The association between the timing of initial hepatitis B vaccination and seropositivity in healthcare personnel.

This study reports on the relationship between timing of initial hepatitis B virus (HBV) vaccine series and HBV antibody immunity in healthcare personnel (HCP) screened prior to employment. HCPs vaccinated as neonates were significantly more likely to have negative or indeterminate antibodies. An alternative screening approach is considered.

Safety implications of mask use: a systematic review and evidence map.

BACKGROUND: Widespread use of respiratory protection masks has become a critical component of public health response. OBJECTIVES: This systematic review synthesises the evidence on the acute physiological, cognitive and psychological impacts associated with different types of masks and provides an evidence map of research gaps. METHODS: A comprehensive search from 2000 to 2023 was conducted across multiple databases (MEDLINE, EMBASE, Cochrane databases, Scopus and PubMed). An umbrella systematic overview was conducted for physiological outcomes using existing systematic reviews. We conducted de novo systematic reviews for cognitive and psychological outcomes. Pairs of independent reviewers determined eligibility, extracted data and assessed risk of bias. Certainty at an outcome level was appraised using the Grading of Recommendations Assessment, Development and Evaluation approach. RESULTS: The search resulted in 13 370 potential citations, leading to the inclusion of nine systematic reviews for physiological outcomes (87 primary studies) and 10 primary studies for cognitive and psychological outcomes (3815 participants), with the majority of participants being healthy adults. Studies evaluating physiological outcomes demonstrated that various types of masks have little to no significant difference in heart rate (surgical mask (mean difference (MD): 0.96 (-1.01 to 2.93)), N95 mask (MD: 1.63 (-2.79 to 6.05)) and cloth mask (MD: -0.94 (-6.39 to 4.52))) or respiratory rate during rest or exercise (surgical mask (MD: -1.35 (-3.00 to 0.29)), N95 mask (MD: 0.10 (-3.10 to 3.29)) and cloth mask (MD: -2.57 (-6.44 to 1.29)) (low certainty for most outcomes)). Mask use may be associated with very small changes in minute ventilation (surgical mask (MD: -13.9 (-20.30 to -7.53)) and N95 mask (MD: -16.3 (-28.7 to -3.9))), tidal volume (surgical mask (MD: -0.14 (-0.23 to -0.05)) and N95 mask (MD: -0.10 (-0.33 to 0.13))), oxygen saturation (surgical mask (MD: -0.59% (-0.87 to -0.30)), N95 mask (MD: -0.35% (-0.75 to 0.05)) and cloth mask (MD: -0.50% (-1.23; 0.24))), carbon dioxide partial pressure (surgical mask (standardised MD (SMD): 1.17 (0.70 to 1.64)) and N95 mask (SMD: 0.43 (0.08 to 0.79))) and exercise performance (surgical mask (SMD: -0.12 (-0.39 to 0.15)), N95 mask (SMD: -0.42 (-0.76 to -0.08)) and cloth mask (SMD: -0.26 (-0.54 to 0.02)) (low certainty for most outcomes)). Studies evaluating cognitive outcomes showed mixed results. Some studies reported reduced mental workload, and others showed no significant effect or decreased performance. The impact on attention, errors and reaction time was variable. These studies were small and at moderate to high risk of bias. Evidence was insufficient to estimate the effect of mask use on psychological outcomes (claustrophobia, depression and anxiety) as these studies were small, non-longitudinal and at high risk of bias. CONCLUSION: This evidence map provides a comprehensive insight into the multifaceted impact of respiratory protection mask use, and highlights the limited certainty in the available body of evidence. This evidence map supports the development of future research agenda.

Wide variability of the definitions used for native vertebral osteomyelitis: walking the path for a unified diagnostic framework with a meta-epidemiological approach.

