RESUMO
OBJECTIVE: The objective is to determine whether unsupervised machine learning identifies traumatic brain injury (TBI) phenotypes with unique clinical profiles. METHODS: Pilot self-reported survey data of over 10,000 adults were collected from the Centers for Disease Control and Prevention (CDC)'s National Concussion Surveillance System (NCSS). Respondents who self-reported a head injury in the past 12 months (n = 1,364) were retained and queried for injury, outcome, and clinical characteristics. An unsupervised machine learning algorithm, partitioning around medoids (PAM), that employed Gower's dissimilarity matrix, was used to conduct a cluster analysis. RESULTS: PAM grouped respondents into five TBI clusters (phenotypes A-E). Phenotype C represented more clinically severe TBIs with a higher prevalence of symptoms and association with worse outcomes. When compared to individuals in Phenotype A, a group with few TBI-related symptoms, individuals in Phenotype C were more likely to undergo medical evaluation (odds ratio [OR] = 9.8, 95% confidence interval[CI] = 5.8-16.6), have symptoms that were not currently resolved or resolved in 8+ days (OR = 10.6, 95%CI = 6.2-18.1), and more likely to report at least moderate impact on social (OR = 54.7, 95%CI = 22.4-133.4) and work (OR = 25.4, 95%CI = 11.2-57.2) functioning. CONCLUSION: Machine learning can be used to classify patients into unique TBI phenotypes. Further research might examine the utility of such classifications in supporting clinical diagnosis and patient recovery for this complex health condition.
RESUMO
OBJECTIVES: To quantify norms and changes in eye-tracking proficiency, and determine vestibular symptom correlations in varsity college athletes following acute mild traumatic brain injury (mTBI). We hypothesized that mTBI impacts central coordination between the vestibular and oculomotor systems with resultant changes in eye-tracking proficiency that are correlated with vestibular symptom provocation. DESIGN: Retrospective cohort study. SETTING: Sports medicine care at a single institution. PATIENTS: One hundred and nineteen college athletes diagnosed with mTBI by a physician between 2013 and 2019. INTERVENTIONS: N/A. MAIN OUTCOME MEASURES: Standard deviation of tangential error, standard deviation of radian error, mean phase error, and horizontal gain from virtual reality-based, circular eye-tracking goggles used at baseline and within 72 hours post-mTBI. Headache, dizziness, nausea, and fogginess provocation after the Vestibular Ocular Motor Screening (VOMS) smooth pursuits subtest compared with pretest baseline, assessed within 72 hours post-mTBI. RESULTS: One hundred and nineteen college athletes (N = 56 women and 63 men) aged 18 to 24 years sustained a total of 177 mTBI. Forty-four percent of athletes displayed abnormal eye-tracking on at least 1 eye-tracking measure following acute mTBI compared with their baseline. From the VOMS, horizontal gain showed medium-sized to large-sized positive correlations with headache ( r = 0.34) and dizziness ( r = 0.54), respectively. Mean phase error showed a medium-sized negative correlation with nausea ( r = -0.32) on the VOMS. CONCLUSIONS: Eye-tracking proficiency was impaired and correlated with vestibular symptom provocation following acute mTBI in college athletes. Future research should examine eye-tracking proficiency testing in other acute care settings to support mTBI diagnosis.
RESUMO
The development of novel antibacterial agents that are effective against Gram-negative bacteria is limited primarily by transport issues. This class of bacteria maintains a complex cell envelope consisting of two membrane bilayers, preventing the passage of most antibiotics. These drugs must therefore pass through protein channels called porins; however, many antibiotics are too large to pass through porins, and a common mechanism of acquired resistance is down-regulation of porins. To overcome this transport limitation, we have proposed the use of outer membrane vesicles (OMVs), released by Gram-negative bacteria, which deliver cargo to other bacterial cells in a porin-independent manner. In this work, we systematically studied the ability to load fluoroquinolones into purified Escherichia coli OMVs using in vivo and in vitro passive loading methods, and active loading methods such as electroporation and sonication. We observed limited loading of all of the antibiotics using passive loading techniques; sonication and electroporation significantly increased the loading, with electroporation at low voltages (200 and 400V) resulting in the greatest encapsulation efficiencies. We also demonstrated that imipenem, a carbapenem antibiotic, can be readily loaded into OMVs, and its administration via OMVs increases the effectiveness of the drug against E. coli. Our results demonstrate that small molecule antibiotics can be readily incorporated into OMVs to create novel delivery vehicles to improve antibiotic activity.
