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.

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.

Accuracy of blood-based biomarkers for staging liver fibrosis in chronic liver disease: A systematic review supporting the AASLD Practice Guideline.

BACKGROUND AND AIMS: Blood-based biomarkers have been proposed as an alternative to liver biopsy for non-invasive liver disease assessment (NILDA) in chronic liver disease (CLD). Our aims for this systematic review were to evaluate the diagnostic utility of selected blood-based tests either alone, or in combination, for identifying significant fibrosis (F2-4), advanced fibrosis (F3-4) and cirrhosis (F4), as compared to biopsy in CLD. APPROACH AND RESULTS: We included a comprehensive search of databases including Ovid MEDLINE(R), EMBASE, Cochrane Database, and Scopus through to April 2022. Two independent reviewers selected 286 studies with 103,162 patients. The most frequently identified studies included the simple aminotransferase-to-platelet ratio index (APRI) and fibrosis (FIB)-4 markers (with low-to-moderate risk of bias) in hepatitis B virus (HBV) and C virus (HCV), HIV-HCV/HBV co-infection, and nonalcoholic fatty liver disease (NAFLD). Positive (LR+) and negative (LR) likelihood ratios across direct and indirect biomarker tests for HCV and HBV for F2-4, F3-4, or F4 were 1.66-6.25 and 0.23-0.80, 1.89-5.24 and 0.12-0.64, and 1.32-7.15 and 0.15-0.86 respectively; LR+ and LR for NAFLD F2-4, F3-4 and F4 were 2-65-3.37 and 0.37-0.39, 2.25-6.76 and 0.07-0.87, and 3.90 and 0.15 respectively. Overall, proportional odds ratio indicated FIB-4 <1.45 was better than APRI <0.5 for F2-4. FIB-4 >3.25 was also better than APRI >1.5 for F3-4 and F4. There was limited data for combined tests. CONCLUSIONS: Blood-based biomarkers are associated with small-to-moderate change in pre-test probability for diagnosing F2-4, F3-4, and F4 in viral hepatitis, HIV-HCV co-infection, and NAFLD, with limited comparative or combination studies for other CLD.

Infectious Diseases Society of America Guidelines on the Diagnosis of COVID-19: Serologic Testing.

BACKGROUND: The role of serologic testing for SARS-CoV-2 has evolved during the pandemic as seroprevalence in global populations has increased. The Infectious Diseases Society of America (IDSA) convened an expert panel to perform a systematic review of the coronavirus disease 2019 (COVID-19) serology literature and construct updated best practice guidance related to SARS-CoV-2 serologic testing. This guideline is an update to the fourth in a series of rapid, frequently updated COVID-19 guidelines developed by IDSA. OBJECTIVE: To develop evidence-based recommendations and identify unmet research needs pertaining to the use of anti-SARS-CoV-2 antibody tests for diagnosis, decisions related to vaccination and administration of monoclonal antibodies or convalescent plasma in immunocompromised patients, and identification of a serologic correlate of immunity. METHODS: A multidisciplinary panel of infectious diseases clinicians, clinical microbiologists and experts in systematic literature reviewed, identified, and prioritized clinical questions related to the use of SARS-CoV-2 serologic tests. Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess the certainty of evidence and make testing recommendations. RESULTS: The panel recommends against serologic testing to diagnose SARS-CoV-2 infection in the first two weeks after symptom onset (strong recommendations, low certainty of evidence). Serologic testing should not be used to provide evidence of COVID-19 in symptomatic patients with a high clinical suspicion and repeatedly negative nucleic acid amplification test results (strong recommendation, very low certainty of evidence). Serologic testing may assist with the diagnosis of multisystem inflammatory syndrome in children (strong recommendation, very low certainty of evidence). To seek evidence for prior SARS-CoV-2 infection, the panel suggests testing for IgG, IgG/IgM, or total antibodies to nucleocapsid protein three to five weeks after symptom onset (conditional recommendation, low certainty of evidence). In individuals with previous SARS-CoV-2 infection or vaccination, we suggest against routine serologic testing given no demonstrated benefit to improving patient outcomes (conditional recommendation, very low certainty of evidence.) The panel acknowledges further that a negative spike antibody test may be a useful metric to identify immunocompromised patients who are candidates for immune therapy. CONCLUSIONS: The high seroprevalence of antibodies against SARS-CoV-2 worldwide limits the utility of detecting anti-SARS CoV-2 antibody. The certainty of available evidence supporting the use of serology for diagnosis was graded as very low to low. Future studies should use serologic assays calibrated to a common reference standard.

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.

Clinical presentation and outcomes in patients with antiphospholipid syndrome-associated adrenal hemorrhage. A multicenter cohort study and systematic literature review.

