Temporal trends in use of antisecretory agents among patients administered clopidogrel-based dual antiplatelet therapy after percutaneous coronary intervention.

BACKGROUND: Antisecretory drugs are commonly prescribed with clopidogrel-based dual antiplatelet therapy (DAPT) to prevent gastrointestinal bleeding in high-risk patients after percutaneous coronary intervention (PCI). However, omeprazole and esomeprazole (inhibiting proton pump inhibitors [PPIs]) may increase cardiovascular event rates on co-administration with clopidogrel. This study aimed to examine trends in the use of antisecretory agents in patients administered clopidogrel-based DAPT and the concomitant use of clopidogrel and inhibiting PPIs. METHODS: We used National Inpatient Sample data compiled by the Health Insurance Review & Assessment Service from 2009 to 2020. Further, we identified patients who were prescribed clopidogrel-based DAPT after PCI and investigated the concomitant use of antisecretory agents with clopidogrel. To verify the annual trend of drug utilization, we used the Cochran-Armitage trend test. RESULTS: From 2009 to 2020, the percentage of H2 receptor antagonist users decreased steadily (from 82.5% in 2009 to 25.3% in 2020); instead, the percentage of PPI users increased (from 23.7% in 2009 to 82.0% in 2020). The use of inhibiting PPI also increased (from 4.2% in 2009 to 30.7% in 2020). Potassium competitive acid blockers (P-CABs) were rarely used before 2019; however, in 2020, it accounted for 7.8% of the antisecretory users. CONCLUSIONS: Our study demonstrates that the use of inhibiting PPIs increased steadily in patients administered clopidogrel-based DAPT therapy. This is a major concern since the concomitant use of inhibiting PPIs with clopidogrel could increase the risk of cardiovascular events.

Improved differentiation of cavernous malformation and acute intraparenchymal hemorrhage on CT using an AI algorithm.

This study aimed to evaluate the utility of an artificial intelligence (AI) algorithm in differentiating between cerebral cavernous malformation (CCM) and acute intraparenchymal hemorrhage (AIH) on brain computed tomography (CT). A retrospective, multireader, randomized study was conducted to validate the performance of an AI algorithm in differentiating AIH from CCM on brain CT. CT images of CM and AIH (< 3 cm) were identified from the database. Six blinded reviewers, including two neuroradiologists, two radiology residents, and two emergency department physicians, evaluated CT images from 288 patients (CCM, n = 173; AIH, n = 115) with and without AI assistance, comparing diagnostic performance. Brain CT interpretation with AI assistance resulted in significantly higher diagnostic accuracy than without (86.92% vs. 79.86%, p < 0.001). Radiology residents and emergency department physicians showed significantly improved accuracy of CT interpretation with AI assistance than without (84.21% vs. 75.35%, 80.73% vs. 72.57%; respectively, p < 0.05). Neuroradiologists showed a trend of higher accuracy with AI assistance in the interpretation but lacked statistical significance (95.83% vs. 91.67%, p = 0.56). The use of an AI algorithm can enhance the differentiation of AIH from CCM in brain CT interpretation, particularly for nonexperts in neuroradiology.

Practice guidelines for managing extrahepatic biliary tract cancers.

Backgrounds/Aims: Reported incidence of extrahepatic bile duct cancer is higher in Asians than in Western populations. Korea, in particular, is one of the countries with the highest incidence rates of extrahepatic bile duct cancer in the world. Although research and innovative therapeutic modalities for extrahepatic bile duct cancer are emerging, clinical guidelines are currently unavailable in Korea. The Korean Society of Hepato-Biliary-Pancreatic Surgery in collaboration with related societies (Korean Pancreatic and Biliary Surgery Society, Korean Society of Abdominal Radiology, Korean Society of Medical Oncology, Korean Society of Radiation Oncology, Korean Society of Pathologists, and Korean Society of Nuclear Medicine) decided to establish clinical guideline for extrahepatic bile duct cancer in June 2021. Methods: Contents of the guidelines were developed through subgroup meetings for each key question and a preliminary draft was finalized through a Clinical Guidelines Committee workshop. Results: In November 2021, the finalized draft was presented for public scrutiny during a formal hearing. Conclusions: The extrahepatic guideline committee believed that this guideline could be helpful in the treatment of patients.

