A simple, clinically usable whole-body MRI system of joint assessment in adolescents and young people with juvenile idiopathic arthritis.

OBJECTIVES: To introduce and evaluate a simple method for assessing joint inflammation and structural damage on whole-body MRI (WBMRI) in juvenile idiopathic arthritis (JIA), which is usable in clinical practice. METHODS: The proposed system utilises post-contrast Dixon WBMRI scans. Joints are assessed for synovitis (grade 0-2) and structural damage (present/absent) at 81 sites. The synovitis grading is based on features including above-normal intensity synovial enhancement, synovial hypertrophy, joint effusion, subarticular bone marrow oedema and peri-articular soft tissue oedema.This system was evaluated in a prospective study of 60 young people (47 patients with JIA and 13 controls with non-inflammatory musculoskeletal pain) who underwent a WBMRI. Three readers (blinded to diagnosis) independently reviewed all images and re-reviewed 20 individual scans. The intra- and inter-reader overall agreement (OA) and the intra- and inter-reader Gwet's agreement coefficients 2 (GAC2) were measured for the detection of a) participants with ≥1 joint with inflammation or structural damage and b) joint inflammation or structural damage for each joint. RESULTS: The inter-reader OA for detecting patients with ≥1 joint with inflammation, defined as grade 2 synovitis (G2), and ≥1 joint with structural damage were 80% and 73%, respectively. The intra-reader OA for readers 1-3 were 80-90% and 75-90% respectively. The inter-reader OA and GAC2 for joint inflammation (G2) at each joint were both ≥85% for all joints but were lower if grade 1 synovitis was included as positive. CONCLUSION: The intra- and inter-reader agreements of this WBMRI assessment system are adequate for assessing objective joint inflammation and damage in JIA.

Detection of inflammation by whole-body MRI in young people with juvenile idiopathic arthritis.

OBJECTIVES: To assess the frequency of joint inflammation detected by whole-body MRI (WBMRI) in young people (YP) with JIA and controls, and to determine the relationship between WBMRI-detected inflammation and clinical findings. METHODS: YP aged 14-24 years, with JIA (patients) or arthralgia without JIA (controls), recruited from one centre, underwent a WBMRI scan after formal clinical assessment. Consensus between at least two of the three independent radiologists was required to define inflammation and damage on WBMRI, according to predefined criteria. YP with JIA were deemed clinically active as per accepted definitions. The proportions of YP with positive WBMRI scans for joint inflammation (≥1 inflamed joint) as well as serum biomarkers were compared between active vs inactive JIA patients and controls. RESULTS: Forty-seven YP with JIA (25 active and 22 inactive patients) and 13 controls were included. WBMRI detected joint inflammation in 60% (28/47) patients with JIA vs 15% (2/13) controls (difference: 44%, 95% CI 20%, 68%). More active than inactive JIA patients had WBMRI-detected inflammation [76% (19/25) vs 41% (9/22), difference: 35% (95% CI 9%, 62%)], and this was associated with a specific biomarker signature. WBMRI identified inflammation in ≥ 1 clinically inactive joint in 23/47 (49%) patients (14/25 active vs 9/22 inactive JIA patients). CONCLUSIONS: WBMRI's validity in joint assessment was demonstrated by the higher frequency of inflammation in JIA patients vs controls, and in active vs inactive JIA patients. WBMRI found unsuspected joint inflammation in 49% YP with JIA, which needs further investigation of potential clinical implications.

Diagnostic performance of sonographic activity scores for adult terminal ileal Crohn's disease compared to magnetic resonance and histological reference standards: experience from the METRIC trial.

