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1.
Brain Behav Immun ; 108: 279-291, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36549577

RESUMO

Age-related cognitive decline, a common component of the brain aging process, is associated with significant impairment in daily functioning and quality of life among geriatric adults. While the complexity of mechanisms underlying cognitive aging are still being elucidated, microbial exposure and the multifactorial inflammatory cascades associated with systemic infections are emerging as potential drivers of neurological senescence. The negative cognitive and neurobiological consequences of a single pathogen-associated inflammatory experience, such as that modeled through treatment with lipopolysaccharide (LPS), are well documented. Yet, the brain aging impacts of repeated, intermittent inflammatory challenges are less well studied. To extend the emerging literature assessing the impact of infection burden on cognitive function among normally aging mice, here, we repeatedly exposed adult mice to intermittent LPS challenges during the aging period. Male 10-month-old C57BL6 mice were systemically administered escalating doses of LPS once every two weeks for 2.5 months. We evaluated cognitive consequences using the non-spatial step-through inhibitory avoidance task, and both spatial working and reference memory versions of the Morris water maze. We also probed several potential mechanisms, including cortical and hippocampal cytokine/chemokine gene expression, as well as hippocampal neuronal function via extracellular field potential recordings. Though there was limited evidence for an ongoing inflammatory state in cortex and hippocampus, we observed impaired learning and memory and a disruption of hippocampal long-term potentiation. These data suggest that a history of intermittent exposure to LPS-induced inflammation is associated with subtle but significantly impaired cognition among normally aging mice. The broader impact of these findings may have important implications for standard of care involving infections in aging individuals or populations at-risk for dementia.


Assuntos
Lipopolissacarídeos , Potenciação de Longa Duração , Camundongos , Animais , Masculino , Lipopolissacarídeos/farmacologia , Lipopolissacarídeos/metabolismo , Qualidade de Vida , Camundongos Endogâmicos C57BL , Cognição/fisiologia , Envelhecimento/metabolismo , Inflamação/complicações , Hipocampo/metabolismo , Aprendizagem em Labirinto
2.
BMC Neurol ; 23(1): 57, 2023 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-36737749

RESUMO

BACKGROUND: Small vessel childhood primary angiitis of the central nervous system (SV-cPACNS) is a rare disease characterized by inflammation within small vessels such as arterioles or capillaries. CASE PRESENTATION: We report a case of SV-cPACNS in an 8-year-old boy confirmed by brain biopsy. This patient was also incidentally found to have anti-glial fibrillary acidic protein (GFAP) antibodies in the cerebrospinal fluid (CSF) but had no evidence of antibody-mediated disease on brain biopsy. A literature review highlighted the rarity of SV-cPACNS and found no prior reports of CSF GFAP-associated SV-cPACNS in the pediatric age group. CONCLUSION: We present the first case of biopsy proven SV-cPACNS vasculitis associated with an incidental finding of CSF GFAP antibodies. The GFAP antibodies are likely a clinically insignificant bystander in this case and possibly in other diseases with CNS inflammation. Further research is needed to determine the clinical significance of newer CSF autoantibodies such as anti-GFAP before they are used for medical decision-making in pediatrics.


Assuntos
Vasculite do Sistema Nervoso Central , Masculino , Humanos , Criança , Vasculite do Sistema Nervoso Central/diagnóstico , Autoanticorpos , Inflamação/patologia
3.
Public Health ; 207: 113-118, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35636263

RESUMO

OBJECTIVES: Predictors of negative outcomes related to hepatitis A virus (HAV) need to be studied at a national level. STUDY DESIGN AND METHODS: A retrospective analysis using the Nationwide Inpatient Sample (2002-2013) and Nationwide Readmission Database (2010-2014) was performed to evaluate the outcomes of hospitalized patients with HAV. The Nationwide Inpatient Sample and the Nationwide Readmission Database included a varying number of states during the studied time and reflect the range of implementation dates of the HAV vaccines. Multivariable analyses were fit to determine predictors of outcomes. RESULTS: A total of 13,514 patients were admitted with HAV during the studied time. Thirty-day and 90-day readmission rates were 11.4% and 15%, respectively. Predictors of readmission, longer length of stay, and mortality included patients aged >60 years ([odds ratio [OR]: 1.02; 95% confidence interval [CI]: 1.001-1.03], [OR: 1.15; CI: 1.07-1.24], [OR: 4.06; 95% CI: 1.47-11.16], respectively), Medicare insurance ([OR:3.63; 95% CI: 2.18-6.03], [OR: 1.26; 95% CI: 1.17-1.37], [OR: 2.67; 95% CI: 1.18-6.04], respectively), and cirrhosis ([OR: 1.83; 95% CI: 1.05-3.21], [OR: 1.33; 95% CI: 1.20-1.47], [OR: 2.83; 95% CI: 1.14-7.05], respectively). Predictors of higher cost of admission included patients aged >60 years (OR: 1.32, 95% CI: 1.19-1.46), Hispanic (OR: 1.14; 95% CI: 1.05-1.24), Medicare insurance (OR: 1.22; 95% CI: 1.10-1.35), Medicaid insurance (OR: 1.10; 95% CI: 1.02-1.20), and cirrhosis (OR: 1.28; 95% CI: 1.11-1.46). CONCLUSIONS: Patients at increased healthcare utilization and mortality should be prioritized for HAV vaccination.


