The balance between antiviral and antibacterial responses during M. tuberculosis infection is regulated by the ubiquitin ligase CBL.

As a first line of host defense, macrophages must be able to effectively sense and respond to diverse types of pathogens, and while a particular type of immune response may be beneficial in some circumstances, it can be detrimental in others. Upon infecting a macrophage, M. tuberculosis (Mtb) induces proinflammatory cytokines that activate antibacterial responses. Surprisingly, Mtb also triggers antiviral responses that actually hinder the ability of macrophages to control Mtb infection. The ubiquitin ligase CBL suppresses these antiviral responses and shifts macrophages toward a more antibacterial state during Mtb infection, however, the mechanisms by which CBL regulates immune signaling are unknown. We found that CBL controls responses to multiple stimuli and broadly suppresses the expression of antiviral effector genes. We then used mass-spectrometry to investigate potential CBL substrates and identified over 46,000 ubiquitylated peptides in Mtb-infected macrophages, as well as roughly 400 peptides with CBL-dependent ubiquitylation. We then performed genetic interaction analysis of CBL and its putative substrates, and identified the Fas associated factor 2 (FAF2) adapter protein as a key signaling molecule protein downstream of CBL. Together, these analyses identify thousands of new ubiquitin-mediated signaling events during the innate immune response and reveal an important new regulatory hub in this response.

Prehospital Ground and Helicopter-Based Extracorporeal Cardiopulmonary Resuscitation (ECPR) Reduce Barriers to ECPR: A GIS Model.

INTRODUCTION: Evidence suggests that Extracorporeal Cardiopulmonary Resuscitation (ECPR) can improve survival rates for nontraumatic out-of-hospital cardiac arrest (OHCA). However, when ECPR is indicated over 50% of potential candidates are unable to qualify in the current hospital-based system due to geographic limitations. This study employs a Geographic Information System (GIS) model to estimate the number of ECPR eligible patients within the United States in the current hospital-based system, a prehospital ECPR ground-based system, and a prehospital ECPR Helicopter Emergency Medical Services (HEMS)-based system. METHODS: We constructed a GIS model to estimate ground and helicopter transport times. Time-dependent rates of ECPR eligibility were derived from the Resuscitation Outcome Consortium (ROC) database, while the Cardiac Arrest Registry to Enhance Survival (CARES) registry determined the number of OHCA patients meeting ECPR criteria within designated transportation times. Emergency Medical Services (EMS) response time, ECPR candidacy determination time, and on-scene time were modeled based on data from the EROCA trial. The combined model was used to estimate the total ECPR eligibility in each system. RESULTS: The CARES registry recorded 736,066 OHCA patients from 2013 to 2021. After applying clinical criteria, 24,661 (3.4%) ECPR-indicated OHCA were identified. When considering overall ECPR eligibility within 45 min from OHCA to initiation, only 11.76% of OHCA where ECPR was indicated were eligible in the current hospital-based system. The prehospital ECPR HEMS-based system exhibited a four-fold increase in ECPR eligibility (49.3%), while the prehospital ground-based system showed a more than two-fold increase (28.4%). CONCLUSIONS: The study demonstrates a two-fold increase in ECPR eligibility for a prehospital ECPR ground-based system and a four-fold increase for a prehospital ECPR HEMS-based system compared to the current hospital-based ECPR system. This novel GIS model can inform future ECPR implementation strategies, optimizing systems of care.

Exogenous Metabolic Modulators Improve Response to Carboplatin in Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) lacks targeted therapies, leaving cytotoxic chemotherapy as the current standard treatment. However, chemotherapy resistance remains a major clinical challenge. Increased insulin-like growth factor 1 signaling can potently blunt chemotherapy response, and lysosomal processes including the nutrient scavenging pathway autophagy can enable cancer cells to evade chemotherapy-mediated cell death. Thus, we tested whether inhibition of insulin receptor/insulin-like growth factor 1 receptor with the drug BMS-754807 and/or lysosomal disruption with hydroxychloroquine (HCQ) could sensitize TNBC cells to the chemotherapy drug carboplatin. Using in vitro studies in multiple TNBC cell lines, in concert with in vivo studies employing a murine syngeneic orthotopic transplant model of TNBC, we show that BMS-754807 and HCQ each sensitized TNBC cells and tumors to carboplatin and reveal that exogenous metabolic modulators may work synergistically with carboplatin as indicated by Bliss analysis. Additionally, we demonstrate the lack of overt in vivo toxicity with our combination regimens and, therefore, propose that metabolic targeting of TNBC may be a safe and effective strategy to increase sensitivity to chemotherapy. Thus, we conclude that the use of exogenous metabolic modulators, such as BMS-754807 or HCQ, in combination with chemotherapy warrants additional study as a strategy to improve therapeutic responses in women with TNBC.

