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Müller-Weiss disease (MWD) is a poorly understood orthopedic condition first described in 1927 that causes chronic pain across the midfoot and hindfoot. The etiology is uncertain but includes navicular dysplasia, osteochondritis, and trauma. The initial management is conservative, aiming to reduce the patient's symptoms, and includes analgesia, footwear, and activity modification. Surgical interventions such as joint fusion are considered when conservative measures fail, but there is little recorded for treatment beyond this. This case outlines the difficult management of a 52-year-old female patient with a long history of MWD. She had no history of previous trauma or neurological problems. A talonavicular fusion failed to unite, resulting in significant necrosis of the lateral navicular and navicular-cuneiform arthritis. We describe the novel use of a reverse vascularized pedicled fibular flap and extended midfoot fusion to manage the navicular bone defect. At six-year follow-up, the patient remains virtually pain-free and has returned to work with radiographs confirming good incorporation of the bone graft. We understand this to be the first documented use of a reverse vascularized fibular bone graft for recalcitrant MWD. Given the excellent clinical outcome in this case, surgeons should consider this combined ortho-plastics approach in the management of complex non-union with a bone defect in the midfoot.
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Objective: The COVID-19 pandemic required unprecedented changes to emergency medical services (EMS) educational frameworks in the United States. It is unclear if pandemic-related changes impacted paramedic educational outcomes. We aimed to evaluate curricular and performance changes resulting from the initial COVID-19 pandemic on paramedic educational programs. Methods: We performed a retrospective cross-sectional evaluation of paramedic educational programs in 2019 and 2020 using the Committee on Accreditation of Educational Programs for the Emergency Medical Services Professions annual reports. These reports contain detailed program components and measures of program success. We included programs reporting at least one graduate in the study period. Descriptive statistics (proportions [%], median [interquartile range, IQR]) were calculated for paramedic program characteristics in 2019 and 2020, as well as pandemic specific curriculum changes. Wilcoxon rank-sum and Fisher's exact tests were used to evaluate differences in characteristics by year. Results: The number of paramedic educational programs in our population decreased from 640 programs in 2019 to 612 in 2020, with a statistically significant decrease in clinical hours (2019: 219 [IQR 168â272]; 2020: 200.5 [IQR 157â261]). There was no difference in first or third-attempt certification examination success between years. Temporary shutdown was experienced in 34% of programs (duration: 3 weeks [2â7]) and 72% of required curricular changes. Curricular changes commonly included decreased in-person education (86%), traditional classroom lectures (78%), number of clinical sites (78%), and increased online didactic education (92%). Only 20% of programs decreased laboratory simulation or total training hours. Conclusion: During the pandemic, paramedic educational programs changed educational delivery with no observed differences on overall program performance. Identifying key curricular changes and best practices for implementation may be necessary to better optimize future educational delivery.
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Importance: Layperson-administered naloxone (LAN) is a powerful but incompletely characterized intervention to prevent opioid-related overdose mortality. LAN trends are relevant to policy and strategic planning in naloxone distribution initiatives. Objective: To assess the 2-year LAN trend for persons in the United States receiving naloxone during emergency medical services (EMS) activations. Design, Setting, and Participants: This retrospective cross-sectional study was conducted in the United States from June 2020 to June 2022 among 65â¯621â¯195 EMS activations from 911 responses, EMS standbys, or when EMS crews functioned in an ambulance intercept role or during mutual aid to another ambulance response. Activations within health care settings and interfacility or medical transports were excluded. Data are from the National Emergency Medical Services Information System (NEMSIS), the national EMS patient care record database. From June 2020 to June 2022, NEMSIS included more than 96 million EMS activations from nearly 14â¯000 agencies across 54 states and territories. Exposures: EMS clinician-reported LAN. Main Outcome and Measures: The primary outcome was the trend of receiving LAN, measured by EMS clinician documentation. Results: From June 2020 to June 2022, EMS reported 744â¯078 patients receiving naloxone, with 24â¯990 (3.4%) involving LAN. Patients were predominantly male (17â¯331 [69.4%]) and had a median (IQR) age of 42 (31-56) years, with the majority treated in urban homes or residences (21â¯692 [86.8%] urban; 13â¯223 [52.9%] in-home or residence). Of the total naloxone recipients, 243â¯985 patients (32.8%) had suspected drug overdose documentation as either the primary or secondary impression. Overall, the percentage change in naloxone administration rates decreased 6.1% over the study period (from 1140.1 [95% CI, 1135.1-1145.1] per 100â¯000 EMS activations to 1070.1 [95% CI, 1064.9-1075.3] per 100â¯000 EMS activations), while the percentage change of persons receiving LAN increased 43.5% (from 30.0 [95% CI, 29.2-30.8] per 100â¯000 EMS activations to 43.1 [95% CI, 42.0-44.1] per 100â¯000 EMS activations). Conclusions and Relevance: In this cross-sectional study, the LAN rate increased from June 2020 to June 2022 as reported in the national EMS database. These findings help inform policies and practices aimed at mitigating the devastating impacts of the opioid epidemic and saving lives. Novel public health strategies are needed to measure the effects of this intervention nationally, evaluate approaches to expand naloxone distribution, and address naloxone usage barriers.
