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Few young people with type 1 diabetes (T1D) meet glucose targets. Continuous glucose monitoring improves glycemia, but access is not equitable. We prospectively assessed the impact of a systematic and equitable digital-health-team-based care program implementing tighter glucose targets (HbA1c < 7%), early technology use (continuous glucose monitoring starts <1 month after diagnosis) and remote patient monitoring on glycemia in young people with newly diagnosed T1D enrolled in the Teamwork, Targets, Technology, and Tight Control (4T Study 1). Primary outcome was HbA1c change from 4 to 12 months after diagnosis; the secondary outcome was achieving the HbA1c targets. The 4T Study 1 cohort (36.8% Hispanic and 35.3% publicly insured) had a mean HbA1c of 6.58%, 64% with HbA1c < 7% and mean time in the range (70-180 mg dl -1 ) of 68% at 1 year after diagnosis. Clinical implementation of the 4T Study 1 met the prespecified primary outcome and improved glycemia without unexpected serious adverse events. The strategies in the 4T Study 1 can be used to implement systematic and equitable care for individuals with T1D and translate to care for other chronic diseases. ClinicalTrials.gov registration: NCT04336969 ., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: Recent therapeutic advances and screening technologies have improved survival among patients with lung cancer, who are now at high risk of developing second primary lung cancer (SPLC). Recently, an SPLC risk-prediction model (called SPLC-RAT) was developed and validated using data from population-based epidemiological cohorts and clinical trials, but real-world validation has been lacking. The predictive performance of SPLC-RAT was evaluated in a hospital-based cohort of lung cancer survivors., Methods: The authors analyzed data from 8448 ever-smoking patients diagnosed with initial primary lung cancer (IPLC) in 1997-2006 at Mayo Clinic, with each patient followed for SPLC through 2018. The predictive performance of SPLC-RAT and further explored the potential of improving SPLC detection through risk model-based surveillance using SPLC-RAT versus existing clinical surveillance guidelines., Results: Of 8448 IPLC patients, 483 (5.7%) developed SPLC over 26,470 person-years. The application of SPLC-RAT showed high discrimination area under the receiver operating characteristics curve: 0.81). When the cohort was stratified by a 10-year risk threshold of ≥5.6% (i.e., 80th percentile from the SPLC-RAT development cohort), the observed SPLC incidence was significantly elevated in the high-risk versus low-risk subgroup (13.1% vs. 1.1%, p < 1 × 10 -6 ). The risk-based surveillance through SPLC-RAT (≥5.6% threshold) outperformed the National Comprehensive Cancer Network guidelines with higher sensitivity (86.4% vs. 79.4%) and specificity (38.9% vs. 30.4%) and required 20% fewer computed tomography follow-ups needed to detect one SPLC (162 vs. 202)., Conclusion: In a large, hospital-based cohort, the authors validated the predictive performance of SPLC-RAT in identifying high-risk survivors of SPLC and showed its potential to improve SPLC detection through risk-based surveillance., Plain Language Summary: Lung cancer survivors have a high risk of developing second primary lung cancer (SPLC). However, no evidence-based guidelines for SPLC surveillance are available for lung cancer survivors. Recently, an SPLC risk-prediction model was developed and validated using data from population-based epidemiological cohorts and clinical trials, but real-world validation has been lacking. Using a large, real-world cohort of lung cancer survivors, we showed the high predictive accuracy and risk-stratification ability of the SPLC risk-prediction model. Furthermore, we demonstrated the potential to enhance efficiency in detecting SPLC using risk model-based surveillance strategies compared to the existing consensus-based clinical guidelines, including the National Comprehensive Cancer Network., (© 2023 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Introduction: Diabetic ketoacidosis (DKA) at diagnosis is associated with short- and long-term complications. We assessed the relationship between DKA status and hemoglobin A1c (A1c) levels in the first year following type 1 diabetes (T1D) diagnosis. Research Design and Methods: The Pilot Teamwork, Targets, Technology, and Tight Control (4T) study offered continuous glucose monitoring to youth with T1D within 1 month of diagnosis. A1c levels were compared between historical ( n  = 271) and Pilot 4T ( n  = 135) cohorts stratified by DKA status at diagnosis (DKA: historical = 94, 4T = 67 versus without DKA: historical = 177, 4T = 68). A1c was evaluated using locally estimated scatter plot smoothing. Change in A1c from 4 to 12 months postdiagnosis was evaluated using a linear mixed model. Results: Median age was 9.7 (interquartile range [IQR]: 6.6, 12.7) versus 9.7 (IQR: 6.8, 12.7) years, 49% versus 47% female, 44% versus 39% non-Hispanic White in historical versus Pilot 4T. In historical and 4T cohorts, DKA at diagnosis demonstrated higher A1c at 6 (0.5% [95% confidence interval (CI): 0.21-0.79; P  < 0.01] and 0.38% [95% CI: 0.02-0.74; P  = 0.04], respectively), and 12 months (0.62% [95% CI: -0.06 to 1.29; P  = 0.07] and 0.39% [95% CI: -0.32 to 1.10; P  = 0.29], respectively). The highest % time in range (TIR; 70-180 mg/dL) was seen between weeks 15-20 (69%) versus 25-30 (75%) postdiagnosis for youth with versus without DKA in Pilot 4T, respectively. Conclusions: Pilot 4T improved A1c outcomes versus the historical cohort, but those with DKA at diagnosis had persistently elevated A1c throughout the study and intensive diabetes management did not mitigate this difference. DKA prevention at diagnosis may translate into better glycemic outcomes in the first-year postdiagnosis. Clinical Trial Registration: clinicaltrials.gov: NCT04336969.

Purpose: We aimed to use machine learning (ML) algorithms with clinical, lab, and imaging data as input to predict various outcomes in traumatic brain injury (TBI) patients., Methods: In this retrospective study, blood samples were analyzed for glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase L1 (UCH-L1). The non-contrast head CTs were reviewed by two neuroradiologists for TBI common data elements (CDE). Three outcomes were designed to predict: discharged or admitted for further management (prediction 1), deceased or not deceased (prediction 2), and admission only, prolonged stay, or neurosurgery performed (prediction 3). Five ML models were trained. SHapley Additive exPlanations (SHAP) analyses were used to assess the relative significance of variables., Results: Four hundred forty patients were used to predict predictions 1 and 2, while 271 patients were used in prediction 3. Due to Prediction 3's hospitalization requirement, deceased and discharged patients could not be utilized. The Random Forest model achieved an average accuracy of 1.00 for prediction 1 and an accuracy of 0.99 for prediction 2. The Random Forest model achieved a mean accuracy of 0.93 for prediction 3. Key features were extracranial injury, hemorrhage, UCH-L1 for prediction 1; The Glasgow Coma Scale, age, GFAP for prediction 2; and GFAP, subdural hemorrhage volume, and pneumocephalus for prediction 3, per SHAP analysis., Conclusion: Combining clinical and laboratory parameters with non-contrast CT CDEs allowed our ML models to accurately predict the designed outcomes of TBI patients. GFAP and UCH-L1 were among the significant predictor variables, demonstrating the importance of these biomarkers., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Motivation: Providing a dynamic assessment of prognosis is essential for improved personalized medicine. The landmark model for survival data provides a potentially powerful solution to the dynamic prediction of disease progression. However, a general framework and a flexible implementation of the model that incorporates various outcomes, such as competing events, have been lacking. We present an R package, dynamicLM, a user-friendly tool for the landmark model for the dynamic prediction of survival data under competing risks, which includes various functions for data preparation, model development, prediction and evaluation of predictive performance., Implementation: dynamicLM as an R package., General Features: The package includes options for incorporating time-varying covariates, capturing time-dependent effects of predictors and fitting a cause-specific landmark model for time-to-event data with or without competing risks. Tools for evaluating the prediction performance include time-dependent area under the ROC curve, Brier Score and calibration., Availability: Available on GitHub [https://github.com/thehanlab/dynamicLM]., (© The Author(s) 2023. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Importance: The revised 2021 US Preventive Services Task Force (USPSTF) guidelines for lung cancer screening have been shown to reduce disparities in screening eligibility and performance between African American and White individuals vs the 2013 guidelines. However, potential disparities across other racial and ethnic groups in the US remain unknown. Risk model-based screening may reduce racial and ethnic disparities and improve screening performance, but neither validation of key risk prediction models nor their screening performance has been examined by race and ethnicity., Objective: To validate and recalibrate the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial 2012 (PLCOm2012) model-a well-established risk prediction model based on a predominantly White population-across races and ethnicities in the US and evaluate racial and ethnic disparities and screening performance through risk-based screening using PLCOm2012 vs the USPSTF 2021 criteria., Design, Setting, and Participants: In a population-based cohort design, the Multiethnic Cohort Study enrolled participants in 1993-1996, followed up through December 31, 2018. Data analysis was conducted from April 1, 2022, to May 19. 2023. A total of 105 261 adults with a smoking history were included., Exposures: The 6-year lung cancer risk was calculated through recalibrated PLCOm2012 (ie, PLCOm2012-Update) and screening eligibility based on a 6-year risk threshold greater than or equal to 1.3%, yielding similar eligibility as the USPSTF 2021 guidelines., Outcomes: Predictive accuracy, screening eligibility-incidence (E-I) ratio (ie, ratio of the number of eligible to incident cases), and screening performance (sensitivity, specificity, and number needed to screen to detect 1 lung cancer)., Results: Of 105 261 participants (60 011 [57.0%] men; mean [SD] age, 59.8 [8.7] years), consisting of 19 258 (18.3%) African American, 27 227 (25.9%) Japanese American, 21 383 (20.3%) Latino, 8368 (7.9%) Native Hawaiian/Other Pacific Islander, and 29 025 (27.6%) White individuals, 1464 (1.4%) developed lung cancer within 6 years from enrollment. The PLCOm2012-Update showed good predictive accuracy across races and ethnicities (area under the curve, 0.72-0.82). The USPSTF 2021 criteria yielded a large disparity among African American individuals, whose E-I ratio was 53% lower vs White individuals (E-I ratio: 9.5 vs 20.3; P < .001). Under the risk-based screening (PLCOm2012-Update 6-year risk ≥1.3%), the disparity between African American and White individuals was substantially reduced (E-I ratio: 15.9 vs 18.4; P < .001), with minimal disparities observed in persons of other minoritized groups, including Japanese American, Latino, and Native Hawaiian/Other Pacific Islander. Risk-based screening yielded superior overall and race and ethnicity-specific performance to the USPSTF 2021 criteria, with higher overall sensitivity (67.2% vs 57.7%) and lower number needed to screen (26 vs 30) at similar specificity (76.6%)., Conclusions: The findings of this cohort study suggest that risk-based lung cancer screening can reduce racial and ethnic disparities and improve screening performance across races and ethnicities vs the USPSTF 2021 criteria.