Association of Geographic Distance and Hospital Characteristics With Use of Interhospital Transfer by Air: A Multicenter Retrospective Study.

OBJECTIVE: Interhospital transfer by air (IHTA) represents the majority of helicopter air ambulance transports in the United States, but the evaluation of what factors are associated with utilization has been limited. We aimed to assess the association of geographic distance and hospital characteristics (including patient volume) with the use of IHTA. METHODS: This was a multicenter, retrospective study of helicopter flight request data from 2018 provided by a convenience sample of 4 critical care transport medicine programs in 3 US census regions. Nonfederal referring hospitals located in the home state of the associated critical care transport medicine program and within 100 miles of the primary receiving facility in the region were included if complete data were available. We fit a Poisson principal component regression model incorporating geographic distance, the number of emergency department visits, the number of hospital discharges, case mix index, the number of intensive care unit beds, and the number of general beds and tested the association of the variables with helicopter emergency medical services utilization. RESULTS: A total of 106 referring hospitals were analyzed, 21 of which were hospitals identified as having a consistent request pattern. Using the hospitals with a consistent referral pattern, geographic distance had a significant positive association with flight request volume. Other variables, including emergency department visit volume, were not associated. Overall, the included variables offered poor explanatory power for the observed variation between referring facilities in the use of IHTA (r2 = 0.09). Predicted flights based on the principal component regression model for all referring hospitals suggested the majority of referring hospitals used multiple flight programs. CONCLUSION: Geographic distance is associated with the use of IHTA. Unexpectedly, most basic hospital characteristics are not associated with the use of IHTA, and the degree of variation between referring facilities that is explained by patient volume is limited. The evaluation of nonhospital factors, such as the density and availability of critical care or advanced life support ground emergency medical services resources, is needed.

Host E3 ubiquitin ligase ITCH mediates Toxoplasma gondii effector GRA35-triggered NLRP1 inflammasome activation and cell-autonomous immunity.

Toxoplasma gondii is an intracellular parasite that can activate the NLRP1 inflammasome leading to macrophage pyroptosis in Lewis rats, but the underlying mechanism is not well understood. In this study, we performed a genome-wide CRISPR screen and identified the dense granule proteins GRA35, GRA42, and GRA43 as the Toxoplasma effectors mediating cell death in Lewis rat macrophages. GRA35 localizes on the parasitophorous vacuole membrane, where it interacts with the host E3 ubiquitin ligase ITCH. Inhibition of proteasome activity or ITCH knockout prevented pyroptosis in Toxoplasma-infected Lewis rat macrophages, consistent with the "NLRP1 functional degradation model." However, there was no evidence that ITCH directly ubiquitinates or interacts with rat NLRP1. We also found that GRA35-ITCH interaction affected Toxoplasma fitness in IFNγ-activated human fibroblasts, likely due to ITCH's role in recruiting ubiquitin and the parasite-restriction factor RNF213 to the parasitophorous vacuole membrane. These findings identify a new role of host E3 ubiquitin ligase ITCH in mediating effector-triggered immunity, a critical concept that involves recognizing intracellular pathogens and initiating host innate immune responses.IMPORTANCEEffector-triggered immunity represents an innate immune defense mechanism that plays a crucial role in sensing and controlling intracellular pathogen infection. The NLRP1 inflammasome in the Lewis rats can detect Toxoplasma infection, which triggers proptosis in infected macrophages and eliminates the parasite's replication niche. The work reported here revealed that host E3 ubiquitin ligase ITCH is able to recognize and interact with Toxoplasma effector protein GRA35 localized on the parasite-host interface, leading to NLRP1 inflammasome activation in Lewis rat macrophages. Furthermore, ITCH-GRA35 interaction contributes to the restriction of Toxoplasma in human fibroblasts stimulated by IFNγ. Thus, this research provides valuable insights into understanding pathogen recognition and restriction mediated by host E3 ubiquitin ligase.

Safety, tolerability, and effect of a single aural dose of Dornase alfa at the time of ventilation tube surgery for otitis media: A Phase 1b double randomized control trial.

