Imaging-based non-invasive liver disease assessment for staging liver fibrosis in chronic liver disease: A systematic review supporting the AASLD Practice Guideline.

BACKGROUND AND AIMS: Transient elastography (TE), shear-wave elastography (SWE), and/or magnetic resonance elastography (MRE), each providing liver stiffness measurement (LSM), are the most studied imaging-based noninvasive liver disease assessment (NILDA) techniques. To support the American Association for the Study of Liver Diseases guidelines on NILDA, we summarized the evidence on the accuracy of these LSM methods to stage liver fibrosis (F). APPROACH AND RESULTS: A comprehensive search for studies assessing LSM by TE, SWE, or MRE for the identification of significant fibrosis (F2-4), advanced fibrosis (F3-4), or cirrhosis (F4), utilizing histopathology as standard of reference by liver disease etiology in adults or children from inception to April 2022 was performed. We excluded studies with <50 patients with a single disease entity and mixed liver disease etiologies (with the exception of HCV/HIV co-infection). Out of 9447 studies, 240 with 61,193 patients were included in this systematic review. In adults, sensitivities for the identification of F2-4 ranged from 51% to 95%, for F3-4 from 70% to 100%, and for F4 from 60% to 100% across all techniques/diseases, whereas specificities ranged from 36% to 100%, 74% to 100%, and 67% to 99%, respectively. The largest body of evidence available was for TE; MRE appeared to be the most accurate method. Imaging-based NILDA outperformed blood-based NILDA in most comparisons, particularly for the identification of F3-4/F4. In the pediatric population, imaging-based NILDA is likely as accurate as in adults. CONCLUSION: LSM from TE, SWE, and MRE show acceptable to outstanding accuracy for the detection of liver fibrosis across various liver disease etiologies. Accuracy increased from F2-4 to F3-4 and was the highest for F4. Further research is needed to better standardize the use of imaging-based NILDA, particularly in pediatric liver diseases.

Non-invasive liver disease assessment to identify portal hypertension: A systematic review supporting the AASLD Practice Guideline.

INTRODUCTION: Portal hypertension is a serious complication of cirrhosis, which leads to life-threatening complications. Hepatic venous pressure gradient (HVPG), a surrogate of portal pressure, is the reference standard test to assess the severity of portal hypertension. However, since HVPG is limited by its invasiveness and by its availability, non-invasive liver disease assessments (NILDAs) to assess portal pressure, especially clinically significant portal hypertension (CSPH), are needed. METHODS: We conducted a systematic review of Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations, and Daily, Ovid EMBASE, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, and Scopus from each database's inception to April 22 nd , 2022. We included only studies in English that examined ≥50 patients in single liver disease etiologies which compared non-invasive tests (blood, and/or imaging) to HVPG for predicting clinically significant portal hypertension (CSPH; defined as HVPG ≥10 mm Hg) in patients with chronic liver disease (this therefore limited the number of studies that could be included). Outcomes reported included measures of diagnostic test accuracy. Additionally, a narrative review of studies not eligible for the systematic review is also provided. RESULTS: Nine studies with 2,492 patients met the inclusion criteria. There was substantial heterogeneity with regard to liver disease studied and cutoff values used to detect CSPH. Blood based tests, including aspartate to platelet ratio index (APRI) (56% sensitivity and 68% specificity) and fibrosis-4 (FIB-4) (54% sensitivity and 73% specificity) had low accuracy measures. Imaging based tests (transient elastography (TE) and shear wave elastography detection of liver stiffness (LSM)) had better accuracy, but also had substantial variation; at 15 kPa, TE sensitivity was 90%-96% and specificity was 48%-50% while at 25 kPa, its sensitivity and specificity were 57%-85% and 82%-93%, respectively. The narrative review suggested that imaging based tests are the best available NILDA to detect CSPH, CSPH is highly unlikely to be present at an LSM ≤15 kPa and likely to be present at an LSM ≥25 kPa. CONCLUSION: While imaging-based NILDA appeared to have higher accuracy than blood-based tests to detect CSPH, only 9 studies fit the a priori established inclusion criteria for the SR. In addition, there was substantial study heterogeneity and variation in cutoffs for LSM to detect CSPH, limiting the ability to establish definitive cutoffs to detect CSPH.

