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.

Interventions to Improve Statin Tolerance and Adherence in Patients at Risk for Cardiovascular Disease : A Systematic Review for the 2020 U.S. Department of Veterans Affairs and U.S. Department of Defense Guidelines for Management of Dyslipidemia.

BACKGROUND: Strategies to improve patients' tolerance of and adherence to statins may enhance the effectiveness of dyslipidemia treatment in those at risk for cardiovascular disease (CVD). PURPOSE: To assess the benefits and harms of interventions to improve statin adherence in patients at risk for CVD. DATA SOURCES: MEDLINE, EMBASE, PubMed, and the Cochrane Library from December 2013 through May 2019 (English language only). STUDY SELECTION: Systematic reviews (SRs), randomized controlled trials (RCTs), and cohort studies that addressed interventions for improving statin tolerance and adherence. DATA EXTRACTION: One investigator abstracted data and assessed study quality, and a second investigator checked abstractions and assessments for accuracy. DATA SYNTHESIS: One SR, 1 RCT, and 4 cohort studies were included. The SR found that intensified patient care improved adherence and decreased levels of total serum cholesterol and low-density lipoprotein cholesterol (LDL-C) at 6 months or more of follow-up. Compared with statin treatment discontinuation, nondaily statin dosing lowered total cholesterol and LDL-C levels. One large cohort study suggested that more than 90% of patients who discontinued statin treatment could be rechallenged with the same or a different statin and be adherent 1 year after a statin-related adverse event led to discontinuation. Two small cohort studies reported that more than 90% of patients who were previously intolerant to statins and who had low baseline levels of vitamin D were able to adhere to statins 1 year after vitamin D supplementation. LIMITATION: This is a qualitative synthesis of new evidence with existing meta-analyses, and studies had several methodological shortcomings. CONCLUSION: Although the strength of evidence for most interventions was low or very low, intensified patient care and rechallenge with the same or a different statin (or a lower dose) seem to be favorable options for improving statin adherence. PRIMARY FUNDING SOURCE: U.S. Department of Veterans Affairs.

Urotrauma: AUA guideline.

PURPOSE: The authors of this guideline reviewed the urologic trauma literature to guide clinicians in the appropriate methods of evaluation and management of genitourinary injuries. MATERIALS AND METHODS: A systematic review of the literature using the MEDLINE® and EMBASE databases (search dates 1/1/90-9/19/12) was conducted to identify peer-reviewed publications relevant to urotrauma. The review yielded an evidence base of 372 studies after application of inclusion/exclusion criteria. These publications were used to inform the statements presented in the guideline as Standards, Recommendations or Options. When sufficient evidence existed, the body of evidence for a particular treatment was assigned a strength rating of A (high), B (moderate) or C (low). In the absence of sufficient evidence, additional information is provided as Clinical Principles and Expert Opinions. RESULTS: Guideline statements were created to inform clinicians on the initial observation, evaluation and subsequent management of renal, ureteral, bladder, urethral and genital traumatic injuries. CONCLUSIONS: Genitourinary organ salvage has become increasingly possible as a result of advances in imaging, minimally invasive techniques, and reconstructive surgery. As the field of genitourinary reconstruction continues to evolve, clinicians must strive to approach clinical problems in a creative, multidisciplinary, evidence-based manner to ensure optimal outcomes.

In-facility delirium prevention programs as a patient safety strategy: a systematic review.

Delirium, an acute decline in attention and cognition, occurs among hospitalized patients at rates estimated to range from 14% to 56% and increases the risk for morbidity and mortality. The purpose of this systematic review was to evaluate the effectiveness and safety of in-facility multicomponent delirium prevention programs. A search of 6 databases (including MEDLINE, EMBASE, and CINAHL) was conducted through September 2012. Randomized, controlled trials; controlled clinical trials; interrupted time series; and controlled before-after studies with a prospective postintervention portion were eligible for inclusion. The evidence from 19 studies that met the inclusion criteria suggests that most multicomponent interventions are effective in preventing onset of delirium in at-risk patients in a hospital setting. Evidence was insufficient to determine the benefit of such programs in other care settings. Future comparative effectiveness studies with standardized protocols are needed to identify which components in multicomponent interventions are most effective for delirium prevention.

A framework for best evidence approaches can improve the transparency of systematic reviews.