OBJECTIVES: The simple ultrasound activity score for Crohn's disease (SUS-CD) and bowel ultrasound score (BUSS) are promising intestinal ultrasound (IUS) indices of CD, but studied mainly in small settings with few sonographers. We compared SUS-CD and BUSS against histological and magnetic resonance enterography (MRE) reference standards in a post hoc analysis of a prospective multicentre, multireader trial. METHODS: Participants recruited to the METRIC trial (ISRCTN03982913) were studied, including those with available terminal ileal (TI) biopsies. Sensitivity and specificity of SUS-CD and BUSS for TI CD activity were calculated with 95% confidence intervals (CI), from the prospective observations of the original METRIC trial sonographers against the histological activity index (HAI) and the simplified magnetic resonance index of activity (sMARIA). RESULTS: We included 284 patients (median 31.5 years, IQR 23-46) from 8 centres, who underwent IUS and MRE. Of these, 111 patients had available terminal ileal biopsies with HAI scoring. Against histology, sensitivity and specificity for active disease were 79% (95% CI 69-86%) and 50% (31-69%) for SUS-CD, and 66% (56-75%) and 68% (47-84%) for BUSS, respectively. Compared to sMARIA, the sensitivity and specificity for active CD were 81% (74-86%) and 75% (66-83%) for SUS-CD, and 68% (61-74%) and 85% (76-91%) for BUSS, respectively. The sensitivity of SUS-CD was significantly greater than that of BUSS against HAI and sMARIA (p < 0.001), but its specificity was significantly lower than of BUSS against the MRE reference standard (p = 0.003). CONCLUSIONS: Particularly when compared to MRE activity scoring, SUS-CD and BUSS are promising tools in a real-world clinical setting. CLINICAL RELEVANCE STATEMENT: When tested using data from a multicentre, multireader diagnostic accuracy trial, the simple ultrasound activity score for Crohn's disease (SUS-CD) and bowel ultrasound score (BUSS) were clinically viable intestinal ultrasound indices that were reasonably sensitive and specific for terminal ileal Crohn's disease, especially when compared to a magnetic resonance reference standard. KEY POINTS: The simple ultrasound activity score for Crohn's disease and bowel ultrasound score are promising intestinal ultrasound indices of Crohn's disease but to date studied mainly in small settings with few sonographers. Compared to histology and the magnetic resonance reference standard in a multicentre, multireader setting, the sensitivity of simple ultrasound activity score for Crohn's disease is significantly greater than that of bowel ultrasound score. The specificity of simple ultrasound activity score for Crohn's disease was significantly lower than that of bowel ultrasound score compared to the magnetic resonance enterography reference standard. The specificity of both indices was numerically higher when the magnetic resonance enterography reference standard was adopted.

Assessment of the Performances of the Protein Modeling Techniques Participating in CASP15 Using a Structure-Based Functional Site Prediction Approach: ResiRole.

BACKGROUND: Model quality assessments via computational methods which entail comparisons of the modeled structures to the experimentally determined structures are essential in the field of protein structure prediction. The assessments provide means to benchmark the accuracies of the modeling techniques and to aid with their development. We previously described the ResiRole method to gauge model quality principally based on the preservation of the structural characteristics described in SeqFEATURE functional site prediction models. METHODS: We apply ResiRole to benchmark modeling group performances in the Critical Assessment of Structure Prediction experiment, round 15. To gauge model quality, a normalized Predicted Functional site Similarity Score (PFSS) was calculated as the average of one minus the absolute values of the differences of the functional site prediction probabilities, as found for the experimental structures versus those found at the corresponding sites in the structure models. RESULTS: The average PFSS per modeling group (gPFSS) correlates with standard quality metrics, and can effectively be used to rank the accuracies of the groups. For the free modeling (FM) category, correlation coefficients of the Local Distance Difference Test (LDDT) and Global Distance Test-Total Score (GDT-TS) metrics with gPFSS were 0.98239 and 0.87691, respectively. An example finding for a specific group is that the gPFSS for EMBER3D was higher than expected based on the predictive relationship between gPFSS and LDDT. We infer the result is due to the use of constraints imprinted by function that are a part of the EMBER3D methodology. Also, we find functional site predictions that may guide further functional characterizations of the respective proteins. CONCLUSION: The gPFSS metric provides an effective means to assess and rank the performances of the structure prediction techniques according to their abilities to accurately recount the structural features at predicted functional sites.

First-in-human in-vivo depiction of paraganglioma metabolism by hyperpolarised 13C-magnetic resonance.

