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OBJECTIVES: ST-elevation myocardial infarction (STEMI) is an Acute Myocardial Infarction (AMI) with the greatest risk of death and disability. Getting diagnosed patients rapid definitive treatment at the correct facility is crucial in improving their outcome. Using a Question-and-Answer algorithm (Mobile Priority Dispatch System (MPDS®)), trained Emergency Medical Dispatchers (EMDs) can help identifying STEMI at the time of dispatch. This can assist Emergency Medical Services (EMS) pre-planning transport to potential STEMI-receiving hospitals. The study aimed to determine whether hospital-confirmed STEMI cases transported by ambulance are associated with certain dispatch determinant codes and identify the treatments performed. METHODS: The retrospective study analyzed deidentified dispatch and hospital data of STEMI patients who were transported by Qatar's Ambulance Service between January 2018 and May 2021. Data analysis compared patient demographics with dispatch measures, considering chief complaint and determinant codes, and Percutaneous Coronary Intervention (PCI) treatment received. RESULTS: A total of 3,724 STEMI cases with MPDS® dispatch codes were retrieved. After excluding patient transfer and pandemic-related cases, a final sample of 2,607 cases was analyzed. Most STEMI patients (86.0%) were classified as high priority levels at dispatch, had chest pain as chief complaint (62.9%), and were male (90.8%). Approximately, 99.0% of the STEMI patients received PCI treatment. Distributions of STEMI cases and PCI treatment did not significantly differ by patient demographics and dispatch measures. CONCLUSIONS: Qatar's STEMI patients are more likely to be male and to receive adequate acute care irrespective of any demographic factor and despite potential language issues. This study highlights that the chief complaint may be described or interpreted differently when the questioning language is not their mother tongue, or when there is a language barrier between the caller, call taker, or when using the MPDS® protocols language or when self-translating questions instantly in another language. Therefore, EMDs should be made aware of the language differences and be encouraged to further clarify the chief complaint when appropriate. There may be a need for potential refinements of the MPDS® questioning algorithm and EMD training with AMI symptoms reinforcement. This could help improve their early identification of STEMI cases with non-classic chest pain symptoms.
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Historically, dispatch-directed cardiopulmonary resuscitation (CPR) protocols only allow chest compression instructions to be delivered for patients able to be placed in the traditional supine position. For patients who are unable to be positioned supine, the telecommunicator and caller have no option except to continue attempts to position supine, which may result in delayed or no chest compressions being delivered prior to emergency medical services arrival. Any delay or lack of bystander chest compressions may result in worsening clinical outcomes of out-of-hospital cardiac arrest (OHCA) victims. We present the first two cases, to the best of our knowledge, of successfully delivered, bystander-administered, prone CPR instructions by a trained telecommunicator for two OHCA victims unable to be positioned supine.
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Reanimação Cardiopulmonar , Serviços Médicos de Emergência , Parada Cardíaca Extra-Hospitalar , Humanos , Parada Cardíaca Extra-Hospitalar/terapia , Reanimação Cardiopulmonar/métodosRESUMO
Podoplanin, PDPN, is a mucin-type transmembrane glycoprotein widely expressed in many tissues, including lung, kidney, lymph nodes, and mineralized tissues. Its function is critical for lymphatic formation, differentiation of type I alveolar epithelial lung cells, and for bone response to biomechanical loading. It has previously been shown that Pdpn null mice die at birth due to respiratory failure emphasizing the importance of Pdpn in alveolar lung development. During the course of generation of Pdpn mutant mice, we found that most Pdpn null mice in the 129S6 and C57BL6/J mixed genetic background die at the perinatal stage, similar to previously published studies with Pdpn null mice, while all Pdpn null mice bred with Swiss outbred mice survived. Surviving mutant mice in the 129S6 and C57BL6/J mixed genetic background showed alterations in the osteocyte lacunocanalicular network, especially reduced osteocyte canaliculi in the tibial cortex with increased tibial trabecular bone. However, adult Pdpn null mice in the Swiss outbred background showed no overt differences in their osteocyte lacunocnalicular network, bone density, and no overt differences when challenged with exercise. Together, these data suggest that genetic variations present in the Swiss outbred mice compensate for the loss of function of PDPN in lung, kidney, and bone.
