Reducing Opioid Analgesic Prescribing in Dentistry Through Prescribing Defaults: A Cluster-Randomized Controlled Trial.

OBJECTIVE: To determine the effect of a uniform, reduced, default dispense quantity for new opioid analgesic prescriptions on the quantity of opioids prescribed in dentistry practices. METHODS: We conducted a cluster-randomized controlled trial within a health system in the Bronx, NY, USA. We randomly assigned three dentistry sites to a 10-tablet default, a 5-tablet default, or no change (control). The primary outcome was the quantity of opioid analgesics prescribed in the new prescription. Secondary outcomes were opioid analgesic reorders and health service utilization within 30 days after the new prescription. We analyzed outcomes from 6 months before implementation through 18 months after implementation. RESULTS: Overall, 6,309 patients received a new prescription. Compared with the control site, patients at the 10-tablet-default site had a significantly larger change in prescriptions for 10 tablets or fewer (38.7 percentage points; confidence interval [CI]: 11.5 to 66.0), lower number of tablets prescribed (-3.3 tablets; CI: -5.9 to -0.7), and lower morphine milligram equivalents (MME) prescribed (-14.1 MME; CI: -27.8 to -0.4), which persisted in the 30 days after the new prescription despite a higher percentage of reorders (3.3 percentage points; CI: 0.2 to 6.4). Compared with the control site, patients at the 5-tablet-default site did not have a significant difference in any outcomes except for a significantly higher percentage of reorders (2.6 percentage points; CI: 0.2 to 4.9). CONCLUSIONS: Our findings further support the efficacy of strategies that lower default dispense quantities, although they indicate that caution is warranted in the selection of the default. TRIAL REGISTRATION: ClinicalTrials.org ID: NCT03030469.

Social Media Use and Health and Well-being of Lesbian, Gay, Bisexual, Transgender, and Queer Youth: Systematic Review.

BACKGROUND: Lesbian, gay, bisexual, transgender, and queer (LGBTQ) individuals are at higher risk of poor mental health and well-being. Social media platforms can provide LGBTQ youths with a space that counters heteronormative environments and potentially supports mental health and well-being. Mental health includes an individual's state of psychological and emotional well-being and not merely the absence of mental disorders. OBJECTIVE: We sought to identify how LGBTQ youths and adolescents use social media for connection with other LGBTQ peers and groups, identity development, and social support and how these affect mental health and well-being. METHODS: PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) procedures were used to guide this review. Searches were conducted in ACM Digital Library, CINAHL, Ovid Embase, Ovid MEDLINE, and Web of Science in March 2021. This review focused on LGBTQ youths aged 10 to 24 years. Included peer-reviewed studies must comprise social media; explore peer connection, identity development, or social support; and be published from 2012 onward. In total, 2 researchers extracted data and performed quality assessments independently using the Newcastle-Ottawa Scale for quantitative articles and the Critical Appraisal Skills Programme for qualitative articles. Qualitative synthesis was performed on articles that satisfied the eligibility criteria. RESULTS: A total of 26 studies (n=15, 58% qualitative; n=8, 31% quantitative; n=3, 12% mixed methods) met the inclusion criteria. Of the 8 quantitative studies, 6 (75%) were cross-sectional, and 2 (25%) were cohort studies. All studies ranged from moderate to high quality. Social media was a popular tool used by LGBTQ youths to connect with LGBTQ communities. In qualitative data, we found that LGBTQ youths negotiated and explored identity and obtained support from peers on social media. Instagram, Tumblr, and Twitter were commonly used to access LGBTQ content owing to ease of anonymity. Identity management was the most studied social media affordance, important to LGBTQ youths for strategic disclosure. Key strategies for managing identities included being anonymous, censoring locations or content, restricting audiences, and using multiple accounts. Quantitative studies (3/8, 38%) showed that social media was associated with reduced mental health concerns and increased well-being among LGBTQ youths. Mental health concerns arising from social media use were attributed to discrimination, victimization, and policies that did not accommodate changed identities. CONCLUSIONS: We found that social media may support the mental health and well-being of LGBTQ youths through peer connection, identity management, and social support, but findings were limited by weaknesses in the evidence. More robust and longitudinal studies are needed to determine the relationship between social media use and LGBTQ mental health, particularly among adolescents. The findings may inform interventions to promote social media health literacy and the mental health and well-being of this vulnerable group. TRIAL REGISTRATION: PROSPERO CRD42020222535; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=222535.