Certainty of Evidence Assessment in Systematic Reviews Published by High-Impact Sports Science Journals: A Meta-epidemiological Study.

BACKGROUND: Assessing certainty of evidence is a key element of any systematic review. The aim of this meta-epidemiology study was to understand the frequency and ways with which certainty of evidence is assessed in contemporary systematic reviews published in high-impact sports science journals. METHODS: We searched PubMed and relevant journal web sites from 1 August 2016 to 11 October 2022 for systematic reviews published in the top-ten highest-impact journals within the 2020 Journal Citation Report for the Sports Sciences category. Pairs of independent reviewers screened items using a priori established criteria. RESULTS: Of 1250 eligible documents, 258 (20.6%) assessed the certainty of evidence, defined as using two or more distinct domains to provide an overall rating of the trustworthiness of findings across studies. Nine methods were cited for assessing certainty, with the most common being the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach (61.6%). The proportion of systematic reviews assessing certainty of evidence appeared to increase over the 6-year timeframe analyzed. Across all reviews analyzed, a large majority addressed the domains of risk of bias, imprecision, and inconsistency of the results. Other certainty domains including indirectness/applicability were less commonly assessed. DISCUSSION: Only one in five recent contemporary systematic reviews in the field of exercise and sports science assessed certainty of evidence. Organizational and institutional education on methods for assessing evidence may help further increase uptake of these methods and improve both the quality and clinical impact of systematic reviews in the field.

American Gastroenterological Association-American College of Gastroenterology Clinical Practice Guideline: Pharmacological Management of Chronic Idiopathic Constipation.

INTRODUCTION: Chronic idiopathic constipation (CIC) is a common disorder associated with significant impairment in quality of life. This clinical practice guideline, jointly developed by the American Gastroenterological Association and the American College of Gastroenterology, aims to inform clinicians and patients by providing evidence-based practice recommendations for the pharmacological treatment of CIC in adults. METHODS: The American Gastroenterological Association and the American College of Gastroenterology formed a multidisciplinary guideline panel that conducted systematic reviews of the following agents: fiber, osmotic laxatives (polyethylene glycol, magnesium oxide, lactulose), stimulant laxatives (bisacodyl, sodium picosulfate, senna), secretagogues (lubiprostone, linaclotide, plecanatide), and serotonin type 4 agonist (prucalopride). The panel prioritized clinical questions and outcomes and used the Grading of Recommendations Assessment, Development, and Evaluation framework to assess the certainty of evidence for each intervention. The Evidence to Decision framework was used to develop clinical recommendations based on the balance between the desirable and undesirable effects, patient values, costs, and health equity considerations. RESULTS: The panel agreed on 10 recommendations for the pharmacological management of CIC in adults. Based on available evidence, the panel made strong recommendations for the use of polyethylene glycol, sodium picosulfate, linaclotide, plecanatide, and prucalopride for CIC in adults. Conditional recommendations were made for the use of fiber, lactulose, senna, magnesium oxide, and lubiprostone. DISCUSSION: This document provides a comprehensive outline of the various over-the-counter and prescription pharmacological agents available for the treatment of CIC. The guidelines are meant to provide a framework for approaching the management of CIC; clinical providers should engage in shared decision making based on patient preferences as well as medication cost and availability. Limitations and gaps in the evidence are highlighted to help guide future research opportunities and enhance the care of patients with chronic constipation.

American Gastroenterological Association-American College of Gastroenterology Clinical Practice Guideline: Pharmacological Management of Chronic Idiopathic Constipation.