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Serviços Médicos de Emergência , Naloxona , Antagonistas de Entorpecentes , Naloxona/uso terapêutico , Naloxona/administração & dosagem , Humanos , Estudos Transversais , Serviços Médicos de Emergência/estatística & dados numéricos , Masculino , Estudos Retrospectivos , Feminino , Antagonistas de Entorpecentes/uso terapêutico , Antagonistas de Entorpecentes/administração & dosagem , Adulto , Estados Unidos , Pessoa de Meia-Idade , Overdose de Drogas/tratamento farmacológico , Overdose de Drogas/prevenção & controle , Adolescente , Overdose de Opiáceos/tratamento farmacológico , Adulto JovemRESUMO
Intervertebral disc degeneration in dogs occurs in an accelerated way and involves calcification, which is associated with disc herniation or extrusion. The degenerative process is complex and involves the transformation of collagen fibres, loss of proteoglycans and notochord cells and a reduction in water content; however, how these processes are linked to future disc extrusion remains unknown. We have employed techniques including Fourier Transform Infra-red Spectroscopy (FTIR), Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), Uniaxial Compression Loading and Atomic Force Microscopy (AFM) in an attempt to gain a greater understanding of the degenerative process and its consequences on the physical properties of the disc. FTIR verified by TEM demonstrated that calcium phosphate exists in an amorphous state within the disc and that the formation of crystalline particles of hydroxyapatite occurs prior to disc extrusion. AFM identified crystalline agglomerates consistent with hydroxyapatite as well as individual collagen fibres. SEM enabled the identification of regions rich in calcium, phosphorous and oxygen and allowed the visualization of the topographical landscape of the disc. Compression testing generated stress/strain curves which will facilitate investigation into disc stiffness. Ongoing work is aimed at identifying potential areas of intervention in the degenerative process as well as further characterizing the role of calcification in disc extrusion.
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OBJECTIVES: While clinical judgment is vital for all clinicians, it is not clearly assessed in initial or continuing emergency medical services (EMS) education due to unclear definitions. Recently, clarity of this concept has been provided through the development of a theoretical framework for clinical judgment in EMS that considers the broad and evolving nature of prehospital care delivery. To facilitate standardization of clinical judgment assessments, in this educational practice review we present a template for item development leveraging the new framework. METHODS: We developed this template with input from EMS clinicians, educators, and subject matter experts from the nursing field with experience in clinical judgment item development. This template includes the basic cognitive steps of EMS clinical judgment, including recognizing cues, analyzing cues, defining a hypothesis, generating solutions, taking action, and evaluating the outcomes of those actions. RESULTS: We provide a transparent and reproducible template for item generation for clinical judgment assessments evaluating the six basic cognitive reasoning steps. Further, we provide a fully developed example of template application using a hypoglycemic patient case. This template can be used to support item generation for specific event phases (e.g., en route, scene, and post scene) in a clinical scenario. CONCLUSIONS: This template allows for generation of items for each EMS event phase that can be repeated serially for any combination of prehospital clinical situations.
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OBJECTIVES: Clinical judgment (CJ) encompasses clinical reasoning (process of evaluating a problem) and clinical decision-making (choice made). A theoretical model to better define emergency medical services (EMS) CJ has been developed but its use has not been evaluated in EMS training and assessments. Our objective was to evaluate the performance of this EMS CJ model to assess clinical reasoning and decision-making in a simulated environment. METHODS: In this evaluation, EMS clinician teams (2-3 members) were directed to care for a simulated older adult patient in their home following a fall. Simulations were video recorded, clinician team actions coded, and evaluated for whether proper CJ reasoning and decisions were made. We evaluated CJ in two ways: 1) EMS medical directors' (MD) determination of whether the CJ questions were addressed (MD score) and 2) objective rubric evaluation of CJ questions using the EMS CJ model focused on recognition of appropriate cues, performance of actions, and revaluation after action (rubric score). The CJ questions addressed in this simulation included: 1) Is the patient stable/unstable?, 2) Are interventions necessary before movement?, 3) How should the patient be transferred from the floor?, and 4) Does the cause of the fall require hospital evaluation? Descriptive statistics were calculated, and concordance between the two assessments was evaluated (mean, 95% CI). Percent concordance was calculated with a validity threshold set at 70%. RESULTS: Four EMS MDs reviewed 20 videos addressing 80 clinical judgment decisions. Overall concordance between MD score and rubric score for CJ decisions was above the threshold at 88.1% (85.0, 91.2). Concordance between MD score and rubric score for each CJ decision was 92.0% (87.3, 96.7) for question 1, 79.9% (71.5, 88.3) for question 2, 95.0% (90.4, 99.6) for question 3, and 85.4% (79.5, 91.2) for question 4. CONCLUSION: An objective evaluation of CJ decisions using a rubric derived from an EMS CJ theoretical framework demonstrated high concordance to subjective evaluations of CJ made by EMS MDs. This approach may allow for reproducible and objective CJ evaluations that could be used for competency assessment in EMS.