A Nationwide Study on HER2-low Breast Cancer in South Korea: Its Incidence of 2022 Real World Data and the Importance of Immunohistochemical Staining Protocols.

Purpose: Notable effectiveness of trastuzumab deruxtecan (T-DXd) in patients with HER2-low advanced breast cancer (BC) has focused pathologists' attention. We studied the incidence and clinicopathologic characteristics of HER2-low BC, and the effects of immunohistochemistry (IHC) associated factors on HER2 IHC results. Materials and Methods: The Breast Pathology Study Group of the Korean Society of Pathologists conducted a nationwide study using real-world data on HER2 status generated between January 2022 and December 2022. Information on HER2 IHC protocols at each participating institution was also collected. Results: Total 11,416 patients from twenty-five institutions included in this study. Of these patients, 40.7% (range: 6.0%-76.3%) were classified as HER2-zero, 41.7% (range: 10.5%-69.1%) as HER2-low, and 17.5% (range: 6.7%-34.0%) as HER2-positive. HER2-low tumors were associated with positive ER and PR statuses (p<0.001 and p<0.001, respectively). Antigen retrieval times (≥ 36 min vs. < 36 min) and antibody incubation times (≥ 12 min vs. < 12 min) affected on the frequency of HER2 IHC 1+ BC at institutions using the PATHWAY HER2 (4B5) IHC assay and BenchMark XT or Ultra staining instruments. Furthermore, discordant results between core needle biopsy (CNB) and subsequent resection specimen HER2 statuses were observed in 24.1% (787/3259) of the patients. Conclusion: The overall incidence of HER2-low BC in South Korea concurs with those reported in previously published studies. Significant inter-institutional differences in HER2 IHC protocols were observed, and it may have impact on HER2-low status. Thus, we recommend standardizing HER2 IHC conditions to ensure precise patient selection for targeted therapy.

Bright diffusion sign: A sensitive and specific radiologic biomarker for multinodular and vacuolating neuronal tumor.

BACKGROUND AND PURPOSE: Accurate differentiation between multinodular and vacuolating neuronal tumor (MVNT) and dysembryoplastic neuroepithelial tumor (DNET) is important for treatment decision-making. We aimed to develop an accurate radiologic diagnostic model for differentiating MVNT from DNET using T2WI and diffusion-weighted imaging (DWI). MATERIALS AND METHODS: A total of 56 patients (mean age, 47.48±17.78 years; 31 women) diagnosed with MVNT (n = 37) or DNET (n = 19) who underwent brain MRI, including T2WI and DWI, were included. Two board-certified neuroradiologists performed qualitative (bubble appearance, cortical involvement, bright diffusion sign, and bright apparent diffusion coefficient [ADC] sign) and quantitative (nDWI and nADC) assessments. A diagnostic tree model was developed with significant and reliable imaging findings using an exhaustive chi-squared Automatic Interaction Detector (CHAID) algorithm. RESULTS: In visual assessment, the imaging features that showed high diagnostic accuracy and interobserver reliability were the bright diffusion sign and absence of cortical involvement (bright diffusion sign: accuracy, 94.64 %; sensitivity, 91.89 %; specificity, 100.00 %; interobserver agreement, 1.00; absence of cortical involvement: accuracy, 92.86 %; sensitivity, 89.19 %; specificity, 100.00 %; interobserver agreement, 1.00). In quantitative analysis, nDWI was significantly higher in MVNT than in DENT (1.52 ± 0.34 vs. 0.91 ± 0.27, p < 0.001), but the interobserver agreement was fair (intraclass correlation coefficient = 0.321). The overall diagnostic accuracy of the tree model with visual assessment parameters was 98.21 % (55/56). CONCLUSION: The bright diffusion sign and absence of cortical involvement are accurate and reliable imaging findings for differentiating MVNT from DNET. By using simple, intuitive, and reliable imaging findings, such as the bright diffusion sign, MVNT can be accurately differentiated from DNET.

