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1.
BMJ Glob Health ; 8(1)2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36707093

RESUMO

Unexpected pathogen transmission between animals, humans and their shared environments can impact all aspects of society. The Tripartite organisations-the Food and Agriculture Organization of the United Nations (FAO), the World Health Organization (WHO), and the World Organisation for Animal Health (WOAH)-have been collaborating for over two decades. The inclusion of the United Nations Environment Program (UNEP) with the Tripartite, forming the 'Quadripartite' in 2021, creates a new and important avenue to engage environment sectors in the development of additional tools and resources for One Health coordination and improved health security globally. Beginning formally in 2010, the Tripartite set out strategic directions for the coordination of global activities to address health risks at the human-animal-environment interface. This paper highlights the historical background of this collaboration in the specific area of health security, using country examples to demonstrate lessons learnt and the evolution and pairing of Tripartite programmes and processes to jointly develop and deliver capacity strengthening tools to countries and strengthen performance for iterative evaluations. Evaluation frameworks, such as the International Health Regulations (IHR) Monitoring and Evaluation Framework, the WOAH Performance of Veterinary Services (PVS) Pathway and the FAO multisectoral evaluation tools for epidemiology and surveillance, support a shared global vision for health security, ultimately serving to inform decision making and provide a systematic approach for improved One Health capacity strengthening in countries. Supported by the IHR-PVS National Bridging Workshops and the development of the Tripartite Zoonoses Guide and related operational tools, the Tripartite and now Quadripartite, are working alongside countries to address critical gaps at the human-animal-environment interface.


Assuntos
Saúde Única , Animais , Humanos , Organização Mundial da Saúde , Saúde Global , Nações Unidas , Regulamento Sanitário Internacional
2.
Prehosp Emerg Care ; 27(7): 955-966, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36264569

RESUMO

OBJECTIVES: The objectives of this study were to describe the characteristics, management, and outcomes of patients treated by paramedics for hypoglycemia, and to determine the predictors of hospital admission for these patients within 72 hours of the initial hypoglycemia event. METHODS: We performed a health record review of paramedic call reports and emergency department records over a 12-month period. We queried prehospital databases to identify cases, which included all patients ⩾18 years with prehospital glucose readings of <72 mg/dl (<4.0 mmol/L) and excluded terminally ill and cardiac arrest patients. We developed and piloted a standardized data collection tool and obtained consensus on all data definitions before initiation of data extraction by trained investigators. Data analyses included descriptive statistics univariate and logistic regression presented as adjusted odds ratios (aOR) with 95% confidence intervals (95%CI). RESULTS: There were 791 patients with the following characteristics: mean age 56.2, male 52.3%, type 1 diabetes 11.6%, on insulin 43.3%, median initial glucose 54.0 mg/dl (3.0 mmol/L), from home 56.4%. They were treated by advanced care paramedics 80.1%, received intravenous D50 37.8%, intramuscular glucagon 17.8%, oral complex carbs/protein 25.7%, and accepted transport to hospital 70.2%. Among those transported, 134 (24.3%) were initially admitted and four more were admitted within 72 hours. One patient was admitted, discharged, and admitted again within 72 hours. Patients without documented histories of diabetes (aOR 2.35, CI 1.13-4.86), with cardiovascular disease (aOR 1.81, CI 1.10-3.00), on corticosteroids (aOR 4.63, CI 2.15-9.96), on oral hypoglycemic agent(s) (aOR 1.92, CI 1.02-3.62), or those given glucagon (aOR 1.77, CI 1.07-2.93) on scene were more likely to be admitted to hospital, whereas patients on insulin (aOR 0.49, CI 0.27-0.91), able to tolerate complex oral carbs/protein (aOR 0.22, CI 0.10-0.48), with final GCS scores of 15 (aOR 0.53, CI 0.34-0.83), or from public locations (aOR 0.40, CI 0.21-0.75) were less likely to be admitted. CONCLUSIONS: There are several patient and prehospital management characteristics which, in combination, could be incorporated into a safe clinical decision tool for patients who present with hypoglycemia.