BACKGROUND: Adrenal hemorrhage (AH) can occur in patients with antiphospholipid Syndrome (APS). We aimed to characterize the clinical manifestations, treatments, and outcomes of patients presenting with APS-associated AH (APS-AH) through a retrospective cohort and a systematic literature review (SLR). METHODS: We performed a mixed-source approach combining a multicenter cohort with an SLR of patients with incident APS-AH. We included patients from Mayo Clinic and published cases with persistent positivity for antiphospholipid antibodies and presenting with AH, demonstrated by imaging or biopsy. We extracted demographics, clinical characteristics, laboratory findings, treatment strategies, and outcomes (primary adrenal insufficiency and mortality). We used Kaplan-Meier and Cox models for survival analysis. RESULTS: We included 256 patients in total, 61 (24%) from Mayo Clinic and 195 (76%) from the SLR. The mean age was 46.8 (SD 15.2) years, and 45% were female. 69% of patients had bilateral adrenal involvement and 64% presented adrenal insufficiency. The most common symptoms at presentation were abdominal pain in 79%, and nausea and vomiting 46%. Hyponatremia (77%) was the most common electrolyte abnormality. Factors associated with primary adrenal insufficiency were bilateral adrenal involvement at initial imaging (OR 3.73, CI; 95%, 1.47-9.46) and anticardiolipin IgG positivity (OR 3.80, CI; 95%, 1.30-11.09). The survival rate at five years was 82%. History of stroke was associated with 3.6-fold increase in mortality (HR 3.62, 95% CI; 1.33-9.85). CONCLUSION: AH is a severe manifestation of APS with increased mortality. Most patients developed permanent primary adrenal insufficiency, particularly those positive for anticardiolipin IgG and bilateral adrenal involvement.

Health-Related Factors Among Pilots in Aviation Accidents.

INTRODUCTION: Health-related factors can impact aviation safety. This study investigated the published, historical aviation accidents that have been investigated by the U.S. National Transportation Safety Board (NTSB) to understand medical conditions and medication use that have been determined to be causal to mishaps.METHODS: A two-part approach was adopted for this study: 1) a scoping review was conducted to provide an overview of the current medical literature addressing medical factors and flight safety; and 2) a comprehensive review of aviation accident reports from the NTSB database from January 2013 to October 2022.RESULTS: The literature review demonstrated that psychiatric, cardiovascular, and neurological medications were the major categories of medications reported in fatal aircraft accidents. Age was not found to be a risk factor. Review of the NTSB database demonstrated that, among 15,654 mishaps, medical factors were associated in 703 (4.5%) accidents. NTSB data showed that cardiovascular (1.3%), psychiatric (0.23%), and endocrine diseases (0.17%) were the most commonly reported diseases among pilots. In accident reports, cardiovascular medications (1.49%), sedating antihistamines (0.91%), and alcohol (0.70%) were the most commonly used medications at the time of the accidents.DISCUSSION: Health-related factors were a small yet likely underestimated proportion of the factors associated with accidents. Cardiovascular diseases and treatment were the most important factors. It is important to continue to investigate the association between health-related factors and the commission of mishaps.Zhu Y, Wolf ME, Alsibai RA, Abbas AS, Alsawaf Y, Saadi S, Farah MH, Wang Z, Murad MH. Health-related factors among pilots in aviation accidents. Aerosp Med Hum Perform. 2024; 95(2):79-83.

Outcomes From a Physician Health Center.

This retrospective cohort study describes the population of physicians seeking medical evaluation in a dedicated physician health center and identifies factors associated with needing practice restrictions. Participants had an initial evaluation between January 1, 2016, and December 31, 2022. We report personal and professional demographics and types of medical conditions in this cohort. An ordinal logistic regression analysis was used to identify factors associated with occupational outcomes. Physicians in a wide variety of specialties from 34 different states presented for evaluation of diverse medical problems. More than half of the participants presented with occupational concerns. The presence of a neurologic or psychiatric illness were the only factors associated with temporary or permanent restrictions. Physicians with medical conditions impacting their ability to practice have a professional obligation to obtain a thorough, objective medical evaluation. Such evaluations should support and protect patients, employers, and the physicians themselves.

Perceptions of Suicide among Pakistanis: Results of an Online Survey.

