Search

This practice parameter (PP) for Lutetium-177 (Lu-177) DOTATATE peptide receptor radionuclide therapy (PRRT) aims to guide authorized users in selection of appropriate adult candidates with gastroeneropancreatic neuroendocrine tumors (GEP-NETs) from foregut, midgut, and hindgut. The essential selection criteria include somatostatin receptor-positive GEP-NETs, which are usually inoperable and progressed despite standard therapy. Lu-177 DOTATATE is a radiopharmaceutical with high avidity for somatostatin receptors that are overexpressed by these tumors. This document ensures safe handling of Lu-177 DOTATATE by the authorized users and safe management of affected patients.The document was developed according to the systematic process developed by the American College of Radiology (ACR) and described on the ACR Web site (https://www.acr.org/Clinical-Resources/Practice-Parameters-and-Technical-Standards). The PP development was led by 2 ACR Committees on Practice Parameters (Nuclear Medicine and Molecular Imaging and Radiation Oncology) collaboratively with the American College of Nuclear Medicine, American Society of Radiation Oncology, and Society of Nuclear Medicine and Molecular Imaging.The Lu-177 DOTATATE PP reviewed pharmacology, indications, adverse effects, personnel qualifications, and required clinical evaluation before starting the treatment, as well as the recommended posttherapy monitoring, quality assurance, documentation, and appropriate radiation safety instructions provided in written form and explained to the patients.Lu-177 DOTATATE is available for therapy of inoperable and/or advanced GEP-NETs when conventional therapy had failed. It can reduce tumor size, improve symptoms, and increase the progression free survival. The PP document provides clinical guidance for authorized users to assure an appropriate, consistent, and safe practice of Lu-177 DOTATATE.

Acute aortic syndrome (AAS) includes the entities of acute aortic dissection, intramural hematoma, and penetrating atherosclerotic ulcer. AAS typically presents with sudden onset of severe, tearing, anterior, or interscapular back pain. Symptoms may be dominated by malperfusion syndrome, due to obstruction of the lumen of the aorta and/or a side branch when the intimal and medial layers are separated. Timely diagnosis of AAS is crucial to permit prompt management; for example, early mortality rates are reported to be 1% to 2% per hour after the onset of symptoms for untreated ascending aortic dissection. The appropriateness assigned to each imaging procedure was based on the ability to obtain key information that is used to plan open surgical, endovascular, or medical therapy. This includes, but is not limited to, confirming the presence of AAS; classification; characterization of entry and reentry sites; false lumen patency; and branch vessel compromise. Using this approach, CT, CTA, and MRA are all considered usually appropriate in the initial evaluation of AAS if those procedures include intravenous contrast administration. Ultrasound is also considered usually appropriate if the acquisition is via a transesophageal approach. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Aim/objectives/background The goal of therapy with unsealed radiopharmaceutical sources is to provide either cure or significant prolongation of disease-specific survival, and effective reduction and/or prevention of adverse disease-related symptoms or untoward events while minimizing treatment-associated side effects and complications. Radium-223 dichloride (radium-223) is an alpha particle-emitting isotope used for targeted bone therapy. This practice parameter is intended to guide appropriately trained and licensed physicians performing therapy with radium-223. Such therapy requires close cooperation and communication between the physicians who are responsible for the clinical management of the patient and those who administer radiopharmaceutical therapy and manage the attendant side effects. Adherence to this parameter should help to maximize the efficacious use of radium-223, maintain safe conditions, and ensure compliance with applicable regulations. Methods This practice parameter was developed according to the process described on the American College of Radiology (ACR) website ("The Process for Developing ACR Practice Parameters and Technical Standards," www.acr.org/ClinicalResources/Practice-Parameters-and-Technical-Standards) by the Committee on Practice Parameters of the ACR Commission on Radiation Oncology in collaboration with the American College of Nuclear Medicine (ACNM), the American Society for Radiation Oncology (ASTRO), and the Society of Nuclear Medicine and Molecular Imaging (SNMMI). All these societies contributed to the development of the practice parameter and approved the final document. Results This practice parameter addresses the many factors which contribute to appropriate, safe, and effective clinical use of radium-223. Topics addressed include qualifications and responsibilities of personnel, specifications of patient examination and treatment; documentation, radiation safety, quality control/improvement, infection control, and patient education. Conclusions This practice parameter is intended as a tool to guide clinical use of radium-223 with the goal of facilitating safe and effective medical care based on current knowledge, available resources and patient needs. The sole purpose of this document is to assist practitioners in achieving this objective.

Hydatidiform mole (HM) is an aberrant human pregnancy characterized by excessive trophoblastic proliferation and abnormal embryonic development. HM has two morphological types, complete (CHM) and partial (PHM), and non-recurrent ones have three genotypic types, androgenetic monospermic, androgenetic dispermic, and triploid dispermic. Most available studies on risk factors predisposing to different types of HM and their malignant transformation mainly suffer from the lack of comprehensive genotypic analysis of large cohorts of molar tissues combined with accurate postmolar hCG follow-up. Moreover, 10–20% of patients with one HM have at least one non-molar miscarriage, which is higher than the frequency of two pregnancy losses in the general population (2–5%), suggesting a common genetic susceptibility to HM and miscarriages. However, the underlying causes of the miscarriages in these patients are unknown. Here, we comprehensively analyzed 204 HM, mostly from patients referred to the Quebec Registry of Trophoblastic Diseases and for which postmolar hCG monitoring is available, and 30 of their non-molar miscarriages. We revisited the risk of maternal age and neoplastic transformation across the different HM genotypic categories and investigated the presence of chromosomal abnormalities in their non-molar miscarriages. We confirm that androgenetic CHM is more prone to gestational trophoblastic neoplasia (GTN) than triploid dispermic PHM, and androgenetic dispermic CHM is more prone to high-risk GTN and choriocarcinoma (CC) than androgenetic monospermic CHM. We also confirm the association between increased maternal age and androgenetic CHM and their malignancies. Most importantly, we demonstrate for the first time that patients with an HM and miscarriages are at higher risk for aneuploid miscarriages [83.3%, 95% confidence interval (CI): 0.653–0.944] than women with sporadic (51.5%, 95% CI: 50.3–52.7%, p value = 0.0003828) or recurrent miscarriages (43.8%, 95% CI: 40.7–47.0%, p value = 0.00002). Our data suggest common genetic female germline defects predisposing to HM and aneuploid non-molar miscarriages in some patients.