Phaeochromocytomas (PCC) and paragangliomas (PGL), cumulatively referred to as PPGLs, are neuroendocrine tumours arising from neural crest-derived cells in the sympathetic and parasympathetic nervous systems. Predicting future tumour behaviour and the likelihood of metastatic disease remains problematic as genotype-phenotype correlations are limited, the disease has variable penetrance and, to date, no reliable molecular, cellular or histological markers have emerged. Tumour metabolism quantification can be considered as a method to delineating tumour aggressiveness by utilising hyperpolarised 13 C-MR (HP-MR). The technique may provide an opportunity to non-invasively characterise disease behaviour. Here, we present the first instance of the analysis of PPGL metabolism via HP-MR in a single case.

Chest radiograph classification and severity of suspected COVID-19 by different radiologist groups and attending clinicians: multi-reader, multi-case study.

OBJECTIVES: To quantify reader agreement for the British Society of Thoracic Imaging (BSTI) diagnostic and severity classification for COVID-19 on chest radiographs (CXR), in particular agreement for an indeterminate CXR that could instigate CT imaging, from single and paired images. METHODS: Twenty readers (four groups of five individuals)-consultant chest (CCR), general consultant (GCR), and specialist registrar (RSR) radiologists, and infectious diseases clinicians (IDR)-assigned BSTI categories and severity in addition to modified Covid-Radiographic Assessment of Lung Edema Score (Covid-RALES), to 305 CXRs (129 paired; 2 time points) from 176 guideline-defined COVID-19 patients. Percentage agreement with a consensus of two chest radiologists was calculated for (1) categorisation to those needing CT (indeterminate) versus those that did not (classic/probable, non-COVID-19); (2) severity; and (3) severity change on paired CXRs using the two scoring systems. RESULTS: Agreement with consensus for the indeterminate category was low across all groups (28-37%). Agreement for other BSTI categories was highest for classic/probable for the other three reader groups (66-76%) compared to GCR (49%). Agreement for normal was similar across all radiologists (54-61%) but lower for IDR (31%). Agreement for a severe CXR was lower for GCR (65%), compared to the other three reader groups (84-95%). For all groups, agreement for changes across paired CXRs was modest. CONCLUSION: Agreement for the indeterminate BSTI COVID-19 CXR category is low, and generally moderate for the other BSTI categories and for severity change, suggesting that the test, rather than readers, is limited in utility for both deciding disposition and serial monitoring. KEY POINTS: • Across different reader groups, agreement for COVID-19 diagnostic categorisation on CXR varies widely. • Agreement varies to a degree that may render CXR alone ineffective for triage, especially for indeterminate cases. • Agreement for serial CXR change is moderate, limiting utility in guiding management.

Quantification of Prostate Cancer Metabolism Using 3D Multiecho bSSFP and Hyperpolarized [1-13 C] Pyruvate: Metabolism Differs Between Tumors of the Same Gleason Grade.

BACKGROUND: Three-dimensional (3D) multiecho balanced steady-state free precession (ME-bSSFP) has previously been demonstrated in preclinical hyperpolarized (HP) 13 C-MRI in vivo experiments, and it may be suitable for clinical metabolic imaging of prostate cancer (PCa). PURPOSE: To validate a signal simulation framework for the use of sequence parameter optimization. To demonstrate the feasibility of ME-bSSFP for HP 13 C-MRI in patients. To evaluate the metabolism in PCa measured by ME-bSSFP. STUDY TYPE: Retrospective single-center cohort study. PHANTOMS/POPULATION: Phantoms containing aqueous solutions of [1-13 C] lactate (2.3 M) and [13 C] urea (8 M). Eight patients (mean age 67 ± 6 years) with biopsy-confirmed Gleason 3 + 4 (n = 7) and 4 + 3 (n = 1) PCa. FIELD STRENGTH/SEQUENCES: 1 H MRI at 3 T with T2 -weighted turbo spin-echo sequence used for spatial localization and spoiled dual gradient-echo sequence used for B0 -field measurement. ME-bSSFP sequence for 13 C MR spectroscopic imaging with retrospective multipoint IDEAL metabolite separation. ASSESSMENT: The primary endpoint was the analysis of pyruvate-to-lactate conversion in PCa and healthy prostate regions of interest (ROIs) using model-free area under the curve (AUC) ratios and a one-directional kinetic model (kP ). The secondary objectives were to investigate the correlation between simulated and experimental ME-bSSFP metabolite signals for HP 13 C-MRI parameter optimization. STATISTICAL TESTS: Pearson correlation coefficients with 95% confidence intervals and paired t-tests. The level of statistical significance was set at P < 0.05. RESULTS: Strong correlations between simulated and empirical ME-bSSFP signals were found (r > 0.96). Therefore, the simulation framework was used for sequence optimization. Whole prostate metabolic HP 13 C-MRI, observing the conversion of pyruvate into lactate, with a temporal resolution of 6 seconds was demonstrated using ME-bSSFP. Both assessed metrics resulted in significant differences between PCa (mean ± SD) (AUC = 0.33 ± 012, kP  = 0.038 ± 0.014) and healthy (AUC = 0.15 ± 0.10, kP  = 0.011 ± 0.007) ROIs. DATA CONCLUSION: Metabolic HP 13 C-MRI in the prostate using ME-bSSFP allows for differentiation between aggressive PCa and healthy tissue. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 1.