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Células Epiteliais Alveolares/metabolismo , Diferenciação Celular/genética , Linfangiogênese/genética , Glicoproteínas de Membrana/genética , Animais , Calcificação Fisiológica/genética , Osso Esponjoso/crescimento & desenvolvimento , Osso Esponjoso/metabolismo , Regulação da Expressão Gênica no Desenvolvimento/genética , Rim/crescimento & desenvolvimento , Pulmão/crescimento & desenvolvimento , Pulmão/metabolismo , Linfonodos/crescimento & desenvolvimento , Camundongos , Osteócitos/metabolismo , Tíbia/crescimento & desenvolvimento , Tíbia/metabolismoRESUMO
The identity of the gonads is determined by which fate, ovarian granulosa cell or testicular Sertoli cell, the bipotential somatic cell precursors choose to follow. In most vertebrates, the conserved transcription factor FOXL2 contributes to the fate of granulosa cells. To understand FOXL2 functions during gonad differentiation, we performed genome-wide analysis of FOXL2 chromatin occupancy in fetal ovaries and established a genetic mouse model that forces Foxl2 expression in the fetal testis. When FOXL2 was ectopically expressed in the somatic cell precursors in the fetal testis, FOXL2 was sufficient to repress Sertoli cell differentiation, ultimately resulting in partial testis-to-ovary sex-reversal. Combining genome-wide analysis of FOXL2 binding in the fetal ovary with transcriptomic analyses of our Foxl2 gain-of-function and previously published Foxl2 loss-of-function models, we identified potential pathways responsible for the feminizing action of FOXL2. Finally, comparison of FOXL2 genome-wide occupancy in the fetal ovary with testis-determining factor SOX9 genome-wide occupancy in the fetal testis revealed extensive overlaps, implying that antagonistic signals between FOXL2 and SOX9 occur at the chromatin level.
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Proteína Forkhead Box L2/genética , Fatores de Transcrição SOX9/genética , Processos de Determinação Sexual/genética , Diferenciação Sexual/genética , Animais , Cromatina/genética , Feminino , Desenvolvimento Fetal/genética , Feto/metabolismo , Regulação da Expressão Gênica no Desenvolvimento/genética , Genoma/genética , Gônadas/crescimento & desenvolvimento , Masculino , Camundongos , Ovário/crescimento & desenvolvimento , Ligação Proteica , Testículo/crescimento & desenvolvimento , Transcriptoma/genéticaRESUMO
Aberrant wound healing presents as inappropriate or insufficient tissue formation. Using a model of musculoskeletal injury, we demonstrate that loss of transforming growth factor-ß activated kinase 1 (TAK1) signaling reduces inappropriate tissue formation (heterotopic ossification) through reduced cellular differentiation. Upon identifying increased proliferation with loss of TAK1 signaling, we considered a regenerative approach to address insufficient tissue production through coordinated inactivation of TAK1 to promote cellular proliferation, followed by reactivation to elicit differentiation and extracellular matrix production. Although the current regenerative medicine paradigm is centered on the effects of drug treatment ("drug on"), the impact of drug withdrawal ("drug off") implicit in these regimens is unknown. Because current TAK1 inhibitors are unable to phenocopy genetic Tak1 loss, we introduce the dual-inducible COmbinational Sequential Inversion ENgineering (COSIEN) mouse model. The COSIEN mouse model, which allows us to study the response to targeted drug treatment ("drug on") and subsequent withdrawal ("drug off") through genetic modification, was used here to inactivate and reactivate Tak1 with the purpose of augmenting tissue regeneration in a calvarial defect model. Our study reveals the importance of both the "drug on" (Cre-mediated inactivation) and "drug off" (Flp-mediated reactivation) states during regenerative therapy using a mouse model with broad utility to study targeted therapies for disease. Stem Cells 2019;37:766-778.
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Regeneração Óssea/efeitos dos fármacos , Fraturas Ósseas/genética , MAP Quinase Quinase Quinases/genética , Células-Tronco Mesenquimais/enzimologia , Osteoblastos/enzimologia , Cicatrização/genética , Animais , Regeneração Óssea/genética , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , DNA Nucleotidiltransferases/genética , DNA Nucleotidiltransferases/metabolismo , Feminino , Efeito Fundador , Fraturas Ósseas/tratamento farmacológico , Fraturas Ósseas/enzimologia , Fraturas Ósseas/patologia , Regulação da Expressão Gênica , Integrases/genética , Integrases/metabolismo , MAP Quinase Quinase Quinases/antagonistas & inibidores , MAP Quinase Quinase Quinases/deficiência , Masculino , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Osteoblastos/citologia , Osteoblastos/efeitos dos fármacos , Cultura Primária de Células , Inibidores de Proteínas Quinases/farmacologia , Transdução de Sinais , Crânio/efeitos dos fármacos , Crânio/lesões , Crânio/metabolismo , Cicatrização/efeitos dos fármacosRESUMO
Introduction: One of the greatest casualty-care improvements resulting from US military operations in Iraq and Afghanistan has been the reduction of preventable death from massive extremity hemorrhage - largely due to the widespread use of limb tourniquets. More recently, tourniquet use in civilian, prehospital settings has shown promise in reducing deaths in cases of catastrophic arterial limb hemorrhage. Telephone instructions by trained emergency medical dispatchers (EMDs) on applying an available tourniquet may help achieve such a benefit.Objectives: The objective of the study was to determine whether layperson callers can effectively stop simulated bleeding using an improvised or a commercial tourniquet, when provided with scripted instructions via phone from a trained protocol-aided EMD.Methods: This was a prospective, randomized trial involving layperson volunteers, done at four locations in Salt Lake City, Utah, USA. Volunteers were assigned randomly to three groups: one for each of two commonly available commercial tourniquets and one for an improvised tourniquet.Results: A total of 246 subjects participated in the study at the four locations between February 11, 2019 and June 22, 2019. The overall median time for all trials (i.e., elapsed time from the start to the end of the simulation) was 3 minutes and 19 seconds. Median time to stop the bleeding (i.e., elapsed time from the start of the simulation to the time the participant was able to successfully stop the bleeding) was 2 minutes and 57 seconds. Median tourniquet pressure was 256 mmHg and median-end blood loss was 1,365 mL. A total of 198 participants (80.49%) were able to completely stop the bleeding while 16 participants (6.5%) had the tourniquet applied with some bleeding still occurring, and 32 participants (13.01%) exceeded the threshold of 2,500 mL of blood loss, resulting in the "patient" not surviving.Conclusions: The study findings demonstrated that untrained bystanders provided with instructions via phone from a trained Emergency Medical Dispatcher applied a tourniquet and successfully stopped the bleeding completely in most cases.
