RESUMEN
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces a wide range of disease severity, ranging from asymptomatic infection to a life-threating illness, particularly in the elderly population and individuals with comorbid conditions. Among individuals with serious coronavirus 2019 (COVID-19) disease, acute respiratory distress syndrome (ARDS) is a common and often fatal presentation. Animal models of SARS-CoV-2 infection that manifest severe disease are needed to investigate the pathogenesis of COVID-19-induced ARDS and evaluate therapeutic strategies. We report two cases of ARDS in two aged African green monkeys (AGMs) infected with SARS-CoV-2 that had pathological lesions and disease similar to severe COVID-19 in humans. We also report a comparatively mild COVID-19 phenotype characterized by minor clinical, radiographic, and histopathologic changes in the two surviving, aged AGMs and four rhesus macaques (RMs) infected with SARS-CoV-2. Notable increases in circulating cytokines were observed in three of four infected, aged AGMs but not in infected RMs. All the AGMs had increased levels of plasma IL-6 compared with baseline, a predictive marker and presumptive therapeutic target in humans infected with SARS-CoV-2. Together, our results indicate that both RMs and AGMs are capable of modeling SARS-CoV-2 infection and suggest that aged AGMs may be useful for modeling severe disease manifestations, including ARDS.
Asunto(s)
COVID-19/etiología , Pulmón/virología , SARS-CoV-2/patogenicidad , Envejecimiento , Animales , Chlorocebus aethiops/virología , Infecciones por Coronavirus/tratamiento farmacológico , Citocinas/metabolismo , Humanos , Pulmón/patología , Macaca mulatta/virología , Carga Viral/métodosRESUMEN
Lifestyle-based disease prevention and self-management strategies play an important role in the mitigation of health, social, and economic burdens associated with type 2 diabetes mellitus (T2DM) and other chronic diseases. However, there are significant implementation and translational challenges associated with the design and delivery of effective interventions. In this study, data-driven techniques for the identification of optimal target audiences and intervention targets for T2DM prevention interventions were applied. Australian adults (N = 3159) with differing T2DM status (no diabetes diagnosis, pre-diabetes, or T2DM) completed self-report assessments of diet quality, physical activity, psychological distress, future orientation, health literacy, and socio-demographic characteristics. K-medoids cluster analysis was conducted to identify homogenous groups within the research sample and proportional odds ordinal logistic regressions conducted to identify signficant predictors of T2DM status within each cluster. Results identified a two-factor optimal solution that stratified participants based on sex (male/female). Within each cluster, psychosocial variables explained approximately 25% of the variance in T2DM status, with future orientation identified as a significant modifiable predictor of T2DM. For the male cluster, health literacy was also significant (p ≤0.01). Findings indicate that men and women should be targeted separately in T2DM prevention or management programs and that future interventional research targeting future orientation is warranted.
Asunto(s)
Diabetes Mellitus Tipo 2 , Estado Prediabético , Adulto , Australia/epidemiología , Análisis por Conglomerados , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/prevención & control , Femenino , Humanos , Estilo de Vida , MasculinoRESUMEN
BACKGROUND: Risk assessment models must be continuously validated and updated to ensure that predictions remain valid. Here, the Endovascular Aneurysm Repair Risk Assessment Model, developed in 2008, is updated and improved. METHODS: We used prospectively collected data from Australian patients who underwent elective endovascular aneurysm repair between 2009 and 2013 (n = 695). Data were provided by treating surgeons and the National Death Index. Key outcomes were early and midterm survival, early complications (endoleak, operative, and graft-related) and late complications (endoleak and graft-related). Multinomial logistic regression determined which preoperative variables best predicted each outcome. Area under Receiver Operating Characteristic curve (AUROC), model P-value and internal validation statistics were used to select the best model. RESULTS: Ten preoperative variables were included in the modeling for 10 key outcomes. The most valid outcomes with AUROC>0.7 were 1- and 3-year survival, 30 and 90-day mortality, early and late endoleak (types I, III and IV) and type II endoleak (with an increase in sac size ≥5 mm). The 10 preoperative variables that contributed to outcome models were self-reported fitness, American Society of Anesthesiologists physical status score, history of stroke/transient ischemic attack, age, aneurysm angle, infrarenal neck length, white cell count, respiratory assessment, diabetes and statin therapy. Fitness alone statistically significantly predicted 30 and 90-day deaths better than any other preoperative variable; achieving high AUROCs (0.78 and 0.80), and high odds ratios (12.8 [95% CI: 1.5-110.4] and 18.1 [95% CI: 2.2-149]). CONCLUSIONS: An updated interactive predictive model of outcomes after endovascular aneurysm repair has been created. Many of the variables used in the 2008 model continued to be significant, however, new variables including fitness and respiratory assessment, improved the model. The new model uses variables routinely collected preoperatively, and hence can better support surgeon-patient discussions prior to operation. Informing patients of potential risks or likely outcomes following elective surgery can assist with preoperative shared decision-making.