Social media's role in support networks among LGBTQ adolescents: a qualitative study.

Background Adolescents use social media more frequently than other age groups. Social media has been described as a safe environment for lesbian, gay, bisexual, transgender and queer and/or questioning (LGBTQ) adolescents. As part of mixed-methods research investigating the association between social networks and sexual agency, we present qualitative findings on how LGBTQ adolescents connect online to form support networks. Methods We recruited 30 adolescents aged 14-17years who identified as LGBTQ in terms of their gender or attraction in the longitudinal Social Networks and Agency Project. Semi-structured interviews were conducted online or face-to-face across Australia. Thematic analysis was used to explore perceptions and experiences of participants in relation to social media use and relationships. Results Two overarching themes were identified: LGBTQ adolescents use social media for identity, relationships and wellbeing support. Social media is not always free of discrimination for LGBTQ adolescents. Many LGBTQ participants joined Facebook groups to connect with LGBTQ peers. Facebook was considered a vital support for those with mental health concerns including suicidal ideation. Participants gave and received support from group members, which was considered useful for those feeling isolated or victimised. LGBTQ adolescents formed friendships, romantic relationships and gained information on sex, relationships, and sexual health from these groups. Participants described negative experiences including discrimination within Facebook groups, mismanaged groups and exposure to anti-LGBTQ sentiments. Conclusion Social media is an environment where LGBTQ adolescents can connect, educate and support each other, which may have beneficial effects for this marginalised group. There remain issues with social media including discrimination against and within LGBTQ communities.

Corrigendum to: Social media's role in support networks among LGBTQ adolescents: a qualitative study.

Background:Adolescents use social media more frequently than other age groups. Social media has been described as a safe environment for lesbian, gay, bisexual, transgender and queer and/or questioning (LGBTQ) adolescents. As part of mixed-methods research investigating the association between social networks and sexual agency, we present qualitative findings on how LGBTQ adolescents connect online to form support networks.Methods:We recruited 30 adolescents aged 14-17years who identified as LGBTQ in terms of their gender or attraction in the longitudinal Social Networks and Agency Project. Semi-structured interviews were conducted online or face-to-face across Australia. Thematic analysis was used to explore perceptions and experiences of participants in relation to social media use and relationships.Results:Two overarching themes were identified: LGBTQ adolescents use social media for identity, relationships and wellbeing support. Social media is not always free of discrimination for LGBTQ adolescents. Many LGBTQ participants joined Facebook groups to connect with LGBTQ peers. Facebook was considered a vital support for those with mental health concerns including suicidal ideation. Participants gave and received support from group members, which was considered useful for those feeling isolated or victimised. LGBTQ adolescents formed friendships, romantic relationships and gained information on sex, relationships, and sexual health from these groups. Participants described negative experiences including discrimination within Facebook groups, mismanaged groups and exposure to anti-LGBTQ sentiments.Conclusion:Social media is an environment where LGBTQ adolescents can connect, educate and support each other, which may have beneficial effects for this marginalised group. There remain issues with social media including discrimination against and within LGBTQ communities.

Medical student remote eConsult participation during the COVID-19 pandemic.