OBJECTIVE: Systematic reviewers often use a "best evidence" approach to address the key questions, but what is meant by "best" is often unclear. The goal of this project was to create a decision framework for "best evidence" approaches to increase transparency in systematic reviews. STUDY DESIGN AND SETTING: The project was separated into three areas: 1) inclusion criteria, 2) evidence prioritization strategies, and 3) evaluative approaches. This commentary focuses only on the second task. The full report is available on the Effective Healthcare Web site of the Agency for Healthcare Research and Quality. RESULTS: The four identified strategies were as follows: 1) Use only the single best study; 2) Use the best set of studies; 3) Same as 2, but also consider whether the evidence permits a conclusion; and 4) Same as 3, but also consider the overall strength of the evidence. Simpler strategies (such as #1) are less likely to produce false conclusions, but are also more likely to yield insufficient evidence (possibly because of imprecise data). CONCLUSION: Systematic reviewers routinely prioritize evidence in numerous ways. This document provides a conceptual construct to enhance the transparency of systematic reviewers' decisions.

Autologous hematopoietic cell transplantation for multiple sclerosis: a systematic review.

BACKGROUND AND OBJECTIVES: The purpose of this systematic review was to evaluate the safety and efficacy of autologous hematopoietic cell transplantation in patients with progressive multiple sclerosis (MS) refractory to conventional medical treatment. METHODS: Eight case series met our a priori inclusion criteria for the primary outcome of progression-free survival. Individual study quality was rated using an 11-item scale for case series. The strength of the overall body of evidence for each outcome was rated using a system developed by the ECRI Institute. Data from different studies were statistically combined using meta-analysis. An additional six studies were included for a summary of mortality and morbidity. RESULTS: For secondary progressive MS, immunoablative therapy with autologous bone marrow/peripheral blood stem cell transplantation was associated with higher progression-free survival (up to 3 years following treatment) when using intermediate-intensity conditioning regimens compared with high-intensity conditioning regimens. The evidence was insufficient to determine whether the treatment was effective in patients with other types of MS. Treatment-related mortality was about 2.7%. CONCLUSIONS: Patients with secondary progressive MS refractory to conventional medical treatment have longer progression-free survival following autologous stem cell transplantation with intermediate-intensity conditioning regimens than with high-intensity conditioning regimens.

AHRQ series paper 5: grading the strength of a body of evidence when comparing medical interventions--agency for healthcare research and quality and the effective health-care program.

OBJECTIVE: To establish guidance on grading strength of evidence for the Evidence-based Practice Center (EPC) program of the U.S. Agency for Healthcare Research and Quality. STUDY DESIGN AND SETTING: Authors reviewed authoritative systems for grading strength of evidence, identified domains and methods that should be considered when grading bodies of evidence in systematic reviews, considered public comments on an earlier draft, and discussed the approach with representatives of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) working group. RESULTS: The EPC approach is conceptually similar to the GRADE system of evidence rating; it requires assessment of four domains: risk of bias, consistency, directness, and precision. Additional domains to be used when appropriate include dose-response association, presence of confounders that would diminish an observed effect, strength of association, and publication bias. Strength of evidence receives a single grade: high, moderate, low, or insufficient. We give definitions, examples, mechanisms for scoring domains, and an approach for assigning strength of evidence. CONCLUSION: EPCs should grade strength of evidence separately for each major outcome and, for comparative effectiveness reviews, all major comparisons. We will collaborate with the GRADE group to address ongoing challenges in assessing the strength of evidence.

A system for rating the stability and strength of medical evidence.

BACKGROUND: Methods for describing one's confidence in the available evidence are useful for end-users of evidence reviews. Analysts inevitably make judgments about the quality, quantity consistency, robustness, and magnitude of effects observed in the studies identified. The subjectivity of these judgments in several areas underscores the need for transparency in judgments. DISCUSSION: This paper introduces a new system for rating medical evidence. The system requires explicit judgments and provides explicit rules for balancing these judgments. Unlike other systems for rating the strength of evidence, our system draws a distinction between two types of conclusions: quantitative and qualitative. A quantitative conclusion addresses the question, "How well does it work?", whereas a qualitative conclusion addresses the question, "Does it work?" In our system, quantitative conclusions are tied to stability ratings, and qualitative conclusions are tied to strength ratings. Our system emphasizes extensive a priori criteria for judgments to reduce the potential for bias. Further, the system makes explicit the impact of heterogeneity testing, meta-analysis, and sensitivity analyses on evidence ratings. This article provides details of our system, including graphical depictions of how the numerous judgments that an analyst makes can be combined. We also describe two worked examples of how the system can be applied to both interventional and diagnostic technologies. SUMMARY: Although explicit judgments and formal combination rules are two important steps on the path to a comprehensive system for rating medical evidence, many additional steps must also be taken. Foremost among these are the distinction between quantitative and qualitative conclusions, an extensive set of a priori criteria for making judgments, and the direct impact of analytic results on evidence ratings. These attributes form the basis for a logically consistent system that can improve the usefulness of evidence reviews.