Purpose: This study aimed to assess and externally validate the performance of a deep learning (DL) model for the interpretation of non-contrast computed tomography (NCCT) scans of patients with suspicion of traumatic brain injury (TBI)., Methods: This retrospective and multi-reader study included patients with TBI suspicion who were transported to the emergency department and underwent NCCT scans. Eight reviewers, with varying levels of training and experience (two neuroradiology attendings, two neuroradiology fellows, two neuroradiology residents, one neurosurgery attending, and one neurosurgery resident), independently evaluated NCCT head scans. The same scans were evaluated using the version 5.0 of the DL model icobrain tbi. The establishment of the ground truth involved a thorough assessment of all accessible clinical and laboratory data, as well as follow-up imaging studies, including NCCT and magnetic resonance imaging, as a consensus amongst the study reviewers. The outcomes of interest included neuroimaging radiological interpretation system (NIRIS) scores, the presence of midline shift, mass effect, hemorrhagic lesions, hydrocephalus, and severe hydrocephalus, as well as measurements of midline shift and volumes of hemorrhagic lesions. Comparisons using weighted Cohen's kappa coefficient were made. The McNemar test was used to compare the diagnostic performance. Bland-Altman plots were used to compare measurements., Results: One hundred patients were included, with the DL model successfully categorizing 77 scans. The median age for the total group was 48, with the omitted group having a median age of 44.5 and the included group having a median age of 48. The DL model demonstrated moderate agreement with the ground truth, trainees, and attendings. With the DL model's assistance, trainees' agreement with the ground truth improved. The DL model showed high specificity (0.88) and positive predictive value (0.96) in classifying NIRIS scores as 0-2 or 3-4. Trainees and attendings had the highest accuracy (0.95). The DL model's performance in classifying various TBI CT imaging common data elements was comparable to that of trainees and attendings. The average difference for the DL model in quantifying the volume of hemorrhagic lesions was 6.0 mL with a wide 95% confidence interval (CI) of - 68.32 to 80.22, and for midline shift, the average difference was 1.4 mm with a 95% CI of - 3.4 to 6.2., Conclusion: While the DL model outperformed trainees in some aspects, attendings' assessments remained superior in most instances. Using the DL model as an assistive tool benefited trainees, improving their NIRIS score agreement with the ground truth. Although the DL model showed high potential in classifying some TBI CT imaging common data elements, further refinement and optimization are necessary to enhance its clinical utility., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Previous studies comparing percutaneous coronary intervention (PCI) with coronary artery bypass grafting (CABG) in patients with multivessel coronary disease not involving the left main have shown significantly lower rates of death, myocardial infarction (MI), or stroke after CABG. These studies did not routinely use current-generation drug-eluting stents or fractional flow reserve (FFR) to guide PCI., Methods: FAME 3 (Fractional Flow Reserve versus Angiography for Multivessel Evaluation) is an investigator-initiated, multicenter, international, randomized trial involving patients with 3-vessel coronary artery disease (not involving the left main coronary artery) in 48 centers worldwide. Patients were randomly assigned to receive FFR-guided PCI using zotarolimus drug-eluting stents or CABG. The prespecified key secondary end point of the trial reported here is the 3-year incidence of the composite of death, MI, or stroke., Results: A total of 1500 patients were randomized to FFR-guided PCI or CABG. Follow-up was achieved in >96% of patients in both groups. There was no difference in the incidence of the composite of death, MI, or stroke after FFR-guided PCI compared with CABG (12.0% versus 9.2%; hazard ratio [HR], 1.3 [95% CI, 0.98-1.83]; P =0.07). The rates of death (4.1% versus 3.9%; HR, 1.0 [95% CI, 0.6-1.7]; P =0.88) and stroke (1.6% versus 2.0%; HR, 0.8 [95% CI, 0.4-1.7]; P =0.56) were not different. MI occurred more frequently after PCI (7.0% versus 4.2%; HR, 1.7 [95% CI, 1.1-2.7]; P =0.02)., Conclusions: At 3-year follow-up, there was no difference in the incidence of the composite of death, MI, or stroke after FFR-guided PCI with current-generation drug-eluting stents compared with CABG. There was a higher incidence of MI after PCI compared with CABG, with no difference in death or stroke. These results provide contemporary data to allow improved shared decision-making between physicians and patients with 3-vessel coronary artery disease., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT02100722., Competing Interests: Disclosures Dr Pijls receives research funding from Abbott, has consulting relationships with Abbott and Opsens, and has stock or stock options with ASML, General Electric, HeartFlow, Hexacath, and Philips. Dr Mansour has consulting relationships with Abbott Vascular, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Novartis, Pfizer, and Servier Affaires, and received a research grant from Opsens Inc and Abbott Vascular. Dr Kala has a consulting relationship with Boston Scientific, Medtronic, and Servier Affaires, and receives honoraria from AstraZeneca and Bayer. Dr Angeras receives research funding from Abbott Vascular and AstraZeneca and has a consulting relationship with Abbott Vascular and Boston Scientific. Dr Miner has a consulting relationship with Abbott, Amgen, Astra Zeneca, Bayer, Boehringer, Novartis, Opsens, Pfizer, and Servier Affaires Medicales. Dr Engstrøm has a consulting relationship with Abbott Vascular, Bayer, and Novo Nordisk. Dr Christiansen has a consulting relationship with Abbott Vascular and has received research grants from Abbott Vascular. Dr Tonino has received research grants from Biosensors and Opsens. Dr Reardon has a consulting relationship with Boston Scientific and W.L. Gore & Associates. Dr Otsuki has received research grants from the Uehara Memorial Foundation, Abbott, Medtronic, Boston Scientific, and Terumo. Dr Kobayashi has a consulting relationship with Abbott Vascular. Dr Hlatky has a consulting relationship with Blue Cross and Blue Shield and research support from HeartFlow. Dr Mahaffey has received research grants or contracts from the American Heart Association, Apple, Inc, Bayer, California Institute Regenerative Medicine, Eidos, Ferring, Gilead, Google (Verily), Idorsia, Johnson & Johnson, Luitpold, PAC-12, Precordior, and Sanifit; has provided consulting or other services for Amgen, Applied Therapeutics, AstraZeneca, Bayer, CSL Behring, Elsevier, FibroGen, Inova, Johnson & Johnson, Lexicon, MyoKardia, Novartis, Novo Nordisk, Otsuka, PhaseBio, Portola, Quidel, Sanofi, and Theravance; and has equity in Precordior. Dr Yeung has a consulting relationship with Medtronic. Dr De Bruyne has an institutional consulting relationship with Boston Scientific, Abbott Vascular, CathWorks, Siemens, GE Healthcare, and Coroventis Research; receives institutional research grants from Abbott Vascular, Coroventis Research, CathWorks, and Boston Scientific; and holds minor equities in Philips, Siemens, GE Healthcare, CathWorks, Edwards Life Sciences, HeartFlow, Opsens, Celyad, Xenter, Medyria, Bayer, and Sanofi. Dr Fearon receives research funding from Abbott, Medtronic, and Boston Scientific and has a consulting relationship with Siemens and CathWorks and stock options with HeartFlow. The other authors report no conflicts of interest.

Introduction: Traumatic brain injury (TBI) is a major public health concern in the U.S. Recommendations for patients admitted in the emergency department (ED) to receive head computed tomography (CT) scan are currently guided by various clinical decision rules., Objective: To compare how a blood biomarker approach compares with clinical decision rules in terms of predicting a positive head CT in adult patients suspected of TBI., Methods: We retrospectively identified patients transported to our emergency department and underwent a noncontrast head CT due to suspicion of TBI and who had blood samples available. Published thresholds for serum and plasma glial fibrillary acidic protein (GFAP), ubiquitin carboxyl-terminal hydrolase-L1 (UCH-L1), and serum S100β were used to make CT recommendations. These blood biomarker-based recommendations were compared to those achieved under widely used clinical head CT decision rules (Canadian, New Orleans, NEXUS II, and ACEP Clinical Policy)., Results: Our study included 463 patients, of which 122 (26.3%) had one or more abnormalities presenting on head CT. Individual blood biomarkers achieved high negative predictive value (NPV) for abnormal head CT findings (88%-98%), although positive predictive value (PPV) was consistently low (25%-42%). A composite biomarker-based decision rule (GFAP+UCH-L1)'s NPV of 100% and PPV of 29% were comparable or better than those achieved under the clinical decision rules., Conclusion: Blood biomarkers perform at least as well as clinical rules in terms of selecting TBI patients for head CT and may be easier to implement in the clinical setting. A prospective study is necessary to validate this approach.

