RESUMEN
BACKGROUND: Emodin, a natural anthraquinone, has shown potential as an effective therapeutic agent in the treatment of many diseases including cancer. However, its clinical development is hindered by uncertainties surrounding its potential toxicity. The primary purpose of this study was to uncover any potential toxic properties of emodin in mice at doses that have been shown to have efficacy in our cancer studies. In addition, we sought to assess the time course of emodin clearance when administered both intraperitoneally (I.P.) and orally (P.O.) in order to begin to establish effective dosing intervals. METHODS: We performed a subchronic (12 week) toxicity study using 3 different doses of emodin (~ 20 mg/kg, 40 mg/kg, and 80 mg/kg) infused into the AIN-76A diet of male and female C57BL/6 mice (n = 5/group/sex). Body weight and composition were assessed following the 12-week feeding regime. Tissues were harvested and assessed for gross pathological changes and blood was collected for a complete blood count and evaluation of alanine transaminase (ALT), aspartate transaminase (AST) and creatinine. For the pharmacokinetic study, emodin was delivered intraperitoneally I.P. or P.O. at 20 mg/kg or 40 mg/kg doses to male and female mice (n = 4/group/sex/time-point) and circulating levels of emodin were determined at 1, 4 and 12 h following administration via liquid chromatography with tandem mass spectrometry (LC-MS/MS) analysis. RESULTS: We found that 12 weeks of low (20 mg/kg), medium (40 mg/kg), or high (80 mg/kg) emodin feeding did not cause pathophysiological perturbations in major organs. We also found that glucuronidated emodin peaks at 1 h for both I.P. and P.O. administered emodin and is eliminated by 12 h. Interestingly, female mice appear to metabolize emodin at a faster rate than male mice as evidenced by greater levels of glucuronidated emodin at the 1 h time-point (40 mg/kg for both I.P. and P.O. and 20 mg/kg I.P.) and the 4-h time-point (20 mg/kg I.P.). CONCLUSIONS: In summary, our studies establish that 1) emodin is safe for use in both male and female mice when given at 20, 40, and 80 mg/kg doses for 12 weeks and 2) sex differences should be considered when establishing dosing intervals for emodin treatment.
Asunto(s)
Antineoplásicos/toxicidad , Emodina/toxicidad , Inhibidores de Proteínas Quinasas/toxicidad , Animales , Antineoplásicos/sangre , Antineoplásicos/farmacocinética , Colon/anatomía & histología , Colon/efectos de los fármacos , Emodina/sangre , Emodina/farmacocinética , Femenino , Glucurónidos/metabolismo , Corazón/anatomía & histología , Corazón/efectos de los fármacos , Intestino Delgado/anatomía & histología , Intestino Delgado/efectos de los fármacos , Riñón/anatomía & histología , Riñón/efectos de los fármacos , Hígado/anatomía & histología , Hígado/efectos de los fármacos , Masculino , Ratones Endogámicos C57BL , Inhibidores de Proteínas Quinasas/sangre , Inhibidores de Proteínas Quinasas/farmacocinética , Caracteres Sexuales , Bazo/anatomía & histología , Bazo/efectos de los fármacos , Pruebas de Toxicidad SubcrónicaRESUMEN
BACKGROUND: Implementation of evidence-based interventions aimed at reducing and treating HIV can have a wider spread if funneled through faith-based organizations. However, there is a paucity of frameworks or process models aimed at providing the best practices to implement HIV interventions into faith-based community organizations. SETTING: Implementation framework and process model for African American faith settings. RESULTS: Presented here is a systems multilevel implementation framework and implementation process model for integrating HIV interventions into faith-based organizations. We conclude with presentation of key methodological considerations and recommendations and discuss strategies for moving implementation science forward in faith-based organizations. CONCLUSION: Because of their key role in the African American community, faith-based settings must be engaged in implementing evidence-based HIV interventions. Through use of a multilevel systems framework and process model, the methods and approaches of implementation science can be leveraged to encourage the spread of HIV interventions in the African American community.
