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BACKGROUND: The benefit of virtual emergency department observation unit (EDOU) care relative to traditional observation care in an inpatient bed is unknown. OBJECTIVE: To determine if virtual observation care in an EDOU is associated with improved length of stay, cost, inpatient admission rate, and adverse events relative to traditional observation care in non-observation unit (NOU) inpatient bed. METHODS: This is a retrospective observational cohort study of observation patients managed over 24 months in two urban teaching hospitals. Following an ED visit, observation care occurred in a virtual-EDOU or NOU inpatient setting based on bed availability, physician discretion, and observation guidelines. Primary outcomes were length of stay, total cost, inpatient admission rate, and adverse events (death or ICU admission). Hospital cost and clinical databases were used. Analysis with a doubly-robust regression with entropy balancing and propensity scores was used to control for subgroup differences. RESULTS: 30,191 observation patients were divided into 13,753 NOU patients and 16,438 EDOU patients with similar distributions for age and gender, and differences in health insurance and diagnosis. For both discharged and admitted patients, the mean cost was higher in the NOU setting at $7989 than the virtual-EDOU setting at $4876 with an adjusted difference of $1951 (95% CI: $1762-$2133). The mean total length of stay was higher in the NOU setting (60.5 h) than the virtual-EDOU setting (36.4 h) with an adjusted difference of 20.4 h (95% CI: 19.2 h - 21.3 h). NOU inpatient admission rates were higher (25.3% vs 18.4%). Cost and length of stays were lower in discharged observation patients, with differences favoring the virtual-EDOU group. Adverse events were higher in the NOU setting (2.1% vs 0.8%). 30-day ED recidivism did not differ significantly between NOU and virtual-EDOU study groups. The virtual-EDOU saved the two hospitals $16,036,913 and 6986 bed-days annually. CONCLUSION: Management of observation patients in a virtual-EDOU setting is superior to care in a traditional inpatient setting in terms of costs, length of stays, inpatient admission and adverse events rates.
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Immigrants, nearly half of whom prefer a language other than English (LOE), face structural barriers to healthcare. This subgroup is believed to be at increased risk for reduced access to quality healthcare, yet few studies have examined the health needs and utilization patterns of LOE-preferring patients who seek care in the Emergency Department (ED). Given that the ED is often an entry point to the health system, we sought to characterize the health patterns of this population in an urban ED setting. We conducted a retrospective chart review of the electronic medical records of 1,566 patients who utilized interpreter services in the ED or Urgent Care) at an urban safety net hospital. We found that LOE-preferring patients had high levels of chronic disease. We also found that the majority of these patients had not seen a primary care provider (PCP) within the study period. PCP visits were positively associated with ED utilization suggesting that those without a PCP are less likely to receive ED care. These findings point to a need for greater policy and community health solutions addressing the high burden of chronic disease and underutilization of healthcare for those with LOE preferences.
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BACKGROUND: Use of high-sensitivity troponin (hs-cTn) might lead to an increase in hospital observation visits due to higher number of abnormal troponin levels. STUDY OBJECTIVES: To determine the impact of incorporating hs-cTn into a chest pain clinical decision protocol (CDP) on observation visits in a large academic health system. METHODS: This is a retrospective observational cohort study of all chest pain observation patients in four hospitals in an academic health system over 24 months. All hospitals used the Beckman Coulter Unicel Dxi instrument, and all shared the same emergency department (ED) chest pain protocol, which used the HEART pathway and serial troponins and directed ED dispositions to either an observation stay, ED discharge, or inpatient admission. Outcomes studied before and after introduction of a hs-cTn protocol included daily chest pain observation census, cost, observation hours, and inpatient admit rate. Census was reported as the daily chest pain observation census and as a proportion of all observation visits. Data was retrieved from a health system data warehouse and a cost accounting program. RESULTS: There were 6,712 chest pain observation visits over 24-months, with 4,087 visits before and 2,634 visits after the hs-cTn protocol implementation. Comparison groups were similar in terms of age, gender, and type of insurance. There were 10.59 (95% CI: 10.24 - 10.95) daily chest pain observation visits before and 7.66 (95% CI: 7.34 - 7.97) visits after implementation, with a 28% (95% CI: 35% - 20%) decrease in the total daily census. As a portion of all observation visits, there was a 22% drop in the proportion that were observed for chest pain. The daily number of chest pain patients requiring inpatient admission was unchanged. The daily total direct cost for chest pain observation decreased with an effective daily cost savings of $4,313 USD (95% CI: $1,534 - $6,998). The total daily number of chest pain observation bed hours also decreased by 41.5 hours (95% CI 13.4 - 96.4 hr). CONCLUSION: Implementation of a hs-cTn chest pain protocol was associated with a significant decrease in the number and proportion of observation visits, a decrease in total daily cost and bed hours used, and no increase in inpatient admissions.