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Operador de Emergência Médica , Primeiros Socorros/métodos , Torniquetes , Serviços Médicos de Emergência , Hemorragia/terapia , Humanos , Simulação de Paciente , Estudos Prospectivos , Tempo para o Tratamento , UtahRESUMO
Objective: The aim of this study was to determine the frequency of automatic external defibrillator (AED) retrieval and placement by bystander callers when prompted by an Emergency Medical Dispatcher (EMD). Methods: This retrospective descriptive study utilized a convenience sample of emergency dispatch data collected from 23 Emergency Communication Centers (ECCs) spanning 14 states across the United States (U.S.) from July 11, 2014 to August 13, 2018, including all cases in which the EMD recorded any response to the AED availability prompt. Data were collected using ProQA, the software version of the Medical Priority Dispatch System. Primary outcome measures were (a) distribution of responses to the AED prompt; (b) percentage of cases in which an AED was retrieved; and (c) percentage of cases in which AED pads were placed by the bystander-caller. Results: A total of 2,200,285 cases were collected during the study period, in 18,904 (0.86%) of which the AED prompt was displayed (indicating suspected out of hospital cardiac arrest, or OHCA). Overall, an AED was reported as available 5.8% (n = 1,091) of the time the EMD recorded an answer to the AED prompt. In multiple-rescuer situations, a rescuer was sent to get the AED 2.8% (n = 523) of the time, as opposed to only 0.30% (n = 56) for single-rescuer calls. The AED was reported to be already on scene, by the patient, in 2.7% (n = 512) of the cases. A majority (72.0%; n = 417) of the time, rescuers who were sent to get an AED were unable to retrieve it, with single rescuers being successful more often (57.1% unable to retrieve, vs 73.6% for multiple rescuers). Conclusions: AEDs are reported as available by only a small percentage of callers to 911, and in the majority of cases in which a bystander rescuer is sent to retrieve an AED, one is never located or used. Sending someone to retrieve the AED may be more appropriate in multiple-rescuer situations than when a single bystander rescuer is alone on scene.
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Reanimação Cardiopulmonar/estatística & dados numéricos , Desfibriladores/estatística & dados numéricos , Despacho de Emergência Médica , Serviços Médicos de Emergência/estatística & dados numéricos , Parada Cardíaca Extra-Hospitalar/terapia , Sistemas de Comunicação entre Serviços de Emergência , Feminino , Humanos , Masculino , Parada Cardíaca Extra-Hospitalar/diagnóstico , Parada Cardíaca Extra-Hospitalar/epidemiologia , Estudos Retrospectivos , Estados UnidosRESUMO
Ellis-van Creveld (EvC) syndrome is a skeletal dysplasia, characterized by short limbs, postaxial polydactyly, and dental abnormalities. EvC syndrome is also categorized as a ciliopathy because of ciliary localization of proteins encoded by the two causative genes, EVC and EVC2 (aka LIMBIN). While recent studies demonstrated important roles for EVC/EVC2 in Hedgehog signaling, there is still little known about the pathophysiological mechanisms underlying the skeletal dysplasia features of EvC patients, and in particular why limb development is affected, but not other aspects of organogenesis that also require Hedgehog signaling. In this report, we comprehensively analyze limb skeletogenesis in Evc2 mutant mice and in cell and tissue cultures derived from these mice. Both in vivo and in vitro data demonstrate elevated Fibroblast Growth Factor (FGF) signaling in Evc2 mutant growth plates, in addition to compromised but not abrogated Hedgehog-PTHrP feedback loop. Elevation of FGF signaling, mainly due to increased Fgf18 expression upon inactivation of Evc2 in the perichondrium, critically contributes to the pathogenesis of limb dwarfism. The limb dwarfism phenotype is partially rescued by inactivation of one allele of Fgf18 in the Evc2 mutant mice. Taken together, our data uncover a novel pathogenic mechanism to understand limb dwarfism in patients with Ellis-van Creveld syndrome.