Chest pain is a frequent cause for emergency department visits and inpatient evaluation, with particular concern for acute coronary syndrome as an etiology, since cardiovascular disease is the leading cause of death in the United States. Although history-based, electrocardiographic, and laboratory evaluations have shown promise in identifying coronary artery disease, early accurate diagnosis is paramount and there is an important role for imaging examinations to determine the presence and extent of anatomic coronary abnormality and ischemic physiology, to guide management with regard to optimal medical therapy or revascularization, and ultimately to thereby improve patient outcomes. A summary of the various methods for initial imaging evaluation of suspected acute coronary syndrome is outlined in this document. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

A technology for automatically obtaining patient photographs along with portable radiographs was implemented clinically at a large academic hospital. This article highlights several cases in which image-related clinical context, provided by the patient photographs, provided quality control information regarding patient identification, laterality, or position and assisted the radiologist with the interpretation. The information in the photographs can easily minimize unnecessary calls to the patient's nursing staff for clarifications and can lead to new methods of physically assessing patients. Published under a CC BY 4.0 license.

Rationale and Objectives The journal impact factor (JIF) is often used to assess the prestige of scientific journals. Citations from original articles and reviews as well as citations from noncitable items contribute to the numerator in these calculations. However, since noncitable articles are not included in the denominator, the JIF may be skewed by the types of articles and not accurately reflect the prestige of the journal. The purpose of our study was to develop an alternative and complementary metric by which journals may be assessed. This “adjusted citation rate metric” is based on citations that originate only from citable items in the journal. Material and Methods We tabulated the number of citations and citable items for original articles from the Web of Science Core Collection for 5 consecutive years (2010–2014) for 20 general radiology journals. The adjusted citation rates (CR) per original article and reviews were calculated using only citations that originated from citable items. Results The adjusted CR in 2015 was similar to the JIF in 14 of the 20 journals, higher in four journals, and lower in two journals. Using this system, Radiology, Investigative Radiology, and European Radiology remained first, second, and third respectively among journals published in the field of general radiology. To allow for equal distribution of original articles vs reviews among general radiology journals, we calculated the adjusted CR where the standard distribution of original articles is 50%. Conclusion Adjusted citation rate is an objective index for assessing journal impact that can serve as an alternative and complementary metric with which to measure the journal impact.

Purpose The aim of this study was to perform, from the patient’s point of view, a nationwide assessment of nuclear medicine practices regarding diabetic management before 18F-fluorodeoxyglucose (FDG) PET/CT for oncologic indications. Methods This prospective observational study was exempt from institutional review board oversight. Sixty-five nuclear medicine scheduling lines (33 academic, 32 private practice, 12-17 in each of the five US regions) were called using a prewritten script under the guise of a nonexpert patient’s family member about scheduling a patient with diabetes with “cancer” for FDG PET/CT. Each center was called three times on three different days. The following data were collected: (1) blood glucose threshold for rescheduling an examination, (2) when or if to stop various medications, (3) fasting requirements, and (4) time-of-day scheduling preferences. Withheld information was not specifically requested. Descriptive statistics were calculated. Results There were 195 phone calls (mean duration, 2.9 min; range, 2-6 min). Relevant information was often withheld; withholding rates were as follows: blood glucose threshold, 71% (138 of 195); short-acting insulin instructions, 30% (59 of 195); long-acting insulin instructions, 99% (193 of 195); metformin instructions, 88% (179 of 195); fasting duration, 37% (72 of 195); and time-of-day scheduling preference, 91% (177 of 195). Mean provided data were as follows: blood glucose threshold, 195 mg/dL (range, 150-210 mg/dL); short-acting insulin withholding, 4.9 hours (range, 4-8 hours); long-acting insulin withholding, 12 hours (range, 12-24 hours); fasting duration, 5 hours (range, 4-8 hours); and preferred examination time, 91% (177 of 195). When specified (n = 18), morning scheduling was preferred (8% [15 of 195] versus 2% [3 of 195]). Conclusions Diabetes-specific information is commonly withheld by nuclear medicine call centers throughout the United States when discussing oncologic FDG PET/CT despite local and national policies indicating its importance.

A large hepatic mixed echoic mass occupying the left fetal abdomen was identified at 266/7 weeks. The mass showed peripheral and internal vascularity. Other ultrasound findings included edema of the fetal head and face, macrosomia, shortened long bones, abnormal posture of hands, small stomach, polyhydramnios and biventricular hypertrophy. Fetal magnetic resonance imaging confirmed a hypervascular mass replacing the lateral left hepatic lobe, suggestive of a congenital hemangioma. The fetus was delivered by cesarean section at 282/7 weeks. The baby was stabilized at day 3 of life, and underwent successful selective tumor embolization. The baby remained stable for 3 days, then deteriorated with a progressive thickening of the myocardium. The child then passed away on day 11 from severe progressive hypertrophic cardiomyopathy, with almost complete obliteration of the left ventricular cavity; an autopsy was declined. Postnatal investigations reported a de novo heterozygous pathogenic HRAS variant (NM_005343.3(HRAS): c.35_36 delinsTT, p.Gly21Val), previously reported in 8 cases associated with the early, lethal form of Costello syndrome.