Assuntos
Hepatite A , Idoso , Hepatite A/epidemiologia , Humanos , Cirrose Hepática , Medicare , Aceitação pelo Paciente de Cuidados de Saúde , Estudos Retrospectivos , Estados Unidos/epidemiologia
4.
HIV Med ; 19(10): 708-715, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30051565

RESUMO

OBJECTIVES: In persons with hepatitis C virus (HCV) infection, HIV coinfection leads to faster progression to advanced liver disease. The aim of our study was to estimate diagnosed HIV prevalence among people with evidence of current HCV infection (polymerase chain reaction positive) and examine predictors of coinfection. METHODS: Adults (≥ 15 years old) with a current HCV infection reported to the Public Health England (PHE) sentinel surveillance of blood-borne viruses were linked to the PHE national HIV database using a deterministic methodology. Descriptive and multivariate analyses were conducted. RESULTS: Between 2008 and 2014, 5.0% (999/20 088) of adults with a current HCV infection were diagnosed with HIV coinfection. The majority acquired HIV through sex between men (441; 64.9%), followed by injecting drug use (153; 22.5%) and heterosexual contact (84; 12.4%). Of persons who were coinfected, 65.5% had been diagnosed with HIV infection > 6 months before their HCV diagnosis, 41.4% of whom had a negative anti-HCV test between their HIV and HCV diagnoses. In a multivariable model among persons with current HCV infection, an HIV diagnosis was more likely among men [adjusted odds ratio (aOR) 3.29; 95% confidence interval (CI) 2.60-4.16] and persons of black ethnicity (aOR 3.19; 95% CI 1.36-7.46), and less likely among older adults (aOR 0.85 per 10-year increase; 95% CI 0.79-0.92) and persons of Asian ethnicity (aOR 0.59; 95% CI 0.41-0.86). CONCLUSIONS: Our results indicate that the majority of diagnosed HIV and current HCV coinfections are among men who have sex with men. Safer sex campaigns should include awareness of transmission of HCV among MSM living with HIV.


Assuntos
Coinfecção/epidemiologia , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Hepatite C/complicações , Hepatite C/epidemiologia , Adolescente , Adulto , Transmissão de Doença Infecciosa , Inglaterra/epidemiologia , Feminino , Homossexualidade Masculina , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Adulto Jovem
5.
HIV Med ; 19(1): 33-41, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28762652

RESUMO

OBJECTIVES: Estonia has one the highest number of new HIV diagnoses in the European Union, mainly among injecting drug users and heterosexuals. Little is known of HIV incidence, which is crucial for limiting the epidemic. Using a recent HIV infection testing algorithm (RITA) assay, we aimed to estimate HIV incidence in 2013. METHODS: All individuals aged ≥18 years newly-diagnosed with HIV in Estonia January- December 2013, except blood donors and those undergoing antenatal screening, were included. Demographic and clinical data were obtained from the Estonian Health Board and the Estonian HIV-positive patient database. Serum samples were tested for recent infection using the LAg-avidity EIA assay. HIV incidence was estimated based on previously published methods. RESULTS: Of 69,115 tested subjects, 286 (0.41%) were newly-diagnosed with HIV with median age of 33 years (IQR: 28-42) and 65% male. Self-reported routes of HIV transmission were mostly heterosexual contact (n = 157, 53%) and injecting drug use (n = 62, 21%); 64 (22%) were with unknown risk group. Eighty two (36%) were assigned recent, resulting in estimated HIV incidence of 0.06%, corresponding to 642 new infections in 2013 among the non-screened population. Incidence was highest (1.48%) among people who inject drugs. CONCLUSIONS: These high HIV incidence estimates in Estonia call for urgent action of renewed targeted public health promotion and HIV testing campaigns.