INTRODUCTION: Chronic idiopathic constipation (CIC) is a common disorder associated with significant impairment in quality of life. This clinical practice guideline, jointly developed by the American Gastroenterological Association and the American College of Gastroenterology, aims to inform clinicians and patients by providing evidence-based practice recommendations for the pharmacological treatment of CIC in adults. METHODS: The American Gastroenterological Association and the American College of Gastroenterology formed a multidisciplinary guideline panel that conducted systematic reviews of the following agents: fiber, osmotic laxatives (polyethylene glycol, magnesium oxide, lactulose), stimulant laxatives (bisacodyl, sodium picosulfate, senna), secretagogues (lubiprostone, linaclotide, plecanatide), and serotonin type 4 agonist (prucalopride). The panel prioritized clinical questions and outcomes and used the Grading of Recommendations Assessment, Development, and Evaluation framework to assess the certainty of evidence for each intervention. The Evidence to Decision framework was used to develop clinical recommendations based on the balance between the desirable and undesirable effects, patient values, costs, and health equity considerations. RESULTS: The panel agreed on 10 recommendations for the pharmacological management of CIC in adults. Based on available evidence, the panel made strong recommendations for the use of polyethylene glycol, sodium picosulfate, linaclotide, plecanatide, and prucalopride for CIC in adults. Conditional recommendations were made for the use of fiber, lactulose, senna, magnesium oxide, and lubiprostone. DISCUSSION: This document provides a comprehensive outline of the various over-the-counter and prescription pharmacological agents available for the treatment of CIC. The guidelines are meant to provide a framework for approaching the management of CIC; clinical providers should engage in shared decision making based on patient preferences as well as medication cost and availability. Limitations and gaps in the evidence are highlighted to help guide future research opportunities and enhance the care of patients with chronic constipation.

GRADE guidance 35: update on rating imprecision for assessing contextualized certainty of evidence and making decisions.

OBJECTIVES: Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidance to rate the certainty domain of imprecision is presently not fully operationalized for rating down by two levels and when different baseline risk or uncertainty in these risks are considered. In addition, there are scenarios in which lowering the certainty of evidence by three levels for imprecision is more appropriate than lowering it by two levels. In this article, we conceptualize and operationalize rating down for imprecision by one, two and three levels for imprecision using the contextualized GRADE approaches and making decisions. METHODS: Through iterative discussions and refinement in online meetings and through email communication, we developed draft guidance to rating the certainty of evidence down by up to three levels based on examples. The lead authors revised the approach according to the feedback and the comments received during these meetings and developed GRADE guidance for how to apply it. We presented a summary of the results to all attendees of the GRADE Working Group meeting for feedback in October 2021 (approximately 80 people) where the approach was formally approved. RESULTS: This guidance provides GRADE's novel approach for the considerations about rating down for imprecision by one, two and three levels based on serious, very serious and extremely serious concerns. The approach includes identifying or defining thresholds for health outcomes that correspond to trivial or none, small, moderate or large effects and using them to rate imprecision. It facilitates the use of evidence to decision frameworks and also provides guidance for how to address imprecision about implausible large effects and trivial or no effects using the concept of the 'review information size' and for varying baseline risks. The approach is illustrated using practical examples, an online calculator and graphical displays and can be applied to dichotomous and continuous outcomes. CONCLUSION: In this GRADE guidance article, we provide updated guidance for how to rate imprecision using the partially and fully contextualized GRADE approaches for making recommendations or decisions, considering alternate baseline risks and for both dichotomous and continuous outcomes.

Community Health Needs Assessment Data and Community Recovery From COVID-19.