Focused deterrence approaches to domestic violence have been developed in the US to increase offender accountability and ensure appropriately targeted responses to victims. While innovative, the model has strong theoretical and empirical foundations. It is based on a set of fundamental principles and detailed analysis of domestic violence patterns and responses. This paper uses recent Australian research to explore the feasibility of adapting this model to an Australian context. Arguments in favour of the model, and possible barriers to implementation, are described. Based on an extensive body of Australian research on patterns of domestic violence offending and reoffending, and in light of recent developments in responses to domestic violence, this paper recommends trialling focused deterrence and ‘pulling levers’ to reduce domestic violence reoffending in an Australian pilot site.

BACKGROUND 18F-fluorodeoxyglucose positron emission tomography is an imaging modality critical to the diagnosis and staging of esophageal cancer. Despite this, the genetic abnormalities associated with increased 18F-fluorodeoxyglucose (FDG)-maximum standardized uptake value (SUVmax) have not been previously explored in esophageal adenocarcinoma. MATERIALS AND METHODS Treatment-naive patients, for whom frozen tissue and 18F-fluorodeoxyglucose positron emission tomography data were available, undergoing esophagectomy from 2003 to 2012, were identified. Primary tumor FDG-uptake (SUVmax) was quantified as low ( 10). Genome-wide expression analyses (e.g., microarray) were used to examine gene expression differences associated with FDG-uptake. RESULTS Eighteen patients with stored positron emission tomography data and tissue were reviewed. Overall survival was similar between patients with high (n = 9) and low (n = 6) FDG-uptake tumors (P = 0.71). Differences in gene expression between tumors with high and low FDG-uptake included enriched expression of various matrix metalloproteinases, extracellular-matrix components, oncogenic signaling members, and PD-L1 (fold-change>2.0, P

Chronic chest pain (CCP) of a cardiac etiology is a common clinical problem. The diagnosis and classification of the case of chest pain has rapidly evolved providing the clinician with multiple cardiac imaging strategies. Though scintigraphy and rest echocardiography remain as appropriate imaging tools in the diagnostic evaluation, new technology is available. Current evidence supports the use of alternative imaging tests such as coronary computed tomography angiography (CCTA), cardiac MRI (CMRI), or Rb-82 PET/CT. Since multiple imaging modalities are available to the clinician, the most appropriate noninvasive imaging strategy will be based upon the patient's clinical presentation and clinical status. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

While there is no single diagnostic test for heart failure (HF), imaging plays a supportive role beginning with confirmation of HF, especially by detecting ventricular dysfunction ( Variant 1 ). Ejection fraction (EF) is important in HF classification, and imaging plays a subsequent role in differentiation between HF with reduced EF (HFrEF) versus preserved EF (HFpEF) ( Variant 2 ). Once HFrEF is identified, distinction between ischemic and nonischemic etiologies with imaging support ( Variant 3 ) facilitates further planning. Imaging approaches which are usually appropriate include: both resting transthoracic echocardiography (TTE) and chest radiography for Variant 1 ; resting TTE and/or MRI (including functional, without absolute need for contrast) for Variant 2 ; and for Variant 3 , a. Coronary CTA or coronary arteriography (if high pretest probability/symptoms for ischemic disease) for coronary assessment; b. Rest/vasodilator stress SPECT/CT, PET/CT, or MRI for myocardial perfusion assessment; c. Rest/exercise or inotropic stress TTE for myocardial contraction assessment; or d. MRI (including morphologic with contrast) for myocardial characterization. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Imaging surveillance after treatment for head and neck cancer is challenging because of complicated resection and reconstruction surgery, in addition to posttreatment changes from radiation and chemotherapy. The posttreatment neck is often a source of anxiety for diagnostic radiologists, leading to suboptimal reporting and no standardized guidance for next management steps. Nevertheless, imaging is critical for detecting submucosal recurrences in a timely manner, so that patients remain candidates for salvage surgery. In 2016, the ACR convened the Neck Imaging Reporting and Data Systems (NI-RADS) Committee with the goals to (1) provide recommendations for surveillance imaging; (2) produce a lexicon to distinguish between benign posttreatment change and residual or recurrent tumor in the posttreatment neck; and (3) propose a NI-RADS template for reporting on the basis of this lexicon with defined levels of suspicion and management recommendations. In this article, the authors present the ACR NI-RADS Committee's recommendations, which provide guidance regarding the management of patients after treatment for head and neck cancer.

Rationale and Objectives This study aimed to determine the preferences of radiology and referring provider residents regarding direct communication of radiology test results. Methods This Health Insurance Portability and Accountability Act-compliant quality improvement effort was exempt from institutional review board oversight. An anonymous survey was emailed to 44 radiology residents and 364 referring resident providers who routinely provide or receive direct communication of test results at our quaternary care medical center. The survey focused on the frequency, indication, clinical utility, and methods of direct communication of radiology results. Proportions were compared to chi-square or Fisher exact test. Results The response rates were 86% (37 of 43) (radiology) and 41% (151 of 364) (referring providers). Approximately half of radiology residents (49% [18 of 37]) thought the frequency of direct verbal communication was excessive, and none (0 of 37) thought more communication was needed. In contrast, only 1.3% (2 of 151; P Conclusions Referring providers prefer direct communication of radiology results, even for non-urgent unexpected findings, whereas radiology residents prefer less direct communication and are more likely to consider radiologist-to-provider communication superfluous.