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Nanismo/genética , Síndrome de Ellis-Van Creveld/genética , Fatores de Crescimento de Fibroblastos/genética , Proteínas de Membrana/genética , Animais , Modelos Animais de Doenças , Nanismo/patologia , Síndrome de Ellis-Van Creveld/patologia , Fatores de Crescimento de Fibroblastos/biossíntese , Lâmina de Crescimento/crescimento & desenvolvimento , Lâmina de Crescimento/patologia , Humanos , Peptídeos e Proteínas de Sinalização Intercelular , Proteínas de Membrana/biossíntese , Camundongos , Proteínas Mutantes/biossíntese , Proteínas Mutantes/genética , Polidactilia/genética , Polidactilia/patologia , Transdução de Sinais , Anormalidades Dentárias/genética , Anormalidades Dentárias/patologiaRESUMO
P0-Cre and Wnt1-Cre mouse lines have been widely used in combination with loxP-flanked mice to label and genetically modify neural crest (NC) cells and their derivatives. Wnt1-Cre has been regarded as the gold standard and there have been concerns about the specificity of P0-Cre because it is not clear about the timing and spatial distribution of the P0-Cre transgene in labeling NC cells at early embryonic stages. We re-visited P0-Cre and Wnt1-Cre models in the labeling of NC cells in early mouse embryos with a focus on cranial NC. We found that R26-lacZ Cre reporter responded to Cre activity more reliably than CAAG-lacZ Cre reporter during early embryogenesis. Cre immunosignals in P0-Cre and reporter (lacZ and RFP) activity in P0-Cre/R26-lacZ and P0-Cre/R26-RFP embryos was detected in the cranial NC and notochord regions in E8.0-9.5 (4-19 somites) embryos. P0-Cre transgene expression was observed in migrating NC cells and was more extensive in the forebrain and hindbrain but not apparent in the midbrain. Differences in the Cre distribution patterns of P0-Cre and Wnt1-Cre were profound in the midbrain and hindbrain regions, that is, extensive in the midbrain of Wnt1-Cre and in the hindbrain of P0-Cre embryos. The difference between P0-Cre and Wnt1-Cre in labeling cranial NC may provide a better explanation of the differential distributions of their NC derivatives and of the phenotypes caused by Cre-driven genetic modifications.
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Crista Neural/citologia , Células-Tronco Neurais/citologia , Neurogênese , Animais , Linhagem da Célula , Integrases/genética , Integrases/metabolismo , Mesencéfalo/citologia , Camundongos , Camundongos Endogâmicos C57BL , Crista Neural/embriologia , Crista Neural/metabolismo , Células-Tronco Neurais/metabolismo , Prosencéfalo/citologia , Transgenes , Proteína Wnt1/genética , Proteína Wnt1/metabolismoRESUMO
OBJECTIVE: Chest pain is one of the most common reasons people seek emergency care-and one of the most critical. In the United States, chest pain is the second most common reason for emergency department (ED) visits. A patient's primary complaint of "chest pain" may reflect a broad range of underlying causes; therefore, it is important that emergency medical service (EMS) agencies gain a thorough understanding of these cases, beginning with the initial management of chest pain in the 9-1-1 center. The primary objective of this study was to compare hospital-confirmed patient discharge diagnoses to all calls handled by emergency medical dispatchers (EMDs) using the Chest Pain/Chest Discomfort (Non-Traumatic) Chief Complaint Protocol. METHODS: The retrospective descriptive study utilized emergency medical dispatch, EMS, and hospital datasets, collected at two emergency communication centers in North America, from January 1, 2013 to December 31, 2014. Patients who were dispatched using the Chest Pain/Chest Discomfort Chief Complaint Protocol and matched to hospital datasets were included. The primary outcome was the number and percentage of cases classified as ischemic heart disease (IHD), other cardiac-related conditions, or non-cardiac-related conditions associated with chest pain. We also evaluated the distribution of causes of chest pain across demographic indicators and dispatch determinants. RESULTS: 3,007 cases were identified as "chest pain" at dispatch for which corresponding hospital records were identified. Cases in the study were obtained by linking EMS/Hospital and Emergency Medical Dispatch datasets. Of these cases, 47.1% (n = 1,417) were due to cardiac-related causes of chest pain, 61.5% of which were Ischemic Heart Disease (IHD), while the rest had other cardiac-related causes. Of the IHDs, 32.1% were Acute Myocardial Infarction (AMI). CONCLUSIONS: Underlying causes of non-traumatic chest pain reported to 9-1-1 demonstrate a wide range of etiologies, with a mix similar to that of chest pain patients in several other healthcare settings, including hospital emergency departments. Most IHD events are triaged by EMDs to the (highest) DELTA priority level, while the CHARLIE level captures nearly all of the remaining IHD cases.