RESUMO
OBJECTIVES: Expedited partner therapy (EPT) is a partner treatment strategy for sexually transmitted infections (STIs) including gonorrhea and chlamydia as well as trichomoniasis in some states. The process allows healthcare providers to write prescriptions for STI treatment among partners of infected patients without a previous medical evaluation. The Centers for Disease Control (CDC) has recommended EPT as a useful option to facilitate partner treatment, particularly male partners of women with chlamydia or gonorrhea infections. Our institution implemented EPT in 2016 after Ohio legislation was passed to authorize its use. We aim to describe the implementation process and descriptive outcomes of EPT adoption in a pediatric emergency department. METHODS: This study describes use of the electronic health record for implementation of EPT in our institution. We conducted a retrospective review of EPT utilization from implementation. Electronic records from the implementation date of January 1, 2017, through December 31, 2021, were reviewed. We describe basic demographics and overall uptake of the intervention. Fisher exact tests were used for categorical variables and two-sample t-tests for continuous variables. RESULTS: There was a total of 3275 positive test results and 739 EPT prescriptions written. Adolescent patients who received prescriptions for EPT were more likely to be female (78.7% of all EPT prescriptions, P = 0.007) and older than other patients (average age 17.7 vs 17.4 years, P = 0.004). There was no significant difference in race, insurance, or ethnicity among adolescent patients receiving and not receiving EPT. The percentage of positive STI tests associated with an EPT prescription ranged between 11.4% and 18.2%. Metronidazole was the most prescribed EPT medication. CONCLUSIONS: The use of the electronic health record provides a platform for implementation of EPT. Our study highlights a potential strategy for increasing treatments of STIs through EPT prescribing in the emergency department setting.
RESUMO
OBJECTIVE: To develop new diagnostic criteria for mild traumatic brain injury (TBI) that are appropriate for use across the lifespan and in sports, civilian trauma, and military settings. DESIGN: Rapid evidence reviews on 12 clinical questions and Delphi method for expert consensus. PARTICIPANTS: The Mild Traumatic Brain Injury Task Force of the American Congress of Rehabilitation Medicine Brain Injury Special Interest Group convened a Working Group of 17 members and an external interdisciplinary expert panel of 32 clinician-scientists. Public stakeholder feedback was analyzed from 68 individuals and 23 organizations. RESULTS: The first 2 Delphi votes asked the expert panel to rate their agreement with both the diagnostic criteria for mild TBI and the supporting evidence statements. In the first round, 10 of 12 evidence statements reached consensus agreement. Revised evidence statements underwent a second round of expert panel voting, where consensus was achieved for all. For the diagnostic criteria, the final agreement rate, after the third vote, was 90.7%. Public stakeholder feedback was incorporated into the diagnostic criteria revision prior to the third expert panel vote. A terminology question was added to the third round of Delphi voting, where 30 of 32 (93.8%) expert panel members agreed that 'the diagnostic label 'concussion' may be used interchangeably with 'mild TBI' when neuroimaging is normal or not clinically indicated.' CONCLUSIONS: New diagnostic criteria for mild TBI were developed through an evidence review and expert consensus process. Having unified diagnostic criteria for mild TBI can improve the quality and consistency of mild TBI research and clinical care.
