Real-World Validation of a Computer-Aided Diagnosis System for Prediction of Polyp Histology in Colonoscopy: A Prospective Multicenter Study.

INTRODUCTION: Computer-aided diagnosis (CADx) of polyp histology could support endoscopists in clinical decision-making. However, this has not been validated in a real-world setting. METHODS: We performed a prospective, multicenter study comparing CADx and endoscopist predictions of polyp histology in real-time colonoscopy. Optical diagnosis based on visual inspection of polyps was made by experienced endoscopists. After this, the automated output from the CADx support tool was recorded. All imaged polyps were resected for histological assessment. Primary outcome was difference in diagnostic performance between CADx and endoscopist prediction of polyp histology. Subgroup analysis was performed for polyp size, bowel preparation, difficulty of location of the polyps, and endoscopist experience. RESULTS: A total of 661 eligible polyps were resected in 320 patients aged ≥40 years between March 2021 and July 2022. CADx had an overall accuracy of 71.6% (95% confidence interval [CI] 68.0-75.0), compared with 75.2% (95% CI 71.7-78.4) for endoscopists ( P = 0.023). The sensitivity of CADx for neoplastic polyps was 61.8% (95% CI 56.9-66.5), compared with 70.3% (95% CI 65.7-74.7) for endoscopists ( P < 0.001). The interobserver agreement between CADx and endoscopist predictions of polyp histology was moderate (83.1% agreement, κ 0.661). When there was concordance between CADx and endoscopist predictions, the accuracy increased to 78.1%. DISCUSSION: The overall diagnostic accuracy and sensitivity for neoplastic polyps was higher in experienced endoscopists compared with CADx predictions, with moderate interobserver agreement. Concordance in predictions increased this diagnostic accuracy. Further research is required to improve the performance of CADx and to establish its role in clinical practice.

The utility of non-invasive tests to assess advanced fibrosis in Asian subjects with chronic hepatitis B and concomitant hepatic steatosis.

BACKGROUND: Chronic hepatitis B (CHB) is endemic to Asia and is a leading cause of liver-related morbidity. The prevalence of concomitant CHB and hepatic steatosis (HS) is increasing in Asia. Non-invasive tests (NITs) including FIB-4, NFS and APRI assess fibrosis in populations with a single aetiology, but not in subjects with concomitant CHB and HS. AIM: To explore the accuracy of NITs in predicting advanced fibrosis in patients with concomitant CHB and HS. METHODOLOGY: This multicentre study of CHB patients who underwent liver biopsy explored clinical characteristics of these subjects, stratified by presence of HS. Fibrosis scores from NITs were compared against histological fibrosis stage in CHB subjects with and without HS. RESULTS: 2262 subjects were enrolled, 74.5% were males, and the mean age was 39.5 years ±11.8 SD. 984 (44.4%) had HS, 824 (36.4%) had advanced fibrosis. In the CHB group, the AUROC for advanced fibrosis were 0.65 (95% CI 0.62-0.69) for FIB-4 and 0.63 (95% CI 0.60-0.66) for APRI. The specificities were 0.94 for FIB-4 greater than 3.25 and 0.81 for APRI greater than 1.5. In the CHBHS group, the AUROC for advanced fibrosis were 0.67 (95% CI 0.63-0.71) for FIB-4, 0.60 (95% CI 0.56-0.64) for APRI and 0.65 (95% CI 0.61-0.69) for NFS. The specificities were 0.95 for FIB-4 greater than 3.25, 0.88 for APRI greater than 1.5 and 0.99 for NFS greater than 0.675. CONCLUSION: The performance of NITs to exclude advanced fibrosis did not differ greatly regardless of HS. FIB-4 and NFS have the best negative predictive values of 0.80 and 0.78, respectively, to exclude advanced fibrosis in CHBHS subjects.

Emergence of Interlayer Coherence in Twist-Controlled Graphene Double Layers.