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Objectives: Injury-related visits constitute a sizeable portion of emergency department (ED) visits in the United States. Individuals with language other than English (LOE) preference face barriers to healthcare and visits for traumatic injury may be the first point of contact with the healthcare system. Yet, the prevalence of traumatic injuries in this population is relatively unknown. Our objective was to characterize the prevalence and purpose of trauma encounters, and healthcare utilization, among a LOE cohort. Methods: We conducted a retrospective chart review of LOE patients who presented for a trauma encounter at a level 1 trauma and emergency care center between January 1, 2019 and December 31, 2021. LOE participants were identified by utilization of video-based language interpretive services. Variables evaluated included injury patterns and primary and subspeciality healthcare utilization. Quantitative analysis of categorical and continuous variables was performed. Results: A total of 429 patients were included. Most patients presented for one trauma encounter and the majority spoke Spanish. The most common causes of injury were motor vehicle collisions (MVCs) (28.5%, n = 129), ground-level falls (15.9%, n = 72), and falls from heights (14.2%, n = 64). Occupational injuries made up 27.2% of trauma encounters (n = 123) and only 12.6% (n = 54) of patients had a primary care visit. Conclusion: Our findings highlight the need for increased research and attention to all causes of injury, especially MVCs and occupational injuries, among those with LOE preference. Results reaffirm an underutilization of healthcare among this population and the opportunity for trauma encounters as points of access to care.
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Nutritional status has clinical relevance and is a target of guidance to parents of children with cystic fibrosis (CF). Growth is routinely monitored in CF clinics but there is no standardized way of assessing appetitive behaviors or parents' perceptions of their children's appetite. Greater understanding of these factors could improve clinical guidance regarding parent feeding behaviors. We therefore aimed to assess parent perceptions of child weight, and parent reports of child appetite using the Baby Eating Behavior Questionnaire (BEBQ), in a sample of infants and toddlers with CF, compared with a community sample. We additionally assessed relationships of parent perceptions of child weight with parent feeding behaviors in the sample with CF. Anthropometric and questionnaire data were collected for 32 infants and toddlers with CF, as well as 193 infants and toddlers drawn from RESONANCE, a community cohort study. Parents perceived children with CF to be lower in weight than their actual weight, to a greater extent than was evident in the community sample. Parents who perceived their children with CF to be underweight vs. right weight reported greater slowness in eating on the BEBQ. Parents perceived children with CF to have greater slowness in eating and lower enjoyment of food, compared to parents of children in the community sample, independent of sample differences in child weight, age, and sex. Our results demonstrate the potential utility of the BEBQ in a clinical sample and suggest it may be helpful for clinicians to assess parents' perceptions of their child's weight and appetite to promote a fuller understanding of the child's nutritional status, facilitate appropriate feeding behaviors and alleviate unnecessary concerns.