BACKGROUND: One third of children require repeat ventilation tube insertion (VTI) for otitis media. Disease recurrence is associated with persistent middle ear bacterial biofilms. With demonstration that Dornase alfa (a DNase) disrupts middle ear effusion biofilms ex vivo, we identified potential for this as an anti-biofilm therapy to prevent repeat VTI. First, safety and tolerability needed to be measured. METHODS: This was a phase 1B double-blinded randomized control trial conducted in Western Australia. Children between 6 months and 5 years undergoing VTI for bilateral middle ear effusion were recruited between 2012 and 2014 and followed for two years. Children's ears were randomized to receive either Dornase alfa (1 mg/mL) or 0.9 % sodium chloride (placebo) at time of surgery. Children were followed up at 2 weeks post-VTI and at 3-monthly intervals for 2 years. Outcomes assessed were: 1) safety and tolerability, 2) otorrhoea frequency, 3) blocked or extruded ventilation tube (VT) frequency, 4) time to blockage or extrusion, 5) time to infection recurrence and/or need for repeat VTI. RESULTS: Sixty children (mean age 2.3 years) were enrolled with 87 % reaching study endpoint. Treatment did not change otorrhoea frequency. Hearing improved in all children following VTI, with no indication of ototoxicity. Dornase alfa had some effect on increasing time until VT extrusion (p = 0.099); and blockage and/or extrusion (p = 0.122). Frequency of recurrence and time until recurrence were similar. Fourteen children required repeat VTI within the follow-up period. CONCLUSION: A single application of Dornase alfa into the middle ear at time of VTI was safe, non-ototoxic, and well-tolerated. TRIAL REGISTRATION: ACTRN12623000504617.

Emergency Medicine Resident Needs Assessment and Preferences for a High-value Care Curriculum.

Introduction: Consideration of the cost of care and value in healthcare is now a recognized element of physician training. Despite the urgency to educate trainees in high-value care (HVC), educational curricula and evaluation of these training paths remain limited, especially with respect to emergency medicine (EM) residents. We aimed to complete a needs assessment and evaluate curricular preferences for instruction on HVC among EM residents. Methods: This was a qualitative, exploratory study using content analysis of two focus groups including a total of eight EM residents from a single Midwestern EM residency training program. Participants also completed a survey questionnaire. Results: There were two themes. Within the overall theme of resident experience with and perception of HVC, we found five sub-themes: 1) understanding of HVC focuses on diagnosis and decision-making; 2) concern about patient costs, including the effects on patients' lives and their ability to engage with recommended outpatient care; 3) conflict between internal beliefs and external expectations, including patients' perceptions of value; 4) approach to HVC changes with increasing clinical experience; and 5) slow-moving, political discussion around HVC. Within the overall theme of desired education and curricular design, we identified four sub-themes: 1) limited prior education on HVC and health economics; 2) motivation to receive training on HVC and health economics; 3) desire for discussion-based format for HVC curriculum; and 4) curriculum targeted to level of training. Respondents indicated greatest acceptability of interactive, discussion-based formats. Discussion: We conducted a targeted needs assessment for HVC among EM residents. We identified broad interest in the topic and limited self-reported baseline knowledge. Curricular content may benefit from incorporating resident concerns about patient costs and conflict between external expectations and internal beliefs about HVC. Curricular design may benefit from a focus on interactive, discussion-based modalities and tailoring to the learner's level of training.

High-Efficiency Gene Disruption in Primary Bone Marrow-Derived Macrophages Using Electroporated Cas9-sgRNA Complexes.

Bone marrow-derived macrophages (BMDMs) from mice are a key tool for studying the complex biology of tissue macrophages. As primary cells, they model the physiology of macrophages in vivo more closely than immortalized macrophage cell lines and can be derived from mice already carrying defined genetic changes. However, disrupting gene function in BMDMs remains technically challenging. Here, we provide a protocol for efficient CRISPR/Cas9 genome editing in BMDMs, which allows for the introduction of small insertions and deletions (indels) that result in frameshift mutations that disrupt gene function. The protocol describes how to synthesize single-guide RNAs (sgRNA-Cas9) and form purified sgRNA-Cas9 ribonucleoprotein complexes (RNPs) that can be delivered by electroporation. It also provides an efficient method for monitoring editing efficiency using routine Sanger sequencing and a freely available online analysis program. The protocol can be performed within 1 week and does not require plasmid construction; it typically results in 85% to 95% editing efficiency.