The Pharmacorank Search Tool for the Retrieval of Prioritized Protein Drug Targets and Drug Repositioning Candidates According to Selected Diseases.

We present the Pharmacorank search tool as an objective means to obtain prioritized protein drug targets and their associated medications according to user-selected diseases. This tool could be used to obtain prioritized protein targets for the creation of novel medications or to predict novel indications for medications that already exist. To prioritize the proteins associated with each disease, a gene similarity profiling method based on protein functions is implemented. The priority scores of the proteins are found to correlate well with the likelihoods that the associated medications are clinically relevant in the disease's treatment. When the protein priority scores are plotted against the percentage of protein targets that are known to bind medications currently indicated to treat the disease, which we termed the pertinency score, a strong correlation was observed. The correlation coefficient was found to be 0.9978 when using a weighted second-order polynomial fit. As the highly predictive fit was made using a broad range of diseases, we were able to identify a general threshold for the pertinency score as a starting point for considering drug repositioning candidates. Several repositioning candidates are described for proteins that have high predicated pertinency scores, and these provide illustrative examples of the applications of the tool. We also describe focused reviews of repositioning candidates for Alzheimer's disease. Via the tool's URL, https://protein.som.geisinger.edu/Pharmacorank/, an open online interface is provided for interactive use; and there is a site for programmatic access.

Diagnostic Performance of Magnetic Resonance Enterography Disease Activity Indices Compared with a Histological Reference Standard for Adult Terminal Ileal Crohn's Disease: Experience from the METRIC Trial.

BACKGROUND AND AIMS: The simplified magnetic resonance enterography [MRE] index of activity [sMARIA], London, and 'extended' London, scoring systems are widely used in Crohn's disease [CD] to assess disease activity, although validation studies have usually been single-centre, retrospective, and/or used few readers. Here, we evaluated these MRE indices within a prospective, multicentre, multireader, diagnostic accuracy trial. METHODS: A subset of participants [newly diagnosed or suspected of relapse] recruited to the METRIC trial with available terminal ileal [TI] biopsies was included. Using pre-specified thresholds, the sensitivity and specificity of sMARIA, London, and 'extended' London scores for active and severe [sMARIA] TI CD were calculated using different thresholds for the histological activity index [HAI]. RESULTS: We studied 111 patients [median age 29 years, interquartile range 21-41, 75 newly diagnosed, 36 suspected relapse] from seven centres, of whom 22 had no active TI CD [HAI = 0], 39 mild [HAI = 1], 13 moderate [HAI = 2], and 37 severe CD activity [HAI = 3]. In total, 26 radiologists prospectively scored MRE datasets as per their usual clinical practice. Sensitivity and specificity for active disease [HAI >0] were 83% [95% confidence interval 74% to 90%] and 41% [23% to 61%] for sMARIA, 76% [67% to 84%] and 64% [43% to 80%] for the London score, and 81% [72% to 88%] and 41% [23% to 61%] for the 'extended' London score, respectively. The sMARIA had 84% [69-92%] sensitivity and 53% [41-64%] specificity for severe CD. CONCLUSIONS: When tested at their proposed cut-offs in a real-world setting, sMARIA, London, and 'extended' London indices achieve high sensitivity for active TI disease against a histological reference standard, but specificity is low.

Insights into the Role of Employers Supporting Obesity Management in People with Obesity: Results of the National ACTION Study.