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Atención a la Salud/organización & administración , Organizaciones Religiosas , Infecciones por VIH/terapia , Negro o Afroamericano , Promoción de la Salud/organización & administración , Humanos , Modelos Organizacionales , ReligiónRESUMEN
PURPOSE: Cognitive screening upon hospital admission can provide important information about the patient's ability to process information during the inpatient stay. The Clock-in-the-Box (CIB) is a rapidly administered cognitive screening measure which has been previously validated with cognitive screening and neuropsychological assessments. The purpose of this study is to demonstrate the predictive validity of the CIB for discharge location among a sample of older medical inpatients. PATIENTS AND METHODS: Hospitalized Veterans (N=218), aged 55 years and older, were recruited on the day after admission after they gave their consent. These participants completed the CIB, the Montreal Cognitive Assessment, and self-report measures of daily functioning. Using logistic regression models, the bivariable and multivariable impact of the cognitive screening and functional assessments were examined for their ability to predict whether the participants did not return home after hospitalization (eg, admission to subacute rehabilitation facilities or nursing facilities). RESULTS: The participants were older (mean 71.5±9.5 years) and predominantly male (92.7%). The CIB score was independently associated with discharge to locations other than home (odds ratio =0.72, 95% confidence interval =0.60-0.87, P=0.001) and remained associated after adjusting for demographics, prehospitalization functional abilities, and Montreal Cognitive Assessment score (adjusted odds ratio =0.55, 95% confidence interval =0.36-0.83, P=0.004). CONCLUSION: The current evidence, combined with its brevity and ease of use, supports the use of the CIB as a cognitive screen for inpatient older adults, in order to help inform clinical treatment decisions and discharge planning.
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Envejecimiento/psicología , Cognición , Disfunción Cognitiva/diagnóstico , Hospitalización/estadística & datos numéricos , Tamizaje Masivo/métodos , Actividades Cotidianas , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Oportunidad Relativa , Alta del Paciente , Escalas de Valoración Psiquiátrica , Factores de Riesgo , Estados UnidosRESUMEN
Increasing demands on palliative care teams point to the need for continuous improvement to ensure teams are working collaboratively and efficiently. This quality improvement initiative focused on improving interprofessional team meeting efficiency and subsequently patient care. Meeting start and end times improved from a mean of approximately 9 and 6 minutes late in the baseline period, respectively, to a mean of 4.4 minutes late (start time) and ending early in our sustainability phase. Mean team satisfaction improved from 2.4 to 4.5 on a 5-point Likert-type scale. The improvement initiative clarified communication about patients' plans of care, thus positively impacting team members' ability to articulate goals to other professionals, patients, and families. We propose several recommendations in the form of a team meeting "toolkit."
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Procesos de Grupo , Cuidados Paliativos/organización & administración , Planificación de Atención al Paciente/organización & administración , Grupo de Atención al Paciente/organización & administración , Mejoramiento de la Calidad/organización & administración , Comunicación , Conducta Cooperativa , Eficiencia Organizacional , Humanos , Satisfacción en el Trabajo , Factores de TiempoRESUMEN
OBJECTIVE: Identifying patients at risk for delirium allows prompt application of prevention, diagnostic, and treatment strategies; but is rarely done. Once delirium develops, patients are more likely to need posthospitalization skilled care. This study developed an a priori electronic prediction rule using independent risk factors identified in a National Center of Clinical Excellence meta-analysis and validated the ability to predict delirium in 2 cohorts. DESIGN: Retrospective analysis followed by prospective validation. SETTING: Tertiary VA Hospital in New England. PARTICIPANTS: A total of 27,625 medical records of hospitalized patients and 246 prospectively enrolled patients admitted to the hospital. MEASUREMENTS: The electronic delirium risk prediction rule was created using data obtained from the patient electronic medical record (EMR). The primary outcome, delirium, was identified 2 ways: (1) from the EMR (retrospective cohort) and (2) clinical assessment on enrollment and daily thereafter (prospective participants). We assessed discrimination of the delirium prediction rule with the C-statistic. Secondary outcomes were length of stay and discharge to rehabilitation. RESULTS: Retrospectively, delirium was identified in 8% of medical records (n = 2343); prospectively, delirium during hospitalization was present in 26% of participants (n = 64). In the retrospective cohort, medical record delirium was identified in 2%, 3%, 11%, and 38% of the low, intermediate, high, and very high-risk groups, respectively (C-statistic = 0.81; 95% confidence interval 0.80-0.82). Prospectively, the electronic prediction rule identified delirium in 15%, 18%, 31%, and 55% of these groups (C-statistic = 0.69; 95% confidence interval 0.61-0.77). Compared with low-risk patients, those at high- or very high delirium risk had increased length of stay (5.7 ± 5.6 vs 3.7 ± 2.7 days; P = .001) and higher rates of discharge to rehabilitation (8.9% vs 20.8%; P = .02). CONCLUSIONS: Automatic calculation of delirium risk using an EMR algorithm identifies patients at risk for delirium, which creates a critical opportunity for gaining clinical efficiencies and improving delirium identification, including those needing skilled care.