Assuntos
Concussão Encefálica , Lesões Encefálicas , Militares , Humanos , Estados Unidos , Concussão Encefálica/diagnóstico , Lesões Encefálicas/reabilitação , Consenso , Técnica DelphiRESUMO
BACKGROUND: Current guidelines recommend healthcare professionals avoid routine use of neuroimaging for diagnosing mild traumatic brain injury (mTBI). OBJECTIVE: This study aimed to examine current use of CT and MRI among children and young adult patients with mTBI and factors that increase likelihood of neuroimaging in this population. MATERIALS AND METHODS: Data were analyzed using the 2019 MarketScan commercial claims and encounters database for the commercially insured population for both inpatient and outpatient claims. Descriptive statistics and logistic regression models for patients ≤24 years of age who received an ICD-10-CM code indicative of a possible mTBI were analyzed. RESULTS: Neuroimaging was performed in 16.9% (CT; 95% CI=16.7-17.1) and 0.9% (MRI; 95% CI=0.8-0.9) of mTBI outpatient visits (including emergency department visits) among children (≤18 years old). Neuroimaging was performed in a higher percentage of outpatient visits for patients 19-24 years old (CT=47.1% [95% CI=46.5-47.6] and MRI=1.7% [95% CI=1.5-1.8]), and children aged 15-18 years old (CT=20.9% [95% CI=20.5-21.2] and MRI=1.4% [95% CI=1.3-1.5]). Outpatient visits for males were 1.22 (95% CI=1.10-1.25) times more likely to include CT compared to females, while there were no differences by sex for MRI or among inpatient stays. Urban residents, as compared to rural, were less likely to get CT in outpatient settings (adjusted odds ratio [aOR]=0.55, 95% CI=0.53-0.57). Rural residents demonstrated a larger proportion of inpatient admissions that had a CT. CONCLUSIONS: Despite recommendations to avoid routine use of neuroimaging for mTBI, neuroimaging remained common practice in 2019.
Assuntos
Concussão Encefálica , Masculino , Feminino , Adulto Jovem , Humanos , Criança , Adulto , Adolescente , Concussão Encefálica/diagnóstico por imagem , Concussão Encefálica/epidemiologia , Estudos Transversais , Neuroimagem , Imageamento por Ressonância Magnética , Serviço Hospitalar de EmergênciaRESUMO
The role of an advanced nurse practitioner encompasses the assessment, diagnosis and treatment of a range of conditions. This case study presents a patient with newly diagnosed hypertension. It demonstrates effective history taking, physical examination, differential diagnoses and the shared decision making which occurred between the patient and the professional. It is widely acknowledged that adherence to medications is poor in long-term conditions, such as hypertension, but using a concordant approach in practice can optimise patient outcomes. This case study outlines a concordant approach to consultations in clinical practice which can enhance adherence in long-term conditions.
Assuntos
Hipertensão , Profissionais de Enfermagem , Humanos , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Diagnóstico DiferencialRESUMO
BACKGROUND: Hypertension remains the major risk factor for cardiovascular diseases (CVDs) worldwide with a prevalence and mortality in low- and middle-income countries (LMICs) among the highest. The early detection of hypertension risk factors is a crucial pillar for CVD prevention. DESIGN AND METHOD: This cross-sectional study included 4284 subjects, mean age 46 ± 16SD, 56.4% females and mean BMI 26.6 ± 3.7 SD. Data were collected through a screening campaign in rural area of Kirehe District, Eastern of Rwanda, with the objective to characterize and examine the prevalence of elevated blood pressure (BP) and other CVD risk factors. An adapted tool from the World Health Organization STEPwise Approach was used for data collection. Elevated BP was defined as ≥ 140/90 mm/Hg and elevated blood glucose as blood glucose ≥ 100 mg/dL after a 6-h fast. RESULTS: Of the sampled population, 21.2% (n = 910) had an elevated BP at screening; BP was elevated among individuals not previously known to have HTN in 18.7% (n = 752). Among individuals with a prior diagnosis of HTN, 62.2% (n = 158 of 254) BP was uncontrolled. Age, weight, smoking, alcohol history and waist circumference were associated with BP in both univariate analyses and multivariate analysis. CONCLUSION: High rates of elevated BP identified through a health screening campaign in this Rwandan district were surprising given the rural characteristics of the district and relatively low population age. These data highlight the need to implement an adequate strategy for the prevention, diagnosis, and control of HTN that includes rural areas of Rwanda as part of a multicomponent strategy for CVD prevention.
