Spatially patterned 3D model mimics key features of cancer metastasis to bone.

Bone is the most common target of metastasis in breast cancer and prostate cancer, leading to significant mortality due to lack of effective treatments. The discovery of novel therapies has been hampered by a lack of physiologically relevant in vitro models that can mimic key clinical features of bone metastases. To fill this critical gap, here we report spatially patterned, tissue engineered 3D models of breast cancer and prostate cancer bone metastasis which mimic bone-specific invasion, cancer aggressiveness, cancer-induced dysregulation of bone remodeling, and in vivo drug response. We demonstrate the potential of integrating such 3D models with single-cell RNA sequencing to identify key signaling drivers of cancer metastasis to bone. Together, these results validate that spatially patterned 3D bone metastasis models mimic key clinical features of bone metastasis and can serve as a novel research tool to elucidate bone metastasis biology and expedite drug discovery.

Proceedings from the 2021 SAEM Consensus Conference: Research Priorities for Interventions to Address Social Risks and Needs Identified in Emergency Department Patients.

INTRODUCTION: Emergency departments (ED) function as a health and social safety net, regularly taking care of patients with high social risk and need. Few studies have examined ED-based interventions for social risk and need. METHODS: Focusing on ED-based interventions, we identified initial research gaps and priorities in the ED using a literature review, topic expert feedback, and consensus-building. Research gaps and priorities were further refined based on moderated, scripted discussions and survey feedback during the 2021 SAEM Consensus Conference. Using these methods, we derived six priorities based on three identified gaps in ED-based social risks and needs interventions: 1) assessment of ED-based interventions; 2) intervention implementation in the ED environment; and 3) intercommunication between patients, EDs, and medical and social systems. RESULTS: Using these methods, we derived six priorities based on three identified gaps in ED-based social risks and needs interventions: 1) assessment of ED-based interventions, 2) intervention implementation in the ED environment, and 3) intercommunication between patients, EDs, and medical and social systems. Assessing intervention effectiveness through patient-centered outcome and risk reduction measures should be high priorities in the future. Also noted was the need to study methods of integrating interventions into the ED environment and to increase collaboration between EDs and their larger health systems, community partners, social services, and local government. CONCLUSION: The identified research gaps and priorities offer guidance for future work to establish effective interventions and build relationships with community health and social systems to address social risks and needs, thereby improving the health of our patients.

Implementation Fidelity of Chatbot Screening for Social Needs: Acceptability, Feasibility, Appropriateness.

OBJECTIVES: Patient and provider-facing screening tools for social determinants of health have been explored in a variety of contexts; however, effective screening and resource referral remain challenging, and less is known about how patients perceive chatbots as potential social needs screening tools. We investigated patient perceptions of a chatbot for social needs screening using three implementation outcome measures: acceptability, feasibility, and appropriateness. METHODS: We implemented a chatbot for social needs screening at one large public hospital emergency department (ED) and used concurrent triangulation to assess perceptions of the chatbot use for screening. A total of 350 ED visitors completed the social needs screening and rated the chatbot on implementation outcome measures, and 22 participants engaged in follow-up phone interviews. RESULTS: The screened participants ranged in age from 18 to 90 years old and were diverse in race/ethnicity, education, and insurance status. Participants (n = 350) rated the chatbot as an acceptable, feasible, and appropriate way of screening. Through interviews (n = 22), participants explained that the chatbot was a responsive, private, easy to use, efficient, and comfortable channel to report social needs in the ED, but wanted more information on data use and more support in accessing resources. CONCLUSION: In this study, we deployed a chatbot for social needs screening in a real-world context and found patients perceived the chatbot to be an acceptable, feasible, and appropriate modality for social needs screening. Findings suggest that chatbots are a promising modality for social needs screening and can successfully engage a large, diverse patient population in the ED. This is significant, as it suggests that chatbots could facilitate a screening process that ultimately connects patients to care for social needs, improving health and well-being for members of vulnerable patient populations.

Models for Implementing Emergency Department-Initiated Buprenorphine With Referral for Ongoing Medication Treatment at Emergency Department Discharge in Diverse Academic Centers.