Utilization of triple antithrombotic therapy in patients with atrial fibrillation undergoing percutaneous coronary intervention.

BACKGROUND: Triple antithrombotic therapy (TAT), a combination of an oral anticoagulant and dual antiplatelet therapy (DAPT), is a key treatment for prevention of ischemic events in patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI). However, TAT is not extensively used because of the risk of bleeding. This study aimed to determine the utilization and influencing factors of TAT using real-world data in the non-vitamin K antagonist oral anticoagulants (NOACs) era. METHODS: We analyzed National Inpatient Sample data compiled by the Health Insurance Review & Assessment Service (HIRA-NIS) from 2011 to 2020. Patients with AF who underwent PCI with stent implantation and with an increased stroke risk were selected as candidates for TAT therapy. Demographic and clinical factors associated with TAT use were investigated using the chi-squared test and the Student t-test, and influencing factors were identified using multiple logistic regression. RESULTS: The TAT utilization rate steadily increased from 30.3% in 2011 to 65.4% in 2020 (Cochran-Armitage trend test: p < 0.001) with an average of 45.9%. Positive influencing factors for TAT use were identified as congestive heart failure, history of previous stroke/transient ischemic attack/thromboembolism, valvular heart disease, and year. Negative influencing factors included insurance type (medical aid or Patriots & Veterans Insurance), type of medical institution (general hospitals or primary medical institutions), and comorbidities such as renal disease, liver disease, and history of the previous hemorrhage. CONCLUSIONS: The utilization of TAT following PCI among high-stroke risk AF patients steadily increased from 2011 to 2020, reaching 65.4% by the end of the study period. However, in 2020, a significant proportion of 29.4% of patients still received DAPT, indicating that many AF patients undergoing PCI did not receive adequate antithrombotic therapy.

Association of cerebral white matter hyperintensities with coronary artery calcium in a healthy population: a cross-sectional study.

In brain magnetic resonance imaging (MRI), white matter hyperintensity (WMH) is a commonly encountered finding and is known to reflect cerebral small vessel disease. The aim of our study was to investigate the association of coronary artery calcium (CAC) with WMH and elucidate the relationship between WMH and atherosclerotic risk factors in a large-scale healthy population. This retrospective study included 1337 individuals who underwent brain MRI and CAC scoring computed tomography at healthcare centers affiliated with a tertiary hospital. Cerebral WMH was defined as Fazekas score greater than 2 on brain MRI. Intracranial artery stenosis (ICAS) was also assessed and determined to be present when stenosis was more than 50% on angiography. The associations of risk factors, CAC score, and ICAS with cerebral WMH were assessed by multivariable regression analysis. In multivariable analysis, categories of higher CAC scores showed increased associations with both periventricular and deep WMHs in a dose-dependent relationship. The presence of ICAS was also significantly related to cerebral WMH, and among the clinical variables, age and hypertension were independent risk factors. In conclusion, CAC showed a significant association with cerebral WMH in a healthy population, which might provide evidence for referring to the CAC score to identify individuals with risk of cerebral WMH.

The Impact of Parent-Child Closeness and Romantic Attachment on Dating Violence Perpetration in Adolescence.