Assuntos
Testes Diagnósticos de Rotina/métodos , Infecções por HIV/epidemiologia , HIV-1/isolamento & purificação , Técnicas Imunoenzimáticas/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estônia/epidemiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto Jovem
6.
Clin Genet ; 93(5): 962-971, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29293279

RESUMO

With the expansion of carrier screening to general preconception and prenatal patient populations, most patients will receive negative results, which we define as indicating <25% risk of having a child with a genetic condition. Because there is limited experience with expanded carrier screening, it is important to understand how receiving negative results affects patients, especially as providers, payers, and policymakers consider whether to offer it. In this mixed-methods study, we asked preconception patients enrolled in the NextGen study about their expectations and experiences receiving negative expanded carrier screening results. Participants completed surveys at study enrollment (n = 110 women, 51 male partners), after receiving carrier results (n = 100 women, 38 male partners), after receiving secondary findings (n = 98 women, 36 male partners), and 6 months after receiving results (n = 95 women, 28 male partners). We also interviewed a subset of participants 12 to 24 months after receiving results (n = 24 women, 12 male partners). We found minimal negative emotional impact and privacy concerns, increased confidence in reproductive plans, and few changes to health behaviors, although some patients made health decisions based on misunderstandings of their results. These findings suggest that expanded carrier screening causes minimal psychosocial harms, but systems are needed to reduce the risk of misinterpreting results.


Assuntos
Triagem de Portadores Genéticos , Aconselhamento Genético/psicologia , Participação do Paciente/psicologia , Diagnóstico Pré-Natal/psicologia , Adulto , Feminino , Humanos , Masculino , Resultados Negativos , Gravidez , Inquéritos e Questionários
7.
Clin Radiol ; 73(4): 410.e1-410.e8, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29229178

RESUMO

AIM: To assess current practice in cervical spine clearance across major trauma centres in England and review current guidelines. MATERIALS AND METHODS: An electronic survey was sent to lead trauma clinicians at 22 major trauma centres in England. This assessed the clinical decision tools used, the choice of initial imaging technique, and the methods used to clear the cervical spine in alert and obtunded patients without focal neurology, and where initial imaging was normal. British Orthopaedic Association Standards for Trauma (BOAST) 2 and Eastern Association for Surgery for Trauma (EAST) guidelines were used as standards. RESULTS: Eighteen out of the 22 (82%) centres responded by completing the survey. Most (71%) centres used the Canadian C-Spine Rule for clearing the cervical spine clinically. Seventy-two percent of centres preferred computed tomography (CT) as the first-line imaging technique, the choice based on age of patient and mechanism of injury. If the initial CT imaging was normal, magnetic resonance imaging (MRI) was performed in 52% of centres to clear the cervical spine, with half of these centres stating that they would discuss further imaging with a radiologist first. The practice across centres was highly variable for the obtunded patient, with most centres preferring continuing immobilisation or MRI to clear the cervical spine, with a small minority removing spinal precautions when a high-quality multidetector CT was normal. CONCLUSION: Multidetector CT is the preferred initial imaging technique across most major trauma centres in England when blunt cervical spine trauma is suspected. There is widespread reliance on MRI to clear the cervical spine in both alert and obtunded patients, if initial CT imaging is normal and there is no focal neurology on clinical assessment. This calls for greater awareness of the reliability of a high-quality normal multidetector CT examination in clearing the cervical spine in the absence of focal neurology.


Assuntos
Medula Cervical/diagnóstico por imagem , Inquéritos Epidemiológicos , Traumatismos da Coluna Vertebral/diagnóstico por imagem , Centros de Traumatologia , Ferimentos não Penetrantes , Vértebras Cervicais/diagnóstico por imagem , Inglaterra , Humanos , Imageamento por Ressonância Magnética , Reprodutibilidade dos Testes , Tomografia Computadorizada por Raios X
8.
Neuroimage ; 158: 126-135, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28669909

RESUMO

Recent evidence suggests that the function of the core system for face perception might extend beyond visual face-perception to a broader role in person perception. To critically test the broader role of core face-system in person perception, we examined the role of the core system during the perception of others in 7 congenitally blind individuals and 15 sighted subjects by measuring their neural responses using fMRI while they listened to voices and performed identity and emotion recognition tasks. We hypothesised that in people who have had no visual experience of faces, core face-system areas may assume a role in the perception of others via voices. Results showed that emotions conveyed by voices can be decoded in homologues of the core face system only in the blind. Moreover, there was a specific enhancement of response to verbal as compared to non-verbal stimuli in bilateral fusiform face areas and the right posterior superior temporal sulcus showing that the core system also assumes some language-related functions in the blind. These results indicate that, in individuals with no history of visual experience, areas of the core system for face perception may assume a role in aspects of voice perception that are relevant to social cognition and perception of others' emotions.