Asunto(s)
Aneurisma de la Aorta/cirugía , Implantación de Prótesis Vascular , Técnicas de Apoyo para la Decisión , Anciano , Anciano de 80 o más Años , Aneurisma de la Aorta/diagnóstico , Aneurisma de la Aorta/mortalidad , Australia , Implantación de Prótesis Vascular/efectos adversos , Implantación de Prótesis Vascular/mortalidad , Toma de Decisiones Clínicas , Toma de Decisiones Conjunta , Procedimientos Endovasculares/efectos adversos , Procedimientos Endovasculares/mortalidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Participación del Paciente , Complicaciones Cognitivas Postoperatorias/etiología , Valor Predictivo de las Pruebas , Estudios Prospectivos , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Resultado del TratamientoRESUMEN
Elemental mercury (Hg0) contamination in artisanal and small-scale gold mining (ASGM) communities is widespread, and Hg0-contaminated tailings are often reprocessed with cyanide (-CN) to extract residual gold remaining after amalgamation. Hg0 reacts with -CN under aerobic conditions to produce Hg(CN)42- and other Hg(CN)nn-2 complexes. The production of solvated Hg(CN)nn-2 complexes increases upon agitation in the presence of synthetic and authentic Hg0-contaminated tailings that aid in dispersing the Hg0, increasing its reactive surface area. Adult rats were exposed to various concentrations of Hg(CN)2, and accumulation in organs and tissues was quantified using direct mercury analysis. The primary site of Hg(CN)2 accumulation was the kidney, although accumulation was also detected in the liver, spleen, and blood. Little accumulation was observed in the brain, suggesting that Hg(CN)2 complexes do not cross the blood-brain barrier. Renal tissue was particularly sensitive to the effects of Hg(CN)2, with pathological changes observed at low concentrations. Hg(CN)2 complexes are handled by mammalian systems in a manner similar to other inorganic species of Hg, yet appear to be more toxic to organ systems. The findings from this study are the first to show that Hg(CN)2 complexes are highly stable complexes that can lead to cellular injury and death in mammalian organ systems.
Asunto(s)
Cianuros/toxicidad , Oro/toxicidad , Compuestos de Mercurio/toxicidad , Mercurio/toxicidad , Animales , Encéfalo/efectos de los fármacos , Monitoreo del Ambiente , Riñón/efectos de los fármacos , Hígado/efectos de los fármacos , Masculino , Minería , Ratas , Ratas Wistar , Solubilidad , Bazo/efectos de los fármacosRESUMEN
Age-related cataract is the major cause of blindness worldwide. Both genetic and environmental factors contribute to the disease. Genetic variation in the Ephrin type-A receptor 2 (EPHA2) gene is associated with the risk of age-related cataract in multiple populations, and exposure to ultraviolet-B (UV-B) radiation is a well-established risk factor for the disease. Epha2 knockout and UV-B radiation independently lead to cataract in mice, and UV-B radiation reportedly alters EPHA2 expression in cultured cells. We hypothesised that an interaction between UV-B radiation exposure and Epha2 signalling may influence cataract development. To test this hypothesis, 5-week-old Epha2+/+ and Epha2+/- mice (nâ¯=â¯8 per group) were exposed to repeated below-threshold doses of UV-B radiation (0.0125-0.05â¯J/cm2), before development of Epha2-mediated cataract. Cataract development was monitored after termination of exposure and at least one month later. Histological analysis of exposed and unexposed lenses was performed to assess pathological changes, and gene expression analysis to investigate the mechanism underlying cataract. Both Epha2+/+ and Epha2+/- mice developed UV-B dose-dependent anterior polar cataract; cataract severity in both genotypes of mice exposed to either 0.025 or 0.05â¯J/cm2 UV-B was significantly higher than that in matched unexposed mice (pâ¯<â¯0.05). Histological analysis of lenses of both genotypes of mice exposed to 0.025 or 0.05â¯J/cm2 UV-B radiation consistently revealed disruption of the lens architecture. A month after the exposure, cataract severity increased in Epha2+/+ mice treated with the highest dose of UV-B radiation (pâ¯=â¯0.03) but remained unchanged in Epha2+/- mice. Gene expression analysis of lenses of both genotypes of mice showed significant upregulation of the cell proliferation marker Mki67 in Epha2+/+ (pâ¯=â¯0.036) but not in Epha2+/- mice exposed to the highest dose of UV-B radiation compared to matched unexposed mice. In conclusion, this study suggests that repeated exposure to doses of UV-B radiation lower than the single minimum dose required for inducing cataract leads to cataract in wild-type and Epha2 heterozygous knockout mice. Furthermore, this study indicates, for the first time, a potentially favourable effect of partial Epha2 deficiency against UV radiation-induced damage in the lens.