Lateral Canthotomy Task Trainer in an Educational Small Group for Flight Providers.

OBJECTIVE: Lateral canthotomy is a rare, emergent, vision-preserving procedure to treat orbital compartment syndrome. Using Ericsson's deliberate practice model, we aimed to develop a multimodal small group intervention including a modified low-fidelity task trainer to improve flight physician knowledge and technical competency for lateral canthotomy in the prehospital context. METHODS: Two cohorts of resident (postgraduate year 1) flight physicians received small group training during an all-day competency-based flight physician orientation. The first cohort completed self-report pre- and postintervention assessments. In the second cohort, examiners assessed pre- and postintervention performance. RESULTS: Comparing pre- and postintervention responses (N = 27), the mean agreement with the knowledge of indications increased from 3.7 to 4.8. The mean agreement regarding confidence in skills increased from 2.2 to 4.2 (P < .001). The majority of participants (20/27) indicated the trainer "definitely helped," whereas 7 of 27 residents indicated the trainer "somewhat helped" them to learn skills. Examiners assessed holistic learner performance (n = 13) as improved from a mean of 3.2 preintervention to 4.7 postintervention, with 11 of 13 learners demonstrating improvement (P < .005). CONCLUSION: We demonstrate the feasibility of a brief small group training combining multimodal didactics with a modified low-fidelity task trainer. Resident self-assessment and examiner assessment demonstrated improved procedural skill with lateral canthotomy.

Deficiency in Galectin-3, -8, and -9 impairs immunity to chronic Mycobacterium tuberculosis infection but not acute infection with multiple intracellular pathogens.

Macrophages employ an array of pattern recognition receptors to detect and eliminate intracellular pathogens that access the cytosol. The cytosolic carbohydrate sensors Galectin-3, -8, and -9 (Gal-3, Gal-8, and Gal-9) recognize damaged pathogen-containing phagosomes, and Gal-3 and Gal-8 are reported to restrict bacterial growth via autophagy in cultured cells. However, the contribution of these galectins to host resistance during bacterial infection in vivo remains unclear. We found that Gal-9 binds directly to Mycobacterium tuberculosis (Mtb) and Salmonella enterica serovar Typhimurium (Stm) and localizes to Mtb in macrophages. To determine the combined contribution of membrane damage-sensing galectins to immunity, we generated Gal-3, -8, and -9 triple knockout (TKO) mice. Mtb infection of primary macrophages from TKO mice resulted in defective autophagic flux but normal bacterial replication. Surprisingly, these mice had no discernable defect in resistance to acute infection with Mtb, Stm or Listeria monocytogenes, and had only modest impairments in bacterial growth restriction and CD4 T cell activation during chronic Mtb infection. Collectively, these findings indicate that while Gal-3, -8, and -9 respond to an array of intracellular pathogens, together these membrane damage-sensing galectins play a limited role in host resistance to bacterial infection.

The development of a family-based wearable intervention using behaviour change and co-design approaches: move and connect.

BACKGROUND: Previous research has explored the effectiveness of wearable activity trackers (wearables) for increasing child physical activity (PA) levels, but there have been mixed results. The use of theoretical frameworks and co-design techniques are recognised ways of increasing an intervention's acceptability and effectiveness. AIMS: This study aims to use co-design workshops and an evidence-based theoretical framework (the Behaviour Change Wheel) to develop a family-based PA intervention using wearables. METHODS: Three stages of intervention development outlined by the Behaviour Change Wheel were used. Co-design workshops with seven families (11 parents and 12 children) and seven PA experts were conducted where stakeholders discussed how to overcome previously identified barriers to families being active and using wearables. This resulted in the intervention's components being developed, with each component's mechanisms of action (e.g. intervention functions and behaviour change techniques) being retrospectively identified. RESULTS: The 'Move & Connect' intervention was developed, which targets family PA and wearable use. The intervention takes a flexible approach and includes eight components, including wearable devices (Fitbit Alta HR), support resources, an introductory workshop, collective challenges, goal setting and reviewing, engagement prompts, social support and health-related resources (e.g. educational videos). The intervention incorporates six intervention functions targeting PA and wearable use: education, training, modelling, persuasion, incentivisation and environmental restructuring and 24 behaviour change techniques, including goal setting, social comparison, feedback on behaviour and graded task. CONCLUSIONS: This is the first known study to use an evidence-based framework and co-design to develop a family-based wearable intervention. The identification of the intervention's mechanisms of action will prove useful when implementing and evaluating the 'Move & Connect' intervention and allow researchers to replicate its components.