OBJECTIVE: In Pakistan, a predominantly Muslim country, information on the patterning of suicidal thoughts and behaviors, as well as associated public perceptions and opinions, is limited. We sought to advance knowledge on suicide and self-harm in Pakistan with a large, online survey. METHOD: Leveraging results from a twelve-item online survey (N = 5,157) circulated by the largest English language newspaper in Pakistan, we assessed personal experiences, opinions, and attitudes toward help-seeking in the context of suicide. We calculated proportions with 95% confidence intervals for endorsed responses and implemented binomial generalized linear models with odds ratios to assess differing response tendencies by age, gender, and urban/rural residence. RESULTS: Personal experiences related to suicide and self-harm as well as encounters in social circles were common. Mental illness tended to be recognized as a high likelihood contributor to suicide death over and above nonviolent interpersonal problems. Most considered suicide a way to escape pain, and few considered suicide to be immoral. Barriers to help-seeking included social deterrents, inaccessibility, and unaffordability. Women and youth emerged as higher risk groups, though the status of rural Pakistanis remained unclear. CONCLUSION: The survey provides a preliminary basis for considering the unique experiences and perspectives of the public in shaping suicide prevention and intervention efforts in Pakistan.

A voluntary online survey about suicide with over 5,000 responses from a cross-section of Pakistani populationResults illuminate popular opinions on suicide risk and mental health treatmentWomen and youth appear to be especially vulnerable warranting targeted intervention.

Interventions to Increase Cancer Screening Adherence Among Somali Immigrants in the US and Europe: A Systematic Review.

Cancer screening rates among immigrant and refugee populations in high income countries is significantly lower than native born populations. The objective of this study is to systematically review the effectiveness of interventions to improve screening adherence for breast, cervical and colorectal cancer among Somali immigrants. A literature search was conducted for the years 2000-2021 and eight studies met eligibility criteria. The following intervention components were found to increase adherence to cervical cancer screening: home HPV test, educational workshop for women and education for general practitioners. A patient navigator intervention was found to increase screening for breast cancer. Educational workshops motivated or increased knowledge regarding cancer screening for breast, cervical and colorectal cancer. However, most of the studies had limitations due to methodology with potential for introduction of bias. Therefore, future studies comparing effectiveness of specific intervention components to reduce disparities in cancer screening among Somali immigrants and refugees are encouraged.

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.

Peptidome comparison on the immune regulation effects of different casein fractions in a cyclophosphamide mouse model.

The protein composition of human milk plays a crucial role in infant formula milk powder formulation. Notably, significant differences exist between bovine casein and human milk casein. Previous studies have shown that casein hydrolysates could enhance immune function; however, gastrointestinal dyspepsia in infants affects the type and function of peptides. Therefore, the present study used peptidomics to sequence and analyze hydrolyzed peptides from different casein fractions. Additionally, animal experiments were conducted to assess the functionality of these casein fractions and elucidate their differences. The results revealed variations in peptide composition among the different casein fractions of formula milk powder. Interestingly, milk powder formulated with both ß- and κ-casein (BK) exhibited significant enrichment of peptides related to the immune system. Moreover, the BK group significantly alleviated immune organ damage in cyclophosphamide-treated mice and regulated serum levels of pro-inflammatory and anti-inflammatory factors. Furthermore, feeding different casein fractions influenced the intestinal microflora of cyclophosphamide-treated mice, with the BK group mitigating the changes caused by cyclophosphamide. In conclusion, the findings suggest that BK formula in milk powder has the potential to positively enhance immunity. This study provides a robust theoretical basis for human-emulsified formula milk powder development.

Rifampin Based Therapy for Patients With Staphylococcus aureus Native Vertebral Osteomyelitis: A Systematic Review and Meta-analysis.

BACKGROUND: Native vertebral osteomyelitis (NVO) caused by Staphylococcus aureus is associated with high risk of treatment failure and increased morbidity. The role of rifampin-based therapy for the treatment of this condition is controversial. The goal of this systematic review and meta-analysis is to explore the efficacy and safety of rifampin-based therapy for the treatment of S. aureus NVO. METHODS: We searched Cochrane, Embase, Medline, Scopus, and Web of Science databases for studies published up to May 2023, focusing on adults with NVO treated with or without rifampin-containing regimens. A random-effects model meta-analysis estimated relative risks and risk difference with 95% confidence intervals (CI). RESULTS: Thirteen studies (2 randomized controlled trials and 11 comparative cohort studies), comprising 244 patients with S. aureus NVO who received rifampin and 435 who did not, were analyzed. Meta-analysis showed that rifampin-based regimens were associated with lower risk of clinical failure (risk difference, -14%; 95% CI, -19% to -8%; P < .001; I2 = 0%; relative risk, 0.58; 95% CI, .37-.92, P = .02, I2 = 21%). Only 1 study reported on adverse events. All studies had a high or uncertain risk of bias, and the certainty of evidence was rated as very low. CONCLUSIONS: Adjunctive rifampin therapy might be associated with lower risk of S. aureus NVO treatment failure; however, the low certainty of evidence precludes drawing definitive conclusions that would alter clinical practice. A randomized trial is necessary to corroborate these findings.