Assuntos
Doenças do Sistema Nervoso Autônomo , Doenças Cardiovasculares , Hipertensão , Adulto , Glicemia , Estudos Transversais , Feminino , Humanos , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Masculino , Pessoa de Meia-Idade , Ruanda/epidemiologiaRESUMO
OBJECTIVE: Female athletes may be more likely to sustain a concussion and may vary in symptom presentation and neurocognitive impairments as compared with males. Scientific literature is limited by subjective assessments and underproportioned representation of women-the scope and etiology of sex-based differences are unknown. This study investigates sex-based differences in sports concussion assessments among college varsity athletes. DESIGN AND SETTING: Retrospective study of an institution's athletic head injury database. PARTICIPANTS: Acute postinjury and baseline data from 111 college athletes sustaining concussions between 2016 and 2018, diagnosed by a concussion specialist physician. MAIN OUTCOME MEASURES: Concussion assessments examined included the Sports Concussion Assessment Tool (SCAT5) and Vestibular Oculomotor Screening (VOMS) performed within 3 days (24-72 hours) of injury. RESULTS: No significant difference by sex was observed in the SCAT5 total symptom evaluation scores or severity scores, Standardized Assessment of Concussion, or Balance Error Scoring System ( P > .05) within 3 days of head injury. Females did report more "pressure in the head" severity scores from baseline to postconcussion (2.7 ± 1.5 increased symptomatology in females vs 1.8 ± 1.3 increase in males, P = .007). The VOMS test resulted in significant sex differences in smooth pursuit [0.6 ± 1.4 increase in females ( P < .001) vs 0.2 ± 0.6 increase in males ( P = .364)], horizontal saccades [0.6 ± 1.2 increase in females ( P < .001) vs 0.2 ± 0.5 increase in males ( P = .149)], and vertical saccades [0.9 ± 1.9 increase in females ( P < .001) vs 0.3 ± 0.7 increase in males ( P = .206)]. CONCLUSION: Our study did not show sex-based differences in baseline or acute postconcussive symptom reporting in most concussion assessment parameters, challenging previous research suggesting that females report more symptoms than males. Females did have significant differences in symptom provocation using the VOMS.
Assuntos
Traumatismos em Atletas , Concussão Encefálica , Atletas , Traumatismos em Atletas/complicações , Traumatismos em Atletas/diagnóstico , Traumatismos em Atletas/epidemiologia , Concussão Encefálica/diagnóstico , Concussão Encefálica/epidemiologia , Concussão Encefálica/etiologia , Feminino , Humanos , Masculino , Testes Neuropsicológicos , Estudos Retrospectivos , Caracteres SexuaisRESUMO
Analytical characterization of small biological particles, such as extracellular vesicles (EVs), is complicated by their extreme heterogeneity in size, lipid, membrane protein, and cargo composition. Analysis of individual particles is essential for illuminating particle property distributions that are obscured by ensemble measurements. To enable high-throughput analysis of individual particles, liftoff nanocontact printing (LNCP) is used to define hexagonal antibody and toxin arrays that have a 425 nm dot size, on average, and 700 nm periodicity. The LNCP process is rapid, simple, and does not require access to specialized nanofabrication tools. These densely packed, highly ordered arrays are used to capture liposomes and bacterial outer membrane vesicles on the basis of their surface biomarkers, with a maximum of one particle per array dot, resulting in densely packed arrays of particles. Despite the high particle density, the underlying antibody or toxin array ensured that neighboring individual particles are optically resolvable. Provided target particle biomarkers and suitable capture molecules are identified, this approach can be used to generate high density arrays of a wide variety of small biological particles, including other types of EVs like exosomes.