Past research has demonstrated that romantic attachment insecurity is a risk factor for dating violence in adolescence. However, few studies to date have longitudinally examined whether earlier relational experience, such as perceived closeness with parents, may serve as an antecedent of this relationship. To examine longitudinal associations among youths' perceived closeness with parents, romantic attachment insecurity, and perpetration of dating violence in adolescence. Adolescents (N = 1016) were recruited from seven public high schools in south Texas and reported on their perceived closeness with parents, romantic attachment styles, and perpetration of physical and psychological dating violence at three assessments between 2010 and 2014. Data were analyzed using structural equation modeling. Adolescents' romantic attachment anxiety, but not attachment avoidance, significantly mediated the relationship between low perceived closeness with parents and the perpetration of physical and psychological dating violence in late adolescence. Multi-group analyses showed the mediation model only held for females but not males, and for Hispanic youth but not for Non-Hispanic White, African American, and youth of other races and ethnicities. Through its link to romantic attachment anxiety, perceived closeness with parents could play an important role in the perpetration of dating violence in adolescence, especially for girls and Hispanic youth. Findings suggest that dating violence interventions may benefit from targeting aspects of parent-child relationships.

A prospective multi-centre study of susceptibility map-weighted MRI for the diagnosis of neurodegenerative parkinsonism.

OBJECTIVES: This study aimed to compare susceptibility map-weighted imaging (SMwI) using various MRI machines (three vendors) with N-3-fluoropropyl-2-ß-carbomethoxy-3-ß-(4-iodophe nyl)nortropane (18F-FP-CIT) PET in the diagnosis of neurodegenerative parkinsonism in a multi-centre setting. METHODS: We prospectively recruited 257 subjects, including 157 patients with neurodegenerative parkinsonism, 54 patients with non-neurodegenerative parkinsonism, and 46 healthy subjects from 10 hospitals between November 2019 and October 2020. All participants underwent both SMwI and 18F-FP-CIT PET. SMwI was interpreted by two independent reviewers for the presence or absence of abnormalities in nigrosome 1, and discrepancies were resolved by consensus. 18F-FP-CIT PET was used as the reference standard. Inter-observer agreement was tested using Cohen's kappa coefficient. McNemar's test was used to test the agreement between the interpretations of SMwI and 18F-FP-CIT PET per participant and substantia nigra (SN). RESULTS: The inter-observer agreement was 0.924 and 0.942 per SN and participant, respectively. The diagnostic sensitivity of SMwI was 97.9% and 99.4% per SN and participant, respectively; its specificity was 95.9% and 95.2%, respectively, and its accuracy was 97.1% and 97.7%, respectively. There was no significant difference between the results of SMwI and 18F-FP-CIT PET (p > 0.05, for both SN and participant). CONCLUSIONS: This study demonstrated that the high diagnostic performance of SMwI was maintained in a multi-centre setting with various MRI scanners, suggesting the generalisability of SMwI for determining nigrostriatal degeneration in patients with parkinsonism. KEY POINTS: • Susceptibility map-weighted imaging helps clinicians to predict nigrostriatal degeneration. • The protocol for susceptibility map-weighted imaging can be standardised across MRI vendors. • Susceptibility map-weighted imaging showed diagnostic performance comparable to that of dopamine transporter PET in a multi-centre setting with various MRI scanners.

Polydrug Use and Dating Violence Among Emerging Adults.

We examined sociodemographic and psychosocial risk factors that moderate the (poly) substance use and dating violence victimization and perpetration relationship among emerging adults. Using an ethnically diverse sample (N = 698), we used latent class analyses to identify mutually exclusive groups based on monthly and past-year substance use. We then examined these groups as they relate to dating violence victimization and perpetration and the moderating effect of various risk factors. Five classes were identified based on substance use patterns: (a) Regular Alcohol use, (b) Polysubstance use, (c) Heavy Alcohol and Marijuana use, (d) Mild Alcohol use, and (e) Occasional Alcohol and Marijuana use classes. Participants in the Polysubstance use class were the most likely to perpetrate dating violence followed by Heavy Alcohol and Marijuana use, Occasional Alcohol and Marijuana use, Regular Alcohol, and Mild Alcohol use classes. Similarly, participants in the Polysubstance use class were the most likely to be victims of dating violence followed by Occasional Alcohol and Marijuana, Heavy Alcohol and Marijuana, Regular Alcohol, and Mild Alcohol use classes. Depending on substance use class, gender, ethnicity, socioeconomic status, history of dating violence, and trauma symptoms differentially influenced dating violence perpetration and victimization at 1-year follow-up. Our findings support the need to comprehensively address dating violence among emerging adults. Intimate partner violence prevention and intervention programs may benefit from targeting emerging adults who misuse substances and incorporating substance use interventions into dating violence prevention efforts.