Assuntos
Percepção Auditiva/fisiologia , Cegueira/fisiopatologia , Plasticidade Neuronal/fisiologia , Lobo Temporal/fisiopatologia , Estimulação Acústica , Adulto , Mapeamento Encefálico , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Percepção Visual/fisiologia
9.
HIV Med ; 18(2): 73-79, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27167600

RESUMO

OBJECTIVES: Involvement of people living with HIV (PLHIV) in the design of HIV cure studies is important, given the potential risks to participants. We present results of an international survey of PLHIV to define these issues and inform cure research. METHODS: PLHIV were recruited in June-November 2014 through HIV websites, advocacy forums, social media and 12 UK HIV clinics. The survey included questions concerning demographics, HIV disease history, the desirability of types of cure and the patient's willingness to accept potential toxicity and treatment interruption (TI). We examined factors associated with TI and willingness to accept substantial risks. RESULTS: A total of 982 PLHIV completed the survey; 87% were male, 79% white and 81% men who have sex with men (MSM). Fifty-one per cent were aged 25-44 years and 69% were UK residents. The median time since diagnosis was 7 years [interquartile range (IQR) 2-17 years]. Eighty-eight per cent were receiving antiretrovirals (91% reported undetectable viral load). Health/wellbeing improvements (96%) and an inability to transmit HIV (90%) were more desirable cure characteristics than testing HIV-negative (69%). Ninety-five per cent were interested in participating in cure studies, and 59% were willing to accept substantial risks. PLHIV with a low CD4 count [201-350 cells/µL vs. ≥ 350 cells/µL; odds ratio (OR) 2.11; 95% confidence interval (CI) 1.11-4.00] were more likely to accept risks, whereas those with limited knowledge of HIV treatments vs. excellent/good knowledge and those aged ≥ 65 years vs. 45-64 years were less likely to accept risks [OR 0.58 (95% CI 0.37-0.90) and OR 0.18 (95% CI 0.07-0.45), respectively]. TI was acceptable for 62% of participants, with the main concerns being becoming unwell (82%), becoming infectious (76%) and HIV spreading through the body (76%). CONCLUSIONS: Cure research was highly acceptable to the PLHIV surveyed. Most individuals would accept risks, including TI, even in the absence of personal benefit. An optimal cure would improve health and minimize onward transmission risk.


Assuntos
Atitude , Ensaios Clínicos como Assunto , Infecções por HIV/tratamento farmacológico , Infecções por HIV/psicologia , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Participação do Paciente/psicologia , Adolescente , Adulto , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reino Unido , Adulto Jovem
10.
Support Care Cancer ; 25(7): 2063-2073, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28197848

RESUMO

PURPOSE: To compare patient-triggered follow-up (PTFU) for curatively treated colorectal cancer against traditional outpatient follow-up (OPFU). METHODS: Questionnaires were mailed at four time points over one-year post-treatment to two prospectively-recruited cohorts: A, patients entering follow-up and receiving OPFU pre-implementation of PTFU; B, patients entering follow-up (FU) and receiving either OPFU (B1) or PTFU (B2) post-implementation of PTFU. Bi-variate tests were used to compare patient characteristics and outcomes eight months after entering follow-up (generic and cancer-specific quality of life (QoL), satisfaction). Regression analysis explored associations between follow-up model and outcomes. Resource implications and costs of models were compared. RESULTS: Patients in Cohort B1 were significantly more likely to have received chemotherapy (p < 0.001), radiotherapy (p < 0.05), and reported poorer QoL (p = 0.001). Having a longstanding co-morbid condition was the most important determinant of QoL (p < 0.001); model of care was not significant. Patients were satisfied with their follow-up care regardless of model. Health service costs were higher in PTFU over the first year CONCLUSIONS: PTFU is acceptable to patients with colorectal cancer and can be considered to be a realistic alternative to OPFU for clinically suitable patients. The initial costs are higher due to provision of a self-management (SM) programme and remote surveillance. Further research is needed to establish long-term outcomes and costs.