There has been a substantial rise in the number of publications and training opportunities on the care and treatment of emergency department (ED) patients with opioid use disorder over the past several years. The American College of Emergency Physicians recently published recommendations for providing buprenorphine to patients with opioid use disorder, but barriers to implementing this clinical practice remain. We describe the models for implementing ED-initiated buprenorphine at 4 diverse urban, academic medical centers across the country as part of a federally funded effort termed "Project ED Health." These 4 sites successfully implemented unique ED-initiated buprenorphine programs as part of a comparison of implementation facilitation to traditional educational dissemination on the uptake of ED-initiated buprenorphine. Each site describes the elements central to the ED process, including screening, treatment initiation, referral, and follow-up, while harnessing organizational characteristics, including ED culture. Finally, we discuss common facilitators to program success, including information technology and electronic medical record integration, hospital-level support, strong connections with outpatient partners, and quality improvement processes.

Who is coming back for more chlamydia testing within non-specialist health services and where do they go? England, 2013-2016.

OBJECTIVES: To investigate patient demographics and venue type preferences within community settings associated with re-attendance for chlamydia testing. STUDY DESIGN: Data used for this analysis were obtained from the English National Chlamydia Screening Programme (NCSP) which focuses on prevention, control and treatment of chlamydia in sexually active under-25 year olds. A greater understanding of how young adults attend services helps to inform commissioners regarding where to focus resources within community settings. METHODS: Data from the Chlamydia surveillance system (CTAD) were used to count patient attendances at non-specialist sexual health services (SHSs) among 15-24-year-olds and monitor re-attendance for chlamydia testing within and between community services between 6 and 18 months of their first visit. RESULTS: From January 2013 to December 2016, 866,847 young people underwent 1,041,245 tests for chlamydia. Re-attendance for chlamydia testing was 20.1% (174,398/866,847). Re-attendance rate was 28.5% after a positive test and 19.5% after a negative test. For re-attenders, 64.2% used the same venue type for both visits. General practice (GP) and sexual and reproductive health services (SRH) were the most commonly re-attended services (31.0% and 30.6% respectively). CONCLUSIONS: Only one in five re-attended for chlamydia testing. Re-attendance was associated with having a positive result, accessibility and convenience. Patients are likely to return for testing to services they know. This should be considered by commissioners implementing new re-attendance guidance based on the NCSP.

The genetic insulator RiboJ increases expression of insulated genes.

A primary objective of synthetic biology is the construction of genetic circuits with behaviors that can be predicted based on the properties of the constituent genetic parts from which they are built. However a significant issue in the construction of synthetic genetic circuits is a phenomenon known as context dependence in which the behavior of a given part changes depending on the choice of adjacent or nearby parts. Interactions between parts compromise the modularity of the circuit, impeding the implementation of predictable genetic constructs. To address this issue, investigators have devised genetic insulators that prevent these unintended context-dependent interactions between neighboring parts. One of the most commonly used insulators in bacterial systems is the self-cleaving ribozyme RiboJ. Despite its utility as an insulator, there has been no systematic quantitative assessment of the effect of RiboJ on the expression level of downstream genetic parts. Here, we characterized the impact of insulation with RiboJ on expression of a reporter gene driven by a promoter from a library of 24 frequently employed constitutive promoters in an Escherichia coli model system. We show that, depending on the strength of the promoter, insulation with RiboJ increased protein abundance between twofold and tenfold and increased transcript abundance by an average of twofold. This result demonstrates that genetic insulators in E. coli can impact the expression of downstream genes, information that is essential for the design of predictable genetic circuits and constructs.

Methods for field measurement of antibiotic concentrations: limitations and outlook.

The growing prevalence of antibiotic resistance poses an increasingly serious threat to human health. Although an important driver of antibiotic resistance is the continuous exposure of bacteria to sublethal concentrations of antibiotics in natural environments, antibiotic pollutants are not currently tracked globally or systematically. This limits the international capacity to address the rise of antibiotic resistance at its source. To address this lack of data, the development of methods to measure antibiotic concentrations on-site is essential. These methods, ideally, must be sensitive to sublethal concentrations of antibiotics and require minimal technical expertise. Furthermore, factors such as cost, selectivity, biosafety and the ability to multiplex must be evaluated in the context of field use. Based on these criteria, we provide a critical review of current methods in antibiotic detection and evaluate their adaptability for use on-site. We categorize these methods into microbiological assays, physical and chemical assays, immunoassays, aptasensors and whole-cell biosensors. We recommend continued development of a dipstick or microfluidics approach with a bacterial promoter-based mechanism and colorimetric output. This technique would incorporate the advantageous aspects of existing methods, maximize shelf-life and ease-of-use, and require minimal resources to implement in the field.

A statewide prescription monitoring program affects emergency department prescribing behaviors.