We report enhanced interlayer tunneling with reduced linewidth at zero interlayer bias in a twist-controlled double monolayer graphene heterostructure in the quantum Hall regime, when the top (ν_{T}) and bottom (ν_{B}) layer filling factors are near ν_{T}=±1/2,±3/2 and ν_{B}=±1/2,±3/2, and the total filling factor ν=±1 or ±3. The zero-bias interlayer conductance peaks are stable against variations of layer filling factor, and signal the emergence of interlayer phase coherence. Our results highlight twist control as a key attribute in revealing interlayer coherence using tunneling.

An Estimate of the US Rate of Overuse of Screening Colonoscopy: a Systematic Review.

BACKGROUND: This study aims to assess the rate at which screening colonoscopy is performed on patients younger or older than the age range specified in national guidelines, or at shorter intervals than recommended. Such non-indicated use of the procedure is considered low-value care, or overuse. This study is the first systematic review of the rate of non-indicated completed screening colonoscopy in the USA. METHODS: PubMed and Embase were queried for relevant studies on overuse of screening colonoscopy published from January 1, 2002, until January 23, 2019. English-language studies that were conducted for screening colonoscopy after 2001 for average-risk patients were included. Studies must have followed national guidelines for detecting rates of overuse. We followed methods outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and the reporting recommendations of the Meta-analysis of Observational Studies in Epidemiology group (MOOSE). RESULTS: A total of 772 papers were reviewed for inclusion; 42 were reviewed in full text. Of those reviewed, six studies met eligibility criteria, including a total of 459,503 colonoscopies of which 242,756 were screening colonoscopies. The rate of overuse ranged credibly from 17 to 25.7%. DISCUSSION: This study demonstrates that screening colonoscopy is regularly performed in the USA more often, and in populations older or younger, than recommended by national guidelines. Such overuse wastes resources and places patients at unnecessary risk of harm. Efforts to reduce non-indicated screening colonoscopy are needed.

A Surrogate Matrix-Based Approach Toward Multiplexed Quantitation of an sGC Stimulator and cGMP in Ocular Tissue and Plasma.

A liquid chromatography-tandem mass spectrometry assay was developed and qualified for the multiplexed quantitation of a small molecule stimulator of soluble guanylate cyclase (sGC) and its target engagement biomarker, 3',5'-cyclic guanosine monophosphate (cGMP), in ocular tissues and plasma from a single surrogate matrix calibration curve. A surrogate matrix approach was used in this assay due to the limited quantities of blank ocular matrices in a discovery research setting. After optimization, the assay showed high accuracy, precision, and recovery as well as parallelism between the surrogate matrix and the biological matrices (rabbit plasma, vitreous, and retina-choroid). This assay provided pharmacokinetic and target engagement data after intravitreal administration of the sGC stimulator. The nitric oxide-sGC-cGMP pathway is a potential target to address glaucoma. Increasing sGC-mediated production of cGMP could improve aqueous humor outflow and ocular blood flow. The sGC stimulator showed dose-dependent exposure in rabbit vitreous, retina-choroid, and plasma. The cGMP exhibited a delayed yet sustained increase in vitreous humor but not retina-choroid. Multiplexed measurement of both pharmacokinetic and target engagement analytes reduced animal usage and provided improved context for interpreting PK and PD relationships.

Nonpharmacologic and Pharmacologic Management of Acute Pain From Non-Low Back, Musculoskeletal Injuries in Adults: A Clinical Guideline From the American College of Physicians and American Academy of Family Physicians.