Background: Small bowel bacterial overgrowth (SBBO) is a common, but difficult to diagnose and treat, problem in pediatric short bowel syndrome (SBS). Lack of clinical consensus criteria and unknown sensitivity and specificity of bedside diagnosis makes research on this potential SBS disease modifier challenging. The objective of this research was to describe clinical care of SBBO among international intestinal rehabilitation and nutrition support (IR&NS) providers treating patients with SBS., Methods: A secure, confidential, international, electronic survey of IR&NS practitioners was conducted between March 2021 and May 2021. All analyses were conducted in the R statistical computing framework, version 4.0., Results: Sixty percent of respondents agreed and 0% strongly disagreed that abdominal pain, distension, emesis, diarrhea, and malodorous stool, were attributable to SBBO. No more than 20% of respondents strongly agreed and no more than 40% agreed that any sign or symptom was specific for SBBO. For a first-time diagnosis, 31 practitioners agreed with use of a 7-day course of a single antibiotic, with a majority citing grade 5 evidence to inform their decisions (case series, uncontrolled studies, or expert opinion). The most common first antibiotic used to treat a new onset SBBO was metronidazole, and rifaximin was the second most commonly used. One hundred percent of respondents reported they would consider a consensus algorithm for SBBO, even if the algorithm may be divergent from their current practice., Conclusion: SBBO practice varies widely among experienced IR&NS providers. Development of a clinical consensus algorithm may help standardize care to improve research and care of this complex problem and to identify risks and benefits of chronic antibiotic use in SBS., (© 2022 American Society for Parenteral and Enteral Nutrition.)

The objective of this work was to analyze the relationships between traumatic brain injury (TBI) on computed tomographic (CT) imaging and blood concentration of glial fibrillary acidic protein (GFAP), ubiquitin C-terminal hydrolase-L1 (UCH-L1), and S100B. This prospective cohort study involved 644 TBI patients referred to Stanford Hospital's Emergency Department between November 2015 and April 2017. Plasma and serum samples of 462 patients were analyzed for levels of GFAP, UCH-L1, and S100B. Glial neuronal ratio (GNR) was calculated as the ratio between GFAP and UCH-L1 concentrations. Admission head CT scans were reviewed for TBI imaging common data elements, and performance of biomarkers for identifying TBI was assessed via area under the receiver operating characteristic curve (ROC). We also dichotomized biomarkers at established thresholds and estimated standard measures of classification accuracy. We assessed the ability of GFAP, UCH-L1, and GNR to discriminate small and large/diffuse lesions based on CT imaging using an ROC analysis. In our cohort of mostly mild TBI patients, GFAP was significantly more accurate in detecting all types of acute brain injuries than UCH-L1 in terms of area under the curve (AUC) values ( p  < 0.001), and also compared with S100B ( p  < 0.001). UCH-L1 and S100B had similar performance (comparable AUC values, p  = 0.342). Sensitivity exceeded 0.8 for each biomarker across all different types of TBI injuries, and no significant differences were observed by type of injury. There was a significant difference between GFAP and GNR in distinguishing between small lesions and large/diffuse lesions in all injuries ( p  = 0.004, p  = 0.007). In conclusion, GFAP, UCH-L1, and S100B show high sensitivity and negative predictive values for all types of TBI lesions on head CT. A combination of negative blood biomarkers (GFAP and UCH-L1) in a patient suspected of TBI may be used to safely obviate the need for a head CT scan. GFAP is a promising indicator to discriminate between small and large/diffuse TBI lesions.

During the COVID-19 pandemic, fewer in-person clinic visits resulted in fewer point-of-care (POC) HbA1c measurements. In this sub-study, we assessed the performance of alternative glycemic measures that can be obtained remotely, such as HbA1c home kits and Glucose Management Indicator (GMI) values from Dexcom Clarity. Home kit HbA1c ( n = 99), GMI, ( n = 88), and POC HbA1c ( n = 32) were collected from youth with T1D (age 9.7 ± 4.6 years). Bland-Altman analyses and Lin's concordance correlation coefficient ( ρ c ) were used to characterize the agreement between paired HbA1c measures. Both the HbA1c home kit and GMI showed a slight positive bias (mean difference 0.18% and 0.34%, respectively) and strong concordance with POC HbA1c ( ρ c = 0.982 [0.965, 0.991] and 0.823 [0.686, 0.904], respectively). GMI showed a slight positive bias (mean difference 0.28%) and fair concordance ( ρ c = 0.750 [0.658, 0.820]) to the HbA1c home kit. In conclusion, the strong concordance of GMI and home kits to POC A1c measures suggest their utility in telehealth visits assessments. Although these are not candidates for replacement, these measures can facilitate telehealth visits, particularly in the context of other POC HbA1c measurements from an individual., Competing Interests: Conflicts of Interest: D.P.Z. has received speaker’s honoraria from Medtronic Diabetes, Ascensia Diabetes, and Insulet Canada; and research support from the Helmsley Charitable Trust and ISPAD-JDRF Research Fellowship. She is also on the Dexcom Advisory board. A.B.K. has served as an external consultant for Roche Diagnostics and received research funding from Siemens Healthcare Diagnostics and Kyowa Kirin Pharmaceutical Development. A.B.K. has also received speaker honoraria from the National Kidney Foundation and the American Kidney Fund. All funding is unrelated to this manuscript. D.M.M. has had research support from the National Kidney Foundation, Juvenile Diabetes Research Foundation, NSF, and the Helmsley Charitable Trust and his institution has had research support from Medtronic, Dexcom, Insulet, Bigfoot Biomedical, Tandem, and Roche. D.M.M. has consulted for Abbott, Aditxt, the Helmsley Charitable Trust, Lifescan, Mannkind, Sanofi, Novo Nordisk, Eli Lilly, Medtronic, Insulet, Dompe, and Biospex. The remaining authors have no conflicts of interest.

Background and Purpose: Dual-energy virtual NCCT has the potential to replace conventional NCCT to detect early ischemic changes in acute ischemic stroke. In this study, we evaluated whether virtual NCCT is noninferior compared with standard linearly blended NCCT, a surrogate of conventional NCCT, regarding the detection of early ischemic changes with ASPECTS., Materials and Methods: Adult patients who presented with suspected acute ischemic stroke and who underwent dual-energy NCCT and CTA and brain MR imaging within 48 hours were included. Standard linearly blended images were reconstructed to match a conventional NCCT. Virtual NCCT images were reconstructed from CTA. ASPECTS was evaluated on conventional NCCT, virtual NCCT, and DWI, which served as the reference standard. Agreement between CT assessments and the reference standard was evaluated with the Lin concordance correlation coefficient. Noninferiority was assessed with bootstrapped estimates of the differences in ASPECTS between conventional and virtual NCCT with 95% CIs., Results: Of the 193 included patients, 100 patients (52%) had ischemia on DWI. Compared with the reference standard, the ASPECTS concordance correlation coefficient for conventional and virtual NCCT was 0.23 (95% CI, 0.15-0.32) and 0.44 (95% CI, 0.33-0.53), respectively. The difference in the concordance correlation coefficient between virtual and conventional NCCT was 0.20 (95% CI, 0.01-0.39) and did not cross the prespecified noninferiority margin of -0.10., Conclusions: Dual-energy virtual NCCT is noninferior compared with conventional NCCT for the detection of early ischemic changes with ASPECTS., (© 2022 by American Journal of Neuroradiology.)

Background: Fetal echocardiography is a major diagnostic imaging modality for prenatal detection of critical congenital heart disease. Diagnostic accuracy is essential for appropriate planning of delivery and neonatal care. The relationship between study comprehensiveness and diagnostic error is not well understood. The aim of this study was to test the hypothesis that high fetal echocardiographic study comprehensiveness would be associated with low diagnostic error. Diagnostic errors were defined as discordant fetal and postnatal diagnoses and were further characterized by potential causes, contributors, and clinical significance., Methods: Fetal echocardiographic examinations performed at Lucile Packard Children's Hospital in which fetuses with critical congenital heart disease were anticipated to require postnatal surgical or catheter intervention in the first year of life were identified using the fetal cardiology program database. For this cohort, initial fetal echocardiographic images were reviewed and given a fetal echocardiography comprehensiveness score (FECS). Fetal diagnoses obtained from initial fetal echocardiographic images and reports were compared with postnatal diagnoses confirmed by transthoracic echocardiography and other imaging studies and/or surgery to determine diagnostic error. The relationship between FECS and diagnostic error was evaluated using multivariable logistic regression., Results: Of the 304 initial fetal echocardiographic studies, diagnostic error (discrepant diagnosis, false negative, or false positive) occurred in 92 cases (30.3%). FECS was not associated with diagnostic error, but low FECS (≤80% complete) was associated with false negatives and procedural/conditional (P < .001) and technical (P = .005) contributors compared with high FECS (>80% complete). Cognitive factors made up the largest proportion of contributors to error., Conclusions: The comprehensiveness of fetal echocardiographic studies was not related to diagnostic error. The most common contributors to error were cognitive factors. Echocardiography laboratories can work to mitigate preventable cognitive error through quality improvement initiatives., (Copyright © 2022 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Background: Previous studies have shown that quality of life improves after coronary revascularization more so after coronary artery bypass grafting (CABG) than after percutaneous coronary intervention (PCI). This study aimed to evaluate the effect of fractional flow reserve guidance and current generation, zotarolimus drug-eluting stents on quality of life after PCI compared with CABG., Methods: The FAME 3 trial (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation) is a multicenter, international trial including 1500 patients with 3-vessel coronary artery disease who were randomly assigned to either CABG or fractional flow reserve-guided PCI. Quality of life was measured using the European Quality of Life-5 Dimensions (EQ-5D) questionnaire at baseline and 1 and 12 months. The Canadian Cardiovascular Class angina grade and working status were assessed at the same time points and at 6 months. The primary objective was to compare EQ-5D summary index at 12 months. Secondary end points included angina grade and work status., Results: The EQ-5D summary index at 12 months did not differ between the PCI and CABG groups (difference, 0.001 [95% CI, -0.016 to 0.017]; P =0.946). The trajectory of EQ-5D during the 12 months differed ( P <0.001) between PCI and CABG: at 1 month, EQ-5D was 0.063 (95% CI, 0.047 to 0.079) higher in the PCI group. A similar trajectory was found for the EQ (EuroQol) visual analogue scale. The proportion of patients with Canadian Cardiovascular Class 2 or greater angina at 12 months was 6.2% versus 3.1% (odds ratio, 2.5 [95% CI, 0.96-6.8]), respectively, in the PCI group compared with the CABG group. A greater percentage of younger patients (<65 years old) were working at 12 months in the PCI group compared with the CABG group (68% versus 57%; odds ratio, 3.9 [95% CI, 1.7-8.8])., Conclusions: In the FAME 3 trial, quality of life after fractional flow reserve-guided PCI with current generation drug-eluting stents compared with CABG was similar at 1 year. The rate of significant angina was low in both groups and not significantly different. The trajectory of improvement in quality of life was significantly better after PCI, as was working status in those <65 years old., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT02100722.