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Apetite , Peso Corporal , Fibrose Cística , Comportamento Alimentar , Pais , Humanos , Fibrose Cística/psicologia , Masculino , Feminino , Lactente , Pais/psicologia , Comportamento Alimentar/psicologia , Inquéritos e Questionários , Pré-Escolar , Estado Nutricional , Percepção , Magreza/psicologia , Estudos de CoortesRESUMO
BACKGROUND: Environmental exposure to peanut through non-oral routes is a risk factor for peanut allergy. Early-life exposure to air pollutants, including particulate matter (PM), is associated with sensitization to foods through unknown mechanisms. We investigated whether PM promotes sensitization to environmental peanut and the development of peanut allergy in a mouse model. METHODS: C57BL/6J mice were co-exposed to peanut and either urban particulate matter (UPM) or diesel exhaust particles (DEP) via the airways and assessed for peanut sensitization and development of anaphylaxis following peanut challenge. Peanut-specific CD4+ T helper (Th) cell responses were characterized by flow cytometry and Th cytokine production. Mice lacking select innate immune signaling genes were used to study mechanisms of PM-induced peanut allergy. RESULTS: Airway co-exposure to peanut and either UPM- or DEP-induced systemic sensitization to peanut and anaphylaxis following peanut challenge. Exposure to UPM or DEP triggered activation and migration of lung dendritic cells to draining lymph nodes and induction of peanut-specific CD4+ Th cells. UPM- and DEP-induced distinct Th responses, but both stimulated expansion of T follicular helper (Tfh) cells essential for peanut allergy development. MyD88 signaling was critical for UPM- and DEP-induced peanut allergy, whereas TLR4 signaling was dispensable. DEP-induced peanut allergy and Tfh-cell differentiation depended on IL-1 but not IL-33 signaling, whereas neither cytokine alone was necessary for UPM-mediated sensitization. CONCLUSION: Environmental co-exposure to peanut and PM induces peanut-specific Tfh cells and peanut allergy in mice.
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Anafilaxia , Hipersensibilidade a Amendoim , Camundongos , Animais , Camundongos Endogâmicos C57BL , Poeira , Citocinas/metabolismo , Material Particulado/efeitos adversosRESUMO
Rationale: Acute respiratory distress syndrome (ARDS) has an unacceptably high mortality rate (35%) and is without effective therapy. Orai1 is a Ca2+ channel involved in store-operated Ca2+ entry (SOCE), a process that exquisitely regulates inflammation. Orai1 is considered a druggable target, but no Orai1-specific inhibitors exist to date. Objectives: To evaluate whether ELD607, a first-in-class Orai1 antagonist, can treat ARDS caused by bacterial pneumonia in preclinical models. Methods: ELD607 pharmacology was evaluated in HEK293T cells and freshly isolated immune cells from patients with ARDS. A murine acute lung injury model caused by bacterial pneumonia was then used: mice were infected with Pseudomonas aeruginosa, Staphylococcus aureus, methicillin-resistant S. aureus, or multidrug-resistant P. aeruginosa and then treated with ELD607 intranasally. Measurements and Main Results: ELD607 specifically inhibited SOCE in HEK293T cells with a half-maximal inhibitory concentration of 9 nM. ELD607 was stable in ARDS airway secretions and inhibited SOCE in ARDS immune cells. In vivo, inhaled ELD607 significantly reduced neutrophilia and improved survival. Surprisingly, Orai1 inhibition by ELD607 caused a significant reduction in lung bacteria, including methicillin-resistant S. aureus. ELD607 worked as an immunomodulator that reduced cytokine levels, reduced neutrophilia, and promoted macrophage-mediated resolution of inflammation and clearance of bacteria. Indeed, when alveolar macrophages were depleted with inhaled clodronate, ELD607 was no longer able to resolve inflammation or clear bacteria. Conclusions: These data indicate that specific Orai1 inhibition by ELD607 may be a novel approach to reduce multiorgan inflammation and treat antibiotic-resistant bacteria.