Assuntos
Exossomos , Vesículas Extracelulares , Membrana Externa Bacteriana , Lipídeos , LipossomosRESUMO
Trichoblastic carcinosarcomas are rare, adnexal-type cutaneous carcinosarcomas that are thought to be related histogenetically to trichoblastomas, yet in which both the epithelial and stromal components show features of malignancy. Ten cases have been described in the literature thus far, with a predilection for the head and neck of older males. We present a case of cutaneous carcinosarcoma in sun-damaged skin of a 34-year-old woman showing features of a trichoblastic carcinosarcoma, with histopathologic analysis along with targeted next-generation sequencing of 50 cancer-associated genes. Two pathogenic variants in TP53 were identified, p.(R158C), p.(R273P), along with a likely pathogenic variant CDKN2A, p.(R58*). In particular, it is noted that the CDKN2A p.(R58*) missense mutation has been described in two previous cases of cutaneous carcinosarcomas, including a case of trichoblastic carcinosarcoma.
Assuntos
Carcinossarcoma , Inibidor p16 de Quinase Dependente de Ciclina , Mutação de Sentido Incorreto , Neoplasias Cutâneas , Adulto , Carcinossarcoma/genética , Carcinossarcoma/metabolismo , Carcinossarcoma/patologia , Inibidor p16 de Quinase Dependente de Ciclina/genética , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Feminino , Humanos , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismoRESUMO
OBJECTIVES: To identify trends in and factors associated with pediatric organ donation authorization after brain death. DESIGN: Retrospective cohort study of data from Virtual Pediatric Systems, LLC (Los Angeles, CA). SETTING: Data from 123 PICUs reporting to Virtual Pediatric Systems from 2009 to 2018. PATIENTS: Patients less than 19 years old eligible for organ donation after brain death. MEASUREMENTS AND MAIN RESULTS: Of 2,777 eligible patients, 1,935 (70%) were authorized for organ donation; the authorization rate remained unchanged over time (ptrend = 0.22). In a multivariable logistic regression model, hospitalizations lasting greater than 7 days had lower odds of authorization (adjusted odds ratio, 0.5; p < 0.001 vs ≤ 1 d) and White patients had higher odds than other race/ethnicity groups. Authorization was higher for trauma-related encounters (adjusted odds ratio, 1.5; p < 0.001) and when donation was discussed with an organ procurement organization coordinator (adjusted odds ratio, 1.7; p < 0.001). Of 123 hospitals, 35 (28%) met or exceeded a 75% organ donation authorization target threshold; these hospitals more often had an organ procurement organization coordinator discussing organ donation (85% vs 72% of encounters; p < 0.001), but no difference was observed by PICU bed size. CONCLUSIONS: Organ donation authorization after brain death among PICU patients was associated with length of stay, race/ethnicity, and trauma-related encounter, and authorization rates were higher when an organ procurement organization coordinator was involved in the donation discussion. This study identified factors that could inform initiatives to improve the authorization process and increase pediatric organ donation rates.
Assuntos
Morte Encefálica , Obtenção de Tecidos e Órgãos , Adulto , Criança , Hospitalização , Humanos , Unidades de Terapia Intensiva Pediátrica , Los Angeles , Estudos Retrospectivos , Doadores de Tecidos , Estados Unidos , Adulto JovemRESUMO
SIGNIFICANCE: The Ohio Contrast Cards are a repeatable test of contrast sensitivity, and they reveal higher contrast sensitivity for low-vision patients than is shown by the Pelli-Robson chart. PURPOSE: This study aimed to compare the contrast sensitivity results and test/retest ±limits of agreement for the Ohio Contrast Cards and the Pelli-Robson letter contrast sensitivity chart on two challenging groups of participants, and to compare the Ohio Contrast Card results with grating acuity and the Pelli-Robson results with letter acuity. METHODS: The Ohio Contrast Card and Pelli-Robson tests were each performed twice by two different examiners within one visit on 40 elder patients in Primary Vision Care (>65 years old) and 23 to 27 low-vision school-aged students. Grating acuity was measured using the Teller Acuity Cards (all participants), and letter acuity was measured using ClearChart (elders) or the Bailey-Lovie chart (students). RESULTS: The ±95% limits of agreement were similar for the Ohio Contrast Cards and the Pelli-Robson chart. The elders' limits of agreement were ±0.27 (Ohio Contrast Cards) and ±0.28 (Pelli-Robson); the students' limits of agreement were ±0.42 (Ohio Contrast Cards) and ±0.51 (Pelli-Robson). However, Ohio Contrast Card results were 0.41 log10 Michelson units more sensitive than the Pelli-Robson chart (over one line on the Pelli-Robson chart) for the elders and 0.90 log10 Michelson units (three lines on the Pelli-Robson chart) more sensitive for the elders (0.11 and 0.6 log10 Weber units, respectively). The Pelli-Robson results were correlated with letter acuities and Ohio Contrast Card results for both groups, and the Ohio Contrast Card results were correlated with Teller Acuity Card acuities for the elders. CONCLUSIONS: The Ohio Contrast Cards and Pelli-Robson chart are similarly repeatable. Both contrast sensitivity tests can provide additional clinical information that is not available through visual acuity testing, and Ohio Contrast Card may provide additional information not available from the Pelli-Robson chart.