Assuntos
Diabetes Mellitus , Serviços Médicos de Emergência , Hipoglicemia , Insulinas , Humanos , Masculino , Pessoa de Meia-Idade , Glucagon , Paramédico , Hipoglicemia/terapia , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/epidemiologia , Glucose , Hospitais
3.
Ann Emerg Med ; 81(2): 187-196, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36328852

RESUMO

STUDY OBJECTIVE: The Canadian C-spine rule was modified and validated for use by the paramedics in a multicenter study where patients were assessed with the Canadian C-spine rule yet all transported with immobilization. This study evaluated the clinical impact of the modified Canadian C-spine rule when implemented by paramedics. METHODS: This single-center prospective cohort implementation study took place in Ottawa, Canada (from 2011 to 2015). Advanced and primary care paramedics were trained to use the modified Canadian C-spine rule, collect data on a standardized study form, and selectively transport eligible patients without immobilization. We evaluated all consecutive low-risk adult patients (Glasgow Coma Scale [GCS] 15, stable vital signs) at risk for a neck injury. We followed all patients without initial radiologic evaluation for 30 days. Analyses included descriptive statistics with 95% confidence intervals (CI), sensitivity, specificity, and kappa coefficients. RESULTS: The 4,034 enrolled patients had a mean age of 43 (range 16 to 99), and 53.4% were female. Motor vehicle collisions were the most common mechanism of injury (55.1%), followed by falls (23.9%). There were 11 clinically important injuries. The paramedics classified these injuries with a sensitivity of 90.9% (95% CI, 58.7 to 99.8) and specificity of 66.5% (95% CI, 65.1 to 68.0). There was no adverse event or resulting spinal cord injury. The kappa agreement between paramedics and investigators was 0.94. A total of 2,583 (64.0%) immobilizations were avoided using the modified Canadian C-spine rule. CONCLUSION: Paramedics could accurately apply the modified Canadian C-spine rule to low-risk trauma patients and significantly reduce the need for spinal immobilization during transport. This resulted in no adverse event or any spinal cord injury.


Assuntos
Traumatismos da Medula Espinal , Traumatismos da Coluna Vertebral , Adulto , Humanos , Feminino , Masculino , Estudos Prospectivos , Paramédico , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/lesões , Traumatismos da Coluna Vertebral/diagnóstico por imagem , Canadá
4.
Sci Rep ; 12(1): 8588, 2022 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-35597789

RESUMO

Effectively preventing and controlling zoonotic diseases requires a One Health approach that involves collaboration across sectors responsible for human health, animal health (both domestic and wildlife), and the environment, as well as other partners. Here we describe the Generalizable One Health Framework (GOHF), a five-step framework that provides structure for using a One Health approach in zoonotic disease programs being implemented at the local, sub-national, national, regional, or international level. Part of the framework is a toolkit that compiles existing resources and presents them following a stepwise schematic, allowing users to identify relevant resources as they are required. Coupled with recommendations for implementing a One Health approach for zoonotic disease prevention and control in technical domains including laboratory, surveillance, preparedness and response, this framework can mobilize One Health and thereby enhance and guide capacity building to combat zoonotic disease threats at the human-animal-environment interface.


Assuntos
Saúde Única , Animais , Animais Selvagens , Fortalecimento Institucional , Laboratórios , Zoonoses/epidemiologia , Zoonoses/prevenção & controle
5.
Prehosp Emerg Care ; 26(3): 428-436, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35191797

RESUMO

Context: As many as 14% of patients transported by ambulance with chest pain die prior to hospital discharge. To date, no high-quality controlled trials have revealed that prehospital advanced life support interventions affect survival for these patients. Objective: The Ontario Prehospital Advanced Life Support (OPALS) Study assessed the effect of adding an advance life support service to an existing basic life support emergency medical service program, on the rate of mortality and morbidity for patients with out-of-hospital chest pain. Design: Controlled clinical trial comparing survival for 9 months before and 9 after instituting an advanced life support program. Setting: Thirteen urban and suburban Ontario communities (populations ranging from 30,000 to 750,000; total, 2.5 million). Patients: All adult patients with a primary complaint of chest pain and transported by paramedics to the emergency department. Intervention: Paramedics were trained in standard advanced life support, which includes endotracheal intubation, intravenous furosemide and morphine, oral ASA, and sublingual NTG. Emergency medical services within each community had to meet predefined criteria in order to qualify for the advanced life support phase. Main Outcome Measure: Survival to hospital discharge. Results: Overall, 12,168 patients were enrolled in either the basic life support phase (N = 5,788) or the advanced life support phase (N = 6,380). The rate of mortality significantly decreased from 4.3% in the basic life support phase to 3.2% in the advanced life support phase (absolute change 1.1, 95% CI 0.4-1.8, P = 0.0013). We also demonstrated a decrease in mortality for the subgroup of patients with a discharge diagnosis of myocardial infarction (13.1 percent vs 8.2 percent, P = 0.002). Conclusions: The addition of a prehospital advanced life support program to an existing basic life support emergency medical service was associated with a significant decrease in the mortality rate among patients complaining of chest pain. Future research should clarify the most effective interventions and target specific populations.