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Dor no Peito/diagnóstico , Serviços Médicos de Emergência/estatística & dados numéricos , Triagem/métodos , Adolescente , Adulto , Idoso , Dor no Peito/etiologia , Criança , Pré-Escolar , Bases de Dados Factuais , Serviços Médicos de Emergência/métodos , Serviço Hospitalar de Emergência , Feminino , Hospitais , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , América do Norte , Alta do Paciente/estatística & dados numéricos , Estudos Retrospectivos , Triagem/estatística & dados numéricos , Estados Unidos , Adulto JovemRESUMO
BACKGROUND: Early hospital notification of a possible stroke arriving via emergency medical services (EMS) can prepare stroke center personnel for timely treatment, especially timely administration of tissue plasminogen activator. Stroke center notification from the emergency dispatch center-before responders reach the scene-may promote even earlier and faster system activation, meaning that stroke center teams may be ready to receive patients as soon as the ambulance arrives. This study evaluates the use of a Medical Priority Dispatch System (MPDS; Priority Dispatch Corp., Salt Lake City, UT) Stroke Diagnostic Tool (SDxT) to identify possible strokes early by comparing the tools' results to on-scene and hospital findings. METHODS: The retrospective descriptive study utilized stroke data from 3 sources: emergency medical dispatch, EMS, and emergency department/hospital. RESULTS: A total of 830 cases were collected between June 2012 and December 2013, of which 603 (72.7%) had matching dispatch records. Of the 603 cases, 304 (50.4%) were handled using MPDS Stroke Protocol 28. The SDxT had an 86.4% ability (OR [95% CI]: 2.3 [1.5, 3.5]) to effectively identify strokes among all the hospital-confirmed stroke cases (sensitivity), and a 26.6% ability to effectively identify nonstrokes among all the hospital-confirmed nonstroke cases (specificity). CONCLUSIONS: The SDxT demonstrated a very high sensitivity, compared to similar tools used in the field and at dispatch. The specificity was somewhat low, but this was expected-and is intended in the creation of protocols to be used over the phone in emergency situations. The tool is a valuable method for identifying strokes early and may allow early hospital notification.
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Despacho de Emergência Médica/métodos , Índice de Gravidade de Doença , Acidente Vascular Cerebral/diagnóstico , Sistemas de Comunicação entre Serviços de Emergência , Feminino , Hospitais , Humanos , Masculino , Valor Preditivo dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade , Acidente Vascular Cerebral/terapia , Resultado do TratamentoRESUMO
Ellis-van Creveld (EvC) syndrome (OMIM 225500) is an autosomal recessive disease characterized with chondrodysplastic dwarfism in association with abnormalities in oral cavity. Ciliary proteins EVC and EVC2 have been identified as causative genes and they play an important role on Hedgehog signal transduction. We have also identified a causative gene LIMBIN for bovine chondrodysplastic dwarfism (bcd) that is later identified as the bovine ortholog of EVC2. Here, we report generation of conventional and conditional mutant Evc2/Limbin alleles that mimics mutations found in EvC patients and bcd cattle. Resulted homozygous mice showed no ciliary localization of EVC2 and EVC and displayed reduced Hedgehog signaling activity in association with skeletal and oral defects similar to the EvC patients. Cartilage-specific disruption of Evc2/Limbin resulted in similar but milder skeletal defects, whereas osteoblast-specific disruption did not cause overt changes in skeletal system. Neural crest-specific disruption of Evc2/Limbin resulted in defective incisor growth similar to that seen in conventional knockouts; however, differentiation of amelobolasts was relatively normal in the conditional knockouts. These results showcased functions of EVC2/LIMBIN during formation of mineralized tissues. Availability of the conditional allele for this gene should facilitate further detailed analyses of the role of EVC2/LIMBIN in pathogenesis of EvC syndrome. genesis 53:612-626, 2015. © 2015 Wiley Periodicals, Inc.