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Objectives: Safety policies enacted in response to the emergence of coronavirus disease 2019 (COVID-19) have greatly affected the working environments of emergency medical service (EMS) clinicians. Our objective was to evaluate whether changes in the EMS environment during the COVID-19 pandemic were associated with increased workplace conflict. Methods: This evaluation was a cross-sectional analysis of a random sample of 19,497 national certified EMS clinicians who were selected to receive an electronic survey in April 2022. The survey included an assessment of their level of stress using the Perceived Stress Scale instrument and examined changes in their working environment they perceived had occurred due to the emergence of COVID-19. Logistic regression modeling was used to evaluate the associations between workforce demographics, infrastructure, scheduling, and policies to and COVID-19-induced coworker conflict. Results: A total of 1686 responses were evaluated (response rate 10%). We found that COVID-19 was reported to have exacerbated conflict between coworkers in 51% of responses. Respondents who perceived an increase in coworker conflict due to COVID-19 self-reported higher levels of stress than the rest of the respondents. Perceptions of the impact of COVID-19 on conflict had also an association with the level of certification, indicating that national registered paramedics were more likely than emergency medical technicians to report coworker conflict due to COVID-19 (adjusted odds ratio [AOR] 1.30, 95% confidence interval [CI] 1.05-1.61). Multivariable analysis highlighted the impact of mandatory overtime policies, reported by 27% of the respondents and associated with higher odds of exacerbated coworker conflict in our model (AOR 2.05, 95% CI 1.62-2.60). Conclusions: These findings indicate that conflict can be considered a potential indicator of high levels of stress in the EMS workforce and may be a reliable signal to monitor when implementing mandates that affect EMS clinicians and their workloads.
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Importance: Identifying longitudinal changes in advanced airway management by emergency medical services (EMS) is crucial for understanding practice patterns and optimizing care. Objective: To examine the longitudinal trends in endotracheal intubation (ETI) and supraglottic airway (SGA) utilization in a national EMS cohort. Design, Setting, and Participants: This retrospective cross-sectional study analyzed 2011 to 2022 data from the ESO Data Collaborative, a national database of US prehospital electronic health records. The study included all 911 EMS events in which advanced airway management was attempted. Data were analyzed from November 2022 to January 2024. Exposures: Advanced airway management attempts, including ETI, SGA, and surgical airways. Main Outcomes and Measures: The annual percentage of ETI and SGA attempts, stratified by underlying condition (cardiac arrest, nonarrest medical, nonarrest trauma, pediatrics). Results: Among 47.5 million EMS activations, 444â¯041 (mean [SD] age, 60.6 [19.8] years; 273â¯296 [61.5%] men) involved advanced airway management, including 305â¯584 (68.8%) that used ETI and 200â¯437 (45.1%) that used SGA. The overall incidence was 9.3 per 1000 EMS events. In the cardiac arrest cohort from 2011 to 2022, EMS events with ETI attempts decreased from 2470 of 2831 (87.3%) to 40â¯083 of 72â¯793 (55.1%) and those with SGA attempts increased from 711 of 2831 (25.1%) to 44â¯386 of 72â¯793 (61.0%). In the pediatric subset, there were similarly large decreases in ETI attempts, from 117 of 182 EMS events (97.3%) to 1573 of 2307 EMS events (68.2%), and increases in SGA attempts, from 11 of 182 EMS events (6.6%) to 1058 of 2307 EMS events (45.9%). In the nonarrest medical and nonarrest trauma cohorts, ETI attempts decreased and SGA attempts increased but to a much lower extent. Conclusions and Relevance: In this national cross-sectional study of EMS care episodes, there were marked shifts in advanced airway management practices, with the increased use of SGA and decreased use of ETI. These observations highlight current trends in EMS airway management practices.