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Staphylococcus aureus Resistente à Meticilina , Pneumonia Bacteriana , Síndrome do Desconforto Respiratório , Humanos , Camundongos , Animais , Canais de Cálcio/metabolismo , Canais de Cálcio/farmacologia , Cálcio/metabolismo , Células HEK293 , Staphylococcus aureus Resistente à Meticilina/metabolismo , Sinalização do Cálcio , Inflamação/tratamento farmacológico , Pulmão/metabolismo , Síndrome do Desconforto Respiratório/tratamento farmacológico , Pneumonia Bacteriana/tratamento farmacológico , Proteína ORAI1/metabolismo , Proteína ORAI1/farmacologiaRESUMO
OBJECTIVE: To evaluate the non-inferiority of endovascular treatment (EVT) alone versus intravenous thrombolysis (IVT) followed by EVT and to assess its heterogeneity across prespecified subgroups. METHODS: We pooled data from two trials (SKIP in Japan; DEVT in China). Individual patient data were pooled to assess outcomes and heterogeneity of treatment effect. The primary outcome was functional independence (modified Rankin Scale score 0-2) at 90 days. Safety outcomes included symptomatic intracranial hemorrhage (sICH) and 90-day mortality. RESULTS: We included 438 patients (217 EVT alone; 221 combined IVT+EVT). The meta-analysis failed to demonstrate the non-inferiority of EVT alone over combined IVT+EVT in achieving 90-day functional independence (56.7% vs 51.6%; adjusted common odds ratio (cOR)=1.27, 95% CI 0.84 to 1.92, pnon-inferiority=0.06). Effect sizes favoring EVT alone were present with stroke onset to puncture time longer than 180 min (cOR=2.28, 95% CI 1.18 to 4.38, pinteraction ≤180 vs >180 min=0.02) and intracranial internal carotid artery ICA occlusions (for ICA cOR=3.04, 95% CI 1.10 to 8.43, pinteraction ICA vs MCA=0.08). The rates of sICH (6.5% vs 9.0%; cOR=0.77, 95% CI 0.37 to 1.61) and 90-day mortality (12.9% vs 13.6%; cOR=1.05, 95% CI 0.58 to 1.89) were comparable. CONCLUSIONS: The cumulative data of these two recent Asian trials failed to unequivocally demonstrate the non-inferiority of EVT alone over combined IVT+EVT. However, our study suggests a potential role for more individualized decision-making. Specifically, Asian patients with stroke onset to EVT longer than 180 min, as well as those with intracranial ICA occlusions and those with atrial fibrillation might have better outcomes with EVT alone than with combined IVT+EVT.
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Arteriopatias Oclusivas , Isquemia Encefálica , Procedimentos Endovasculares , Acidente Vascular Cerebral , Humanos , Isquemia Encefálica/terapia , Procedimentos Endovasculares/efeitos adversos , Fibrinolíticos/uso terapêutico , Hemorragias Intracranianas , Distribuição Aleatória , Acidente Vascular Cerebral/terapia , Trombectomia , Terapia Trombolítica , Resultado do Tratamento , Ensaios Clínicos como AssuntoRESUMO
Individuals with anorexia nervosa (AN) exhibit dangerous weight loss due to restricted eating and hyperactivity. Those with AN are predominantly women and most cases have an age of onset during adolescence. Activity-based anorexia (ABA) is a rodent behavioral paradigm that recapitulates many of the features of AN including restricted food intake and hyperactivity, resulting in precipitous weight loss. In addition, there is enhanced sensitivity to the paradigm during adolescence. In ABA, animals are given time-restricted access to food and unlimited access to a running wheel. Under these conditions, most animals increase their running and decrease their food intake resulting in precipitous weight loss until they either die or researchers discontinue the paradigm. Some animals learn to balance their food intake and energy expenditure and are able to stabilize and eventually reverse their weight loss. For these studies, adolescent (postnatal day 33-42), female Sprague Dawley (n = 68) rats were placed under ABA conditions (unlimited access to a running wheel and 1.5 hrs access to food) until they either reached 25% body weight loss or for 7 days. 70.6% of subjects reached 25% body weight loss before 7 days and were designated susceptible to ABA while 29.4% animals were resistant to the paradigm and did not achieve the weight loss criterion. We used discrete time survival analysis to investigate the contribution of food intake and running behavior during distinct time periods both prior to and during ABA to the likelihood of reaching the weight loss criterion and dropping out of ABA. Our analyses revealed risk factors, including total running and dark cycle running, that increased the likelihood of dropping out of the paradigm, as well as protective factors, including age at the start of ABA, the percent of total running exhibited as food anticipatory activity (FAA), and food intake, that reduced the likelihood of dropping out. These measures had predictive value whether taken before or during exposure to ABA conditions. Our findings suggest that certain running and food intake behaviors may be indicative of a phenotype that predisposes animals to susceptibility to ABA. They also provide evidence that running during distinct time periods may reflect functioning of distinct neural circuitry and differentially influence susceptibility and resistance to the paradigm.