Assuntos
Neoplasias Colorretais/tratamento farmacológico , Qualidade de Vida/psicologia , Estudos de Coortes , Seguimentos , Humanos , Estudos Longitudinais , Estudos Prospectivos , Inquéritos e Questionários , Fatores de Tempo
11.
J Endocrinol Invest ; 40(9): 1015-1021, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28510122

RESUMO

OBJECTIVE: Post-operative thyroglobulin (Tg) levels can predict the likelihood of residual cancer, including distant metastases, thereby influencing postsurgical treatment strategies even in patients with low-risk disease. Circulating anti-thyroglobulin antibodies (anti-Tg Abs) interfere with Tg measurement preventing this clinical use. It is not known if the presence of anti-Tg Abs predicts metastatic disease on post-therapy scan in patients with low-risk disease or if they should influence the use or dose of I-131 therapy. In the present study, we compare post-therapy scans in low-risk patients with and without anti-Tg Abs. METHODS: This is a single-institution retrospective study. The study population (Group A) included all patients with low-risk differentiated thyroid cancer (DTC) who underwent total thyroidectomy and RAI between 1/1/2006 to 9/11/2015 with intrathyroidal T1-T2, Nx, N0 or N1a (≤5 nodes all measuring, when reported, <2 mm) that had anti-thyroglobulin antibodies. Patients were excluded if they had known distant metastases and/or extensive vascular invasion. A second group of patients (Group B) treated during the same period but without anti-Tg antibodies was selected to match group A by propensity core matching with a logistic regression model. RESULTS: Each group included 37 patients. In group A: Median age was 40 years, 86% female and 76% PTC. Median tumor size was 2 cm (0.2-3.8), 32% had multifocal disease, 16% were N1a and 4% had vascular invasion. Parameters in group B were not statistically different from Group A, as expected based on the selection criteria, except being less likely to have Hashimoto's thyroiditis on pathology (p < 0.001). Post-therapy scan results were compared by Chi-square test with 86% negative post therapy scan frequency in group A and 92% in group B without evidence of a difference (p = 0.45). CONCLUSION: In patients with low-risk DTC, anti-Tg Abs did not significantly predict metastatic disease on post-therapy scan. If confirmed, these data suggest that the presence of anti-Tg Abs alone should not influence initial therapy in patients with low-risk DTC.


Assuntos
Autoanticorpos/sangue , Radioisótopos do Iodo/uso terapêutico , Neoplasias da Glândula Tireoide/sangue , Neoplasias da Glândula Tireoide/radioterapia , Adolescente , Adulto , Idoso , Estudos de Coortes , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Adulto Jovem
12.
Emerg Med J ; 34(5): 318-325, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28264877

RESUMO

This consensus statement seeks to provide clear guidance for the management of pregnant trauma patients in the prehospital setting. Pregnant patients sustaining trauma injuries have certain clinical management priorities beyond that of the non-pregnant trauma patients and that if overlooked may be detrimental to maternal and fetal outcomes.


Assuntos
Consenso , Serviços Médicos de Emergência/métodos , Guias como Assunto , Complicações na Gravidez/terapia , Ferimentos e Lesões/terapia , Adulto , Reanimação Cardiopulmonar/métodos , Serviços Médicos de Emergência/normas , Feminino , Humanos , Hipovolemia/terapia , Intubação Intratraqueal/métodos , Monitorização Fisiológica/métodos , Oxigênio/administração & dosagem , Oxigênio/uso terapêutico , Gravidez , Complicações na Gravidez/patologia , Decúbito Dorsal
13.
HIV Med ; 17(6): 445-52, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26492497