Asunto(s)
Catarata/genética , Interacción Gen-Ambiente , Cristalino/efectos de la radiación , Traumatismos Experimentales por Radiación/genética , Receptor EphA2/genética , Rayos Ultravioleta/efectos adversos , Animales , Catarata/patología , Relación Dosis-Respuesta en la Radiación , Proteínas del Ojo/genética , Regulación de la Expresión Génica/fisiología , Genotipo , Técnicas de Genotipaje , Cristalino/patología , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Dosis de Radiación , Traumatismos Experimentales por Radiación/patología , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
Humans throughout the world are exposed regularly to mixtures of environmental toxicants. Four of the most common heavy metal toxicants in the environment are mercury (Hg), cadmium (Cd), lead (Pb), and arsenic (As). Numerous studies have assessed the effects and disposition of individual metals in organ systems; however, humans are usually exposed to mixtures of toxicants or metals rather than to a single toxicant. Therefore, the purpose of the current study was to test the hypothesis that exposure to a mixture of toxic heavy metals alters the disposition of single metals in target organs. Wistar rats (Rattus norvegicus) were exposed to Hg, Cd, Pb, or As as a single metal or as a mixture of metals. Rats were injected intravenously for three days, following which kidneys, liver, brain, and blood were harvested. Samples were analyzed for content of Hg, Cd, Pb, and As via inductively coupled plasma mass spectrometry. In general, exposure to a mixture of metals reduced accumulation of single metals in target organs. Interestingly, exposure to mixtures of metals with Pb and/or As increased the concentration of these metals specifically in the liver. The findings from this study indicate that exposure to mixtures of toxic heavy metals may alter significantly the distribution and accumulation of these metals in target organs and tissues.
RESUMEN
As "taste" is a primary driver of food choice, the objective of this study was to understand how the sensory properties of diets relate to energy intake (EI). A database of 720 frequently consumed foods, described by a trained panel for basic tastes (sweetness, saltiness) and fatty mouthfeel, was systematically applied to all foods reportedly consumed in 24hr recalls as part of the 2011-2012 Australian National Nutrition and Physical Activity Survey (nâ¯=â¯12,153 adults and children). Food groups were classified according to the Australian Guide to Healthy Eating, and their contribution to total nutrient and sensory intake estimated. There were significant positive correlations between the nutrient and sensory properties of diets, for example, for adults, EI and fatty mouthfeel râ¯=â¯0.740; EI and saltiness râ¯=â¯0.623 and EI and sweetness râ¯=â¯0.517 (all pâ¯<â¯0.01). Core foods (e.g. fruits, vegetables, grains, dairy) can provide similar sensory stimulation whilst being of lower energy content than discretionary foods (e.g. confectionary, snacks). Regression models in adults, controlling for age, sex and BMI, revealed that fatty mouthfeel (ßâ¯=â¯0.492), saltiness (ßâ¯=â¯0.161) and sweetness (ßâ¯=â¯0.138) were significant predictors of EI, explaining 56% variance (pâ¯<â¯0.01). Similar results were found for children. Fatty mouthfeel was the primary driver of energy intake but such sensory stimulation can be derived from core (e.g. dairy foods), rather than discretionary foods, at lower energy content.
Asunto(s)
Ingestión de Energía , Preferencias Alimentarias , Gusto , Adolescente , Adulto , Anciano , Niño , Bases de Datos Factuales , Grasas de la Dieta , Azúcares de la Dieta , Femenino , Humanos , Masculino , Persona de Mediana Edad , Sodio en la Dieta , Encuestas y Cuestionarios , Adulto JovenRESUMEN
OBJECTIVES: The purpose of this study was to examine the impact telemedicine in the intensive care unit (ICU) has on the competency, satisfaction, and education of resident physicians. METHODS: Telemedicine in the ICU was implemented in 2014 at a community hospital with 24 family medicine residents. Comfort with the performance of various common procedures; management of major medical diseases in the ICU; and level of comfort, attitudes, and satisfaction in work relationships with various staff members in the ICU were assessed before and 1 year after the telemedicine implementation. This was done by the residents' respective training year and by all year groups combined. The Likert scores for each category were averaged by year group and by the three year groups combined, and these averages were compared pre- and posttelemedicine implementation using the t test method. RESULTS: All of the residents in the program participated voluntarily in the study, a 100% response rate. The results showed significant positive effects on resident education and satisfaction among ICU nurses and residents after the implementation of telemedicine-ICU. There were negative effects on residents' learning opportunities with the family medicine attending physicians, feelings of being a valued team member, and comfort with ventilator management. CONCLUSIONS: Telemedicine-ICU implementation had mixed effects on residents' perceptions of their ICU experience and training. Further studies should be conducted to assess how to maximize resident training in this setting.