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Anorexia Nervosa , Anorexia , Adolescente , Ratos , Feminino , Humanos , Animais , Masculino , Ratos Sprague-Dawley , Atividade Motora , Modelos Animais de Doenças , Redução de Peso , Ingestão de AlimentosRESUMO
Background: Early dietary introduction of peanut has shown efficacy in clinical trials and driven pediatric recommendations for early introduction of peanut to children with heightened allergy risk worldwide. Unfortunately, tolerance is not induced in every case, and a subset of patients are allergic prior to introduction. Here we assess peanut allergic sensitization and oral tolerance in genetically diverse mouse strains. Objective: We aimed to determine whether environmental adjuvant-driven airway sensitization and oral tolerance to peanut could be induced in various genetically diverse mouse strains. Methods: C57BL/6J and 12 Collaborative Cross (CC) mouse strains were fed regular chow or ad libitum peanut butter to induce tolerance. Tolerance was tested by attempting to sensitize mice via intratracheal exposure to peanut and lipopolysaccharide (LPS), followed by intraperitoneal peanut challenge. Peanut-specific immunoglobulins and peanut-induced anaphylaxis were assessed. Results: Without oral peanut feeding, most CC strains (11/12) and C57BL/6J induced peanut-specific IgE and IgG1 following airway exposure to peanut and LPS. With oral peanut feeding none of the CC strains nor C57BL/6J mice became sensitized to peanut or experienced anaphylaxis following peanut challenge. Conclusion: Allergic sensitization and oral tolerance to peanut can be achieved across a range of genetically diverse mice. Notably, the same strains that became allergic via airway sensitization were tolerized by feeding high doses of peanut butter before sensitization, suggesting that the order and route of peanut exposure are critical for determining the allergic fate.
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BACKGROUND: Indoor dust (ID) is a source of peanut proteins and immunostimulatory adjuvants (e.g. LPS) that can promote airway sensitization to peanut. We aimed to determine whether a single airway exposure to peanut plus adjuvant is sufficient to prevent oral tolerance. METHODS: To determine the effect of a single priming event, C57BL/6J mice were exposed once to peanut plus adjuvant through the airway, followed by either airway or low-dose oral exposure to peanut, and assessed for peanut allergy. Oral tolerance was investigated by feeding high-dose peanut followed by airway sensitization. To determine whether a single priming could prevent oral tolerance, the high-dose peanut regimen was applied after a single airway exposure to peanut plus adjuvant. Peanut-specific IgE and IgG1 were quantified, and mice were challenged to peanut to assess allergy. Peanut-specific CD4+ memory T cells (CD4+ TCRß+ CD44hi CD154+ ) were quantified in mediastinal lymph nodes following airway priming. RESULTS: Mice co-exposed to peanut with LPS or ID through the airway were primed to develop peanut allergy after subsequent low-dose oral or airway exposures to peanut. Oral tolerance was induced in mice fed high-dose peanut prior to airway sensitization. In contrast, mice fed high-dose peanut following a single airway exposure to peanut plus adjuvant led to allergy. Peanut-specific CD4+ memory T cells were detected as early as 7 days after the single airway priming with peanut plus adjuvant, however, delaying peanut feeding even 1 day following priming led to allergy, whereas peanut feeding the same day as priming led to tolerance. CONCLUSIONS: A single airway exposure to peanut plus adjuvant is sufficient to prime the immune system to develop allergy following subsequent high-dose oral exposure. These results highlight the importance of introducing peanut as early as possible to prevent sensitization through a non-oral priming event.