The Measurement of Female Early Adolescent Sexual Desire.

We used the developmental systems model to deduce a definition of female early adolescent sexual desire. We evaluated a measure of this phenomenon with a secondary analysis of data from a randomized group sexual health intervention trial involving low-income, English-speaking, seventh grade Latinas enrolled in a Miami-Dade County public school (n = 542). As part of this study, girls completed a four-item early adolescent sexual desire (EASD) measure. Study findings supported internal consistency (Cronbach's alpha = .81 to .82) and stability over a 1-month period (r = .74). Developmental sensitivity was supported by a decline in stability over 12- (r = .66) and 24-month periods (r = .56). Validity was supported by correlations with puberty changes, sexual intentions, sexting, and sexual behavior, and hypothesized mean differences associated with dating and preference for shoes culturally associated with female sexual attractiveness (p < .01). Research implications include validation work with other ethnic/racial groups and using the EASD as a starting point for a measurement continuum tracking development of sexual desire across adolescence and into adulthood. Directions for future research also include measuring the development of sexual desire in boys and transgendered youth across adolescence and into adulthood.

Corrigendum: Integrating a Statistical Topic Model and a Diagnostic Classification Model for Analyzing Items in a Mixed Format Assessment.

[This corrects the article DOI: 10.3389/fpsyg.2020.579199.].

A multicenter study of interobserver variability in pathologic diagnosis of papillary breast lesions on core needle biopsy with WHO classification.

BACKGROUND: Papillary breast lesions (PBLs) comprise diverse entities from benign and atypical lesions to malignant tumors. Although PBLs are characterized by a papillary growth pattern, it is challenging to achieve high diagnostic accuracy and reproducibility. Thus, we investigated the diagnostic reproducibility of PBLs in core needle biopsy (CNB) specimens with World Health Organization (WHO) classification. METHODS: Diagnostic reproducibility was assessed using interobserver variability (kappa value, κ) and agreement rate in the pathologic diagnosis of 60 PBL cases on CNB among 20 breast pathologists affiliated with 20 medical institutions in Korea. This analysis was performed using hematoxylin and eosin (H&E) staining and immunohistochemical (IHC) staining for cytokeratin 5 (CK5) and p63. The pathologic diagnosis of PBLs was based on WHO classification, which was used to establish simple classifications (4-tier, 3-tier, and 2-tier). RESULTS: On WHO classification, H&E staining exhibited 'fair agreement' (κ = 0.21) with a 47.0% agreement rate. Simple classifications presented improvement in interobserver variability and agreement rate. IHC staining increased the kappa value and agreement rate in all the classifications. Despite IHC staining, the encapsulated/solid papillary carcinoma (EPC/SPC) subgroup (κ = 0.16) exhibited lower agreement compared to the non-EPC/SPC subgroup (κ = 0.35) with WHO classification, which was similar to the results of any other classification systems. CONCLUSIONS: Although the use of IHC staining for CK5 and p63 increased the diagnostic agreement of PBLs in CNB specimens, WHO classification exhibited a higher discordance rate compared to any other classifications. Therefore, this result warrants further intensive consensus studies to improve the diagnostic reproducibility of PBLs with WHO classification.

Suppression of Osteoarthritis progression by post-natal Induction of Nkx3.2.