Management of patients with impella devices or intra-aortic balloon pumps during helicopter air ambulance transport in observational data.

INTRODUCTION: Placement of percutaneous ventricular support devices such as an intraaortic balloon pump (IABP) or Abiomed Impella device can treat severe cardiogenic shock. Critical care transport medicine (CCTM) providers frequently manage patients supported by these devices during interfacility transfers, often using a helicopter air ambulance (HAA). An understanding of patient needs and management during transport is essential to informing crew configuration and training, and this study adds to the limited existing data on the HAA transport of this complex patient population. METHODS: We performed a retrospective chart review of all HAA transports of patients with an IABP (n = 38) or Impella (n = 11) device at a single CCTM program from 2016 to 2020. We evaluated transport times and composite variables for the frequency of adverse events, condition changes requiring critical care evaluation, and critical care interventions. RESULTS: In this observational cohort, patients with an Impella device more frequently had an advanced airway and at least 1 vasopressor or inotrope active prior to transport. While flight times were similar, CCTM teams remained at referring facilities longer for patients with an Impella device (99 vs 68 minutes; p = 0.0097). Compared to patients with an IABP, patients with an Impella device more frequently had a condition change requiring critical care evaluation (100% vs 42%; p = 0.0005) and more frequently received critical care interventions (100% vs 53%; p = 0.0037). Adverse events were uncommon and did not differ for patients with an Impella device compared to an IABP (27% vs 11%; p = 0.178). CONCLUSION: Patients requiring mechanical circulatory support with IABP and Impella devices frequently require critical care management during transport. Clinicians should ensure the CCTM team has appropriate staffing, training, and resources to meet the critical care needs of these high acuity patients.

Host E3 ubiquitin ligase ITCH mediates Toxoplasma gondii effector GRA35-triggered NLRP1 inflammasome activation and cell-autonomous immunity.

Toxoplasma gondii is an intracellular parasite that can activate the NLRP1 inflammasome leading to macrophage pyroptosis in Lewis rats, but the underlying mechanism is not well understood. In this study, we performed a genome-wide CRISPR screen and identified the dense granule proteins GRA35, GRA42, and GRA43 as the Toxoplasma effectors mediating cell death in Lewis rat macrophages. GRA35 localizes on the parasitophorous vacuole membrane, where it interacts with the host E3 ubiquitin ligase ITCH. Inhibition of proteasome activity or ITCH knockout prevented pyroptosis in Toxoplasma-infected Lewis rat macrophages, consistent with the "NLRP1 functional degradation model". However, there was no evidence that ITCH directly ubiquitinates or interacts with rat NLRP1. We also found that GRA35-ITCH interaction affected Toxoplasma fitness in IFNγ-activated human fibroblasts, likely due to ITCH's role in recruiting ubiquitin and the parasite-restriction factor RNF213 to the parasitophorous vacuole membrane. These findings identify a new role of host E3 ubiquitin ligase ITCH in mediating effector-triggered immunity, a critical concept that involves recognizing intracellular pathogens and initiating host innate immune responses.

Selective Serotonin Reuptake Inhibitors and Associated Bleeding Risks: A Narrative and Clinical Review.

Major Depressive Disorder (MDD) is a major cause of disability worldwide and is associated with serious lasting impairment. A leading hypothesis of the pathophysiology of MDD is the monoamine deficiency hypothesis which suggests that depression is caused by depletion of serotonin, norepinephrine, or dopamine in the central nervous system. Serotonin is the most widely studied neurotransmitter in the pathophysiology of depression, with studies showing that reduced central serotonin synthesis leads to depressive symptoms in individuals at risk for depression. Selective Serotonin Reuptake Inhibitors (SSRI) inhibit serotonin reuptake and subsequently increase the amount of serotonin available in synapses. Common side effects of SSRIs include increased suicidality of patients under the age of 25, sexual dysfunction, anxiety, dizziness, weight gain, gastrointestinal distress, and headache. Other side effects include prolonging the QT interval, coagulopathy, and the risk of serotonin syndrome, as well as SSRI discontinuation syndrome. Sites of increased bleeding related to SSRI use have been reported to occur in the upper gastrointestinal tract, as well as intracranially. Based on the current literature, three studies have found that SSRIs are not associated with increased bleeding and/or increased perioperative risk, while others have demonstrated that SSRIs are associated with an increased risk in perioperative use. The inhibition of serotonin reuptake can affect platelet aggregation since platelets also express the serotonin transporter. SSRIs can result in decreased storage of serotonin in platelet dense granules. Increased serotonin can also increase gastric acid secretion, which increases the risk for ulceration. SSRIs in combination with NSAIDs also show a significantly increased risk of upper GI bleeding. Some studies show an increased bleeding risk from 30% to 70% when taking a combination of vitamin K antagonists and SSRIs in hospitalized patients. Related to the high prevalence of conditions that are treated with SSRIs, the bleeding risk associated with this class of medication merits further study.