Assuntos
Serviços Médicos de Emergência , Adulto , Ambulâncias , Dor no Peito/terapia , Hospitais , Humanos , Ontário
6.
Biochemistry ; 60(7): 500-512, 2021 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-33557518

RESUMO

We previously reported a family of hydrocarbon-stapled peptides designed to interact with the epidermal growth factor receptor (EGFR) juxtamembrane (JM) segment, blocking its ability to form a coiled coil dimer that is essential for receptor activation. These hydrocarbon-stapled peptides, most notably E1S, decreased the proliferation of cell lines that express wild-type EGFR (H2030 and A431) as well as those expressing the oncogenic mutants EGFR L858R (H3255) and L858R/T790M (H1975). Although our previous investigations provided evidence that E1S interacted with EGFR directly, the location and details of these interactions were not established. Here we apply biochemical and cross-linking mass spectrometry tools to better define the interactions between E1S and EGFR. Taken with previously reported structure-activity relationships, our results support a model in which E1S interacts simultaneously with both the JM and the C-lobe of the activator kinase, effectively displacing the JM of the receiver kinase. Our results also reveal potential interactions between E1S and the N-terminal region of the C-terminal tail. We propose a model in which E1S inhibits EGFR by both mimicking and inhibiting JM coiled coil formation. This model could be used to design novel, allosteric (and perhaps nonpeptidic) EGFR inhibitors.


Assuntos
Receptores ErbB/antagonistas & inibidores , Receptores ErbB/química , Receptores ErbB/metabolismo , Sequência de Aminoácidos/genética , Linhagem Celular Tumoral , Membrana Celular/metabolismo , Receptores ErbB/genética , Humanos , Mutação , Inibidores de Proteínas Quinases/química , Relação Estrutura-Atividade
7.
Prehosp Emerg Care ; 23(3): 364-376, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30111210

RESUMO

BACKGROUND: In Ontario, Canada, there currently are no prehospital treat-and-release protocols and the safety of this practice remains unclear. We sought to describe the characteristics, management, and outcomes of patients with hypoglycemia treated by paramedics, and to determine the predictors of repeat access to prehospital or emergency department (ED) care within 72 hours of initial paramedic assessment. METHODS: We performed a health record review of paramedic call reports and ED records over a 12-month period. We queried prehospital databases to identify cases, which included all adult patients (≥ 18 years) with a prehospital glucose reading of <72mg/dl (4.0mmol/L) and excluded terminally ill and cardiac arrest patients. We developed and piloted a standardized data collection tool and obtained consensus on all data definitions before initiation of data extraction by trained investigators. Data analyses include descriptive statistics with standard deviations, Chi-square, t-tests, and logistic regression with adjusted odds ratios (AdjOR). RESULTS: There were 791 patients with the following characteristics: mean age 56.2, male 52.3%, known diabetic 61.6%, on insulin 46.1%, mean initial glucose 50.0 dl/mg (2.8 mmol/L), from home 56.3%. They were treated by an Advanced Care Paramedic 80.1%, received IV D50W 38.0%, IM glucagon 18.3%, PO complex carbs 26.6%, and accepted transport to hospital 69.4%. Of those transported, 134/556 (24.3%) were admitted and 9 (1.6%) died in the ED. Overall, 43 patients (5.4%) had repeat access to prehospital/ED care, among those, 8 (18.6%) were related to hypoglycemia. Patients on insulin were less likely to have repeat access to prehospital/ED care (AdjOR 0.4; 95%CI 0.2-0.9). This was not impacted by initial (or refusal of) transport (AdjOR 1.1; 95%CI 0.5-2.4). CONCLUSION: Although risk of repeat access to prehospital/ED care for patients with hypoglycemia exists, it was less common among patients taking insulin and was not predicted by an initial refusal of transport.