Background: In 2021, the US Preventive Services Task Force (USPSTF) revised its lung cancer screening guidelines to expand screening eligibility. We evaluated screening sensitivities and racial and ethnic disparities under the 2021 USPSTF criteria vs alternative risk-based criteria in a racially and ethnically diverse population., Methods: In the Multiethnic Cohort, we evaluated the proportion of ever-smoking lung cancer cases eligible for screening (ie, screening sensitivity) under the 2021 USPSTF criteria and under risk-based criteria through the PLCOm2012 model (6-year risk ≥1.51%). We also calculated the screening disparity (ie, absolute sensitivity difference) for each of 4 racial or ethnic groups (African American, Japanese American, Latino, Native Hawaiian) vs White cases., Results: Among 5900 lung cancer cases, 43.3% were screen eligible under the 2021 USPSTF criteria. Screening sensitivities varied by race and ethnicity, with Native Hawaiian (56.7%) and White (49.6%) cases attaining the highest sensitivities and Latino (37.3%), African American (38.4%), and Japanese American (40.0%) cases attaining the lowest. Latino cases had the greatest screening disparity vs White cases at 12.4%, followed by African American (11.2%) and Japanese American (9.6%) cases. Under risk-based screening, the overall screening sensitivity increased to 75.7%, and all racial and ethnic groups had increased sensitivities (54.5%-91.9%). Whereas the screening disparity decreased to 5.1% for African American cases, it increased to 28.6% for Latino cases and 12.8% for Japanese American cases., Conclusions: In the Multiethnic Cohort, racial and ethnic disparities decreased but persisted under the 2021 USPSTF lung cancer screening guidelines. Risk-based screening through PLCOm2012 may increase screening sensitivities and help to reduce disparities in some, but not all, racial and ethnic groups. Further optimization of risk-based screening strategies across diverse populations is needed., (© The Author(s) 2022. Published by Oxford University Press.)

Context: Youth with type 1 diabetes (T1D) do not meet glycated hemoglobin A1c (HbA1c) targets., Objective: This work aimed to assess HbA1c outcomes in children with new-onset T1D enrolled in the Teamwork, Targets, Technology and Tight Control (4T) Study., Methods: HbA1c levels were compared between the 4T and historical cohorts. HbA1c differences between cohorts were estimated using locally estimated scatter plot smoothing (LOESS). The change from nadir HbA1c (month 4) to 12 months post diagnosis was estimated by cohort using a piecewise mixed-effects regression model accounting for age at diagnosis, sex, ethnicity, and insurance type. We recruited 135 youth with newly diagnosed T1D at Stanford Children's Health. Starting July 2018, all youth within the first month of T1D diagnosis were offered continuous glucose monitoring (CGM) initiation and remote CGM data review was added in March 2019. The main outcomes measure was HbA1c., Results: HbA1c at 6, 9, and 12 months post diagnosis was lower in the 4T cohort than in the historic cohort (-0.54% to -0.52%, and -0.58%, respectively). Within the 4T cohort, HbA1c at 6, 9, and 12 months post diagnosis was lower in those patients with remote monitoring than those without (-0.14%, -0.18% to -0.14%, respectively). Multivariable regression analysis showed that the 4T cohort experienced a significantly lower increase in HbA1c between months 4 and 12 (P < .001)., Conclusion: A technology-enabled, team-based approach to intensified new-onset education involving target setting, CGM initiation, and remote data review statistically significantly decreased HbA1c in youth with T1D 12 months post diagnosis., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Patients with three-vessel coronary artery disease have been found to have better outcomes with coronary-artery bypass grafting (CABG) than with percutaneous coronary intervention (PCI), but studies in which PCI is guided by measurement of fractional flow reserve (FFR) have been lacking., Methods: In this multicenter, international, noninferiority trial, patients with three-vessel coronary artery disease were randomly assigned to undergo CABG or FFR-guided PCI with current-generation zotarolimus-eluting stents. The primary end point was the occurrence within 1 year of a major adverse cardiac or cerebrovascular event, defined as death from any cause, myocardial infarction, stroke, or repeat revascularization. Noninferiority of FFR-guided PCI to CABG was prespecified as an upper boundary of less than 1.65 for the 95% confidence interval of the hazard ratio. Secondary end points included a composite of death, myocardial infarction, or stroke; safety was also assessed., Results: A total of 1500 patients underwent randomization at 48 centers. Patients assigned to undergo PCI received a mean (±SD) of 3.7±1.9 stents, and those assigned to undergo CABG received 3.4±1.0 distal anastomoses. The 1-year incidence of the composite primary end point was 10.6% among patients randomly assigned to undergo FFR-guided PCI and 6.9% among those assigned to undergo CABG (hazard ratio, 1.5; 95% confidence interval [CI], 1.1 to 2.2), findings that were not consistent with noninferiority of FFR-guided PCI (P = 0.35 for noninferiority). The incidence of death, myocardial infarction, or stroke was 7.3% in the FFR-guided PCI group and 5.2% in the CABG group (hazard ratio, 1.4; 95% CI, 0.9 to 2.1). The incidences of major bleeding, arrhythmia, and acute kidney injury were higher in the CABG group than in the FFR-guided PCI group., Conclusions: In patients with three-vessel coronary artery disease, FFR-guided PCI was not found to be noninferior to CABG with respect to the incidence of a composite of death, myocardial infarction, stroke, or repeat revascularization at 1 year. (Funded by Medtronic and Abbott Vascular; FAME 3 ClinicalTrials.gov number, NCT02100722.)., (Copyright © 2021 Massachusetts Medical Society.)

Background: With advancing therapeutics, lung cancer (LC) survivors are rapidly increasing in number. Although mounting evidence suggests LC survivors have high risk of second primary lung cancer (SPLC), there is no validated prediction model available for clinical use to identify high-risk LC survivors for SPLC., Methods: Using data from 6325 ever-smokers in the Multiethnic Cohort (MEC) study diagnosed with initial primary lung cancer (IPLC) in 1993-2017, we developed a prediction model for 10-year SPLC risk after IPLC diagnosis using cause-specific Cox regression. We evaluated the model's clinical utility using decision curve analysis and externally validated it using 2 population-based data-Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) and National Lung Screening Trial (NLST)-that included 2963 and 2844 IPLC (101 and 93 SPLC cases), respectively., Results: Over 14 063 person-years, 145 (2.3%) ever-smoking IPLC patients developed SPLC in MEC. Our prediction model demonstrated a high predictive accuracy (Brier score = 2.9, 95% confidence interval [CI] = 2.4 to 3.3) and discrimination (area under the receiver operating characteristics [AUC] = 81.9%, 95% CI = 78.2% to 85.5%) based on bootstrap validation in MEC. Stratification by the estimated risk quartiles showed that the observed SPLC incidence was statistically significantly higher in the 4th vs 1st quartile (9.5% vs 0.2%; P < .001). Decision curve analysis indicated that in a wide range of 10-year risk thresholds from 1% to 20%, the model yielded a larger net-benefit vs hypothetical all-screening or no-screening scenarios. External validation using PLCO and NLST showed an AUC of 78.8% (95% CI = 74.6% to 82.9%) and 72.7% (95% CI = 67.7% to 77.7%), respectively., Conclusions: We developed and validated a SPLC prediction model based on large population-based cohorts. The proposed prediction model can help identify high-risk LC patients for SPLC and can be incorporated into clinical decision making for SPLC surveillance and screening., (© The Author(s) 2021. Published by Oxford University Press.)

Objective: The CyberKnife (CK) has emerged as an effective frameless and noninvasive method for treating a myriad of neurosurgical conditions. Here, the authors conducted an extensive retrospective analysis and review of the literature to elucidate the trend for CK use in the management paradigm for common neurosurgical diseases at their institution., Methods: A literature review (January 1990-June 2019) and clinical review (January 1999-December 2018) were performed using, respectively, online research databases and the Stanford Research Repository of patients with intracranial and spinal lesions treated with CK at Stanford. For each disease considered, the coefficient of determination (r2) was estimated as a measure of CK utilization over time. A change in treatment modality was assessed using a t-test, with statistical significance assessed at the 0.05 alpha level., Results: In over 7000 patients treated with CK for various brain and spinal lesions over the past 20 years, a positive linear trend (r2 = 0.80) in the system's use was observed. CK gained prominence in the management of intracranial and spinal arteriovenous malformations (AVMs; r2 = 0.89 and 0.95, respectively); brain and spine metastases (r2 = 0.97 and 0.79, respectively); benign tumors such as meningioma (r2 = 0.85), vestibular schwannoma (r2 = 0.76), and glomus jugulare tumor (r2 = 0.89); glioblastoma (r2 = 0.54); and trigeminal neuralgia (r2 = 0.81). A statistically significant difference in the change in treatment modality to CK was observed in the management of intracranial and spinal AVMs (p < 0.05), and while the treatment of brain and spine metastases, meningioma, and glioblastoma trended toward the use of CK, the change in treatment modality for these lesions was not statistically significant., Conclusions: Evidence suggests the robust use of CK for treating a wide range of neurological conditions.