INTRODUCTION: The COVID-19 pandemic has had a significant impact beyond physical morbidity and mortality. A mid-cycle Community Health Needs Assessment survey was administered in 1 community to generate data to evaluate change in community well-being since the beginning of the pandemic. METHODS: Surveys were mailed to 2,000 randomly selected residents in Olmsetd County, Minnesota. The surveys included the WHO Well-being Index (previously included in the 2018 Community Health Needs Assessment) and new subjective questions regarding behavior change. Changes in well-being were calculated using a propensity-matched cohort, and behavior change was reported as proportions of the whole. Data analysis was completed in 2021. RESULTS: Total survey respondents were 569 people in 2018 and 723 people in 2021. Well-being scores from the WHO Well-being Index showed a statistically significant decrease (score reduction of -8.44) from 2018 to 2021. All the 5 questions from the WHO Well-being Index also had an individual significant decrease; with the question regarding interest in life showing the greatest decrease. Individuals reported decreased subjective physical and mental well-being and increased substance use (alcohol, marijuana, and tobacco). Households also reported decreased household incomes and worse household finances since the start of the pandemic. CONCLUSIONS: Using the Community Health Needs Assessment infrastructure, 1 community was able to compare prepandemic with postpandemic data, which showed decreased well-being and increased substance use and financial stress. Other public health planners can similarly conduct interval surveys on the basis of their Community Health Needs Assessment questionnaires to tailor ongoing Community Health Improvement Plan programming to postpandemic needs and track community mental health and well-being recovery.

An International Needs Assessment Survey of Guideline Developers Demonstrates Variability in Resources and Challenges to Collaboration between Organizations.

BACKGROUND: The development of rigorous, high-quality clinical guidelines increases the need for resources and skilled personnel within guideline-producing organizations. While collaboration between organizations provides a unique opportunity to pool resources and save time and effort, the collaboration presents its own unique challenges. OBJECTIVE: To assess the perceived needs and current challenges of guideline producers worldwide related to guideline development and collaboration efforts. DESIGN: Survey questions were developed by the Guidelines International Network and the US GRADE Network, pilot-tested among attendees of a guideline development workshop, and disseminated electronically using convenience and snowball sampling methods. PARTICIPANTS: A total of 171 respondents representing 30 countries and more than 112 unique organizations were included in this analysis. MAIN MEASURES: The survey included free-response, multiple-choice, and seven-point Likert-scale questions. Questions assessed respondents' perceived value of guidelines, resource availability and needs, guideline development processes, and collaboration efforts of their organization. KEY RESULTS: Time required to develop high-quality systematic reviews and guidelines was the most relevant need (median=7; IQR=5.5-7). In-house resources to conduct literature searches (median=4; IQR=3-6) and the resources to develop rigorous guidelines rapidly (median=4; IQR=2-5) were perceived as the least available resources. Difficulties reconciling differences in guideline methodology (median=6; IQR=4-7) and the time required to establish collaborative agreements (median=6; IQR=5-6) were the most relevant barriers to collaboration between organizations. Results also indicated a general need for improvement in conflict of interest (COI) disclosure policies. CONCLUSION: The survey identified organizational challenges in supporting rigorous guideline development, including the time, resources, and personnel required. Connecting guideline developers to existing databases of high-quality systematic reviews and the use of freely available online platforms may facilitate guideline development. Guideline-producing organizations may also consider allocating resources to hiring or training personnel with expertise in systematic review methodologies or utilizing resources more effectively by establishing collaborations with other organizations.

Health Care Delivery Interventions for Hypertension Management in Underserved Populations in the United States: A Systematic Review.

[Figure: see text].

Users' Guide to Medical Decision Analysis.

Clinicians regularly have to trade benefits and harms to choose between testing and treatment strategies. This process is often done by making global and implicit judgments. A decision analysis is an analytic method that makes this process more explicit, reproducible, and evidence-based. While clinicians are unlikely to conduct their own decision analysis, they will read publications of such analyses or use guidelines based on them. This review outlines the anatomy of a decision tree and provides clinicians with the tools to critically appraise a decision analysis and apply its results to medical decision making. Clinicians reading about a decision analysis can make two judgments. The first judgment is about the credibility of the methods, such as whether the decision analysis addressed a relevant clinical question, included all important outcomes, used the current best evidence to derive variables in the model, and adopted the appropriate time horizon. The second judgment is about rating confidence in the preferred course of action by determining the certainty in the model variables, whether the results are robust in sensitivity analyses and if the results are applicable to a specific patient. Results from a valid and robust decision analysis can inform both guideline panels and the patient-clinician dyad engaged in shared decision-making.