Assuntos
Serviços Médicos de Emergência , Hipoglicemia/terapia , Admissão do Paciente , Adulto , Idoso , Bases de Dados Factuais , Feminino , Humanos , Hipoglicemia/diagnóstico , Modelos Logísticos , Masculino , Auditoria Médica , Pessoa de Meia-Idade , Ontário , Admissão do Paciente/estatística & dados numéricos , Estudos Retrospectivos , Fatores de Tempo
8.
CJEM ; 20(6): 865-873, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30484420

RESUMO

OBJECTIVE: The aim of this study was to determine what clinically important events occur in ST-elevation myocardial infarction (STEMI) patients transported for primary percutaneous coronary intervention (PCI) via a primary care paramedic (PCP) crew, and what proportion of such events could only be treated by advanced care paramedic (ACP) protocols. METHODS: We conducted a health record review of STEMI transports by PCP-only crews and those transferred from PCP to ACP crews (ACP-intercept) from 2011 to 2015. A piloted data collection form was used to extract clinically important events, interventions during transport, and mortality. RESULTS: We identified 214 STEMI bypass cases (118 PCP-only and 96 ACP-intercept). Characteristics were mean age 61.4 years; 44.4% inferior infarcts; mean response time 6 minutes, 19 seconds; total paramedic contact time 29 minutes, 40 seconds; and, in cases of ACP-intercept, 7 minutes, 46 seconds of PCP-only contact time. A clinically important event occurred in 127 (59.3%) of cases: SBP < 90 mm Hg (26.2%), HR < 60 (30.4%), HR > 100 (20.6%), arrhythmias 7.5%, altered mental status 6.5%, airway intervention 2.3%. Two patients (0.9%) arrested, both survived. Of the events identified, 42.5% could be addressed differently by ACP protocols. The majority related to fluid boluses for hypotension (34.6%). In the ACP-intercept group, ACPs acted on 51.6% of events. There were six (2.8%) in-hospital deaths. CONCLUSIONS: Although clinically important events are common in STEMI bypass patients, a smaller proportion of events would be addressed differently by ACP compared with PCP protocols. The majority of clinically important events were transient and of limited clinical significance. PCP-only crews can safely transport STEMI patients directly to primary PCI.


Assuntos
Serviços Médicos de Emergência/métodos , Auxiliares de Emergência/normas , Serviço Hospitalar de Emergência/normas , Segurança do Paciente/normas , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Transporte de Pacientes/normas , Adulto , Idoso , Idoso de 80 Anos ou mais , Eletrocardiografia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Ontário/epidemiologia , Estudos Retrospectivos , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , Infarto do Miocárdio com Supradesnível do Segmento ST/mortalidade , Taxa de Sobrevida/tendências , Fatores de Tempo , Adulto Jovem
9.
J Emerg Med ; 55(6): 792-798, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30314928

RESUMO

BACKGROUND: Most patients transferred from a non-percutaneous coronary intervention (PCI) facility for primary PCI do not meet target reperfusion times. Direct transportation of patients with ST-elevation myocardial infarction (STEMI) from the scene by advanced life support (ALS) paramedics has been shown to improve reperfusion times and outcomes. OBJECTIVE: The aim of this study was to determine whether it is safe to bypass the closest hospital and transport by basic life support (BLS) provider to a PCI facility. METHODS: This was a health records review of consecutive patients transported to a regional PCI center under an STEMI bypass protocol. Under the PCI bypass protocol, patients were eligible if they presented with symptoms of chest pain, a 12-lead electrocardiogram meeting STEMI criteria, and if transported to the regional PCI center within 60 min. The occurrence of predefined adverse events during transport was determined, which included bradycardia < 50 beats/min, tachycardia > 140 beats/min, hypotension, cardiac arrest, and death. RESULTS: There were 46 cases of STEMI bypass between February 2005 and February 2013. Mean transport time was 29.9 min (range 20-62 min). Mean contact-to-balloon time was 95.2 min (range 68-159 min). Twenty-five adverse events occurred in 20 patients during transport. In 16 of the 20 patients, the adverse events were transiently abnormal vital sign requiring no intervention. In 3 of the patients, the adverse event was clinically significant and it is believed that the patient would have benefitted from advanced cardiac life support care not within the scope of practice of the BLS providers. CONCLUSIONS: In our region, STEMI patients can be diagnosed accurately and transported safely on bypass to a PCI center for primary PCI while respecting target reperfusion times.