RESUMO

OBJECTIVES: The objective of the 1st European AIDS Clinical Society meeting on Standard of Care in Europe was to raise awareness of the European scenario and come to an agreement on actions that could be taken in the future. METHODS: Data-driven presentations were given on specific topics followed by interactive panel discussions. RESULTS: In Eastern European countries, the epidemic is largely driven by injecting drug use, in contrast with Western Europe where the infection mainly occurs through heterosexual contact. A high proportion of people living with HIV remain unaware of their infection. Substantial differences exist in Eastern Europe and Central Asia with respect to treatment coverage, regimen availability and continuity of drug supply. In 2012, tuberculosis case notification rates were 5-10 times higher in Eastern Europe compared with Western Europe, with an alarming proportion of newly diagnosed multi-drug-resistant cases. Hepatitis C is widespread in selected geographical areas and risk groups. CONCLUSIONS: The key conclusion from the meeting was that a high-priority group of actions could be identified, including: increasing HIV awareness and testing, improving training for health care providers, ensuring equitable patient access to treatments and diagnostics for HIV and comorbidities, and implementing best practices in infection control and treatment of HIV-infected patients coinfected with tuberculosis and hepatitis C virus, for whom direct acting antiviral treatment. should be considered.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Infecções Oportunistas Relacionadas com a AIDS/prevenção & controle , Coinfecção/epidemiologia , Coinfecção/prevenção & controle , Infecções por HIV/complicações , Padrão de Cuidado , Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Infecções Oportunistas Relacionadas com a AIDS/terapia , Coinfecção/diagnóstico , Coinfecção/terapia , Controle de Doenças Transmissíveis/métodos , Controle de Doenças Transmissíveis/organização & administração , Europa (Continente) , Saúde Global , Humanos , Sociedades Científicas
14.
Eur J Clin Microbiol Infect Dis ; 35(9): 1433-9, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27230510

RESUMO

Currently, in vitro synergy with colistin has not translated into improved clinical outcomes. This study aimed to compare colistin combination therapy to colistin monotherapy in critically ill patients with multi-drug resistant gram-negative (MDR-GN) pneumonia. This was a retrospective analysis of critically ill adult patients receiving intravenous colistin for MDR-GN pneumonia comparing colistin combination therapy to colistin monotherapy with a primary endpoint of clinical cure. Combination therapy was defined by administration of another antibiotic to which the MDR-GN pathogen was reported as susceptible or intermediate. Ninety patients were included for evaluation (41 combination therapy and 49 monotherapy). Baseline characteristics were similar between groups. No difference in clinical cure was observed between combination therapy and monotherapy in univariate analysis, nor when adjusted for APACHE II score and time to appropriate antibiotic therapy (57.1 vs. 63.4 %, adjusted OR 1.15, p = 0.78). Microbiological cure was significantly higher for combination therapy (87 vs. 35.5 %, p < 0.001). Colistin combination therapy was associated with a significant improvement in microbiological cure, without improvement in clinical cure. Based on the in vitro synergy and improvement in microbiological clearance, colistin combination therapy should be prescribed for MDR-GN pneumonia. Further research is warranted to determine if in vitro synergy with colistin translates into improved clinical outcomes.


Assuntos
Antibacterianos/uso terapêutico , Colistina/uso terapêutico , Estado Terminal , Farmacorresistência Bacteriana Múltipla , Bactérias Gram-Negativas/efeitos dos fármacos , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Pneumonia Bacteriana/tratamento farmacológico , Administração Intravenosa , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Combinada/métodos , Feminino , Bactérias Gram-Negativas/isolamento & purificação , Infecções por Bactérias Gram-Negativas/microbiologia , Infecções por Bactérias Gram-Negativas/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia Bacteriana/microbiologia , Pneumonia Bacteriana/patologia , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
15.
Health Educ Res ; 31(4): 492-508, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27173641

RESUMO

SIPsmartER is a 6-month behavioral intervention designed using a health literacy universal precautions approach that has been found effective at reducing sugary beverage intake in rural, low socioeconomic adults. The purpose of this mixed-methods study is to determine if health literacy status influenced participants' satisfaction and perceptions of each intervention component: small group classes, interactive-voice response (IVR) calls, personal action plans and self-monitoring logs. Of the 155 participants enrolled in SIPsmartER, 105 (68%) completed an interview-administered summative evaluation including 68 high and 37 low health literate participants. The quantitative findings show participant satisfaction with each intervention component was high (i.e. classes = 9.6, IVR calls = 8.1, action plans = 8.9-9.1, logs = 8.7 on a 10-point scale) and similar across both health literacy groups. The majority of qualitative responses were positive (81.8%) and code counts were comparable between literacy groups with a few exceptions. As compared with high health literacy respondents, low health literacy respondents more frequently mentioned liking the content and length of IVR calls, liking the motivational aspects of the personal action plans, and identified numeracy issues with the self-monitoring logs. Overall, applying a health literacy universal precautions approach is an effective and acceptable strategy for both high and low health literacy groups.