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Arachis , Hipersensibilidade a Amendoim , Camundongos , Animais , Citocinas/metabolismo , Lipopolissacarídeos , Camundongos Endogâmicos C57BL , Adjuvantes Imunológicos , Poeira , Tolerância Imunológica , AlérgenosRESUMO
OBJECTIVE: To evaluate the association between medication for opioid use disorder (MOUD) initiation and addiction consultation and outcomes for patients hospitalized with infectious complications of injecting opioids. METHOD: This was a retrospective cohort study performed at four academic medical centers in the United States. The participants were patients who had been hospitalized with infectious complications of injecting opioids in 2018. Three hundred and twenty-two patients were included and their individual patient records were manually reviewed to identify inpatient receipt of medication for opioid use disorder (MOUD), initiation of MOUD, and addiction consultation. The main outcomes of interest were premature discharge, MOUD on discharge, linkage to outpatient MOUD, one-year readmission and death. RESULTS: Three hundred and twenty-two patients were predominately male (59%), white (66%), and median age 38 years, with 36% unstably housed, and 30% uninsured. One hundred and forty-five (45%) patients received MOUD during hospitalization, including only 65 (28%) patients not on baseline MOUD. Discharge was premature for 64 (20%) patients. In the year following discharge, 27 (9%) patients were linked to MOUD, and 159 (50%) patients had at least one readmission. Being on MOUD during hospitalization was significantly associated with higher odds of planned discharge [odds ratio (OR) 3.87, P â<â0.0001], MOUD on discharge (OR 129.7, P â<â0.0001), and linkage to outpatient MOUD (OR 1.25, P â<â0.0001), however, was not associated with readmission. Study limitations were the retrospective nature of the study, so post-discharge data are likely underestimated. CONCLUSION: There was dramatic undertreatment with MOUD from inpatient admission to outpatient linkage, and high rates of premature discharge and readmission. Engagement in addiction care during hospitalization is a critical first step in improving the care continuum for individuals with opioid use disorder; however, additional interventions may be needed to impact long-term outcomes like readmission.
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Infecções por HIV , Transtornos Relacionados ao Uso de Opioides , Nascimento Prematuro , Humanos , Masculino , Feminino , Adulto , Estudos Retrospectivos , Assistência ao Convalescente , Alta do Paciente , Analgésicos Opioides/efeitos adversos , Tratamento de Substituição de OpiáceosRESUMO
The overconsumption of palatable energy-dense foods drives obesity, but few human studies have investigated dopamine (DA) release in response to the consumption of a palatable meal, a putative mediator of excess intake in obesity. We imaged [11C]raclopride in the brain with positron emission tomography (PET) to assess striatal dopamine (DA) receptor binding pre- and post-consumption of a highly palatable milkshake (250 mL, 420 kcal) in 11 females, 6 of whom had severe obesity, and 5 of whom had healthy-weight. Those with severe obesity underwent assessments pre- and 3 months post-vertical sleeve gastrectomy (VSG). Our results demonstrated decreased post- vs. pre-meal DA receptor binding in the ventral striatum (p = 0.032), posterior putamen (p = 0.012), and anterior caudate (p = 0.018), consistent with meal-stimulated DA release. Analysis of each group separately suggested that results in the caudate and putamen were disproportionately driven by meal-associated changes in the healthy-weight group. Baseline (pre-meal) DA receptor binding was lower in severe obesity than in the healthy-weight group. Baseline DA receptor binding and DA release did not change from pre- to post-surgery. The results of this small pilot study suggest that milkshake acutely stimulates DA release in the ventral and dorsal striatum. This phenomenon likely contributes to the overconsumption of highly palatable foods in the modern environment.
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Cirurgia Bariátrica , Obesidade Mórbida , Estriado Ventral , Feminino , Humanos , Dopamina/metabolismo , Projetos Piloto , Obesidade Mórbida/cirurgia , Obesidade Mórbida/metabolismo , Receptores de Dopamina D2 , Obesidade/cirurgia , Obesidade/metabolismo , Tomografia por Emissão de Pósitrons , Estriado Ventral/diagnóstico por imagem , Estriado Ventral/metabolismoRESUMO
BACKGROUND: Stigma surrounding opioid use disorder (OUD) is a barrier to treatment. The use of stigmatizing language may be evidence of negative views toward patients. OBJECTIVE: We aimed to identify associations between language and clinical outcomes in patients admitted for infectious complications of OUD. DESIGNS: We performed a retrospective medical record review. SETTINGS AND PARTICIPANTS: Four U.S. academic health systems. Participants were patients with OUD admitted for infectious complications of injection opioid use from January 1, 2018, to December 31, 2018, identified through international classification of diseases, 10th revision codes consistent with OUD and acute bacterial/fungal infection. MAIN OUTCOME AND MEASURES: Discharge summaries were reviewed for language, specifically: abuse, addiction, dependence, misuse, use disorder, intravenous drug use, and others. Binary outcomes including medication for OUD, planned discharge, naloxone provision, and an OUD treatment plan were evaluated using logistic regressions and admission duration was evaluated using Gamma regression. RESULTS: A total of 1285 records were reviewed and 328 met inclusion criteria. Of those, 191 (58%) were male, with a median age of 38 years. The most common term was "abuse" (219, 67%), whereas "use disorder" was recorded in 75 (23%) records. Having "use disorder" in the discharge summary was associated with increased odds of having a documented plan for ongoing OUD treatment (adjusted odds ratio [AOR]: 4.11, 95% confidence interval [CI]: 1.89-8.93) and having a documented plan for addiction-specific follow-up care (AOR: 2.31, 95% CI: 1.30-4.09). CONCLUSIONS: Stigmatizing language was common in this study of patients hospitalized for infectious complications of OUD. Best-practice language was uncommon, but when used was associated with increased odds of addiction treatment and specialty care referrals.
