RESUMO
Risk assessment is the cornerstone of working safely with biological agents. The World Health Organization (WHO) Laboratory Biosafety Manual Fourth Edition Monograph on Risk Assessment provides stepwise guidance for completing a risk assessment, from information gathering and identifying hazards to evaluating the risks, developing, and implementing controls and review.To support the development of a mature safety culture within laboratories, it is important that all staff who handle biological agents understand the fundamentals of risk assessment and receive training in identifying hazards created by their work activities (or tasks) and understand how to mitigate the risks arising from carrying out that work. Any "competent" person may be involved in assessing the risks posed by carrying out an activity. Those closest to the work, who understand the details of the task being undertaken, should be involved in creating the risk assessment. The guidance in this chapter is not just applicable to biosafety professionals, laboratory scientists, or facility managers but can be used by any competent worker familiar with the activity being assessed.This chapter uses the guidance from the WHO to apply the principles of risk assessment to working with Epizootic hemorrhagic disease virus (EHDV), using an example activity-virus isolation from EHDV test samples in cell culture.
Assuntos
Vírus da Doença Hemorrágica Epizoótica , Animais , Vírus da Doença Hemorrágica Epizoótica/isolamento & purificação , Medição de Risco/métodos , Humanos , Gestão de Riscos , Contenção de Riscos Biológicos/métodos , Infecções por Reoviridae/virologia , Infecções por Reoviridae/veterinária , Organização Mundial da Saúde , Orbivirus/genéticaAssuntos
Meio Ambiente , Nível de Saúde , Estilo de Vida , Doença Pulmonar Obstrutiva Crônica , Telemedicina , Adulto , Idoso , Estudos de Coortes , DNA , Feminino , Interação Gene-Ambiente , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Fumar , Meio Social , Reino UnidoRESUMO
BACKGROUND: Racial differences in endogenous pain facilitatory processes have been previously reported. Evidence suggests that psychological and behavioral factors, including depressive symptoms and sleep, can alter endogenous pain facilitatory processes. Whether depressive symptoms and sleep might help explain racial differences in endogenous pain facilitatory processes has yet to be determined. PURPOSE: This observational, microlongitudinal study examined whether depressive symptoms and sleep were sequential mediators of racial differences in endogenous pain facilitatory processes. METHODS: A total of 50 (26 African American and 24 non-Hispanic white) community-dwelling adults without chronic pain (mean 49.04 years; range 21-77) completed the Center for Epidemiological Studies Depression Scale prior to seven consecutive nights of sleep monitoring with actigraphy in the home environment. Participants subsequently returned to the laboratory for assessment of endogenous pain facilitation using a mechanical temporal summation protocol. RESULTS: Findings revealed greater depressive symptoms, poorer sleep efficiency, and greater temporal summation of mechanical pain in African Americans compared to non-Hispanic whites. In a sequential mediation model, greater depressive symptoms predicted poorer sleep efficiency (t = -2.55, p = .014), and poorer sleep efficiency predicted enhanced temporal summation of mechanical pain (t = -4.11, p < .001), particularly for African Americans. CONCLUSIONS: This study underscores the importance of examining the contribution of psychological and behavioral factors when addressing racial differences in pain processing. Additionally, it lends support for the deleterious impact of depressive symptoms on sleep efficiency, suggesting that both sequentially mediate racial differences in endogenous pain facilitation.