BACKGROUND CONTEXT: Native Vertebral Osteomyelitis (NVO) has seen a rise in incidence, yet clinical outcomes remain poor with high relapse rates and significant long-term sequelae. The 2015 IDSA Clinical Practice Guidelines initiated a surge in scholarly activity on NVO, revealing a patchwork of definitions and numerous synonyms used interchangeably for this syndrome. PURPOSE: To systematically summarize these definitions, evaluate their content, distribution over time, and thematic clustering. STUDY DESIGN/SETTING: Meta-epidemiological study with a systematic review of definitions. PATIENTS SAMPLE: An extensive search of multiple databases was conducted, targeting trials and cohort studies dating from 2005 to present, providing a definition for NVO and its synonyms. OUTCOME MEASURES: Analysis of the diagnostic criteria that composed the definitions and the breaking up of the definitions in the possible combinations of diagnostic criteria. METHODS: We pursued a thematic synthesis of the published definitions with Boolean logic, yielding single or multiple definitions per included study. Using 8 predefined diagnostic criteria, we standardized definitions, focusing on the minimum necessary combinations used. Definition components were visualized using Sankey diagrams. RESULTS: The literature search identified 8,460 references, leading to 171 studies reporting on 21,963 patients. Of these, 91.2% were retrospective, 7.6% prospective, and 1.2% RCTs. Most definitions originated from authors, with 29.2% referencing sources. We identified 92 unique combinations of diagnostic criteria across the literature. Thirteen main patterns emerged, with the most common being clinical features with imaging, followed by clinical features combined with imaging and microbiology, and lastly, imaging paired with microbiology. CONCLUSIONS: Our findings underscore the need for a collaborative effort to develop standardized diagnostic criteria. We advocate for a future Delphi consensus among experts to establish a unified diagnostic framework for NVO, emphasizing the core components of clinical features and MRI while incorporating microbiological and histopathological insights to improve both patient outcomes and research advancements.

Causally interpretable meta-analysis combining aggregate and individual participant data.

Recent work in causally-interpretable meta-analysis (CIMA) has bridged the gap between traditional meta-analysis and causal inference. While traditional meta-analysis results generally do not apply to any well-defined population, CIMA approaches specify a target population to which meta-analytic treatment effect estimates are transported. While theoretically attractive, these approaches currently have some practical limitations. Most assume that all studies in the meta-analysis have individual participant data (IPD), which is rare in practice because most trials share only aggregate data. We propose a method to perform CIMA using a combination of aggregate data and IPD. This method borrows information from studies with IPD to augment the aggregate data and create aggregate-matched synthetic IPD (AMSIPD), which can be used readily in the existing CIMA framework. By allowing use of both aggregate data and IPD, the method opens CIMA to more applications and can avoid biases arising from using only studies with IPD. We present a case study and simulations showing the AMSIPD approach is promising and merits further investigation as an advancement of CIMA.

Simultaneous evaluation of the imprecision and inconsistency domains of GRADE can be performed using prediction intervals.

OBJECTIVES: To explore the use of prediction interval (PI) for the simultaneous evaluation of the imprecision and inconsistency domains of Grading of Recommendations, Assessment, and Evaluation using stakeholder-provided decision thresholds. STUDY DESIGN AND SETTING: We propose transforming the PI of a meta-analysis from a relative risk scale to an absolute risk difference using an appropriate baseline risk. The transformed PI is compared to stakeholder-provided thresholds on an absolute scale. We applied this approach to a large convenience sample of meta-analyses extracted from the Cochrane Database of Systematic Reviews and compared it against the traditional approach of rating imprecision and inconsistency separately using confidence intervals and statistical measures of heterogeneity, respectively. We used empirically derived thresholds following Grading of Recommendations, Assessment, and Evaluation guidance. RESULTS: The convenience sample consisted of 2516 meta-analyses (median of 7 studies per meta-analysis; interquartile range: 5-11). The main analysis showed the percentage of meta-analyses in which both approaches had the same number of certainty levels rated down was 59%. The PI approach led to more levels of rating down (lower certainty) in 27% and to fewer levels of rating down (higher certainty) in 14%. Multiple sensitivity analyses using different thresholds showed similar results, but the PI approach had particularly increased width with a larger number of included studies and higher I2 values. CONCLUSION: Using the PI for simultaneous evaluation of imprecision and inconsistency seems feasible and logical but can lead to lower certainty ratings. The PI-based approach requires further testing in future systematic reviews and guidelines using context-specific thresholds and evidence-to-decision criteria. PLAIN LANGUAGE SUMMARY: The prediction interval (PI) addresses both the imprecision and inconsistency domains of certainty. In this study, we applied this PI approach to simultaneously judge both domains and compared this to the traditional approach of making these separate judgments. The 2 approaches had moderate agreement. The PI-based approach requires further testing in future systematic reviews and guidelines using context-specific thresholds and evidence-to-decision criteria.