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Transtornos Relacionados ao Uso de Opioides , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Seguimentos , Hospitalização , Transtornos Relacionados ao Uso de Opioides/terapia , Estudos Retrospectivos , Resultado do Tratamento , IdiomaRESUMO
Among asthmatics, there is significant heterogeneity in the clinical presentation and underlying pathophysiological mechanisms, leading to the recognition of multiple disease endotypes (e.g., T2-high vs. T2-low). This heterogeneity extends to severe asthmatics, who may struggle to control symptoms even with high-dose corticosteroid treatment and other therapies. However, there are limited mouse models available to model the spectrum of severe asthma endotypes. We sought to identify a new mouse model of severe asthma by first examining responses to chronic allergen exposure among strains from the Collaborative Cross (CC) mouse genetics reference population, which contains greater genetic diversity than other inbred strain panels previously used for models of asthma. Mice from five CC strains and the often-used classical inbred strain BALB/cJ were chronically exposed to house dust mite (HDM) allergen for five weeks followed by measurements of airway inflammation. CC strain CC011/UncJ (CC011) exhibited extreme responses to HDM including high levels of airway eosinophilia, elevated lung resistance, and extensive airway wall remodeling, and even fatalities among ~ 50% of mice prior to study completion. Compared to BALB/cJ mice, CC011 mice had stronger Th2-mediated airway responses demonstrated by significantly elevated total and HDM-specific IgE and increased Th2 cytokines during tests of antigen recall, but not enhanced ILC2 activation. Airway eosinophilia in CC011 mice was completely dependent upon CD4+ T-cells. Notably, we also found that airway eosinophilia in CC011 mice was resistant to dexamethasone steroid treatment. Thus, the CC011 strain provides a new mouse model of T2-high, severe asthma driven by natural genetic variation likely acting through CD4+ T-cells. Future studies aimed at determining the genetic basis of this phenotype will provide new insights into mechanisms underlying severe asthma.
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Asma , Imunidade Inata , Camundongos , Animais , Citocinas , Linfócitos , Asma/tratamento farmacológico , Pulmão , Alérgenos , Pyroglyphidae , Modelos Animais de Doenças , Camundongos Endogâmicos BALB C , Células Th2RESUMO
Respiratory macrophage subpopulations exhibit unique phenotypes depending on their location within the respiratory tract, posing a challenge to in vitro macrophage model systems. Soluble mediator secretion, surface marker expression, gene signatures, and phagocytosis are among the characteristics that are typically independently measured to phenotype these cells. Bioenergetics is emerging as a key central regulator of macrophage function and phenotype but is often not included in the characterization of human monocyte-derived macrophage (hMDM) models. The objective of this study was to expand the phenotype characterization of naïve hMDMs, and their M1 and M2 subsets by measuring cellular bioenergetic outcomes and including an expanded cytokine profile. Known markers of M0, M1 and M2 phenotypes were also measured and integrated into the phenotype characterization. Peripheral blood monocytes from healthy volunteers were differentiated into hMDM and polarized with either IFN-γ + LPS (M1) or IL-4 (M2). As expected, our M0, M1, and M2 hMDMs exhibited cell surface marker, phagocytosis, and gene expression profiles indicative of their different phenotypes. M2 hMDMs however were uniquely characterized and different from M1 hMDMs by being preferentially dependent on oxidativte phosphorylation for their ATP generation and by secreting a distinct cluster of soluble mediators (MCP4, MDC, and TARC). In contrast, M1 hMDMs secreted prototypic pro-inflammatory cytokines (MCP1, eotaxin, eotaxin-3, IL12p70, IL-1α, IL15, TNF-ß, IL-6, TNF-α, IL12p40, IL-13, and IL-2), but demonstrated a relatively constitutively heightened bioenergetic state, and relied on glycolysis for ATP generation. These data are similar to the bioenergetic profiles we previously observed in vivo in sputum (M1) and BAL (M2)-derived macrophages in healthy volunteers, supporting the notion that polarized hMDMs can provide an acceptable in vitro model to study specific human respiratory macrophage subtypes.