BACKGROUND: Undergraduate medical education was severely impacted by the COVID-19 pandemic. As traditional clinical rotations were suspended, medical students quickly began alternative, novel educational experiences. Third-year medical students at an academic medical center were given the opportunity to join inpatient eConsult teams within the department of medicine. This study describes the development and implementation of this program as well as the experiences of student and faculty participants. METHODS: Student eConsult participation was rapidly developed and implemented within medical subspecialty teams in either infectious diseases (ID) or nephrology. Twelve third-year medical students and 15 subspecialty attendings participated in this program during an eight-week period from April 6 through May 29, 2020. Breadth of student clinical experience was assessed via review of clinical documentation and surveys. Participating students and attending physicians completed surveys to reflect upon their impressions of the program. Surveys were returned by nine students and eight faculty members. Survey responses were summarized with descriptive statistics. RESULTS: Over an eight-week period, student consultants wrote 126 notes on 100 patients; 74 of these patients (74%) were hospitalized with COVID-19. Student experiences were largely positive with most strongly agreeing that attendings promoted interactive and engaged learning (N = 8 of 8, 100%), that the experience helped to expand their knowledge about consultant roles (N = 6, 75%), and that they would participate in a remote eConsult program again if given the opportunity (N = 6, 75%). Faculty also were largely positive about the experience with most agreeing or strongly agreeing with the importance of teaching medical students about telehealth (N = 7 of 8, 88%) and eConsults (N = 6, 75%). In narrative responses, students and faculty agreed that teaching was a strength of the program whereas lack of in-person contact was a challenge. CONCLUSIONS: Rapid development of an inpatient eConsult-based educational experience for third-year medical students was feasible and successful. Student-consultants saw a range of pathology including COVID-19 and related complications. Students were satisfied with the program. They were able to develop a strong relationship with attendings while learning about the role of a consultant. Faculty agreed with the importance of teaching students about telehealth and eConsults specifically.

Effect of Restriction of the Number of Concurrently Open Records in an Electronic Health Record on Wrong-Patient Order Errors: A Randomized Clinical Trial.

Importance: Recommendations in the United States suggest limiting the number of patient records displayed in an electronic health record (EHR) to 1 at a time, although little evidence supports this recommendation. Objective: To assess the risk of wrong-patient orders in an EHR configuration limiting clinicians to 1 record vs allowing up to 4 records opened concurrently. Design, Setting, and Participants: This randomized clinical trial included 3356 clinicians at a large health system in New York and was conducted from October 2015 to April 2017 in emergency department, inpatient, and outpatient settings. Interventions: Clinicians were randomly assigned in a 1:1 ratio to an EHR configuration limiting to 1 patient record open at a time (restricted; n = 1669) or allowing up to 4 records open concurrently (unrestricted; n = 1687). Main Outcomes and Measures: The unit of analysis was the order session, a series of orders placed by a clinician for a single patient. The primary outcome was order sessions that included 1 or more wrong-patient orders identified by the Wrong-Patient Retract-and-Reorder measure (an electronic query that identifies orders placed for a patient, retracted, and then reordered shortly thereafter by the same clinician for a different patient). Results: Among the 3356 clinicians who were randomized (mean [SD] age, 43.1 [12.5] years; mean [SD] experience at study site, 6.5 [6.0] years; 1894 females [56.4%]), all provided order data and were included in the analysis. The study included 12 140 298 orders, in 4 486 631 order sessions, placed for 543 490 patients. There was no significant difference in wrong-patient order sessions per 100 000 in the restricted vs unrestricted group, respectively, overall (90.7 vs 88.0; odds ratio [OR], 1.03 [95% CI, 0.90-1.20]; P = .60) or in any setting (ED: 157.8 vs 161.3, OR, 1.00 [95% CI, 0.83-1.20], P = .96; inpatient: 185.6 vs 185.1, OR, 0.99 [95% CI, 0.89-1.11]; P = .86; or outpatient: 7.9 vs 8.2, OR, 0.94 [95% CI, 0.70-1.28], P = .71). The effect did not differ among settings (P for interaction = .99). In the unrestricted group overall, 66.2% of the order sessions were completed with 1 record open, including 34.5% of ED, 53.7% of inpatient, and 83.4% of outpatient order sessions. Conclusions and Relevance: A strategy that limited clinicians to 1 EHR patient record open compared with a strategy that allowed up to 4 records open concurrently did not reduce the proportion of wrong-patient order errors. However, clinicians in the unrestricted group placed most orders with a single record open, limiting the power of the study to determine whether reducing the number of records open when placing orders reduces the risk of wrong-patient order errors. Trial Registration: clinicaltrials.gov Identifier: NCT02876588.