Asunto(s)
Actitud del Personal de Salud , Unidades de Cuidados Intensivos , Internado y Residencia , Telemedicina , Humanos , Kentucky , PercepciónRESUMEN
BACKGROUND: To review the trends in patient selection and early death rate for patients undergoing elective endovascular repair of infrarenal abdominal aortic aneurysms (EVAR) in 3 countries. For this study, audit data from 4,163 patients who had undergone elective infrarenal EVAR were amalgamated. The data originated from Australia, Canada (Ontario), and England (London, Cambridge, and Leicester). METHODS: Statistical analyses were undertaken to determine whether patient characteristics and early death rate varied between and within study groups and over time. The study design was retrospective analysis of data collected prospectively between 1999 and 2012. RESULTS: One-year survival improved over time (P = 0.0013). Canadian patients were sicker than those in Australia or England (P < 0.001). American Society of Anesthesiologists classification (ASA) increased over time across all countries although more significantly in Canada. Age at operation remained constant, although older patients were treated more recently in London (P < 0.001). English centers treated larger aneurysms compared with Australia and Canada (P < 0.001). Australian centers treated a much larger proportion of aneurysms that were <55 mm than other countries. Preoperative creatinine levels decreased over time for all countries and centers (P < 0.001). Infrarenal neck angles have significantly decreased over time (P < 0.001). Recent data from London (UK) showed that operations were performed on longer (P < 0.001) and wider (P < 0.001) infrarenal necks than elsewhere. CONCLUSIONS: In this international comparison, several trends were noted including improved 1-year survival despite declining patient health (as measured by increasing ASA status). This may reflect greater knowledge regarding EVAR that centers from different countries have gained over the last decade and improved medical management of patients with aneurysmal disease.
Asunto(s)
Aneurisma de la Aorta Abdominal/cirugía , Implantación de Prótesis Vascular/tendencias , Procedimientos Endovasculares/tendencias , Pautas de la Práctica en Medicina/tendencias , Anciano , Aneurisma de la Aorta Abdominal/diagnóstico , Aneurisma de la Aorta Abdominal/mortalidad , Australia , Implantación de Prótesis Vascular/efectos adversos , Implantación de Prótesis Vascular/mortalidad , Procedimientos Quirúrgicos Electivos , Procedimientos Endovasculares/efectos adversos , Procedimientos Endovasculares/mortalidad , Inglaterra , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ontario , Selección de Paciente , Estudios Retrospectivos , Factores de Riesgo , Análisis de Supervivencia , Factores de Tiempo , Resultado del TratamientoRESUMEN
OBJECTIVE: The purpose of this study was to gain information on the current status of fieldwork training facilities to understand facilitators of and barriers to fieldwork education, including fieldwork educators' perceptions of benefits, challenges, and valued supports. METHOD: A descriptive, nonexperimental exploratory design was used. A pilot survey was conducted, and a revised online survey, consisting of 49 items, was distributed nationwide in Fall 2013. RESULTS: Opportunity to update practice was the most commonly perceived benefit associated with fieldwork, and workload or time was the greatest perceived challenge. Readiness and high-quality preparation of students by academic programs were the most valued supports. Participants also identified preferred time frames and supervisory models of fieldwork education. CONCLUSION: Interpretation of these data provides valuable information for the profession, notably academic programs, regarding needs and resources to foster collaborative relationships with fieldwork facilities to meet the growing need for fieldwork education.
RESUMEN
OBJECTIVE: The Endovascular aneurysm repair Risk Assessment (ERA) model predicts survival (early death, 3-year survival, and 5-year survival), reinterventions, and endoleaks after elective endovascular aneurysm repair. We externally validated the ERA model in our cohort of patients. METHODS: This was a retrospective validation study of 433 consecutive patients with an asymptomatic abdominal aortic aneurysm treated with endovascular aneurysm repair in three hospitals (Amsterdam, The Netherlands) between 1997 and 2010. The area under the receiver operating characteristic curve was used as measure of accuracy (>0.70 was considered as sufficiently accurate). RESULTS: The early death rate was 1% (3 of 433; 95% confidence interval [CI], 0%-2%), the 5-year survival rate was 65% (95% CI, 61%-70%), the 5-year reintervention rate was 18% (95% CI, 14-78%), and the 5-year rate of type I, II, or III endoleak was 25% (95% CI, 20%-29%). The areas under the curve varied between 0.64 and 0.66 for predictions of survival and between 0.47 and 0.61 for reinterventions and endoleaks. CONCLUSIONS: The predictions of survival, reinterventions, and endoleaks made by the ERA model were not sufficiently accurate to be used in our clinical practice.