Eligibility of out-of-hospital cardiac arrest patients for extracorporeal cardiopulmonary resuscitation in the United States: A geographic information system model.

BACKGROUND: Recent evidence suggest that extracorporeal cardiopulmonary resuscitation (ECPR) may improve survival rates for nontraumatic out-of-hospital cardiac arrest (OHCA). Eligibility criteria for ECPR are often based on patient age, clinical variables, and facility capabilities. Expanding access to ECPR across the U.S. requires a better understanding of how these factors interact with transport time to ECPR centers. METHODS: We constructed a Geographic Information System (GIS) model to estimate the number of ECPR candidates in the U.S. We utilized a Resuscitation Outcome Consortium (ROC) database to model time-dependent rates of ECPR eligibility and the Cardiac Arrest Registry to Enhance Survival (CARES) registry to determine the total number of OHCA patients who meet pre-specified ECPR criteria within designated transportation times. The combined model was used to estimate the total number of ECPR candidates. RESULTS: There were 588,203 OHCA patients in the CARES registry from 2013 to 2020. After applying clinical eligibility criteria, 22,104 (3.76%) OHCA patients were deemed eligible for ECPR. The rate of ROSC increased with longer resuscitation time, which resulted in fewer ECPR candidates. The proportion of OHCA patients eligible for ECPR increased with older age cutoffs. Only 1.68% (9,889/588,203) of OHCA patients in the U.S. were eligible for ECPR based on a 45-minute transportation time to an ECMO-ready center model. CONCLUSIONS: Less than 2% of OHCA patients are eligible for ECPR in the U.S. GIS models can identify the impact of clinical criteria, transportation time, and hospital capabilities on ECPR eligibility to inform future implementation strategies.

Statin Administration for ST-Elevation Myocardial Infarction During Rotor Wing Transport.

OBJECTIVE: The aim of this study was to evaluate the feasibility of statin administration by a critical care transport medicine (CCTM) team during rotor wing transport for ST-elevation myocardial infarction patients to a percutaneous intervention-capable center. METHODS: We conducted a retrospective study at a single CCTM program after an intervention focused on statin administration for ST-elevation myocardial infarction that included a formulary change and a single brief educational presentation to flight physicians. A comparison group of flight nurse practitioners underwent training after the study period and were used as a control. Two authors completed an independent chart review to collect data. Descriptive statistics and chi-square or Mann-Whitney U testing were used to compare groups. RESULTS: Statin administration (or documentation of statin administration before CCTM crew arrival or contraindication to statin administration) occurred during 15 of 19 (79%) transports staffed by trained providers and 3 of 18 (17%) transports staffed by untrained providers (P < .001 by chi-square test). Scene times were not significantly different between transports by trained and untrained providers. CONCLUSION: In summary, we demonstrate the feasibility and safety of a protocol for statin administration in the CCTM setting.

Cross-sectional characteristics of pediatric-onset discoid lupus erythematosus: Results of a multicenter, retrospective cohort study.

