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 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.

Special Article: 2018 American College of Rheumatology/National Psoriasis Foundation Guideline for the Treatment of Psoriatic Arthritis.

OBJECTIVE: To develop an evidence-based guideline for the pharmacologic and nonpharmacologic treatment of psoriatic arthritis (PsA), as a collaboration between the American College of Rheumatology (ACR) and the National Psoriasis Foundation (NPF). METHODS: We identified critical outcomes in PsA and clinically relevant PICO (population/intervention/comparator/outcomes) questions. A Literature Review Team performed a systematic literature review to summarize evidence supporting the benefits and harms of available pharmacologic and nonpharmacologic therapies for PsA. GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology was used to rate the quality of the evidence. A voting panel, including rheumatologists, dermatologists, other health professionals, and patients, achieved consensus on the direction and the strength of the recommendations. RESULTS: The guideline covers the management of active PsA in patients who are treatment-naive and those who continue to have active PsA despite treatment, and addresses the use of oral small molecules, tumor necrosis factor inhibitors, interleukin-12/23 inhibitors (IL-12/23i), IL-17 inhibitors, CTLA4-Ig (abatacept), and a JAK inhibitor (tofacitinib). We also developed recommendations for psoriatic spondylitis, predominant enthesitis, and treatment in the presence of concomitant inflammatory bowel disease, diabetes, or serious infections. We formulated recommendations for a treat-to-target strategy, vaccinations, and nonpharmacologic therapies. Six percent of the recommendations were strong and 94% conditional, indicating the importance of active discussion between the health care provider and the patient to choose the optimal treatment. CONCLUSION: The 2018 ACR/NPF PsA guideline serves as a tool for health care providers and patients in the selection of appropriate therapy in common clinical scenarios. Best treatment decisions consider each individual patient situation. The guideline is not meant to be proscriptive and should not be used to limit treatment options for patients with PsA.

Special Article: 2018 American College of Rheumatology/National Psoriasis Foundation Guideline for the Treatment of Psoriatic Arthritis.

OBJECTIVE: To develop an evidence-based guideline for the pharmacologic and nonpharmacologic treatment of psoriatic arthritis (PsA), as a collaboration between the American College of Rheumatology (ACR) and the National Psoriasis Foundation (NPF). METHODS: We identified critical outcomes in PsA and clinically relevant PICO (population/intervention/comparator/outcomes) questions. A Literature Review Team performed a systematic literature review to summarize evidence supporting the benefits and harms of available pharmacologic and nonpharmacologic therapies for PsA. GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology was used to rate the quality of the evidence. A voting panel, including rheumatologists, dermatologists, other health professionals, and patients, achieved consensus on the direction and the strength of the recommendations. RESULTS: The guideline covers the management of active PsA in patients who are treatment-naive and those who continue to have active PsA despite treatment, and addresses the use of oral small molecules, tumor necrosis factor inhibitors, interleukin-12/23 inhibitors (IL-12/23i), IL-17 inhibitors, CTLA4-Ig (abatacept), and a JAK inhibitor (tofacitinib). We also developed recommendations for psoriatic spondylitis, predominant enthesitis, and treatment in the presence of concomitant inflammatory bowel disease, diabetes, or serious infections. We formulated recommendations for a treat-to-target strategy, vaccinations, and nonpharmacologic therapies. Six percent of the recommendations were strong and 94% conditional, indicating the importance of active discussion between the health care provider and the patient to choose the optimal treatment. CONCLUSION: The 2018 ACR/NPF PsA guideline serves as a tool for health care providers and patients in the selection of appropriate therapy in common clinical scenarios. Best treatment decisions consider each individual patient situation. The guideline is not meant to be proscriptive and should not be used to limit treatment options for patients with PsA.

Male Urethral Stricture: American Urological Association Guideline.

PURPOSE: The purpose of this Guideline is to provide a clinical framework for the diagnosis and treatment of male urethral stricture. MATERIALS AND METHODS: A systematic review of the literature using the Pubmed, Embase, and Cochrane databases (search dates 1/1/1990 to 12/1/2015) was conducted to identify peer-reviewed publications relevant to the diagnosis and treatment of urethral stricture. The review yielded an evidence base of 250 articles after application of inclusion/exclusion criteria. These publications were used to create the Guideline statements. Evidence-based statements of Strong, Moderate, or Conditional Recommendation were developed based on benefits and risks/burdens to patients. Additional guidance is provided as Clinical Principles and Expert Opinion when insufficient evidence existed. RESULTS: The Panel identified the most common scenarios seen in clinical practice related to the treatment of urethral strictures. Guideline statements were developed to aid the clinician in optimal evaluation, treatment, and follow-up of patients presenting with urethral strictures. CONCLUSIONS: Successful treatment of male urethral stricture requires selection of the appropriate endoscopic or surgical procedure based on anatomic location, length of stricture, and prior interventions. Routine use of imaging to assess stricture characteristics will be required to apply evidence based recommendations, which must be applied with consideration of patient preferences and personal goals. As scientific knowledge relevant to urethral stricture evolves and improves, the strategies presented here will be amended to remain consistent with the highest standards of clinical care.