Asunto(s)
Aneurisma de la Aorta Abdominal/cirugía , Endofuga/epidemiología , Procedimientos Endovasculares , Medición de Riesgo/métodos , Anciano , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Países Bajos/epidemiología , Curva ROC , Reoperación/estadística & datos numéricos , Reproducibilidad de los Resultados , Estudios Retrospectivos , Tasa de Supervivencia/tendencias , Factores de TiempoRESUMEN
BACKGROUND AND AIM OF THE STUDY: The study aim was to evaluate the performance of a new stented pericardial bioprosthesis, the Trifecta (St. Jude Medical, St. Paul, MN, USA), for aortic valve replacement (AVR) with respect to valvular hemodynamics and frequency of patient-prosthesis mismatch (PPM). PPM has been reported in a wide range of bioprosthetic valves following AVR, and has been associated with multiple adverse outcomes. It was hypothesized that the Trifecta aortic valve would have superior hemodynamics and an acceptable incidence of PPM following AVR. METHODS: A prospective cohort study was performed between January 2010 and May 2012, following 75 patients (mean age 71.9 _ 11.1 years) who had undergone AVR with a Trifecta valve for aortic stenosis (88%) or regurgitation (12%) at the authors' institutions. Intraoperative three-dimensional and Doppler transesophageal echocardiography were used to evaluate hemodynamic variables before and after AVR, as well as pre-discharge. RESULTS: Echocardiographic evaluation showed a preoperative average mean gradient (MG) of 40.6 ± 21.6 mmHg, an average peak gradient (PG) of 72.1 ± 19.4 mmHg, and an average effective orifice area index (EOAI) of 0.39 ± 0.20 cm2/m2. Postoperative mean pressure gradient measurements showed a postoperative average MG of 8.76 ± 3.75 mmHg (p < 0.001), an average PG of 19.4 ± 8.6 mmHg (p < 0.001), and EOAI of 1.09 ± 0.36 cm2/m2 (p < 0.001), which demonstrated a significantly improved hemodynamic performance across all valve sizes. Postoperative MG versus measured EOAI demonstrated a fairly linear relationship (R2 = 0.0703), rather than a rapid increase in MG with EOAI < 0.85 and < 0.65, as was seen with previous valve designs. Severe PPM (defined as EOAI ≤ 0.65 cm2/m2) was found in four patients (6%), while moderate PPM (EOAI > 0.65 and < 0.85 cm2/m2) was seen in 11 patients (16%). CONCLUSION: The Trifecta pericardial valve demonstrated excellent hemodynamic performance at all valve sizes, and resulted in very low postoperative transvalvular pressure gradients and PPM, without the need for aortic root enlargement.
Asunto(s)
Insuficiencia de la Válvula Aórtica/fisiopatología , Insuficiencia de la Válvula Aórtica/cirugía , Válvula Aórtica/fisiopatología , Válvula Aórtica/cirugía , Bioprótesis , Prótesis Valvulares Cardíacas , Ajuste de Prótesis , Adulto , Anciano , Anciano de 80 o más Años , Válvula Aórtica/diagnóstico por imagen , Insuficiencia de la Válvula Aórtica/diagnóstico por imagen , Femenino , Prótesis Valvulares Cardíacas/efectos adversos , Implantación de Prótesis de Válvulas Cardíacas/efectos adversos , Hemodinámica , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Diseño de Prótesis , Stents , UltrasonografíaRESUMEN
Human immunodeficiency virus (HIV) and malaria, caused by infection with Plasmodium spp., are endemic in similar geographical locations. As a result, there is high potential for HIV/Plasmodium co-infection, which increases the pathology of both diseases. However, the immunological mechanisms underlying the exacerbated disease pathology observed in co-infected individuals are poorly understood. Moreover, there is limited data available on the impact of Plasmodium co-infection on antiretroviral (ART)-treated HIV infection. Here, we used the rhesus macaque (RM) model to conduct a pilot study to establish a model of Plasmodium fragile co-infection during ART-treated simian immunodeficiency virus (SIV) infection, and to begin to characterize the immunopathogenic effect of co-infection in the context of ART. We observed that P. fragile co-infection resulted in parasitemia and anemia, as well as persistently detectable viral loads (VLs) and decreased absolute CD4+ T-cell counts despite daily ART treatment. Notably, P. fragile co-infection was associated with increased levels of inflammatory cytokines, including monocyte chemoattractant protein 1 (MCP-1). P. fragile co-infection was also associated with increased levels of neutrophil elastase, a plasma marker of neutrophil extracellular trap (NET) formation, but significant decreases in markers of neutrophil degranulation, potentially indicating a shift in the neutrophil functionality during co-infection. Finally, we characterized the levels of plasma markers of gastrointestinal (GI) barrier permeability and microbial translocation and observed significant correlations between indicators of GI dysfunction, clinical markers of SIV and Plasmodium infection, and neutrophil frequency and function. Taken together, these pilot data verify the utility of using the RM model to examine ART-treated SIV/P. fragile co-infection, and indicate that neutrophil-driven inflammation and GI dysfunction may underlie heightened SIV/P. fragile co-infection pathogenesis.