Objective: To compare assessment of collaterals by single-phase computed tomography (CT) angiography (CTA) and CT perfusion-derived 3-phase CTA, multiphase CTA and temporal maximum-intensity projection (tMIP) images to digital subtraction angiography (DSA), and relate collateral assessments to clinical outcome in patients with acute ischemic stroke., Methods: Consecutive acute ischemic stroke patients who underwent CT perfusion, CTA, and DSA before thrombectomy with occlusion of the internal carotid artery, the M1 or the M2 segments were included. Two observers assessed all CT images and one separate observer assessed DSA (reference standard) with static and dynamic (modified American Society of Interventional and Therapeutic Neuroradiology) collateral grading methods. Interobserver agreement and concordance were quantified with Cohen-weighted κ and concordance correlation coefficient, respectively. Imaging assessments were related to clinical outcome (modified Rankin Scale, ≤ 2)., Results: Interobserver agreement (n = 101) was 0.46 (tMIP), 0.58 (3-phase CTA), 0.67 (multiphase CTA), and 0.69 (single-phase CTA) for static assessments and 0.52 (3-phase CTA) and 0.54 (multiphase CTA) for dynamic assessments. Concordance correlation coefficient (n = 80) was 0.08 (3-phase CTA), 0.09 (single-phase CTA), and 0.23 (multiphase CTA) for static assessments and 0.10 (3-phase CTA) and 0.27 (multiphase CTA) for dynamic assessments. Higher static collateral scores on multiphase CTA (odds ratio [OR], 1.7; 95% confidence interval [CI], 1.1-2.7) and tMIP images (OR, 2.0; 95% CI, 1.1-3.4) were associated with modified Rankin Scale of 2 or less as were higher modified American Society of Interventional and Therapeutic Neuroradiology scores on 3-phase CTA (OR, 1.5; 95% CI, 1.1-2.2) and multiphase CTA (OR, 1.7; 95% CI, 1.1-2.6)., Conclusions: Concordance between assessments on CT and DSA was poor. Collateral status evaluated on 3-phase CTA and multiphase CTA, but not on DSA, was associated with clinical outcome.

The ICU Liberation (ABCDEF) Bundle can help to improve care and outcomes for ICU patients, but bundle implementation is far from universal. Understanding how ICU organizational characteristics influence bundle implementation could inform quality improvement efforts. We surveyed all hospitals in Michigan with adult ICUs to determine whether organizational characteristics were associated with bundle implementation and to determine the level of agreement between ICU physician and nurse leaders around ICU organizational characteristics and bundle implementation., Design: We surveyed ICU physician and nurse leaders, assessing their safety culture, ICU team collaboration, and work environment. Using logistic and linear regression models, we compared these organizational characteristics to bundle element implementation, and also compared physician and nurse leaders' perceptions about organizational characteristics and bundle implementation., Setting: All ( n = 72) acute care hospitals with adult ICUs in Michigan., Subjects: ICU physician and nurse leader pairs from each hospital's main ICU., Interventions: We developed, pilot-tested, and deployed an electronic survey to all subjects over a 3 month period in 2016., Results: Results from 73 surveys (28 physicians, 45 nurses, 60% hospital response rate) demonstrated significant variation in hospital and ICU size and type, organizational characteristics, and physician/nurse perceptions of ICU organization and bundle implementation. We found that a robust safety culture and collaborative work environment that uses checklists to facilitate team communication are strongly associated with bundle implementation. There is also a significant dose-response effect between safety culture, a collaborative work environment, and overall bundle implementation., Conclusions: We identified several specific ICU practices that can facilitate ABCDEF Bundle implementation. Our results can be used to develop effective bundle implementation strategies that leverage safety culture, interprofessional collaboration, and routine checklist use in ICUs to improve bundle implementation and performance., Competing Interests: Dr. Barr has received speaking honoraria from the Society of Critical Care Medicine and the Ohio Hospital Association and is a Scientific Advisor for Medasense Biometrics and Masimo. The remaining authors have disclosed that they do not have any potential conflicts of interest.

Background: Protease-activated receptor-1 antagonism by vorapaxar could facilitate arteriovenous fistula maturation but may increase bleeding risk., Objective: The primary objective of the Vorapaxar Study for Maturation of arteriovenous fistula for Hemodialysis Access (VorapAccess) was to determine if vorapaxar improves arteriovenous fistula functional maturation in patients with end-stage renal disease., Methods: VorapAccess was a randomized, placebo-controlled, double-blind pilot trial comparing 2.5 mg vorapaxar per day with placebo for twelve weeks starting on day two after arteriovenous fistula creation. The primary outcome was time to functional maturation defined as successful cannulation for six hemodialysis sessions within three weeks. The planned sample size was 50 participants. The study was terminated early after withdrawal of planned financial support. Given the small number of randomized patients, we performed descriptive analyses without inference testing., Results: A total of 13 participants were randomly allocated study drug (six vorapaxar and seven placebo). The median age was 56 years and seven participants (54%) were female. The median (minimum-maximum) days to functional maturation were 169 (77-287) days in the vorapaxar group and 145 (48-198) days in the placebo group. Six of the 13 (46%) participants had arteriovenous fistula functional maturation within 180 days; two of six (33%) in the vorapaxar group and four of seven (57%) in the placebo group. There was one bleeding event in the placebo group., Conclusion: Fewer than half of participants had functional maturation within 180 days after surgery, suggesting a major need for agents or strategies that enhance arteriovenous fistula maturation.

The purpose of this study was to determine the interobserver variability among providers of different specialties and levels of experience across five established computed tomography (CT) scoring systems for acute traumatic brain injury (TBI). One hundred cases were selected at random from a retrospective population of adult patients transported to our emergency department and subjected to a non-contrast head CT due to suspicion of TBI. Eight neuroradiologists and neurosurgeons in trainee (residents and fellows) and attending roles independently scored each non-contrast head CT scan on the Marshall, Rotterdam, Helsinki, Stockholm, and NeuroImaging Radiological Interpretation System (NIRIS) head CT scales. Interobserver variability of scale scores-overall and by specialty and level of training-was quantified using the intraclass correlation coefficient (ICC), and agreement with respect to National Institutes of Health Common Data Elements (NIH CDEs) was assessed using Cohen's kappa. All CT severity scoring systems showed high interobserver agreement as evidenced by high ICCs, ranging from 0.75-0.89. For all scoring systems, neuroradiologists (ICC range from 0.81-0.94) tended to have higher interobserver agreement than neurosurgeons (ICC range from 0.63-0.76). For all scoring systems, attendings (ICC range from 0.76-0.89) had similar interobserver agreement to trainees (ICC range from 0.73-0.89). Agreement with respect to NIH CDEs was high for ascertaining presence/absence of hemorrhage, skull fracture, and mass effect, with estimated kappa statistics of least 0.89. Acute TBI CT scoring systems demonstrate high interobserver agreement. These results provide scientific rigor for future use of these systems for the classification of acute TBI.

Objective: Cavernous sinus meningioma (CSM) can affect visual function and require expeditious treatment to prevent permanent visual loss. Authors of this retrospective study sought to determine the factors associated with visual functional outcomes in CSM patients treated with surgery, stereotactic radiosurgery (SRS), or stereotactic radiation therapy (SRT), alone or in combination., Methods: Consecutive patients with CSM who had presented at an academic tertiary care hospital from 2000 to 2018 were identified through retrospective chart review. Visual function-visual eye deficit (VED), optic disc (OD) appearance, intraocular pressure (IOP), and extraocular movement (EOM)-was assessed before and after treatment for CSM. VED with visual acuity (VA) ≤ 20/200 and visual field defect ≥ -11 dB, pale OD appearance in the ipsilateral or contralateral eye, increased ipsilateral IOP, and/or EOM restriction were defined as a poor visual functional outcome. Multivariable logistic regression was used to evaluate the associations between pretreatment visual functional assessment and posttreatment visual outcomes., Results: The study cohort included 44 patients (73% female; median age 55 years), with a median clinical follow-up of 14 months. Ipsilateral VED improved, remained stable, or worsened, respectively, in 0%, 33.4%, and 66.6% of the patients after subtotal resection (STR) alone; in 52.6%, 31.6%, and 15.8% after STR plus radiation treatment; in 28.5%, 43.0%, and 28.5% after gross-total resection (GTR) alone; and in 56.3%, 43.7%, and 0% after radiation treatment (SRS or SRT) alone. Contralateral VED remained intact in all the patients after STR alone and those with radiation treatment (SRS or SRT) alone; however, it improved, remained stable, or worsened in 10.5%, 84.2%, and 5.3% after STR plus radiation treatment and in 43.0%, 28.5%, and 28.5% after GTR alone. EOM remained intact, fully recovered, remained stable, and worsened, respectively, in 0%, 50%, 50%, and 0% of the patients after STR alone; in 36.8%, 47.4%, 15.8%, and 0% of the patients after STR with radiation treatment; in 57.1%, 0%, 28.6%, and 14.3% of the patients after GTR alone; and in 56.2%, 37.5%, 6.3%, and 0% of the patients after radiation treatment (SRS or SRT) alone. In multivariable analyses adjusted for age, tumor volume, and treatment modality, initial ipsilateral poor VED (OR 10.1, 95% CI 1.05-97.2, p = 0.04) and initial ipsilateral pale OD appearance (OR 21.1, 95% CI 1.6-270.5, p = 0.02) were associated with poor ipsilateral VED posttreatment. Similarly, an initial pale OD appearance (OR 15.7, 95% CI 1.3-199.0, p = 0.03), initial poor VED (OR 21.7, 95% CI 1.2-398.6, p = 0.03), and a higher IOP in the ipsilateral eye (OR 55.3, 95% CI 1.7-173.9, p = 0.02) were associated with an ipsilateral pale OD appearance posttreatment. Furthermore, a higher initial ipsilateral IOP (OR 35.9, 95% CI 3.3-400.5, p = 0.004) was indicative of a higher IOP in the ipsilateral eye posttreatment. Finally, initial restricted EOM was indicative of restricted EOM posttreatment (OR 20.6, 95% CI 18.7-77.0, p = 0.02)., Conclusions: Pretreatment visual functional assessment predicts visual outcomes in patients with CSM and can be used to identify patients at greater risk for vision loss.