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Delirio/etiología , Registros Electrónicos de Salud , Anciano , Anciano de 80 o más Años , Femenino , Hospitales de Veteranos , Humanos , Masculino , New England , Seguridad del Paciente , Estudios Retrospectivos , Medición de Riesgo/métodosRESUMEN
BACKGROUND: Though often recommended, hospital cognitive assessment is infrequently completed due to clinical and time constraints. OBJECTIVE: This analysis aimed to evaluate the relationship between performance on ultrabrief cognitive screening instruments and hospital outcomes. DESIGN: This is a secondary data analysis of a quality improvement project. SETTING: Tertiary Veterans Administration hospital in New England. PATIENTS: Patients, ≥ 60 years old, admitted to the hospital. INTERVENTION: None. MEASUREMENTS: Upon admission, patients were administered 2 cognitive screening tools. The modified Richmond Agitation and Sedation Scale (mRASS) is a measure of arousal that can be completed in 15 seconds. The months of the year backward (MOYB) is a measure of attention that can be administered in ≤1 minute. In-hospital outcomes included restraints and mortality, whereas discharge outcomes included length of stay, discharge not home, and variable direct costs. Risk ratios were calculated for dichotomous outcomes and unadjusted Poisson regression for continuous outcomes. RESULTS: Patients (n = 3232) were screened. Altered arousal occurred in 15% of patients (n = 495); incorrect MOYB was recorded in 45% (n = 1457). Relative to those with normal arousal and attention, those with abnormal mRASS and incorrect MOYB had increased length of stay (incident rate ratio [IRR]: 1.23, 95% confidence interval [CI]: 1.17-1.30); restraint use (risk ratio [RR]: 5.05, 95% CI: 3.29-7.75), in-hospital mortality (RR: 3.46, 95% CI: 1.24-9.63), and decreased discharge home (RR: 2.97, 95% CI: 2.42-3.64). Hospital variable direct costs were slightly, but not significantly, higher (IRR: 1.02, 95% CI: 0.88-1.17). CONCLUSION: Impaired performance on ultrabrief cognitive assessments of arousal and attention provide valuable insights regarding hospital outcomes.
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Trastornos del Conocimiento/diagnóstico , Hospitalización , Pruebas Neuropsicológicas , Evaluación de Resultado en la Atención de Salud/métodos , Anciano , Anciano de 80 o más Años , Atención , Femenino , Hospitales , Humanos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Mejoramiento de la Calidad , Factores de Riesgo , Estados Unidos , United States Department of Veterans AffairsRESUMEN
BACKGROUND: Poor cognitive function is associated with negative consequences across settings of care, but research instruments are arduous for routine clinical implementation. This study examined the association between impaired arousal, as measured using an ultra-brief screen, and risk of 2 adverse clinical outcomes: hospital length of stay and discharge to a skilled nursing facility (SNF). DESIGN, SETTING, AND PARTICIPANTS: A secondary data analysis was conducted using 2 separate groups of medical ward patients: a Veterans Affairs medical center in the northeast (N = 1487, between 2010 and 2012) 60 years and older and a large tertiary care, university-based medical center (N = 669, between 2007 and 2013) 65 years and older in the southeastern United States. MEASUREMENTS: The impact of impaired arousal, defined by the Richmond Agitation Sedation Scale as anything other than "awake and alert," was determined using Cox Proportional Hazard Regression for time to hospital discharge and logistic regression for discharge to a SNF. Hazard ratios (HRs) and odds ratios (OR) with their 95% confidence intervals (CI) are reported, respectively. Both models were adjusted age, sex, and dementia. RESULTS: The 2156 total patients included in these groups had a mean age of 76 years, of whom 16.4% in group 1 and 28.5% in group 2 had impaired arousal. In the first group, patients with normal arousal spent an average of 5.9 days (standard deviation 6.2) in the hospital, while those with impaired arousal spent 8.5 days (9.2). On any given day, patients with impaired arousal had 27% lower chance of being discharged (adjusted HR 0.73 (95% CI 0.63-0.84). In the second group, individuals with normal arousal spent 3.8 (4.1) days in the hospital compared with 4.7 (4.6) for those with impaired arousal; indicating a 21% lower chance of being discharged [adjusted HR 0.79 (95% CI 0.66-0.95). With regard to risk of discharge to SNF, those with impaired arousal in group 1 had a 65% higher risk than those without impaired arousal [adjusted OR 1.65 (95% CI 1.21-2.25)], and those in group 2 had a nonsignificant 27% higher risk [adjusted OR 1.27 (0.80-2.03)]. Because of the quality improvement nature, this analysis did not control for comorbidities, which is a significant limitation. CONCLUSIONS: In this study of over 2000 older hospitalized patients, the simple observation of an abnormal arousal level may be an independent predictor of a longer hospital stay and discharge to SNF.