Assuntos
Serviços Médicos de Emergência/métodos , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Transporte de Pacientes , Adulto , Idoso , Idoso de 80 Anos ou mais , Auxiliares de Emergência , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo
10.
Prehosp Emerg Care ; 22(6): 762-772, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29787325

RESUMO

BACKGROUND: A minimal amount of research exists examining the extent to which patient safety events occur within paramedicine and even fewer studies investigating patient safety systems for self-reporting by paramedics. The purpose of this study was to identify barriers to paramedic self-reporting of patient safety incidents (PSIs). METHODS: We randomly distributed paper-based surveys among 1,153 paramedics in an Ontario region in Canada. The survey described one of 5 different PSI clinical scenarios (near miss, adverse event, and minor, major or critical patient care variances) and listed 18 potential barriers to self-reporting PSIs as statements presented for rating on a 5-point Likert scale (very significant = 1 - very insignificant = 5). We invited comments on PSI self-reporting with 2 open-ended questions. We analyzed data with descriptive statistics, chi-square tests and Kruskal-Wallis H test. We used an inductive approach to qualitatively analyze emerging themes. RESULTS: We received responses from 1,133 paramedics (98.3%). Almost one third (28.4%) were Advanced Care Paramedics and 45.1% had >10 years' experience. The top 5 barriers to PSI self-reporting (very significant or significant, %) were the fear of being: punished (81.4%), suspended (79.6%), terminated (79.1%), investigated by Ministry of Health and Long-Term Care (78.4%), and decertified (78.0%). Overall, 64.1% responded they would self-report a given PSI. Intention to self-report a PSI varied according to scenario (22.8% near miss, 46.6% adverse event, 74.4% minor, 92.6% major, 95.6% critical). No association was found between level of training (p = 0.55) or years of experience (p = 0.10) and intention to self-report a PSI. Seven themes to improve PSI self-reporting by paramedics emerged from the qualitative data. CONCLUSIONS: A high proportion of fear-based barriers to self-reporting of PSIs exist among this study population. This suggests that a culture change is needed to facilitate the identification of future patient safety threats.


Assuntos
Auxiliares de Emergência , Erros Médicos , Segurança do Paciente , Autorrelato , Serviços Médicos de Emergência , Humanos , Masculino , Ontário , Inquéritos e Questionários
11.
Cell Chem Biol ; 25(7): 857-870.e7, 2018 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-29731426

RESUMO

Epidermal growth factor receptor (EGFR) interacts through its extracellular domain with seven different growth factors. These factors induce different structures within the cytoplasmic juxtamembrane (JM) segment of the dimeric receptor and propagate different growth factor-dependent signals to the cell interior. How this process occurs is unknown. Here we apply diverse experimental and computational tools to show that growth factor identity is encoded by the EGFR transmembrane (TM) helix into discrete helix dimer populations that differ in both cross-location and cross-angle. Helix dimers with smaller cross-angles at multiple cross locations are decoded to induce an EGF-type coiled coil in the adjacent JM, whereas helix dimers with larger cross-angles at fewer cross locations induce the TGF-α-type coiled coil. We propose an updated model for how conformational coupling across multiple EGFR domains results in growth factor-specific information transfer, and demonstrate that this model applies to both EGFR and the related receptor ErbB2.