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Interleucina-12 , Macrófagos , Humanos , Glicólise , Fagocitose , Trifosfato de AdenosinaRESUMO
PURPOSE OF REVIEW: The increasing global prevalence of food allergy indicates that environmental exposures are likely contributing to food allergy development. This review summarizes recent studies on how specific factors within the external exposome may impact the development of food allergy. RECENT FINDINGS: There is strong evidence that nonoral exposure to food allergens within the living environment is a risk factor for food sensitization and food allergy. The role of air pollution in food allergy development remains unclear, as cohort studies have not found consistent relationships between air pollutant exposure and food sensitization. Early-life microbial exposures linked to a rural lifestyle are likely protective against food allergy development, possibly through alteration of the infant microbiome. In contrast, factors associated with urbanization and decreased exposure to microbes may contribute to food allergy development. Recent studies on the role of residential greenness in food allergy development suggest either no relationship or a possible increased risk for food allergy. SUMMARY: The external exposome comprises a number of exposures that can modify food allergy risk. Improved understanding of how complex environmental exposures interact with genetic factors will be necessary for developing effective interventions aimed at preventing food allergy development in children.
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Poluição do Ar , Expossoma , Hipersensibilidade Alimentar , Criança , Lactente , Humanos , Hipersensibilidade Alimentar/epidemiologia , Alérgenos , Fatores de Risco , Exposição Ambiental/efeitos adversosRESUMO
BACKGROUND: Individuals with non-English language preferences (NELP) represent a growing proportion of the USA population. Prior studies demonstrate disparate health outcomes related to NELP status; however, this patient population is often excluded from medical research. There is a paucity of literature describing the impact of NELP status on trauma, specifically injury and outcomes related to vehicle occupants injured during motor vehicle collisions (MVCs). The goal of this study was to evaluate the representation of patients with NELP in both emergency medicine and trauma literature. METHODS: We conducted a systematic search of US-based publications from 2010 to 2021. Titles, abstracts and full texts of eligible articles were evaluated. Data were extracted using an a priori determined standardised reporting tool to evaluate language as study inclusion/exclusion criteria, manuscript reporting of language, assessment of language as a primary variable and consideration of language in study methodology. RESULTS: A total of 82 studies met inclusion criteria. Twenty-three studies (28%) excluded NELP populations and only one study explicitly included the NELP population. None of the studies evaluated language as a primary outcome of the study or included language as a variable in the analysis. Over half of the studies (53.6%) used a public data set or registry. CONCLUSION: NELP populations are routinely excluded from and are difficult to identify in MVC trauma research. Without appropriate inclusion and identification, it will be difficult to understand the prevalence and outcomes of traumatic injury in NELP patients and to develop culturally and linguistically appropriate interventions.
Assuntos
Lesões Acidentais , Pesquisa Biomédica , Humanos , Acidentes de Trânsito , Veículos AutomotoresRESUMO
Anorexia Nervosa (AN) is associated with a high rate of morbidity and mortality as well as a high rate of relapse. The molecular mechanisms underlying the progression of the disorder or the relapses are largely unknown. Patients with AN have been shown to have increased oxidative stress, but its involvement in the development in the disease is unknown. We have previously shown that adolescent female rats undergoing the activity-based anorexia (ABA) paradigm also show signs of oxidative stress. Due to their role in the release of reactive oxygen species (ROS), mitochondria are of high interest in diseases exhibiting oxidative stress. In this study, the impact of ABA on brain mitochondrial dynamics was examined. We found transient changes in the medial prefrontal cortex, hypothalamus, and hippocampus following 25% weight loss and changes in the amygdala at a 10-day weight recovery timepoint. These changes point towards damage in the mitochondria contributing to the oxidative stress.