Asunto(s)
Coinfección , Inflamación , Macaca mulatta , Malaria , Neutrófilos , Plasmodium , Síndrome de Inmunodeficiencia Adquirida del Simio , Virus de la Inmunodeficiencia de los Simios , Animales , Coinfección/tratamiento farmacológico , Coinfección/parasitología , Coinfección/virología , Malaria/tratamiento farmacológico , Malaria/inmunología , Malaria/complicaciones , Síndrome de Inmunodeficiencia Adquirida del Simio/tratamiento farmacológico , Síndrome de Inmunodeficiencia Adquirida del Simio/inmunología , Síndrome de Inmunodeficiencia Adquirida del Simio/complicaciones , Proyectos Piloto , Neutrófilos/inmunología , Antirretrovirales/uso terapéutico , Carga Viral , Biomarcadores/sangre , Citocinas/sangre , Modelos Animales de Enfermedad , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/inmunologíaRESUMEN
BACKGROUND: Melioidosis is a disease caused by the bacterium Burkholderia pseudomallei, infecting humans and non-human primates (NHP) through contaminated soil or water. World-wide there are an estimated 165,000 human melioidosis cases each year, but recordings of NHP cases are sporadic. Clinical detection of melioidosis in humans is primarily by culturing B. pseudomallei, and there are no standardized detection protocols for NHP. NHP are an important animal model for melioidosis research including clinical trials and development of biodefense countermeasures. METHODOLOGY/PRINCIPLE FINDINGS: We evaluated the diagnostic potential of the multiple antigen serological assay, BurkPx, in NHP using two sera sets: (i) 115 B. pseudomallei-challenged serum samples from 80 NHP collected each week post-exposure (n = 52) and at euthanasia (n = 47), and (ii) 126 B. pseudomallei-naïve/negative serum samples. We observed early IgM antibody responses to carbohydrate antigens followed by IgG antibody recognition to multiple B. pseudomallei protein antigens during the second week of infection. B. pseudomallei negative serum samples had low to intermediate antibody cross reactivity to the antigens in this assay. Infection time was predicted as the determining factor in the variation of antibody responses, with 77.67% of variation explained by the first component of the principal component analysis. A multiple antigen model generated a binary prediction metric ([Formula: see text]), which when applied to all data resulted in 100% specificity and 63.48% sensitivity. Removal of week 1 B. pseudomallei challenged serum samples increased the sensitivity of the model to 95%. CONCLUSION/SIGNIFICANCE: We employed a previously standardized assay for humans, the BurkPx assay, and assessed its diagnostic potential for detection of B. pseudomallei exposure in NHP. The assay is expected to be useful for surveillance in NHP colonies, in investigations of suspected accidental releases or exposures, and for identifying vaccine correlates of protection.
Asunto(s)
Burkholderia pseudomallei , Melioidosis , Animales , Humanos , Melioidosis/diagnóstico , Melioidosis/veterinaria , Melioidosis/epidemiología , Anticuerpos Antibacterianos , Antígenos Bacterianos , PrimatesRESUMEN
We investigated the impact of rhesus macaque (RM) B-cell depletion before inoculation with the isolate SIVsmmD215. Seven RMs were treated every 3 weeks with 50 mg/kg of an anti-CD20 antibody (rituximab) starting 7 days before inoculation for 2 (n = 4) and 5 (n = 3) months. Four control animals received no antibody. Three animals were completely depleted of CD20(+) B cells, but 4 were only partially depleted of CD20 cells in the LNs and intestine. The decrease in antibody production was consistent with the efficacy of tissue CD20 depletion. Seroconversion and neutralizing antibody production was significantly delayed in animals showing complete tissue CD20 depletion and remained at low titers in all CD20-depleted RMs. Surprisingly, there was no significant difference in acute or chronic viral loads between CD20-depleted and control animal groups. There was a tendency for lower viral set points in CD20-depleted animals. At 6 weeks after inoculation, cellular immune responses were significantly stronger in CD20-depleted animals than in controls. There was no significant difference in survival between CD20-depleted and control animals. Our data suggest that a deficiency of Ab responses did not markedly affect viral replication or disease progression and that they may be compensated by more robust cellular responses.
