Effectiveness of Substance Use Navigation for Emergency Department Patients With Substance Use Disorders: An Implementation Study.

STUDY OBJECTIVE: We implemented a whole person care-informed intervention delivered by substance use navigators (SUN) for emergency department (ED) patients with substance use disorders. METHODS: This was an implementation study of adult patients discharged from 3 public hospital EDs between September 1, 2021 through January 31, 2022 with cocaine, methamphetamine, alcohol, and opioid use-related diagnoses. The primary effectiveness outcome was treatment engagement within 30 days of ED discharge among patients with and without the SUN intervention. We used logistic regression and nearest neighbor propensity score matching without replacement to control for confounding effects. RESULTS: There were 1,328 patients in the cohort, and 119 (9.0%) received the SUN intervention; 50.4% of patients in the SUN intervention group and 15.9% of patients without the SUN intervention were engaged in outpatient treatment within 30 days of ED discharge (difference in proportions: 34.5%, 95% confidence interval [CI] 25.3% to 43.8%). In the unadjusted analysis, the SUN intervention was associated with higher rates of treatment engagement after ED discharge for patients with alcohol, opioid, and cocaine-related diagnoses; patients with methamphetamine-related diagnoses had low engagement rates with or without the SUN intervention. In addition, the SUN intervention was associated with higher odds of treatment engagement in the multivariable model (aOR 3.7, 95% CI 2.4 to 5.8) and in the propensity score-matched analysis (OR 2.1, 95% CI 1.2 to 3.5). CONCLUSION: A whole person care-informed intervention delivered by SUNs for ED patients with substance use disorders was strongly associated with higher engagement rates in addiction treatment after discharge.

Estrogen modulation of endosome-associated toll-like receptor 8: an IFNα-independent mechanism of sex-bias in systemic lupus erythematosus.

Females of child-bearing age are more resistant to infectious disease and have an increased risk of systemic lupus erythematosus (SLE). We hypothesized that estrogen-induced gene expression could establish an immunoactivated state which would render enhanced defense against infection, but may be deleterious in autoimmune development. Using peripheral blood mononuclear cells (PBMCs), we demonstrate enhanced responses with immunogen stimulation in the presence of 17ß-estradiol (E2) and gene array analyses reveal toll-like receptor 8 (TLR8) as an E2-responsive candidate gene. TLR8 expression levels are up-regulated in SLE and PBMCs stimulated with TLR8 agonist display a female sex-biased, E2-sensitive response. Moreover, we identify a putative ERα-binding region near the TLR8 locus and blocking ERα expression significantly decreases E2-mediated TLR8 induction. Our findings characterize TLR8 as a novel estrogen target gene that can lower the inflammatory threshold and implicate an IFNα-independent inflammatory mechanism that could contribute to higher SLE incidence in women.

Aberrant muscle antigen exposure in mice is sufficient to cause myositis in a Treg cell-deficient milieu.

OBJECTIVE: Myositis is associated with muscle-targeted inflammation and is observed in some Treg cell-deficient mouse models. Because an autoimmune pathogenesis has been strongly implicated, the aim of this study was to investigate the hypothesis that abnormal exposure to muscle antigens, as observed in muscle injury, can induce autoimmune-mediated myositis in susceptible hosts. METHODS: FoxP3 mutant (scurfy) mice were mated to synaptotagmin VII (Syt VII) mutant mice, which resulted in a new mouse strain that combines impaired membrane resealing with Treg cell deficiency. Lymphocyte preparations from double-mutant mice were adoptively transferred intraperitoneally, with or without purified Treg cells, into recombination-activating gene 1 (RAG-1)-null recipients. Lymph node cells from mice with the FoxP3 mutation were transferred into RAG-1-null mice either 1) intraperitoneally in conjunction with muscle homogenate or purified myosin protein or 2) intramuscularly with or without cotransfer of purified Treg cells. RESULTS: FoxP3-deficient mouse lymph node cells transferred in conjunction with myosin protein or muscle homogenate induced robust skeletal muscle inflammation. The infiltrates consisted predominantly of CD4+ and CD8+ T cells, a limited number of macrophages, and no B cells. Significant inflammation was also seen in similar experiments using lymph node cells from FoxP3/Syt VII double-mutant mice but was absent in experiments using adoptive transfer of FoxP3 mutant mouse cells alone. The cotransfer of Treg cells completely suppressed myositis. CONCLUSION: These data, derived from a new, reproducible model, demonstrate the critical roles of Treg cell deficiency and aberrant muscle antigen exposure in the priming of autoreactive cells to induce myositis. This mouse system has multifaceted potential for examining the interplay in vivo between tissue injury and autoimmunity.

Developing an ethical framework for short-term international dental and medical activities.