Assuntos
Testes Visuais , Baixa Visão , Idoso , Criança , Sensibilidades de Contraste , Humanos , Ohio , Acuidade VisualRESUMO
Repeats-in-toxin leukotoxin (LtxA) produced by the oral bacterium Aggregatibacter actinomycetemcomitans kills human leukocytes in a lymphocyte function-associated antigen 1 (LFA-1, integrin αL /ß2 )-dependent manner, although the mechanism for this interaction has not been identified. The LtxA internalisation by LFA-1-expressing cells was explored with florescence resonance energy transfer (FRET) microscopy using a cell line that expresses LFA-1 with a cyan fluorescent protein-tagged cytosolic αL domain and a yellow fluorescent protein-tagged ß2 domain. Phorbol 12-myristate 13-acetate activation of LFA-1 caused transient cytosolic domain separation. However, addition of LtxA resulted in an increase in FRET, indicating that LtxA brings the cytosolic domains closer together, compared with the inactive state. Unlike activation, this effect was not transient, lasting more than 30 min. Equilibrium constants of LtxA binding to the cytoplasmic domains of both αL and ß2 were determined using surface plasmon resonance. LtxA has a strong affinity for the cytosolic domains of both the αL and ß2 subunits (Kd = 15 and 4.2 nM, respectively) and a significantly lower affinity for the cytoplasmic domains of other integrin αM , αX , and ß3 subunits (Kd = 400, 180, and 230 nM, respectively), used as controls. Peptide fragments of αL and ß2 show that LtxA binds membrane-proximal domain of αL and intermediate domain of ß2 .
Assuntos
Aggregatibacter actinomycetemcomitans/imunologia , Exotoxinas/metabolismo , Interações Hospedeiro-Patógeno , Imunossupressores/metabolismo , Antígeno-1 Associado à Função Linfocitária/metabolismo , Transferência Ressonante de Energia de Fluorescência , Humanos , Células Jurkat , Microscopia de Fluorescência , Ligação ProteicaRESUMO
OBJECTIVES: The Centers for Disease Control and Prevention (CDC) published an evidence-based guideline on the diagnosis and management of pediatric mild traumatic brain injury (mTBI) in 2018. This commentary provides key practice takeaways for sports medicine providers outlined in the Guideline recommendations. DATA SOURCES: The CDC Pediatric mTBI Guideline was developed through a rigorous scientific process using a modified Grading of Recommendations, Assessment, Development and Evaluations (GRADE) methodology. A systematic review of the scientific literature published over a 25-year period for all causes of pediatric mTBI formed the basis of the Guideline. MAIN RESULTS: The key practice takeaways for sports medicine providers focus on preseason evaluations, neuroimaging, symptom-based assessment, managing recovery, monitoring for persistent symptoms, and return to activity, including sport and school. CONCLUSIONS: Sports medicine providers play an integral part in the implementation of evidence-based practices that promote appropriate diagnosis and management of mTBI in children. This commentary highlights key practice takeaways that sports medicine providers can implement.