PCR Multiplexes Discriminate Fusarium Symbionts of Invasive Euwallacea Ambrosia Beetles that Inflict Damage on Numerous Tree Species Throughout the United States.

Asian Euwallacea ambrosia beetles vector Fusarium mutualists. The ambrosial fusaria are all members of the ambrosia Fusarium clade (AFC) within the Fusarium solani species complex (FSSC). Several Euwallacea-Fusarium mutualists have been introduced into nonnative regions and have caused varying degrees of damage to orchard, landscape, and forest trees. Knowledge of symbiont fidelity is limited by current identification methods, which typically requires analysis of DNA sequence data from beetles and the symbionts cultured from their oral mycangia. Here, polymerase chain reaction (PCR)-based diagnostic tools were developed to identify the six Fusarium symbionts of exotic Euwallacea spp. currently known within the United States. Whole-genome sequences were generated for representatives of six AFC species plus F. ambrosium and aligned to the annotated genome of F. euwallaceae. Taxon-specific primer-annealing sites were identified that rapidly distinguish the AFC species currently within the United States. PCR specificity, reliability, and sensitivity were validated using a panel of 72 Fusarium isolates, including 47 reference cultures. Culture-independent multiplex assays accurately identified two AFC fusaria using DNA isolated from heads of their respective beetle partners. The PCR assays were used to show that Euwallacea validus is exclusively associated with AF-4 throughout its sampled range within eastern North America. The rapid assay supports federal and state agency efforts to monitor spread of these invasive pests and mitigate further introductions.

Development of myotendinous-like junctions that anchor cardiac valves requires fibromodulin and lumican.

BACKGROUND: There are many patients that exhibit connective tissue related cardiac malformations but do not have mutations in collagen genes. The Small Leucine Rich Proteoglycans (SLRP) fibromodulin (FMOD) and lumican (LUM) bind collagen and regulate fibril assembly in other biological contexts. RESULTS: FMOD deficient mice and double deficient FMOD; LUM mice exhibited anomalies in regions where cardiac valve tissue interdigitates with adjacent muscle for support. Ectopic connective and/or myocardial tissue(s) was associated with the more severe cardiac valve anomalies in FMOD; LUM deficient mice. At postnatal day 0 (P0) there was an increase in the mesenchymal cell number in the regions where valve cusps anchor in FMOD; LUM deficient mice compared to WT. The cardiac valve anomalies correlated with the highest levels of FMOD expression in the heart and also where myotendinous junctions (MTJ) components biglycan, collagen type I alpha 1, and collagen type VI, are also localized. CONCLUSIONS: The postnatal assembly of the collagen-rich ECM in regions where cardiac valves anchor, that we have designated 'myotendinous-like junctions' (MTLJ) requires the SLRPs FMOD and LUM. Moreover, FMOD and LUM may facilitate mesenchymal cell differentiation in late stages of cardiac valve development. Developmental Dynamics 245:1029-1042, 2016. © 2016 Wiley Periodicals, Inc.

Lumican deficiency results in cardiomyocyte hypertrophy with altered collagen assembly.

The ability of the heart to adapt to increased stress is dependent on the modification of its extracellular matrix (ECM) architecture that is established during postnatal development as cardiomyocytes differentiate, a process that is poorly understood. We hypothesized that the small leucine-rich proteoglycan (SLRP) lumican (LUM), which binds collagen and facilitates collagen assembly in other tissues, may play a critical role in establishing the postnatal murine myocardial ECM. Although previous studies suggest that LUM deficient mice (lum(-/-)) exhibit skin anomalies consistent with Ehlers-Danlos syndrome, lum(-/-) hearts have not been evaluated. These studies show that LUM was immunolocalized to non-cardiomyocytes of the cardiac ventricles and its expression increased throughout development. Lumican deficiency resulted in significant (50%) perinatal death and further examination of the lum(-/-) neonatal hearts revealed an increase in myocardial tissue without a significant increase in cell proliferation. However cardiomyocytes from surviving postnatal day 0 (P0), 1 month (1 mo) and adult (4 mo) lum(-/-) hearts were significantly larger than their wild type (WT) littermates. Immunohistochemistry revealed that the increased cardiomyocyte size in the lum(-/-) hearts correlated with alteration of the cardiomyocyte pericellular ECM components collagenα1(I) and the class I SLRP decorin (DCN). Western blot analysis demonstrated that the ratio of glycosaminoglycan (GAG) decorated DCN to core DCN was reduced in P0 and 1 mo lum(-/-) hearts. There was also a reduction in the ß and γ forms of collagenα1(I) in lum(-/-) hearts. While the total insoluble collagen content was significantly reduced, the fibril size was increased in lum(-/-) hearts, indicating that LUM may play a role in collagen fiber stability and lateral fibril assembly. These results suggest that LUM controls cardiomyocyte growth by regulating the pericellular ECM and also indicates that LUM may coordinate multiple factors of collagen assembly in the murine heart. Further investigation into the role of LUM may yield novel therapeutic targets and/or biomarkers for patients with cardiovascular disease.