Decompression Sickness Risk Assessment and Awareness in General Aviation.

INTRODUCTION: Decompression sickness (DCS) can occur during unpressurized flight to altitudes >18,000 ft (FL180; 5486 m). To our knowledge, this has not been studied in general aviation (GA). This knowledge gap may have public health and safety implications because the most popular models of GA aircraft by sales volume are capable of flying >FL180.METHODS: Data from a 1-yr period in a commercial flight tracking database were analyzed to identify flights >FL180 in unpressurized, piston aircraft in the United States. Peak altitude and duration at that altitude were used to calculate DCS risk employing the U.S. Air Force (USAF) Altitude Decompression Sickness Risk Assessment Computer (ADRAC). Registration numbers were cross referenced in publicly available federal databases to identify any events that might be attributable to impairment due to DCS. A web-based survey of practices and associated symptoms was also made available to GA pilots through an online discussion forum.RESULTS: During the data collection period, 1696 flights occurred. The DCS risk was calculated to be 1.9 4.2%. There were 42 responses to the survey. Of these, 25 (59.5%) pilots reported having flown at altitudes >FL180 and 21 (84%) of them reported symptoms possibly attributable to DCS. None sought medical attention. No safety events were identified for any of the aircraft during the study period.CONCLUSION: The risk of DCS in the GA community is not zero. As GA aircraft performance profiles advance and sales increase, this may have significant implications from a public health and safety perspective. Further study is warranted.Harrison MF, Butler WP, Murad MH, Toups GN. Decompression sickness risk assessment and awareness in general aviation. Aerosp Med Hum Perform. 2021; 92(3):138145.

Assessment of Heterogeneity in Heart Failure-Related Meta-Analyses.

BACKGROUND: Assessment of heterogeneity in meta-analyses is critical to ensure the consistency of pooled results. Therefore, we sought to assess the evaluation and reporting of heterogeneity in heart failure (HF) meta-analyses. METHODS: Study level meta-analyses pertaining to HF were selected from January 2009 to July 2019, published in 11 high impact factor journals. We tabulated the overall proportion of the meta-analyses reporting statistical heterogeneity and specific metrics and methods employed to quantify and explore heterogeneity. RESULTS: Of 126 HF meta-analyses (612 outcomes), heterogeneity was reported for 422 outcomes (68.9 %) in 108 meta-analyses. Out of the 422 outcomes reporting statistical heterogeneity, 137 outcomes (32.5%) had no observable heterogeneity: (I2=0%), 40 outcomes (9.5%) had low heterogeneity (I2<25%), 76 outcomes (18%) had moderate heterogeneity (I2=25%-50%), and 169 outcomes (40%) had high heterogeneity (I2>50%). Reporting of statistical heterogeneity was not significantly associated with year of publication, funding source, disclosure information, or the type of studies pooled. Sensitivity analysis (n=68) was the most common statistical technique employed to evaluate the source of heterogeneity followed by subgroup analyses (n=59) and meta-regression (n=40). CONCLUSIONS: Despite being an essential component of meta-analyses, heterogeneity was not reported for nearly 30% of outcomes and variably handled in contemporary HF meta-analyses. As meta-analyses increase across HF science, interpreting and handling of heterogeneity should be standardized.

Systemic Therapy and Sequencing Options in Advanced Hepatocellular Carcinoma: A Systematic Review and Network Meta-analysis.