Supplementing systematic review findings with healthcare system data: pilot projects from the Agency for Healthcare Research and Quality Evidence-based Practice Center program.

OBJECTIVES: The US Agency for Healthcare Research and Quality, through the Evidence-based Practice Center (EPC) Program, aims to provide health system decision makers with the highest-quality evidence to inform clinical decisions. However, limitations in the literature may lead to inconclusive findings in EPC systematic reviews (SRs). The EPC Program conducted pilot projects to understand the feasibility, benefits, and challenges of utilizing health system data to augment SR findings to support confidence in healthcare decision-making based on real-world experiences. STUDY DESIGN AND SETTING: Three contractors (each an EPC located at a different health system) selected a recently completed SR conducted by their center and identified an evidence gap that electronic health record (EHR) data might address. All pilot project topics addressed clinical questions as opposed to care delivery, care organization, or care disparities topics that are common in EPC reports. Topic areas addressed by each EPC included infantile epilepsy, migraine, and hip fracture. EPCs also tracked additional resources needed to conduct supplemental analyses. The workgroup met monthly in 2022-2023 to discuss challenges and lessons learned from the pilot projects. RESULTS: Two supplemental data analyses filled an evidence gap identified in the SRs (raised certainty of evidence, improved applicability) and the third filled a health system knowledge gap. Project challenges fell under three themes: regulatory and logistical issues, data collection and analysis, and interpretation and presentation of findings. Limited ability to capture key clinical variables given inconsistent or missing data within the EHR was a major limitation. The workgroup found that conducting supplemental data analysis alongside an SR was feasible but adds considerable time and resources to the review process (estimated total hours to complete pilot projects ranged from 283 to 595 across EPCs), and that the increased effort and resources added limited incremental value. CONCLUSION: Supplementing existing SRs with analyses of EHR data is resource intensive and requires specialized skillsets throughout the process. While using EHR data for research has immense potential to generate real-world evidence and fill knowledge gaps, these data may not yet be ready for routine use alongside SRs.

Home and Community-Based Services: A Systematic Review and Evidence Map.

BACKGROUND: Many adults aged 60 years or older have functional limitations and require home and community-based services (HCBS) to support their independence and delay the transition to an institutionalized setting. This systematic review provides an evidence map of the existing literature on HCBS identifying evidence gaps for policy and research. METHODS: A comprehensive literature search of multiple databases including Medline, Embase, and Scopus was conducted through December 7, 2023. Interviews with various stakeholders were conducted to solicit additional perspectives. Narrative and thematic synthesis was conducted to evaluate HCBS in terms of populations, interventions, outcomes, person-centeredness, and relevant quality measures. RESULTS: We identified 27 primary studies and 29 quality measures. Populations of HCBS studies can be categorized as those with functional disability, cognitive impairment, high-risk/frail conditions, and disease-specific conditions (Parkinson's disease, Alzheimer's disease, and post-stroke). HCBS interventions targeted optimization of person-centered planning, nonpharmacological approaches for dementia care, physical rehabilitation, self-directed home care, geriatric resources for practical support at home, and interdisciplinary care coordination for high-risk conditions. Person-centered planning and self-direction of HCBS services were not explicitly described in many studies and very few studies focused on addressing health-related social needs, whereas the majority reported primary clinical outcomes. Numerous quality measures exist for HCBS, some of which were validated, addressed multiple person-centered domains, and may apply across various conditions and populations. Key challenges in the literature on HCBS include limited number of randomized trials, inadequate descriptions of interventions to determine person-centeredness, limited information on facilitators and barriers, and limited information on workforce challenges in recruiting, retaining, and training personnel delivering HCBS. DISCUSSION: This evidence map describes the current state of HCBS and identifies evidence gaps for future research and policy decisions.