The incidence of congenital heart disease (CHD) has been increasing in the adult patient population in part as a result of better patient survival. Patients with more severe CHD are living longer. Nearly all adults with known CHD require periodic imaging as a means of monitoring their disease process. Furthermore, adult patients with suspected CHD require imaging as a means of definitive diagnosis. As a result, it is important for both the referring clinician and the imager to be aware of the most appropriate imaging modality needed to obtain the data most needed to direct the next steps in patient care. Imaging procedures for the diagnosis of known or suspected CHD in the adult include chest radiography, fluoroscopy, echocardiography, nuclear scintigraphy, cardiac-gated CT, MRI, and cardiac catheterization/angiography. The physician trying to diagnose these often complex conditions needs complete and reliable information that includes details about intracardiac and vascular anatomy, hemodynamics, and function. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer-reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

In patients with chronic chest pain in the setting of high probability of coronary artery disease (CAD), imaging has major and diverse roles. First, imaging is valuable in determining and documenting the presence, extent, and severity of myocardial ischemia, hibernation, scarring, and/or the presence, site, and severity of obstructive coronary lesions. Second, imaging findings are important in determining the course of management of patients with suspected chronic myocardial ischemia and better defining those patients best suited for medical therapy, angioplasty/stenting, or surgery. Third, imaging is also necessary to determine the long-term prognosis and likely benefit from various therapeutic options by evaluating ventricular function, diastolic relaxation, and end-systolic volume. Imaging studies are also required to demonstrate other abnormalities, such as congenital/acquired coronary anomalies and severe left ventricular hypertrophy, that can produce angina in the absence of symptomatic coronary obstructive disease due to atherosclerosis. Clinical risk assessment is necessary to determine the pretest probability of CAD. Multiple methods are available to categorize patients as low, medium, or high risk for developing CAD. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

This article discusses imaging guidelines for five dyspnea variants: (1) dyspnea due to heart failure, ischemia not excluded; (2) dyspnea due to suspected nonischemic heart failure, ischemia excluded; (3) dyspnea due to suspected valvular heart disease, ischemia excluded; (4) dyspnea due to suspected cardiac arrhythmia, ischemia excluded; and (5) dyspnea due to suspected pericardial disease, ischemia excluded. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Pulmonary embolism (PE) remains a common and important clinical condition that cannot be accurately diagnosed on the basis of signs, symptoms, and history alone. The diagnosis of PE has been facilitated by technical advancements and multidetector CT pulmonary angiography, which is the major diagnostic modality currently used. Ventilation and perfusion scans remain largely accurate and useful in certain settings. Lower-extremity ultrasound can substitute by demonstrating deep vein thrombosis; however, if negative, further studies to exclude PE are indicated. In all cases, correlation with the clinical status, particularly with risk factors, improves not only the accuracy of diagnostic imaging but also overall utilization. Other diagnostic tests have limited roles. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer-reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Purpose To determine the magnitude of subject-level and population-level cost savings that could be realized by moving from fixed-volume low-osmolality iodinated contrast material administration to an effective weight-based dosing regimen for contrast-enhanced abdominopelvic CT. Methods HIPAA-compliant, institutional review board–exempt retrospective cohort study of 6,737 subjects undergoing contrast-enhanced abdominopelvic CT from 2014 to 2015. Subject height, weight, lean body weight (LBW), and body surface area (BSA) were determined. Twenty-six volume- and weight-based dosing strategies with literature support were compared with a fixed-volume strategy used at the study institution: 125 mL 300 mgI/mL for routine CT, 125 mL 370 mgI/mL for multiphasic CT (single-energy, 120 kVp). The predicted population- and subject-level effects on cost and contrast material utilization were calculated for each strategy and sensitivity analyses were performed. Results Most subjects underwent routine CT (91% [6,127/6,737]). Converting to lesser-volume higher-concentration contrast material had the greatest effect on cost; a fixed-volume 100 mL 370 mgI/mL strategy resulted in $132,577 in population-level savings with preserved iodine dose at routine CT (37,500 versus 37,000 mgI). All weight-based iodine-content dosing strategies (mgI/kg) with the same maximum contrast material volume (125 mL) were predicted to contribute mean savings compared with the existing fixed-volume algorithm ($4,053-$116,076/strategy in the overall study population, $1-$17/strategy per patient). Similar trends were observed in all sensitivity analyses. Conclusions Large cost and material savings can be realized at abdominopelvic CT by adopting a weight-based dosing strategy and lowering the maximum volume of administered contrast material.

Frostbite remains a challenging clinical scenario with multiple treatment algorithms and variable results. Currently, frostbite management often follows a conservative approach with rewarming followed by wound care and delayed amputation. We review seven patients where single-photon emission computed tomography (SPECT) fused with conventional computed tomography was used to evaluate tissue viability for earlier directed debridement and limb salvage. The goal of this report is to evaluate SPECT/CT as an appropriate modality for the screening of necrotic bone for earlier amputation in patients with frostbite. We retrospectively analyzed the records of seven patients (19 extremities) with frostbite who received SPECT/CT scans to evaluate deep tissue necrosis before digit amputation. All patients who presented within the first 24 hr following their injury without contraindications were initially treated with tissue plasminogen activator. Three patients met criteria and were treated with tissue plasminogen activator. Of the seven patients analyzed, none required revision amputation beyond the level predicted on SPECT/CT scan. No patients had viable tissue distal to the most distal extent of bone perfusion. In six of the patients, the SPECT/CT scan led to more distal amputation with proximal debridement of soft tissues thus maintaining extremity length. Frostbite remains a challenging clinical scenario for which there are a wide number of clinical algorithms. SPECT/CT appears to be valuable in the evaluation of frostbite to determine the need for amputation. Fusion of the nuclear images with the CT allows for more exact delineation of the level of amputation than a bone scan alone.