Osteoarthritis (OA) is an incurable joint disease affecting 240 million elderly population, and major unmet medical needs exist for better therapeutic options for OA. During skeletal development, Nkx3.2 has been shown to promote chondrocyte differentiation and survival, but to suppress cartilage hypertrophy and blood vessel invasion. Here we show that Nkx3.2 plays a key role in osteoarthritis (OA) pathogenesis. Marked reduction of Nkx3.2 expression was observed in three different murine OA models. Consistent with these findings, analyses of surgery-induced and age-driven OA models revealed that cartilage-specific post-natal induction of Nkx3.2 can suppress OA progression in mice. These results suggest that Nkx3.2 may serve as a promising target for OA drug development.

Patterns of sexting and sexual behaviors in youth: A Latent Class Analysis.

INTRODUCTION: A sizable minority of youth are sexting; however there are likely large individual differences in sexting and sexual behaviors, yet to be captured. A Latent Class Analysis was used to identify subgroups of youth characterized by differential engagement in sexting and sexual behaviors. METHODS: Participants were an ethnically diverse sample of 894 youth (55.8% female; Mage = 17.04, SD = 0.77) from a longitudinal survey study in southeast Texas. Latent classes were identified through participants' responses to the following indicator variables: sending, receiving, and requesting sexts, sexual activity, contraception use, ≥ three partners, and substance use prior to sexual activity. Gender, ethnicity, impulsivity, and living situation were analyzed as predictors, and depressive symptoms as an outcome, of class membership. RESULTS: The analysis revealed four distinct classes: No sexting-Low sex (42.2%), Sexting-Low sex (4.5%), No sexting-Moderately risky sex (28.3%), and Sexting-Moderately risky sex (24.9%). Gender and ethnicity predicted class membership wherein females and ethnic minority youth were less likely to be in groups displaying higher rates of sexting. Impulsivity and living situation predicted class membership, such that youth reporting higher impulsivity and living in a situation other than with two biological parents were less likely to be in classes displaying low sexting and sexual behaviors. Group membership predicted depressive symptoms. CONCLUSIONS: Results suggest that not all youth who are sexting are having sex, and not all youth who are having sex are sexting. Evidence of individual differences in youth sexual behaviors should inform educational initiatives aimed at teaching youth about sexual and online health.

T2 gallbladder cancer shows substantial survival variation between continents and this is not due to histopathologic criteria or pathologic sampling differences.

Published data on survival of T2 gallbladder carcinoma (GBC) from different countries show a wide range of 5-year survival rates from 30-> 70%. Recently, studies have demonstrated substantial variation between countries in terms of their approach to sampling gallbladders, and furthermore, that pathologists from different continents apply highly variable criteria in determining stage of invasion in this organ. These findings raised the question of whether these variations in pathologic evaluation could account for the vastly different survival rates of T2 GBC reported in the literature. In this study, survival of 316 GBCs from three countries (Chile n = 137, South Korea n = 105, USA n = 74), all adequately sampled (with a minimum of five tumor sections examined) and histopathologically verified as pT2 (after consensus examination by expert pathologists from three continents), was analyzed. Chilean patients had a significantly worse prognosis based on 5-year all-cause mortality (HR: 1.89, 95% CI: 1.27-2.83, p = 0.002) and disease-specific mortality (HR: 2.41, 95% CI: 1.51-3.84, p < 0.001), compared to their South Korean counterparts, even when controlled for age and sex. Comparing the USA to South Korea, the survival differences in all-cause mortality (HR: 1.75, 95% CI: 1.12-2.75, p = 0.015) and disease-specific mortality (HR: 1.94, 95% CI: 1.14-3.31, p = 0.015) were also pronounced. The 3-year disease-specific survival rates in South Korea, the USA, and Chile were 75%, 65%, and 55%, respectively, the 5-year disease-specific survival rates were 60%, 50%, and 50%, respectively, and the overall 5-year survival rates were 55%, 45%, and 35%, respectively. In conclusion, the survival of true T2 GBC in properly classified cases is neither as good nor as bad as previously documented in the literature and shows notable geographic differences even in well-sampled cases with consensus histopathologic criteria. Future studies should focus on other potential reasons including biologic, etiopathogenetic, management-related, populational, or healthcare practice-related factors that may influence the survival differences of T2 GBC in different regions.