BACKGROUND: The incidence of systemic lupus in children with discoid lupus is unknown. OBJECTIVE: This study assessed the baseline characteristics of patients with pediatric discoid lupus erythematosus (pDLE). METHODS: Medical records at 17 sites were reviewed for pediatric dermatology and rheumatology patients with discoid lupus erythematosus. The inclusion criteria were clinical and/or histopathologic diagnosis of discoid lupus erythematosus with an age at onset of <18 years. Baseline data were collected at the first documented visit. Outcomes included diagnosis of systemic lupus erythematosus (SLE) at the baseline visit using the 1997 American College of Rheumatology (primary) and the 2012 Systemic Lupus International Collaborating Clinics (secondary) criteria. RESULTS: Of the >1500 charts reviewed, 438 patients met the inclusion criteria. The cohort was predominantly female (72%) and racially/ethnically diverse. A diagnosis of SLE at the baseline visit (pDLE + SLE) was rendered in 162 (37%) patients using the American College of Rheumatology and in 181 (41%) patients using the Systemic Lupus International Collaborating Clinics criteria. Patients with pDLE + SLE were older at the time of rash onset (median, 12.9 vs 8.9 years; P < .001), with shorter time from discoid lupus erythematosus onset to diagnosis, compared with patients with pDLE-only (median, 2 vs 7 months; P < .001). Patients with pDLE + SLE were more likely to be female (P = .004), with generalized discoid lupus erythematosus and clinically aggressive disease, including end-organ involvement, positive serologies, and higher- titer levels of antinuclear antibodies (P < .001). LIMITATIONS: Retrospective study. CONCLUSION: A diagnosis of discoid lupus erythematosus in adolescence should prompt thorough screening for SLE.

An Update on Peroneal Nerve Entrapment and Neuropathy.

Peroneal neuropathy is the most common compressive neuropathy of the lower extremity. It should be included in the differential diagnosis for patients presenting with foot drop, the pain of the lower extremity, or numbness of the lower extremity. Symptoms of peroneal neuropathy may occur due to compression of the common peroneal nerve (CPN), superficial peroneal nerve (SPN), or deep peroneal nerve (DPN), each with different clinical presentations. The CPN is most commonly compressed by the bony prominence of the fibula, the SPN most commonly entrapped as it exits the lateral compartment of the leg, and the DPN as it crosses underneath the extensor retinaculum. Accurate and timely diagnosis of any peroneal neuropathy is important to avoid progression of nerve injury and permanent nerve damage. The diagnosis is often made with physical exam findings of decreased strength, altered sensation, and gait abnormalities. Motor nerve conduction studies, electromyography studies, and diagnostic nerve blocks can also assist in diagnosis and prognosis. First-line treatments include removing anything that may be causing external compression, providing stability to unstable joints, and reducing inflammation. Although many peroneal nerve entrapments will resolve with observation and activity modification, surgical treatment is often required when entrapment is refractory to these conservative management strategies. Recently, additional options including microsurgical decompression and percutaneous peripheral nerve stimulation have been reported; however, large studies reporting outcomes are lacking.

Variation in Participation in Nurse-Driven Emergency Department Hepatitis C Screening.

Emergency departments (EDs) are an important potential site for public health screening programs, although implementation of such programs can be challenging. Potential barriers include system-level issues (e.g., funding and time pressures) and individual provider-level issues (e.g., awareness and acceptance). This cross-sectional evaluation of a nurse-driven, triage-based hepatitis C virus (HCV) screening program in an urban, academic ED assessed variation in nurse participation from April to November 2017. For this program, electronic health record (EHR) prompts for HCV screening were integrated into nurses' triage workflow. Process measures evaluating HCV screening participation were abstracted from the EHR for all ED encounters with patient year of birth between 1945 and 1965. Registered nurses who routinely worked in triage and were full-time employees throughout the study period were included for analysis. The primary outcome was the proportion of eligible ED encounters with completed HCV screening, by nurse. Of 14,375 ED encounters, 3,375 (23.5%, 95% confidence interval [CI]: 22.8, 24.2) had completed HCV screening and 1,408 (9.8%, 95% CI: 3.9, 10.3) had HCV screening EHR sections opened by the triage nurse but closed without action; the remainder of encounters had no activity in HCV screening EHR sections. Among the 93 eligible nurses, 22 nurses (24%, 95% CI: 16, 34) completed HCV screening for more than 70% of encounters, whereas 10 nurses (11%, 95% CI: 6, 19) never completed HCV screening. The proportion of eligible encounters with completed HCV screening was 11.0% higher (95% CI: 9.8, 12.6) for encounters seen between 7 a.m. and 7 p.m. than between 7 p.m. and 7 a.m. (27.5% and 16.3%, respectively). In conclusion, wide variation in individual nurse participation in HCV screening suggests individual-level barriers are a more significant barrier to ED screening than previously recognized. Implementation research should expand beyond questions of resource availability and procedural streamlining to evaluate and address staff knowledge, beliefs, attitudes, and motivation.