Asunto(s)
Anticuerpos Antivirales/inmunología , Síndrome de Inmunodeficiencia Adquirida del Simio/inmunología , Virus de la Inmunodeficiencia de los Simios/patogenicidad , Viremia/prevención & control , Animales , Anticuerpos Monoclonales/farmacología , Anticuerpos Monoclonales de Origen Murino , Formación de Anticuerpos/fisiología , Antígenos CD20/inmunología , Linfocitos B/fisiología , Citometría de Flujo , Inmunidad Celular , Técnicas para Inmunoenzimas , Factores Inmunológicos/farmacología , Intestinos/inmunología , Intestinos/virología , Activación de Linfocitos/efectos de los fármacos , Depleción Linfocítica , Macaca mulatta , Masculino , Rituximab , Linfocitos T/inmunología , Carga Viral , Replicación Viral/efectos de los fármacosRESUMEN
INTRODUCTION: Endovascular abdominal aortic aneurysm (AAA) repair (EVAR) has been associated with lower operative mortality and morbidity than open surgery but comparable long-term mortality and higher delayed complication and reintervention rates. Attention has therefore been directed to identifying preoperative and operative variables that influence outcomes after EVAR. Risk-prediction models, such as the EVAR Risk Assessment (ERA) model, have also been developed to help surgeons plan EVAR procedures. The aims of this study were (1) to describe outcomes of elective EVAR at the Royal Brisbane and Women's Hospital (RBWH), (2) to identify preoperative and operative variables predictive of outcomes after EVAR, and (3) to externally validate the ERA model. METHODS: All elective EVAR procedures at the RBWH before July 1, 2009, were reviewed. Descriptive analyses were performed to determine the outcomes. Univariate and multivariate analyses were performed to identify preoperative and operative variables predictive of outcomes after EVAR. Binomial logistic regression analyses were used to externally validate the ERA model. RESULTS: Before July 1, 2009, 197 patients (172 men), who were a mean age of 72.8 years, underwent elective EVAR at the RBWH. Operative mortality was 1.0%. Survival was 81.1% at 3 years and 63.2% at 5 years. Multivariate analysis showed predictors of survival were age (P = .0126), American Society of Anesthesiologists (ASA) score (P = .0180), and chronic obstructive pulmonary disease (P = .0348) at 3 years and age (P = .0103), ASA score (P = .0006), renal failure (P = .0048), and serum creatinine (P = .0022) at 5 years. Aortic branch vessel score was predictive of initial (30-day) type II endoleak (P = .0015). AAA tortuosity was predictive of midterm type I endoleak (P = .0251). Female sex was associated with lower rates of initial clinical success (P = .0406). The ERA model fitted RBWH data well for early death (C statistic = .906), 3-year survival (C statistic = .735), 5-year survival (C statistic = .800), and initial type I endoleak (C statistic = .850). CONCLUSIONS: The outcomes of elective EVAR at the RBWH are broadly consistent with those of a nationwide Australian audit and recent randomized trials. Age and ASA score are independent predictors of midterm survival after elective EVAR. The ERA model predicts mortality-related outcomes and initial type I endoleak well for RBWH elective EVAR patients.
Asunto(s)
Aneurisma de la Aorta Abdominal/cirugía , Implantación de Prótesis Vascular , Procedimientos Endovasculares , Indicadores de Salud , Factores de Edad , Anciano , Anciano de 80 o más Años , Aneurisma de la Aorta Abdominal/diagnóstico por imagen , Aneurisma de la Aorta Abdominal/mortalidad , Aortografía/métodos , Implantación de Prótesis Vascular/efectos adversos , Implantación de Prótesis Vascular/mortalidad , Distribución de Chi-Cuadrado , Procedimientos Quirúrgicos Electivos , Endofuga/etiología , Procedimientos Endovasculares/efectos adversos , Procedimientos Endovasculares/mortalidad , Femenino , Humanos , Estimación de Kaplan-Meier , Modelos Logísticos , Masculino , Valor Predictivo de las Pruebas , Queensland , Reproducibilidad de los Resultados , Medición de Riesgo , Factores de Riesgo , Factores Sexuales , Factores de Tiempo , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
Approximately one quarter of all hospitalized patients over age 75 years have a secondary diagnosis of dementia. A unique hospital-wide program to encourage appropriate communication techniques with patients who have dementia was provided to all departments of a hospital. Evaluation indicated improvement in some communication techniques. Additional education is needed to disperse the information to as many staff as possible and to sustain the change.
Asunto(s)
Competencia Clínica , Comunicación , Demencia/enfermería , Relaciones Enfermero-Paciente , Desarrollo de Personal/métodos , Factores de Edad , Anciano , Distribución de Chi-Cuadrado , Escolaridad , Humanos , Modelos Organizacionales , Innovación Organizacional , Proyectos Piloto , Desarrollo de Programa/métodos , Evaluación de Programas y Proyectos de SaludRESUMEN
As the population ages, the number of patients with dementia will increase rapidly. Nurses caring for patients with dementia will need knowledge of interventions for communicating; managing agitation, nutrition, hygiene, and pain; providing spiritual care; and determining decision-making capacity.