Coexistence of the Absence of the Left Common Carotid Artery, a Common Origin of the Left External Carotid Artery and the Right Common Carotid Artery, and an Aberrant Right Subclavian Artery: A Case Report.

The absence of the common carotid artery (CCA) and the common origin of the left external carotid artery (ECA) and the right CCA are rare anomalies of the cervical vascular system. We report here a case involving the coexistence of these vascular anomalies with an aberrant right subclavian artery, which is a common congenital anomaly in the aortic arch, and review the embryologic mechanism and clinical importance of this case.

Safety and efficacy of Wharton's jelly-derived mesenchymal stem cells with teriparatide for osteoporotic vertebral fractures: A phase I/IIa study.

Osteoporotic vertebral compression fractures (OVCFs) are serious health problems. We conducted a randomized, open-label, phase I/IIa study to determine the feasibility, safety, and effectiveness of Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) and teriparatide (parathyroid hormone 1-34) in OVCFs. Twenty subjects with recent OVCFs were randomized to teriparatide (20 µg/day, daily subcutaneous injection for 6 months) treatment alone or combined treatment of WJ-MSCs (intramedullary [4 × 107 cells] injection and intravenous [2 × 108 cells] injection after 1 week) and teriparatide (20 µg/day, daily subcutaneous injection for 6 months). Fourteen subjects (teriparatide alone, n = 7; combined treatment, n = 7) completed follow-up assessment (visual analog scale [VAS], Oswestry Disability Index [ODI], Short Form-36 [SF-36], bone mineral density [BMD], bone turnover measured by osteocalcin and C-terminal telopeptide of type 1 collagen, dual-energy x-ray absorptiometry [DXA], computed tomography [CT]). Our results show that (a) combined treatment with WJ-MSCs and teriparatide is feasible and tolerable for the patients with OVCFs; (b) the mean VAS, ODI, and SF-36 scores significantly improved in the combined treatment group; (c) the level of bone turnover markers were not significantly different between the two groups; (d) BMD T-scores of spine and hip by DXA increased in both control and experimental groups without a statistical difference; and (e) baseline spine CT images and follow-up CT images at 6 and 12 months showed better microarchitecture in the combined treatment group. Our results indicate that combined treatment of WJ-MSCs and teriparatide is feasible and tolerable and has a clinical benefit for fracture healing by promoting bone architecture. Clinical trial registration: https://nedrug.mfds.go.kr/, MFDS: 201600282-30937.

The Role of Engagement in Effective, Digital Prevention Interventions: the Function of Engagement in the REAL Media Substance Use Prevention Curriculum.

Prevention curricula rely on audience engagement to effectively communicate their messages. However, to date, measurement of engagement has primarily focused on self-report that is often an indicator of liking or satisfaction. Emerging technologies for intervention delivery hold promise not only for additional engagement indicators but also for dissemination outside of traditional vehicles such as classroom delivery. The present study, grounded in the theory of active involvement (Greene 2013), explores the role of engagement (as measured by self-report, program analytics, and observation) with short-term substance use prevention outcomes such as self-efficacy to counter-argue and descriptive and injunctive norms. The study tracks 4-H youth (N = 310) engaged with a media literacy focused e-learning substance prevention curriculum, REAL media. Results indicate that self-reports of engagement predicted self-efficacy to counter-argue, but a program-analytic indicator of dosage predicted lower injunctive and descriptive norms, all at 3 months. The observational indicator was correlated with self-efficacy to counter-argue but not significant in the predictive models. The implications and directions for future research regarding how engagement is measured in prevention and included in studying program effects are discussed. Clinical trial: NCT03157700, May 2017.