Subgroup Variation in Diagnostic Tests: Sources and Solutions

Diagnostic tests are an essential component of clinical medicine today. Like any other clinical study, the results of studies evaluating new diagnostic tests must be interpreted in the context of underlying methodological problems and generalizability. Subgroup variation in diagnostic test accuracy, the focus of this paper, can arise in two ways: the test truly performs differently in the two subgroups or it is an artifact. Real subgroup variation affects the generalizability of the results. Artifacts, however, arise from biased measurement (e.g. an imperfect reference standard) and affect the believability of the results. The question is whether real subgroup variation can be separated from artifact. Sources of subgroup variation and examples are presented with the specific focus on true subgroup variation and spurious variation due to the use of . imperfect reference standards. Both true variation and the use of imperfect reference standards are shown to be quite common. Frequently used tests, such as the urine dipstick for urinary tract infection, exhibit true subgroup variation. Observed test characteristics derived from comparison to an imperfect reference are shown to be prevalence-dependent. The effect of measurement reliability is discussed as a third source of potential subgroup variation. Two basic approaches for managing imperfect reference standards are reviewed: estimation techniques and methods for augmenting imperfect references. The emphasis is on the method ofHui and Walter, which provides a closed form expression for identifYing the unknown characteristics of the new test and the reference test in two populations. An alternate derivation is also provided that may be more accessible to the non-statistician. Methods for identifying true subgroup variation, simple stratification and regression analysis, as well as methods for incorporating subgroup variation into clinical decision making are presented to round out the general discussion of subgroup variation. IdentifYing subgroup variation and accounting for covariates in diagnostic test parameters is not significantly different from similar analyses in studies of interventions. The use of likelihood ratios to measure the impact of subgroup variation on decision making as well as a means for mitigating poor generalizability (spectrum bias) of a test when used in a population with a different severity of disease completes the discussion. The paper is concluded with a methodology for distinguishing true subgroup variation from spurious subgroup variation due to an imperfect reference standard.Master of Public Healt

Investigating the relationship between radiographic joint space width loss and deep learning-derived magnetic resonance imaging-based cartilage thickness loss in the medial weight-bearing region of the tibiofemoral joint

Objective To investigate the relationship between measures of radiographic joint space width (JSW) loss and magnetic resonance imaging (MRI)-based cartilage thickness loss in the medial weight-bearing region of the tibiofemoral joint over 12–24 months. To stratify this relationship by clinically meaningful subgroups (sex and pain status). Design We analyzed a subset of knees (n ​= ​256) from the Osteoarthritis Initiative (OAI) likely in early stage OA based on joint space narrowing (JSN) measurements. Natural logarithm transformation was used to approximate near normal distributions for JSW loss. Pearson Correlation coefficients described the relationship between ln-transformed JSW loss and several versions of deep learning-derived MRI-based cartilage thickness loss parameters (minimum, maximum, and mean) in subregions of the femoral condyle, tibial plateau, and combined femoral and tibial regions. Linear mixed-effects models evaluated the associations between the ln-transformed radiographic and MRI-derived measures including potential confounders. Results We found weak correlations between ln-transformed JSW loss and MRI-based cartilage thickness ranging from R ​= ​−0.13 (p ​= ​0.20) to R ​= ​0.26 (p ​< ​0.01). Correlations were higher (still poor) among females compared to males and painful compared to non-painful knees. Model results showed weak associations for nearly all MRI-based measures, ranging from no association to β (95% CI) ​= ​0.25 (0.11, 0.39). Associations were higher among females compared to males and minimal differences between painful and non-painful knees. Conclusions Despite its recommended use in disease-modifying OA drug clinical trials, results suggest that JSW loss is an ineffective proxy measure of cartilage thickness loss over 12–24 months and within a localized region of the tibiofemoral joint

Multimodal Diagnostic Approaches to Advance Precision Medicine in Sarcopenia and Frailty