Diagnostic Accuracy of a Handheld Ultrasound vs a Cart-based Model: A Randomized Clinical Trial.

Introduction: Numerous studies have demonstrated the accuracy of point-of-care ultrasound (POCUS). Portable, handheld devices have expanded the clinical scope of POCUS at a fraction of the cost of traditional, cart-based models. There is a paucity of data assessing the diagnostic accuracy of portable devices. Our objective in this study was to compare the diagnostic accuracy of a portable device with a cart-based model. Methods: This was an institutional review board-approved, observational, prospective, randomized clinical trial (NCT05196776) of a convenience sample of adult patients who presented to a university-based health system. Patients who required a cardiac, lung, renal, aorta, or biliary POCUS were randomized to a portable device or to a cart-based model. We hypothesized that the cart-based model would have a 90% diagnostic accuracy vs 70% for the handheld device. To detect a 20% difference, the sample size was calculated to be 98, with 49 patients randomized to each arm. We used standard 2x2 tables to calculate test characteristics with 95% confidence intervals (CI). Results: A total of 110 patients were enrolled, with 56 patients randomized to the cart-based model and 54 to the handheld device. The sensitivity, specificity, and diagnostic accuracy of the cart-based vs handheld were 77.8% (40-97.2) vs 92.9% (66.1-99.8), 91.5% (79.6-97.6) vs 92.3% (79.1-98.4%), and 89.3% (78.1-96) vs 92.5% (81.8-97.9), respectively. Conclusion: The diagnostic accuracy of a portable, handheld device is similar to that of a cart-based model.

Clinical characteristics and treatment exposure of patients with marked treatment-resistant unipolar major depressive disorder: A RECOVER trial report.

BACKGROUND: RECOVER is a randomized sham-controlled trial of vagus nerve stimulation and the largest such trial conducted with a psychiatric neuromodulation intervention. OBJECTIVE: To describe pre-implantation baseline clinical characteristics and treatment history of patients with unipolar, major depressive disorder (MDD), overall and as a function of exposure to interventional psychiatric treatments (INTs), including electroconvulsive therapy, transcranial magnetic stimulation, and esketamine. METHODS: Medical, psychiatric, and treatment records were reviewed by study investigators and an independent Study Eligibility Committee prior to study qualification. Clinical characteristics and treatment history (using Antidepressant Treatment History [Short] Form) were compared in those qualified (N = 493) versus not qualified (N = 228) for RECOVER, and among the qualified group as a function of exposure to INTs during the current major depressive episode (MDE). RESULTS: Unipolar MDD patients who qualified for RECOVER had marked TRD (median of 11.0 lifetime failed antidepressant treatments), severe disability (median WHODAS score of 50.0), and high rate of baseline suicidality (77% suicidal ideation, 40% previous suicide attempts). Overall, 71% had received at least one INT. Compared to the no INT group, INT recipients were younger and more severely depressed (QIDS-C, QIDS-SR), had greater suicidal ideation, earlier diagnosis of MDD, and failed more antidepressant medication trials. CONCLUSIONS: RECOVER-qualified unipolar patients had marked TRD and marked treatment resistance with most failing one or more prior INTs. Treatment with ≥1 INTs in the current MDE was associated with earlier age of MDD onset, more severe clinical presentation, and greater treatment resistance relative to patients without a history of INT. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT03887715.

pyPheWAS Explorer: a visualization tool for exploratory analysis of phenome-disease associations.