The popularity of volunteering to provide charity health care in third-world countries has increased dramatically in recent years. While there are advantages to both those being helped and to volunteers, there are also ethical issues that need to be addressed. A framework for analyzing the ethical impact of such service is presented which continues 27 principles that should be addressed.

Improved antibacterial and antibiofilm activity of magnesium fluoride nanoparticles obtained by water-based ultrasound chemistry.

Antibiotic resistance has prompted the search for new agents that can inhibit bacterial growth. We recently reported on the antimicrobial and antibiofilm activities of nanosized magnesium fluoride (MgF(2)) nanoparticles (NPs) synthesized in ionic liquid using microwave chemistry. In this article, we describe a novel water-based synthesis of MgF(2) NPs using sonochemistry. The sonochemical irradiation of an aqueous solution of [Mg(OAc)(2)⋅(H(2)O)(4)] containing acidic HF as the fluorine ion source afforded crystalline well-shaped spherical MgF(2) NPs that showed much improved antibacterial properties against two common bacterial pathogens (Escherichia coli and Staphylococcus aureus). We were also able to demonstrate that the antimicrobial activity was dependent on the size of the NPs. In addition, using the described sonochemical process, we coated glass surfaces and demonstrated inhibition of bacterial colonization for 7 days. Finally, the antimicrobial activity of MgF(2) NPs against established biofilms was also examined. Taken together our results highlight the potential to further develop the concept of utilizing these metal fluoride NPs as novel antimicrobial and antibiofilm agents. FROM THE CLINICAL EDITOR: In this article, the authors describe a novel aqueous synthesis of magnesium fluoride NPs using sonochemistry. These nanoparticles have improved antibacterial and antibiofilm activity compared to their counterparts with traditional synthesis methods.

Pre-course online cases for the world health organization's basic emergency care course in Uganda: A mixed methods analysis.

Introduction: The Ministry of Health - Uganda implemented the World Health Organization's Basic Emergency Care course (BEC) to improve formal emergency care training and address its high burden of acute illness and injury. The BEC is an open-access, in-person, short course that provides comprehensive basic emergency training in low-resource settings. A free, open-access series of pre-course online cases available as downloadable offline files were developed to improve knowledge acquisition and retention. We evaluated BEC participants' knowledge and self-efficacy in emergency care provision with and without these cases and their perceptions of the cases. Methods: Multiple Choice Questions (MCQs) and Likert-scale surveys assessed 137 providers' knowledge and self-efficacy in emergency care provision, respectively, and focus group discussions explored 74 providers' perceptions of the BEC course with cases in Kampala in this prospective, controlled study. Data was collected pre-BEC, post-BEC and six-months post-BEC. We used liability analysis and Cronbach alpha coefficients to establish intercorrelation between categorised Likert-scale items. We used mixed model analysis of variance to interpret Likert-scale and MCQ data and thematic content analysis to explore focus group discussions. Results: Participants gained and maintained significant increases in MCQ averages (15%) and Likert-scale scores over time (p < 0.001). The intervention group scored significantly higher on the pre-test MCQ than controls (p = 0.004) and insignificantly higher at all other times (p > 0.05). Nurses experienced more significant initial gains and long-term decays in MCQ and self-efficacy than doctors (p = 0.009, p < 0.05). Providers found the cases most useful pre-BEC to preview course content but did not revisit them post-course. Technological difficulties and internet costs limited case usage. Conclusion: Basic emergency care courses for low-resource settings can increase frontline providers' long-term knowledge and self-efficacy in emergency care. Nurses experienced greater initial gains and long-term losses in knowledge than doctors. Online adjuncts may enhance health professional education in low-to-middle income countries.

Mobile application adjunct to the WHO basic emergency care course: a mixed methods study.

OBJECTIVES: The WHO developed a 5-day basic emergency care (BEC) course using the traditional lecture format. However, adult learning theory suggests that lecture-based courses alone may not promote long-term knowledge retention. We assessed whether a mobile application adjunct (BEC app) can have positive impact on knowledge acquisition and retention compared with the BEC course alone and evaluated perceptions, acceptability and barriers to adoption of such a tool. DESIGN: Mixed-methods prospective cohort study. PARTICIPANTS: Adult healthcare workers in six health facilities in Tanzania who enrolled in the BEC course and were divided into the control arm (BEC course) or the intervention arm (BEC course plus BEC app). MAIN OUTCOME MEASURES: Changes in knowledge assessment scores, self-efficacy and perceptions of BEC app. RESULTS: 92 enrolees, 46 (50%) in each arm, completed the BEC course. 71 (77%) returned for the 4-month follow-up. Mean test scores were not different between the two arms at any time period. Both arms had significantly improved test scores from enrolment (prior to distribution of materials) to day 1 of the BEC course and from day 1 of BEC course to immediately after BEC course completion. The drop-off in mean scores from immediately after BEC course completion to 4 months after course completion was not significant for either arm. No differences were observed between the two arms for any self-efficacy question at any time point. Focus groups revealed five major themes related to BEC app adoption: educational utility, clinical utility, user experience, barriers to access and barriers to use. CONCLUSION: The BEC app was well received, but no differences in knowledge retention and self-efficacy were observed between the two arms and only a very small number of participants reported using the app. Technologic-based, linguistic-based and content-based barriers likely limited its impact.