Sarcopenia, defined as the loss of muscle mass, strength, and function with aging, is a geriatric syndrome with important implications for patients and healthcare systems. Sarcopenia increases the risk of clinical decompensation when faced with physiological stressors and increases vulnerability, termed frailty. Sarcopenia develops due to inflammatory, hormonal, and myocellular changes in response to physiological and pathological aging, which promote progressive gains in fat mass and loss of lean mass and muscle strength. Progression of these pathophysiological changes can lead to sarcopenic obesity and physical frailty. These syndromes independently increase the risk of adverse patient outcomes including hospitalizations, long-term care placement, mortality, and decreased quality of life. This risk increases substantially when these syndromes co-exist. While there is evidence suggesting that the progression of sarcopenia, sarcopenic obesity, and frailty can be slowed or reversed, the adoption of broad-based screening or interventions has been slow to implement. Factors contributing to slow implementation include the lack of cost-effective, timely bedside diagnostics and interventions that target fundamental biological processes. This paper describes how clinical, radiographic, and biological data can be used to evaluate older adults with sarcopenia and sarcopenic obesity and to further the understanding of the mechanisms leading to declines in physical function and frailty

Emergency and trauma radiology: a teaching file Teaching file./ Daniel B. Nissman ; associate editors, Katherine R. Birachard, Benjamin Y. Huang.

Includes bibliographical references and index."Part of the popular Teaching Files series, Emergency and Trauma Radiology: A Teaching File is an exceptional resource for radiology trainees and practicing radiologists who are interested in reviewing the basics of this diverse and challenging field. 300 cases, both in print and online, are portrayed through high-quality images similar to those you see in daily practice. Each emergency or trauma case includes images, along with descriptions of clinical history, findings, differential diagnosis, a discussion of diagnosis, relevant questions with appropriate answers, reporting requirements, and key information to relay to the treating physician. It's an ideal review tool both for practicing clinicians as well as those studying for board and certification exams. Key Features More than 300 cases (100 in print and an additional 200 in the interactive eBook) help you make accurate and informed diagnoses and study for exams. Actual cases have been taken from extensive teaching files in major medical centers. Each case is presented as an unknown, and in random order, for a close approximation to daily decision-making. Cases follow the same consistent format: a brief clinical history, several images, relevant findings, differential diagnosis, and final diagnosis, followed by a discussion of the case. Realistic case discussions mimic those between residents and faculty members in all radiology departments. Now with the print edition, enjoy the bundled interactive eBook edition, which can be downloaded to your tablet and smartphone or accessed online and includes features like: Complete content with enhanced navigation Powerful search tools and smart navigation cross-links that pull results from content in the book, your notes, and even the web Cross-linked pages, references, and more for easy navigation Highlighting tool for easier reference of key content throughout the text Ability to take and share notes with friends and colleagues Quick reference tabbing to save your favorite content for future use "--Hemorrhagic venous sinus thrombosis -- Adenocarcinoma mimicking pneumonia -- Bladder rupture -- Open book pelvis with arterial extravasation -- Mastoiditis -- Infected aortic stent graft with aortitis -- Adrenal hemorrhage -- Radiographic signs of ACL tear -- Jumped facets -- Bronchiectasis caused by aspiration -- Duodenal perforation -- Infected hip prosthesis -- Cerebral metastases -- Acute asthma exacerbation -- Ectopic pregnancy -- Medial epicondyle avulsion -- Cauda equina syndrome secondary to lumbar disk extrusion -- Traumatic bronchial injury -- Rectus sheath hematoma -- Lateral process of talus fracture -- ZMC fracture -- Empyema -- Cecal volvulus -- Posterior shoulder dislocation -- Hypoxic ischemic brain injury -- Flail chest -- Hangman fracture -- Trimalleolar ankle fracture -- Lemierre's syndrome -- Hydropneumothorax -- Testicular torsion -- Perilunate dislocation -- Chance fracture -- Acute aortic intramural hematoma -- Ingested foreign body -- Both column acetabular fracture -- Cerebral contusions -- Lung abscess -- Duodenal injury -- Tibial plateau fracture with meniscal entrapment -- Orbital cellulitis, epidural abscess, and meningitis -- Mediastinal hematoma -- Ovarian torsion -- Lisfranc fracture-dislocation -- Acute right MCA occlusion--"dense MCA" sign -- Myocardial ischemia -- Liver laceration -- Obscured cervicothoracic junction with anterolisthesis -- Acute subdural hematoma -- Pericarditis -- Malgaigne fracture -- Pediatric septic hip -- Carotid dissection -- Pneumocystis jiroveci pneumonia -- Mesenteric injury -- Monteggia fracture -- Retropharyngeal abscess -- Pneumothorax with deep sulcus sign -- Pneumoperitoneum -- Jefferson fracture -- Aneurysmal subarachnoid hemorrhage -- Posterior mediastinal hematoma -- Appendicitis -- Base of thumb metacarpal fracture -- Head and neck squamous cell cancer with nodal metastases -- Post-primary tuberculosis -- Ureteral injury -- Base of fifth metatarsal fracture -- Diffuse axonal injury -- Pulmonary edema (interstitial) -- Ulcerative proctocolitis -- Necrotizing fasciitis: pediatric -- Temporal bone fracture -- Pulmonary hemorrhage due to granulomatosis with polyangiitis -- Choledocholithiasis -- AC joint separation -- Ruptured AVM -- Tension pneumothorax -- Acute mesenteric ischemia -- Radio-occult hip fracture -- Pyogenic discitis and epidural abscess -- Knee dislocation -- Shotgun wounds -- Scaphoid fracture -- Acute multiple sclerosis flare -- Foreign body--ultrasound -- Foreign body urethra -- Septic arthritis (knee) -- Craniocervical dissociation -- Rib fracture with hemopneumothorax -- Pyloric stenosis -- Posterior hip dislocation with intra-articular fragment -- Acute transverse myelitis -- Medial head of gastrocnemius muscle tear -- Gastric volvulus -- Patellar tendon rupture -- Hypertensive basal ganglia hemorrhage -- Ventriculoperitoneal shunt malfunction -- Acute cholecystitis -- Diabetic foot with gas-forming infection.1 online resource (242 pages)