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.

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.

Alcohol consumption and cancer risk: understanding possible causal mechanisms for breast and colorectal cancers.

OBJECTIVES: The purpose of this report is to systematically examine the possible causal mechanism(s) that may explain the association between alcohol (ethanol) consumption and the risk of developing breast and colorectal cancers. DATA SOURCES: We searched 11 external databases, including PubMed® and Embase, for studies on possible mechanisms. These searches used Medical Subject Headings and free text words to identify relevant evidence. REVIEW METHODS: Two reviewers independently screened search results, selected studies to be included, and reviewed each trial for inclusion. We manually examined the bibliographies of included studies, scanned the content of new issues of selected journals, and reviewed relevant gray literature for potential additional articles. RESULTS: Breast Cancer. Five human and 15 animal studies identified in our searches point to a connection between alcohol intake and changes in important metabolic pathways that when altered may increase the risk of developing breast cancer. Alterations in blood hormone levels, especially elevated estrogen-related hormones, have been reported in humans. Several cell line studies suggest that the estrogen receptor pathways may be altered by ethanol. Increased estrogen levels may increase the risk of breast cancer through increases in cell proliferation and alterations in estrogen receptors. Human studies have also suggested a connection with prolactin and with biomarkers of oxidative stress. Of 15 animal studies, six reported increased mammary tumorigenesis (four administered a co-carcinogen and two did not). Other animal studies reported conversion of ethanol to acetaldehyde in mammary tissue as having a significant effect on the progression of tumor development. Fifteen cell line studies suggested the following mechanisms: Increased hormonal receptor levels. Increased cell proliferation. A direct stimulatory effect. DNA adduct formation. Increase cyclic adenosine monophosphate (camp). Change in potassium channels. Modulation of gene expression. Colorectal Cancer. One human tissue study, 19 animal studies (of which 12 administered a co-carcinogen and seven did not), and 10 cell line studies indicate that ethanol and acetaldehyde may alter metabolic pathways and cell structures that increase the risk of developing colon cancer. Exposure of human colonic biopsies to acetaldehyde suggests that acetaldehyde disrupts epithelial tight junctions. Among 19 animal studies the mechanisms considered included: Mucosal damage after ethanol consumption. Increased degradation of folate. Stimulation of rectal carcinogenesis. Increased cell proliferation. Increased effect of carcinogens. Ten cell line studies suggested: Folate uptake modulation. Tumor necrosis factor modulation. Inflammation and cell death. DNA adduct formation. Cell differentiation. Modulation of gene expression. One study used a combination of animal and cell line and suggested intestinal cell proliferation and disruption of cellular signals as possible mechanisms. CONCLUSIONS: Based on our systematic review of the literature, many potential mechanisms by which alcohol may influence the development of breast or colorectal cancers have been explored but the exact connection or connections remain unclear. The evidence points in several directions but the importance of any one mechanism is not apparent at this time.

Time to intervention during cardiac interventions. Are we forgetting a confounder?

As we evolve in the field of contemporary cardiothoracic surgery and witness modern applications of new techniques and technology, we need to be careful of how statistical methods are executed. Publications with hidden mediators that are not adequately addressed can lead to biased conclusions, especially when meta-analyzed. Public health policies need to be sure that their statements are as unbiased as possible for correct inference, leading to optimal patient safety and well-being. Careful analysis of hidden mediators is important in studies comparing the effectiveness of procedures and devices. Such analysis is critical in identifying mediators such as waiting time that should be considered when constructing interventions to be evaluated in the next RCT. In particular, RCTs of devices and procedures should always conduct (and report) ITT analysis, capturing all events from the time of randomization forward to control for differential waiting time. Similarly, observational registries and databases should count time zero as the time when patients are first referred for therapy, rather than when they enter a hospital to receive treatment; this would ensure that events during the waiting period are captured.

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.