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Manuseio das Vias Aéreas , Serviços Médicos de Emergência , Intubação Intratraqueal , Humanos , Masculino , Feminino , Serviços Médicos de Emergência/estatística & dados numéricos , Estudos Transversais , Estudos Retrospectivos , Manuseio das Vias Aéreas/métodos , Manuseio das Vias Aéreas/estatística & dados numéricos , Pessoa de Meia-Idade , Idoso , Intubação Intratraqueal/estatística & dados numéricos , Adulto , Estudos Longitudinais , Estados UnidosRESUMO
Importance: While widely measured, the time-varying association between exhaled end-tidal carbon dioxide (EtCO2) and out-of-hospital cardiac arrest (OHCA) outcomes is unclear. Objective: To evaluate temporal associations between EtCO2 and return of spontaneous circulation (ROSC) in the Pragmatic Airway Resuscitation Trial (PART). Design, Setting, and Participants: This study was a secondary analysis of a cluster randomized trial performed at multicenter emergency medical services agencies from the Resuscitation Outcomes Consortium. PART enrolled 3004 adults (aged ≥18 years) with nontraumatic OHCA from December 1, 2015, to November 4, 2017. EtCO2 was available in 1172 cases for this analysis performed in June 2023. Interventions: PART evaluated the effect of laryngeal tube vs endotracheal intubation on 72-hour survival. Emergency medical services agencies collected continuous EtCO2 recordings using standard monitors, and this secondary analysis identified maximal EtCO2 values per ventilation and determined mean EtCO2 in 1-minute epochs using previously validated automated signal processing. All advanced airway cases with greater than 50% interpretable EtCO2 signal were included, and the slope of EtCO2 change over resuscitation was calculated. Main Outcomes and Measures: The primary outcome was ROSC determined by prehospital or emergency department palpable pulses. EtCO2 values were compared at discrete time points using Mann-Whitney test, and temporal trends in EtCO2 were compared using Cochran-Armitage test of trend. Multivariable logistic regression was performed, adjusting for Utstein criteria and EtCO2 slope. Results: Among 1113 patients included in the study, 694 (62.4%) were male; 285 (25.6%) were Black or African American, 592 (53.2%) were White, and 236 (21.2%) were another race; and the median (IQR) age was 64 (52-75) years. Cardiac arrest was most commonly unwitnessed (n = 579 [52.0%]), nonshockable (n = 941 [84.6%]), and nonpublic (n = 999 [89.8%]). There were 198 patients (17.8%) with ROSC and 915 (82.2%) without ROSC. Median EtCO2 values between ROSC and non-ROSC cases were significantly different at 10 minutes (39.8 [IQR, 27.1-56.4] mm Hg vs 26.1 [IQR, 14.9-39.0] mm Hg; P < .001) and 5 minutes (43.0 [IQR, 28.1-55.8] mm Hg vs 25.0 [IQR, 13.3-37.4] mm Hg; P < .001) prior to end of resuscitation. In ROSC cases, median EtCO2 increased from 30.5 (IQR, 22.4-54.2) mm HG to 43.0 (IQR, 28.1-55.8) mm Hg (P for trend < .001). In non-ROSC cases, EtCO2 declined from 30.8 (IQR, 18.2-43.8) mm Hg to 22.5 (IQR, 12.8-35.4) mm Hg (P for trend < .001). Using adjusted multivariable logistic regression with slope of EtCO2, the temporal change in EtCO2 was associated with ROSC (odds ratio, 1.45 [95% CI, 1.31-1.61]). Conclusions and Relevance: In this secondary analysis of the PART trial, temporal increases in EtCO2 were associated with increased odds of ROSC. These results suggest value in leveraging continuous waveform capnography during OHCA resuscitation. Trial Registration: ClinicalTrials.gov Identifier: NCT02419573.
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Capnografia , Reanimação Cardiopulmonar , Parada Cardíaca Extra-Hospitalar , Humanos , Parada Cardíaca Extra-Hospitalar/terapia , Masculino , Capnografia/métodos , Feminino , Pessoa de Meia-Idade , Idoso , Reanimação Cardiopulmonar/métodos , Retorno da Circulação Espontânea , Serviços Médicos de Emergência/métodos , Dióxido de Carbono/análise , Dióxido de Carbono/metabolismo , Fatores de TempoRESUMO
OBJECTIVES: The strength and stability of the paramedic workforce is dependent on the continual flow of EMS clinicians into the field. Workforce entry requires three distinct steps: program completion, certification attainment, and affiliation with an EMS agency. At each of these steps, future EMS clinicians may be lost to the workforce but the contribution of each is unknown. Our objective was to evaluate these inflection points using a state-based registry of EMS clinicians from their point of entry into the EMS education system to eventual EMS agency affiliation. METHODS: This is a retrospective cohort evaluation of paramedic students in the Commonwealth of Virginia. We included any student who enrolled in a paramedic program in 2017 or 2018. Data were provided by the Virginia Office of Emergency Medical Services, who tracks the development of EMS clinicians from the point of entry into an educational program through their affiliation with an EMS agency upon employment. Our primary outcomes include proportions of enrolled students who complete a program, graduating students who attain national/state certification, and nationally certified EMS clinicians who affiliate with an EMS agency. Proportions were calculated at each step and compared to the overall population of students enrolled. RESULTS: In 2017 and 2018, 775 and 603 students were enrolled in paramedic programs, respectively. Approximately a quarter of students did not complete their paramedic program (2017: 25% [192/775]; 2018: 28% [170/603]). Of those who graduated, the proportion of students not gaining certification was lower (2017: 11% [62/583]; 2018: 17% [75/433]). Of those who certified, those not affiliating was similarly low (2017: 15% [77/521]; 2018: 13% [46/358]). Evaluating the effect of each of these steps on the total entry into the workforce, nearly half of those who originally enrolled did not join the workforce through agency affiliation (2017: 43% [331/775]; 2018: 48% [291/603]). CONCLUSIONS: There are multiple areas to enhance retention of potential EMS trainees from program enrollment to EMS agency affiliation. This analysis suggests that educational attrition has a larger impact on the availability of new paramedics than certification examinations or agency affiliation decisions, though is limited to a singular state evaluation.