Importance: The treatment landscape for advanced hepatocellular carcinoma (HCC) has recently changed and become relatively confusing. Head-to-head comparisons between most of the available agents have not been performed and are less likely to be examined in a prospective fashion in the future. Therefore, a network meta-analysis (NMA) is helpful to compare different agents from across different trials. Objective: To evaluate comparative effectiveness of different systemic treatments in advanced patients with HCC across lines of therapy. Data Sources: We searched various databases for abstracts and full-text articles published from database inception through March 2020. Study Selection: We included phase 3 trials evaluating different vascular endothelial growth factor inhibitors (VEGFis), checkpoint inhibitors (CPIs), or their combinations in advanced HCC, in the first-line or refractory setting. Data Extraction and Synthesis: The reporting of this systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. The overall effect was pooled using the random effects model. Main Outcomes and Measures: Outcomes of interest included overall (OS) and progression-free survival (PFS). Findings: Fourteen trials (8 in the first-line setting and 6 in the second-line setting) at low risk of bias were included. The 8 trials in the first-line setting encompassed a total of 6290 patients, with an age range of 18 to 89 years. The 5 trials included in the second-line analysis encompassed a total of 2653 patients, with an age range of 18 to 91 years. Network meta-analysis showed the combination of atezolizumab and bevacizumab was superior in patients with HCC treated in the first-line setting compared with lenvatinib (HR, 0.63; 95% CI, 0.44-0.89), sorafenib (HR, 0.58; 95% CI, 0.42-0.80), and nivolumab (HR, 0.68; 95% CI, 0.48-0.98). In the refractory setting, NMA showed that all studied drugs had PFS benefit compared with placebo. However, this only translated into OS benefit with regorafenib (HR, 0.62; 95% CI, 0.51-0.75) and cabozantinib (HR, 0.76; 95% CI, 0.63-0.92) compared with placebo. In the NMA of patients with α-fetoprotein (AFP) levels of 400 ng/mL or greater, regorafenib, cabozantinib, and ramucirumab showed PFS and OS benefit compared with placebo with no superiority of an active drug compared with any others. Conclusions and Relevance: This systematic review and NMA of 14 trials found that atezolizumab and bevacizumab in combination is now considered the standard of care in the first-line setting in patients with advanced HCC. Regorafenib and cabozantinib are preferred options in refractory patients, with ramucirumab as an additional option in those with levels of AFP of 400 ng/mL or higher. Future trials should focus on other potential combinations and best treatment strategy in patients with prior VEGFi/CPI exposure.

Health Care Utilization and Pain Outcomes Following Early Imaging for Low Back Pain in Older Adults.

BACKGROUND: Professional societies have provided inconsistent guidance regarding whether older patients should receive early imaging for low back pain, in the absence of clinical indications. The study assesses the implications of early imaging by evaluating its association with downstream utilization in an elderly population. METHODS: Patients were included if they had a Medicare Advantage plan, had claims-based evidence of low back pain in 2014, and lacked conditions justifying early imaging. The outcomes examined were short-term, nonchronic, and chronic opioid use, steroid injections, and spinal surgery in the following 730 days, and persistent low back pain at 180 to 365 days. Morphine dose equivalents of opioid use was used as a measure of intensity. Logistic and γ regressions were used to assess the association between imaging in the first 6 weeks and the outcomes. RESULTS: Among the 57,293 patients meeting inclusion criteria, the mean age was 71.2, and 26,606 (46.4%) received early imaging. Early imaging was associated with increased adjusted odds of short-term (odds ratio [OR], 1.21; 95% CI, 1.15 to 1.28), nonchronic (OR, 1.78; 95% CI, 1.69 to 1.88), and chronic (OR, 1.13; 95% CI, 1.07 to 1.18) opioid use, as well as steroid injections (OR, 2.55; 95% CI, 2.28 to 2.85) and spinal surgery (OR, 3.40; 95% CI, 2.97 to 3.90). Patients that received early imaging were more likely to experience persistent pain (OR, 1.09; 95% CI, 1.05 to 1.14) and used significantly more morphine dose equivalents if they had nonchronic opioid use. CONCLUSIONS: Early imaging for low back pain in older individuals was common, and was associated with greater utilization of downstream services and persistent pain.