Assuntos
Membrana Celular/metabolismo , Regulação Alostérica , Receptores ErbB/metabolismo , Humanos , Receptor ErbB-2/metabolismo
12.
MMWR Morb Mortal Wkly Rep ; 64(49): 1359-62, 2015 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-26678293

RESUMO

Canine rabies virus variant has been eliminated in the United States and multiple other countries. Globally, however, dogs remain the principal source for human rabies infections. The World Health Organization recommends that when dogs cross international borders, national importing authorities should require an international veterinary certificate attesting that the animal did not show signs of rabies at the time of shipment, was permanently identified, vaccinated, or revaccinated, and had been subjected to a serologic test for rabies before shipment. On June 8, 2015, an adult female dog that had recently been picked up from the streets of Cairo, Egypt, and shipped by a U.S. animal rescue organization to the United States was confirmed to have rabies by the Virginia Department of General Services Division of Consolidated Laboratory Services (DCLS). This dog was part of a large shipment of dogs and cats from Egypt that rescue organizations had distributed to multiple states for adoption. During the investigation, public health officials learned that the rabies vaccination certificate used for entry of the rabid dog into the United States had intentionally been falsified to avoid exclusion of the dog from entry under CDC's current dog importation regulations. This report underscores the ongoing risk posed by U.S. importation of domestic animals that have not been adequately vaccinated against rabies.


Assuntos
Doenças do Cão/diagnóstico , Fraude , Vacina Antirrábica/administração & dosagem , Raiva/veterinária , Registros/veterinária , Vacinação/veterinária , Animais , Gatos , Doenças do Cão/prevenção & controle , Cães , Egito , Feminino , Humanos , Saúde Pública , Raiva/diagnóstico , Raiva/prevenção & controle , Registros/normas , Trabalho de Resgate , Viagem , Virginia
13.
Org Lett ; 16(18): 4916-9, 2014 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-25207804

RESUMO

The hydrocarbon-stapled peptide E1(S) allosterically inhibits the kinase activity of the epidermal growth factor receptor (EGFR) by blocking a distant but essential protein-protein interaction: a coiled coil formed from the juxtamembrane segment (JM) of each member of the dimeric partnership.1 Macrocyclization is not required for activity: the analogous unstapled (but alkene-bearing) peptide is equipotent in cell viability, immunoblot, and bipartite display experiments to detect coiled coil formation on the cell surface.


Assuntos
Receptores ErbB/antagonistas & inibidores , Membrana Celular/metabolismo , Relação Dose-Resposta a Droga , Fator de Crescimento Epidérmico/metabolismo , Receptores ErbB/química , Receptores ErbB/metabolismo , Estrutura Molecular , Fosforilação , Ligação Proteica
14.
J Am Chem Soc ; 136(32): 11232-5, 2014 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-25075632

RESUMO

The epidermal growth factor receptor (EGFR) tyrosine kinase is implicated in a large number of human cancers. Most EGFR inhibitors target the extracellular, growth factor-binding domain or the intracellular, ATP-binding domain. Here we describe molecules that inhibit the kinase activity of EGFR in a new way, by competing with formation of an essential intradimer coiled coil containing the juxtamembrane segment from each member of the receptor partnership. The most potent molecules we describe bind EGFR directly, decrease the proliferation of wild-type and mutant EGFR-dependent cells lines, inhibit phosphorylation of EGFR and downstream targets, and block coiled coil formation as judged by bipartite tetracysteine display. Potency is directly correlated with the ability to block coiled coil formation within full-length EGFR in cells.


Assuntos
Inibidores Enzimáticos/química , Receptores ErbB/antagonistas & inibidores , Trifosfato de Adenosina/química , Sítio Alostérico , Animais , Células CHO , Linhagem Celular Tumoral , Proliferação de Células , Sobrevivência Celular , Cricetulus , Cisteína/química , Receptores ErbB/química , Humanos , Hidrocarbonetos/química , Indóis/química , Mutação , Peptídeos/química , Fosforilação , Ligação Proteica , Estrutura Terciária de Proteína , Pirazinas/química
15.
PLoS One ; 9(4): e94290, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24747300