Time to Loss of Behavioral and Brainstem Responses of Ducks following Non-Stunned Slaughter.

Non-stunned slaughter has been extensively described for other farmed species but there has been limited research on waterfowl. The study assessed 34 White Pekin ducks (Anas platyrhynchos) (study 1) in a non-stunned halal slaughterhouse in Brazil for time to loss of consciousness using various behavioral and brainstem indices (balance, cranial nerve reflexes, and muscle tension) and assessed the relationship between extent of clotting, location of neck cut, level of damage to neck vessels/tissues, and the time to onset of unconsciousness. In addition, operator practices were separately observed and neck pathology following the cut was examined in 217 carcasses after bleeding (study 2). In study 1 following the neck cut there was a wide variation between birds in the time to loss of behavioral and brainstem indices, ranging from 20 to 334 and 20 to 383 s for neck and beak tension, respectively. The median time to loss of balance following the neck cut was 166 ± 14 (22-355) seconds. There was a moderate correlation (R = 0.60 and 0.62) between distance of the neck cut and time to loss of balance and neck tension, respectively. This is the first investigation of the time to loss of consciousness following non-stunned slaughter of ducks in commercial conditions. The findings could be used to improve the welfare of ducks during non-stunned slaughter, such as recommending performance of the neck cut closer to the jaw line and ensuring appropriate waiting periods between slaughter and birds entering the scalding tanks.

Advanced life support courses in Africa: Certification, availability and perceptions.

BACKGROUND: Advanced life support (ALS) short training courses are in demand across Africa, though overwhelmingly designed and priced for non-African contexts. The continental expansion of emergency care is driving wider penetration of these courses, but their relevance and accessibility is not known. We surveyed clinicians within emergency settings to describe ALS courses' prevalence and perceived value in Africa. METHODS: We conducted a cross-sectional quantitative analysis of 235 clinicians' responses to the African Federation for Emergency Medicine's online needs assessment for an open-access ALS course in Africa. Participants responded to multiple-choice and open answer questions assessing demographics, ALS course certification and availability, perceptions of ALS courses, and barriers and facilitators to undertaking such courses. RESULTS: 235 clinicians working in 23 African nations responded. Most clinicians reported ALS course completion within the past three years (73%) and in-country access to ALS courses (76%). Most believed the content adequately met their region's needs (60%). Price and course availability were the most common barriers to taking an ALS course. The most common courses were cardiac and paediatric-focused, and the most common reasons to take a course included general career development, personal interest, and departmental requirements. CONCLUSION: One-quarter of emergency care clinicians lack access to ALS courses in twenty-three African nations. Most clinicians believe that ALS courses have value in their clinical settings and meet the needs of their region. Our findings illustrate the need for an affordable, widely available ALS course tailored to lower-resource African settings that could reach rural and peri-urban clinicians.

Community health workers improve disease control and medication adherence among patients with diabetes and/or hypertension in Chiapas, Mexico: an observational stepped-wedge study.

BACKGROUND: Non-communicable diseases (NCDs) contribute greatly to morbidity and mortality in low-income and middle-income countries (LMICs). Community health workers (CHWs) may improve disease control and medication adherence among patients with NCDs in LMICs, but data are lacking. We assessed the impact of a CHW-led intervention on disease control and adherence among patients with diabetes and/or hypertension in Chiapas, Mexico. METHODS: We conducted a prospective observational study among adult patients with diabetes and/or hypertension, in the context of a stepped-wedge roll-out of a CHW-led intervention. We measured self-reported adherence to medications, blood pressure and haemoglobin A1c at baseline and every 3 months, timed just prior to expansion of the intervention to a new community. We conducted individual-level mixed effects analyses of study data, adjusting for time and clustering by patient and community. FINDINGS: We analysed 108 patients. The CHW-led intervention was associated with a twofold increase in the odds of disease control (OR 2.04, 95% CI 1.15 to 3.62). It was also associated with optimal adherence assessed by 30-day recall (OR 1.86; 95% CI 1.15 to 3.02) and a positive self-assessment of adherence behaviour (OR 2.29; 95% CI 1.26 to 4.15), but not by 5-day recall. INTERPRETATION: A CHW-led adherence intervention was associated with disease control and adherence among adults with diabetes and/or hypertension. This study supports a role of CHWs in supplementing comprehensive primary care for patients with NCDs in LMICs. TRIAL REGISTRATION NUMBER: NCT02549495.