STUDY OBJECTIVE: Ohio recently instituted an online prescription monitoring program, the Ohio Automated Rx Reporting System (OARRS), to monitor controlled substance prescriptions within Ohio. This study is undertaken to identify the influence of OARRS data on clinical management of emergency department (ED) patients with painful conditions. METHODS: This prospective quasiexperimental study was conducted at the University of Toledo Medical Center Emergency Department during June to July 2008. Eligible participants included ED patients with painful conditions. Patients with acute injuries were excluded. After clinical evaluation, and again after presentation of OARRS data, providers answered a set of questions about anticipated pain prescription for the patient. Outcome measures included changes in opioid prescription and other potential factors that influenced opioid prescription. RESULTS: Among 179 participants, OARRS data revealed high numbers of narcotics prescriptions filled in the most recent 12 months (median 7; range 0 to 128). Numerous providers prescribed narcotics for patients (median 3 per patient; range 0 to 40). Patients had filled narcotics prescriptions at different pharmacies (mean [SD] 3.5 [4.4]). Eighteen providers are represented in the study. Four providers treated 63% (N=114) of the patients in the study. After review of the OARRS data, providers changed the clinical management in 41% (N=74) of cases. In cases of altered management, the majority (61%; N=45) resulted in fewer or no opioid medications prescribed than originally planned, whereas 39% (N=29) resulted in more opioid medication than previously planned. CONCLUSION: The use of data from a statewide narcotic registry frequently altered prescribing behavior for management of ED patients with complaints of nontraumatic pain.

Infiltration of epinephrine in tonsillectomy: a randomized, prospective, double-blind study.

A variety of hemostatic agents and techniques have been used in an attempt to reduce intraoperative blood loss and postoperative bleeding in tonsillectomy. The efficacy of most of these substances and techniques has been judged primarily on clinical impressions. Because of the paucity of prospective studies, a randomized, prospective, double-blind study, using the patients as their own controls, was conducted. Ninety-two patients were injected before tonsillectomy in a random, double-blind fashion with normal saline solution in one tonsil and 1:100,000 epinephrine in the other. The blood loss, time of dissection, and postoperative bleeding were recorded separately for each tonsil. Cardiac manifestations were also monitored. The tonsils injected with epinephrine had a statistically significant reduction in blood loss and dissection time when compared with those injected with normal saline. Subjectively, dissection was easier on the epinephrine-injected side. There was no difference in the incidence of postoperative hemorrhage. Cardiac manifestations of epinephrine were minimal and transient. This study demonstrates that epinephrine is useful in reducing hemorrhage during tonsillectomy and can be used safely with the appropriate inhalation anesthetics.

"Saber-sheath" trachea.

Narrowing of the intrathoracic trachea in the coronal plane with anteroposterior lengthening is characteristic of the "saber-sheath" trachea deformity. This structural disorder is strongly associated with chronic obstructive pulmonary disease and may be related to chronic bronchitis. Although lateral compression suggests weakening and collapse, the supporting tracheal cartilage is usually thickened and densely calcified. We present a patient who was discharged after uneventful total laryngectomy but later complained of increasing airway obstruction from crusted secretions, resulting in visits to the emergency room and admission to the hospital. After the diagnosis was made by computed tomography, tracheal dilation was performed with some improvement. The diagnostic findings of the saber-sheath trachea, differential diagnosis, possible causes, and clinical implications are discussed.

Facial paralysis and Bell's palsy: a protocol for differential diagnosis.

In the past, most cases of facial paralysis have been erroneously labeled Bell's palsy. Bell's palsy has been synonymous with and defined as idiopathic facial paralysis affecting only the facial nerve within the confines of the temporal bone. In the last ten years, Bell's palsy has been redefined as viral polyneuritis, probably caused by herpes simplex reactivation, and its diagnosis is no longer reached by exclusion. This article discusses the signs, symptoms, and testing necessary to confidently and accurately differentiate Bell's palsy from other forms of facial paralysis. The nonspecificity of topographic diagnosis is discussed and statistical analysis of factors affecting prognosis are included.

Cytoplasmic DNA synthesis induced by RNA tumor viruses.

Infection of mouse embryo cells with two strains of murine sarcoma virus and one strain of murine leukemia virus was followed rapidly by synthesis of DNA in the cytoplasm. Persistently infected cells have not shown such synthesis, and ultraviolet-irradiated virus did not induce DNA synthesis. This new DNA presumably represents an intermediate in the virus replication cycle specified by the virion DNA polymerase(s). Failure to observe cytoplasmic DNA synthesis in persistently infected cells suggests, in keeping with the results of inhibitor experiments, that the new "viral" DNA becomes associated with cellular DNA in some form of stable interaction.