RESUMO

BACKGROUND: Many schools throughout the United States reported an increase in dismissals due to the 2009 influenza A H1N1 pandemic (pH1N1). During the fall months of 2009, more than 567 school dismissals were reported from the state of Michigan. In December 2009, the Michigan Department of Community Health, in collaboration with the United States Centers for Disease Control and Prevention, conducted a survey to describe the knowledge, attitudes, and practices (KAPs) of households with school-aged children and classroom teachers regarding the recommended use of nonpharmaceutical interventions (NPIs) to slow the spread of influenza. METHODS: A random sample of eight elementary schools (kindergarten through 5th grade) was selected from each of the eight public health preparedness regions in the state. Within each selected school, a single classroom was randomly identified from each grade (K-5), and household caregivers of the classroom students and their respective teachers were asked to participate in the survey. RESULTS: In total, 26% (2,188/8,280) of household caregivers and 45% (163/360) of teachers from 48 schools (of the 64 sampled) responded to the survey. Of the 48 participating schools, 27% (13) experienced a school dismissal during the 2009 fall term. Eighty-seven percent (1,806/2,082) of caregivers and 80% (122/152) of teachers thought that the 2009 influenza A H1N1 pandemic was severe, and >90% of both groups indicated that they told their children/students to use NPIs, such as washing hands more often and covering coughs with tissues, to prevent infection with influenza. CONCLUSIONS: Knowledge and instruction on the use of NPIs appeared to be high among household caregivers and teachers responding to the survey. Nevertheless, public health officials should continue to explain the public health rationale for NPIs to reduce pandemic influenza. Ensuring this information is communicated to household caregivers and teachers through trusted sources is essential.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Vírus da Influenza A Subtipo H1N1/fisiologia , Influenza Humana/epidemiologia , Influenza Humana/prevenção & controle , Pandemias/prevenção & controle , Instituições Acadêmicas/estatística & dados numéricos , Criança , Pré-Escolar , Comunicação , Coleta de Dados , Características da Família , Humanos , Influenza Humana/transmissão , Michigan/epidemiologia , Saúde Pública
16.
J Sch Health ; 84(1): 56-62, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24320153

RESUMO

BACKGROUND: In fall 2009, many US communities experienced school closures during the influenza A H1N1 pandemic (pH1N1) and the state of Michigan reported 567 closures. We conducted an investigation in Michigan to describe pH1N1-related school policies, practices, and identify factors related to school closures. METHODS: We distributed an online survey to all Michigan K-12 school principals. Descriptive statistics and chi-square tests summarize school policies, practices, adherence to government guidelines, and differences between schools that closed and those that remained open during the pandemic. RESULTS: Of 4441 traditional K-12 Michigan schools, 937 (21%) principals responded to our survey representing approximately 374,000 students and 17,700 teachers. The majority (88%) of schools had influenza preparedness plans and followed government school influenza guidelines. Among respondents, 15% (137/937) of schools closed in fall 2009 with high absenteeism as the primary reason for closure. Schools that closed reported significant illness in their school, had <300 students, and had invested substantial resources preparing and responding to influenza. CONCLUSIONS: Adherence to government guidelines for schools appears high in Michigan. Closures occurred in schools that reported significant illness and were likely motivated by excessive absenteeism. Understanding factors related to closures during pH1N1 may inform future pandemic preparedness efforts.


Assuntos
Absenteísmo , Controle de Doenças Transmissíveis/organização & administração , Influenza Humana/epidemiologia , Influenza Humana/prevenção & controle , Pandemias/prevenção & controle , Instituições Acadêmicas/organização & administração , Adolescente , Criança , Feminino , Programas Governamentais , Política de Saúde , Humanos , Vírus da Influenza A Subtipo H1N1 , Masculino , Michigan/epidemiologia , Pandemias/estatística & dados numéricos , Serviços Preventivos de Saúde/organização & administração , Análise de Regressão , Instituições Acadêmicas/estatística & dados numéricos
17.
J Psychosom Res ; 71(6): 392-4, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22118381

RESUMO

OBJECTIVES: To determine the prevalence of significant health anxiety (hypochondriasis) in patients aged 16-75 in cardiology, respiratory medicine, neurological, endocrine and gastrointestinal clinics in general hospitals in London, Middlesex and North Nottinghamshire. METHOD: The Health Anxiety Inventory (HAI) (short form) was administered to patients attending the five clinics over a 21 month period and all those who scored 20 or more invited to take part in a further assessment for a randomised controlled trial. RESULTS: Of 43,205 patients attending the clinics 28,991 (67.1%) were assessed and of these, after exclusion of ineligible patients 5747 (19.8%) had significant health anxiety. 444 subsequently agreed to take part in a randomised controlled trial of treatment. The prevalence levels varied by clinic with neurology (24.7%) having the highest prevalence followed by respiratory medicine (20.9%), gastroenterology (19.5%), cardiology (19.1%), and endocrinology (17.5%). CONCLUSION: Abnormal health anxiety is common and a significant problem in those attending medical clinics and deserves greater awareness.