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CONTEXT: New approaches to emergency response are a national focus due to evolving needs and growing demands on the system, but perspectives of first responders and potential partners have not been evaluated. OBJECTIVE: This project aimed to inform the development and implementation of alternative emergency response models, including interdisciplinary partnerships, by identifying the perspectives of the frontline workforce regarding their evolving roles. DESIGN: An electronic survey was sent, querying respondents about their perceived roles in emergency response, interdisciplinary partnerships, and resources needed. SETTING: This study took place in a metropolitan, midwestern county with participants from 2 public health agencies and 1 emergency medical services (EMS) agency. PARTICIPANTS: The survey was completed by 945 EMS clinicians and 58 public health workers. MAIN OUTCOME MEASURES: The main outcome measures were agreement levels on each group's roles in prevention, response, and recovery after emergencies, as well as general feedback on new models. RESULTS: Overall, 97% of EMS clinicians and 42% of public health workers agreed that they have a role in immediate response to 9-1-1 emergencies. In mental health emergencies, 87% of EMS clinicians and 52% of public health workers agreed that they have a role, compared to 87% and 30%, respectively, in violent emergencies. Also, 84% of respondents felt multidisciplinary models are a needed change. However, 35% of respondents felt their agency has the resources necessary for changes. CONCLUSIONS: We observed differences between EMS clinicians and public health workers in their perceived roles during emergency response and beliefs about the types of emergencies within their scope. There is strong support for alternative approaches and a perception that this model may improve personal well-being and job satisfaction, but a need for additional resources to develop and implement.
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Serviços Médicos de Emergência , Saúde Pública , Humanos , Serviços Médicos de Emergência/estatística & dados numéricos , Saúde Pública/métodos , Inquéritos e Questionários , Masculino , Feminino , AdultoRESUMO
Glutamine metabolism in tumor microenvironments critically regulates antitumor immunity. Using the glutamine-antagonist prodrug JHU083, we report potent tumor growth inhibition in urologic tumors by JHU083-reprogrammed tumor-associated macrophages (TAMs) and tumor-infiltrating monocytes. We show JHU083-mediated glutamine antagonism in tumor microenvironments induced by TNF, proinflammatory, and mTORC1 signaling in intratumoral TAM clusters. JHU083-reprogrammed TAMs also exhibited increased tumor cell phagocytosis and diminished proangiogenic capacities. In vivo inhibition of TAM glutamine consumption resulted in increased glycolysis, a broken tricarboxylic acid (TCA) cycle, and purine metabolism disruption. Although the antitumor effect of glutamine antagonism on tumor-infiltrating T cells was moderate, JHU083 promoted a stem cell-like phenotype in CD8+ T cells and decreased the abundance of regulatory T cells. Finally, JHU083 caused a global shutdown in glutamine-utilizing metabolic pathways in tumor cells, leading to reduced HIF-1α, c-MYC phosphorylation, and induction of tumor cell apoptosis, all key antitumor features. Altogether, our findings demonstrate that targeting glutamine with JHU083 led to suppressed tumor growth as well as reprogramming of immunosuppressive TAMs within prostate and bladder tumors that promoted antitumor immune responses. JHU083 can offer an effective therapeutic benefit for tumor types that are enriched in immunosuppressive TAMs.