Assuntos
Concussão Encefálica/diagnóstico , Concussão Encefálica/terapia , Centers for Disease Control and Prevention, U.S. , Medicina Esportiva , Criança , Humanos , Volta ao Esporte , Instituições Acadêmicas , Avaliação de Sintomas , Estados UnidosRESUMO
The "Guidelines for the Management of Pediatric Severe Traumatic Brain Injury, Third Edition: Update of the Brain Trauma Foundation Guidelines" published in Pediatric Critical Care Medicine in 2019 provides new and updated recommendations applicable to the emergency department management of children with severe traumatic brain injury. Practice-changing takeaways include specific recommendations for administration of 3% hypertonic saline, administration of seizure prophylaxis, and avoiding hyperventilation.
Assuntos
Lesões Encefálicas Traumáticas/terapia , Serviço Hospitalar de Emergência/normas , Pediatria/normas , Guias de Prática Clínica como Assunto , Criança , Escala de Coma de Glasgow , Implementação de Plano de Saúde , Humanos , Solução Salina Hipertônica/uso terapêuticoRESUMO
BACKGROUND: Transgender women of color (TWC) are an underserved population who often experience high rates of HIV and barriers to care including stigma, violence, and trauma. Few health information technology interventions are tailored to serve TWC. The purpose of this study was to inform the development of a TWC-specific telehealth intervention to increase access to care. METHODS: Formative qualitative semi-structured interviews and focus groups were conducted to develop a customized telehealth intervention for TWC. Participants were TWC ≥ 18 years living in the Washington, DC metropolitan area, with at least one structural barrier to care and clinicians ≥18 years who provide care to TWC. Transcripts were analyzed using thematic coding and content analysis; barriers for TWC were categorized into Individual, Organizational, and Environmental levels. Several day-long meetings with TWC and stakeholders were convened to develop the intervention. RESULTS: Saturation of theme on barriers to care was reached with 22 interviews. Identified barriers to service receipt included survival, instability, temporal discounting, and prioritizing hormone therapy over care, incongruence between providers and patients, pessimism, and lack of cultural competency. Each was intentionally addressed with the telehealth intervention. CONCLUSIONS: Data informed the development of an innovative and customized telehealth intervention for TWC. Through the integration of technology and peer consultant outreach, we developed a novel approach that can address population-specific challenges to care. Further development of this model may be able to improve health outcomes among TWC.
Assuntos
Etnicidade/psicologia , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Grupos Raciais/psicologia , Telemedicina/organização & administração , Pessoas Transgênero/psicologia , Adulto , Estudos Transversais , District of Columbia , Etnicidade/estatística & dados numéricos , Feminino , Grupos Focais , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Humanos , Masculino , Pesquisa Qualitativa , Grupos Raciais/estatística & dados numéricos , Pessoas Transgênero/estatística & dados numéricosRESUMO
The primary virulence factor of Vibrio cholerae, cholera toxin (CT), initiates a pathway in epithelial cells that leads to the severe diarrhoea characteristic of cholera. Secreted CT binds to GM1 on the surface of host cells to facilitate internalisation. Many bacterial toxins, including CT, have been shown to be additionally delivered via outer membrane vesicles (OMVs). A fraction of the closely related heat labile toxin produced by enterotoxigenic Escherichia coli has been demonstrated to reside on the surface of OMVs, where it binds GM1 to facilitate OMV internalisation by host cells. In this work, we investigated whether OMV-associated CT is likewise trafficked to host cells in a GM1-dependent mechanism. We demonstrated that a majority of CT is secreted in its OMV-associated form and is located exclusively inside the vesicle. Therefore, the toxin is unable to bind GM1 on the host cell surface, and the OMVs are trafficked to the host cells in a GM1-independent mechanism. These findings point to a secondary, noncompeting mechanism for secretion and delivery of CT, beyond its well-studied secretion via a Type II secretion system and underscore the importance of focusing future studies on understanding this GM1-independent delivery mechanism to fully understand Vibrio cholerae pathogenesis.