The objective of the present study is to evaluate patient understanding of radiology and radiologists and to assess patient interest in direct consultation with a radiologist.A total of 1976 adult radiology outpatients at both a university and a nearby community hospital were surveyed. After an initial survey was administered, educational material with an attached follow-up survey was distributed to the patients. A McNemar test was used to assess the difference between patients who correctly chose the radiologist as the image interpreter before and after educational material was provided, whereas a paired t test was used to test the difference between patient levels of comfort with various image interpreters.Of the respondents, 84% expressed interest in meeting with a radiologist, with 43% willing to pay $0, 37% willing to pay $10-$30, and 20% willing to pay $40 or more to do so. Small percentages of respondents incorrectly identified ultrasound (10%) and MRI (45%) examinations as using radiation, whereas larger percentages of respondents correctly identified radiography (87%), CT (63%), and nuclear medicine imaging (62%) examinations as using radiation. A total of 73% of respondents (1002/1369) initially chose the radiologist as the image interpreter; this percentage improved to 81% (1109/1369) after the respondents received educational material (p0.0001). Both before and after educational material was provided, respondents had a statistically significantly lower mean (± SD) comfort level score (scale, 1-10) when faced with the prospect of a nurse or physician assistant interpreting their examination versus a trained physician (i.e., a radiologist) (mean score, 5.2 ± 3.27 and 9.4 ± 1.47, respectively, before education [p0.0001] and 5.2 ± 2.94 and 9.56 ± 1.24, respectively, after education [p0.0001]).The level of comfort with radiologists as image interpreters was statistically significantly higher than the level of comfort with nonradiologist interpreters, and most patients were interested in meeting with radiologists. Educational material improved patient perception and knowledge of radiology.

Nuclear medicine studies are often performed in patients with breast cancer; however, incidental radiotracer uptake in the breasts can be observed in patients with nonbreast malignancies. Benign and malignant lesions can be identified on planar, SPECT, and PET scans. This review will outline the molecular and radiographic imaging appearance of benign and malignant breast lesions on sestamibi scans, bone scans, radioiodine studies, as well as PET studies using fluorine 18 ((18)F) fluorodeoxyglucose, gallium 68 ((68)Ga) tetraazacyclododecane tetraacetic acid octreotate (or DOTATATE), (68)Ga prostate-specific membrane antigen, and (18)F-fluciclovine radiotracers. Recognizing these lesions at molecular and anatomic imaging is important to ensure accurate diagnosis and appropriate management. Keywords: Breast, Mammography, Molecular Imaging, PET/CT, Radionuclide Studies, SPECT/CT © RSNA, 2020

Virtual reality (VR) systems can offer benefits of improved ergonomics, but their resolution may currently be limited for the detection of small features. For detection of lung nodules, we compared the performance of VR versus standard picture archiving and communication system (PACS) monitor. Four radiologists and 1 novice radiologist reviewed axial computed tomography (CTs) of the thorax using standard PACS monitors (SM) and a VR system (HTC Vive, HTC). In this study, 3 radiologists evaluated axial lung-window CT images of a Lungman phantom. One radiologist and the novice radiologist reviewed axial lung-window patient CT thoracic images (32 patients). This HIPAA-compliant study was approved by the institutional review board. Detection of 227 lung nodules on patient CTs did not result in different sensitivity with SM compared with VR. Detection of 23 simulated Lungman phantom lung nodules on CT with SM resulted in statistically greater sensitivity (78.3%) than with VR (52.2%, P = 0.041) for 1 of 3 radiologists. The trend was similar but not significant for the other radiologists. There was no significant difference in the time spent by readers reviewing CT images with VR versus SM. These findings indicate that performance of a commercially available VR system for detection of lung nodules may be similar to traditional radiology monitors for assessment of small lung nodules on CTs of the thorax for most radiologists. These results, along with the potential of improving ergonomics for radiologists, are promising for the future development of VR in diagnostic radiology.

The purpose of this study was to evaluate the clinical utility of Deauville scores in interpretation of end-of-chemotherapy FDG PET scans.Deauville scores improve the clinical utility of end-of-chemotherapy PET, as evidenced by an increase in positive predictive value to 72.7% from 44.4% on the basis of report alone. The negative predictive value remains greater than 95%.

Magnetic resonance imaging (MRI) is an extremely useful tool for the detection and characterization of numerous pathologic processes. Although patients can benefit from the use of MRI, claustrophobia is a major issue in some cases. This fear alone can lead to cancellation of the scanning procedure in some cases and the need for conscious sedation in others. Patient anxiety during the scan can also lead to increased motion-related artifacts on the images with associated degradation of the diagnostic quality of the study. To alleviate these problems, our team developed a virtual reality (VR) tool (app) to educate patients about MRI and simulate the experience of actually being scanned. The app is totally immersive and incorporates both the visual and auditory sensations that patients encounter during an MRI scan. Patients also learn about potential conditions and implanted devices that may preclude the safe performance of the examination. This VR tool not only educates patients about MRI and its importance in their care, but also allows them to virtually experience what it is like to have a MRI scan. This technology has the potential to decrease both claustrophobic cancellations and patient anxiety before a MRI scan.