Objective: To enable interactive visualization of phenome-wide association studies (PheWAS) on electronic health records (EHR). Materials and Methods: Current PheWAS technologies require familiarity with command-line interfaces and lack end-to-end data visualizations. pyPheWAS Explorer allows users to examine group variables, test assumptions, design PheWAS models, and evaluate results in a streamlined graphical interface. Results: A cohort of attention deficit hyperactivity disorder (ADHD) subjects and matched non-ADHD controls is examined. pyPheWAS Explorer is used to build a PheWAS model including sex and deprivation index as covariates, and the Explorer's result visualization for this model reveals known ADHD comorbidities. Discussion: pyPheWAS Explorer may be used to rapidly investigate potentially novel EHR associations. Broader applications include deployment for clinical experts and preliminary exploration tools for institutional EHR repositories. Conclusion: pyPheWAS Explorer provides a seamless graphical interface for designing, executing, and analyzing PheWAS experiments, emphasizing exploratory analysis of regression types and covariate selection.

Immunogenicity, safety, usability and acceptability of microarray patches for vaccination: a systematic review and meta-analysis.

BACKGROUND: Microarray patches (MAPs) deliver vaccines to the epidermis and the upper dermis, where abundant immune cells reside. There are several potential benefits to using MAPs, including reduced sharps risk, thermostability, no need for reconstitution, tolerability and self-administration. We aimed to explore and evaluate the immunogenicity, safety, usability and acceptability of MAPs for vaccination. METHODS: We searched CINAHL, Cochrane Library, Ovid Embase, Ovid MEDLINE and Web of Science from inception to January 2023. Eligibility criteria included all research studies in any language, which examined microarrays or microneedles intended or used for vaccination and explored immunogenicity, safety, usability or acceptability in their findings. Two reviewers conducted title and abstract screening, full-text reviewing and data extraction. RESULTS: Twenty-two studies were included (quantitative=15, qualitative=2 and mixed methods=5). The risk of bias was mostly low, with two studies at high risk of bias. Four clinical trials were included, three using influenza antigens and one with Japanese encephalitis delivered by MAP. A meta-analysis indicated similar or higher immunogenicity in influenza MAPs compared with needle and syringe (N&S) (standardised mean difference=10.80, 95% CI: 3.51 to 18.08, p<0.00001). There were no significant differences in immune cell function between MAPs and N&S. No serious adverse events were reported in MAPs. Erythema was more common after MAP application than N&S but was brief and well tolerated. Lower pain scores were usually reported after MAP application than N&S. Most studies found MAPs easy to use and highly acceptable among healthcare professionals, laypeople and parents. CONCLUSION: MAPs for vaccination were safe and well tolerated and evoked similar or enhanced immunogenicity than N&S, but further research is needed. Vaccine uptake may be increased using MAPs due to less pain, enhanced thermostability, layperson and self-administration. MAPs could benefit at-risk groups and low and middle-income countries. PROSPERO REGISTRATION NUMBER: CRD42022323026.

Training Deep Network Ultrasound Beamformers With Unlabeled In Vivo Data.

Conventional delay-and-sum (DAS) beamforming is highly efficient but also suffers from various sources of image degradation. Several adaptive beamformers have been proposed to address this problem, including more recently proposed deep learning methods. With deep learning, adaptive beamforming is typically framed as a regression problem, where clean ground-truth physical information is used for training. Because it is difficult to know ground truth information in vivo, training data are usually simulated. However, deep networks trained on simulations can produce suboptimal in vivo image quality because of a domain shift between simulated and in vivo data. In this work, we propose a novel domain adaptation (DA) scheme to correct for domain shift by incorporating unlabeled in vivo data during training. Unlike classification tasks for which both input domains map to the same target domain, a challenge in our regression-based beamforming scenario is that domain shift exists in both the input and target data. To solve this problem, we leverage cycle-consistent generative adversarial networks to map between simulated and in vivo data in both the input and ground truth target domains. Additionally, to account for separate as well as shared features between simulations and in vivo data, we use augmented feature mapping to train domain-specific beamformers. Using various types of training data, we explore the limitations and underlying functionality of the proposed DA approach. Additionally, we compare our proposed approach to several other adaptive beamformers. Using the DA DNN beamformer, consistent in vivo image quality improvements are achieved compared to established techniques.