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Glutamina , Neoplasias da Próstata , Microambiente Tumoral , Macrófagos Associados a Tumor , Neoplasias da Bexiga Urinária , Glutamina/metabolismo , Masculino , Animais , Macrófagos Associados a Tumor/imunologia , Macrófagos Associados a Tumor/efeitos dos fármacos , Macrófagos Associados a Tumor/metabolismo , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/imunologia , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/patologia , Camundongos , Humanos , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/imunologia , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/imunologia , Linhagem Celular Tumoral , Camundongos Endogâmicos C57BL , Reprogramação MetabólicaRESUMO
Silicon (Si) may be a mineral beneficial for bone health. Pregnancy and lactation have major impacts on maternal bone metabolism as bone minerals, including calcium (Ca), are required for growth of the foetus and for milk production. Like urinary Ca excretion, Si excretion has been reported to be high in pregnant women, but there are no data post-partum and during lactation. The aim of the present study was to investigate the urinary excretion of Si (U-Si), from the third trimester of pregnancy until 18 months post-partum, and in relation to the length of lactation, to determine if changes in U-Si are associated with changes in areal bone mineral density (aBMD). This longitudinal study included 81 pregnant women, of whom 56 completed the study. Spot urine samples were collected at the third trimester and at 0.5, 4, 12, and 18 months post-partum and were analysed for Si and Ca by ICP-OES. The aBMD was measured post-partum at lumbar spine and femoral neck by dual-energy x-ray absorptiometry. Women lactating for 4-8.9 and ≥ 9 months had significantly higher U-Si at 4 months post-partum, compared with the third trimester. No significant longitudinal differences in U-Si were found after correcting for creatinine. Changes in U-Si and in aBMD were not correlated, except at the lumbar spine from 0.5 to 12 months post-partum in the women lactating for 4-8.9 months. Taken together, our results suggest that there is a possibility that U-Si increases post-partum in women lactating for 4 months or longer, although it is not related to changes in aBMD.
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Pulmonary fibrosis is a devastating disease with no effective treatments to cure, stop or reverse the unremitting, fatal fibrosis. A critical barrier to treating this disease is the lack of understanding of the pathways leading to fibrosis as well as those regulating the resolution of fibrosis. Fibrosis is the pathologic side of normal tissue repair that results when the normal wound healing programs go awry. Successful resolution of tissue injury requires several highly coordinated pathways, and this research focuses on the interplay between these overlapping pathways: immune effectors, inflammatory mediators and fibroproliferation in the resolution of fibrosis. Previously we have successfully prevented, mitigated, and even reversed established fibrosis using vaccinia vaccination immunotherapy in two models of murine lung fibrosis. The mechanism by which vaccinia reverses fibrosis is by vaccine induced lung specific Th1 skewed tissue resident memory (TRMs) in the lung. In this study, we isolated a population of vaccine induced TRMs - CD49a+ CD4+ T cells - that are both necessary and sufficient to reverse established pulmonary fibrosis. Using adoptive cellular therapy, we demonstrate that intratracheal administration of CD49a+ CD4+ TRMs into established fibrosis, reverses the fibrosis histologically, by promoting a decrease in collagen, and functionally, by improving lung function, without the need for vaccination. Furthermore, co-culture of in vitro derived CD49+ CD4+ human TRMs with human fibroblasts from individuals with idiopathic pulmonary fibrosis (IPF) results in the down regulation of IPF fibroblast collagen production. Lastly, we demonstrate in human IPF lung histologic samples that CD49a+ CD4+ TRMs, which can down regulate human IPF fibroblast function, fail to increase in the IPF lungs, thus potentially failing to promote resolution. Thus, we define a novel unappreciated role for tissue resident memory T cells in regulating established lung fibrosis to promote resolution of fibrosis and re-establish lung homeostasis. We demonstrate that immunotherapy, in the form of adoptive transfer of CD49a+ CD4+ TRMs into the lungs of mice with established fibrosis, not only stops progression of the fibrosis but more importantly reverses the fibrosis. These studies provide the insight and preclinical rationale for a novel paradigm shifting approach of using cellular immunotherapy to treat lung fibrosis.
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Background: While maternal pertussis vaccination is a strategy to reduce infant morbidity, safety and immunogenicity data are limited in sub-Saharan Africa. We aimed to evaluate the safety of a single dose of tetanus, diphtheria and acellular pertussis vaccine (Tdap) vaccine compared to tetanus and diphtheria vaccine (Td) vaccine in pregnant women in Bamako, Mali and to assess the pertussis toxin (PT) antibody response at birth. Methods: In this phase 2, single-centre, randomised, double-blind, active-controlled study, from 23 January 2019 to 10 July 2019, healthy 18-39 year old women in the second trimester of a singleton pregnancy were randomised 2:1 to receive Tdap or Td. Blood was tested for serum immunoglobulin G (IgG) against PT and other vaccine antigens using a qualified Meso Scale Discovery multiplex immunoassay. The co-primary objectives evaluated safety and birth anti-PT levels. Infant immune responses to whole-cell pertussis vaccine (DTwP) were assessed. Statistical analysis was descriptive. This trial is registered with clinicaltrials.gov, NCT03589768. Findings: 133 women received Tdap and 67 received Td, with 126 and 66 livebirths, respectively. In the Tdap group, 22 serious adverse events (SAEs) including one maternal