In the pursuit of realistically achievable design options for demonstrating fusion electricity generation and tritium self-sufficiency in a device to follow ITER, it is vital to explore as fully as possible the available design space and technology options which might lead to a fusion power plant within the timescales envisioned by the EU Roadmap to Fusion Energy. The usual tool for exploring this space is a systems code, such as PROCESS, which seeks to model all important plant systems and physics to provide an integrated power plant design point. However, currently many of these models are tied to assumptions of ITER-like technology and therefore tend to lead to ITER-like plant solutions. This contribution describes a broader set of plant configurations being considered alongside the main baseline design, investigating the impacts on design and costs of designing for (1) flexi-pulsed-steady-state operation, (2) double-null divertors, and (3) the use of high-temperature superconductors. The focus of the work presented here, however, is on (4) advanced magnetic configurations such as snowflake and super-X divertors. We discuss the modifications necessary for the systems code to simulate these configurations and their performance, particularly the divertor geometry and power handling capability; rapid engineering analysis of TF and PF coil positions which can achieve both the required equilibrium and remote-handling access; and initial wider analysis of the physics, neutronics, and other considerations. The reductions in wall area available for breeding tritium affect the choice of blanket technology, and remote handling considerations have a strong impact on the configurations which can be considered reasonable from an engineering and availability perspective. The benefits, disadvantages, risks, and power plant relevance of each configuration over the baseline DEMO design are discussed.

Background 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) is critical for staging non-small-cell lung cancer (NSCLC). While PET intensity carries prognostic significance, the genetic abnormalities associated with increased intensity remain unspecified. Methods NSCLC samples (N = 34) from 1999 to 2011 for which PET data were available were identified from a prospectively collected tumor bank. PET intensity was classified as mild, moderate, or intense based on SUVmax measurement or radiology report. Associations between genome-wide expression (RNAseq) and PET intensity were determined. Associations with overall survival were then validated in two external NSCLC cohorts. Results Overall survival was significantly worse in patients with PET-intense (N = 11) versus mild (N = 10) tumors (p = 0.039). Glycolytic gene expression patterns were markedly similar between intense and mild tumors. Gene ontology analysis demonstrated significant enhancement of cell-cycle and proliferative processes in FDG-intense tumors (p

The study aimed to determine if intrathoracic fat volumes are associated with the presence and severity of systemic sclerosis (SSc), defined by the presence of pulmonary arterial hypertension (PAH).A total of 265 patients were included in the study, 202 of whom had SSc (134 had SSc with no PAH and 68 had SSc-associated PAH) and who underwent high-resolution computed tomography, and 63 controls who underwent coronary computed tomography angiography with calcium scoring. Intrathoracic and epicardial (EFV) fat volumes were quantified by manual tracing of the mediastinum and the pericardium, the difference of which represents the extrapericardial fat volume. Associations between these three fat volumes and the presence and severity of SSc, adjusted for cardiovascular risk factors and interstitial lung disease, were evaluated by logistic regression analysis.Of the 202 patients with SSc, the mean age was 55 years (ranged from 20 to 86), and 79% (159 of 202) were women. Adjusted EFV (odds ratio [OR]: 1.065; 95% confidence interval [CI]: 1.046-1.084, P = 0.0001), extrapericardial fat volume (OR: 1.028, 95% CI: 1.017-1.038, P = 0.0001), and intrathoracic fat volume (OR: 1.033, 95% CI: 1.023-1.043, P = 0.001) were associated with the presence of SSc. Only EFV was associated with SSc severity (adjusted OR: 1.010, 95% CI: 1.003-1.018, P = 0.007).Increased epicardial fat volume is associated with the presence and severity of SSc, independent of cardiovascular risk factors and interstitial lung disease.

The diagnosis of dementia syndromes can be challenging for clinicians, particularly in the early stages of disease. Patients with higher education levels may experience a marked decline in cognitive function before their dementia is detectable with routine testing methods. In addition, comorbid conditions (eg, depression) and the use of certain medications can confound the clinical assessment. Clinicians require a high degree of certainty before making a diagnosis of Alzheimer disease or some other neurodegenerative disorder, since the impact on patients and their families can be devastating. Moreover, accurate diagnosis is important because emerging therapeutic regimens vary depending on the cause of the dementia. Clinically based testing is useful; however, the results usually do not enable the clinician to make a definitive diagnosis. For this reason, imaging biomarkers are playing an increasingly important role in the workup of patients with suspected dementia. Positron emission tomography with 2-[fluorine-18]fluoro-2-deoxy-D-glucose allows detection of neurodegenerative disorders earlier than is otherwise possible. Accurate interpretation of these studies requires recognition of typical metabolic patterns caused by dementias and of artifacts introduced by image processing. Although visual interpretation is a vital component of image analysis, computer-assisted diagnostic software has been shown to increase diagnostic accuracy.

Radioiodine imaging has a well-established role in depicting metastatic disease after thyroidectomy in patients with well-differentiated thyroid cancer. Uptake of radioiodine in thyroid metastases depends on expression of sodium-iodide symporter (NIS) by tumor tissues. However, because radioiodine may also accumulate in normal structures and tissues, it is important to distinguish physiologic radioiodine activity from metastatic disease. Furthermore, secretions that contain radioiodine may also simulate pathologic uptake. A spectrum of physiologic distributions, normal variants, and benign mimics of disease have been described in the literature; yet, even when armed with a comprehensive knowledge of these patterns, interpreting radiologists and nuclear physicians may still encounter diagnostic uncertainty. Single-photon emission computed tomography (SPECT) with integrated computed tomography (CT) is a novel technology that, when applied to diagnostic iodine 123 or iodine 131 ((131)I) radioiodine scintigraphy, may accurately localize and help distinguish benign mimics of disease, with the potential to alter the management plan. SPECT/CT is increasingly being used with radioiodine scintigraphy to evaluate patients with thyroid cancer and shows promise for improving imaging specificity and reducing false-positive results.