Lack of both awareness and application of evidence-based principles for obesity care for people with obesity (PwO) limit employers' role in supporting effective obesity management among employees with obesity (EwO). The aim of the ACTION (Awareness, Care, and Treatment In Obesity maNagement) study was to explore the current state of employer wellness programs related to obesity management, evaluate the impact of obesity in the workplace, assess attitudes regarding the role of employers in managing obesity, and identify challenges in implementing workplace wellness programs as perceived by employer representatives (ERs) and EwO. An online survey was conducted among ERs and adult PwO (BMI ≥30 by self-reported height and weight) using a cross-sectional, US-based stratified sample design. There were 153 ER respondents and 3008 adult PwO respondents; 1478 PwO were employed full-time, part-time, or were self-employed. ERs recognize the seriousness of obesity and its negative impact on work productivity; however, wellness programs tend to fall short of addressing specific needs of EwO, evidenced by low participation and success rates reported by EwO. This study highlights the need for programs that address the complexities of obesity and the specific needs of EwO, which currently are inadequately addressed according to EwO.

Perceptions of Barriers to Effective Obesity Care: Results from the National ACTION Study.

OBJECTIVE: ACTION (Awareness, Care, and Treatment in Obesity maNagement) examined obesity-related perceptions, attitudes, and behaviors among people with obesity (PwO), health care providers (HCPs), and employer representatives (ERs). METHODS: A total of 3,008 adult PwO (BMI ≥ 30 by self-reported height and weight), 606 HCPs, and 153 ERs completed surveys in a cross-sectional design. RESULTS: Despite several weight loss (WL) attempts, only 23% of PwO reported 10% WL during the previous 3 years. Many PwO (65%) recognized obesity as a disease, but only 54% worried their weight may affect future health. Most PwO (82%) felt "completely" responsible for WL; 72% of HCPs felt responsible for contributing to WL efforts; few ERs (18%) felt even partially responsible. Only 50% of PwO saw themselves as "obese," and 55% reported receiving a formal diagnosis of obesity. Despite HCPs' reported comfort with weight-related conversations, time constraints deprioritized these efforts. Only 24% of PwO had a scheduled follow-up to initial weight-related conversations. Few PwO (17%) perceived employer-sponsored wellness offerings as helpful in supporting WL. CONCLUSIONS: Although generally perceived as a disease, obesity is not commonly treated as such. Divergence in perceptions and attitudes potentially hinders better management. This study highlights inconsistent understanding of the impact of obesity and need for both self-directed and medical management.

Emergency Department use of Apneic Oxygenation Versus Usual Care During Rapid Sequence Intubation: A Randomized Controlled Trial (The ENDAO Trial).

OBJECTIVES: Desaturation leading to hypoxemia may occur during rapid sequence intubation (RSI). Apneic oxygenation (AO) was developed to prevent the occurrence of oxygen desaturation during the apnea period. The purpose of this study was to determine if the application of AO increases the average lowest oxygen saturation during RSI when compared to usual care (UC) in the emergency setting. METHODS: A randomized controlled trial was conducted at an academic, urban, Level I trauma center. All patients requiring intubation were included. Exclusion criteria were patients in cardiac or traumatic arrest or if preoxygenation was not performed. An observer, blinded to study outcomes and who was not involved in the procedure, recorded all times, while all saturations were recorded in real time by monitors on a secured server. Two-hundred patients were allocated to receive AO (n = 100) or UC (n = 100) by predetermined randomization in a 1:1 ratio. RESULTS: A total of 206 patients were enrolled. There was no difference in lowest mean oxygen saturation between the two groups (92, 95% confidence interval [CI] = 91 to 93 in AO vs. 93, 95% CI = 92 to 94 in UC; p = 0.11). CONCLUSION: There was no difference in lowest mean oxygen saturation between the two groups. The application of AO during RSI did not prevent desaturation of patients in this study population.

Bringing Workforce Health to the Top Line-Expanding the Value Proposition for Workforce Health Improvement.