death occurred in 20 participants (15·0%), with 10 SAEs in 10 participants (14·9%) in the Td group. Among infants, 18 events occurred among 13 participants (10.3%) and 8 SAEs in 6 participants (9.1%), including three and two infant deaths, occurred in Tdap and Td groups, respectively. None were related to study vaccines. Anti-PT geometric mean concentration (GMC) at birth in the Tdap group was higher than in the Td group (55.4 [46.2-66.6] IU/ml vs 7.9 [5.4-11.5] IU/ml). One month after the third dose of DTwP, the GMC in infants born to mothers in the Tdap group were lower compared to the Td group (20.2 [13.7-29.9] IU/ml vs 77.2 [32.2-184.8] IU/ml). By 6 months of age, the anti- PT GMCs were 17.3 [12.8-23.4] IU/ml and 67.1 [35.5-126.7] IU/ml in Tdap and Td groups, respectively. At birth, anti-tetanus toxin (TT) GMCs were higher in infants in the Td vs Tdap group (5.9 [5.0-7.0] IU/ml vs 4.1 [3.5-4.8] IU/ml). Anti-diphtheria toxin GMCs were similar in both groups. Interpretation: Tdap administered to pregnant women in Mali is safe and well-tolerated. Infants of mothers who received Tdap were born with high PT and protective anti-TT antibody levels. By six months of age, after primary vaccination, the PT levels were lower in the Tdap group compared to the Td group. The blunted immune responses to primary DTwP vaccination in the Tdap infant group warrant further study. Funding: This project was funded by National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), under contract numbers 75N93021C00012 (The Emmes Company), and HHSN27220130000221 (University of Maryland, Baltimore). Dr. Susana Portillo was supported by NIH award no. T32AI007524. NIAID, NIH provided Tdap vaccine (BOOSTRIX).
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Objective: Public health surveillance is essential for improving community health. The Cardiac Arrest Registry to Enhance Survival (CARES) is a surveillance system for out-of-hospital cardiac arrest (OHCA). We describe results of the organized statewide implementation of Ohio CARES. Methods: We performed a retrospective analysis of CARES enactment in Ohio. Key elements included: establishment of statewide leadership, appointment of a dedicated coordinator, conversion to a statewide subscription, statewide dissemination of information, fundraising from internal and external stakeholders, and conduct of resuscitation academies. We identified all adult (≥18 years) OHCA reported in the registry during 2013-2020. We evaluated OHCA characteristics before (2013-2015) and after (2016-2019) statewide implementation using chi-square test. We evaluated trends in OHCA outcomes using the Cochran-Armitage test of trend. Results: Statewide CARES promotion increased participation from 2 (urban) to 136 (129 urban, 7 rural) EMS agencies. Covered population increased from 1.2 M (10% of state) to 4.8 M (41% of state). After statewide implementation, OHCA populations increased male (58.1% vs 60.8%, p < 0.01), white (50.1% vs 63.7%, p < 0.01), bystander witnessed (26.9% vs 32.9%, p < 0.01) OHCAs. Bystander CPR (34.7% vs 33.2%, p = 0.22), bystander AED (13.5% vs 12.3%, p = 0.55) and initial rhythm (shockable 18.0% vs 18.3%, p = 0.32) did not change. From 2013 to 2019 there were temporal increases in ROSC (29.7% to 31.9%, p-trend = 0.028), survival (7.4% to 12.3%, p-trend < 0.001) and survival with good neurologic outcome (5.6% to 8.6%, p-trend = 0.047). Conclusion: The organized statewide implementation of CARES in Ohio was associated with marked increases in community uptake and concurrent observed improvements in patient outcomes. These results highlight key lessons for community-wide fostering of OHCA surveillance.
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BACKGROUND: The prehospital care provided by emergency medical services (EMS) personnel is a critical component of the public health, public safety, and health care systems in the U.S.; however, the population-level value of EMS care is often overlooked. No studies have examined how the density of EMS personnel relates to population-level health outcomes. Our objectives were to examine the geographic distribution and density of EMS personnel in the U.S.; and quantify the association between EMS personnel density and population-level health outcomes. METHODS: We conducted a cross-sectional evaluation of county-level EMS personnel density using estimates from the National Registry of Emergency Medical Technicians in nine states that require continuous national certification (Alabama, Louisiana, Massachusetts, Minnesota, New Hampshire, North Dakota, South Carolina, Vermont, and Washington, D.C.). Outcomes of interest included life expectancy, all-cause mortality, and cardiac arrest mortality. We used quantile regression models to examine the association between a 10-person increase in EMS personnel density and each outcome at the 10th, 50th (median), and 90th percentiles, controlling for population characteristics and area health resources. RESULTS: There were 356 counties included, with a mean EMS density of 223 EMS personnel per 100,000 population. Density was higher in rural compared to urban counties (247 versus 186 per 100,000 population; p = 0.001). In unadjusted models, there was a significant association between increase in EMS personnel density and an increase in life expectancy at each examined percentile (e.g., 50th percentile, increase of 52.9 days; 95% CI 40.2, 65.5; p < 0.001), decrease in all-cause mortality at each examined percentile, and decrease in cardiac arrest mortality at the 50th and 90th percentiles. These associations were not statistically significant in the adjusted models. CONCLUSIONS: EMS personnel density differs between urban and rural areas, with higher density per population in rural areas. There were no statistically significant associations between EMS density and population-level health outcomes after controlling for population characteristics and other health resources. The best approach to quantifying the community-level value that EMS care may or may not provide remains unclear.