Assuntos
Bebidas Gaseificadas/estatística & dados numéricos , Letramento em Saúde , Promoção da Saúde/métodos , Satisfação do Paciente , População Rural , Adulto , Feminino , Letramento em Saúde/estatística & dados numéricos , Humanos , Entrevistas como Assunto , Masculino , Satisfação do Paciente/estatística & dados numéricos , População Rural/estatística & dados numéricos , Virginia
16.
J Toxicol Environ Health A ; 78(23-24): 1385-408, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26594896

RESUMO

Anecdotal reports in the press and epidemiological studies suggest that deployment to Iraq and Afghanistan may be associated with respiratory diseases and symptoms in U.S. military personnel and veterans. Exposures during military operations were complex, but virtually all service members were exposed to high levels of respirable, geogenic dust. Inhalation of other dusts has been shown to be associated with adverse health effects, but the pulmonary toxicity of ambient dust from Iraq has not been previously studied. The relative toxicity of Camp Victory dust was evaluated by comparing it to particulate matter from northern Kuwait, a standard U.S. urban dust, and crystalline silica using a single intratracheal instillation in rats. Lung histology, protein levels, and cell counts were evaluated in the bronchoalveolar lavage fluid 1-150 d later. The Iraq dust provoked an early significant, acute inflammatory response. However, the level of inflammation in response to the Iraq dust, U.S. urban dust, and Kuwait dust rapidly declined and was nearly at control levels by the end of the study At later times, animals exposed to the Iraq, U.S. urban, or Kuwait dusts showed increased small airway remodeling and emphysema compared to silica-exposed and control animals without evidence of fibrosis or premalignant changes. The severity and persistence of pulmonary toxicity of these three dusts from the Middle East resemble those of a U.S. urban dust and are less than those of silica. Therefore, Iraq dust exposure is not highly toxic, but similar to other poorly soluble low-toxicity dusts.


Assuntos
Poluentes Atmosféricos/toxicidade , Líquido da Lavagem Broncoalveolar/química , Exposição por Inalação , Pulmão/efeitos dos fármacos , Material Particulado/toxicidade , Animais , Poeira/análise , Iraque , Pulmão/patologia , Masculino , Ratos , Ratos Sprague-Dawley , Estações do Ano , Fatores de Tempo
17.
Genes Immun ; 15(6): 392-403, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24871464

RESUMO

Pseudogenes are duplicated yet defunct copies of functional parent genes. However, some pseudogenes have gained or retained function. In this study, we consider a functional role for the NLRP2-related, higher primate-specific, processed pseudogene NLRP2P, which is closely related to Pyrin-only protein 2 (POP2/PYDC2), a regulator of nuclear factor-κB (NF-κB) and the inflammasome. The NLRP2P open-reading frame on chromosome X has features consistent with a processed pseudogene (retrotransposon), yet encodes a 45-amino-acid, Pyrin-domain-related protein. The open-reading frame of NLRP2P shares 80% identity with POP2 and is under purifying selection across Old World primates. Although widely expressed, NLRP2P messenger RNA is upregulated by lipopolysaccharide in human monocytic cells. Functionally, NLRP2P impairs NF-κB p65 transactivation by reducing activating phosphorylation of RelA/p65. Reminiscent of POP2, NLRP2P reduces production of the NF-κB-dependent cytokines tumor necrosis factor alpha and interleukin (IL)-6 following toll-like receptor stimulation. In contrast to POP2, NLRP2P fails to inhibit the ASC-dependent NLRP3 inflammasome. In addition, beyond regulating cytokine production, NLRP2P has a potential role in cell cycle regulation and cell death. Collectively, our findings suggest that NLRP2P is a resurrected processed pseudogene that regulates NF-κB RelA/p65 activity and thus represents the newest member of the POP family, POP4.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Pseudogenes/genética , Fator de Transcrição RelA/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Apoptose/genética , Proteínas Reguladoras de Apoptose , Sequência de Bases , Western Blotting , Ciclo Celular/genética , Linhagem Celular , Linhagem Celular Tumoral , Núcleo Celular/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Células HEK293 , Células HeLa , Humanos , Lipopolissacarídeos/farmacologia , Microscopia de Fluorescência , Dados de Sequência Molecular , Fosforilação , Interferência de RNA , Proteínas Repressoras/metabolismo , Retroelementos/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Serina/metabolismo , Fator de Transcrição RelA/metabolismo , Fator de Necrose Tumoral alfa/farmacologia
18.
Epidemiol Infect ; 142(6): 1317-27, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24001479