Hemolytic Anemia in Inflammatory Bowel Disease: Our "Gut" Tells Us to Blame the Drug.

Background: Several studies determined that autoimmune hemolytic anemia (AIHA) is a rare extraintestinal IBD manifestation, related to the underlying disease activity. However, evidence linking biologic therapy to AIHA is sparse. Methods: This article reviews the evidence on the association of these clinical phenomena. Results: There are two retrospective studies and a few case reports linking biologic therapies to AIHA. Conclusions: While some autoimmune phenomenon triggered by our biologic therapies have been well recognized, we do not find the evidence associating these therapies to AIHA sufficiently compelling.

Evaluating Input Domain and Model Selection for Deep Network Ultrasound Beamforming.

Improving ultrasound B-mode image quality remains an important area of research. Recently, there has been increased interest in using deep neural networks (DNNs) to perform beamforming to improve image quality more efficiently. Several approaches have been proposed that use different representations of channel data for network processing, including a frequency-domain approach that we previously developed. We previously assumed that the frequency domain would be more robust to varying pulse shapes. However, frequency- and time-domain implementations have not been directly compared. In addition, because our approach operates on aperture domain data as an intermediate beamforming step, a discrepancy often exists between network performance and image quality on fully reconstructed images, making model selection challenging. Here, we perform a systematic comparison of frequency- and time-domain implementations. In addition, we propose a contrast-to-noise ratio (CNR)-based regularization to address previous challenges with model selection. Training channel data were generated from simulated anechoic cysts. Test channel data were generated from simulated anechoic cysts with and without varied pulse shapes, in addition to physical phantom and in vivo data. We demonstrate that simplified time-domain implementations are more robust than we previously assumed, especially when using phase preserving data representations. Specifically, 0.39- and 0.36-dB median improvements in in vivo CNR compared to DAS were achieved with frequency- and time-domain implementations, respectively. We also demonstrate that CNR regularization improves the correlation between training validation loss and simulated CNR by 0.83 and between simulated and in vivo CNR by 0.35 compared to DNNs trained without CNR regularization.

Attention Flows: Analyzing and Comparing Attention Mechanisms in Language Models.

Advances in language modeling have led to the development of deep attention-based models that are performant across a wide variety of natural language processing (NLP) problems. These language models are typified by a pre-training process on large unlabeled text corpora and subsequently fine-tuned for specific tasks. Although considerable work has been devoted to understanding the attention mechanisms of pre-trained models, it is less understood how a model's attention mechanisms change when trained for a target NLP task. In this paper, we propose a visual analytics approach to understanding fine-tuning in attention-based language models. Our visualization, Attention Flows, is designed to support users in querying, tracing, and comparing attention within layers, across layers, and amongst attention heads in Transformer-based language models. To help users gain insight on how a classification decision is made, our design is centered on depicting classification-based attention at the deepest layer and how attention from prior layers flows throughout words in the input. Attention Flows supports the analysis of a single model, as well as the visual comparison between pre-trained and fine-tuned models via their similarities and differences. We use Attention Flows to study attention mechanisms in various sentence understanding tasks and highlight how attention evolves to address the nuances of solving these tasks.

Effect of Changing Electronic Health Record Opioid Analgesic Dispense Quantity Defaults on the Quantity Prescribed: A Cluster Randomized Clinical Trial.