Purpose: The aim of this study was to determine whether participation in Radiology Support, Communication and Alignment Network (R-SCAN) results in a reduction of inappropriate imaging in a wide range of real-world clinical environments., Methods: This quality improvement study used imaging data from 27 US academic and private practices that completed R-SCAN projects between January 25, 2015, and August 8, 2018. Each project consisted of baseline, educational (intervention), and posteducational phases. Baseline and posteducational imaging cases were rated as high, medium, or low value on the basis of validated ACR Appropriateness Criteria®. Four cohorts were generated: a comprehensive cohort that included all eligible practices and three topic-specific cohorts that included practices that completed projects of specific Choosing Wisely topics (pulmonary embolism, adnexal cyst, and low back pain). Changes in the proportion of high-value cases after R-SCAN intervention were assessed for each cohort using generalized estimating equation logistic regression, and changes in the number of low-value cases were analyzed using Poisson regression., Results: Use of R-SCAN in the comprehensive cohort resulted in a greater proportion of high-value imaging cases (from 57% to 79%; odds ratio, 2.69; 95% confidence interval, 1.50-4.86; P = .001) and 345 fewer low-value cases after intervention (incidence rate ratio, 0.45; 95% confidence interval, 0.29-0.70; P < .001). Similar changes in proportion of high-value cases and number of low-value cases were found for the pulmonary embolism, adnexal cyst, and low back pain cohorts., Conclusions: R-SCAN participation was associated with a reduced likelihood of inappropriate imaging and is thus a promising tool to enhance the quality of patient care and promote wise use of health care resources., (Copyright © 2020 American College of Radiology. All rights reserved.)

Background: Understanding factors that impact tissue oxygen extraction may guide red blood cell (RBC) transfusion decision making in preterm infants. Our objective was to assess the influence of enteral feeding and anemia on cerebral and mesenteric oxygen saturation (Csat and Msat) and fractional tissue oxygen extraction (cFTOE and mFTOE) over the entire time course of RBC transfusion., Study Design and Methods: Preterm, very low-birth-weight infants receiving RBC transfusions at a single center were enrolled. Near-infrared spectroscopy sensors measured Csat and Msat levels from an hour before transfusion to 24 hours after. During this period, changes in Csat, Msat, cFTOE, and mFTOE were described, and their association with enteral feeding status and pretransfusion degree of anemia were assessed using generalized estimating equations., Results: RBC transfusion data from 31 preterm infants were included. Infants receiving enteral feeds exhibited lower pretransfusion Msat. Infants with pretransfusion hematocrit greater than 30% exhibited higher pretransfusion Csat and lower pretransfusion cFTOE. Such differences in baseline measurements persisted through 24 hours after transfusion. However, no statistically significant differences in oxygenation measures over time by enteral feeding or anemia status were identified., Conclusion: Compared to NPO, enteral feeding was associated with lower Msat; anemia (hematocrit ≤30%) was associated with lower Csat and higher cFTOE. Over the time course of RBC transfusion, trajectories of Csat, Msat, cFTOE and mFTOE did not differ by enteral feeding or anemia status., (© 2020 AABB.)

Objectives: To assess the reliability and effect of exercise on sideline dynamic visual performance measures of ocular-motor function using a portable visual assessment system (EYE-SYNC®)., Design: Prospective cohort study., Methods: Healthy student athletes, ages 18-25 years, performed eye-tracking six times-three times consecutively prior to and after practice-using EYE-SYNC® goggles. Ocular-motor performance was assessed by calculating five gaze error outcomes between target position and actual gaze position to inform dynamic visual synchronization. We assessed reliability by calculating the intraclass correlation coefficient (ICC) for each outcome (we defined the standard deviation of tangential error (SDTE) as our primary outcome) and calculated differences in mean pre- and post-practice scores., Results: ICCs for the SDTE score were 0.86 (95% confidence interval, CI: 0.82-0.9) and 0.88 (0.84-0.91) at pre- and post-practice, respectively. 133 (89%) and 135 (90%) of 150 athletes had at least one measurement at pre- and post-practice, respectively. 117 (78%) and 122 (81%) athletes had more than one SDTE score at pre- and post-practice, respectively. The absolute mean (SD) differences between pre- and post-practice mean scores ranged from 0.02 (0.05) for horizontal gain to 0.1 (0.5) for SDTE., Conclusions: We observed high ICC scores indicating excellent reliability of visual synchronization measurements, suggesting that one measurement would be sufficient. Most athletes had similar scores before and after practice, indicating little change in visual performance following exercise. EYE-SYNC® goggles have the potential for use in obtaining objective visual performance measures of ocular-motor function for sideline assessment of concussion and return to play decisions., (Copyright © 2019 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.)

Rationale & Objective: Vascular access type (arteriovenous fistula [AVF] vs arteriovenous graft [AVG] vs central venous catheter [CVC]) associates with clinical outcomes in patients with end-stage kidney disease undergoing hemodialysis. Whether a similar association exists with outcomes after kidney transplantation is unknown. We hypothesized that AVGs would associate with worse outcomes, perhaps owing to persistent subclinical inflammation., Study Design: Retrospective cohort study., Setting & Participants: Using US registry data merged with electronic health records of a large dialysis organization (2006-2011), we selected patients receiving a first-ever kidney transplant after undergoing more than 30 days of hemodialysis., Exposure: Hemodialysis access used during the patient's last pretransplantation hemodialysis session., Outcomes: Patients were followed up from kidney transplantation for all-cause mortality, kidney allograft loss from any cause, and allograft loss not from death., Analytical Approach: Time-to-event analysis including Kaplan-Meier plots and Cox proportional hazards regression estimated cause-specific HRs and 95% CIs., Results: Among 9,291 patients who underwent kidney transplantation between 2006 and 2011, a total of 65.3% used an AVF, 20.4% used an AVG, and 14.3% used a CVC for hemodialysis before transplantation. Multivariable regression models adjusted for demographic variables, comorbid conditions, transplant characteristics, and laboratory parameters identified no independent associations between vascular access type and all-cause mortality (HR AVG , 1.13 [95% CI, 0.97-1.33]; HR CVC , 1.00 [95% CI, 0.83-1.21]). Similarly, AVG and CVC use were not independently associated with all-cause allograft loss compared with AVF use (HR AVG , 1.13 [95% CI, 1.00-1.28]; HR CVC , 1.12 [95% CI, 0.96-1.29]). CVC use was associated with 30% higher risk for allograft loss from causes other than death compared with AVF use (HR CVC , 1.30 [95% CI, 1.06-1.57]), but AVGs were not (HR AVG , 1.17 [95% CI, 0.98-1.39])., Limitations: Nonrandomized exposure leading to potential residual confounding., Conclusions: No association was found for AVG use before kidney transplantation with mortality, all-cause allograft loss, and allograft loss from all causes other than death, compared with AVF use. The association of CVC use with allograft loss from causes other than death requires further investigation., (© 2019 The Authors.)

Purpose: The aim of the study was to refine and validate the NeuroImaging Radiological Interpretation System (NIRIS), which was developed to predict management and clinical outcome based on noncontrast head computerized tomography findings in patients suspected of acute traumatic brain injury (TBI)., Methods: We assessed the performance of the NIRIS score in a prospective, single-center cohort of patients suspected of TBI (n = 648) and compared the performance of NIRIS with that of the Marshall and Rotterdam scoring systems. We also revised components of the NIRIS scoring system using decision tree methodologies implemented on pooled data from the retrospective and prospective studies (N = 1190)., Results: The NIRIS performed similarly to the Marshall and Rotterdam scoring systems in predicting mortality and markedly better in terms of predicting more granular elements of disposition and management of TBI patients, such as admission, follow-up imaging, intensive care unit stay, and neurosurgical procedures. The revised NIRIS classification correctly predicted disposition and outcome in 91.2% (331/363) after excluding patients with other major extracranial traumatic injuries or intracranial nontraumatic injuries., Conclusions: The present study further demonstrates the predictive value of NIRIS in guiding standardized clinical management and decision-making regarding treatment options for TBI patients.

Background: Telemedicine holds great promise for changing healthcare delivery. While telemedicine has been used significantly in the direct-to-consumer setting, the use of telemedicine in a preventive primary care setting is not well studied. Introduction: ClickWell Care (CWC) is the first known implementation of a technology-enabled primary care model. We wanted to quantify healthcare utilization of primary care by patient characteristics and modality of care delivery. Materials and Methods: Our study population included those who completed a visit to a CWC clinic between January 1, 2015 and September 30, 2015. We compared patients based on utilization of CWCs in-person and virtual visits across the following domains: patient demographics, distance from clinic, responses to a Health Risk Assessment, and top 10 conditions treated. Results: Thousand two hundred seven patients completed a visit with a CWC physician in 2015. Nearly three-quarters of our patients were ≤40 years and sex was significantly different ( p  = 0.015) between visit cohorts. The greatest representation of men (47%) was seen in the virtual-only cohort. Patients' proximity to the clinic was also significantly different across visit cohorts ( p  = 0.018) with 44% of in-person-only and 34% of virtual-only patients living within 5 miles of Stanford Hospital. Discussion: We found men were more likely to engage in virtual-only care. Young patients are willing to accept virtual care although many prefer to complete an in-person visit first. Conclusions: Our findings suggest that a "bricks-and-clicks" care model where telemedicine is supported by a brick-and-mortar location may be an effective way to leverage telemedicine to deliver primary care.