Meta-analysis of clinical outcomes of maze-related surgical procedures for medically refractory atrial fibrillation.

OBJECTIVE: Although maze-related surgical procedures have shown success at eliminating atrial fibrillation, published controlled studies have generally been too small to detect clinically significant differences in morbidity and mortality. We pooled available studies to determine whether a simultaneous maze procedure reduces the risk of stroke or death in patients with chronic or paroxysmal atrial fibrillation who receive mitral valve surgery. Secondary outcomes included post-operative bleeding and need for pacemaker. METHODS: Our systematic review identified four randomized controlled trials and six retrospective comparative studies that met minimum quality criteria. We conducted meta-analyses of clinical outcomes using Cohen's h, a statistic appropriate for analysis of infrequent events. RESULTS: The findings suggest that maze may reduce stroke risk but also increase the need for pacemaker implantation, as well as increase the risk of post-operative bleeding unless radiofrequency ablation is used. However, the statistically significant findings for stroke, need for pacemaker, and post-operative bleeding were overturned by sensitivity analysis, indicating that the findings are not robust. CONCLUSION: The literature evaluating maze clinical outcomes suffers from several shortcomings, particularly small sample sizes and selection bias. However, weak evidence supports a reduction in stroke rates and an increase in need for pacemakers among patients receiving the maze procedure. Radiofrequency maze may avoid an excess risk of post-operative bleeding associated with maze incisions. Larger, well-designed RCTs are needed to confirm these findings and evaluate outcomes such as survival and quality of life.

Meta-analysis of short-term and mid-term outcomes following off-pump coronary artery bypass grafting.

BACKGROUND: Uncertainty continues to surround the relative benefits and harms of conventional coronary artery bypass grafting (CABG) and off-pump coronary artery bypass grafting (OPCABG). Possible reasons are that high-quality studies have not comprehensively examined relevant patient outcomes and have enrolled a limited range of patients. Some studies may have been too small to detect clinically important differences in patient outcomes. The present study addresses these issues using meta-analysis. METHODS: We comprehensively retrieved randomized and nonrandomized controlled studies according to predetermined criteria. We performed meta-analyses for each outcome and empirically determined whether potential biases that might result from differences in study design or patient characteristics actually biased a study's results. We also conducted sensitivity analyses and tested for publication bias. RESULTS: Rates of perioperative myocardial infarction, stroke, reoperation for bleeding, renal failure, and mortality were lower after OPCABG than after CABG. Reductions in length of hospital stay, atrial fibrillation, and wound infection were also associated with OPCABG, but statistically significant differences among study results for these outcomes could not be explained by available information. Midterm (3 to 25 months) angina recurrence did not appear to differ between treatments; a trend was noticed toward lower reintervention rates with CABG, and a trend toward lower overall mortality with OPCABG, at least when performed at experienced centers. These midterm outcome results require confirmation. CONCLUSIONS: Off-pump coronary artery bypass grafting appears to reduce length of hospital stay, operative morbidity, and operative mortality relative to on-pump CABG. More studies are required before firm conclusions can be drawn concerning the effect of OPCABG on midterm mortality, angina recurrence, and repeat intervention.

Meta-analysis of surgical treatments for temporomandibular articular disorders.

PURPOSE: Temporomandibular joint articular disorders may cause severe pain and dysfunction. We addressed the following questions. Can any surgical procedures effectively treat these disorders? If so, which procedures are most effective? MATERIALS AND METHODS: We performed meta-analyses of surgical trial results to determine whether certain surgical procedures are effective in specific patient groups. To compensate for the lack of parallel control groups in published studies and for the improvement that has been observed in untreated patients, we used historical data from nonsurgical trials to derive 3 estimates of historical control group improvement (0%, 37.5%, and 75%). To our knowledge, this is the first meta-analytic evaluation of surgical treatments for temporomandibular joint disorders. RESULTS: Among patients refractory to nonsurgical therapies, surgical arthrocentesis and arthroscopy were effective for patients with disc displacement without reduction at all assumed control group improvement rates. Disc repair/repositioning had a statistically significant effect at all but the highest improvement rate. In patients with disc displacement with reduction, arthroscopy and disc repair/repositioning had statistically significant effects at all but the highest assumed rate of control group improvement. There were no statistically significant differences between the effects of any treatments. CONCLUSIONS: Surgical treatments appear to provide some benefit to patients refractory to nonsurgical therapies. The most reliable evidence supports the effectiveness of arthrocentesis and arthroscopy for patients with disc displacement without reduction. Better designed trials are needed before one can accurately determine the magnitude of the benefits of surgery.