Purpose The aim of this study was to determine if direct in-person communication between an acute care surgical team and radiologists alters surgical decision making. Methods Informed consent was waived for this institutional review board-exempt, HIPAA-compliant, prospective quality improvement study. From January 29, 2015 to December 10, 2015, semiweekly rounds lasting approximately 60 min were held between the on-call acute care surgery team (attending surgeon, chief resident, and residents) and one of three expert abdominal radiologists. A comprehensive imaging review was performed of recent and comparison examinations for cases selected by the surgeons in which medical and/or surgical decision making was pending. All reviewed examinations had available finalized reports known to the surgical team. RADPEER interradiologist concordance scores were assigned to all reviewed examinations. The impression and plan of the attending surgeon were recorded before and after each in-person review. Results One hundred patients were reviewed with 11 attending surgeons. The in-person meetings led to changes in surgeons' diagnostic impressions in 43% (43 of 100) and changes in medical and/or surgical planning in 43% (43 of 100; 20 acute changes, 23 nonacute changes, 19 changes in operative management) of cases. There were major discrepancies (RADPEER score ≥3) between the impression of the reviewing radiologist and the written report in 11% of cases (11 of 100). Conclusions Targeted in-person collaboration between radiologists and acute care surgeons is associated with substantial and frequent changes in patient management, even when the original written report contains all necessary data. The primary mechanism seems to be promotion of a shared mental model that facilitates the exchange of complex information.

This document outlines the usefulness of available diagnostic imaging for patients without known coronary artery disease and at low probability for having coronary artery disease who do not present with classic signs, symptoms, or electrocardiographic abnormalities indicating acute coronary syndrome but rather with nonspecific chest pain leading to a differential diagnosis, including pulmonary, gastrointestinal, or musculoskeletal pathologies. A number of imaging modalities are available to evaluate the broad spectrum of possible pathologies in these patients, such as chest radiography, multidetector CT, MRI, ventilation-perfusion scans, cardiac perfusion scintigraphy, transesophageal and transthoracic echocardiography, PET, spine and rib radiography, barium esophageal and upper gastrointestinal studies, and abdominal ultrasound. It is considered appropriate to start the assessment of these patients with a low-cost, low-risk diagnostic test such as a chest x-ray. Contrast-enhanced gated cardiac and ungated thoracic multidetector CT as well as transthoracic echocardiography are also usually considered as appropriate in the evaluation of these patients as a second step if necessary. A number of rest and stress single-photon emission CT myocardial perfusion imaging, ventilation-perfusion scanning, aortic and chest MR angiographic, and more specific x-ray and abdominal examinations may be appropriate as a third layer of testing, whereas MRI of the heart or coronary arteries and invasive testing such as transesophageal echocardiography or selective coronary angiography are not considered appropriate in these patients. Given the low risk of these patients, it is mandated to minimize radiation exposure as much as possible using advanced and appropriate testing protocols. The ACR Appropriateness Criteria® are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

There has been no comparison of concordance rates for residents' and faculty members' interpretations of pulmonary embolism (PE) CT and ventilation/perfusion (V/Q) studies. If significantly different rates of agreement are demonstrable, this could influence which test is ordered during off hours. The purpose of this study was to evaluate how the performance of residents compared with that of faculty members in interpreting these two modalities.Interobserver agreement between preliminary resident reports and final attending radiologist interpretations was calculated retrospectively for PE CT studies (n = 1,179) and V/Q scans (n = 331) interpreted by on-call residents from April 2007 to October 2008. Discordant cases were reviewed for clinical significance and outcomes at 3 months. Interobserver variability was also evaluated relative to residents' training levels and faculty members' years of experience.Interobserver agreement between faculty members and residents was substantial, at 95% for PE CT (κ = 0.77) and 77.9% for V/Q scans (κ = 0.67). Although changes in interpretation were significantly more common with V/Q scans (22.1% vs 5%; χ(2).0001), the rates of clinically significant discrepancy did not differ significantly between the modalities (2.1% for V/Q vs 1.2% for PE CT; χ(2)P = .20). The overall discrepancy rate and the rate of clinically significant discrepancy did not correlate with residents' training levels or faculty members' years of experience.Concordance rates for residents' interpretations of V/Q scans and PE CT studies were high, and discrepancies resulting in changes in patient management were rare for both modalities. Residents' preliminary interpretations of both modalities are reliable and safe for making initial patient management decisions.

Focal incidental renal lesions are commonly encountered on positron emission tomography (PET)/computed tomography (CT) imaging. The vast majority of these lesions are benign. However, the interpretation of renal lesions can be problematic if the imaging criteria of simple cysts are not met. Limited literature exists on the characterisation of renal masses with metabolic imaging. The purpose of this article is to focus on the imaging features of benign and malignant renal masses with PET/CT. The lesions discussed include renal cyst, angiomyolipoma, oncocytoma, renal cell carcinoma, renal metastases and other infiltrating neoplastic processes affecting the kidney. Both the anatomical and metabolic features which characterise these benign and malignant entities are described. We emphasise the importance of viewing the CT component to identify the typical morphological features and discuss how to best use hybrid imaging for management of renal lesions. Metabolic imaging has a promising role in the imaging of renal lesions and can help prevent unnecessary biopsies and ensure optimal management of suspicious lesions.

Esophageal cancer has been increasing in incidence for the last several decades. The current staging evaluation includes computed tomography, endoscopic ultrasonography, and F-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT), which influences the treatment options. PET/CT is limited in its ability to differentiate hypermetabolic metastatic disease from acute/chronic inflammatory conditions, and this must be considered during interpretation. This is the case report of a 77-year-old man with esophageal cancer whose PET/CT demonstrated increased F-18 FDG uptake in the right lobe of the liver. This was originally interpreted at an outside institution as suspicious for metastatic disease, which would have precluded potential surgical cure. Subsequent reinterpretation and additional imaging including magnetic resonance imaging suggested that the uptake in the liver was likely due to adjacent gallbladder inflammation. On the basis of this interpretation, an abdominal exploration, liver biopsy, cholecystectomy, and transhiatal esophagectomy were performed. Final pathology of the gallbladder revealed perforated cholecystitis and a pericholecystic abscess (related to a prior septic episode), which were responsible for the increased radiotracer uptake. This case is presented to illustrate the importance of considering benign etiologies that may mimic metastatic disease when interpreting PET/CT scans.

