumatology and ophthalmology experts, current literature, and patient/parent preferences and values.

2019 American College of Rheumatology/Arthritis Foundation Guideline for the Treatment of Juvenile Idiopathic Arthritis: Therapeutic Approaches for Non-Systemic Polyarthritis, Sacroiliitis, and Enthesitis.

OBJECTIVE: To develop treatment recommendations for children with juvenile idiopathic arthritis manifesting as non-systemic polyarthritis, sacroiliitis, or enthesitis. METHODS: The Patient/Population, Intervention, Comparison, and Outcomes (PICO) questions were developed and refined by members of the guideline development teams. A systematic review was conducted to compile evidence for the benefits and harms associated with treatments for these conditions. GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology was used to rate the quality of evidence. A group consensus process was conducted among the Voting Panel to generate the final recommendations and grade their strength. A Parent and Patient Panel used a similar consensus approach to provide patient/caregiver preferences for key questions. RESULTS: Thirty-nine recommendations were developed (8 strong and 31 conditional). The quality of supporting evidence was very low or low for 90% of the recommendations. Recommendations are provided for the use of nonsteroidal antiinflammatory drugs, disease-modifying antirheumatic drugs, biologics, and intraarticular and oral glucocorticoids. Recommendations for the use of physical and occupational therapy are also provided. Specific recommendations for polyarthritis address general medication use, initial and subsequent treatment, and adjunctive therapies. Good disease control, with therapeutic escalation to achieve low disease activity, was recommended. The sacroiliitis and enthesitis recommendations primarily address initial therapy and adjunctive therapies. CONCLUSION: This guideline provides direction for clinicians, caregivers, and patients making treatment decisions. Clinicians, caregivers, and patients should use a shared decision-making process that accounts for patients' values, preferences, and comorbidities. These recommendations should not be used to limit or deny access to therapies.

2019 American College of Rheumatology/Arthritis Foundation Guideline for the Treatment of Juvenile Idiopathic Arthritis: Therapeutic Approaches for Non-Systemic Polyarthritis, Sacroiliitis, and Enthesitis.

OBJECTIVE: To develop treatment recommendations for children with juvenile idiopathic arthritis manifesting as non-systemic polyarthritis, sacroiliitis, or enthesitis. METHODS: The Patient/Population, Intervention, Comparison, and Outcomes (PICO) questions were developed and refined by members of the guideline development teams. A systematic review was conducted to compile evidence for the benefits and harms associated with treatments for these conditions. GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology was used to rate the quality of evidence. A group consensus process was conducted among the Voting Panel to generate the final recommendations and grade their strength. A Parent and Patient Panel used a similar consensus approach to provide patient/caregiver preferences for key questions. RESULTS: Thirty-nine recommendations were developed (8 strong and 31 conditional). The quality of supporting evidence was very low or low for 90% of the recommendations. Recommendations are provided for the use of nonsteroidal antiinflammatory drugs, disease-modifying antirheumatic drugs, biologics, and intraarticular and oral glucocorticoids. Recommendations for the use of physical and occupational therapy are also provided. Specific recommendations for polyarthritis address general medication use, initial and subsequent treatment, and adjunctive therapies. Good disease control, with therapeutic escalation to achieve low disease activity, was recommended. The sacroiliitis and enthesitis recommendations primarily address initial therapy and adjunctive therapies. CONCLUSION: This guideline provides direction for clinicians, caregivers, and patients making treatment decisions. Clinicians, caregivers, and patients should use a shared decision-making process that accounts for patients' values, preferences, and comorbidities. These recommendations should not be used to limit or deny access to therapies.

2019 American College of Rheumatology/Arthritis Foundation Guideline for the Screening, Monitoring, and Treatment of Juvenile Idiopathic Arthritis-Associated Uveitis.

OBJECTIVE: To develop recommendations for the screening, monitoring, and treatment of uveitis in children with juvenile idiopathic arthritis (JIA). METHODS: Pediatric rheumatologists, ophthalmologists with expertise in uveitis, patient representatives, and methodologists generated key clinical questions to be addressed by this guideline. This was followed by a systematic literature review and rating of the available evidence according to the GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology. A group consensus process was used to compose the final recommendations and grade their strength as conditional or strong. RESULTS: Due to a lack of literature with good quality of evidence, recommendations were formulated on the basis of available evidence and a consensus expert opinion. Regular ophthalmic screening of children with JIA is recommended because of the risk of uveitis, and the frequency of screening should be based on individual risk factors. Regular ophthalmic monitoring of children with uveitis is recommended, and intervals should be based on ocular examination findings and treatment regimen. Ophthalmic monitoring recommendations were strong primarily because of concerns of vision-threatening complications of uveitis with infrequent monitoring. Topical glucocorticoids should be used as initial treatment to achieve control of inflammation. Methotrexate and the monoclonal antibody tumor necrosis factor inhibitors adalimumab and infliximab are recommended when systemic treatment is needed for the management of uveitis. The timely addition of nonbiologic and biologic drugs is recommended to maintain uveitis control in children who are at continued risk of vision loss. CONCLUSION: This guideline provides direction for clinicians and patients/parents making decisions on the screening, monitoring, and management of children with JIA and uveitis, using GRADE methodology and informed by a consensus process with input from rheumatology and ophthalmology experts, current literature, and patient/parent preferences and values.