Assuntos
Negro ou Afro-Americano/psicologia , Depressão/psicologia , Dor/psicologia , Somação de Potenciais Pós-Sinápticos , Distúrbios do Início e da Manutenção do Sono/psicologia , População Branca/psicologia , Adulto , Idoso , Depressão/complicações , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Dor/complicações , Medição da Dor/métodos , Adulto JovemRESUMO
OBJECTIVE: Research on chronic low back pain (cLBP) has focused heavily on structural abnormalities with emphasis on diagnostic imaging. However, for many cLBP patients, clinical pain and disability are not clearly associated with identifiable pathology of the spine or associated tissues. Therefore, alternative determinants such as psychological factors and dysfunctional pain modulatory processes have been suggested to be important. METHODS: This observational study examined differences in pain catastrophizing and endogenous pain modulation between 25 cLBP patients and 25 pain-free controls. Associations among pain catastrophizing, endogenous pain modulatory processes, clinical pain reports, and disability were also examined in cLBP patients. Endogenous pain modulation was examined using temporal summation (TS) of mechanical and heat pain stimuli as well as conditioned pain modulation (CPM) with algometry (test stimulus) and the cold pressor task (conditioning stimulus). RESULTS: Findings demonstrated significantly greater pain catastrophizing as well as greater TS of mechanical and heat pain for cLBP patients compared with controls. CPM was not present in cLBP patients or controls. Among cLBP patients, pain catastrophizing was significantly associated with disability, while TS of mechanical pain was significantly associated with clinical pain severity and disability. CONCLUSIONS: This study suggests that endogenous pain modulatory processes are altered for cLBP patients, particularly TS of mechanical and heat stimuli. Pain catastrophizing and TS of mechanical pain may have important clinical relevance for cLBP, given associations with clinical pain and disability; however, future research is needed to replicate these findings.
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Catastrofização/psicologia , Dor Lombar/fisiopatologia , Dor Lombar/psicologia , Idoso , Idoso de 80 Anos ou mais , Dor Crônica/fisiopatologia , Dor Crônica/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Limiar da Dor/fisiologia , Limiar da Dor/psicologiaRESUMO
Patients with asthma and chronic obstructive pulmonary disease (COPD) are susceptible to exacerbations, often caused by microbial pathogens. We hypothesised that intracellular Toll-like receptor (TLR) function in blood mononuclear cells (PBMCs) from these subjects would be impaired and that this impairment is related to exacerbation frequency. PBMCs stimulated with a TLR-9 agonist (but not TLR-3 or 7/8) produced significantly less IFN-α in asthma (26 [3-696]pg/ml) compared to control (943 [164-1651]) and COPD (597 [127-1186]) subjects (p = 0.0019) but this was not related to the number of exacerbations per year in asthma or COPD. In COPD, IFN-α levels were related to KCO (% predicted) in COPD (r = -0.41, p = 0.01). IFN-α was derived from plasmacytoid dendritic cells (pDCs) and their frequency was lower in asthma compared to control subjects (control 0.48% [0.33-0.64] versus asthma 0.29% [0.13-0.34], p = 0.019) whereas pDC function per se was not significantly impaired between groups. The mechanism underlying reduced IFN-α production and the clinical consequences in severe asthma remains to be established.
Assuntos
Asma/imunologia , Interferon-alfa/metabolismo , Doença Pulmonar Obstrutiva Crônica/imunologia , Receptor Toll-Like 9/imunologia , Idoso , Células Dendríticas/imunologia , Feminino , Humanos , Interferon-alfa/imunologia , Leucócitos Mononucleares/imunologia , Masculino , Pessoa de Meia-Idade , Receptor 7 Toll-Like/imunologiaRESUMO
RATIONALE: Exacerbations of chronic obstructive pulmonary disease (COPD) and responses to treatment are heterogeneous. OBJECTIVES: Investigate the usefulness of blood eosinophils to direct corticosteroid therapy during exacerbations. METHODS: Subjects with COPD exacerbations were entered into a randomized biomarker-directed double-blind corticosteroid versus standard therapy study. Subjects in the standard arm received prednisolone for 2 weeks, whereas in the biomarker-directed arm, prednisolone or matching placebo was given according to the blood eosinophil count biomarker. Both study groups received antibiotics. Blood eosinophils were measured in the biomarker-directed and standard therapy arms to define biomarker-positive and -negative exacerbations (blood eosinophil count > and ≤ 2%, respectively). The primary outcome was to determine noninferiority in health status using the chronic respiratory questionnaire (CRQ) and in the proportion of exacerbations associated with a treatment failure between subjects allocated to the biomarker-directed and standard therapy arms. MEASUREMENTS AND MAIN RESULTS: There were 86 and 80 exacerbations in the biomarker-directed and standard treatment groups, respectively. In the biomarker-directed group, 49% of the exacerbations were not treated with prednisolone. CRQ improvement after treatment in the standard and biomarker-directed therapy groups was similar (0.8 vs. 1.1; mean difference, 0.3; 95% confidence interval, 0.0-0.6; P = 0.05). There was a greater improvement in CRQ in biomarker-negative exacerbations given placebo compared with those given prednisolone (mean difference, 0.45; 95% confidence interval, 0.01-0.90; P = 0.04). In biomarker-negative exacerbations, treatment failures occurred in 15% given prednisolone and 2% of those given placebo (P = 0.04). CONCLUSIONS: The peripheral blood eosinophil count is a promising biomarker to direct corticosteroid therapy during COPD exacerbations, but larger studies are required.