What Free Flaps Are Surgeons Using for Palatal Fistula Repair in Patients with Cleft Palate? A Systematic Review.

OBJECTIVE: Recalcitrant palatal fistulas in patients with cleft palate history sometimes require free flap reconstruction. This study reviews the literature on described flaps and outcomes. DESIGN: A systematic review was conducted per the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. SETTING: All study designs were included. Non-English articles were excluded. PATIENTS AND PARTICIPANTS: Patients with a history of cleft palate who underwent free flap reconstruction for a oronasal fistula. INTERVENTIONS: Free tissue transfer for a palatal fistula repair. MAIN OUTCOMEE MEASURES: Information regarding defect and flap characteristics were reviewed. Surgical outcomes such as flap loss rates, rates of recurrent fistula formation, and speech outcomes were also obtained. RESULTS: Our search returned 894 articles, of which 23 were included. All studies were retrospective case series and reports. A total of 65 patients were described with an average age of 19.3 (range 3-55) years and a median fistula size of 8.00 cm2 (range 2.54 cm2 - 24 cm2). The most common flap was the radial forearm flap (n = 37). Nine patients (13.8%) had recurrent fistula formation with surgical revision successful in all cases in which the patient returned to the operating room. There were two partial flap losses and no total flap losses. Speech outcomes showed improvement in 27 patients across 10 studies. CONCLUSIONS: Palatal fistula repair with free tissue transfer is safe with an acceptable risk profile and low flap loss rate. Early recurrence due to partial flap necrosis and dehiscence are successfully managed with flap readvancement.

Measuring Documentation Burden in Healthcare.

BACKGROUND: The enactment of the Health Information Technology for Economic and Clinical Health Act and the wide adoption of electronic health record (EHR) systems have ushered in increasing documentation burden, frequently cited as a key factor affecting the work experience of healthcare professionals and a contributor to burnout. This systematic review aims to identify and characterize measures of documentation burden. METHODS: We integrated discussions with Key Informants and a comprehensive search of the literature, including MEDLINE, Embase, Scopus, and gray literature published between 2010 and 2023. Data were narratively and thematically synthesized. RESULTS: We identified 135 articles about measuring documentation burden. We classified measures into 11 categories: overall time spent in EHR, activities related to clinical documentation, inbox management, time spent in clinical review, time spent in orders, work outside work/after hours, administrative tasks (billing and insurance related), fragmentation of workflow, measures of efficiency, EHR activity rate, and usability. The most common source of data for most measures was EHR usage logs. Direct tracking such as through time-motion analysis was fairly uncommon. Measures were developed and applied across various settings and populations, with physicians and nurses in the USA being the most frequently represented healthcare professionals. Evidence of validity of these measures was limited and incomplete. Data on the appropriateness of measures in terms of scalability, feasibility, or equity across various contexts were limited. The physician perspective was the most robustly captured and prominently focused on increased stress and burnout. DISCUSSION: Numerous measures for documentation burden are available and have been tested in a variety of settings and contexts. However, most are one-dimensional, do not capture various domains of this construct, and lack robust validity evidence. This report serves as a call to action highlighting an urgent need for measure development that represents diverse clinical contexts and support future interventions.

Vitamin D for the Prevention of Disease: An Endocrine Society Clinical Practice Guideline.