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Nivel de Alerta , Tiempo de Internación , Alta del Paciente , Instituciones de Cuidados Especializados de Enfermería , Centros Médicos Académicos , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Sudeste de Estados UnidosRESUMEN
Social workers can play an important role as part of the health care team in delirium risk identification, prevention, and care.
RESUMEN
BACKGROUND: When a hospitalized older patient falls or develops delirium, there are significant consequences for the patient and the health care system. Assessments of inattention and altered consciousness, markers for delirium, were analyzed to determine if they were also associated with falls. METHODS: This retrospective case-control study from a regional tertiary Veterans Affairs referral center identified falls and delirium risk factors from quality databases from 2010 to 2012. Older fallers with complete delirium risk assessments prior to falling were identified. As a control, non-fallers were matched at a 3:1 ratio. Admission risk factors that were compared in fallers and non-fallers included altered consciousness, cognitive performance, attention, sensory deficits, and dehydration. Odds ratio (OR) was reported (95% confidence interval [CI]). RESULTS: After identifying 67 fallers, the control population (n=201) was matched on age (74.4±9.8 years) and ward (83.6% medical; 16.4% intensive care unit). Inattention as assessed by the Months of the Year Backward test was more common in fallers (67.2% versus 50.8%, OR=2.0; 95% CI: 1.1-3.7). Fallers tended to have altered consciousness prior to falling (28.4% versus 12.4%, OR=2.8; 95% CI: 1.3-5.8). CONCLUSION: In this case-control study, alterations in consciousness and inattention, assessed prior to falling, were more common in patients who fell. Brief assessments of consciousness and attention should be considered for inclusion in fall prediction.
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Accidentes por Caídas/estadística & datos numéricos , Atención , Trastornos de la Conciencia/epidemiología , Delirio/epidemiología , Hospitalización/estadística & datos numéricos , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Cognición , Delirio/diagnóstico , Femenino , Humanos , Masculino , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Estados Unidos/epidemiología , United States Department of Veterans AffairsRESUMEN
BACKGROUND: Delirium has been associated with negative health consequences, which can potentially be improved by delirium risk modification. This study sought to determine if a quality improvement project to identify and modify delirium risk and discharge to rehabilitation is associated with improved outcomes for patients and health care systems. METHODS: In older veterans admitted to a tertiary VA hospital, delirium risk was assessed using cognitive impairment, vision impairment, and dehydration. Delirium risk was communicated to providers via electronic medical record. To modify delirium risk, interventions were provided in cognitive stimulation, sensory improvement, and sleep promotion. Primary outcomes included length of stay, restraint use, discharge to rehabilitation, and hospital variable direct costs. Outcomes were compared using a propensity-matched cohort of patients without intervention. Number of intervention categories was compared with primary outcomes. RESULTS: Patients (n = 1527) were older (78.2 ± 8.3 years) and male (98%). Propensity-matched patients (n = 566) were well matched for age, gender, cognitive deficits, vision impairment, and dehydration. Patients with interventions were discharged to rehabilitation similarly (mean difference [MD] 2.2%, 95% CI -2.5-6.9) and had lower lengths of stay (MD -0.7 day, 95% CI -1.3 to -0.1), lower restraint use (MD -4.0%, 95% CI -6.7 to -1.2) and trended toward lower variable direct costs (MD -$1390, 95% CI -3586-807). Increasing number of interventions was associated with shorter length of stay, lower rate of restraint use, and lower variable direct costs. CONCLUSIONS: This delirium risk modification project was associated with patient outcomes and reduced costs. Serious consideration should be given to delirium risk identification and modification programs.