Due to limited and conflicting data in pediatric patients, long-term routine surveillance endomyocardial biopsy (RSB) in pediatric heart transplant (HT) remains controversial. We sought to characterize the rate of positive RSB and determine factors associated with RSB-detected rejection. Records of patients transplanted at a single institution from 1995 to 2015 with >2 year of post-HT biopsy data were reviewed for RSB-detected rejections occurring >2 year post-HT. We illustrated the trajectory of significant rejections (ISHLT Grade ≥3A/2R) among total RSB performed over time and used multivariable logistic regression to model the association between time and risk of rejection. We estimated Kaplan-Meier freedom from rejection rates by patient characteristics and used the log-rank test to assess differences in rejection probabilities. We identified the best-fitting Cox proportional hazards regression model. In 140 patients, 86% did not have any episodes of significant RSB-detected rejection >2 year post-HT. The overall empirical rate of RSB-detected rejection >2 year post-HT was 2.9/100 patient-years. The percentage of rejection among 815 RSB was 2.6% and remained stable over time. Years since transplant remained unassociated with rejection risk after adjusting for patient characteristics (OR = 0.98; 95% CI 0.78-1.23; P = 0.86). Older age at HT was the only factor that remained significantly associated with risk of RSB-detected rejection under multivariable Cox analysis (P = 0.008). Most pediatric patients did not have RSB-detected rejection beyond 2 years post-HT, and the majority of those who did were older at time of HT. Indiscriminate long-term RSB in pediatric heart transplant should be reconsidered given the low rate of detected rejection., (© 2018 Wiley Periodicals, Inc.)

The purpose of the study was to develop an outcome-based NeuroImaging Radiological Interpretation System (NIRIS) for patients with acute traumatic brain injury (TBI) that would standardize the interpretation of noncontrast head computer tomography (CT) scans and consolidate imaging findings into ordinal severity categories that would inform specific patient management actions and that could be used as a clinical decision support tool. We retrospectively identified all patients transported to our emergency department by ambulance or helicopter for whom a trauma alert was triggered per established criteria and who underwent a noncontrast head CT because of suspicion of TBI, between November 2015 and April 2016. Two neuroradiologists reviewed the noncontrast head CTs and assessed the TBI imaging common data elements (CDEs), as defined by the National Institutes of Health (NIH). Using descriptive statistics and receiver operating characteristic curve analyses to identify imaging characteristics and associated thresholds that best distinguished among outcomes, we classified patients into five mutually exclusive categories: 0-discharge from the emergency department; 1-follow-up brain imaging and/or admission; 2-admission to an advanced care unit; 3-neurosurgical procedure; 4-death up to 6 months after TBI. Sensitivity of NIRIS with respect to each patient's true outcome was then evaluated and compared with that of the Marshall and Rotterdam scoring systems for TBI. In our cohort of 542 patients with TBI, NIRIS was developed to predict discharge (182 patients), follow-up brain imaging/admission (187 patients), need for advanced care unit (151 patients), neurosurgical procedures (10 patients), and death (12 patients). NIRIS performed similarly to the Marshall and Rotterdam scoring systems in terms of predicting death. We developed an interpretation system for neuroimaging using the CDEs that informs specific patient management actions and could be used as a clinical decision support tool for patients with TBI. Our NIRIS classification, with evidence-based grouping of the CDEs into actionable categories, will need to be validated in different TBI populations.

Background: Controversies exist over the appropriate definition for peri-procedural myocardial infarction (PPMI) and its association with mortality. This study aims to evaluate one-year survival following percutaneous coronary intervention (PCI) and the association of different definitions of PPMI with survival among patients with stable angina (SA) or acute coronary syndrome (ACS) in the contemporary era., Methods: We used data from the CHAMPION PLATFORM and CHAMPION PCI trials of patients undergoing PCI and conducted univariable and multivariable Cox proportional hazard regression models to evaluate mortality risk during the first year after PCI. A blinded events committee adjudicated suspected PPMI defined by biomarker elevations ≥3× the upper limit of normal (ULN) or new Q-waves. We further analyzed PPMI by the magnitude of CK-MB elevation ([a] 3 to <5× ULN, [b] 5 to <10× ULN, [c] ≥10× ULN) or by the 2 nd universal definition of myocardial infarction (UDMI CK-MB ) excluding patients with evidence of myocardial infarction (MI) prior to PCI., Results: Of 13,968 patients, 11% initially presented with SA, and 89% with ACS. One-year mortality was 3.4% (SA: 1.5%; ACS: 3.6%). PPMI occurred in 6.3% of the patients (3 to <5× ULN: 2.5%; 5 to <10× ULN: 2.1%; ≥10× ULN: 1.6%; UDMI CK-MB : 2.7%). After multivariable adjustment, a significantly higher risk of one-year mortality was observed for patients with PPMI compared with patients without PPMI (HR 2.35 [1.74-3.18], p < 0.001; 3 to <5× ULN: 1.55 [0.92-2.62], p = 0.10; 5 to <10× ULN: 1.22 [0.67-2.20], p = 0.52; ≥10× ULN: 4.78 [3.06-7.47], p < 0.001; UDMI CK-MB : 2.19 [1.29-3.73], p = 0.004)., Conclusion: PPMI occurred in 6.3% of the patients and was associated with increased risk of death within one year. Survival was not significantly impacted by PPMI if defined by periprocedural CK-MB elevations <10× ULN alone and without additional evaluation of symptoms or evidence of ischemia. These findings highlight the importance of PPMI for long-term outcome in the contemporary era and of its definition in the planning and interpretation of clinical trials., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Little is known about the cardiovascular risks of incident atrial fibrillation/flutter (AF) in patients with end-stage renal disease (ESRD) undergoing hemodialysis (HD)., Methods: We studied older US patients who newly initiated HD for ESRD (2006-11) and who had not previously been diagnosed with AF, stroke, myocardial infarction (MI) or hip fracture. We used Cox regression with AF as a time-varying covariate, adjusted for socio-demographic characteristics and comorbidities to estimate hazard ratios [HRs (95% confidence intervals)] for the events of ischemic stroke, MI and death. Hip fracture served as a negative control outcome., Results: We identified 85 377 older patients (mean age: 76.5 years) who initiated HD; of these, 14.3% were subsequently diagnosed with AF (14.9% thereof as primary diagnosis) and 49.8% died during follow-up. Incident AF was associated with nine times higher adjusted mortality during the first 30 days [9.2 (8.8-9.6)], 5-fold higher mortality between 31 and 90 days [4.6 (4.3-4.8)] and double the mortality beyond 90 days from first AF diagnosis [2.2 (2.1-2.3)]. Incident AF was similarly associated with higher adjusted risk of ischemic stroke: 2.1 (1.6-2.7) during the first 30 days, 2.5 (2.0-3.0) between 31 and 90 days and 1.5 (1.3-1.7) beyond 90 days. Similar findings were obtained for MI. However, the risk of hip fracture was only marginally increased following AF diagnosis [≤30 days: 1.1 (0.7-1.6); 31-90 days: 1.4 (1.0-1.8); >90 days: 1.2 (1.1-1.4)]. All associations were attenuated and the association with hip fracture was null when incident AF was defined by a primary diagnosis code., Conclusions: AF was strongly associated with increased risks of ischemic stroke, MI and death, with risks highest soon after AF diagnosis but extending beyond 90 days.

Objective: To examine the safety and efficacy of cangrelor in patients with single-vessel disease (SVD) and multi-vessel disease (MVD)., Background: Cangrelor, an intravenous, rapidly acting P2Y 12 inhibitor, is superior to clopidogrel in reducing ischemic events among patients receiving percutaneous coronary intervention (PCI)., Methods: We studied a modified intention to treat population of patients with SVD and MVD from the CHAMPION PHOENIX trial. The primary efficacy outcome was the composite of death, myocardial infarction (MI), ischemia-driven revascularization (IDR), and stent thrombosis (ST) at 48hours. The key safety outcome was non-coronary artery bypass grafting GUSTO severe bleeding at 48hours., Results: Among 10,921 patients, 5,220 (48%) had SVD and 5,701 (52%) had MVD. MVD patients were older and more often had diabetes, hyperlipidemia, hypertension, prior stroke, and prior MI. After adjustment, MVD patients had similar rates of 48-hour death/MI/IDR/ST (6.3% vs 4.2%, adjusted odds ratio [OR] 1.6 [95% CI 0.42-6.06]) and GUSTO severe bleeding (0.1% vs 0.2%, P=.67) compared with SVD patients. Consistent with overall trial findings, cangrelor use reduced ischemic complications in patients with both SVD (3.9% vs 4.5%; OR 0.86, 95% CI 0.65-1.12) and MVD (5.5% vs 7.2%; OR 0.74, 95% CI 0.6-0.92, P-interaction=.43). GUSTO severe bleeding outcomes were not significantly increased with cangrelor or clopidogrel in either SVD or MVD patients., Conclusion: In the CHAMPION PHOENIX trial, MVD and SVD patients had similar ischemic outcomes at 48hours and 30days. Cangrelor consistently reduced ischemic complications in both SVD and MVD patients without a significant increase in GUSTO severe bleeding. CLINICAL PERSPECTIVES., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Controversy exists about any differences in longer-term safety across different intravenous iron formulations routinely used in hemodialysis (HD) patients. We exploited a natural experiment to compare outcomes of patients initiating HD therapy in facilities that predominantly (in ≥90% of their patients) used iron sucrose versus sodium ferric gluconate complex., Study Design: Retrospective cohort study of incident HD patients., Setting & Participants: Using the US Renal Data System, we hard-matched on geographic region and center characteristics HD facilities predominantly using ferric gluconate with similar ones using iron sucrose. Subsequently, incident HD patients were assigned to their facility iron formulation exposure., Intervention: Facility-level use of iron sucrose versus ferric gluconate., Outcomes: Patients were followed up for mortality from any, cardiovascular, or infectious causes. Medicare-insured patients were followed up for infectious and cardiovascular (stroke or myocardial infarction) hospitalizations and for composite outcomes with the corresponding cause-specific deaths., Measurements: HRs., Results: We matched 2,015 iron sucrose facilities with 2,015 ferric gluconate facilities, in which 51,603 patients (iron sucrose, 24,911; ferric gluconate, 26,692) subsequently initiated HD therapy. All recorded patient characteristics were balanced between groups. Over 49,989 person-years, 10,381 deaths (3,908 cardiovascular and 1,209 infectious) occurred. Adjusted all-cause (HR, 0.98; 95% CI, 0.93-1.03), cardiovascular (HR, 0.96; 95% CI, 0.89-1.03), and infectious mortality (HR, 0.98; 95% CI, 0.86-1.13) did not differ between iron sucrose and ferric gluconate facilities. Among Medicare beneficiaries, no differences between ferric gluconate and iron sucrose facilities were observed in fatal or nonfatal cardiovascular events (HR, 1.01; 95% CI, 0.93-1.09). The composite infectious end point occurred less frequently in iron sucrose versus ferric gluconate facilities (HR, 0.92; 95% CI, 0.88-0.96)., Limitations: Unobserved selection bias from nonrandom treatment assignment., Conclusions: Patients initiating HD therapy in facilities almost exclusively using iron sucrose versus ferric gluconate had similar longer-term outcomes. However, there was a small decrease in infectious hospitalizations and deaths in patients dialyzing in facilities predominantly using iron sucrose. This difference may be due to residual confounding, random chance, or a causal effect., (Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