American Society of Hematology 2018 Guidelines for management of venous thromboembolism: treatment of pediatric venous thromboembolism.

BACKGROUND: Despite an increasing incidence of venous thromboembolism (VTE) in pediatric patients in tertiary care settings, relatively few pediatric physicians have experience with antithrombotic interventions. OBJECTIVE: These guidelines of the American Society of Hematology (ASH), based on the best available evidence, are intended to support patients, clinicians, and other health care professionals in their decisions about management of pediatric VTE. METHODS: ASH formed a multidisciplinary guideline panel that included 2 patient representatives and was balanced to minimize potential bias from conflicts of interest. The McMaster University GRADE Centre supported the guideline-development process, including updating or performing systematic evidence reviews (up to April of 2017). 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 30 recommendations, covering symptomatic and asymptomatic deep vein thrombosis, with specific focus on management of central venous access device-associated VTE. The panel also addressed renal and portal vein thrombosis, cerebral sino venous thrombosis, and homozygous protein C deficiency. CONCLUSIONS: Although the panel offered many recommendations, additional research is required. Priorities include understanding the natural history of asymptomatic thrombosis, determining subgroup boundaries that enable risk stratification of children for escalation of treatment, and appropriate study of newer anticoagulant agents in children.

2019 American College of Rheumatology/Arthritis Foundation Guideline for the Screening, Monitoring, and Treatment of Juvenile Idiopathic Arthritis­Associated Uveitis

To develop recommendations for the screening, monitoring, and treatment of uveitis in children with juvenile idiopathic arthritis (JIA).Methods. Pediatric rheumatologists, ophthalmologists with expertise in uveitis, patient representatives, and methodologists generated key clinical questions to be addressed by this guideline. This was followed by a system-atic literature review and rating of the available evidence according to the GRADE (Grading of Recommendations Assessment, Development and Evaluation). A group consensus process was used to compose the nal recommendations and grade their strength as conditional or strong. Due to a lack of literature with good quality of evidence, recommendations were formulated on the basis of available evidence and a consensus expert opinion. Regular ophthalmic screening of children with JIA is recom-mended because of the risk of uveitis, and the frequency of screening should be based on individual risk factors.

2019 American College of Rheumatology/Arthritis Foundation Guideline for the Treatment of Juvenile Idiopathic Arthritis: Therapeutic Approaches for Non- Systemic Polyarthritis, Sacroiliitis, and Enthesitis

To develop treatment recommendations for children with juvenile idiopathic arthritis manifesting as non- systemic polyarthritis, sacroiliitis, or enthesitis.Methods. The Patient/Population, Intervention, Comparison, and Outcomes (PICO) questions were developed and recined by members of the guideline development teams. A systematic review was conducted to compile evidence for the benefits and harms associated with treatments for these conditions. GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology was used to rate the quality of evidence. A group consensus process was conducted among the Voting Panel to generate the nal recommendations and grade their strength. A Parent and Patient Panel used a similar consensus approach to provide patient/caregiver preferences for key questions. Thirty- nine recommendations were developed (8 strong and 31 conditional). The quality of supporting evidence was very low or low for 90% of the recommendations. Recommendations are provided for the use of nonsteroidal antiinflammatory drugs, disease- modifying antirheumatic drugs, biologics, and intraarticular and oral glucocorticoids. Recommendations for the use of physical and occupational therapy are also provided. Specific recommendations for polyarthritis address general medication use, initial and subsequent treatment, and adjunctive therapies. Good disease control, with therapeutic escalation to achieve low disease activity, was recommended. The sacroiliitis and enthesitis recommendations primarily address initial therapy and adjunctive therapies. This guideline provides direction for clinicians, caregivers, and patients making treatment decisions. Clinicians, caregivers, and patients should use a shared decision- making process that accounts for patients' values, preferences, and comorbidities. These recommendations should not be used to limit or deny access to therapies.