Assuntos
Toxina da Cólera/metabolismo , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/microbiologia , Gangliosídeo G(M1)/metabolismo , Vesículas Secretórias/metabolismo , Vibrio cholerae/metabolismo , Transporte Proteico , Sistemas de Secreção Tipo II/metabolismoRESUMO
OBJECTIVE: The recently published Centers for Disease Control and Prevention evidence-based guideline on pediatric mild traumatic brain injury (mTBI) was developed following an extensive review of the scientific literature. Through this review, experts identified limitations in existing pediatric mTBI research related to study setting and generalizability, mechanism of injury and age of cohorts studied, choice of control groups, confounding, measurement issues, reporting of results, and specific study design considerations. This report summarizes those limitations and provides a framework for optimizing the future quality of research conduct and reporting. RESULTS: Specific recommendations are provided related to diagnostic accuracy, population screening, prognostic accuracy, and therapeutic interventions. CONCLUSION: Incorporation of the recommended approaches will increase the yield of eligible research for inclusion in future systematic reviews and guidelines for pediatric mTBI.
Assuntos
Pesquisa Biomédica , Concussão Encefálica/terapia , Centers for Disease Control and Prevention, U.S. , Medicina Baseada em Evidências , Pesquisa Biomédica/tendências , Criança , Confiabilidade dos Dados , Medicina Baseada em Evidências/tendências , Previsões , Humanos , Projetos de Pesquisa/tendências , Estados UnidosRESUMO
BACKGROUND AND AIMS: Spontaneous subarachnoid hemorrhage (SAH) from a brain aneurysm, if untreated in the acute phase, leads to loss of functional independence in about 30% of patients and death in 27-44%. To evaluate for SAH, the American College of Emergency Physicians (ACEP) Clinical Policy recommends obtaining a non-contrast brain computed tomography (CT) scan followed by a lumbar puncture (LP) if the CT is negative. On the other hand, current evidence from prospectively collected data suggests that CT alone may be sufficient to rule out SAH in patients who present within 6 h of symptom onset while anecdotal evidence suggests that CT angiogram (CTA) may be used to detect aneurysms, which are the probable cause of SAH. Since many different options are available to emergency physicians, we examined their practice pattern variation by observing their diagnostic approaches and their adherence to the ACEP Clinical Policy. METHODS: We developed, validated, and distributed a survey to emergency physicians at three practice sites: (1) Stanford Healthcare, California, (2) Intermountain Healthcare (five emergency departments), Utah, and (3) Ottawa General Hospital, Toronto. The survey questions examined physician knowledge on CT and LP's test performance and used case-based scenarios to assess diagnostic approaches, variation in practice, and adherence to guidelines. Results were presented as proportions with 95% CIs. RESULTS: Of the 216 physicians surveyed, we received 168 responses (77.8%). The responses by site were: (1) (n = 38, 23.2%), (2) (n = 70, 42.7%), (3) (n = 56, 34.1%). To the CT and LP test performance question, most physicians indicated that CT alone detects > 90% of SAH in those with a confirmed SAH [n = 150 (89.3%, 95% CI 83.6-93.5]. To the case-based questions, most physicians indicated that they would perform a CTA along with a CT [n = 110 (65.5%, 95% CI 57.8-72.6)], some indicated a LP along with a CT [n = 57, 33.9% 95% CI 26.8-41.6)], and a few indicated both a CTA and a LP [n = 16, 9.5%, 95% CI 5.5-15.0]. We also observed practice site variation in the proportion of physicians who indicated that they would use CTA: (1) (n = 25, 65.8%), (2) (n = 54, 77.1%), and (3) (n = 28, 50.0%) (p = 0.006). CONCLUSIONS: Survey responses indicate that physicians use some or all of the imaging tests, with or without LP to diagnose SAH. We observed variation in the use of CTA by site and academic setting and divergence from ACEP Clinical Policy.