RESUMO

SUMMARY: Acinetobacter is a well-recognized nosocomial pathogen. Previous reports of community-associated Acinetobacter infections have lacked clear case definitions and assessment of healthcare-associated (HCA) risk factors. We identified Acinetobacter bacteraemia cases from blood cultures obtained <3 days after hospitalization in rural Thailand and performed medical record reviews to assess HCA risk factors in the previous year and compare clinical and microbiological characteristics between cases with and without HCA risk factors. Of 72 Acinetobacter cases, 32 (44%) had no HCA risk factors. Compared to HCA infections, non-HCA infections were more often caused by Acinetobacter species other than calcoaceticus-baumannii complex species and by antibiotic-susceptible organisms. Despite similar symptoms, the case-fatality proportion was lower in non-HCA than HCA cases (9% vs. 45%, P < 0·01). Clinicians should be aware of Acinetobacter as a potential cause of community-associated infections in Thailand; prospective studies are needed to improve understanding of associated risk factors and disease burden.


Assuntos
Infecções por Acinetobacter/epidemiologia , Bacteriemia/epidemiologia , Infecções Comunitárias Adquiridas/microbiologia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Infecções Comunitárias Adquiridas/epidemiologia , Infecção Hospitalar/epidemiologia , Feminino , Hospitais , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Vigilância da População , Fatores de Risco , Tailândia/epidemiologia , Adulto Jovem
19.
Ecotoxicology ; 23(5): 929-38, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24723096

RESUMO

A major contaminant of concern for mountaintop removal/valley fill (MTR/VF) coal mining is selenium (Se), an essential micronutrient that can be toxic to fish. Creek chubs (Semotilus atromaculatus), green sunfish (Lepomis cyanellus), and composite insect samples were collected in March-July, 2011-2013 at two sites within the Mud River, West Virginia. One site (MR7) receives MTR/VF coal mining effluent, while the reference site (LFMR) does not. MR7 water had significantly higher concentrations of soluble Se (p < 0.01) and conductivity (p < 0.005) compared to LFMR. MR7 whole insects contained significantly higher concentrations of Se compared to LFMR insects (p < 0.001). MR7 creek chubs had significantly higher Se in fillets, liver, and ovary tissues compared to LFMR samples (p < 0.0001, p < 0.0001, and p < 0.02, respectively). MR7 green sunfish fillets contained significantly higher Se (p < 0.0001). Histological examination showed LFMR creek chub gills contained a typical amount of parasitic infestations; however MR7 gills contained minimal to no visible parasites. X-ray absorption spectroscopic analyses revealed that MR7 whole insects and creek chub tissues primarily contained organic Se and selenite. These two species of Mud River fish were shown to specifically accumulate Se differently in tissues compartments. Tissue-specific concentrations of Se may be useful in determining potential reproductive consequences of Se exposure in wild fish populations.


Assuntos
Cyprinidae/metabolismo , Insetos/metabolismo , Perciformes/metabolismo , Selênio/metabolismo , Poluentes Químicos da Água/metabolismo , Animais , Minas de Carvão , Feminino , Brânquias/química , Insetos/química , Fígado/química , Músculos/química , Ovário/química , Selênio/análise , Água/análise , Espectroscopia por Absorção de Raios X
20.
Emerg Med J ; 30(12): 1065-6, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24232010

RESUMO

This paper outlines the emerging best practice when packaging a prehospital trauma patient while providing spinal immobilisation. The best practice described is based on the recommendations of a consensus meeting held by the Faculty of Pre-Hospital Care, Royal College of Surgeons of Edinburgh, in the West Midlands in April 2012, where the opinion of experienced practitioners from across the prehospital and emergency care community considered the currently available evidence and reviewed current clinical practice. Initial consensus points were then subject to further review and dialogue with stakeholders from the initial meeting. The recommendations drawn from the meeting and subsequent dialogue represent a 'general agreement' to the principles and practices described in the paper. The recommendations will provide guidance for clinical practice and governance alongside other consensus statements from the Faculty of Pre-Hospital Care that seek to address prehospital spinal immobilisation and pelvic immobilisation.


Assuntos
Consenso , Serviços Médicos de Emergência/métodos , Movimentação e Reposicionamento de Pacientes/métodos , Medicina Baseada em Evidências , Humanos , Imobilização/métodos , Guias de Prática Clínica como Assunto , Traumatismos da Coluna Vertebral/terapia
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