Novel estrogen target gene ZAS3 is overexpressed in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a prototypic, inflammatory autoimmune disease characterized by significant gender bias. Previous studies have established a role for hormones in SLE pathogenesis, including the sex hormone estrogen. Estrogen regulates gene expression by translocating estrogen receptors (ER) α and ß into the nucleus where they induce transcription by binding to estrogen response elements (EREs) of target genes. The ZAS3 locus encodes a signaling and transcriptional molecule involved in regulating inflammatory responses. We show that ZAS3 is significantly up-regulated in SLE patients at both the protein and mRNA levels in peripheral blood mononuclear cells (PBMCs). Furthermore, estrogen stimulates the expression of ZAS3 in vitro in several leukocyte and breast cancer cell lines of both human and murine origin. In vivo estrogen treatment mediates induction of tissue specific ZAS3 expression in several lymphoid organs in mice. Estrogen stimulation also significantly up-regulates ZAS3 expression in primary PBMCs, while treatment with testosterone has no effect. Mechanistically, estrogen induces differential ERα binding to putative EREs within the ZAS3 gene and ERα knockdown with siRNA prevents estrogen induced ZAS3 up-regulation. In contrast, siRNA targeting IFNα has no effect. These data demonstrate that ZAS3 expression is directly regulated by estrogen and that ZAS3 is overexpressed in lupus. Since ZAS3 has been shown to regulate inflammatory pathways, its up-regulation by estrogen could play a critical role in female-biased autoimmune disorders.

Antibacterial and antibiofilm properties of yttrium fluoride nanoparticles.

Antibiotic resistance has prompted the search for new agents that can inhibit bacterial growth. Moreover, colonization of abiotic surfaces by microorganisms and the formation of biofilms is a major cause of infections associated with medical implants, resulting in prolonged hospitalization periods and patient mortality. In this study we describe a water-based synthesis of yttrium fluoride (YF(3)) nanoparticles (NPs) using sonochemistry. The sonochemical irradiation of an aqueous solution of yttrium (III) acetate tetrahydrate [Y(Ac)(3) · (H(2)O)(4)], containing acidic HF as the fluorine ion source, yielded nanocrystalline needle-shaped YF(3) particles. The obtained NPs were characterized by scanning electron microscopy and X-ray elemental analysis. NP crystallinity was confirmed by electron and powder X-ray diffractions. YF(3) NPs showed antibacterial properties against two common bacterial pathogens (Escherichia coli and Staphylococcus aureus) at a µg/mL range. We were also able to demonstrate that antimicrobial activity was dependent on NP size. In addition, catheters were surface modified with YF(3) NPs using a one-step synthesis and coating process. The coating procedure yielded a homogeneous YF(3) NP layer on the catheter, as analyzed by scanning electron microscopy and energy dispersive spectroscopy. These YF(3) NP-modified catheters were investigated for their ability to restrict bacterial biofilm formation. The YF(3) NP-coated catheters were able to significantly reduce bacterial colonization compared to the uncoated surface. Taken together, our results highlight the potential to further develop the concept of utilizing these metal fluoride NPs as novel antimicrobial and antibiofilm agents, taking advantage of their low solubility and providing extended protection.

Antibiofilm surface functionalization of catheters by magnesium fluoride nanoparticles.

The ability of bacteria to colonize catheters is a major cause of infection. In the current study, catheters were surface-modified with MgF(2) nanoparticles (NPs) using a sonochemical synthesis protocol described previously. The one-step synthesis and coating procedure yielded a homogenous MgF(2) NP layer on both the inside and outside of the catheter, as analyzed by high resolution scanning electron microscopy and energy dispersive spectroscopy. The coating thickness varied from approximately 750 nm to 1000 nm on the inner walls and from approximately 450 nm to approximately 580 nm for the outer wall. The coating consisted of spherical MgF(2) NPs with an average diameter of approximately 25 nm. These MgF(2) NP-modified catheters were investigated for their ability to restrict bacterial biofilm formation. Two bacterial strains most commonly associated with catheter infections, Escherichia coli and Staphylococcus aureus, were cultured in tryptic soy broth, artificial urine and human plasma on the modified catheters. The MgF(2) NP-coated catheters were able to significantly reduce bacterial colonization for a period of 1 week compared to the uncoated control. Finally, the potential cytotoxicity of MgF(2) NPs was also evaluated using human and mammalian cell lines and no significant reduction in the mitochondrial metabolism was observed. Taken together, our results indicate that the surface modification of catheters with MgF(2) NPs can be effective in preventing bacterial colonization and can provide catheters with long-lasting self-sterilizing properties.