In Vivo Compositional Changes in the Articular Cartilage of the Patellofemoral Joint Following Anterior Cruciate Ligament Reconstruction

OBJECTIVE: To compare T1ρ relaxation times of the medial and lateral regions of the patella and femoral trochlea at 6 and 12 months following anterior cruciate ligament reconstruction (ACLR) on the ACLR and contralateral extremity. Greater T1ρ relaxation times are associated with a lower proteoglycan density of articular cartilage. METHODS: This study involved 20 individuals (11 males, 9 females; mean ± SD age 22 ± 3.9 years, weight 76.11 ± 13.48 kg, and height 178.32 ± 12.32 cm) who underwent a previous unilateral ACLR using a patellar tendon autograft. Magnetic resonance images from both extremities were acquired at 6 and 12 months post-ACLR. Voxel by voxel T1ρ relaxation times were calculated using a 5-image sequence. The medial and lateral regions of the femoral trochlea and patellar articular cartilage were manually segmented on both extremities. Separate extremity (ACLR and contralateral extremity) by time (6 months and 12 months) analysis of variance tests were performed for each region (P \u3c 0.05). RESULTS: For the medial patella and lateral trochlea, T1ρ relaxation times increased in both extremities between 6 and 12 months post-ACLR (medial patella P = 0.012; lateral trochlea P = 0.043). For the lateral patella, T1ρ relaxation times were significantly greater on the contralateral extremity compared to the ACLR extremity (P = 0.001). The T1ρ relaxation times of the medial trochlea on the ACLR extremity were significantly greater at 6 (P = 0.005) and 12 months (P \u3c 0.001) compared to the contralateral extremity. T1ρ relaxation times of the medial trochlea significantly increased from 6 to 12 months on the ACLR extremity (P = 0.003). CONCLUSION: Changes in T1ρ relaxation times occur within the first 12 months following ACLR in specific regions of the patellofemoral joint on the ACLR and contralateral extremity