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We generated a new Bmp2 conditional-knockout allele without a neo cassette that removes the Bmp2 gene from osteoblasts (Bmp2-cKO(ob)) using the 3.6Col1a1-Cre transgenic model. Bones of Bmp2-cKO(ob) mice are thinner, with increased brittleness. Osteoblast activity is reduced as reflected in a reduced bone formation rate and failure to differentiate to a mature mineralizing stage. Bmp2 in osteoblasts also indirectly controls angiogenesis in the periosteum and bone marrow. VegfA production is reduced in Bmp2-cKO(ob) osteoblasts. Deletion of Bmp2 in osteoblasts also leads to defective mesenchymal stem cells (MSCs), which correlates with the reduced microvascular bed in the periosteum and trabecular bones. Expression of several MSC marker genes (α-SMA, CD146 and Angiopoietin-1) in vivo, in vitro CFU assays and deletion of Bmp2 in vitro in α-SMA(+) MSCs support our conclusions. Critical roles of Bmp2 in osteoblasts and MSCs are a vital link between bone formation, vascularization and mesenchymal stem cells.
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Proteína Morfogenética Óssea 2/metabolismo , Células-Tronco Mesenquimais/metabolismo , Neovascularização Patológica/metabolismo , Osteoblastos/metabolismo , Animais , Diferenciação Celular , Células-Tronco Mesenquimais/fisiologia , Camundongos , Periósteo , Transdução de SinaisRESUMO
BACKGROUND: Hepatitis B virus (HBV) is a vaccine preventable infection yet vaccination rates are low among injection drug users (IDUs) despite the high risk of infection and longstanding recommendations to promote vaccination. We sought to improve vaccination rates by reaching IDUs through syringe exchange programs (SEPs) in three U.S. cities. METHODS: IDUs were randomized in a trial comparing the standard HBV vaccination schedule (0, 1, and 6 months) to an accelerated schedule (0, 1, and 2 months) and participation data were analyzed to identify determinants of completion of the three-dose vaccine series. Independent variables explored included sociodemographics, injection and syringe access behaviors, assessment of health beliefs, HBV-associated knowledge, and personal health status. RESULTS: Covariates associated with completion of the three-dose vaccine series were accelerated vaccine schedule (aOR 1.92, 95% CI 1.34, 2.58, p = <0.001), older age (aOR 1.05, 95% CI 1.03, 1.07, p = <0.001), and poorer self-rated health score (aOR 1.26, 95% CI 1.05, 1.5, p = 0.02). Completion was less likely for those getting syringes from SEP customers than for SEP customers (OR 0.33, 95% CI 0.19, 0.58, p = <0.001). CONCLUSIONS: SEPs should offer hepatitis vaccination in a manner that minimizes time between first and last visits by accelerating the dosing schedule. Public health interventions should target younger, less healthy, and non-SEP customer participants. Other health interventions at SEPs may benefit from similar approaches that reach out beyond regular SEP customers.
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Usuários de Drogas , Vacinas contra Hepatite B/administração & dosagem , Vírus da Hepatite B , Hepatite B/prevenção & controle , Programas de Troca de Agulhas , Abuso de Substâncias por Via Intravenosa , Vacinação , Adolescente , Adulto , Fatores Etários , Idoso , Cidades , Feminino , Nível de Saúde , Hepatite B/etiologia , Hepatite B/imunologia , Hepatite B/virologia , Vírus da Hepatite B/imunologia , Humanos , Esquemas de Imunização , Masculino , Pessoa de Meia-Idade , Razão de Chances , Abuso de Substâncias por Via Intravenosa/complicações , Seringas , Estados Unidos , Adulto JovemRESUMO
INTRODUCTION: Diabetes mellitus, although a chronic disease, also can cause acute, sudden symptoms requiring emergency intervention. In these cases, Emergency Medical Dispatchers (EMDs) must identify true diabetic complaints in order to determine the correct care. In 911 systems utilizing the Medical Priority Dispatch System (MPDS), International Academies of Emergency Dispatch-certified EMDs determine a patient's chief complaint by matching the caller's response to an initial pre-scripted question to one of 37 possible chief complaints protocols. The ability of EMDs to identify true diabetic-triggered events reported through 911 has not been studied. OBJECTIVE: The primary objective of this study was to determine the percentage of EMD-recorded patient cases (using the Diabetic Problems protocol in the MPDS) that were confirmed by either attending paramedics or the hospital as experiencing a diabetic-triggered event. METHODS: This was a retrospective study involving six hospitals, one fire department, and one ambulance service in Salt Lake City, Utah USA. Dispatch data for one year recorded under the Diabetic Problems protocol, along with the associated paramedic and hospital outcome data, were reviewed/analyzed. The outcome measures were: the percentage of cases that had diabetic history, percentage of EMD-identified diabetic problems cases that were confirmed by Emergency Medical Services (EMS) and/or hospital records as true diabetic-triggered events, and percentage of EMD-identified diabetic patients who also had other medical conditions. A diabetic-triggered event was defined as one in which the patient's emergency was directly caused by diabetes or its medical management. Descriptive statistics were used for categorical measures and parametric statistical methods assessed the differences between study groups, for continuous measures. RESULTS: Three-hundred ninety-three patient cases were assigned to the Diabetic Problems Chief Complaint protocol. Of the 367 (93.4%) patients who had a documented history of diabetes, 279 (76%) were determined to have had a diabetic-triggered event. However, only 12 (3.6%) initially assigned to this protocol did not have a confirmed history of diabetes. CONCLUSIONS: Using the MPDS to select the Diabetic Problems Chief Complaint protocol, the EMDs correctly identified a true diabetic-triggered event the majority of the time. However, many patients had other medical conditions, which complicated the initial classification of true diabetic-triggered events. Future studies should examine the associations between the five specific Diabetic Problems Chief Complaint protocol determinant codes (triage priority levels) and severity measures, eg, blood sugar level and Glasgow Coma Score.