BACKGROUND: Numerous studies demonstrate associations between serum concentrations of 25-hydroxyvitamin D (25[OH]D) and a variety of common disorders, including musculoskeletal, metabolic, cardiovascular, malignant, autoimmune, and infectious diseases. Although a causal link between serum 25(OH)D concentrations and many disorders has not been clearly established, these associations have led to widespread supplementation with vitamin D and increased laboratory testing for 25(OH)D in the general population. The benefit-risk ratio of this increase in vitamin D use is not clear, and the optimal vitamin D intake and the role of testing for 25(OH)D for disease prevention remain uncertain. OBJECTIVE: To develop clinical guidelines for the use of vitamin D (cholecalciferol [vitamin D3] or ergocalciferol [vitamin D2]) to lower the risk of disease in individuals without established indications for vitamin D treatment or 25(OH)D testing. METHODS: A multidisciplinary panel of clinical experts, along with experts in guideline methodology and systematic literature review, identified and prioritized 14 clinically relevant questions related to the use of vitamin D and 25(OH)D testing to lower the risk of disease. The panel prioritized randomized placebo-controlled trials in general populations (without an established indication for vitamin D treatment or 25[OH]D testing), evaluating the effects of empiric vitamin D administration throughout the lifespan, as well as in select conditions (pregnancy and prediabetes). The panel defined "empiric supplementation" as vitamin D intake that (a) exceeds the Dietary Reference Intakes (DRI) and (b) is implemented without testing for 25(OH)D. Systematic reviews queried electronic databases for publications related to these 14 clinical questions. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology was used to assess the certainty of evidence and guide recommendations. The approach incorporated perspectives from a patient representative and considered patient values, costs and resources required, acceptability and feasibility, and impact on health equity of the proposed recommendations. The process to develop this clinical guideline did not use a risk assessment framework and was not designed to replace current DRI for vitamin D. RESULTS: The panel suggests empiric vitamin D supplementation for children and adolescents aged 1 to 18 years to prevent nutritional rickets and because of its potential to lower the risk of respiratory tract infections; for those aged 75 years and older because of its potential to lower the risk of mortality; for those who are pregnant because of its potential to lower the risk of preeclampsia, intra-uterine mortality, preterm birth, small-for-gestational-age birth, and neonatal mortality; and for those with high-risk prediabetes because of its potential to reduce progression to diabetes. Because the vitamin D doses in the included clinical trials varied considerably and many trial participants were allowed to continue their own vitamin D-containing supplements, the optimal doses for empiric vitamin D supplementation remain unclear for the populations considered. For nonpregnant people older than 50 years for whom vitamin D is indicated, the panel suggests supplementation via daily administration of vitamin D, rather than intermittent use of high doses. The panel suggests against empiric vitamin D supplementation above the current DRI to lower the risk of disease in healthy adults younger than 75 years. No clinical trial evidence was found to support routine screening for 25(OH)D in the general population, nor in those with obesity or dark complexion, and there was no clear evidence defining the optimal target level of 25(OH)D required for disease prevention in the populations considered; thus, the panel suggests against routine 25(OH)D testing in all populations considered. The panel judged that, in most situations, empiric vitamin D supplementation is inexpensive, feasible, acceptable to both healthy individuals and health care professionals, and has no negative effect on health equity. CONCLUSION: The panel suggests empiric vitamin D for those aged 1 to 18 years and adults over 75 years of age, those who are pregnant, and those with high-risk prediabetes. Due to the scarcity of natural food sources rich in vitamin D, empiric supplementation can be achieved through a combination of fortified foods and supplements that contain vitamin D. Based on the absence of supportive clinical trial evidence, the panel suggests against routine 25(OH)D testing in the absence of established indications. These recommendations are not meant to replace the current DRIs for vitamin D, nor do they apply to people with established indications for vitamin D treatment or 25(OH)D testing. Further research is needed to determine optimal 25(OH)D levels for specific health benefits.

Navigating Complexities: Vitamin D, Skin Pigmentation, and Race.

Vitamin D plays a critical role in many physiological functions, including calcium metabolism and musculoskeletal health. This commentary aims to explore the intricate relationships among skin complexion, race, and 25-hydroxyvitamin D (25[OH]D) levels, focusing on challenges the Endocrine Society encountered during clinical practice guideline development. Given that increased melanin content reduces 25(OH)D production in the skin in response to UV light, the guideline development panel addressed the potential role for 25(OH)D screening in individuals with dark skin complexion. The panel discovered that no randomized clinical trials have directly assessed vitamin D related patient-important outcomes based on participants' skin pigmentation, although race and ethnicity often served as presumed proxies for skin pigmentation in the literature. In their deliberations, guideline panel members and selected Endocrine Society leaders underscored the critical need to distinguish between skin pigmentation as a biological variable and race and ethnicity as socially determined constructs. This differentiation is vital to maximize scientific rigor and, thus, the validity of resulting recommendations. Lessons learned from the guideline development process emphasize the necessity of clarity when incorporating race and ethnicity into clinical guidelines. Such clarity is an essential step toward improving health outcomes and ensuring equitable healthcare practices.