DESCRIPTION: The American College of Physicians (ACP) and American Academy of Family Physicians (AAFP) developed this guideline to provide clinical recommendations on nonpharmacologic and pharmacologic management of acute pain from non-low back, musculoskeletal injuries in adults in the outpatient setting. The guidance is based on current best available evidence about benefits and harms, taken in the context of costs and patient values and preferences. This guideline does not address noninvasive treatment of low back pain, which is covered by a separate ACP guideline that has also been endorsed by AAFP. METHODS: This guideline is based on a systematic evidence review on the comparative efficacy and safety of nonpharmacologic and pharmacologic management of acute pain from non-low back, musculoskeletal injuries in adults in the outpatient setting and a systematic review on the predictors of prolonged opioid use. We evaluated the following clinical outcomes using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system: pain (at ≤2 hours and at 1 to 7 days), physical function, symptom relief, treatment satisfaction, and adverse events. TARGET AUDIENCE AND PATIENT POPULATION: The target audience is all clinicians, and the target patient population is adults with acute pain from non-low back, musculoskeletal injuries. RECOMMENDATION 1: ACP and AAFP recommend that clinicians treat patients with acute pain from non-low back, musculoskeletal injuries with topical nonsteroidal anti-inflammatory drugs (NSAIDs) with or without menthol gel as first-line therapy to reduce or relieve symptoms, including pain; improve physical function; and improve the patient's treatment satisfaction (Grade: strong recommendation; moderate-certainty evidence). RECOMMENDATION 2A: ACP and AAFP suggest that clinicians treat patients with acute pain from non-low back, musculoskeletal injuries with oral NSAIDs to reduce or relieve symptoms, including pain, and to improve physical function, or with oral acetaminophen to reduce pain (Grade: conditional recommendation; moderate-certainty evidence). RECOMMENDATION 2B: ACP and AAFP suggest that clinicians treat patients with acute pain from non-low back, musculoskeletal injuries with specific acupressure to reduce pain and improve physical function, or with transcutaneous electrical nerve stimulation to reduce pain (Grade: conditional recommendation; low-certainty evidence). RECOMMENDATION 3: ACP and AAFP suggest against clinicians treating patients with acute pain from non-low back, musculoskeletal injuries with opioids, including tramadol (Grade: conditional recommendation; low-certainty evidence).

Increased tibiofemoral rotation on MRI with increasing clinical severity of patellar instability.

PURPOSE: Tibiofemoral rotation through the knee joint, specifically relative external tibial rotation, has been identified as a potential contributing factor to patellar instability. The purpose of this study is to investigate the relationship between severity of instability with degree of tibiofemoral rotation in three clinical cohorts: fixed or obligatory dislocators (in which the patella either is constantly laterally dislocated or laterally dislocates with every instance of knee flexion, respectively), standard traumatic instability patients, and normal controls. METHODS: A retrospective study was performed with three cohorts from April 2009 to February 2019: fixed or obligatory dislocators, standard traumatic instability patients, and controls with normal magnetic resonance imaging (MRI) of the knee. All fixed or obligatory dislocation patients from the study time frame were analyzed; controls and standard traumatic instability patients were randomly selected. Inclusion criteria were age under 18 years and qualifying diagnosis; exclusion criteria were outside institution MRI and previous MPFL reconstruction or tibial tubercle osteotomy. Tibiofemoral rotation was measured blindly on initial axial MRI using the posterior femoral and tibial condylar lines. Tibial tubercle to trochlear groove distance (TT-TG) was measured. Intraclass correlation coefficient (ICC) was calculated among four measurers. RESULTS: A total of 100 patients were included, 20 fixed or obligatory dislocators, 40 standard traumatic instability patients, and 40 controls. Median age was 13.2 years (range 10-17 years), with 55 females. Age was significantly higher in the standard traumatic instability group than both the control (p < 0.001) and fixed or obligatory dislocator groups (p = 0.003). ICC for TT-TG and tibiofemoral rotation were 0.92 and 0.96, respectively. Fixed or obligatory dislocator patients averaged 8.5° external tibiofemoral rotation, standard traumatic instability patients 1.6° external tibiofemoral rotation, and controls 3.8° internal tibiofemoral rotation. Both tibiofemoral rotation and TT-TG were highest in the fixed or obligatory dislocator cohort, followed by the standard traumatic instability cohort, and lowest in the controls (p < 0.0001 for tibiofemoral rotation and TT-TG). Multivariate analysis showed no correlation between age and tibiofemoral rotation. CONCLUSIONS: Measurement of tibiofemoral rotation was reproducible with excellent interrater reliability. The degree of tibiofemoral rotation is correlated with severity of patellar instability, with the greatest external tibiofemoral rotation in fixed or obligatory dislocator patients, followed by standard traumatic instability patients, and slight internal tibiofemoral rotation in controls. High external tibiofemoral rotation may be an important pathoanatomic factor in fixed or obligatory dislocators, and with further understanding may become a prognostic factor or surgical target. LEVEL OF EVIDENCE: III.