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Eosinófilos/metabolismo , Glucocorticoides/administração & dosagem , Prednisolona/administração & dosagem , Doença Pulmonar Obstrutiva Crônica/sangue , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/análise , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Testes de Função RespiratóriaRESUMO
RATIONALE: Exacerbations of chronic obstructive pulmonary disease (COPD) are heterogeneous with respect to inflammation and etiology. OBJECTIVES: Investigate biomarker expression in COPD exacerbations to identify biologic clusters and determine biomarkers that recognize clinical COPD exacerbation phenotypes, namely those associated with bacteria, viruses, or eosinophilic airway inflammation. METHODS: Patients with COPD were observed for 1 year at stable and exacerbation visits. Biomarkers were measured in sputum and serum. Viruses and selected bacteria were assessed in sputum by polymerase chain reaction and routine diagnostic bacterial culture. Biologic phenotypes were explored using unbiased cluster analysis and biomarkers that differentiated clinical exacerbation phenotypes were investigated. MEASUREMENTS AND MAIN RESULTS: A total of 145 patients (101 men and 44 women) entered the study. A total of 182 exacerbations were captured from 86 patients. Four distinct biologic exacerbation clusters were identified. These were bacterial-, viral-, or eosinophilic-predominant, and a fourth associated with limited changes in the inflammatory profile termed "pauciinflammatory." Of all exacerbations, 55%, 29%, and 28% were associated with bacteria, virus, or a sputum eosinophilia. The biomarkers that best identified these clinical phenotypes were sputum IL-1ß, 0.89 (area under receiver operating characteristic curve) (95% confidence interval [CI], 0.830.95); serum CXCL10, 0.83 (95% CI, 0.700.96); and percentage peripheral eosinophils, 0.85 (95% CI, 0.780.93), respectively. CONCLUSIONS: The heterogeneity of the biologic response of COPD exacerbations can be defined. Sputum IL-1ß, serum CXCL10, and peripheral eosinophils are biomarkers of bacteria-, virus-, or eosinophil-associated exacerbations of COPD. Whether phenotype-specific biomarkers can be applied to direct therapy warrants further investigation.
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Doença Pulmonar Obstrutiva Crônica/microbiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Infecções Bacterianas/metabolismo , Infecções Bacterianas/microbiologia , Biomarcadores/sangue , Biomarcadores/metabolismo , Quimiocina CXCL10/sangue , Análise por Conglomerados , Eosinófilos/metabolismo , Eosinófilos/microbiologia , Feminino , Humanos , Inflamação/metabolismo , Inflamação/microbiologia , Interleucina-1beta/metabolismo , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Estudos Prospectivos , Doença Pulmonar Obstrutiva Crônica/sangue , Doença Pulmonar Obstrutiva Crônica/metabolismo , Curva ROC , Índice de Gravidade de Doença , Escarro/metabolismo , Escarro/microbiologiaRESUMO
Background. Asthma and obesity are common; however the impact of obesity upon asthma remains uncertain. Objectives. To assess relationships between obesity and fat mass with airway inflammation, lung function, and disease control in patients with refractory asthma. Methods. 151 refractory asthma patients were characterised for measures of airway inflammation, lung function, Juniper asthma control questionnaire (JACQ), body mass index (BMI), and fat mass index (FMI) derived from dual energy X-ray absorptiometry. Patients were reassessed over 12 months. Results. 74% of patients had an elevated BMI. BMI and FMI correlated (r = 0.9, P < .001). FMI and JACQ correlated in men (r = 0.3, P = .01). After 12 months 23% lost weight. Weight change over 12 months correlated with FEV(1) change (r = -0.3, P = .03), but not with change in JACQ or exacerbations. Conclusion. Increased fat mass is common in refractory asthma and is associated with asthma symptom control in men. Loss of weight is associated with improvement in lung function in refractory asthma.