The 2023 Society for Vascular Surgery, American Venous Forum, and American Vein and Lymphatic Society clinical practice guidelines for the management of varicose veins of the lower extremities. Part II: Endorsed by the Society of Interventional Radiology and the Society for Vascular Medicine.

The Society for Vascular Surgery, the American Venous Forum, and the American Vein and Lymphatic Society recently published Part I of the 2022 clinical practice guidelines on varicose veins. Recommendations were based on the latest scientific evidence researched following an independent systematic review and meta-analysis of five critical issues affecting the management of patients with lower extremity varicose veins, using the patients, interventions, comparators, and outcome system to answer critical questions. Part I discussed the role of duplex ultrasound scanning in the evaluation of varicose veins and treatment of superficial truncal reflux. Part II focuses on evidence supporting the prevention and management of varicose vein patients with compression, on treatment with drugs and nutritional supplements, on evaluation and treatment of varicose tributaries, on superficial venous aneurysms, and on the management of complications of varicose veins and their treatment. All guidelines were based on systematic reviews, and they were graded according to the level of evidence and the strength of recommendations, using the GRADE method. All ungraded Consensus Statements were supported by an extensive literature review and the unanimous agreement of an expert, multidisciplinary panel. Ungraded Good Practice Statements are recommendations that are supported only by indirect evidence. The topic, however, is usually noncontroversial and agreed upon by most stakeholders. The Implementation Remarks contain technical information that supports the implementation of specific recommendations. This comprehensive document includes a list of all recommendations (Parts I-II), ungraded consensus statements, implementation remarks, and best practice statements to aid practitioners with appropriate, up-to-date management of patients with lower extremity varicose veins.

Risk Factors for Early Fungal Disease in Solid Organ Transplant Recipients: A Systematic Review and Meta-analysis.

BACKGROUND: Invasive fungal infections are associated with high morbidity in solid organ transplant recipients. Risk factor modification may help with preventative efforts. The objective of this study was to identify risk factors for the development of fungal infections within the first year following solid organ transplant. METHODS: We searched for eligible articles through February 3, 2023. Studies published after January 1, 2001, that pertained to risk factors for development of invasive fungal infections in solid organ transplant were reviewed for inclusion. Of 3087 articles screened, 58 were included. Meta-analysis was conducted using a random-effects model to evaluate individual risk factors for the primary outcome of any invasive fungal infections and invasive candidiasis or invasive aspergillosis (when possible) within 1 y posttransplant. RESULTS: We found 3 variables with a high certainty of evidence and strong associations (relative effect estimate ≥ 2) to any early invasive fungal infections across all solid organ transplant groups: reoperation (odds ratio [OR], 2.92; confidence interval [CI], 1.79-4.75), posttransplant renal replacement therapy (OR, 2.91; CI, 1.87-4.51), and cytomegalovirus disease (OR, 2.97; CI, 1.78-4.94). Both posttransplant renal replacement therapy (OR, 3.36; CI, 1.78-6.34) and posttransplant cytomegalovirus disease (OR, 2.81; CI, 1.47-5.36) increased the odds of early posttransplant invasive aspergillosis. No individual variables could be pooled across groups for invasive candidiasis. CONCLUSIONS: Several common risk factors exist for the development of any invasive fungal infections in solid organ transplant recipients. Additional risk factors for invasive candidiasis and aspergillosis may be unique to the pathogen, transplanted organ, or both.

Risk Prediction Models for Hospital Mortality in General Medical Patients: A Systematic Review.

Objective: To systematically review contemporary prediction models for hospital mortality developed or validated in general medical patients. Methods: We screened articles in five databases, from January 1, 2010, through April 7, 2022, and the bibliography of articles selected for final inclusion. We assessed the quality for risk of bias and applicability using the Prediction Model Risk of Bias Assessment Tool (PROBAST) and extracted data using the Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies (CHARMS) checklist. Two investigators independently screened each article, assessed quality, and extracted data. Results: From 20,424 unique articles, we identified 15 models in 8 studies across 10 countries. The studies included 280,793 general medical patients and 19,923 hospital deaths. Models included 7 early warning scores, 2 comorbidities indices, and 6 combination models. Ten models were studied in all general medical patients (general models) and 7 in general medical patients with infection (infection models). Of the 15 models, 13 were developed using logistic or Poisson regression and 2 using machine learning methods. Also, 4 of 15 models reported on handling of missing values. None of the infection models had high discrimination, whereas 4 of 10 general models had high discrimination (area under curve >0.8). Only 1 model appropriately assessed calibration. All models had high risk of bias; 4 of 10 general models and 5 of 7 infection models had low concern for applicability for general medical patients. Conclusion: Mortality prediction models for general medical patients were sparse and differed in quality, applicability, and discrimination. These models require hospital-level validation and/or recalibration in general medical patients to guide mortality reduction interventions.