Public Health Surveillance for Zika Virus: Data Interpretation and Report Validity.

Zika virus provides an example for which public health surveillance is based primarily on health care provider notifications to health departments of potential cases. This case-based surveillance is commonly used to understand the spread of disease in a population. However, case-based surveillance is often biased-whether testing is done and which tests are used and the accuracy of the results depend on a variety of factors including test availability, patient demand, perceptions of transmission, and patient and provider awareness, leading to surveillance artifacts that can provide misleading information on the spread of a disease in a population and have significant public health practice implications. To better understand this challenge, we first summarize the process that health departments use to generate surveillance reports, then describe factors influencing testing and reporting patterns at the patient, provider, and contextual level. We then describe public health activities, including active surveillance, that influence both patient and provider behavior as well as surveillance reports, and conclude with a discussion about the interpretation of surveillance data and approaches that could improve the validity of surveillance reports.

Pediatric and adolescent anterior shoulder instability: clinical management of first-time dislocators.

PURPOSE OF REVIEW: The purpose of this review is to discuss the epidemiology, pathoanatomy, diagnosis, and clinical management of pediatric and adolescent patients following a first-time shoulder dislocation. RECENT FINDINGS: Shoulder instability is becoming increasingly common as pediatric and adolescent patients engage in earlier organized sports competition. Recommended treatment following a first-time glenohumeral dislocation event in adolescents depends on several factors, but surgical stabilization is becoming more frequently performed. Surgical indications include bony Bankart lesion, ALPSA lesion, bipolar injury (e.g. Hill-Sachs humeral head depression fracture) or off-season injury in an overhead or throwing athlete. Complications following surgical treatment are rare but most commonly are associated with recurrent instability. Young children (eg. open proximal humerus growth plate), individuals averse to surgery, or in-season athletes who accept the risk of redislocation may complete an accelerated rehabilitation program for expedited return to play in the absence of the structural abnormalities listed above. SUMMARY: Following a first-time dislocation event in pediatric and adolescent patients, a detailed discussion of the risks and benefits of nonoperative versus operative management is critical to match the recommended treatment with the patient's injury pattern, risk factors, and activity goals.

Automated Risk Assessment for School Violence: a Pilot Study.

School violence has increased over the past ten years. This study evaluated students using a more standard and sensitive method to help identify students who are at high risk for school violence. 103 participants were recruited through Cincinnati Children's Hospital Medical Center (CCHMC) from psychiatry outpatient clinics, the inpatient units, and the emergency department. Participants (ages 12-18) were active students in 74 traditional schools (i.e. non-online education). Collateral information was gathered from guardians before participants were evaluated. School risk evaluations were performed with each participant, and audio recordings from the evaluations were later transcribed and manually annotated. The BRACHA (School Version) and the School Safety Scale (SSS), both 14-item scales, were used. A template of open-ended questions was also used. This analysis included 103 participants who were recruited from 74 different schools. Of the 103 students evaluated, 55 were found to be moderate to high risk and 48 were found to be low risk based on the paper risk assessments including the BRACHA and SSS. Both the BRACHA and the SSS were highly correlated with risk of violence to others (Pearson correlations>0.82). There were significant differences in BRACHA and SSS total scores between low risk and high risk to others groups (p-values <0.001 under unpaired t-test). In particular, there were significant differences in individual SSS items between the two groups (p-value <0.001). Of these items, Previous Violent Behavior (Pearson Correlation = 0.80), Impulsivity (0.69), School Problems (0.64), and Negative Attitudes (0.61) were positively correlated with risk to others. The novel machine learning algorithm achieved an AUC of 91.02% when using the interview content to predict risk of school violence, and the AUC increased to 91.45% when demographic and socioeconomic data were added. Our study indicates that the BRACHA and SSS are clinically useful for assessing risk for school violence. The machine learning algorithm was highly accurate in assessing school violence risk.