Global Vascular Guidelines on the Management of Chronic Limb-Threatening Ischemia.

GUIDELINE SUMMARY: Chronic limb-threatening ischemia (CLTI) is associated with mortality, amputation, and impaired quality of life. These Global Vascular Guidelines (GVG) are focused on definition, evaluation, and management of CLTI with the goals of improving evidence-based care and highlighting critical research needs. The term CLTI is preferred over critical limb ischemia, as the latter implies threshold values of impaired perfusion rather than a continuum. CLTI is a clinical syndrome defined by the presence of peripheral artery disease (PAD) in combination with rest pain, gangrene, or a lower limb ulceration >2 weeks duration. Venous, traumatic, embolic, and nonatherosclerotic etiologies are excluded. All patients with suspected CLTI should be referred urgently to a vascular specialist. Accurately staging the severity of limb threat is fundamental, and the Society for Vascular Surgery Threatened Limb Classification system, based on grading of Wounds, Ischemia, and foot Infection (WIfI) is endorsed. Objective hemodynamic testing, including toe pressures as the preferred measure, is required to assess CLTI. Evidence-based revascularization (EBR) hinges on three independent axes: Patient risk, Limb severity, and ANatomic complexity (PLAN). Average-risk and high-risk patients are defined by estimated procedural and 2-year all-cause mortality. The GVG proposes a new Global Anatomic Staging System (GLASS), which involves defining a preferred target artery path (TAP) and then estimating limb-based patency (LBP), resulting in three stages of complexity for intervention. The optimal revascularization strategy is also influenced by the availability of autogenous vein for open bypass surgery. Recommendations for EBR are based on best available data, pending level 1 evidence from ongoing trials. Vein bypass may be preferred for average-risk patients with advanced limb threat and high complexity disease, while those with less complex anatomy, intermediate severity limb threat, or high patient risk may be favored for endovascular intervention. All patients with CLTI should be afforded best medical therapy including the use of antithrombotic, lipid-lowering, antihypertensive, and glycemic control agents, as well as counseling on smoking cessation, diet, exercise, and preventive foot care. Following EBR, long-term limb surveillance is advised. The effectiveness of nonrevascularization therapies (eg, spinal stimulation, pneumatic compression, prostanoids, and hyperbaric oxygen) has not been established. Regenerative medicine approaches (eg, cell, gene therapies) for CLTI should be restricted to rigorously conducted randomizsed clinical trials. The GVG promotes standardization of study designs and end points for clinical trials in CLTI. The importance of multidisciplinary teams and centers of excellence for amputation prevention is stressed as a key health system initiative.

Congenital Adrenal Hyperplasia Due to Steroid 21-Hydroxylase Deficiency: An Endocrine Society Clinical Practice Guideline.

Objective: To update the congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency clinical practice guideline published by the Endocrine Society in 2010. Conclusions: The writing committee presents updated best practice guidelines for the clinical management of congenital adrenal hyperplasia based on published evidence and expert opinion with added considerations for patient safety, quality of life, cost, and utilization.

Risk Factors Associated With Health Care Utilization and Costs of Patients Undergoing Lower Extremity Joint Replacement.