Heterogeneity in Treatment Effect in Posttraumatic Stress Syndrome Trials: A Meta-Regression Analysis.

Objective: To evaluate the heterogeneity in treatment effect in posttraumatic stress disorder (PTSD) trials. Patients and Methods: We downloaded data from a publicly available repository that captured PTSD trials published from January 1988 through February 2023. We applied restricted maximum-likelihood random-effect meta-analyses and meta-regression to explore potential moderators of treatment effect including methodologic study features (risk of bias domains and control group response rate), characteristics of the population, and intervention features following the theme, intensity, and platform framework. Results: We included 199 PTSD trials that reported the outcomes of diagnosis resolution (122 trials, 8437 patients) and clinically meaningful improvement (133 trials, 9895 patients). Multiple treatments demonstrated effectiveness but with significant heterogeneity. Statistically significant moderators included risk of bias domains of randomization sequence and outcome measurement, control group response rate reflecting severity of PTSD in the enrolled population, and whether the psychotherapeutic approach was trauma focused (P values <0.05). There was no statistically significant effect for the frequency of treatments per week, format of the intervention (eg, individual vs group), duration of the intervention, or delivery method (in person vs not), (P values <0.05). Characteristics of the population such as sex, age, and military status did not appear to significantly affect the treatment effect (P values <0.05). Conclusion: Trauma focused psychotherapies should be considered the first-line intervention to induce remission. Several patient characteristics or treatment context did not modify the treatment effect, which allows tailoring care based on patient values, preferences and logistics.

Impact of Glucocorticoid Dose on Complete Response, Serious Infections, and Mortality During the Initial Therapy of Lupus Nephritis: A Systematic Review and Meta-Analysis of the Control Arms of Randomized Controlled Trials.

OBJECTIVE: Our objective was to evaluate the effect of glucocorticoid regimens on renal response, infections, and mortality among patients with lupus nephritis (LN). METHODS: We performed a systematic review and meta-analysis of the control arms of randomized clinical trials (RCTs). We included RCTs of biopsy-proven LN that used a protocolized regimen of glucocorticoids in combination with mycophenolic acid analogs or cyclophosphamide and reported the outcomes of complete response (CR), serious infections, and death. The starting dosage of glucocorticoids, tapering method, and administration of glucocorticoid pulses were abstracted. Meta-analysis of proportions, meta-regression, and subgroup meta-analysis were performed at 6 and 12 months for all outcomes. RESULTS: Fifty RCT arms (3,231 patients with LN) were included. The predicted rates of CR, serious infections, and death when starting on oral prednisone at 25 mg/day without pulses were 19.5% (95% confidence interval [CI] 7.3-31.5), 3.2% (95% CI 2.4-4.0), and 0.2% (95% CI 0.0-0.4), respectively. Starting on prednisone at 60 mg/day (without pulses) increased the rates to 34.6% (95% CI 16.9-52.3), 12.1% (95% CI 9.3-14.9), and 2.7% (95% CI 0.0-5.3), respectively. Adding glucocorticoid pulses increased the rates of CR and death but not serious infections. We observed a dose-response gradient between the initial glucocorticoid dosage and all the outcomes at six months after accounting for the administration of glucocorticoid pulses, underlying immunosuppressant, and baseline proteinuria. CONCLUSION: A higher exposure to glucocorticoids during the initial therapy of LN was associated with better renal outcomes at the cost of increased infections and death.

GRADE guidance 37: rating imprecision in a body of evidence on test accuracy.