The pressure on employers to justify providing health benefits or to prove the value of health investment has never been greater. Many employers have resorted to cost shifting to employees to dampen the impact of health care costs on their companies or have avoided health investments, believing they don't deliver a return. Both strategies come with significant risk to employees, their dependents and the company's business performance. This article provides a framework for employers to better understand the full impact of workforce health and well-being on bottom-line costs and the opportunities for connecting workforce health and well-being to topline business performance metrics. Application of the principles presented in this commentary can help human resources/benefits personnel better understand the broader business impacts of their workforce health and well-being strategies as well as equip them to have a more meaningful role in workforce strategic planning.

"Stuttering" after minor head trauma.

Traumatic brain injury (TBI) is defined as impairment in brain function as a result of mechanical force. It is classified based on clinical findings using the Glasgow Coma Scale (GCS). Mild TBI is defined as GCS 14-15; moderate, 9-13; and severe, 3-8. Patients with the same TBI classification may have very different underlying pathology. In moderate to severe TBI, the primary pathology may include contusions, hemorrhage, diffuse axonal injury, direct cellular damage, "tearing and shearing of the tissues, loss of the blood-brain barrier, disruption of the neurochemical homeostasis and loss of the electrochemical function". Although the primary pathology associated with mild TBI may be milder versions of the same pathology associated with moderate and severe TBI, it is generally a metabolic injury. However, it is reported that 15% of patients with mild TBI and a GCS score of 14 or 15 will have an intracranial lesion; less than 1% of these require neurosurgical intervention. Although patients with mild TBI may have intracranial lesions, it is rare that the presenting and only physical examination finding is an isolated neurologic finding. Here we present a case of isolated head trauma with a single physical examination finding--expressive aphasia.

Workforce Health--The Transition From Cost to Outcomes to Business Performance.

Although employers can shift the cost/risk of health care to external claims payers through insurance, they can never shift the broader impacts of health-related well-being, lost time and performance outside of their organizational boundaries. This article traces the evolution of employer strategies to manage health, addressing what research tells us about the broader impacts of health and well-being on outcomes and establishing a broader framework for connecting health to business performance. The challenge that employers now face is to integrate a much broader set of factors to meet the goals of improved workforce health, well-being and business performance. Regardless of how employers decide to provide health benefits, these broader issues are a business imperative for every employer in the 21st century.

Retrospective evaluation of factors that influence the implementation of CATCH in southern Illinois schools.

BACKGROUND: Coordinated Approach to Child Health (CATCH) is a school health program implemented in southern Illinois that focuses on physical activity and nutrition and consists of a classroom curriculum, physical education framework, and cafeteria guidelines. Though many schools agreed to implement CATCH, some schools implemented it better than others. This study examined implementation practices of classroom and physical education teachers and cafeteria supervisors. METHOD: We surveyed 284 school employees at 36 elementary schools located in southern Illinois. Attention focused on organizational readiness, commitment to change, school leadership, implementation barriers, and innovation perceptions concerning degree of implementation of CATCH. RESULTS: Organizational readiness and implementation barriers were significant predictors of degree of implementation for school employees. Additionally, organizational readiness was reported a significant predictor of classroom teacher degree of implementation whereas leadership was a significant predictor of degree of implementation by physical education teachers. CONCLUSION: Data from this study can be used to enhance implementation of CATCH as well as other school health programs. This study provides educators evidence of why school employees have different implementation practices, evidence of what constructs influence degree of implementation most, and some explanation of school employee degree of implementation.

Medication adherence, comorbidities, and health risk impacts on workforce absence and job performance.

OBJECTIVE: To understand impacts of medication adherence, comorbidities, and health risks on workforce absence and job performance. METHODS: Retrospective observational study using employees' medical/pharmacy claims and self-reported health risk appraisals. RESULTS: Statin medication adherence in individuals with Coronary Artery Disease was significant predictor (P < 0.05) of decreasing absenteeism. Insulin, oral hypoglycemic, or metformin medication adherence in type 2 diabetics was significant (P < 0.05) predictor of decreasing job performance. Number of comorbidities was found as significant (P < 0.5) predictor of absenteeism in five of nine subsamples. Significant links (P < 0.05) between high health risks and lower job performance were found across all nine subsamples. CONCLUSIONS: Results suggest integrated health and productivity management strategies should include an emphasis on primary and secondary prevention to reduce health risks in addition to tertiary prevention efforts of disease management and medication management.