The adult with congenital heart disease (CHD) is at risk of developing atherosclerotic cardiovascular disease (ASCVD). We performed a cross-sectional study to describe established ASCVD risk factors and estimate 10-year and lifetime risk of ASCVD in adults over age 18 with CHD of moderate or great complexity using 3 validated risk assessment tools-the Framingham Study Cardiovascular Disease Risk Assessment, the Reynolds Risk Score, and the ASCVD Risk Estimator. We obtained extensive clinical and survey data on 178 enrolled patients, with average age 37.1 ± 12.6 years, 51% men. At least 1 modifiable ASCVD risk factor was present in 70%; the 2 most common were overweight/obesity (53%) and systemic hypertension (24%). Laboratory data were available in 103 of the 178 patients. Abnormal levels of glycated hemoglobin, high-sensitivity C-reactive protein, and high-density lipoprotein were each found in around 30% of patients. The 10-year ASCVD predicted risk using all 3 tools was relatively low (i.e., at least 90% of patients <10% risk), yet the median estimated lifetime risk was 36%. In conclusion, ASCVD risk factors are prevalent in adults with CHD. The risk estimation tools suggest that this population is particularly vulnerable to ASCVD with aging and should undergo guideline-based screening and management of modifiable risk factors., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Maintaining tight glycemic control is important for prevention of diabetes-related outcomes in end-stage renal disease patients with diabetes, especially in light of their poor prognosis. This study aimed to determine factors associated with poor glycemic control among U.S. patients with diabetes mellitus initiating hemodialysis for end-stage renal disease., Methods: Using data from the U.S. Renal Data System, electronic health records of a large national dialysis provider, and U.S. Census data, we performed a cross-sectional multivariable Poisson regression analysis to characterize risk factors associated with poor glycemic control, defined as glycated hemoglobin (HbA1c) > 7 vs. ≤ 7 %, in adult patients with diabetes who initiated hemodialysis at an outpatient facility between 2006 and 2011., Results: Of 16,297 patients with diabetes, 21.2 % had HbA1c >7 %. In multivariable analysis, younger patients, patients of Native American race, and those of Hispanic ethnicity had higher prevalence of poor glycemic control. Independent correlates of poor glycemic control further included higher platelet count, white blood cell count, and ferritin; higher body mass index, systolic blood pressure, total cholesterol and triglyceride concentrations; lower HDL and albumin concentrations; lower normalized protein catabolic rate; and higher estimated glomerular filtration rate at initiation of dialysis (all P < 0.05). No independent associations were found with area-level socioeconomic indicators. Occurrence of diabetes in patients < 40 years of age, a proxy for type 1 diabetes, was associated with poor HbA1c control compared with that in patients ≥ 40 years of age, which was classified as type 2 diabetes. These findings were robust to the different outcome definitions of HbA1c > 7.5 % and > 8 %., Conclusion: In this cohort of incident end-stage renal disease patients with diabetes, poor glycemic control was independently associated with younger age, Native American race, Hispanic ethnicity, higher body mass index, and clinical risk factors including atherogenic lipoprotein profile, hypertension, inflammation, and markers indicative of malnutrition and a more serious systemic disease.

Background: Ferumoxytol was first approved for clinical use in 2009 solely based on data from trial comparisons with oral iron on biochemical anemia efficacy end points. To compare the rates of important patient outcomes (infection, cardiovascular events and death) between facilities predominantly using ferumoxytol versus iron sucrose (IS) or ferric gluconate (FG) in patients with end-stage renal disease (ESRD)-initiating hemodialysis (HD)., Methods: Using the United States Renal Data System, we identified all HD facilities that switched (almost) all patients from IS/FG to ferumoxytol (July 2009-December 2011). Each switching facility was matched with three facilities that continued IS/FG use. All incident ESRD patients subsequently initiating HD in these centers were studied and assigned their facility exposure. They were followed for all-cause mortality, cardiovascular hospitalization/death or infectious hospitalization/death. Follow-up ended at kidney transplantation, switch to peritoneal dialysis, transfer to another facility, facility switch to another iron formulation and end of database (31 December 2011). Cox proportional hazards regression was then used to estimate adjusted hazard ratios [HR (95% confidence intervals)]., Results: In July 2009-December 2011, 278 HD centers switched to ferumoxytol; 265 units (95.3%) were matched with 3 units each that continued to use IS/FG. Subsequently, 14 206 patients initiated HD, 3752 (26.4%) in ferumoxytol and 10 454 (73.6%) in IS/FG centers; their characteristics were very similar. During 6433 person-years, 1929 all-cause, 726 cardiovascular and 191 infectious deaths occurred. Patients in ferumoxytol (versus IS/FG) facilities experienced similar all-cause [0.95 (0.85-1.07)], cardiovascular [0.99 (0.83-1.19)] and infectious mortality [0.88 (0.61-1.25)]. Among 5513 Medicare (Parts A + B) beneficiaries, cardiovascular events [myocardial infarction, stroke and cardiovascular death; 1.05 (0.79-1.39)] and infectious events [hospitalization/death; 0.96 (0.85-1.08)] did not differ between the iron exposure groups., Conclusions: In incident HD patients, ferumoxytol showed similar short- to mid-term safety profiles with regard to cardiovascular, infectious and mortality outcomes compared with the more commonly used intravenous iron formulations IS and FG., (© The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Purpose: The objective of this analysis is to examine the relationship between Fragile X Mental Retardation 1 gene (FMR1) cytosine-guanine-guanine (CGG) repeat number and ovarian reserve, with a particular focus exclusively on the range of CGG repeat number below the premutation (PM) range (<55 CGG repeats)., Methods: Our study included female patients who underwent assessment of FMR1 CGG repeat number and serum anti-Mullerian hormone (AMH) in 2009-2014. To examine the association between FMR1 repeat number and serum AMH, we created three summary measures of CGG repeat number for the two alleles-"Sum," "Max," and "Gap" (absolute difference). Using multivariable regression models, controlling for age, we then analyzed the impact of these summary measures on AMH., Results: A total of 566 patients were included in our study. Using multivariable regression models, we found that the relationship between CGG repeat number and AMH differed depending on age. Specifically, in younger women, AMH increased by 7-8 % (Sum p < 0.01, Max p = 0.04) for every 1 unit increase in CGG repeat number. In contrast, starting at age 40, there was a 3 to 5 % decline in AMH for every 1 unit increase in CGG repeat number (Sum p < 0.01, Max p = 0.04)., Conclusions: This is the first study to report a statistically significant correlation of ovarian reserve and CGG repeat number in women with <55 CGG repeats. Although these women are generally considered to have a normal phenotype, our data suggest that increasing CGG repeat number within this normal range is associated with a more rapid decline in ovarian reserve.

Provider profiling as a means to describe and compare the performance of health care professionals has gained momentum in the past decade. As a key component of pay-for-performance programs profiling has been increasingly used to identify top-performing providers. However, rigorous examination of the performance of statistical methods for profiling when used to classify top-performing providers is lacking. The objective of this study was to compare the classification accuracy of three methods for identifying providers exceeding performance thresholds and to analyze data on satisfaction with mental health care providers at Group Health Cooperative using these methods. Questionnaire data on patient satisfaction with mental health care providers at Group Health Cooperative was collected between April 2008 and January 2010. Simulated data were used to compare the classification accuracy of alternative statistical methods. We evaluated sensitivity, specificity, and root mean squared error of alternative statistical methods using simulated data. For Group Health providers, we compared agreement of alternative approaches to classification. We found that when between-provider variability in performance was low, all three methods exhibited poor classification accuracy. When used to evaluate mental health care provider performance, we found substantial uncertainty in the estimates and poor agreement across methods. Based on these findings, we recommend providing uncertainty estimates for provider rankings and caution against the use of any classification method when between-provider variability is low.