OBJECTIVES: To provide guidance on rating imprecision in a body of evidence assessing the accuracy of a single test. This guide will clarify when Grading of Recommendations Assessment, Development and Evaluation (GRADE) users should consider rating down the certainty of evidence by one or more levels for imprecision in test accuracy. STUDY DESIGN AND SETTING: A project group within the GRADE working group conducted iterative discussions and presentations at GRADE working group meetings to produce this guidance. RESULTS: Before rating the certainty of evidence, GRADE users should define the target of their certainty rating. GRADE recommends setting judgment thresholds defining what they consider a very accurate, accurate, inaccurate, and very inaccurate test. These thresholds should be set after considering consequences of testing and effects on people-important outcomes. GRADE's primary criterion for judging imprecision in test accuracy evidence is considering confidence intervals (i.e., CI approach) of absolute test accuracy results (true and false, positive, and negative results in a cohort of people). Based on the CI approach, when a CI appreciably crosses the predefined judgment threshold(s), one should consider rating down certainty of evidence by one or more levels, depending on the number of thresholds crossed. When the CI does not cross judgment threshold(s), GRADE suggests considering the sample size for an adequately powered test accuracy review (optimal or review information size [optimal information size (OIS)/review information size (RIS)]) in rating imprecision. If the combined sample size of the included studies in the review is smaller than the required OIS/RIS, one should consider rating down by one or more levels for imprecision. CONCLUSION: This paper extends previous GRADE guidance for rating imprecision in single test accuracy systematic reviews and guidelines, with a focus on the circumstances in which one should consider rating down one or more levels for imprecision.

Hierarchical models that address measurement error are needed to evaluate the correlation between treatment effect and control group event rate.

OBJECTIVES: To apply a hierarchical model (HM) that addresses measurement error in regression of the treatment effect on the control group event rate (CR). We compare HM to weighted linear regression (WLR) which is subject to measurement error and mathematical coupling. STUDY DESIGN AND SETTING: We reviewed published HMs that address measurement error and implemented a Bayesian version in open-source code to facilitate adoption by meta-analysts. We compared WLR and HM across a very large convenience sample of meta-analyses published in the Cochrane Database of Systematic Reviews. RESULTS: We applied both approaches (WLR and an HM that addresses measurement error) to 3193 meta-analyses that included 33,071 studies (average 10.28 studies per meta-analysis). A statistically significant slope suggesting an association between the treatment effect and CR was demonstrated with both approaches in 568 (17.19%) meta-analyses, with neither approach in 2036 (63.77%) meta-analyses, only with WLS in 229 (7.17%) and only with HM in 360 (11.28%) meta-analyses. The majority of slopes was negative (WLR 85%, HM 83%). In the majority of cases, HM had wider confidence intervals (72.53%) and slopes farther from the null (64.77%). CONCLUSION: Approximately 28% of meta-analyses demonstrate a significant association between the treatment effect and CR when HM is used to address measurement error, which can suggest frequent lack of portability of the relative effect across baseline risks. User-friendly open-source code is provided to meta-analysts interested in exploring this association.

Noninvasive liver disease assessment to identify portal hypertension: Systematic and narrative reviews supporting the AASLD Practice Guideline.

BACKGROUND AND AIMS: Portal hypertension is a serious complication of cirrhosis, which leads to life-threatening complications. 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 availability, noninvasive liver disease assessments to assess portal pressure, especially clinically significant portal hypertension (CSPH), are needed. APPROACH AND RESULTS: We conducted a systematic review of Ovid MEDLINE(R) 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, 2022. We included only studies in English that examined ≥50 patients in single liver disease etiologies, which compared noninvasive 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. Outcomes included measures of diagnostic test accuracy. Additionally, a narrative review of studies not eligible for the systematic review is also provided. Nine studies with 2492 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 FIB-4 (54% sensitivity and 73% specificity) had low accuracy measures. Imaging-based tests (transient elastography and shear wave elastography detection of liver stiffness measurement [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 noninvasive liver disease assessment 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. CONCLUSIONS: While imaging-based noninvasive liver disease assessment appeared to have higher accuracy than blood-based tests to detect CSPH, only 9 studies fit the a priori established inclusion criteria for the systematic review. 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.

Imaging-based noninvasive 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, 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, shear wave elastography, or MRE for the identification of significant fibrosis (F2-4), advanced fibrosis (F3-4), or cirrhosis (F4), using histopathology as the 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 coinfection). 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. CONCLUSIONS: LSM from TE, shear wave elastography, and MRE shows 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.