Value of MRI of the hand and the wrist in evaluation of bone age: Preliminary results

Purpose To evaluate bone age determination using MRI of the hand and wrist. Materials and Methods A total of 179 (78 female and 101 males, 11 to 16 years old) subjects of 252 normal volunteers met entrance criteria. A low field open magnet (0.2 Tesla) was used for this study; coronal T1-weighted images with a slice thickness of 1.3 mm were acquired. Two blinded radiologists evaluated the studies and the following elements were considered: the appearance of cartilage, vacuolization of cartilage, provisional calcification, progression of ossification, and complete ossification. Correlation between chronologic age and MR bone age was determined by means of simple linear regression analysis. Results Strong correlation between MR skeletal age and chronological age was observed for both investigators, Pearson correlation R-2 = 0.9 for each. Conclusion Determination of bone age with MRI is feasible and shows good interobserver reproducibility. Data from this study may be useful to develop an atlas of skeletal development and bone age. J. Magn. Reson. Imaging 2014;39:1198-1205. (c) 2013 Wiley Periodicals, Inc

Association of Jump-Landing Biomechanics With Tibiofemoral Articular Cartilage Composition 12 Months After ACL Reconstruction

Background: Excessively high joint loading during dynamic movements may negatively influence articular cartilage health and contribute to the development of posttraumatic osteoarthritis after anterior cruciate ligament reconstruction (ACLR). Little is known regarding the link between aberrant jump-landing biomechanics and articular cartilage health after ACLR. Purpose/Hypothesis: The purpose of this study was to determine the associations between jump-landing biomechanics and tibiofemoral articular cartilage composition measured using T1ρ magnetic resonance imaging (MRI) relaxation times 12 months postoperatively. We hypothesized that individuals who demonstrate alterations in jump-landing biomechanics, commonly observed after ACLR, would have longer T1ρ MRI relaxation times (longer T1ρ relaxation times associated with less proteoglycan density). Study Design: Cross-sectional study; Level of evidence, 3. Methods: A total of 27 individuals with unilateral ACLR participated in this cross-sectional study. Jump-landing biomechanics (peak vertical ground-reaction force [vGRF], peak internal knee extension moment [KEM], peak internal knee adduction moment [KAM]) and T1ρ MRI were collected 12 months postoperatively. Mean T1ρ relaxation times for the entire weightbearing medial femoral condyle, lateral femoral condyle (global LFC), medial tibial condyle, and lateral tibial condyle (global LTC) were calculated bilaterally. Global regions of interest were further subsectioned into posterior, central, and anterior regions of interest. All T1ρ relaxation times in the ACLR limb were normalized to the uninjured contralateral limb. Linear regressions were used to determine associations between T1ρ relaxation times and biomechanics after accounting for meniscal/chondral injury. Results: Lower ACLR limb KEM was associated with longer T1ρ relaxation times for the global LTC (ΔR2 = 0.24; P =.02), posterior LTC (ΔR2 = 0.21; P =.03), and anterior LTC (ΔR2 = 0.18; P =.04). Greater ACLR limb peak vGRF was associated with longer T1ρ relaxation times for the global LFC (ΔR2 = 0.20; P =.02) and central LFC (ΔR2 = 0.15; P =.05). Peak KAM was not associated with T1ρ outcomes. Conclusion: At 12 months postoperatively, lower peak KEM and greater peak vGRF during jump landing were related to longer T1ρ relaxation times, suggesting worse articular cartilage composition