Shoulder Activity Level is Associated With Type of Employment and Income in the Normative Population Without Shoulder Disorders.

BACKGROUND: Socioeconomic variables influence various healthcare issues in different ways. The effect of socioeconomic variables on the shoulder has not been well studied. Because activity level, defined by how much a patient actually does, is an important patient outcome measure and prognostic factor for the shoulder, studying its association with occupation and income will advance our understanding of how these variables relate to shoulder disorders, treatments, and outcomes. QUESTIONS/PURPOSE: We asked: (1) Does shoulder activity score correlate with income level, stratified by gender? (2) Do different employment groups-heavy, moderate, light, student, retired-have different shoulder activity scores, as stratified by gender? (3) Is type of sports participation (contact or overhead) associated with income level, employment type, race, or household size? METHODS: A survey collected the Brophy and Marx shoulder activity score and demographic information, such as age, gender, race, income, type of employment, and household size from 1625 individuals 18 years and older with no current or previous shoulder pain or injury who are members of a research panel matched to the United States population by age, gender, household income and size, race/ethnicity, and geography. Men and women were analyzed separately. Activity level was controlled for age. RESULTS: Shoulder activity correlated with income level among men (R = 0.03; p < 0.001) and women (R = 0.06; p = 0.0002). For men, heavy employment had the highest Shoulder Activity Scale (SAS) level (12.1 ± 4.9), which was more than SAS levels in sedentary (9.1 ± 4.5; mean difference, 3.0; 95% CI, 2.5-3.6; p = 0.001), student (8.8 ± 5.1; mean difference, 3.3; 95% CI, 3.0-3.7; p = 0.007), retired (8.0 ± 4.6; mean difference, 4.1; 95% CI, 3.6-4.7; p = 0.0001), and not working (7.5 ± 5.3; mean difference, 4.6; 95% CI, 4.6-4.6; p < 0.001) categories; similarly, for women, heavy employment had the highest SAS level (12.0 ± 5.8). However, as there were few women working in heavy labor, the only significant difference in women was between moderate employment (8.8 ± 4.2) and sedentary employment (7.0 ± 4.1; mean difference, 1.8; 95% CI, 1.6-1.9; p = 0.0015). Participation in contact (19.9% vs 12.0%; p = 0.006) and overhead sports (25.2% vs 14.2%; p < 0.001) was greater among males with higher incomes. CONCLUSIONS: Shoulder activity level is related to the socioeconomic factors of income and type of employment. Heavy laborers have higher shoulder activity level, likely directly related to their work. Individuals with higher incomes also have higher shoulder activity level, probably attributable to recreation as evidenced by their greater participation in contact and overhead sports. Independent of the underlying cause, these patients probably are more likely to seek treatment for shoulder disorders and may be more challenging to treat because of their elevated activity level. Future research should focus on how elevated activity level in these populations affects their risk for shoulder disorders, and their use of and outcomes from treatment for these disorders. LEVEL OF EVIDENCE: Level IV, prognostic study.

Multivalent 3D Display of Glycopolymer Chains for Enhanced Lectin Interaction.

Synthetic glycoprotein conjugates were synthesized through the polymerization of glycomonomers (mannose and/or galactose acrylate) directly from a protein macroinitiator. This design combines the multivalency of polymer structures with 3D display of saccharides randomly arranged around a central protein structure. The conjugates were tested for their interaction with mannose binding lectin (MBL), a key protein of immune complement. Increasing mannose number (controlled through polymer chain length) and density (controlled through comonomer feed ratio of mannose versus galactose) result in greater interaction with MBL. Most significantly, mannose glycopolymers displayed in a multivalent and 3D configuration from the protein exhibit dramatically enhanced interaction with MBL compared to linear glycopolymer chains with similar total valency but lacking 3D display. These findings demonstrate the importance of the 3D presentation of ligand structures for designing biomimetic materials.