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Serviços Médicos de Emergência , Parada Cardíaca , Saúde da População , Humanos , Estudos Transversais , Recursos HumanosRESUMO
INTRODUCTION: Prehospital research and evidence-based guidelines (EBGs) have grown in recent decades, yet there is still a paucity of prehospital implementation research. While recent studies have revealed EMS agency leadership perspectives on implementation, the important perspectives and opinions of frontline EMS clinicians regarding implementation have yet to be explored in a systematic approach. The objective of this study was to measure the preferences of EMS clinicians for the process of EBG implementation and whether current agency practices align with those preferences. METHODS: This study was a cross-sectional survey of National Registry of Emergency Medical Technicians registrants. Eligible participants were certified paramedics who were actively practicing EMS clinicians. The survey contained discrete choice experiments (DCEs) for three EBG implementation scenarios and questions about rank order preferences for various aspects of the implementation process. For the DCEs, we used multinomial logistic regression to analyze the implementation preference choices of EMS clinicians, and latent class analysis to classify respondents into groups by their preferences. RESULTS: A total of 183 respondents completed the survey. Respondents had a median age of 39 years, were 74.9% male, 89.6% White, and 93.4% of non-Hispanic ethnicity. For all three DCE scenarios, respondents were significantly more likely to choose options with hospital feedback and individual-level feedback from EMS agencies. Respondents were significantly less likely to choose options with email/online only education, no feedback from hospitals, and no EMS agency feedback to clinicians. In general, respondents' preferences favored classroom-based training over in-person simulation. For all DCE questions, most respondents (66.2%-77.1%) preferred their survey DCE choice to their agency's current implementation practices. In the rank order preferences, most participants selected "knowledge of the underlying evidence behind the change" as the most important component of the process of implementation. CONCLUSIONS: In this study of EMS clinicians' implementation preferences using DCEs, respondents preferred in-person education, feedback on hospital outcomes, and feedback on their individual performance. However, current practice at EMS agencies rarely matched those expressed EMS clinician preferences. Collectively, these results present opportunities for improving EMS implementation from the EMS clinician perspective.
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Serviços Médicos de Emergência , Auxiliares de Emergência , Humanos , Masculino , Adulto , Feminino , Serviços Médicos de Emergência/métodos , Estudos Transversais , Inquéritos e Questionários , HospitaisRESUMO
INTRODUCTION: The transition of Army Combat Medic Specialists (Military Occupational Specialty Code: 68W) from military to civilian emergency medical services (EMS) is challenging, and the pathway is not clearly defined. Our objective was to evaluate the current military requirements for 68W and how they compare to the 2019 EMS National Scope of Practice Model (SoPM) for the civilian emergency medical technician (EMT) and advanced emergency medical technician (AEMT). METHODS: This was a cross-sectional evaluation of the 68W skill floor as defined by the Soldier's Manual and Trainer's Guide Healthcare Specialist and Medical Education and Demonstration of Individual Competence in comparison to the 2019 SoPM, which categorizes EMS tasks into seven skill categories. Military training documents were reviewed and extracted for specific information on military scope of practice and task-specific training requirements. Descriptive statistics were calculated. RESULTS: Army 68Ws were noted to perform all (59/59) tasks that coincide with the EMT SoPM. Further, Army 68W practiced above scope in the following skill categories: airway/ventilation (3 tasks); medication administration route (7 tasks); medical director approved medication (6 tasks); intravenous initiation maintenance fluids (4 tasks); and miscellaneous (1 task). Army 68W perform 96% (74/77) of tasks aligned with the AEMT SoPM, excluding tracheobronchial suctioning of an intubated patient, end-tidal CO2 monitoring or waveform capnography, and inhaled nitrous oxide monitoring. Additionally, the 68W scope included six tasks that were above the SoPM for AEMT; airway/ventilation (2 tasks); medication administration route (2 tasks); and medical director approved medication (2 tasks). CONCLUSIONS: The scope of practice of U.S. Army 68W Combat Medics aligns well with the civilian 2019 Scope of Practice Model for EMTs and AEMTs. Based on the comparative scope of practice analysis, transitioning from Army 68W Combat Medic to civilian AEMT would require minimal additional training. This represents a promising potential workforce to assist with EMS workforce challenges. Although aligning the scope of practice is a promising first step, future research is needed to assess the relationship of Army 68Ws training with state licensure and certification equivalency to facilitate this transition.