Asunto(s)
Demencia , Necesidades y Demandas de Servicios de Salud/organización & administración , Pacientes Internos , Anciano , Trastornos de la Comunicación/etiología , Demencia/complicaciones , Demencia/epidemiología , Demencia/enfermería , Evaluación Geriátrica , Enfermería Geriátrica/organización & administración , Humanos , Higiene , Actividades Recreativas , Competencia Mental , Rol de la Enfermera , Evaluación en Enfermería , Apoyo Nutricional , Dolor/etiología , Agitación Psicomotora/etiología , EspiritualidadRESUMEN
ObjectiveMindStep™ is an Australian low-intensity cognitive behaviour therapy (LICBT) program for individuals with mild-to-moderate symptoms of anxiety and depression. UK-produced LICBT guided self-help (GSH) materials were originally used in the MindStep™ program. In 2017, Australian LICBT GSH materials were developed to better suit Australian users. This study explored whether the Australian-produced materials continued to achieve the benchmark recovery rates established in the UK and maintained in recent Australian studies.MethodsBinomial logistic regression was conducted using retrospective client data, including the Patient Health Questionnaire-9 and the Generalised Anxiety Disorder 7-item scale, between 2016 and 2019.ResultsDuring time periods in which the Australian-produced materials were used, equivalent rates of reliable recovery and improvement were achieved compared with time periods in which the UK-produced materials were used. Australian-trained LICBT coaches, using Australian-produced LICBT GSH materials, achieve client recovery rates of up to 60%, reliable improvement rates of 58% and reliable recovery rates of 46% (with the probability of recovery increasing with client age).ConclusionsThese findings are particularly pertinent with COVID-19 changing the landscape of mental health service delivery, requiring greater flexibility in the use of teleservices to ensure access to effective mental health care for populations that may already experience problems with isolation, access and service engagement.What is known about the topic?LICBT is an acceptable, feasible and effective treatment approach for people experiencing mild-to-moderate anxiety and depression in Australia. LICBT GSH materials used with clients in Australia originated from the UK. However, according to guidelines, LICBT GSH materials should be contextualised to suit the audience they are being used with.What does this paper add?This paper demonstrates that LICBT GSH materials tailored to an Australian context can be used in place of UK-produced materials because they yield equivalent and consistent therapeutic outcomes. Although contextualising the LICBT GSH materials for health services users was important, it is likely that the evidence-based cognitive behaviour therapy techniques sitting 'under the hood' of these materials are most important to ensure successful therapeutic outcomes.What are the implications for practitioners?As we face unprecedented challenges following 2020, the physical, social, psychological and economic impacts of life-changing events must not inhibit access to treatments for common mental health conditions. It is anticipated that more non-traditional, alternative providers of mental health services will be needed to scale-up and respond to increasing demand. This paper shows that the provision of telephone-based LICBT in Australia, by trained coaches using Australian-produced GSH materials, is an evidenced-based support pathway that can reduce the access gap to treatments.
RESUMEN
BACKGROUND: A single state-wide upper gastrointestinal (GI) cancer video-linked multidisciplinary team (MDT) meeting guides management and evidence-based care for all newly diagnosed upper GI cancer patients in South Australia. This study determined the patterns of care and outcomes for patients diagnosed with gastric and gastro-oesophageal junction (GOJ) cancers. METHODS: Patients diagnosed with gastric cancer and GOJ (Siewert III) cancer between June 2012 and June 2016 were included. Patient demographics, cancer stage, histology, diagnostic modalities and treatment data was analysed from a prospective database. Stage-specific survival outcomes were determined and analysed for each treatment modality. RESULTS: The study included 218 patients and at diagnosis 132 (61%) patients had stage I-III and 86 (39%) patients had stage IV disease. One hundred and ninety-five (89%) patients had gastric cancer and 23 (11%) had GOJ cancer (Siewert III). One hundred and nine (50%) patients underwent surgery, with 92% R0 resection rate. Forty-six patients received perioperative chemotherapy and 111 (51%) patients received palliative intent treatment. Median overall survival for stage II, III and IV cancers was 57.6 (95% CI 57.6-NR), 22.8 (95% CI 20.4-43.2), and 6.0 months (95% CI 4.8-8.4) respectively (p < 0.001). Median overall survival for patients who underwent perioperative chemotherapy and surgery was not reached as compared to 44.4 months (95% CI 28.8-NR) for patients who underwent surgery alone. CONCLUSION: Treatment outcomes for patients with gastric and GOJ cancer managed across South Australia met contemporary evidence-based practice. However, as most patients continue to present with late-stage disease, longer-term survival remains poor.