Assuntos
Instituições de Assistência Ambulatorial/estatística & dados numéricos , Ansiedade/epidemiologia , Atitude Frente a Saúde , Hipocondríase/epidemiologia , Adolescente , Adulto , Idoso , Ansiedade/psicologia , Feminino , Humanos , Hipocondríase/psicologia , Masculino , Pessoa de Meia-Idade , Prevalência , Inquéritos e Questionários
18.
Pediatr Infect Dis J ; 29(9): 794-800, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20400927

RESUMO

BACKGROUND: Despite elimination of endemic measles in the United States (US), outbreaks associated with imported measles continue to occur. In 2007, the initiation of a multistate measles outbreak was associated with an imported case occurring in a participant at an international youth sporting event held in Pennsylvania. METHODS: Case finding and contact tracing were conducted. Control measures included isolating ill persons and administering postexposure prophylaxis to exposed persons without documented measles immunity. Laboratory evaluation of suspected cases and contacts included measles serologic testing, viral culture, detection of viral RNA by reverse-transcription polymerase chain reaction, and viral genotyping. RESULTS: The index case occurred in a child from Japan aged 12 years. Contact tracing among 1250 persons in 8 states identified 7 measles cases; 5 (71%) cases occurred among persons without documented measles vaccination. Epidemiologic and laboratory investigation supported a single chain of transmission, linking the outbreak to contemporaneous measles virus genotype D5 transmission in Japan. Of the 471 event participants, 193 (41%) lacked documentation of presumed measles immunity, 94 (49%) of 193 were US-resident adults, 19 (10%) were non-US-resident adults (aged >18 years), and 80 (41%) were non-US-resident children. DISCUSSION: Measles outbreaks associated with imported disease are likely to continue in the US. Participants in international events, international travelers, and persons with routine exposure to such travelers might be at greater risk of measles. To reduce the impact of imported cases, high measles, mumps, and rubella vaccine coverage rates should be maintained throughout the US, and support should continue for global measles control and elimination.


Assuntos
Surtos de Doenças , Vírus do Sarampo/isolamento & purificação , Sarampo/epidemiologia , Viagem , Adulto , Criança , Busca de Comunicante , Feminino , Humanos , Internacionalidade , Japão , Masculino , Vírus do Sarampo/genética , Vacina contra Sarampo-Caxumba-Rubéola/administração & dosagem , Pessoa de Meia-Idade , Isolamento de Pacientes , RNA Viral/sangue , RNA Viral/genética , Estados Unidos/epidemiologia , Adulto Jovem
20.
J Health Care Poor Underserved ; 19(2): 588-95, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-18469429

RESUMO

The Rainbow Family of Living Light (RFLL), a large communal group with no centralized authority, has held an annual gathering on U.S. federal land for the past 34 years. In 2005, RFLL held its annual gathering in the Monongahela National Forest in West Virginia. Surveillance for injuries was established at nearby emergency departments and participants were asked to complete a health and risk assessment. We found that the majority of injuries resulted from outdoor activities and were not associated with violence. Assessments indicate that this is a medically underserved population and that participants would benefit from preventive and crisis services. We recommend early collaborative planning with RFLL members to reduce the potential for burden on local emergency departments and to meet the health care needs of this group. Future host communities should consider providing minor care, health screening, and information or referral services near the main gathering site.


Assuntos
Violência/estatística & dados numéricos , Ferimentos e Lesões/epidemiologia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Área Carente de Assistência Médica , Pessoa de Meia-Idade , Fatores de Risco , Transtornos Relacionados ao Uso de Substâncias/epidemiologia
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