BACKGROUND: The Comprehensive Care for Joint Replacement program implemented by the Centers for Medicare and Medicaid Services did not incorporate risk adjustment for lower extremity joint replacement (LEJR). Lack of adjustment places hospitals at financial risk and creates incentives for adverse patient selection. OBJECTIVE: To identify patient-level risk factors associated with health care utilization and costs of patients undergoing LEJR. METHODS: A comprehensive search of research databases from January 1, 1990, through January 31, 2016, was conducted. The databases included Ovid MEDLINE In-Process & Other Non-Indexed Citations, Ovid MEDLINE, Ovid EMBASE, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, and SCOPUS and is reported according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. The search identified 2020 studies. Eligible studies focused on primary unilateral and bilateral LEJR. Independent reviewers determined study eligibility and extracted utilization and cost data. RESULTS: Seventy-nine of 330 studies (24%) were included and were abstracted for analysis. Comorbidities, age, disease severity, and obesity were associated with increased costs. Increased number of comorbidities and age, presence of specific comorbidities, lower socioeconomic status, and female sex had evidence of increased length of stay. We found no significant association between indication for surgery and the likelihood of readmission. CONCLUSION: Developing a risk adjustment model for LEJR that incorporates clinical variables may serve to reduce the likelihood of adverse patient selection and enhance appropriate reimbursement aligned with procedural complexity.

Treatments for giant cell arteritis: Meta-analysis and assessment of estimates reliability using the fragility index.

BACKGROUND: To better communicate the results of randomized controlled trials (RCTs) of giant cell arteritis (GCA), we propose the use of the fragility index (FI), which is an intuitive measure defined as the minimum number of subjects whose status would have to change (e.g., from having the outcome to not) to render a statistically significant result nonsignificant, or vice-versa. METHODS: We conducted a systematic review and random-effects meta-analysis of RCTs of glucocorticoid (GC) sparing strategies for relapse-free maintenance in GCA, and used the FI to simplify the presentation of results. RESULTS: Ten RCTs (nine phase II and one phase III enrolling 645 subjects) were included. Tocilizumab, IV GC and methotrexate significantly improved the likelihood of being relapse free with relative risks and 95% confidence intervals of 3.54 (2.28, 5.51), 5.11 (1.39, 18.81) and 1.54 (1.02, 2.30); respectively. The median FI was 4.5 (range, 1-28), and was generally higher for negative RCTs (n = 6; median FI 4.5) than for positive RCTs (n = 4; median FI 3.5). The range of FI per treatment was (1-8) for methotrexate, (2-6) for anti-TNF agents, 4 for abatacept, 3 for IV GC pulses and (4-28) for tocilizumab. CONCLUSION: Tocilizumab, IV GC and methotrexate improve the likelihood of being relapse-free in subjects with GCA. Assessment of GC sparing strategies in GCA has long depended on imprecise trials that would change significance if outcomes were reversed for a handful of subjects. FI may be used in rheumatology to simplify communication of statistical significance and overcome limitations of p-value.

Conceptualising paediatric health disparities: a metanarrative systematic review and unified conceptual framework.

OBJECTIVE: There exists a paucity of work in the development and testing of theoretical models specific to childhood health disparities even though they have been linked to the prevalence of adult health disparities including high rates of chronic disease. We conducted a systematic review and thematic analysis of existing models of health disparities specific to children to inform development of a unified conceptual framework. METHODS: We systematically reviewed articles reporting theoretical or explanatory models of disparities on a range of outcomes related to child health. We searched Ovid Medline In-Process & Other Non-Indexed Citations, Ovid MEDLINE, Ovid Embase, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, and Scopus (database inception to 9 July 2015). A metanarrative approach guided the analysis process. RESULTS: A total of 48 studies presenting 48 models were included. This systematic review found multiple models but no consensus on one approach. However, we did discover a fair amount of overlap, such that the 48 models reviewed converged into the unified conceptual framework. The majority of models included factors in three domains: individual characteristics and behaviours (88%), healthcare providers and systems (63%), and environment/community (56%), . Only 38% of models included factors in the health and public policies domain. CONCLUSIONS: A disease-agnostic unified conceptual framework may inform integration of existing knowledge of child health disparities and guide future research. This multilevel framework can focus attention among clinical, basic and social science research on the relationships between policy, social factors, health systems and the physical environment that impact children's health outcomes.