Importance: Interventions to improve judicious prescribing of opioid analgesics for acute pain are needed owing to the risks of diversion, misuse, and overdose. Objective: To assess the effect of modifying opioid analgesic prescribing defaults in the electronic health record (EHR) on prescribing and health service use. Design, Setting, and Participants: A cluster randomized clinical trial with 2 parallel arms was conducted between June 13, 2016, and June 13, 2018, in a large urban health care system comprising 32 primary care and 4 emergency department (ED) sites in the Bronx, New York. Data were analyzed using a difference-in-differences method from 6 months before implementation through 18 months after implementation. Data were analyzed from January 2019 to February 2020. Interventions: A default dispense quantity for new opioid analgesic prescriptions of 10 tablets (intervention) vs no change (control) in the EHR. Main Outcomes and Measures: The primary outcome was the quantity of opioid analgesics prescribed with the new default prescription. Secondary outcomes were opioid analgesic reorders and health service use within 30 days after the new prescription. Intention-to-treat analysis was conducted. Results: Overall, 21 331 patients received a new opioid analgesic prescription from 490 prescribers. Comparing the intervention and control arms, site, prescriber, and patient characteristics were similar. For the new prescription, compared with the control arm, patients in the intervention arm had significantly more prescriptions for 10 tablets or fewer (7.6 percentage points; 95% CI, 6.1-9.2 percentage points), a lower number of tablets prescribed (-2.1 tablets; 95% CI, -3.3 to -0.9 tablets), and lower morphine milligram equivalents (MME) prescribed (-14.6 MME; 95% CI, -22.6 to -6.6 MME). Within 30 days after the new prescription, significant differences remained in the number of tablets prescribed (-2.7 tablets; 95% CI, -4.8 to -0.6 tablets), but not MME (-15.8 MME; 95% CI, -33.8 to 2.2 MME). Within this 30-day period, there were no significant differences between the arms in health service use. Conclusions and Relevance: In this study, implementation of a uniform reduced default dispense quantity of 10 tablets for opioid analgesic prescriptions led to a modest reduction in the quantity prescribed initially, without significantly increasing health service use. However, during 30 days after implementation, the influence on prescribing was mixed. Reducing EHR default dispense quantities for opioid analgesics is a feasible strategy that can be widely disseminated and may modestly reduce prescribing. Trial Registration: ClinicalTrials.gov Identifier: NCT03003832.

Evolutionary relationships among Massospora spp. (Entomophthorales), obligate pathogens of cicadas.

The fungal genus Massospora (Zoopagomycota: Entomophthorales) includes more than a dozen obligate, sexually transmissible pathogenic species that infect cicadas (Hemiptera) worldwide. At least two species are known to produce psychoactive compounds during infection, which has garnered considerable interest for this enigmatic genus. As with many Entomophthorales, the evolutionary relationships and host associations of Massospora spp. are not well understood. The acquisition of M. diceroproctae from Arizona, M. tettigatis from Chile, and M. platypediae from California and Colorado provided an opportunity to conduct molecular phylogenetic analyses and morphological studies to investigate whether these fungi represent a monophyletic group and delimit species boundaries. In a three-locus phylogenetic analysis including the D1-D2 domains of the nuclear 28S rRNA gene (28S), elongation factor 1 alpha-like (EFL), and beta-tubulin (BTUB), Massospora was resolved in a strongly supported monophyletic group containing four well-supported genealogically exclusive lineages, based on two of three methods of phylogenetic inference. There was incongruence among the single-gene trees: two methods of phylogenetic inference recovered trees with either the same topology as the three-gene concatenated tree (EFL) or a basal polytomy (28S, BTUB). Massospora levispora and M. platypediae isolates formed a single lineage in all analyses and are synonymized here as M. levispora. Massospora diceroproctae was sister to M. cicadina in all three single-gene trees and on an extremely long branch relative to the other Massospora, and even the outgroup taxa, which may reflect an accelerated rate of molecular evolution and/or incomplete taxon sampling. The results of the morphological study presented here indicate that spore measurements may not be phylogenetically or diagnostically informative. Despite recent advances in understanding the ecology of Massospora, much about its host range and diversity remains unexplored. The emerging phylogenetic framework can provide a foundation for exploring coevolutionary relationships with cicada hosts and the evolution of behavior-altering compounds.