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Complicações do Diabetes/terapia , Diabetes Mellitus/terapia , Sistemas de Comunicação entre Serviços de Emergência/normas , Serviços Médicos de Emergência/normas , Avaliação de Processos e Resultados em Cuidados de Saúde , Triagem/normas , Humanos , Estudos Retrospectivos , UtahRESUMO
Recent studies indicate that, similar to other covalent modifications, histone lysine methylation is subject to enzyme-catalysed reversion. So far, LSD1 (also known as AOF2) and the jumonji C (JmjC)-domain-containing proteins have been shown to possess histone demethylase activity. LSD1 catalyses removal of H3K4me2/H3K4me1 through a flavin-adenine-dinucleotide-dependent oxidation reaction. In contrast, JmjC-domain-containing proteins remove methyl groups from histones through a hydroxylation reaction that requires alpha-ketoglutarate and Fe(II) as cofactors. Although an increasing number of histone demethylases have been identified and biochemically characterized, their biological functions, particularly in the context of an animal model, are poorly characterized. Here we use a loss-of-function approach to demonstrate that the mouse H3K9me2/1-specific demethylase JHDM2A (JmjC-domain-containing histone demethylase 2A, also known as JMJD1A) is essential for spermatogenesis. We show that Jhdm2a-deficient mice exhibit post-meiotic chromatin condensation defects, and that JHDM2A directly binds to and controls the expression of transition nuclear protein 1 (Tnp1) and protamine 1 (Prm1) genes, the products of which are required for packaging and condensation of sperm chromatin. Thus, our work uncovers a role for JHDM2A in spermatogenesis and reveals transition nuclear protein and protamine genes as direct targets of JHDM2A.
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Proteínas Cromossômicas não Histona/genética , Histonas/metabolismo , Oxirredutases N-Desmetilantes/metabolismo , Protaminas/genética , Espermatogênese , Transcrição Gênica , Alelos , Animais , Cromatina/genética , Cromatina/metabolismo , Histona Desmetilases com o Domínio Jumonji , Masculino , Meiose , Metilação , Camundongos , Mutação/genética , Oxirredutases N-Desmetilantes/genética , Espermátides/citologia , Espermátides/metabolismo , Espermátides/patologiaRESUMO
BACKGROUND: The American College of Cardiology and the American Heart Association recommend early aspirin administration to patients with symptoms of acute coronary syndrome (ACS)/acute myocardial infarction (AMI). The primary objective of this study was to determine if Emergency Medical Dispatchers (EMD) can provide chest pain/heart attack patients with standardised instructions effectively, using an aspirin diagnostic and instruction tool (ADxT) within the Medical Priority Dispatch System (MPDS) before arrival of an emergency response crew. METHODS: This retrospective study involved three dispatch centres in the UK and USA. We analysed 6 months of data involving chest pain/heart attack symptoms taken using the MPDS chest pain and heart problems/automated internal cardiac defibrillator protocols. RESULTS: The EMDs successfully completed the ADxT on 69.8% of the 44141 cases analysed. The patient's mean age was higher when the ADxT was completed, than when it was not (mean ± SD: 53.9 ± 19.9 and 49.9 ± 20.2; p<0.001, respectively). The ADxT completion rate was higher for second-party than first-party calls (70.3% and 69.0%; p=0.024, respectively). A higher percentage of male than female patients took aspirin (91.3% and 88.9%; p=0.001, respectively). Patients who took aspirin were significantly younger than those who did not (mean ± SD: 61.8 ± 17.5 and 64.7 ± 17.9, respectively). Unavailability of aspirin was the major reason (44.4%) why eligible patients did not take aspirin when advised. CONCLUSIONS: EMDs, using a standardised protocol, can enable early aspirin therapy to treat potential ACS/AMI prior to responders' arrival. Further research is required to assess reasons for not using the protocol, and the significance of the various associations discovered.