The purpose of this study was to determine the diagnostic yield and clinical importance of delayed whole-body bone scintigraphy in directed three-phase examinations.The records of 400 consecutively registered patients who underwent combined three-phase and delayed whole-body (99m)Tc-methylene diphosphonate bone scintigraphy for a variety of indications were reviewed. Clinical indications, findings, recommendations, and outcome were assessed.Three-phase bone scintigraphy was performed on 156 men and boys and 244 women and girls (61%). Fifty-two patients (13%) were 17 years old or younger, and 236 patients (59%) were older than 40 years. The mean increase in study duration due to whole-body imaging was 25 minutes (range, 21-31 minutes). Excluding the three-phase area of interest, the whole-body examination had a normal tracer distribution in 131 examinations (33%), showed solely degenerative changes in 103 (26%), and showed findings unrelated to the area of interest in 166 patients (41%). In no case did the findings outside the area of interest alter the diagnosis or diagnostic certainty in the three-phase study, but those findings did generate 82 recommendations for additional diagnostic investigation. As a direct result of the recommendations, clinicians requested 18 radiographic, two CT, one MRI, and one ultrasound examinations, one additional bone scan, and two referrals to a consultant. Recommendations based on findings outside the three-phase area of interest affected treatment in one case: Temporomandibular joint uptake resulted in a referral for physical therapy.For most indications, delayed whole-body imaging after directed three-phase bone scintigraphy does not improve diagnostic yield, does not alter patient care, and may be an unnecessary use of medical resources.

A 27-year-old male presented with recurrent abdominal pain and high volume hematochezia despite undergoing extensive testing and a right hemicolectomy 3 years prior for a linear bleeding ulceration in the ascending colon. Studies at the University of Michigan included esophagogastroduodenoscopy (EGD), colonoscopy and video capsule endoscopy (VCE), revealing an arteriovenous malformation (AVM) in the terminal ileum. He was hospitalized for recurrent symptoms. His presentation suggested a small bowel source of obscure-overt GI bleeding based on prior non-diagnostic colonoscopy and EGD and a bilious nasogastric lavage. Tagged red blood cell scan localized bleeding to the right lower quadrant. Colonoscopy showed fresh blood in the terminal ileum without a clear source. Angiography showed no evidence of bleeding or terminal ileal AVM. A novel Meckel’s scan fused with SPECT imaging showed focal uptake in the terminal ileum. The patient underwent Meckel’s diverticulectomy with sparing of adjacent bowel and has remained asymptomatic for 19 months. This case illustrates that patients with obscure-overt GI bleeding require a step-wise multi-modality diagnostic work-up. Because Meckel’s scans are false-positive in 28% of adults, Meckel’s scan fused with SPECT imaging may offer an approach to refine diagnostic accuracy of either scan alone, but requires further investigation. Exploratory laparotomy should be reserved as a last option and is best performed with intraoperative endoscopy.

Rationale and Objectives We sought to assess the ability of 18F-fluoro-2-deoxy- d -glucose (FDG) PET/CT to distinguish adrenal adenomas from nonadenomas in patients with suspected malignancy. Methods Fifty-nine adrenal masses were evaluated with coregistered 18F-FDG PET (PET/CT). Two reviewers independently graded uptake of 18F-FDG by visual inspection of the adrenal mass in comparison to liver and background. CT attenuation value of the adrenal mass and the standardized uptake value (SUV) of the mass, liver, background, and primary neoplasm (when visible) were measured. Mean SUVs of the adrenal mass, liver, and background and ratios of the SUVs were calculated. Results Of 47 adenomas, 43 measured 10 HU on unenhanced CT. Using qualitative assessment of FDG activity in the adrenal mass compared with liver, adenomas were less than, equal to, or more active than the liver in 51%, 38%, and 10%, respectively. Nonadenomas were less than, equal to, or more active than liver in 0%, 25%, and 75%, respectively. The mean SUV of adenomas (4.2) was significantly lower (P = .002) than that of their primary malignancies (9.2) but not that of liver (4.3). The mean SUV of adenomas was not significantly different than that of nonadenomas (5.2), but the mean adrenal/liver ratio (1.0) for the adenomas was significantly lower (P = .006) than that of the nonadenomas (2.1). Conclusion Adrenal adenomas were better differentiated from nonadenomas using unenhanced CT measurements in combination with ratios of the SUVs. Adrenal mass activity, which was visibly less than liver, was more specific for adenoma, whereas adrenal mass activity visibly greater than liver was more specific for malignancy.

Primary imaging options in patients at low risk for coronary artery disease (CAD) who present with undifferentiated chest pain and without signs of ischemia are functional testing with exercise or pharmacologic stress-based electrocardiography, echocardiography, or myocardial perfusion imaging to exclude myocardial ischemia after rule-out of myocardial infarction and early cardiac CT because of its high negative predictive value to exclude CAD. Although possible, is not conclusive whether triple-rule-out CT (CAD, pulmonary embolism, and aortic dissection) might improve the efficiency of patient management. More advanced noninvasive tests such as cardiac MRI and invasive imaging with transesophageal echocardiography or coronary angiography are rarely indicated. With increased likelihood of noncardiac causes, a number of diagnostic tests, among them ultrasound of the abdomen, MR angiography of the aorta with or without contrast, x-ray rib views, x-ray barium swallow, and upper gastrointestinal series, can also be appropriate. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every three years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. This recommendation is based on excellent evidence, including several randomized comparative effectiveness trials and blinded observational cohort studies.