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Síndrome Coronariana Aguda/diagnóstico , Aspirina/administração & dosagem , Sistemas de Comunicação entre Serviços de Emergência/normas , Socorristas/psicologia , Fidelidade a Diretrizes , Infarto do Miocárdio/diagnóstico , Avaliação de Processos e Resultados em Cuidados de Saúde , Síndrome Coronariana Aguda/tratamento farmacológico , Dor no Peito/complicações , Dor no Peito/diagnóstico , Serviços Médicos de Emergência , Feminino , Guias como Assunto , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/tratamento farmacológico , Estudos Retrospectivos , Triagem , Reino Unido , Estados UnidosRESUMO
INTRODUCTION: The Breathing Problems Chief Complaint (CC) protocol in the Medical Priority Dispatch System (MPDS) was the system's most frequently used protocol. While "severe breathing problems" is a significant predictor of cardiac arrest (CA), previous data have demonstrated that the DELTA-level determinant codes in this CC contain patients across a wide spectrum of acuity. HYPOTHESIS: The hypothesis in this study was that certain combinations of caller answers to the breathing problems protocol key questions (KQs) are correlated with different but specific patient acuities. METHODS: This was a retrospective study conducted at one International Academies of Emergency Dispatch (IAED) Accredited Center of Excellence. Key Question combinations were generated and analyzed from 11 months of dispatch data, and extracted from MPDS software and the computer assisted dispatch system. Descriptive statistics were used to evaluate measures between study groups. RESULTS: Forty-two thousand cases were recorded; 52% of patients were female and the median age was 61 years. Overall, based on the original MPDS Protocol (before generating KQ combinations), patients with abnormal breathing and clammy conditions were the youngest. The MPDS DELTA-level constituted the highest percentage of cases (74.0%) and the difficulty speaking between breaths (DSBB) condition was the most prevalent (50.3%). Ineffective breathing and not alert conditions had the highest cardiac arrest quotient (CAQ). Based on the KQ combinations, the CA patients who also had the not alert condition were significantly older than other patients. The percentage of CA outcomes in asthmatic patients was significantly higher in DSBB plus not alert; DSBB plus not alert plus changing color; and DSBB plus not alert plus clammy conditions cases, compared to asthmatic abnormal breathing cases. CONCLUSIONS: The study findings demonstrated that MPDS KQ answer combinations relate to patient acuity. Cardiac arrest patients are significantly less likely to be asthmatic than those without CA, and vice versa. Using a prioritization scheme that accounts for the presence of either single or multiple signs and/or symptom combinations for the Breathing Problems CC protocol would be a more accurate method of assigning DELTA-level cases in the MPDS.
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Protocolos Clínicos/normas , Sistemas de Comunicação entre Serviços de Emergência , Parada Cardíaca/diagnóstico , Transtornos Respiratórios/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Índice de Gravidade de Doença , Inquéritos e Questionários , Triagem/métodos , Reino UnidoRESUMO
INTRODUCTION: Knowing the pulse rate of a patient in a medical emergency can help to determine patient acuity and the level of medical care required. Little evidence exists regarding the ability of a 911 layperson-caller to accurately determine a conscious patient's pulse rate. Hypothesis The hypothesis of this study was that, when instructed by a trained emergency medical dispatcher (EMD) using the scripted Medical Priority Dispatch System (MPDS) protocol Pulse Check Diagnostic Tool (PCDxT), a layperson-caller can detect a carotid pulse and accurately determine the pulse rate in a conscious person. METHODS: This non-randomized and non-controlled prospective study was conducted at three different public locations in the state of Utah (USA). A healthy, mock patient's pulse rate was obtained using an electrocardiogram (ECG) monitor. Layperson-callers, in turn, initiated a simulated 911 phone call to an EMD call-taker who provided instructions for determining the pulse rate of the patient. Layperson accuracy was assessed using correlations between the layperson-caller's finding and the ECG reading. RESULTS: Two hundred sixty-eight layperson-callers participated; 248 (92.5%) found the pulse of the mock patient. There was a high correlation between pulse rates obtained using the ECG monitor and those found by the layperson-callers, overall (94.6%, P < .001), and by site, gender, and age. CONCLUSIONS: Layperson-callers, when provided with expert, scripted instructions by a trained 911 dispatcher over the phone, can accurately determine the pulse rate of a conscious and healthy person. Improvements to the 911 instructions may further increase layperson accuracy.
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Artérias Carótidas , Sistemas de Comunicação entre Serviços de Emergência , Pulso Arterial , Adolescente , Adulto , Protocolos Clínicos , Eletrocardiografia , Feminino , Humanos , Masculino , Simulação de Paciente , Estudos Prospectivos , Medição de Risco , Interface Usuário-ComputadorRESUMO
â¢We developed a two-session behavioral intervention to prevent HCV reinfection.â¢The intervention was piloted at an OTP and integrated into HCV treatment.â¢Baseline data showed limited knowledge & application of safer injection practices.â¢Implementation barriers included logistics and the lack of financial incentive.â¢Adaptations addressed barriers, yielding a more feasible and acceptable intervention.